COLUMBIA LIBRARIES OFFSITE HEALTH SCIENCES STANDARD mtratinns and col- 6 PREFACE TO VOLUME I. ored plates have not been spared where they could serve utility. IMost of these illustrations will derive an added interest from their originality, prepared, as they have been, especially for this work. Careful study has been bestowed upon the typographical arrangement and sub-head- ings of the various articles, and a system has been followed which will facilitate consultation. ]Much care has been given to the indexes, as upon their completeness depends very greatly the convenience and utilitv of the entire work. Each volume will be separately indexed. Due credit has been awarded in the text and foot-notes for important discoveries in medicine. A closing word is due and affectionately rendered to Professor Loomis. He secured the authors, apportioned their subjects, decided the arrangement and classification of the entire work, and discussed wdth me many important details, so that in completing the editorial duties alone I have been able to carry out the designs which he had alreadv formulated. He was one of the world's great masters of medi- cine ; he leaves it richer for this result of his knowledge of the science and of his contemporaries who could fitly join him in expounding it. His own article on Endocarditis will be read with all the interest at- taching to the latest production of a man universally admired for his attainments and respected for his personality. To the eminent clinicians and teachers who share in the authorship of these volumes I desire to extend thanks for their uniform courtesy and assistance in the execution of an editorial task necessarily large and difficult. W. GILMAN THOMPSON, M. D. ISTew Yoek, .January, 1897. CONTRIBUTORS TO VOLUME I. 1. K. ATKINSON, M.D., Professor of Therapeutics and C linical Medicine in the T'niversity of Maryhmd, Baltimore, Md. JOHN M. P.YROX, M.D., Late Director of tlie Bacteriological Laboratory in tlie Medical Department of the New York University, New York ; late Resident Physician at tlie New Y'ork Quarantine Hospitals. WAKREN COLEMAN, M. D., Instructor in Gross Patliology in the New Y'ork L'niversity, Assistant Curator to Bellevue Hospital, Visiting Physician to the City Hospital, New Y'ork. GEORGE DOCK, A.M., M. D., Pi'ofeSsor of the Tlieorv and Practice of Medicine and of Clinical Medicine, Uni- versity of Michigan, Ann Arbor, Mich. ALVAH H. DOTY', M. D., Health Officer of the Port of New Y'ork, New York Quarantine. ISADORE DYER, M. D., Professor of Dermatology in the New Orleans Polyclinic, Lecturer and Clinical Instructor on Dermatology, Medical Department of Tulane University, Derma- tologist to the Charity Hospital, Consulting Dermatologist to the Eye, Ear, Nose, and Throat Hospital, New Orleans, La. J. P. CROZER GRIFFITH, M. D., Clinical Professor of Diseases of Cliildren in the University of Pennsylvania, Professor of Clinical Medicine in the Philadelphia Polyclinic, Physician to >St. Agnes', tlie Methodist, and the Children's Hospital, Philadelphia. WALTER B. JAMES, M. D., Clinical Lecturer on Medicine in the College of Physicians and Surgeons, Attend- ing Physician to the Presbyterian Hospital, New Y'ork. THOMAS S. LATIMER, M. D., Professor of the Principles and Practice of Medicine in the College of Physicians and Surgeons, Baltimore, Md. 7 8 CONTRIBUTORS TO VOLUME I. WILLIAM OSLER, M. D., F.E. C.P., Professor of Medicine in the Johns Hopkins University, Physician-in-Chief to tlie Johns Hopkins Hospital, Baltimore, Md. WILLIAM HALLOCK PARK, M. D., Assistant Director of the Infectious Diseases Hospital Laboratory ; Visiting Phy- sician to the Hospitals of the Health Department of New York City ; Instructor in Contagious Diseases, Bellevue Hospital Medical College, New York. P. GERVAIS ROBINSON, M.D., LL.D., Professor of Principles of Medicine and Hygiene in the Missouri Medical College, Consulting Physician to the City Hospital, St. Louis, Mo. WILLIAM FRANCIS ROBINSON, M. D., Instructor in Dermatology and Assistant to the Clinic for Skin and Venereal Diseases, Rush Medical College, Chicago, Ills. GEORGE M. STERNBERG, M. D., LL.D., Surgeon-General U. S. A., Washington, D. C. JAMES STEWART, M. D., Professor of Clinical Medicine, McGill Univei-sity, Physician to the Royal Vic- toria Hospital, Montreal, Canada, WILLIAM SYDNEY THAYER, M. D., Associate Professor of Medicine in the Johns Hopkins University, Resident Phy- sician to the Johns Hopkins Hospital, Baltimore, Md. WILLIAM H. WELCH, M. D., Professor of Pathology in the Johns Hopkins University ; Pathologist to the Johns Hopkins Hospital, Baltimore, Md. WILLIAM M. WELCH, M. D., Physician in Charge of the Municipal Hospital for Contagious and Infectious Dis- eases, Philadelphia. HAMILTON ATCHISON WEST, M.D., Professor of General and Clinical Medicine, School of Medicine, University of Texas, Member of the Board of Managers of John Sealy Hospital, Galveston, Texas. JAMES C. WILSON, M. D., Professor of the Practice of Medicine and of Clinical Medicine in the Jefferson Medical College, Attending Physician to the Jefferson Hospital, the German Hospital, and the Pennsylvania Hospital, Philadelphia. CONTENTS OF VOLUME I. THE INFECTIOUS DISEASES. PAGE MALAEIA 17 By William H. Welch, M. D., and William S. Thayer, M. D. DENGUE 155 By Hamilton A. West, M. D. ENTERIC OR TYPHOID FEVER 167 By James C. Wilson, M. D. TYPHUS FEVER 233 By Alvah H. Doty, M. D. RELAPSING FEVER 257 By Warren Coleman, A. B., M. D. YELLOW FEVER 267 By George M. Sternberg, M. D., LL.D. CHOLERA 301 By John M. Byron, M. D. DYSENTERY 339 By Hamilton A. West, M. D. THE PLAGUE 391 By William M. Welch, M. D. INFLUENZA 399 By James C. Wilson, M. D. EPIDEMIC CEREBRO-SPINAL MENINGITIS 425 By Thomas S. Latimer, M. D. 9 10 CONTENTS OF VOLUME I. PAGE EEYSIPELAS 451 By George Dock, A. 31., M. D. PYEMIA 477 By I. E. Atkixsox, M. D. SEPTICEMIA 495 By I. E. Atkixsox, M. D. SMALLPOX AXD VAEIOLOID 513 By William M, Welch, M. D. VACCINIA 555 By William M. Welch, M.D. VAKICELLA ' o69 By William M. Welch, M. D. SCAELET FEVEE 577 By p. Gervais Robixsox, M. D., LL.D. RUBEOLA— MEASLES 625 By J. P. Crozer Griffith, M. D, EUBELLA . . '. 639 By J. P. Crozer Griffith, M. D. DIPHTHEEIA • 647 By William Hallock Park, M. D. PERTUSSIS 713 By J. P. Crozer Griffith, M. D. EPIDEMIC PAEOTIDITIS 725 By J. P. Crozer Griffith, M. D. TUBERCULOSIS 731 By William Osler, M. D., F. R. C. P. SYPHILIS By William Fraxcis Robixsox, M. D. 849 coy TESTS OF VOLUME I. 11 PAfJE LEPROSY . - -.i:.'] By IriAUOKE DvEii, M. D. TETANUS 935 B^' .Iamks Stkwaut, M. D. INFECTIOUS FEVERS OF OBSCURE NATURE 945 By Walter B. James, M. D. MALARIA. By WILLIAM H. WELCH, M. D., and WILLIAM S. THAYER, M. D. DEFINITION, SYNONYMS, HISTORY, AND PARASITOLOGY. By WILLIAM H. WELCH, M. D. Definition. Malaria comprises the diseases caused by tlie specific protozoan parasite called Hcematozoon malarice. The name " malaria/' derived from the Italian mal' aria and signi- fying " bad air," was applied originally to the miasm or poison which was "supposed to produce the disease. It is now used to designate the disease itself, and is the most convenient term for this purpose. The most characteristic malarial manifestations are intermittent or remittent fever, certain forms of the disease described as " pernicious," and a chronic cachexia with enlarged spleen and anaemia. The parasite discovered by Laveran is invariably present in malaria and produces from the haemoglobin of the red blood-corpuscles the brown or black pigment granules which are characteristic of the disease. Synonyms. Malarial fever ; Intermittent fever ; Chills and Fever ; Fever and Ague ; Paludism or Paludal fever ; Swamp or Marsh fever ; Miasmatic fever ; Periodical fever ; Autumnal fever. Names derived from localities where the disease has prevailed with especial intensity have sometimes been used ; as, Walcheren fever, Batavia fever, Hungarian fever, African fever, Panama fever, Chagres fever. Special names have been applied to certain types or manifestations of malaria ; as, remittent fever, bilious remittent fever, hemorrhagic remittent fever, congestive fever, dumb ague, black-water fever, black jaundice. History. There are few diseases which can be traced so surely and continuously as malaria in medical writings from ancient times to the present. Various types of malarial fever are described by Hippocrates, Celsus, Galen, and other ancient writers, although it is often impossible to determine the precise characters of many of the fevers described by these authors. Vol. I.— 2 17 18 3IALARIA. Celsus and Galen divide intermittent fevers into quotidian, tertian, quartan, semi-tertian, and irregular. They recognized intermittent fevers with long intervals. The nature of their semi-tertian fever (hemitritseus) has given rise to much discussion. Certain forms of intermittent fever were believed by Galen to have their seat in the spleen, others in the liver. The influence of marsh effluvia and of seasons of the year in the causation of certain of these fevers was recog- nized. Various symptoms were discriminated as to their prognostic significance, often with much acuteness of observation. A passage in Celsus clearly alludes to the type of malarial fever now called sestivo- autumnal fever. The Arabian physician Rhazes described the so-called subintrant malarial fevers. No important advance beyond the knowledge of Celsus and of Galen concerning malarial fevers was made until toward the end of the sixteenth century, when Mercatus in his work on malignant fevers described various forms of pernicious paroxysms in association with intermittent fever, particularly with the tertian type. The introduction of cinchona bark from Peru into Europe by the Countess del Chinchon and her body-physician, Juan del Vego, in 1640, gave great impetus to the study of malarial fevers, and, indeed, in its revolutionizing influence upon medical doctrines this event marks an epoch in the history of medicine. In the latter half of the seventeenth and the beginning of the eigh- teenth century there appeared a voluminous literature regarding mala- rial fevers. The most notable of the works upon this subject of this period are those of Sydenham, Richard Morton, Torti, Eamazzini, and Lancisi. These works remain to this day the great classics upon malaria. They contain the fundamental clinical and therapeutical facts and many etiological data relating to this disease. Morton and Lancisi demon- strated clearly the relation of malaria to marsh miasm. Sydenham pointed out the differences between vernal and autumnal intermittent fevers. Especially complete and keen in analysis is the nosography of Torti,^ whose classification of the malarial fevers, particularly of the pernicious and mixed forms, has been followed by most subsequent authors. The diagnostic as Avell as the therapeutic value of the prepara- tions of Peruvian bark was recognized, and assisted materially in the discrimination of the malarial fevers from the other so-called essential fevers. It is interesting to note the relative accuracy of diagnosis and of description of the group of malarial fevers from the latter half of the seventeenth century onward, in contrast to the confusion which existed regarding the other essential fevers until the discrimination of the latter by the pathological-anatomical studies of the present century. The military and colonial enterprises of England in the eighteenth century served to extend the knowledge of the geographical distribution of malaria, particularly in tropical climates, the works of Pringle and of Lind containing especially notew^orthy observations on this point. But the great mass of the very extensive literature on the epidemi- ography of malarial diseases which has been so industriously collected and ably analyzed by Hirsch ^ belongs to the present century. ' Torti : Therapeutics s-pedalis adfebres quasdam 'perniciosas, etc., Mutinse, 1712. ^Hirsch: Handbuch der historisch-geograpMschen Pathologic, Stuttgart, 1881. HISTORY. 19 The significance, as rejsrards malaria, of the active studies in morbid anatomy of the first half of the present eentiirv relates to the clear dif- ferentiation of typhoid fever from malarial and other fevers rather than to the actual contributions to the pathology of malaria, although these were not lacking. The occurrence of enlarged spleens, so-called fever- C4ikes or ague-cakes, and even the dark color of the organs in association with malarial fevers, had been occasionally observed by the older writers, notably by Lancisi, but the intimate relation of these altera- tions to malaria was not established until during: the first half of the present century. Andouard (1808, 1812, 1818) emphasized congestion and enlarge- ment of the spleen as the essential anatomical lesion of malarial fever. Bailly (1825) noted in a series of autopsies on cases of pernicious mala- rial fever observed in Rome in 1822 the dark color of the cortical gray matter of the brain and the congestion of the cerebral meninges and substance. He laid especial emphasis upon evidences of supposed inflammation of the central nervous system and of the stomach and intestine. These anatomical observations, together ^*ith those of Xepple (1828, 1835), and, to a less extent, of Maillot (1835), were interpreted in favor of Broussaisism, which at this period exerted such a pernicious influence upon medical practice. Valuable contributions to the pathological anatomy of malarial fevers, especially of the remittent type, were made in the United States during the fourth decade of this century by Stewardson in Philadelphia, Swett in Xew York, and Anderson and Frick in Baltimore. Steward- son demonstrated the bronzed color of the liver in remittent fevers, and regarded this as the characteristic anatomical criterion of the disease. His observations were confirmed and extended by the other ^v^ite^s named. Alonzo Clark in 1855 demonstrated that the bronzed color of these livers is due to the presence of granules of yellow, bro^vn, and black pigment, which he regarded as derived from the coloring matter of red blood-corpuscles. The monumental work of Daniel Drake on The Principal Diseases of the Interior Valley of Xorth America (1850, 1854) contains a large amount of valuable information, based upon personal observation and research, as to the distribution and characters of the malarial fevers in the then AVestern States of this country. In the light of recent discoveries it is interesting to note the ingeni- ous arguments advanced by John K. Mitchell in his work On the Crijp- togamous Origin of Malarious and Epidemic Fevers, published in 1849, in favor of the doctrine of contagium animatum. This book deserves to rank with the more frequently quoted work of Henle relating to the same line of argument. At about the same period Bassi and Rasori in Italy also advocated the parasitic theory of malaria. The discoverer of the malarial pigment is Heinrich Meckel, who found and described the pigment in 1848 in the blood and organs of the dead body of an insane patient. He was, however, ignorant of the relation of this pigment to malaria. The next report concerning the pigment was in 1849 by Virchow, mIio observed it in the body of a man who had suffered from chronic malaria. There soon followed the obser- vations of Heschl, Planer, A. Clark, Tigri, Frerichs, and others, fully establishing the relation of the pigment to malaria. The source of the 20 3IALARIA. pigment was regarded by Meckel and Virchow as in the spleen, and this doctrine was elaborated by Frerichs. Planer (1854) was the first who saw the pigment in the fresh blood of living patients, and he sug- gested that the pigment may be formed in the circulating blood — a view which was more fully presented and advocated by Arnstein (1874) and by Kelsch (1875). Tliere is no doubt that some of the pigmented bodies which are now recognized as parasitic organisms had been seen by earlier observers without knowledge of their true nature. Thus Meckel noted the presence of pigment granules in colorless, hyaline bodies devoid of definite nuclei. He, and more particularly Virchow and Frerichs, observed pigment in fusiform and curved bodies in the blood, which, although interpreted as endothelial cells of splenic, origin, in all proba- bility were, at least in part, the crescentic forms of the parasite. Some of the larger pigmented spherical organisms must have been seen and mistaken for pigmented leucocytes. In November, 1880, Laveran discovered the parasitic nature of these and previously unrecognized forms in the blood of malarial patients, and thereby introduced a new era into our knowledge of the malarial diseases. The discovery of the malarial parasite has furnished an unfailing means of diagnosis of malarial diseases, has materially advanced our knowledge of their pathology, has led to a better understanding of their clinical phenomena and various types, has furnished important data for prognosis, and has led to improvements in methods of treatment.^ Parasitology. Historical. In 1879, A. Laveran, a French military surgeon, stationed at the time in the province of Constantine, Algeria, began to study the path- ological anatomy of malaria, and at once directed his attention to the much discussed question of the origin of the pigment. He observed in the blood of malarial patients certain pigmented bodies different from the melaniferous leucocytes, but he was uncertain as to their nature until, on November 6, 1880, he discovered that some of these pigmented bodies threw out long flagella endowed with such active lashing move- ments as to convince him, as they have convinced every one who has since then seen them, that they are living parasites. Laveran published his observations in a note to the Academic de Medecine in Paris, pre- sented November 23, 1880. This was followed by the publication of several notes in 1880 and 1881, and in the latter year appeared a small monograph by Laveran on the parasitic nature of malaria.^ 1 The so-called bacillus malarise described in 1879 by Klebs and To mtn asi-Crudeli, which for a short period had a certain vogue, chiefly with Italian writers, never rested upon satisfactory observations which indicated that it bore any relation to malaria, and it deserves no more consideration than the palmella of Salisbury and the other alleged malarial organisms described before Laveran's discovery. ■^ Only occasional references to the voluminous literature on the parasitology of malaria are given in this article. A. full table of references to the works treating of malarial fever since the recognition of its parasitic origin up to and partly including the year 1895 will be found in "The Malarial Fevers of Baltimore," by William Sydney Thayer, M. D., and John Hewetson, M. D. {The Johns Hopkins Hospital Reports, vol. v., 1895). PARASITOLOGY. 21 In tlicsc various early publications Lavoran describes (1) pigmented cresoentio and ovoid botlies ; (2) spherical, transparent bodies, sometimes free, sometimes applied to the surface of red blood-corpuscles, the smallest about one-sixth of the diameter of a red blood-coi-puscle and eontaininti: only one or two fine pio-mcnt <;'i'anules, thes(! representin<^ an early stai>;e of development of (o) larger, pigmented, spherical bodies averaging <) n in diameter, but sometimes larger than a red blood-cor- puscle, and containing numerous, often moving, pigment granules ; (4) bodies similar to the last mentioned, but beset with actively motile flagella ; (5) free motile flagella ; and (0) swollen spherical or deformed bodies, 8—10 ii in diameter, containing pigment, and regarded as cadaveric forms of the spherical parasites. Laveran noted amoeboid movements of the spherical forms, grouping of the small spherical bodies together, and the occurrence of small, colorless, motile bodies, without specific characters, which he suggested may perhaps represent the first phase of development of the parasitic elements. He regarded all of the forms as different stages of development of the same species of organism, and considered the free flagella, which he believed were formed within the spherical bodies and escaped by rupture of the enveloping membrane, as the most characteristic and perfect stage of development of the parasite. Laveran communicated his results to his colleague Richard, stationed in Philippe ville, Algiers, who in February, 1882, published a commu- nication confirming Laveran's observations and adding certain points of importance. He describes the development of the parasite from small, perfectly transparent bodies contained in otherwise normal red blood- corpuscles. This clear body grows larger, forms pigment out of the haemoglobin of the enveloping red corpuscle, which thereby becomes gradually decolorized and reduced to a mere colorless shell-like rim, which finally ruptures and sets free the parasite. This now generally accepted view as to the intracorpuscular development of the parasite, which was first announced by Richard, was, however, in the following year abandoned by him in favor of Laveran's view that the parasites develop either free in the plasma or in close attachment to the surface of red corpuscles or in depressed spots on the surface. Richard observed amoeboid movements of the parasites, and noted spherical bodies with a central block of black pigment from which delicate lines radiated so as to produce rosette forms. Laveran continued to publish brief communications in 1882 and 1883, and in 1884 he published a larger work ' presenting his observations and views in detail. In this work lie describes more fully the forms already mentioned, and he notes the occurrence of segmenting forms, which, however, he interpreted as forms of degeneration, not of reproduction. The observations of Laveran and of Richard Avere made by micro- scopical examination of the fresh blood. In 1883 and 1884, Marchia- fava and Celli published in a number of articles the results of their studies of stained specimens of dried malarial blood. With the excep- tion of small, spherical stained bodies in the red blood-corpuscles, which they thought might be micrococci, they interpreted the various other stained and usually pigmented bodies found in the red corpuscles of malarial patients as probably degenerative changes. As a matter of ^ Laveran : Traite des Fieireft palufftres, Paris, 1884. 22 ' MALARIA. fact, the coccus-like clots were probably in part Ehrlich's degenerations, whereas their drawings show that the supposed degenerative forms were in reality the actual parasites, which in many ' of their phases were accurately depicted, although not recognized as such. In 1885, Councilman and Abbott in the organs from two cases of pernicious comatose fever found and described small pigmented hyaline bodies in and outside of red corpuscles, most abundantly in capillaries of the brain. In 1885, Marchiafava and Celli, as the result of the examination of fresh malarial blood, came to a correct interpretation of these bodies and described them fully and accurately. They emphasized especially the amoeboid, unpigmented, transparent intracorpuscular bodies, to which they gave the inaccurate name of plasmodia, which has been widely adopted. They described clearly the intracorpuscular develop- ment of the parasite, the formation of pigment out of the blood coloring matter, the consequent changes in the blood-corpuscles, and they pointed out the probable reproductive nature of the segmenting bodies, which they described more fully and accurately than had been done by Laveran and Richard.^ The publications of Marchiafava and Celli attracted wider attention than had those of Laveran, and from the year 1885 up to the present time there has been a steadily flowing stream of literature upon the various questions connected with the parasitology of malaria. Immediately following the confirmation of Laveran's discoveries by Italian observers came similar confirmation from Sternberg, Council- man, and Osier (1886-87), and somewhat later by James (1888) and Dock (1890), in this country, and within a few years numerous reports from various parts of Europe, America, Asia, and Africa demonstrated "the invariable association of Laveran's parasites with all cases of mala- rial fever. There are no observers of any prominence who, with sujffi- cient opportunity and training for such examinations, have failed to recognize the parasites in cases of malaria, nor is there now any authori- tative voice of dissent from the acceptance of the parasite as the specific cause of this disease. Since the fundamental researches of Laveran, Richard, and Marchia- fava and Celli (1880-85) other observers have greatly extended our knowledge as to many details concerning the structure and life-history of the parasite and its relation to various types, phenomena, and lesions of malaria, although not a few important questions still remain unsettled. The most important of these later discoveries are due to the demonstra- tion by Golgi (1885-86) of a definite relation between the cycle of development of the parasite and the different stages of malarial fever, and to the recognition by Golgi (1885-86) of the two varieties of the parasite belonging respectively to quartan and to tertian fever, and by Marchiafava and Celli and Canalis (1889) of the variety or varieties belonging to sestivo-autumnal fever. These observations have led to ^ Marchiafava and Celli claim for themselves the discovery of the intracorpuscular amoeboid forms with and without pigment, and of the segmenting forms, but, as is appar- ent from the review of Laveran's and Richard's preceding publications, this claim cannot be admitted. Marchiafava and Celli, however, described and interpreted these phases of the parasite far better than Laveran, and to them belongs the credit of demonstrating the intracorpuscular development of the parasite. PA HA SITOL OGY. 23 two schools of (loctrino — the ono, headed by Laveran, holdino; to the unity of a ])leonu)rj)liic' mahirial ])arasite, the other, headed by (rolgi and otlier Italian writers, uj)h()ldinu' the ])Iurality (if malarial parasites. The latter ilOetrine has the larger nimiber of sn[)])orters. Dock (leripheral layers, and have been graphically compared by Richard to the struggles of an animal to get free. Suddenly the flagella shoot out from the periphery, and with their active lashing movements produce a violent commotion among the red blood-corpuscles and other small particles which may be in their neighborhood (Plate I. Figs. 22 and 41 ; Plate II. Figs. 43, 44). The flagella are pale and thin, and present often at their extremities and along their course small olive-shaped swellings which may change their position. Here and there a pigment granule is occasionally seen in a flagellum. The flagella vary in size, number, and position. Their length may be three or four times the diameter of a red blood-corpuscle or not more than half that size. One to six may be attached to the spherical body. They may project from one side or from any part of the circumference of the body. Their movements may be somewhat rhythmical ; they may become slow or even cease, and again start up. Flagella may become detached and move about freely among the red blood-corpuscles. On account of their pallor such free flagella would I'ARASITOLOdY. 29 usually be overlooked were it uot ior the eoiuniotion whieli they produce among the red blood-corpuscles. The motion of the Hagella may be observed on the slide for half an hour, sometiines longer. These flagellate bodies are the most stai'tling forms of the malarial organism, and n<» one who sees them donbts for a moment that he is looking at a living j)arasite. It is not surj)rising that they attracted in an es])e('ial manner the attention of Laveran, who, as already mentioned, regarded the Hagella as the most characteristic and perfect form oi' development of the parasite. Subsequent studies have not, however, tended to (H)nfirm the conception of Laveran as to their significaiu-e. As has already been made clear, the flagellated bodies do not belong to the regular sporulating cycle of development of the malarial parasite in the human blood. The most prominent theories as to their significance are the following: (a) They are forms of degeneration or appearances belonging to the death-agony of the parasite. In support of this view it is urged that the flagellate bodies do not belong to any known cycle of development; that they are developed only outside of the human body ; that they are developed from mature forms which are known frequently to undergo undoubted degeneration, such as hydropic swelling, vacuolation, and fragmentation, and which may already show beginning evidences of degeneration ; that nuclear substance is absent from the flagella ; and that similar appearances of extrusion of motile filaments in other uni- cellular organisms are kriown to zoologists and are interpreted as degen- erative. (6) Sacharoif, from the study of their structure on stained specimens, believes that the flagella are extruded chromatin filaments derived from perverted karyokinetic nuclear division. He regards the process as degenerative. (c) Dock suggests that the flagellate bodies " represent resting states of the organism, capable of existing independently, perhaps even of reproducing themselves, but also able, under favorable circumstances, of reproducing the typical growth of the parasite." (d) Mannaberg's opinion is that the flagellate bodies may represent a state belonging to the saprophytic existence upon which the mature forms of the parasite enter soon after the blood is withdrawn from the body. On account of unsuitable conditions of environment they are unable to continue this existence in the blood outside of the body and soon perish. A similar view is advanced by Manson, who suggests that the flagellate bodies represent the first stage, and the detached flagella, in search of their appropriate host, represent the second stage of life of the parasite outside of the body. Manson ^ conjectures that the mosquito is the extracorporeal host of the malarial parasite, and he reports observations of Ross showing the development of flagellate forms in the stomach of mosquitos fed on malarial blood. There are arguments for and against each of these theories. Reluc- tant as one may be to consider such striking forms as the flagellate ^Manson: "The Goulstonian Lectures on the Life History of the Malaria Germ Outside the Human Body" {The British Medical Journal, 189G, March 14, 21, 28). Man- son lays much emphasis upon supposed analogies between the malarial germ and the filaria sanguinis. Only future investigations can determine the correctness of Manson' s hypothesis. 30 MALARIA. bodies as phases of degeneration, the existing evidence seems upon the whole to be more in favor of this hypothesis than of any other which has been advanced. Still, if Sacharoif 's observation as to the presence of nuclear material in the flagella be correct, the objection of Grassi and Feletti, that the flagella are incapable of reproductive development because the nucleus of the parasite does not divide and enter them, would be overthrown and the hypothesis of Mannaberg and Manson would become more probable. It is evident from the description of these bodies that the use of the word " flagella " to designate the motile filaments is of doubtful propriety, but it is the term commonly employed. (3) There are various bodies, often seen in the examination of mala- rial blood, which are undoubtedly degenerative forms of the parasite, and others which are probably degenerative, although opinions con- cerning the latter are divided. The more common signs of degeneration of the parasite are vacuolation, pseudo-gemmation, fragmentation, deformities of shape, particularly swelling, granular condition of the protoplasm, certain alterations in the arrangement and appearance of the pigment, disappearance of nuclear material, defects and irregulari- ties in staining, and changes in the refraction of the organism. These various degenerative changes produce forms too numerous to describe in detail. They have often been misinterpreted and described as special forms of the parasite, some of them, particularly certain vacuolated and budding forms, as special modes of reproduction. Degenerations may occur in any form of the parasite, but they are particularly common in the extracorpuscular forms. Mannaberg de- scribes the disintegration of young intracorpuscular forms, with dis- appearance of their nuclei. Fragmentation of forms extruded from the blood-corpuscles can sometimes be watched while examining fresh blood under the microscope (Plate I. Fig. 21). As a rule, only a certain number of the mature forms actually enter into reproductive segmenta- tion, and many of the spores or segments perish. If all segmented and the offspring survived, the number of the parasites after a few paroxysms would become enormous. As a matter of fact, degenerations of full- grown parasites are often observed. An interesting form of such degen- eration, found most frequently in the mature forms of the tertian variety, is the appearance of swollen, pigmented, so-called hydropic bodies, often much larger than red blood-corpuscles (Plate I. Figs. 18, 40), and sometimes containing vacuoles (Plate I. Figs. 18, 19, 23, 24, 40, and 42). Pound bodies simulating spores are sometimes seen in these vacuoles, but on properly stained specimens they are devoid of the nuclear mate- rial of genuine spores. Pseudo-gemmation, or the appearance of sarcodic buds on the surface of the organisms, is doubtless a form of degenera- tion. Such buds may become separated, in the form of hyaline balls, from the parent organism (Plate I. Figs. 19, 20). These evidences of degeneration may appear also in crescents and bodies belonging to this group (Plate 11. Figs. 40, 41) and in flagellate bodies. From the latter small hyaline balls with a flagellum attached may break off and move around actively. Such bodies might be mistaken for flagellated spores. There is no good evidence that the malarial parasite ever multiplies PARASITOLOGY. 31 hv l)u«](linix' or by simple cell-division. The only form of multiplica- tion wliieh lias been demonstrated is that of sponihition, also called se) the tertian parasite. (2) " To the second group belong the fevers which appear clinieallv under niultiforni types, very often irregular, of which for the present it is impossible to make a grouping based upon an ascertained biology or cycle of development of the parasite We are dealing in these cases with generations of parasites which, occurring in the parenchyma of organs in different stages of development, give origin, at periods of a certain regularity or in a more or less continuous succession, to colonies of young forms which, in large or small numbers or in insignificant quantity, may escape into the blood current, permitting one to discover by microscopical examination of the blood the presence of the small endoglobular amoebae." Golgi refers to the crescents as " forms the biol- ogy of which has not yet been well determined." VI. Thayer and Hewetson (1895) were likewise unable to confirm Marchiafava and Bignami's subdivision of the sestivo-autumnal parasite into a quotidian and a tertian variety. They say: " We have been unable to trace a constant length of the cycle of development, and we have been unable further to separate two or more types of the [aestivo- autumnal] parasite depending either upon the length of the cycle of development or upon any other morphological or biological differences. We believe that the length of the cycle varies greatly in different cases, lasting usually from twenty-four hours, or even a little less, to forty- eight hours or more. After the infection is five days or a week old certain of the organisms, instead of segmenting, pursue a further growth, developing into the hyaline, refractive, ovoid, and crescentic bodies." They do not feel justified in making any positive statement as to the significance or capacity of reproductive development of the crescentic bodies. The question has been raised whether in tropical regions, where per- nicious types of malaria are common, any form of malarial parasite different from those already mentioned occurs. The observations of Van Dyke Carter, Dock, van der Scheer, Plehn, and others show that the same parasites are found in India, Panama, Java, and other tropical countries as elsewhere. The negative reports which have been published are referable doubtless to insufficient training in such examinations on the part of the observers. The fact that a large part of the tropical malarial fevers are caused by sestivo-autumnal organisms which appear in the red blood-corpuscles as small, pale, feebly-staining, delicate^ diaphanous, often unpigmented amoeboid rings of hyaline protoplasm, difficult to detect in many cases, and sometimes scanty or at times even absent, will account for many of these negative observations. The singular distribution of the haemoglobinuric type of pernicious malarial fevers in certain definite localities suggests the possibility that tliis may be caused by a special type of organism. The sporadic cases of malarial hemoglobinuria examined in Italy have shown, however, 40 MALARIA. ordinary sestivo-autiimnal organisms. Plelm ^ found in cases of black- water fever occurring on the West Coast of Africa small, annular amoe- boid forms, staining with great difficulty and never pigmented, in the red blood-corpuscles. " Out of the amoeba there develops by thickening of the peripheral zone an oval or egg-shaped body, with well-staining double contour. In course of time this divides into five or six small oval forms, staining at one pole, which, when they are set free, move about with great rapidity in the blood. These probably develop into the amoeboid forms." The organism never attained a size larger than one quarter of the red blood-corpuscle. Crescents were occasionally found. Plehn seems to regard this organism as allied to, but not iden- tical with, the sestivo-autumnal parasite described by Italian writers. Although his description presents certain peculiarities of the parasite which he observed in the pernicious malarial hsemoglobinuria and other pernicious fevers of the West Coast of Africa, especially the constant absence of pigment, the extremely small size, the sporulation in the blood, and the apparently motile spores,^ nevertheless it is not suffici- ently complete and satisfactory to justify the inference that the organ- ism differs from forms of the ordinary sestivo-autumnal parasite as previously observed. From the preceding review of the various investigations and opinions concerning the divisions or varieties of the malarial parasite, especially of the sestivo-autumnal form, we may draw the conclusion that whereas the separation into quartan, tertian, and eestivo-autumnal varieties rests upon a sound basis of fact, the various attempts to further subdivide the £estivo- autumnal group have not as yet been sufficiently successful to jus- tify our acceptance at the present time of any of these subdivisions. There is, however, some reason to believe that this last group, as at present constituted, may comprise varieties which will hereafter be satisfactorily differentiated from each other. We will now consider the special characters of each of the three varieties of the malarial parasite. I. The Parasite of Quartan Fever (H^matozoon Ferris Quartans) (Plate I. Figs. 25-42). In most malarial regions this is the rarest form of the malarial parasite, but there are certain places (none of these have been recog- nized in this country) where it is the prevailing variety. Being par- ticularly common in the neighborhood of Pavia in Italy, the quartan parasite was the first to be differentiated and described by Golgi (1885- 86), to whose masterly description nothing of essential importance has been added by subsequent investigators, with the exception of certain details of intimate structure. The quartan parasite completes its cycle of development in seventy- two hours and entirely within the circulating blood. The youngest forms of the parasite are small, amoeboid, when at rest discoidal, hyaline bodies, ^ Plehn : " Ueber das Schwarzwasserfieber an der afrikanischen Westkiiste," Deutsche med. Wochensehrift, 1895, Nos. 25, 26, 27. ^ It may here be mentioned that Plehn considers that the spores of all varieties of the malarial parasite are flagellated — a view which has not been confirmed by other observers. PARASITOLOGY. 41 within the red l)l()<»(l-c'orj)usc'lc'.s. They are about one-fifth to one-fourth tlie si/e of the red hlood-corpusele (PUite I. Fig. 2G). The central part of the l)()dv may appear paler than the ])eripheral. These unpigniented, youngest forms are found during and for several hoursafter the paroxysm ; they may begin to aj)pear two hours i)efore the paroxysm. The very ear- liest forms are not to be distinguished from the youngest tertian parasites, but as they begin to develop they present a sharper outline and somewhat more refractive a])pea ranee, and their amoeboid movements are more slug- gish and restricted than those of the corresponding stages of tlie tertian ori>anism. These movements become more active on the warm staw of the microscope. The presence of more than one parasite in a red blood- corpuscle is sometimes observed. Shortly, or within twelve to eighteen hours, after the paroxysm pig- ment granules appear within these hyaline bodies, which continue to increase slowly in size, and for a while to exhibit lazy amceboid move- ments (Plate I. Figs. 27, 28, 29). The pigment appears in the form of brow'nish or black rods and grains, which are coarser and darker than those seen in tertian parasites. The rod form of pigment is less common than in the tertian organism. These pigment granules are arranged generally in the peripheral part of the parasite, and they present only a sluggish uKjvement in comparison with the active motion of the pigment in the tertian parasite. With the gradual increase in size of the hyaline bodies and in the amount of contained pigment the red blood-corpuscles enclosing them may appear unchanged, or often they become a little smaller, more refractive, and deeper in color, which may be somewhat greenish or coppery in tint (Plate I. Figs. 28, 29). There is not that tendency to decolorization and swelling of the infected red blood-cor- puscles which is noticed in the case of the tertian parasite, although in the more advanced stages of development there is usually some loss of color in red corpuscles containing quartan organisms. In the process of development the amoeboid movements cease, and the parasite appears as a quiescent, pigmented, spherical, or ovoid body occupying perhaps one-half to two-thirds of the red corpuscle (Plate I. Figs. 30, 31). Such bodies are usually seen within forty-eight hours after the paroxysm. These bodies continue to grow, and when they have reached their full development in sixty to seventy hours after the parox- ysm they are somewhat smaller than the normal red blood-corpuscles. These full-grown forms are spherical or ovoid, refractive, hyaline bodies, with nearly or quite motionless dark pigment granules of variable size, but coarser than in the tertian parasite, and with a tendency to periph- eral arrangement, but at times irregularly distributed. Around these bodies a thin layer of the colored, refractive substance of the red blood- corpuscle can usually still be seen (Plate I. Figs. 32, 33, 34), or the haemoglobin may be entirely removed, so that only a delicate, thin, color- less rim or line surrounding the parasite is all that is left of the original red blood-corpuscle. In unstained specimens these latter forms often appear to be free in the plasma (Plate I. Fig. 35), and are sometimes spoken of as free bodies, which may also occur. In six or eight to ten hours before the febrile paroxysm the first phases of reproduction begin to appear. These are ushered in by the gradual withdrawal of the pigment from the periphery toward the centre 42 MALABIA. of the body. The pigment in this process is often arranged in definite radial strise (Plate I. Fig. 36). Such regular stellate arrangements of the pigment as are seen in this stage of the quartan parasite are rarely, if ever, observed in the tertian (Thayer and Hewetson). Finally the pigment is concentrated into a central mass of granules or a solid block of coalesced pigment, less frequently into two or more collections, and the organisms assume a somewhat more refractive and slightly granular appearance. At the same time or soon afterward radial divisional striae begin to appear in the periphery (Plate I. Fig. 37), and quickly extend to the central part of the parasite, whereby the substance of the spherical organism becomes divided into six to twelve ovoid or pear-shaped seg- ments arranged with characteristic and exquisite regularity around the central mass of pigment like the petals of a daisy (rosettes of Golgi) (Plate I. Fig. 38). In each of the segments can be seen a small round glistening body which represents the nucleus or nuclear material. The pyriform segments assume rapidly a round or oval shape, and become separated from the central mass and from each other. The delicate enveloping membrane, which may not be recognized on unstained speci- mens, derived from the red blood-corpuscle ruptures, or it may previ- ously have disappeared, and the small round or oval bodies, each pro- vided with a bright nucleiform dot, are set free in the plasma (Plate I. Fig. 39). These bodies are the so-called spores. Simultaneously with this process of sporulation young amoeboid hyaline bodies, formed di- rectly from the spores, make their appearance in the red blood-corpus- cles, and the cycle of development is completed and another cycle is begun. Segmenting or sporulating forms of the parasite may appear six or eight hours before the paroxysm, and are most abundant shortly before and during the onset of the paroxysm. It is of course not to be under- stood that all of the parasites of one group pass through their develop- mental phases and mature at exactly the same moment. One parasite of the group may be several hours in advance of another, but this does not interfere with the recognition of distinct groups or generations, each standing in definite relation to a paroxysm, or with the establishment of Golgi' s law that the onset of each paroxysm corresponds to the matura- tion of one group of organisms. The cycle of development of the quartan parasite is attended with fewer irregularities than that of any other variety of the malarial para- site. Nevertheless, certain irregularities may occur. As pointed out by Antolisei, segmentation may occur exceptionally in pigmented bodies considerably smaller than the usual full-grown forms, containing less pigment and filling only a part of the red blood-corpuscle. Here the segments do not usually exceed four to six or eight. The accumulation of pigment in the segmenting forms may be peripheral, or distributed between the spores, or otherwise irregular. As the quartan parasite completes its development entirely within the circulating blood, there is no appreciable difference at any stage between the splenic and the peripheral blood as regards the number and variety of the parasitic forms observed. Moreover, segmenting forms of the quartan parasite are often seen in small number in the blood at a PARASITOLOGY. 43 periotl bcfort' the total nunibor of organisms is siifficiontly larfje to pro- duce by their ripening- a paroxysm, whereas se<>;nientin<^ tertian parasites are very rarely seen in the peri])heral blood witiiont the occurrence of a paroxysm in relation to the se_t;incntin<>; forms. Not all of the mature forms proceed to sporulatiou. Some, especially those which may have escaped from the red corpuscles, swell uj), l)ecome transj)arent and larger than a red blood-corpuscle, and j)resent irregu- larly distributed and actively moving pigment granules (Plate I. Fig. 40). These swollen, hydropic forms are probably sterile. It can often be seen in examining these bodies in fresh blood that the pigment becomes quiescent, the outlines of the body become irregular and indistinct, and evidently cadaveric forms result. Or these bodies may break up into a number of fragments which become misshapen and indistinct, or the whole body may become vacuolated, as is represented in Plate I. Fig. 42. Bodies more or less resembling spores, but without the nuclear structure of spores, may appear in these vacuoles. As may occur with any variety of the malarial parasite, the mature forms of the quartan parasite, instead of sporulating^ may develop into flagellate bodies in the manner already described. These bodies are smaller and contain coarser pigment than the flagellate forms of the tertian parasite. (Compare Plate I. Fig. 41 and Plate I. Fig. 22.) De- generated and flagellate forms are less common in quartan than in tertian infections. Not only may mature forms degenerate in the ways described, but forms in earlier stages of development may be liberated from the red corpuscles and likewise degenerate. The phenomena of phagocytosis are observed with regularity during and for some hours after the paroxysm in quartan as well as in other malarial infections. The pigment set free by the process of sporulation is taken up by phagocytes. Extracorpuscular organisms, particularly the various degenerated forms, are engulfed by phagocytes. The assault on the flagellate bodies by leucocytes can be watched with interest on the slide of fresh blood. The leucocytes can also be seen to take up segmenting bodies and spores when the specimen of blood is kept for a while. The details and the significance of these phagocytic phenomena will be considered subsequently (page 65). The intimate structure of the quartan and other malarial parasites, as revealed by methods of staining, will also be described subsequently. Two or more groups of quartan parasites are often present in the blood at the same time, causing double and triple quartan infections. On account of the regularity in the development of the quartan para- site, anticipating, retarding, and irregular fevers are less common in quartan than in the other malarial infections. Careful examination of the blood enables the observer to recognize the presence of two or more groups of the parasite by noting the simultaneous occurrence of bodies in noticeably different stages of development ; as, for example, during the paroxysm the association of segmenting and young hyaline bodies with half-grown pigmented bodies. 44 3IALABIA. II. The Parasite of Tertian Fever (HiEMATOZOON Febris Tertians) (Plate I. Figs. 1-24). This variety of the malarial parasite is common in most malarial regions. Where only mild types of malaria occur it is, as a rule, the prevailing, and sometimes the sole, variety observed. The tertian and the quartan parasites cause most, or in some places all, of the winter and spring intermittents, but they, and especially the tertian parasite, may cause in districts of even severe malaria not a few of the malarial fevers of summer and autumn, although the more severe and irregular of these latter fevers are caused chiefly by the sestivo-autumnal parasite. The tertian parasite may, however, produce severe, as well as mild, types of malaria. The tertian parasite was differentiated from the quartan and described in its essential characters by Golgi in 1886 and 1889. Other observers, particularly Antolisei (1889-90) and Bastianelli and Bignami (1890), have added to, and in some points corrected, Golgi's first description. The chief points to be emphasized in this description of the tertian parasite are those which distinguish it from the quartan parasite. Unlike the quartan parasite, certain stages of development of the tertian — namely, those concerned with sporulation — take place by preference in the spleen and the bone marrow, although segmenting forms are seen also in the peripheral blood. The cycle of development is completed in forty -eight hours. During the paroxysm or shortly after it small, unpigmented, hyaline, amoeboid bodies are found within the red blood-corpuscles, of which they are about one-fifth to one-fourth the size (Plate I. Figs. 2 and 3). Usually one hyaline body is found, but not very infrequently two or more are present, in a single blood-corpuscle. The tertian aracebse, especially in their pigmented stage, change their shape and position within the corpuscles much more actively than the quartan amcebse, these movements being vigorous at ordinary room temperature. Several branching pseudopodia are sent out, often reaching nearly or quite the periphery of the corpuscle, and are retracted. All sorts of shapes may thus be assumed by the parasite, which with its long branching processes may seem to pervade nearly the whole corpuscle. By the union of two pseudopodia the shape may be that of a ring enclosing a bit of the corpuscular substance (Plate I. Fig. 5). The tertian amoebae are paler, less sharply outlined, than the quartan (compare the two varieties in Plate I.). In a short time fine reddish-brown or yellowish- brown rods and granules of pigment, varying somewhat in size, appear in the margins of the amoebae (Plate I. Fig. 5). Pigment granules often collect in the bulbous ends of pseudopodia (Plate I. Figs. 6 and 7), and the intervening parts of the pseudopodia may be so thin and delicate as to be readily overlooked, so that the appearance may be that of several distinct bodies within one red blood-corpuscle. Careful examination will, however, detect the fine connecting processes or the retraction of the apparently separate bodies into the substance of one parasite. Two or more parasites may, however, be present occasionally within one red corpuscle (Plate I. Fig. 4). The pigment is in finer grains and rods, and of a lighter, somewhat different, tint in the tertian, than in the PARASITOLOGY. 45 ([iiartaii parasite. (See Plate I.) It is tiiso in much more active move- ment in the tertian anifeha'. This movement is not altogether like the lirunonian or molecular motion, and is probably due to intrinsic ])roto- plasmic movements or currents. W^ith the continued g-rowtii and increased ])ioincntati()n of the anuebie the infected corpuscles as a rule become distin(;tly swollen and j)aler than normal — a change which may be already indicated even with (juite small pigmented forms, and which is one of the most distinctive cha- racters of the tertian parasite (Plate I, Figs. 4-9). Occasionally the enveloping corpuscle is not noticeably swollen or altered, and exception- ally it may even shrink and acquire something of the brassy appearance commonly seen with red corpuscles infected with the jestivo-autumnal parasite. On the day of apyrexia the parasite, now with somewhat sharper contour and more richly pigmented, may attain a size equalling one-half to two-thirds that of the infected blood-corpuscle. The amoeboid move- ments have become more sluggish, but they persist in stages of develop- ment corresponding to which forms of the quartan parasite have become quiescent. The pigment continues in active motion. The fully developed parasite is about the size of a normal red cor- puscle, sometimes a little smaller, sometimes somewhat larger, and it is therefore smaller than the swollen corpuscle in wdiich it is contained. It is nearly or quite spherical in shape, and without amoebic movements. The pigment for a while preserves its marginal arrangement or less fre- quently is irregularly distributed (Plate I. Fig. 9). The expanded red blood-corpuscle enveloping the parasite becomes still paler. These fully grown forms change into the presegmenting bodies by the collection of the pigment, which has already become quiescent, into a mass of granules or into a solid block situated usually in or near the centre or sometimes near or at the margin. As with the other varie- ties of the malarial parasite, the pigment with the development of the parasite becomes coarser, and the delicate rod-like forms of pigment become relatively less numerous. These spherical bodies with central jiigment clumps are more refractive than is the parasite in preceding stages of development. Stained specimens show that in these preseg- menting bodies there appear multiple, deeply staining chromatin gran- ules, which represent nuclear substance, and which are the first indica- tion of the inception of sporulation. This phase of segmentation presents more variation than is observed in the quartan parasite. Sometimes it begins with the appearance of radial striation extending from the periphery to the centre, and proceeds by a division of the substance of the parasite into twelve to twenty or even more segments arranged in a rosette form around the central clump of pigment. A little later the pigment clump is surrounded by a group of small round bodies, which are the spores. More commonly, without the formation of such regular figures, the protoplasm breaks up into a mass of fourteen to twenty or more spores. Sometimes one sees an outer and an inner ring of spores concentrically arranged around the central mass of pigment. The larger number of segments or spores formed by the tertian as contrasted with the quartan parasite is an important dif- ferential characteristic. 46 3IA LABIA. The modes of segmentation described (Plate I. Figs. 10-14) corre- spond in the main to Golgi's second type of segmentation. His first mode of segmentation of the tertian parasite has not been noted by other observers. It is as follows : After the collection of the pigment in the centre the organism is differentiated into a peripheral zone sharply sepa- rated from a central body containing the pigment. The peripheral ring becomes radially striated, and then divides into fifteen to twenty small hyaline segments. The central pigmented body does not segment, but remains behind after the separation of the spores. Golgi's third variety of segmentation is now generally recognized as a process of degenerative vacuolation. Sometimes the segmenting bodies show, instead of one central accu- mulation of pigment, two or more clumps excentrically placed, or the pigment may be concentrated in the periphery or distributed between the spores or otherwise irregularly arranged. The spores are set free by rupture of the enveloping membrane derived from the red corpuscle, or this membrane may have disappeared before the segmentation is completed. The individual spores are some- what smaller than those of the quartan parasite. They usually show a refractive nucleiform dot, wliich is, as a rule, less distinct than in the quartan spores. Coincidently with sporulation the young, colorless amoebae, formed from the spores, make their appearance in the red blood-corpuscles and start on a fresh cycle of development. The segmenting bodies may make their appearance several hours before the paroxysm. They are most numerous shortly before and dur- ing the onset of the paroxysm. They may be scanty in the peripheral blood, for the process of sporulation takes place largely in the internal organs. The red corpuscles containing mature and presegmenting bodies accumulate especially in the spleen and the bone marrow, and there the organisms complete their reproductive development. During most of the period of apyrexia no noticeable difference is observed in the num- ber and kinds of parasites between the peripheral blood and that with- drawn by hypodermic syringe from the spleen. But shortly before and during the paroxysm far more ripe and sporulating forms are found in the splenic than in the peripheral blood. Precocious segmentation into five to ten spores may occur in bodies, sometimes containing only a grain or two of pigment, which have not attained a size exceeding one-half to t^vo-thirds that of the red blood- corpuscles (Plate I. Figs. 16, 17), the usual size of a segmenting body being about that of a red corpuscle, but sometimes considerably larger. Such immature forms of segmentation are associated by Bastianelli and Bignami with anticipating fevers, but Mannaberg and Thayer and Hew- etson, although not inclined to discredit this interpretation, were unable to convince themselves of this relation. Partly developed and mature tertian parasites are often seen free in the plasma. Swollen, transparent, extracorpuscular forms, which may attain the size of large leucocytes, and which contain scattered dancing pigment granules, are generally considered to be degenerative or inca- pable of reproductive development (Plate I. Fig. 18). These so-called hydropic forms are considerably larger and. paler and more common than PARASITOLOGY. 47 the similar forms of the quartan parasite. These swollen, richly pig- mented forms are ver^' common in tertian infections. In general, the various forms of degeneration which have already l)een described, such as fragmentation, vacuolation, pseudo-gemmation (Plate I, Figs. 19, 20, 21, 23, 24), are more common witii the tertian than tlie quartan parasite. Flagellate bodies are likewise more common. They are, as a rule, larger and contain finer pigment than the cpiartan flagellates (Plate I. Fig. 22), They develop chiefly from the round, swollen, extraccjrpuscular forms with scattered ]iigment, although flagella have been observed to develop from forms still surrounded \\ith a distinct layer of hsemogloljin-con- taining substance of the red blood-corpuscle. Flagellate bodies are most abundant in blood withdrawn from the spleen shortly before and during the paroxysm. Phagocytosis occurs ^vith the same regularity and with similar phenomena in tertian as in quartan infections. Infection with two groups of tertian parasites (double tertian), as described for quartan infection, is more common than with a single group, especially in the later period of the malarial season in the spring and in summer and autumn. The resulting type of fever is quotidian. In some cases there seem to be several irregularly distributed genera- tions causing remittent or subcontinued fevers. It is not necessary to attribute the presence of two or more groups of the same variety of parasite to corresponding multiple infections from ^^■ithout. There is e\'idence that certain members of a group may, in their development, lag behind or advance beyond others of the same group, and in course of time by farther multiplication may constitute a separate group capable of causing its own paroxysms of fever. It is remarkable, however, that the second group should be separated in its cycle of development by such definite intervals from the first as we usually observe in quotidian fevers of tertian origin. Genuine mixed infections with malarial parasites, the most frequent combination being that of the tertian and of the sestivo- autumnal parasites, are not very uncommon. The length of the cycle of development of the tertian parasite may occasionally be noticeably shorter than forty-eight hours, perhaps only forty hours or less, or, on the other hand, it may be longer than the normal period. This may explain the anticipating and the postponing fevers. III. The Parasite of ^STn^o-AUTUMXAE Feyee (H^matozoon Falciparum) (Plate II.), This was first clearly differentiated from other varieties of the mala- rial parasite by Marchiafava and Celli*(1889), and was subsequently more fully described by the same authors and by Canalis (1889-90), (See foot- note, page 32.) The extensive literature concerning the parasitology of malaria during the last six years has been concerned to a large extent ^vith this variety, but we are still far from possessing so full and accurate knowledge regarding the characters and development of the IIsematozo5n falciparum as regarding those of the quartan and tertian parasites. Such knowledge is much to be desired in view of the fre- quency of the aestivo-autumnal parasite in regions, such as the southern part of the United States, where the more severe types of malaria occur. 48 MALARIA. and of the almost exclusive association of this parasite with pernicious malarial fevers. Chief reasons for the difficulty in investigating the entire life history of the Hsematozoon falciparum are that it develops mainly within the internal organs and often in multiple groups, and that the later repro- ductive phases of development are met with in the circulating blood only very exceptionally. Under the Classification of the malarial para- sites we have already presented the more important opinions which have been advanced concerning possible subdivisions of the sestivo-autumnal variety (page 35 et seq.). The youngest forms of this parasite are small hyaline bodies, about one-sixth the diameter of a red blood-corpuscle, which make their appearance in the blood-corpuscles during or shortly after the paroxysm. It is not uncommon to find two or more hyaline bodies in a single cor- puscle. These sestivo-autumnal hyaline bodies are in general the smallest forms of the malarial parasite which are observed in the red blood-corpuscle (Plate II. Figs. 1 and 2). The youngest forms may be quiescent, but as they develop they manifest amoeboid movements resembling in their activity those of the tertian amcebte. The young sestivo-autumnal amoebse may not be readily distinguish- able from the similar forms of the quartan and tertian parasites. Par- ticularly characteristic, however, of the young hyaline forms of the Ha^matozoon falciparum when in repose and in stained specimens is the ring shape. The appearance in fresh specimens is that of a somewhat refractive, clear, hyaline ring, usually thicker on one side, surrounding a small round central, or oftener excentric, shaded j)art, or sometimes two or three such parts, through which the color of the red corpuscle shows. In stained specimens the ring appears thinner than in fresh specimens, and the central or excentric part is unstained, while a minute deeply stained granule is situated in the outer ring. The study of the further development of these forms, especially on stained specimens, has demonstrated that these apparently annular bodies are not actual rings, as some have supposed, enclosing a bit of the red corpuscle, but that the clear area which does not stain is a trans- parent part of the organism, which, as will be subsequently explained, some regard as the nucleus. Actual rings, however, as has already been mentioned, may be formed by the junction of pseudopodia, which thereby enclose some of the corpuscular substance, but such is not the explanation of the typical annular appearance of the sestivo-autumnal hyaline bodies. It is not uncommon to find free hyaline bodies in the blood plasma. These hyaline bodies may, while under observation, become some- what expanded and paler and lose their annular appearance, and again resume the ring shape. While the very smallest intracorpuscular hyaline bodies may present no amoeboid movements, as they grow larger these movements become active. Hyaline bodies are occasionally observed to change their position within the corpuscle without change in their shape. Manifold shapes are assumed during the amoeboid movements (Plate II. Figs. 4-6). Usually in the course of development a few very fine dark reddish- brown or black pigment granules appear in the outer layer of the PARASITOLOGY. 49 hyaline bodies (Plate II. Figs. 8-12). Tliev may be situated neai- the periphery or on the inner margin of the ring near the elear part. Sometimes the pigment does not appear until shortly before a paroxysm. The presence of many bodies containing a considerable number of grains of pigment is generally indicative of an ini])ending paroxysm. The pigment granules are at first very minute and few, and may be readily overlooked. The granules of pigment increase in number and size, but it is one of the characteristics of the aestivo-autumnal amoebae that the formation of pigment is, as a rule, scanty and in fine grains. Often only one or two very fine pigment granules are seen in the periphery or on the inner edge of the refractive border of the hyaline bodies. Usually about six or seven granules of pigment are developed in the hyaline bodies. The pigment generally shows but little motion in con- trast with that in the tertian amoebse. The sestivo-antumnal amoeboid forms do not generally grow larger than one-quarter to one-third the diameter of the red blood-corpuscle, and they may remain smaller. The infected red corpuscles may appear otherwise normal. They do not become swollen and decolorized in this stage, as is the case in the tertian infections. On the other hand, they often become shrunken, creased, or otherwise deformed, and present a deep brassy color (globuli rossi oUonati of the Italian writers) (Plate II. Figs. 7, 16). Sometimes the haemoglobin separates from a part or the whole of the outer part of the stroma of the corpuscle and collects around the enclosed hyaline body (Plate II. Fig. 13). These changes in the red corpuscles, which are particularly characteristic of the sestivo- autmnnal variety, although not absolutely limited to it, are to be regarded as degenerative or necrobiotic. Marchiafava and Celli and some others have thought that the parasite within these profoundly altered corpuscles is also dead or incapable of further development. Bastianelli states that sporulation forms are not observed in the brassy corpuscles, but this statement is opposed to observations of Marchiafava and Bignami and others. The view that parasites within profoundly altered corpuscles are incapable of further clevelopment is by no means proven, and is opposed to the natural interpretation of many observations. As the time for the onset of a paroxysm approaches, the hyaline bodies gradually cease their amoeboid movements, assume a spherical or ovoid shape, become somewhat more refractive and homogeneous, and present a small collection of quiescent or but slightly moving pigment granules at about the centre or often near the periphery (Plate II. Figs. 13, 16, 17, 18). This pigment usually fuses into a single small, black, round or irregular mass or block (Plate II. Figs. 14, 15, 19-24), or there may be two such blocks. These round, refractive bodies with pigment blocks or collections of pigment granules {cor pi con blocchetto) are the presegmenting bodies, and when they are present the onset of a paroxysm, within at most a few hours, may generally be safely predicted. These bodies are much smaller than the corresponding forms of the quartan and tertian parasites. They do not generally exceed one-quarter or one-third of the size of the corpuscle, although they may be considerably larger. They are sur- rounded with haemoglobin-containing substance of the corpuscle, which is often of a brassy color. Vol. I.— 4 50 3IALARIA. The next phase of development is that of sjjorulation, but the seg- menting forms are found in the peripheral blood only most exception- ally, save in some pernicious cases, in which they may in rare instances be even abundant. SacharofF observed in the Transcaucasus sporulating forms in the blood, and on this account, but apparently without suffi- cient reason, he regards this form as a special variety. For a few hours before and during the early stage of the paroxysm very few parasitic forms of any kind are to be found in the circulating blood, and at this period they may be entirely absent, in marked contrast to quartan infec- tion. During this period the presence of pigmented leucocytes in the blood may aid in the diagnosis. In tertian infections an analogous con- dition is found, but not in the same degree. The disappearance of the parasites from the blood is believed by most authorities to be due to their deposition in internal organs, especially the spleen and the bone marrow, and is attributed to the profound changes in the red blood- corpuscles containing them, these changes rendering the corpuscles vir- tually foreign bodies which, like other foreign particles, are caught and retained especially in the spleen and the bone marrow. Blood Avithdrawn by puncture of the spleen at this time will, with rare exceptions, show abundant intracorpuscular and free round bodies with central or peripheral pigment, and also segmenting forms. In certain cases segmenting forms are few in the sj)leen, but abundant in certain other internal organs, as has been shown by post-mortem exam- inations. These sporulating bodies are smaller than those of the quartan and tertian parasites, and occupy, as a rule, only a relatively small part of the corpuscle, which is always altered in appearance, being shrunken and brassy-colored or more frequently decolorized. They may apjoear to be free or may be actually free. In pernicious cases they are jDresent in large, often enormous, numbers in the internal organs, especially in the spleen and bone marrow, and in some types of pernicious fever in the capillaries of the brain and in those of the intestinal mucosa. This varied distribution of the parasites in internal organs is in relation with the types of pernicious fever. The stage of sporulation occupies a rather long period and takes place in successive groups. This circumstance is believed to explain the long duration of the paroxysm in sestivo- autumnal fevers. In pernicious cases sporulation seems to be going on continually in the vascular areas of certain internal organs. In sestivo-autumnal infections the process of sporulation is in general similar to that of the tertian parasite, but it is more irregular and A'ari- able and the spores are much smaller (Plate II. Figs. 25-28). The number of spores formed by a segmenting sestivo-autumnal organism is extremely variable. There may be not more than six to ten spores, or even fewer ; often there are ten to twenty, and the number may exceed thirty. Some segmenting forms are much larger than others. Golgi has observed exceptionally very large ones containing as many as forty to fifty spores. There are slight differences often to be observed in the finer structure between the sestivo-autumnal spores and those of the quartan and tertian parasites, as will be described when we consider the intimate structure of the malarial parasites. The young hyaline bodies of the new generation may be found in the blood in the early part of the paroxysm, but often they do not make PARASITOLOGY. 51 their appearance until several iiuurs after the l)ei;inning of the paroxysm or durinij; its decline. Not all of the festive-autumnal amoebfe develop pi2:ment. 8porula- tion may occur in bodies, usually of small size, entirely devoid of pio;- ment. As a rule in these cases l)oth pigmented and unpijj^inented forms occur, but cases of aestivo-aiitumnal malaria have been observed, especially in tropical climates, in which only unpigmented bodies could be found at any stage of the fever before the appearance at a later period of crescentic bodies which always contain pigment. As has already been mentioned (page 38) Grassi and Feletti regard the parasites which do not develop pigment as belonging to a distinct variety [HiCinainoeba iiiim((cu/afa), but it is difficult to reconcile this view with the frequent association of pigmented and unpigmented forms, the fre(|uent transitions from one to the other as regards the quantity of pigment developed, and the absence of any points of distinction other than the presence or absence of a variable, but generally small, amount of pigment. Still further researches, especially of the grave tropical malarias, may perhaps demonstrate the existence of a distinct unpig- mented variety of the parasite. There is considerable uncertainty as to the length of the cy<3le of development of the Hpematozoon falciparum. This uncertainty is due to the manner of development of the parasite, usually in multiple groups, in the internal organs, the most characteristic reproductive phases being- absent from the circulating blood. So far as one can judge from the study of these phases in connection with the different types of fever with which they may be associated, the length of the cycle of develop- ment may vary from twenty-four hours or less to forty-eight hours or more. The Haematozoon falciparum may be associated with typical quotidian fever or with tertian fever, and in some of these cases the blood shows apparently only one group of organisms. As already mentioned, Marchiafava and Bignami believe that there are two distinct varieties or subvarieties of the aestivo-autumnal parasite, the one a true quotidian organism, with a cycle of twenty-four hours' duration, and the other their so-called malignant or summer-autumn tertian variety, with a cycle of forty-eight hours' duration ; and this division has been accepted by some other authors. This distinction is based mainly upon the apparent duration of the cycle of development — in the quotidian about twenty- four hours, and in the malignant tertian forty-eight hours, more or less — but there are claimed to be other differences of a minor character relating to the pigmentation, the size, and the amoeboid movements of the organisms.^ The differential diagnosis is said to be possible only ^ The following are the biological aud morphological differences between the sestivo- autumnal quotidian and malignant tertian parasites, according to Marcliiafava and Big- nami {On Summer-Autumn Malarial Fevers, translation, jj. S3, The New Sydenham Society, London, 1894) : Duration of cycle of development in the quotidian, about twenty-four hours, in the summer tertian, forty-eight hours, more or less ; in the quotidian sporula- tion on rare occasions is completed before the amceba^ have become pigmented — this is not observed in the summer tertian : the fine granules of pigment in the 2)erip]iery of the summer tertian are sometimes endowed with oscillatory movements — this is not noticed in the quotidian ; in the same relative stage of development the tertian amceba is usually larger than the quotidian, the adult pigmented tertian forms may be one-third of the size of the red blood-corpuscles, and the forms of segmentation may be one-half or two-thirds of it ; 52 MALARIA. with the adult forms. The diiFerential characters claimed to exist between the quotidian and the tertian varieties of the sestivo-autumnal parasite are, for the most part, only such as one would expect with a malarial parasite develojDing more rapidly in some cases than in others, and they, at least so far as at present formulated, scarcely suffice for a distinction into two well-defined varieties. Thayer and Hewetson, while confirming Marchiafava and Bignami's recognition of quotidian and tertian fevers caused by the sestivo-autumnal parasite, emphasize the occurrence of intermediate types of fever, and in general the essential irregularity of the fevers caused by this organ- ism. They were unable to distinguish any morphological or biological differences between the parasites associated with these various types of fever. Although unwilling to commit themselves to a positive conclu- sion, they are " inclined to believe that the irregularity of the febrile manifestations is due chiefly to the tendency on the part of the parasite to irregularities in the length of its cycle of development (this variability being dependent, perhaps, upon the malignity of the organism or upon the resistance of the individual affected) ; to the fact that the period of time required for the sporulation of one group of organisms is materially greater than in the regular infections, owing to the fact that the arrange- ment of the parasites in definite sharp groups, sporulating nearly at the same time, is much less distinct than in the tertian and quartan inter- mittents ; to the fact that, frequently, organisms in all stages of develop- ment are present at one time, segmentation occurring almost contin- uously." ^ Golgi also considers that Marchiafava and Bignami's division into quotidian and tertian sestivo-autumnal organisms is based upon insuf- ficient evidence, and that the duration of the cycle of development of the sestivo-autumnal parasite is indeterminate, or at least has not as yet been accurately ascertained. This cycle is probably, he thinks, longer than is supposed by Marchiafava and Bignami. This form of parasite, accord- ing to Golgi, is characterized by the fact that it develops entirely in the internal organs, and that the forms, chiefly of the earlier stages of development, which appear in the circulation, although they are found there at certain periods of the disease in practically all cases, are, in a sense, accidentally present in this situation, being washed into the circu- lation from their foci of development, as nucleated red blood-corpuscles may be conveyed from the bone marrow into the blood current in certain ansemias. Golgi at first thought that the forms present in the circula- tion degenerate, but he does not now deny that they may lodge in internal organs and there develop into segmenting organisms. Marchia- fava and Bignami with much reason vigorously contest Golgi's concep- tion of the " accidental " nature of the presence of sestivo-autumnal organisms in the circulating blood, although they also believe that a large part of the parasites develop wholly in the internal organs, and in the tertian the amoeboid movements are maintained longer, even in the adult pigmented forms, and the motion is more lively than in the quotidian during the pigmented phase ; the duration of the non-pigmented amoeboid phase in the tertian is relatively long and may exceed twenty-four hours ; the young forms of the new generation in the tertian usually appear in the blood several hours after the beginning of the paroxysm, which is much later than in the quotidian. ^ Op. cit., pp. 151, 153. PARASITOLOGY. 53 that sporiilation occurs only most exceptionally in tlic circiihiting blood. The two most important and oritrinal points in Golgi's doctrine con- cerning the sestivo-autumnal parasite are that groups of" the parasitic org*anisnis are variously distributed in vascular areas in the internal organs, and there develop more or less independently of each other, "with relative stability," and that a large number of the organisms develop within leucocytes, endothelial cells, and other tissue-cells. All phases of develojjment, according to Golgi, are found within these cells. The spleen and the bone marrow are situations preferred by the parasite, but the capillaries of the liver, of the brain, of the lungs, of the intes- tinal mucosa, may also contain them enclosed within cells. A. Monti ^ has recently described these intracellular forms in perni- cious malaria, and he confirms the observation of many others that cells containing parasites frequently degenerate and die. He finds apparently intact parasites not infrequently within cells, particularly endothelial cells. It is contended by Marchiafava, Bignarai, and Bastianelli that the intracellular inclusions of the parasite, upon which Golgi bases his doc- trine, are simply the well-known phagocytic phenomena, and that such enclosed parasites belong chiefly to the later stages of development (presegmenting and segmenting bodies and spores), and that, instead of developing, they degenerate within the cells. The young amoeboid bodies, which, according to Golgi's doctrine, should be frequently found Avithin cells, they found only with comparative infrequency within pha- gocytes, and then almost always within their corpuscular hosts, which had been swallowed by cells. They admit the possibility of some development of intracorpuscular parasites which have been taken up by phagocytes, but not of free parasites within cells. As with the other varieties of the malarial parasite, the sestivo- autumnal do not all mature and segment. Extracorpuscular forms are common, and it is more particularly these forms, deprived of the pro- tective covering of the red blood-corpuscles, which degenerate. Adult and presegmenting bodies and bodies of the crescentic phase frequently become swollen and pale or vacuolated or fragmented, or throw off buds, or present other degenerative changes which have been described. Phagocytism in the sestivo-autumnal, as in all malarial infections, is a phenomenon of much importance, as will be subsequently explained. The frequency with which two or more groups of parasites in differ- ent stages of development are found in sestivo-autumnal infections has already been repeatedly emphasized. Marchiafava and Bignami believe that even in the pernicious fevers there are not generally present more than two groups of the sestivo-autumnal parasite, and that the short cycle of development and the prolonged period of sporulation suffice to explain the simultaneous presence of parasites in notably different stages of development. Combined infections with the aestivo-autumnal para- site and one of the other varieties occasionally occur. It is important to bear in mind the discrepancy which characterizes sestivo-autumnal malaria between the number of parasites in the blood and the number in the internal organs. In the majority of cases the ^ A. Monti : Bollettino della Society medico-chirurgica di Pavia, 1895. 54 MALARIA. more severe the infection the greater the number of parasites found in the circulating blood, but there are so many exceptions to this that the number of parasites in the blood cannot be considered a trustworthy index of the number within the body. Pernicious cases have been repeatedly observed Avhere the splenic blood examined during life or the internal organs examined after death contained enormous numbers of sestivo-autumnal parasites, although the blood of the finger showed very few. The organisms may be few even in the spleen when they are abundant in the cerebral capillaries or in some other situation. As will be explained subsequently, the varying symptoms and types of perni- cious malaria can be explained in large part by the varying distribution of the parasites in internal organs. It is evident from the description which has been given of the ^stivo- autumnal parasite that this variety is characterized especially by its great activity in multiplication, and it will appear from the considera- tion of the clinical features of the infections caused by this parasite that other most important characteristics are its virulence, greater than that of other varieties, and its greater resistance to quinine. There is a group of bodies of crescentic, fusiform, oval, or round shape, presenting certain common and peculiar characters, which develop only from the Hsematozoon falciparum. The crescents are the most typical of these bodies, which may be designated, therefore, as bodies of the crescentic (or semilunar) phase or group. They merit special con- sideration. Bodies of the Crescentic G-roup. — When a malarial fever caused by the Hsematozoon falciparum has lasted a week or more bodies of the crescentic or semilunar phase are likely to appear in the blood. They are very rarely found in the blood in the latter part of the first week. If the fever is treated with sufficient doses of quinine during the early part of the first week, crescents do not appear, but the administration of quinine after the fever has lasted much longer than a week does not prevent their appearance. They may persist in the blood two weeks or more after all other forms of the parasite have disappeared. In such cases they are often unassociated with any febrile manifestations or any symptoms which can be definitely referred to their presence. If a relapse of the fever occurs, then the young hyaline bodies already described are always present. The crescents themselves are very resist- ant to the action of quinine. Councilman in 1887 called attention to the occurrence of crescentic bodies as characteristic of the irregular and remittent forms of malarial fever and malarial cachexia. There was for a time much doubt as to the origin of the crescents, but Marchiafava and Celli's demonstration in 1886 of their intracor- puscular development has been abundantly confirmed by the later studies of Canalis, Bastianelli and Bignarai, and others. The early intracorpuscu- lar stages of development of the bodies of the crescentic group are rarely seen in the circulating blood, except in certain pernicious cases, but they can often be found in the splenic blood. Bastianelli and Bignami have found these early phases so abundantly in the bone marrow that they consider that they develop by preference in this situation. Certain of the intracorpuscular spherical forms of the Hsematozoon falciparum with collected pigment granules, instead of continuing their PARASITOLOGY. 55 regular cyck' of" development into segment! n*;- I'orins, are transfornied into the young bodies of the seniihinar phase. Tliis transformation tiikes phiee only after a number of febrile paroxysms ; that is to say, only after the parasite has repeatedly passed through its regular sporu- lating cycle of development. Tiie young bodies of the ereseentie group occupy perhaps one-fjuartcr of the red corpuscle. Their shape is round, oval, or fusiform. 'J'hey present a characteristic homogeneous, refractive appearance, being more refractive than the presegmenting bodies with central blocks of pigment. They contain dark pigment, usually in the shape of fine rods, sometimes collected in a mass, but oftener irregularly distributed. In the fusiform bodies the pigment is often arranged along the longitudinal axis of the spindle. The h;emogh)bin is frequently retracted into a denser stratum around the l)odies. These bodies increase in size without a correspond- ingly large increase in the amount of pigment, and, as will be explained later, without a corresponding increase in their chromatic or staining substance — a point Avhich distinguishes the direction of ereseentie devel- opment from that of the regular sporulating development. It is some time after these voung semilunar bodies have beo:un to form in the bone marrow and spleen before the adult crescents appear in the circulating blood. These completely developed typical crescents are on the average 8—10 u long, and in the luiddle 2-3 n broad (Plate II. Figs. 31, 32, 33). They do not often exceed in length one and a quarter or one and a half times the diameter of a red corpuscle. They present a characteristic, homogeneous, refractive appearance. An outer double-contoured border can sometimes be seen, especially after treatment with certain reagents, and this is interpreted by Laveran, Mannaberg, and many authors as evidence of a distinct enveloping membrane ; but the weight of evidence is opposed to the view that the crescents, any more than any other form of the malarial parasite, possess a membrane other than that which pertains to the enveloping red cor- puscle. The outer refractive margin of the crescents, as pointed out by Antolisei and Angelini — who interpret it as a cuticular envelope derived from the red blood-corpuscle — may be slightly colored by haemoglobin, and it may show evidence of this presence of blood coloring matter by the staining with eosin. On the typical crescent-shaped forms a fine line can often be seen stretching like a bow across the concavity, its attachment at each end being within the extremities of the horns. This line is derived from the red blood-corpuscle within which the crescent has developed, and represents the outer contour of the partly or com- pletely decolorized corpuscle. This contour of the corpuscle can some- times be detected also on the convexity of the crescent, and parts of the corpuscle still containing haemoglobin may occasionally be seen on the margin of the crescent, or the whole crescent may be surrounded with haemoglobin-containing corpuscular substance (Plate II. Fig. 29). Sim- ilar evidences of the partly or completely decolorized enveloping blood- corpuscle can frequentlv be seen on the maro;in of the round and oval bodies (Plate II. Figs. 34, 35, 36, 38, 39). Bodies of the ereseentie group are always pigmented. The pigment is very dark in color, often black, and mostly in fine rods. In the typ- ical crescents the pigment, which is without movement and in fine rods 56 MALARIA. and grains, is usually collected in the middle, sometimes in a single clump or in two clumps, often in a coronal shape. Mannaberg emphasizes the frequency with which the pigment is arranged in two adjacent clumps near the centre, presenting a ligure-of-8 shape. In the immature cres- cents the pigment is often scattered, or is arranged longitudinally, as it often is in the fusiform bodies. The amount of pigment varies ; it is often considerable. In certain pernicious fevers young crescents with scattered pigment may be abundant in the blood. In the oval and round bodies the pigment is usually concentrated in the centre, often in the form of a circle, but it may be distributed throughout the body. Ovoid, round, and fusiform bodies may be changed into typical crescents, and, on the other hand, crescents may change into fusiform, oval, and round bodies. The appearance of a fusiform or ovoid body may be presented when a crescent is seen from the convex side. From the round bodies flagellate forms may develop in the manner already described (Plate II. Figs. 42, 43, 44). The sestivo-autumnal flagellate bodies develop only from round bodies of the crescentic group. They are smaller than the tertian flagellates, resembling rather the quartan. The process of transformation of crescentic bodies into oval and round forms, and the development of flagella from the latter, can sometimes be observed in studying the fresh blood microscopically. Councilman once observed a rapid undulatory movement of a body presenting the general appearance of a crescent. Crescents and the other bodies belonging to the same phase not infre- quently become vacuolated or contain or throw off from the margin little hyaline balls (pseudo-gemmation), or disintegrate or present other degenerative changes (Plate II. Figs. 34, 41, 40). Danilewsky has observed crescents of unusually large size, as much as 20-22 /x long and 4-6 fj. broad. The biological significance of the crescents is unknown. These bodies do not belong to the regular sporulating cycle of development of the parasite, and there is no positive proof of their capacity for further development. Dr. Thayer in a personal communication to the writer reports a valuable experiment made by himself which demonstrates the incapacity of crescents when inoculated into the blood of healthy individuals to develop or to cause any symptoms. The blood was taken from a patient who had had acute sestivo-autumnal fever, which was arrested by administration of quinine. Crescents persisted in the blood. For seven days the blood was examined without finding hyaline bodies or any form of the malarial parasite other than crescents. Seven days after the disappearance of the hyaline bodies a hypodermic syringeful of blood containing crescents in considerable number was withdrawn from the median basilic vein of the patient and immediately injected into the corresponding vein of a healthy man. No elevation of temperature or other symptoms followed the injection, nor did crescents or any parasitic forms make their appearance in the blood, which was examined daily for two weeks and at intervals for over a month. In the inoculation experi- ments of Gualdi and Antolisei and others in which it is stated that the blood contained only crescents and infection with the Hsematozoon fal- ciparum followed in the inoculated individual, it is probable that hyaline p. I RA SI TO L a Y. 57 bodies were present in the hlood used for the inocnhition in such small number that they escaped detection. Tiie tbUowino' are the ])rincij)al views whieii have been advanced regarding the interj)retation of the crescents : 1. Laveran regards the crescentic bodies as encysted forms from wliicli the fiageUa develop. There is no proof that these bodies are encysted. 2. Canalis and Antolisei and Angelini believe that they iiave found evidences of s})orulation in the crescents and the ovoid and round bodies belonging to the crescentic phase, Grassi and Feletti and 8a(;harott' likewise believe that these bodies may sporulate. Golgi considers them capable of reproductive development in long cycles, and brings them into special relation with relapses and with fevers of long intervals. Most observers have been unable to iind genuine sporulation or other evidences of reproduction in these bodies. 3. Grassi and Feletti consider that the crescents belong to a separate species which they call Laverania, and of which they represent a regidar phase of development. The sporulating hyaline bodies with which the crescents are usually associated constitute, according to these writers, different species. This view is not generally accepted, and is opposed to the observed facts. ■4. Mannaberg regards the crescents as encysted syzygies formed by conjugation of two sestivo-autumnal parasites and capable of reproduc- tion by segmentation. His view is unconfirmed by any other observer, and is improbable. It fails to explain the ovoid and round bodies which belong to the same phase of development, and it cannot be reconciled with the apj)earances noted in the steps of development of the cres- cents, as has been shown by Bastianelli and Bignami. 5. Councilman suggests that the crescents may be of the nature of spores. Several authors have called attention to a resemblance between these bodies and the falciform spores of coccidia, but there are such essential differences between the two that the apparent resemblance is only of the most superficial character. 6. Bastianelli and Bignami have described the crescents as deviate and sterile forms. This has been interpreted to mean that they regard the crescents as degenerative forms — a view held by Kruse and some others — but in their latest publication ^ they suggest that these bodies are a rudimentary phase of a second developmental cycle which cannot be completed within the human body, but requires for its continuation some new environment in the outer world. They call attention to the occurrence of two cycles of development in several unicellular parasites, especially the coccidia, which, after passing through several generations in their ordinary parasitic life, enter upon forms belonging to a second cycle. The forms of this second cycle remain sterile, degenerate, and die, unless the parasite can escape from its host and find its appropriate new conditions of life. Manson independently also has advanced the hypothesis that the crescents are intended for the continuance of the life of the species in the external world. It has already been mentioned that a similar view has been suggested also regarding the significance ^Bastianelli and Bignami: "vStudi suUa Infezione Malarica," Bullettino delta R. Accademia Medica di Eoma, Anno XX., 1893-94. 58 MALARIA. of the flagellate bodies, and that Manson believes that the mosquito may serve as the host for this second cycle of development. Differential Diagnosis of the Yaeieties of the Malaeial. Paeasite. An inexperienced observer may possibly mistake for the unpigmented intracorpuscular hyaline forms of the malarial parasite the vacuoles which occasionally are present within red blood-corpuscles or the clear spots which may result from certain deformities in the shape of the corpuscles. These vacuoles and clear spots may be distinguished in the fresh specimen by their sharp outlines, the absence of amoeboid changes of shape, and a difference in refraction often suggestive of an empty space or hole, and which can be described less readily than it can be appreciated by actual observation. The absence of definite staining readily distinguishes these vacuoles from the hyaline bodies of the para- site in stained specimens. There are occasionally seen in red corpuscles in stained specimens of the blood, especially in anaemic conditions, small stained dots which do not bear much resemblance to forms of the malarial parasite, but which should be known to the observer in order to avoid the possibility of mistake. They are believed by some to be the result of degenerative changes in the corpuscles, and by others to be remnants of nuclear chromatin derived from the originally nucleated condition of the red corpuscle. Blood-plates can be mistaken only for free spores or very small extracorpuscular hyaline bodies. In general no attention should be paid as regards diagnosis to bodies free in the plasma which resemble blood-plates. In fresh specimens it is practically impossible to diagnose free spores with any certainty. Clumps of blood-plates have been mis- taken for sporulating bodies, but they can be readily distinguished from the latter by the absence of pigment. For the sake of convenience the principal characters which enable us to distinguish each of the three varieties of the malarial parasite, and which have already been described in detail, Avill here be summarized. For modifications and amplification of these general statements the reader must consult the detailed descriptions already given. 1. Duration of the Cycle of Development. — In the quartan parasite, seventy-two hours ; in the tertian, forty-eight hours ; in the sestivo-autumnal, irregular, varying from twenty-four hours to forty- eight hours. 2. Amceboid Hyaline Bodies. — In their earliest stages often indis- tinguishable from each other. Later, those of the quartan parasite, sharply outlined, somewhat refractive, sluggishly amoeboid, with develop- ment of dark brown or black, relatively coarse pigment granules, which have but little motion. Amoeboid movements cease in a relatively early stage of development of the pigmented hyaline body. Those of the tertian parasite, pale and indistinct, actively amoeboid, with development of reddish-brown, actively motile, relatively fine pig- ment granules, which tend to accumulate in the bulbous swellings at the extremities of the delicate branching pseudopodia. Amoeboid move- rARASITOLOGY. 59 ments continue in late stajj^es of development of the pijrniented anioebje. Those ,-shape(l, aetively aiufehoid, with development of a few very tine dark reildish-brown or black, only slightly motile, pigment gr.mnles, or sometimes without j)igment throughout all phases of the sporulating cycle of develo])ment. 3. F'JLLY Developed Hyaline Bodies. — Tliose of the quartan parasite are somewhat smaller in size than the normal red blood-corpuscle, and are usually surrounded by a l)order of the colored refractive sub- stance of the enveloping red blood-corpuscle. Those of the tertian parasite attain the full size of a normal red blood-eorj)uscle and lie in swollen decolorized red blood-corpuscles. Swollen, extraeorpuscular, transparent bodies with dancing pigment granules are common. Those of the lestivo-autumnal parasite do not generally exceed one- quarter to one-third the size of the red blood-corpuscle. The enveloping corpuscle is often shrunken and brassy. They contain much less pig- ment than the quartan and tertian forms, and sometimes none at all. 4. Presegmenting Bodies, — In the process of collection of the pig- ment into a mass or block in the centre or excentrically the pigment grannies often assume a more regular stellate arrangement in the quartan than in the tertian forms. The differential points between the three varieties in this stage relate to the same differences in size, in the amount of pigment, and in the condition of the infected corpuscle as have been mentioned under the preceding heading. The presence in the blood of quartan and tertian presegmenting bodies is associated with that of sporulating forms, wdiereas ^vith the sestivo-autumnal presegmenting bodies sporulating forms are almost always missed in the circulating blood. 5. Sporulatixg Bodies. — Those of the quartan parasite in equal proportion in the peripheral and the splenic blood. They are some- what smaller than the red corpuscles, and present typical rosette forms with a division into six to twelve ovoid or pyriform segments, each segment becoming an oval or round spore containing a bright nucleiform dot. Those of the tertian parasite are more numerous in the splenic than in the peripheral blood. They are as large as the red blood-corpuscle, and present less regularity in segmentation than the quartan parasite. They segment usually into from fourteen to twenty spores, which are a little smaller and with less distinct nucleiform dot than those of the quartan organism. Those of the lestivo-autumnal parasite are found only most excep- tionally in the circulating blood in ordinary cases. They are abundant in certain internal organs, including, as a rule, the spleen. They do not generally exceed one-third to one-half the size of the red blood-cor- puscle. They segment irregularly, the number of spores being some- times six to ten, sometimes ten to twenty or even more. The spores are smaller than those of the quartan and the tertian parasites. The stage of sporulation is a prolonged one. 6. Behavior of the Ixfected Corpuscles. — These often become 60 ITALAEIA. somewhat shrunken and deeper in color in the quartan infections; swollen and decolorized in the tertian ; and shrunken and brassy, some- times with retraction of haemoglobin from the outer part of the cor- puscle, in the sestivo-autumnal. 7. Crescentic Bodies. — Crescents and bodies of the crescentic phase appear only in infections with the aestivo-autumnal parasite. 8. Pigmexted Leucocytes. — Most abundant during and shortly after the paroxysm, they usually disappear during the period of apyrexia in quartan and tertian infections, whereas it is not uncommon to find them in all periods of sestivo-autumnal infections. The Intimate Structure of the Malarial Parasite. The first systematic study of the finer structure of the malarial parasite was made by Celli and Guarnieri (1888-89). This was followed by similar investigations by Grassi and Feletti, Romanowsky, SacharoflF, Mannaberg, Antolisei, and Bastianelli and Bignami. The small size and the but slightly differentiated appearance of most forms of the parasite, and the difficulty of obtaining clear differential stain- ings, obscure the insight into their intimate structure. Little detail of structure can be made out in unstained specimens. The substance of the parasite presents in general a homogeneous, color- less, hyaline appearance. In the amoeboid hyaline bodies of the quartan and tertian parasites, particularly in the larger forms, an area of variable size in the centre, or more frequently excentrically placed, may sometimes be differentiated by its clear, pale appearance from the more refractive outer zone. This area corresponds to the unstained structure interpreted by many observers as the nucleus in stained specimens. Occasionally two or more such clear spaces can be seen. Sometimes in the larger amoeboid and the mature forms a finely granular appear- ance of the protoplasm can be detected. It is particularly characteris- tic of the sestivo-autumnal parasite that the young intracorpuscular hyaline bodies show, when at rest, a clear space surrounded by a ring of protoplasm, usually thin and delicate on one side and thicker on the other. This clear space appears unstained on stained specimens. The mature forms in which the pigment has collected into one or more clumps appear uniform in structure in fresh specimens, or may perhaps present a slightly granular appearance. Within the spores, especially distinctly in those of the quartan parasite, a bright body can often be distinguished, which represents the nucleus or a nucleiform material. The methods for staining the parasites will be described under Diagnosis, ^age 139. These methods are useful, not only for the study of the finer structure, but also for the ready detection of the unpig- mented young hyaline forms, particularly of the sestivo-autumnal parasites, which may, without very careful observation, escape recogni- tion on fresh specimens, whereas the presence of pigment at once attracts attention in the fresh specimens to the other parasitic forms. On suitably stained specimens the intracorpuscular young hyaline bodies show a stained outer part, an unstained, usually excentrically placed, internal part, and one or more deeply stained round or elon- gated particles situated, as a rule, near the border of the stained and PARASITOLOGY. 61 unstained parts. Tlie constant unstahu'd [)art is not to he confounded with vacuoles which may occasionally be present. There have been various interpretations of the structures thus ditlerentiated. Celli and Guarnieri desi»>nuted the stained part as ectoplasm and the unstained part as end(»plasni. The deeply staining particles they interpreted as the beginniui;- ditferentiation of a nucleus, whi(!h they thought they could reeogni/e in larger forms as a definite, stained or pale Ixxly with- in the endoplasni. Grassi and Feletti do not recognize a division of the protoplasm into ectoplasm and endoplasm, and in this they are followed by most observers. The clear unstained part they interpret as a relatively large, vesicular nucleus, and the deeply staining particles as nucleoli i'rom which may proceed a delicate reticulum of chromatin connecting them with the nuclear membrane which they assume to exist. The rest of the bladder-like nucleus is filled with clear nuclear juice. Although not all of these details in the structure of the nucleus, such as the membrane and the reticulum, have been observed by sub- sequent investigators, Grassi and Feletti's interpretation of the un- stained })art as a nucleus and of the deeply staining particle as a nu- cleolus or a concentration of nuclear chromatin has been adopted l)y Celli and Sanfelice, Romanowsky, Sacharoff, and Mannaberg, and has been widely accepted. Bastianelli and Bignami, while not denying that this interpretation is applicable to the quartan and tertian amoebae, adopt a different view as to the structure of the aistivo-autumnal amoebae, which they have studied with great care. They differentiate in the latter an outer colored, chromatic cytoplasm in the form of a stained ring, usually thicker on one side, and an inner uncolored, achromatic cytoplasm, which is all of the clear part enclosed by the ring. The deeply staining chromatic particle they find in the chromatic and not in the achromatic cytoplasm. Often there are two particles, each at opposite points in the ring. This particle is the only representative of nuclear material in the parasite, and they interpret it as fulfilling the functions of a nucleus. They consider that the rapidity of development and multiplication of these sestivo-autumnal parasites prevents the formation of a definite nucleus in a resting stage, such as is described for the quartan and tertian forms. According to Grassi and Feletti and Romanowsky, the nucleus and nucleolus can be found in all stages of the regular cycle of development of the parasite. The nucleus di\'ides directly — or, according to Roman- owsky, by karyokinesis — to form multiple nuclei just before sporula- tion, each nucleus then entering into the structure of a spore. The evidence, however, is in favor of the view that at a certain stage of development the nucleus and the nucleolus disappear as differentiated structures, the latter to reappear in multiple form shortly before sporu- lation. Mannaberg was the first to demonstrate this clearly in his studies of the structure of the tertian parasite. He observed that as the amoeboid bodies approach their mature form, and then become the pre- segmenting bodies, the deeply staining particle (nucleolus) disappears, and later the clear, previously unstained part (nucleus) stains diffusely, so that there is in this stage no definite differentiation of structure in the parasite, although the outer part, as a rule, stains more deeply than the 62 3IALABIA. central part. He, however, speaks of the outer part, which contains pigment granules, as the " plasma part," and the inner part, into which the pigment does not penetrate, as the " nuclear part." He attributes the deeper and more diffused staining of the parasite in this stage to the solution of nuclear chromatin into the protoplasm. The first evidence of sporulation on stained specimens is furnished by the appearance of numerous small, deeply staining granules of chromatin in the periphery of the protoplasm. These are the forming nucleoli, which increase in size, and around each the general protoplasmic substance, during the process of segmentation, divides, so that each segment or spore is a cell composed of a nucleiform, deeply staining body surrounded by its pro- toplasmic envelope. In the quartan and tertian spores a clear unstained part later is usually diiferentiated around the chromatin granule, and the nucleus now resembles that seen in the young amoeboid hyaline bodies within the red corpuscle. Bastianelli and Bignami likewise demonstrated the disappearance of the deeply staining nucleiform body in the forms of the sestivo-autumnal parasite containing collected pigment (presegmenting bodies), and soon afterward the appearance of diffuse staining in the previously achro- matic cytoplasm, so that in this stage no sharp differentiation of struc- ture can be made out within the parasite, which is richer in chromatic material than before the disappearance of the nucleiform body. The first sign of sporulation is the formation of multiple nucleiform chro- matin granules in the periphery and the development of spores proceeds in the manner already described, save that the sestivo-autiminal spores are composed only of the deeply staining nucleiform body immediately surrounded by cytoplasm. The presence of the small, clear, unstained part, which with the chromatin particle is interpreted as the nucleus, often seen in the tertian and quartan spores, is rarely observed in the sestivo-autumnal spores. It is evident from this description that the spores of the malarial parasite possess a definite structure, a most important feature being the presence of a deeply staining body which serves the function of a nucleus. The recognition of this structure renders it possible to dis- tinguish from genuine spores the various pseudospores which have been at times erroneously interpreted as phases of reproduction of the para- site, and which belong to the category of degenerative forms. Although Antolisei has described a double contour, which he interprets as a mem- brane, about the spores, this observation has not been confirmed, and the spores are to be regarded as naked, thus belonging to the class of gymnospores. Some have objected to the designation of these segments as spores, but this nomenclature is in accordance with that employed by zoologists for similar bodies formed in a like manner in certain other unicellular organisms. It is evident from the preceding description that investigators are not wholly agreed as to what structure in the malarial parasite shall be called the nucleus, some applying this name to an unstained part con- taining the deeply staining chromatin particle, others regarding the chromatin granule itself as the only representative of the nucleus. There is, however, general agreement that this deeply staining particle or body is an essential constituent of the nucleus, and that the PARASITOLOGY. 63 presence of a nucleus or of a nucleifonn body in tlic parasite has been demonstrated. This (h'luonstratiou fulfils the important hiolo^ieal con- dition that sometiiing- performing' the functions of a nucleus belongs to every cell capable of reproduction, and it has served to remove any lin- gering doubt which may have been entertained as to the recognition of these bodies as j)arasitic organisms. It is interesting to note that during the regular cycle of develop- ment there is a continual increase in the amount of staining or chro- matic substance from the small hyaline body to the sporulating bodies, and that the cell becomes multinucleated just before segmentation occurs. As the chromatic substance is to be regarded as endowed with especial functional activity, these changes are highly significant. The mature crescents, as a rule, stain feebly and diffusely, or often only at the poles, and perhaps also along the margin. Near the middle one or two deeply stained granules, often covered up by the pigment, may be present, but they are not constant. Mannaberg finds often a narrow stained band in which are two or more deeply stained granules, stretching across the middle of the crescent. Bastianelli and Bignami find that the young developing bodies of the crescentic phase stain diifusely and less intensely than the bodies with a central block of pigment which develop into segmenting forms. Whereas in the forms of the parasite which develop into sporulating bodies there is a continual increase in the chromatic substance as the bodies continue to develop, in the develop- ment of the semilunar bodies there is no correspondingly large increase of staining substance. With rare exceptions these observers found no chromatin granules in these developing crescentic bodies, nor did they ever find in any body of this group those changes of structure, such as the appearance of several chromatin granules, which indicate sporu- lation. Laveran, Celli and Guarnieri, and, wdth especial emphasis, Manna- berg, consider that the crescents are enveloped in a double contoured membrane. A number of other observers have also adopted this view. We do not consider that any definite membrane, which can be regarded as a part of the parasite itself, has been satisfactorily demonstrated around the crescents or around any form of the malarial parasite. A double contour can sometimes, but not regularly, be seen in the peripli- ery of the crescents, but this alone cannot be considered as proof of the existence of a membrane. The manner in which little hyaline pieces (pseudo-gemmation) can sometimes be seen to form at the margin of the crescentic bodies speaks against the presence of an actual membrane. The Malarial Pigment. The question as to the origin of the malarial pigment, which was so long discussed without conclusive result before the discovery of the malarial parasite, has been definitely settled by this discovery. The pigment is formed by the parasite out of the haemoglobin of the blood- corjjuscles by w^hat may be regarded as a process of digestion. The pigment occurs in the form of little granules, which may be fine or coarse, and of distinct rods and spicules, which may be as much as 1 fi long. Such rods often present a certain superficial resemblance to 64 MALARIA. deeply stained bacilli. The pigment may occur in the form of extremely fine dust-like particles not easy to detect. It may be fused into black blocks. The color varies from a yellowish-brown or rusty, reddish- brown to black. Laveran speaks of fire-red and even light-blue pig- ment, and Rosenbach observed a greenish hue of the pigment. The malarial pigment is somewhat loosely ranked by pathologists among the melanin pigments. The differences in the characters of the pigment belonging to the different varieties of the malarial parasite have already been sufficiently described. The deposition of the pigment in the various organs will be described under the Pathological Anatomy. Since the examinations of malarial pigment by Meckel and by Frerichs it has been known that concentrated sulphuric acid and hydrochloric acid do not alter it, and that it disappears upon the addition of strong alkalies and of chloride of lime. Kiener observed that the pigment is dissolved by ammonium sulphide. The demonstration of the origin of the malarial pigment from the blood coloring matter at once raised the question whether, like many pigments of hsematogenous origin, it contains iron demonstrable by our micro-chemical tests. A statement by Perls as long ago as 1867, that pigments in the spleen of intermittent fever respond to the test for iron, has given rise to much confusion. It is not wholly clear that Perls examined the malarial pigment, but, if he did, there can be no doubt that he mistook for the true malarial pigment other pigments which are abundantly present in certain organs of those dead of malaria, and which respond to the chemical tests for iron (hsemosiderin). It has been shown by Neumann, Bignami, Stieda, Dock, and others that the pigment formed directly by the malarial parasite does not contain iron in a combination which will respond to our ordinary micro-chemical tests for this element. This, of course, does not prove that it may not contain iron in some combination, such as that in hsemoglobin, which cannot be demonstrated by our micro-chemical reactions. As has been pointed out by the writers named, the organs of those dead of malaria, particularly the spleen, the liver, and the bone marrow, contain a large amount of hsemosiderin, the presence of which is doubtless to be ex- plained by the extensive destruction of red blood-corpuscles in malaria. There is no evidence that hsemosiderin is formed directly by the malarial parasite. Marchiafava (1889), however, has advanced the hypothesis that the black pigment may be formed not only within the malarial parasites, but also within the leucocytes out of red corpuscles altered by the action of the parasite. He thus explains the intense melanosis of the spleen, liver, and bone marrow in certain sestivo-autumnal per- nicious infections where the parasites appear only slightly pigmented. Bignami ^ comes also to the conclusion, from his extensive examinations of melanotic organs in malaria, that the black pigment without micro- chemical iron reaction may have this double origin, being formed either within the malarial parasite without an intermediate hsemosiderin stage or within cells out of hsemosiderin derived from destroyed red corpus- cles. The objection to this conclusion of Bignami is that hsemosiderin is found in the liver, spleen, and bone marrow very commonly in ansemias, but that the black pigment, without micro-chemical iron '■ Bullettino della Beale Accademia Medica di Roma, Anno xix. fasc. ii. p 230, 1893. PARASITOLOGY. 65 reaction, Avliich cluiractcrizcs inalacial iiiicctioiis, docs not n])i)car inidcr those oontlitions. It is possible tliat the niahirial parasite may j)ro(hice some ehemieal ehaii«!:e in the suhstanee of the red hlood-eorpuseU' whieh permits the transformation of the speeitieally altered luemo^lobin into black malarial jiiginent Avithin certain cells of the body. This, how- ever, is a pnre hypothesis. PllA(;()('YTISM. The presence of malarial j)igment in leucocytes and other t-clls has long been known. Since the observation of phagocytic phenom- ena in malaria by Laveran, Marchiafava and Celli, and Metchnikoif, important studies of this subject have been made, especially by Guarnieri, (iolgi, Bastianelli, and Marchiafava and Bignami.' These investigations have shown that phagocytosis is a common and import- ant phenomenon in malaria, although there is much difference of opinion as to the interpretation of some of the observed facts. Some assign to the phagocytes no higher role than that of scavengers charged with the collection and removal of the pigment and debris resulting from the activities of the malarial parasites and from the death and disintegration of the parasites themselves. The amount of slag which is produced in severe cases of malaria in the form of pigment, dead and disintegrating red blood-corpuscles, and degenerated and broken-up parasites is so large that even this office of scavengers becomes an important one. But ]Metchnikoff, Golgi, and some others believe that the phagocytes devour large numbers of intact, healthy parasites in certain phases of their development, and that in this contest between cell and parasite is to be found the most important agency for the de- fence of the body. The arguments for and ag-aiust this latter concep- tion are essentially similar to those which are adduced as to the phago- cytic theory in bacterial infections, the main difficulty being to deter- mine to what extent fully active and virulent parasites are taken up and destroyed by phagocytes, and, even admitting the occurrence of this mode of disposal of the parasites, whether or not it is the most essential and the predominant factor in their destruction. That malarial para- sites, as well as bacteria, may perish in the blood plasma without incor- poration within cells cannot be doubted, as we have direct observations demonstrating this. The cells which assume the functions of phagocytes in malaiia are the leucocytes, the endothelial cells of the walls of the bloodvessels, and large cells, found especially in the spleen, the bone marrow, and the liver, and called by ]Metchnikolf " macrophages." Of the leuco- cytes the large mononuclear, the polymorphonuclear, and the transitional forms act as phagocytes. The small lymphocytes and the eosinophils have never been observed to contain pigment or debris in malaria. Of the leucocytes it is the large mononuclear forms which are the most active and important phagocytes within the body in malaria, but, as has been pointed out by Thayer and Hewetson, the polymorphonuclear leu- ^ Especially valuable are tlie articles of Golgi, "II fagocitismo nell' infezione malarica," liiforma Medica, 188S, and of Bastianelli, "I leucociti nell' infezione malarica," Bull, delta B. Accademia Medica di Bouia, 1892. Vol. I. — 5 66 MALAEIA. oocytes are the ones which can be observed to be active in the fresh blood during examination under the microscope. It is the latter which pick up the pigment and the extracorpuscular and degenerated parasites, and which attack the flagellated bodies in the fresh blood withdrawn from the body, so that there may be a notable diiference between the blood examined immediataly after its withdrawal from the body and that examined at a later period as regards the number of polymorpho- nuclear leucocytes containing foreign elements. Endothelial cells con- taining pigment, parasites, or fragments of parasites or of red corjjuscles are rarely seen in the circulating blood withdrawn for microscopical examination ; but the study of microscopical sections of organs of those dead of malarial infections shows that the endothelial cells lining the capillaries and small bloodvessels, especially those of the spleen, bone marrow, and liver, in certain cases also of the brain, intestine, and other parts, manifest extensive phagocytic activities. So too the macrophages, although they have repeatedly been found in the circulating blood, are met with chiefly in the splenic blood and in the microscoj)ical examina- tion of organs of those dead of malaria. These macrophages, which may attain an enormous size and are frequently destitute of jiuclei, and therefore necrotic, are mononuclear cells derived probably in part from mononuclear leucocytes and certain fixed cells of the pulp of the spleen and bone marrow. Their contents may be varied, consisting sometimes within one cell of pigment, intact or degenerated parasites, and red blood-corpuscles and entire smaller phagocytes. Dock has counted as many as twenty parasites within one phagocyte in the spleen. Under Pathological Anatomy will be described the appearances of these various phagocytes as seen in sections of the diflFerent organs of the body. The foreign elements which are found within these phagocytes in malaria are — (1) malarial pigment; (2) yellowish or reddish-yellow pig- ment derived directly from disintegrated red corpuscles (hemosiderin) ; (3) red corpuscles, sometimes intact, but usually more or less altered and fragmented ; (4) malarial parasites, either free or enclosed within red corpuscles, which are usually altered, such parasites appearing some- times intact, often degenerated and fragmented ; (5) particles which are probably often derived from the disintegration of parasites, but which do not present appearances sufficiently characteristic to enable one to determine their origin. It has already been mentioned that a phagocyte may be enclosed by a macrophage. Leucocytes either with or without pigment may be thus enclosed. As phagocytes and other cells often degenerate and become necrotic and disintegrated in malaria, it is evident that from this source may be derived material for inclusion within living cells. First in order of frequency are phagocytes containing malarial pig- ment. In the examination of malarial blood obtained from the periph- eral circulation the only form of phagocyte which is to be seen with any frequency in the perfectly fresh specimen is the melaniferous leucocyte. Leucocytes containing clearly recognizable parasites are rarely, if ever, seen in the freshly drawn specimen of peripheral blood. Macrophages containing definite parasitic forms may occasionally be found in this situation. Both mononuclear and polymorphonuclear leucocytes may contain the pigment, but in the perfectly fresh specimen the former PARASITOLOGY. 67 preponderate. The })i<>ineiit is t'oiind must fV('(|U('ntly in tlie form of bloeks and eoarse <»ranules, eorresponding to that set free by tlie process of sporulation, but sometimes the pigment within the leucocytes is in fine rods and grains, sucli as belong to the earlier stages of develop- ment of the j)arasite. The inference is a probable one that in the latter ease the leucocyte may have enclosed the ])arasite. As has alri'ady been stated, in tlie fresh blood remo\ed from the body and examined for a while under tlie microscope the ))olyniorpho- nuclear leucocytes can be seen to engulf 2)igment and certain parasitic forms — viz. extracorpuscular forms, es])ecially degenerated and frag- mented forms, segmenting forms and spores, and altered red corpuscles — and es])ecially do they attack the flagellate bodies, as has been demonstrated by Thayer and Hewetson (Plate II. Figs. 45-49). Such enclosed ])arasitic forms, with the exception of the spores, can be seen rapidly to become indistinct and unrecognizable within the leucocytes. From the examination of the fresh circulating blood alone one obtains a very inadequate conception of the extent and nature of the phagocytic ])rocesses in malaria. A fuller idea of these processes can be derived from the study of blood withdrawn by puncture of the spleen, where phagocytic phenomena are far more active than in the circulating blood ; but it is especially in the microscopical examination of the organs of those who have succumbed to a malarial attack that the best oppor- tunity is afforded to learn the extent of phagocytosis in malaria. Here one flnds abundantly leucocytes, endothelial cells, and macrophages con- taining pigment, parasitic forms, and altered red blood-corpuscles. Parasites in their later stages of development, especially when they are free, are frequently taken up by phagocytes — in their early stages rarely, unless they have become extracorpuscular or the corpuscle con- taining them is degenerated. Sporulating forms, and somewhat less frequently forms with collected pigment (presegmenting bodies), are the ones most commonly found in a recognizable condition within the phago- cytes. It is stated by Bastianelli and Bignami that the bodies with pig- ment blocks (presegmenting) are found most frequently within macro- phages, and sporulating forms within polymorphonuclear leucocytes. Pigmented amoebse they found rarely, and red blood-corpuscles contain- ing unpigmented amcebse very rarely, Mithin phagocytes. Bastianelli gives the follomng as the order of frequency in which the various para- sitic elements are found within phagocytes : (1) pigment; (2) sporulat- ing forms and spores ; (3) red corpuscles, normal or decolorized, con- taining sporulating forms or bodies with central pigment blocks ; (4) brassy and decolorized red corpuscles containing plasmodia (hyaline bodies in the amoeboid stage) ; ( 5 ) free bodies with central pigment clumps ; (6) more rarely free amoeba or red corpuscles of normal appear- ance containing parasites in the amoeboid stage. According to the obser- vations of the writer, free bodies with central pigment clumps occupy a higher place in this scale than that assigned to them by Bastianelli. Crescents enclosed in phagocytes may be found even in the circulating blood. The various bodies within phagocytes often lie in an area sur- rounded by a clear zone like a vacuole. Golgi (1887-88) discovered that phagocytosis occurs in quartan and tertian infections with a definite periodicity which stands in relation to 68 MALARIA. certain phases in the cyclical development of the parasite, and therefore to certain periods of malarial fever. This is readily understood Avhen one considers that it is especially the free pigment and the mature and segmenting parasites and the degenerative forms which are taken up by phagocytes. The pigment is liberated by the process of sporulation which, as has already been explained, occurs shortly before and during- the early stages of the paroxysm. Corresponding with this, Golgi found that pigmented leucocytes are present in the circulation during the paroxysm and for a short time afterward, and that they disappear from the circulation during the apyrexia. This periodicity in the appearance of melaniferous leucocytes and of other phagocytes can be observed regularly in quartan and tertian infections. There are frequently indi- cations of it also in sestivo-autumnal infections, but on account of the irregularities in the cyclical development of the Hsematozoon falciparum,, of the prolonged period of sporulation, of the frequent occurrence of multiple groups of parasites, and of the presence at all periods of degenerated red corpuscles, this periodicity in the occurrence of phago- cytosis is often obscured or is not manifest at all. Pigmented leucocytes may be found in many cases of sestivo-autumnal infection during all periods of the disease, although they are more numerous during the paroxysm and shortly afterward. In the severe prolonged cases they are generally abundant, and they may persist in the circulation for sev- eral days after cure is eifected. As long as crescents are present pig- mented leucocytes may be found. Parasites which, to all appearances, are normal are found within phagocytic cells, AVhat is the fate of such enclosed parasites? That many degenerate and die cannot be questioned, for these degenerative alterations can be directly observed in progress under the microscope in examining fresh blood, and in studying malarial blood and tissues one frequently encounters evidences of this fate of the parasites. It is claimed, however, by Marchiafava, Bignami and Bastianelli that enclosed spores, although prevented from further development, may survive for a long time within leucocytes and other cells, and that such latent spores- may after an indefinite period be set free and cause by their development a relapse of the fever. Attention has already been called to Golgi's belief that the astivo- autumnal parasite may, and to a considerable extent does, develop within the leucocytes and endothelial cells of internal organs, in ordinary cases chiefly of the spleen and bone marrow. He adduces a number of considerations in support of this view, but the objective evidence he and his pupil, A. Monti, find in the detection of the frequent presence of this parasite, apparently intact and in all stages of development, within these cells. In opposition to Golgi, however, it is claimed by Marchia- fava, Bignami and Bastianelli that early phases of development of the parasite are rarely seen within the cells, and that, therefore, the much more commonly enclosed late phases cannot have developed within the cells from young parasites. Golgi also brings to his support the obser- vation, made by all who have studied the subject, that many of the cells containing parasites degenerate and die, as is made evident especi- ally by the loss of their nuclei. He interprets this as meaning that in. the conflict between cell and parasite the latter often comes ofl' the PARASITOLOGY. 69 victor. FiirtluT investigations arc needed to determine to what extent Oolgi's doctrine as to the intercellular residence and development of the Hsematozoon falciparum is correct. Certainly the greatly prepon- derating nunii)er of intact tTestivo-autumnal parasites observed in exam- ining the organs of those dead of pernicious malaria are found within free red blood-corpuscles in the vessels of internal organs. The theory of Metchnikoff that the essential factor in the resistance of the body to the malarial parasite resides in the activities of phago- cvtes is opposed by many considerations. The most important factors in determining the gravity and the course of a mahirial infection are the degree and (piality of virulence possessed by the parasite, on the one hand, and the resistance of the individual receiving the parasite, on the other hand. There is no evidence that phagocytic functions are in abeyance in severe and pernicious cases of malaria. On the contrary, we find here often enormous numbers of parasitic enclosures within ])hagocytes. There is no proof that spontaneous recoveries from malaria are associated with an increase of phagocytic activity. Inasmuch as phagocytes regularly attack degenerated and fragmented parasites, and as we know that such degenerations occur frequently \\nthin parasites free in the plasma, it is permissible to suppose that many of the para- sitic forms found within phagocytes were already impaired in their vitality before they were engulfed by cells. After the administration of (piinine, which directly injures the malarial parasite, a distinct increase in the number of phagocytes has been often observed. Certainly qui- nine does not stimulate the leucocytes to swallow the parasites. Here the increase in the phagocytes must be attributed to the increase in the numl^er of damaged parasites. There is evidence that the blood-plasma may exert a parasiticidal effect upon the malarial organism, as well as ujjon other protozoa (Fag- gioli), when the parasite has escaped from the protective covering of the red blood-corpuscle. The period when the largest number of malarial parasites are destroyed is that of sporulation and of free spores, and it is during this phase of the life-history of the parasite that quinine acts most effectively. We may, at least provisionally, adopt a theory to explain natural resistance to the malarial parasite similar to that which many accept regarding resistance to bacteria — \\z. that the parasites are destroyed by parasiticidal substances contained both in the plasma and within leucocytes and other phagocytic cells. The substances injurious to the parasite are in the last analysis furnished to the plasma by the cells, and are in a more concentrated or potent form within the cells than in the fluids. This theory assigns to the phagocytes a higher role than that of mere scavengers. They are endowed in especial degree with the power of destroying the parasite, but this power is shared by the plasma. Pathogexesis. The discovery of the malarial parasite has placed within our reach the means of solving many problems concerning malaria which we could not formerly even attack with any hope of success. Already we have attained a satisfactory understanding of not a few previously unexplained manifestations of malaria, and other formerly obscure malarial phenom- 70 MALARIA. ena have been brought at least within the range of our comprehension. Much still remains to be elucidated, but we cannot doubt that further studies will continue to throw fresh light upon what remains obscure. In the description of the symptoms and lesions of malaria attention will frequently be called to their relations to the parasite, and in this connection only certain salient points, relating more particularly to pathogenic properties of the parasite, require consideration. The mere presence of the malarial parasite in the body is not suf- ficient to cause symptoms. The organisms must have multiplied to a certain point before their presence is manifested by recognizable symp- toms. The bearing of this fact upon certain malarial phenomena, more particularly upon the varying periods of incubation as determined by experimental inoculations of malarial blood and upon fevers with long intervals, will be considered in the clinical part of this article. It may be stated as a general rule, which was first formulated by Golgi, that the larger the number of organisms present in the body the more severe are the manifestations of the disease ; but the number of the organisms is by no means the only factor which determines the gravity of the disease. The variety of parasite which is concerned in the infection is a factor of fundamental importance. The quartan variety produces the mildest attacks, the tertian is more virulent than the quartan, and the sestivo-autumnal variety is the most virulent of all, and is the one which is almost exclusively associated with the pernicious attacks. These variations in virulence are best explained upon the assumption that the malarial organism produces toxic substances of varying virulence according to the variety of parasite. There is also clinical evidence that one and the same variety may vary in virulence, so that, for example, some sestivo-autumnal parasites are more virulent than others. In seeking an explanation of the varying clinical characters of mala- rial infections we have to reckon not only with the number, the varie- ties, and the virulence of the parasites, but also with several other factors, such as predisposing conditions on the part of the individual infected, the occurrence of multiple groups of the parasite, the distri- bution of the organisms in internal parts, the circulatory and other ana- tomical disturbances induced by the parasites. Periodicity is the most striking clinical characteristic of malarial fevers, and the explanation of this phenomenon has exercised the minds of pyretologists from ancient times. It is true that intermittence is not limited to fevers of malarial origin, but regularity of rhythm in the occurrence of the paroxysms is especially characteristic of malaria. One of the most interesting additions to our knowledge resulting from the discovery of the malarial parasite is the demonstration by Golgi, which has been abundantly confirmed, that this rhythm in the malarial paroxysms corresponds to a rhythm in the development of successive generations of the parasite. The onset of each paroxysm corresponds to the ripening and sporu- lation of a generation of parasites and the setting free of a new brood.^ ^ The old idea that the periodicity of malarial fevers depends upon the periodical production in the blood of a materia peccans is thus confirmed. It is interesting in this connection to note the line of argument presented by Griesinger in his admirable and sug- PARASITOLOGY. 71 Kxactlv what the connection is hctwccn this act oi" sporulation, with the lil)crati()n of a fresh brood of yoiin<;- parasites, and tlie cansc of the febrile jjaroxysni, is not dctiniteiy known. It was at first snggested by Golj^i (1887) that the paroxysm is due to the invasion of the red blood- corpusch^s by tiie new grouj) of parasites, but it was shown by Antohsei (181X)) that the paroxysm (lei)ends rather upon the act of segmentation than u|)on the invasion of the bh)od-corpusch'S by a new generation of organisms, for quinine, administered before a paroxysm in suificient (piantity, may, by ck\stroying the fresh brood, completely prevent the invasion of the red corpuscles, but it cannot prcv(;nt the segmentation and the impending paroxysm. The view is now widely held, and seems j)huisible, that in the act of sporulation and of liberation of the spores chemieal poisons are set free, and that these poisons, by their action on the nervous centres concerned in the production of fever, cause the febrile paroxysms. This toxic theory of malaria has been elaborated especially by Baccelli. The fact that the malarial parasite resides in, feeds upon, and de- stroys the red blood-corpuscles furnishes an entirely satisfactory explan- ation of two of the most characteristic and important manifestations of malaria — the melantemia and the anaemia. The malarial pigment, for which we formerly had no adequate explanation, is formed as an un- digested residue within the body of the parasite by metabolic processes directly out of the haemoglobin of the infected red blood-corpuscle. Various stages of the formation of the pigment within the parasite can be seen. The liberation of this pigment, its inclusion by phagocytes, its deposition in various internal organs, have all been described, and will be further considered under the Pathological Anatomy. The relations of the biological characters of the parasite to malarial anaemias and to haemoglobinnria will be fully considered in the anatomical and clinical parts of this article (pages 93, 116, 125, and 130). The ways in which the red blood-corpuscles may be altered by the action of the malarial parasite are various. The extent of these changes varies with the variety and the virulence of the parasite. They are least in quartan infections, greatest in the aestivo-autumnal. The in- fected blood-corpuscle may appear otherwise normal. It may be swollen or shrunken or variously deformed. It may divide into two or more pieces. It may be partly or completely decolorized, or the haemo- globin may separate from the stroma and be dissolved in the plasma, or may be concentrated around the parasite. Especial significance in the aestivo-autumnal infections attaches to that alteration in the cor- gestive article on the malarial diseases ( Virchow's Handb. d. spec. Path. u. Themp., Bd. ii. Abth. 2, 2te Auflage, p. 41, Erlangen, 1864) : "Tlie cause of the periodicity of the fever cannot, therefore, be referred to the disposition of the nervous system to rhytlimical vital actions, as many have formerly done, but it must, at least according to our present although very incomplete knowledge concerning the causes of heat, be attributed to some- thing periodically occurring in the blood, wliich is connected with the increased produc- tion of heat. It has been formerly conceived that a certain substance, a materia peccans, appears periodically in the blood and incites the febrile heat and reaction : this material requires for its production and complete development sometimes longer, sometimes shorter, periods, and herein lies the cause of the rhythm of the fever As an explanatory hypothesis this conception accomplishes more than the later attempts at explanation The continuous morbid process which causes the poisoning incites periodically changes in nutrition or in the blood which arouse the nervous apparatus to abnormal manifestations." 72 MALARIA. puscle which has been repeatedly referred to as the brassy change, on account of the resemblance in the color of the shrunken corpuscles to brass, sometimes compared also to copper or old gold. Nor are the corpuscles which are actually infected by the parasite the only ones which may be altered. Uninfected corpuscles may also be changed in appearance, and may be destroyed, especially in cases of hsemo- globinuria. These changes in the red blood-corpuscles, which must be regarded as degenerative and destructive, cannot be brought wholly into parallel- ism with the development of the malarial pigment. In fact, the most profound lesions and the greatest destruction of the red corpuscles occur in infections with the sestivo-autumnal parasite, which is characterized by the small amount or even the entire absence of pigment. To explain many of these changes we must have recourse again to the theory that toxic substances are produced by the parasite and directly damage the blood-corpuscles. These alterations in the red blood-corpuscles not only explain the malarial ansemias and the h&emoglobinuria with their concomitant symp- toms and lesions, and the accumulation of malarial and other pigments in certain organs, but they are utilized, although less conclusively, to explain certain other malarial phenomena. We know from physiological observations that the physical integrity of the red blood-corpuscles is an important condition in the maintenance of their circulation within the blood current. It is reasonable to suppose that corpuscles as profoundly altered as are many of those infected with the malarial parasite will circidate with difficulty, and will tend to accumulate in certain situa- tions wdiere local conditions of the circulation favor the lodgement of foreign particles which get into the circulation. Many writers, there- fore, attribute to these alterations in the physical properties of the in- fected red corpuscles the accumulation of the parasites within the vessels of certain internal organs, more particularly the spleen, the bone mar- row, the liver, and the brain, and they explain the absence of such accumulation in quartan infections by the comparatively slight lesions of the infected corpuscles, and the large accumulation in tertian, and still more in sestivo-autumnal, infections by the more serious damage inflicted upon the infected red corpuscles by the varieties of the parasite causing these latter infections. Doubtless these factors — changes in the infected red (lorpuscles and local conditions of the circulation — are important in determining the localization of the parasites in certain internal parts, but with our present knowledge we cannot explain the varying distribution of the parasites observed in diflFerent cases exclu- sively by their aid, any more than we can adopt a similar explanation for the localization of the micro-organisms in other infections. The localization of the parasites in some cases, more particularly in sestivo-autumnal infections, within definite vascular areas of internal organs stands in relation to corresponding symptoms and lesions. The comatose and the choleriform types of pernicious malaria are associated with an accumulation, which may be enormous, of the parasites in the capillaries and small vessels of the brain and of the stomach and intes- tine respectively. Other special localizations of the parasites will be mentioned in the subsequent part of this article. In these cases cap- PARASITOLOGY. 73 illarics ami (itlicr .small l)l(»(i(lvi'ssels may be partly or completely ])liiir^ed with })arasitc.s, chiefly within red blood-corpuscles. Swollen, dciiciuTatcd, and (IcscjMamatcfl endothelial cells, ])it::ment, macrophages, and other j)haiiing of the vessels. It is not easy to determine how far these mechanical disturbances of the circulation are responsible for symptoms and lesions with which they are associated. Marchiafava and Bignami and others regard them as the essential cause of the grave nervous svmptoms in comatose j)ernicious fever, and of other sym])toms and of lesions. Many years ago Frerichs likewise attached much importance in the causation of cerebral symptoms to accumulations of pigment and the formation of coagula within the cerebral vessels. It appears, how- ever, to the writer that, aside from certain general pathological consid- erations and analogies with similar conditions in other diseases, this mechanical explanation is inadequate, and that here too the toxic prod- ucts of the parasite are (operative. The pnjmptness with which the grave cerebral symptoms may subside after administration of quinine is not easily reconcilable with the theory that they are due to plugging of the vessels. Even the focal necroses which are common in the liver in pernicious cases, and may occur in the spleen, the kidneys, and elsewhere, are best interpreted as due to the toxic products of the parasite, rather than as the result, as is claimed for the liver by Guarnieri, of plugging of the bloodvessels. These necroses do not differ from those observed in diphtheria, typhoid fever, and streptococcus and other infections, and that they may be purely toxic in origin has been demonstrated by AVelch and Flexner.' The capillary hemorrhages which have been observed in the brain in the comatose form of pernicious fever, and which may occur elsewhere, may be referred to the hyperaemia and stasis resulting from plugging of the vessels. The interesting fact has been observed that in these capillary hemorrhages the extravasated red corpuscles are without parasites, while the neighboring bloodvessels are filled with red corpuscles containing parasites. The explanation of this which is given by Marchiafava and Bignami and adopted by others is that the corpuscles containing para- sites on account of their greater adhesiveness stick to the walls of the vessels and thus are prevented from escaping. The writer offers another explanation as the more probable. The examination of these small hemorrhages shows that they are the result of diapedesis, and not of actual rupture of the vessels (rhexis). It is not difficult to comprehend that red corpuscles altered by the invasion of parasites would not par- ticipate in the process of diapedesis, whereas it is not easy to understand why they should not escape from ruptured vessels. It is evident from what has been said that, while occlusion of vessels and consequent disturbances of the circulation are common in severe malarial affections, and are dovibtless of importance in causing some of the lesions and symptoms, the more important and characteristic symp- toms and lesions are, in the opinion of the writer, w'ith our present ^ The Johns Hopkins Hospital Bulletin, March, 1892. 74 MALARIA. knowledge, better explained by the toxic theory of the pathogenic action of tlie malarial parasite than by any mechanical theories which have yet been offered. We have, however, no positive demonstration of the existence of spe- cific malarial toxins. The investigations as to the toxicity of the urine of malarial patients will be described on page 123. They have not led to any positive results as to the detection of specific malarial poisons. It is a very old conception that the febrile reaction of the malarial paroxysm is conservative in the sense that this response of the body to the presence of pyogenic agents in some way aids in the elimination or destruction of injurious substances. This conception is not altogether without support from the parasitological study of malaria. The fever begins at the time of the birth of a new generation of parasites. These young organisms before they have entered the red blood-corpuscles are, of all phases of development of the parasite, in the most vulnerable condition, as has been shown by investigations of the action of quinine. That a large number of them perish during the febrile paroxysm seems to be demonstrated, at least in quartan and tertian infections, by the contrast between the number of sporulating forms and the number of succeeding infected corpuscles. EsjDecially suggestive of increased potency of parasiticidal agencies during the febrile paroxysm are cases, especially of quartan or tertian infection, in which, after a sharp paroxysm, the symptoms and the parasites disappear, perhaps perma- nently, but often to return after a long interval as a recrudescence of the fever (page 121). Similar H^matozoa in the Lowee Animals. Great interest attaches to the presence in the blood of certain lower animals of protozoan parasites closely resembling the malarial parasite. Attention was first called to this resemblance by Danilewsky (1885-86), who described more fully certain forms which were previously known, and added the discovery of new forms, especially that of hsematozoa in birds which bear close resemblance to the human malarial parasite. Since Danilewsky's first publications there have been a number of investigations on this subject by Kruse, Celli and Sanfelice, Grassi and Feletti, Laveran, Labb6, and others. In the blood of frogs, turtles, lizards, and some other cold-blooded animals hsematozoa presenting some points of resemblance to the mala- rial parasite are not uncommon. Of these the -best studied and most interesting is the Drepanidium ranarum (Lankester), identical with Gaule's "Wlirmchen," in the blood of frogs. It is, however, certain hsematozoa in birds which bear such close resemblance to the malarial parasite that their identity with the latter has been assumed by Dani- lewsky and Grassi and Feletti, who speak of the existence of malaria and of malarial parasites in these animals. Most of the observations thus far reported have come from Russia and Italy, but the parasites have been found in birds also in Germany and France, and recently in the United States. In birds thus infected have been found forms similar to those of the malarial parasite in man — viz. unpigmented and pigmented hyaline PARASITOLOGY. 75 bodies (which, however, in Jistinetion tVoui similar l)()dies in man, iiuuii- fest little or no amoeboid movement), sporulating forms, crescents, and flagellated bodies. The bird's hsematozoa are also parasites of the red blood-corpnscles, from which they produce black pigment : they pass throngh the same stages of development as the latter, and the same diversity of views exists as to the origin and significance of the crescents and flagellated bodies. The name H.i^iMDProteus was introduced by Kruse to designate these so-called mahirial parasites of birds, and various other names have also been suggested. Grassi and Feletti adopt the same names and the same classification for these parasite of birds as for the human parasites (page 38). There are differences between the hiematozoa found in different species of birds, and in the same species apparently different varieties of the parasite have been observed, but there are at present no definite classification and no certainty as to the number of varieties which may exist. Although these hsematozoa of birds evidently belong to the same class of organisms as the malarial parasite, there are several reasons which in- dicate that they are not identical with the latter. They present certain morphological and physiological differences which it would lead too far here to describe. Although found thus far chiefly in birds from mala- rial regions, it is not proven that they may not exist in birds elsewhere. The inoculation of uninfected birds with the blood of birds containing the parasites has been, in a large preponderance of the experiments, unsuccessful in the result. The inoculation of birds with blood from human beings affected with malaria, and the inoculation of human beings with the blood of birds containing the hsematozoa, have been uniformly without positive result (Di Mattel). Large doses of quinine have no influence upon the parasites in birds. The presence of the haematozoa in birds is usually without recognizable disturbance of the health of the birds, although it may cause a chronic or an acute affec- tion. While, then, we must admit a close relationship between certain hsematozoa of birds and the human malarial parasite, the existing evi- dence is opposed to their identification. DESCRIPTION OF PLATES I. AND 11.^ The drawings were made with great care and skill by Mr. Max Broedel, with the assistance of the camera lucida, from specimens of fresh blood. A Winkel microscope, objective, 1-14 (oil-immersion), ocular, 4, was used. Figs. 4, 13, 23, 24, and 42 of Plate I. were drawn from fresh blood, without the camera lucida. PLATE I. The Parasite of Tertian Fever. 1. — Normal red corpuscle. 2, 3, 4. — Young hyaline forms. In 4 a corpuscle contains three distinct parasites. 5, 21. — Beginning of pigmentation. The parasite was observed to form a true ring by the confluence of two pseudopodia. During observation the body burst from the cor- puscle, which became decolorized and disappeared from view. The parasite became, almost immediately, deformed and motionless, as shown in Fig. 21. 6, 7, 8. — Partly developed pigmented forms. 9. — Full-grown body. 10-14. — Segmenting bodies. 15.— Degenerative form simulating a segmenting body. 16, 17. — Precocious segmentation. 18, 19, 20. — Large swollen and fragmenting extracellular bodies. 22.— Flagellate body. 23, 24. — Degenerative forms showing vacuolation. The Parasite of Quartan Fever. ^ 25. — Normal red corpuscle. 26. — Young hyaline form. 27-34 — Gradual development of the intracorpuscular bodies. 35. — Full-grown body. The substance of the red corpuscle is not visible in the fresh specimen. 36-39. — Segmenting bodies. 40. — Large swollen extracellular form. 41. — Flagellate body. 42. — Degenerative form showing vacuolation. PLATE II. The Parasite of vEstivo-atjtumnal Fever {Hcemaiozoon falciparum). 1, 2. — Small refractive ring-like bodies. 3-6. — Larger disk-like and amoeboid forms. 7. — King-like body with a few pigment granules in a brassy, shrunken corpuscle. 8, 9, 10, 12. — Similar pigmented bodies. 11. — Amoeboid body with pigment. 13. — Body with a central clump of pigment in a corpuscle showing a retraction of the haemoglobin-containing substance about the parasite. 14-20. — Bodies with central pigment clumps or blocks. Presegmenting forms. 21-24. — Larger bodies with central pigment blocks. Presegmenting bodies. Seen in the peripheral circulation during a severe paroxysm. 25-28. — Segmenting bodies from the spleen. Figs. 25-27 represent one body where the entire process of segmentation was observed. The segments, eighteen in number, were accurately counted before separation, as in Fig. 27. The sudden separation of the seg- ments, occurring as though some retaining membrane were ruptured, was observed. ' 29-37.— Crescents and ovoid bodies. Figs. 34 and 35 represent one body which was seen to extrude slowly, and later to withdraw, two rounded protrusions. 38, 39. — Round bodies. 40. — Pseudo-gemmation, fragmentation. 41. — Vacuolation of a crescent. 42-44. — Flagellation. The figures represent one organism. The blood was taken from the ear at 4.15 p. M. ; at 4.17 the body was as represented in Fig. 42. At 4.27 the flagella appeared ; at 4.33 two of the flagella had already broken away from the mother body. 45-49. — Phagocytosis. Traced with the camera lucida. 1 These plates are taken by permission from The Johns Hopkins Hospital Reports, vol. v., 1895. Four figures— viz. Figs. 21, 22, 23, and 24— have been added to Plate II., and are also from the draw- ings of Mr. Max Broedel. 2 The color of the pigment in these figures of the quartan parasite has too much of a reddish tint. 76 PLATE I. d y^^'^ '- f . '^? v^ v*v •■'-;'■■■ % ■ <<.i>^' ^■•^t; .^!^' '•'^'\' J^ 9 9 Q & ■^^ PLATE II. :,ite of Aestivo • e # e f 1 k O ' t?^ ^ etioloGtY, pathological anatomy, symptoms, diagnosis, prognosis, and treatment. By WILLIAM S. THAYER, M. D. Etiology. Distribution. — The malarial fevers are widely distributed, occur- ring in almost all regions of the earth. There are, however, certain principal foci where the disease is permanently endemic. These regions are chiefly in the warmer temperate and tropical countries. Generally speaking, the farther one departs from the equator the less common are the malarial fevers. A sharp line of delimitation cannot, however, be drawn. Occasionl cases have, according to Celli,^ been observed as far north as Irkutsk in Siberia, Haparanda in the Gulf of Bothnia (65° N. latitude), Juliushaab, Southern Greenland, and jSTew Archangel in Alas- ka, while to the south malaria has been reported to exist as far as the isotherm of 60°. It must, however, be remembered in considering any statistics concerning the distribution of malaria that the diagnosis of malarial fever has been, until very recently — and is, alas ! far too fre- quently today — made upon a very insufficient basis. In many regions tqday an intermittent fever with chills is without further investigation assumed to be of malarial origin, and even at the present time, in some of the large cities of this country, there are official statistics of mortality due to malaria — statistics showing thousands of deaths every year — which are almost absolutely incorrect. About the main foyers of. malaria there is, however, little doubt. In Europe the disease is common in the low lands about the coasts of Italy, Sicily, Corsica, Greece, the Black and Caspian Seas, and in the lands bordering upon the Po, the Tiber, the Danube, and the Vol- ga. About the coast of certain parts of France, Spain, and in Denmark and Sweden, an occasional case is seen. In Holland and Belgium the milder forms of the disease are not uncommon, while a few cases of the same nature are seen in Germany about the mouth of the Elbe and along the Baltic coast of Prussia, in Silesia, the plain of the river ]\Iark, and in Pomerania. In tropical Africa the disease appears in its most severe forms, especially along the West Coast. The chief foyers of the disease in Europe are in Italy and Southern Russia. In India, Ceylon, and in the East Indies it is particularly common, while in Southern and Southwestern China it is also endemic. In Japan the disease is rare. In the Western Hemisphere malaria is seen in the low- lands about the coast from New England to Florida, though above Vir- ginia the severe forms are rare. In the Gulf States and along the banks of the Mississippi and its tributaries, in most of the Southern States, the disease is almost always present. About some of the Great Lakes, both in the United States and Canada, malarial fevers are occa- ' Verhandl. d. X. Internal. Med. Cong., Bd. v. Abth. xv. p. 68. 77 78 MALARIA. sionally seen, while a certain number of cases are reported from the Pacific coast. In Cuba, Mexico, and Central America some of the most fatal forms of the disease are met with. The much feared Chagres fever of the Isthmus of Panama is a pernicious malarial infection. About the low- lands of the eastern coast of South America, particularly in the Guianas and in Brazil, the disease is endemic in its most malignant forms. On the west coast it is less frequent, though its occurrence in Peru and Bolivia has been known for years. Indeed, it is from the Peruvian Indians that we learned the value of the specific remedy for the disease. In Australia, New Caledonia, and the islands of the Pacific the disease is very rare, and in some regions, such as Hawaii, Samoa, New Zealand, and Van Diemen's Land, notwithstanding the existence of extensive low marshy tracts, it is quite unknown. In cases of malarial fever which occur sporadically in regions where the disease is uncommon the infection may often be traced to a previous sojourn in a malarious district. Extensive epidemics and pan- demics of malarial fever, spreading over the greater part of the earth, have been described. In most of these instances, however, consider- able uncertainty exists as to the true nature of the process. Physical Geography. — The physical geography of the country has much to do with the prevalence of malarial fever. In the words of Laveran, " The principal foyers of paludism are situated on the coast or along the banks of large rivers." High altitudes are usually free from malarial fever, and the mountains and plateaus in the neighbor- hood of malarial districts are often used as sanitaria by the inhabitants. The high altitudes may not, however, be a protection, as, according to Hertz,^ fevers occur in the Tuscan Apennines at a height of 1100 feet, in the Pyrenees at 5000 feet, on the island of Ceylon at 6500 feet, in Peru at from 10,000 to 11,000 feet. It is, however, by no means improbable that many of these fevers which have been called " mala- rial " are, in reality, of some other nature. This has been shown to be true in the case of the " mountain fever " of the Western States, which is for the most part, probably, typhoid fever. The Soil.^Low, marshy regions are particularly likely to be malarious ; hence the term " paludism" which is so generally used. Mixed salt and fresh water marshes seem to be particularly favorable for the development of the disease. Low, moist, ill drained lands, rich in vegetable matters — lands which have been allowed to fall out of cul- tivation — are particularly dangerous. All marshy regions, however, even in tropical countries, are not of necessity malarious, an example of this being shown in some of the South Pacific islands, as already mentioned. And, while the disease is particularly common in marshy districts, it may occur in other regions in sandy or clayey soil, or, indeed, in rocky regions. An impervious subsoil is believed to be particularly dangerous. JEfects of Turning up the Soil. — In many instances the denudation of a soil covered by forests or rank vegetation, or the turning up of the soil in a district which was previously free from the disease, may be fol- lowed by an outbreak of malarial fever, while in other regions where ^ V. Ziemssen's Cyclopcedia of the Practice of Medicine, vol. ii. ETIOLOGY. 79 tlu' disease already exists similar interference with the vegetation or the soil may oreatly intensity the severity of the process. An example of this latter condition is shown in the severe outbreak of malarial fever which was associated with the excavation of the Panama Canal. In Paris, which for many years had been free from paludism, the digging of the Canal Saint Martin, and again, in 1840, the excavations for the fortifications, were, in each instance, followed by an outbreak of characteristic intermittent fever. Irrigation of low lying districts without proper drainage has been followed by an outbreak of mala- ria or an increase in the severity of the cases. Such a condition of things has been noted in some of the irrigated districts in Southern California. Effects of Drainage. — Efficient drainage of marshy districts which have been rich in malarial fevers has a marked effect upon the frequency and severity of the manifestations of the disease. Years ago malaria was common in the surroundings of London, which were marshy and ill-drained ; today, thanks to good drainage, the disease is unknown. The low lands of Holland used to be the seat of very severe malaria ; today, only occasional cases of the mildest forms of the disease occur. The effect of good drainage upon the Roman Campagna has been very striking, the severity of malarial fever diminishing materially. Cultivation. — The cultivation of many marshy, malarious districts has been followed by a marked improvement in the sanitary condition. The planting of trees has been supposed to have a particularly good effect, possibly because of the drainage of the soil which is thus accom- plished. For some time it was supposed that certain trees, particularly the eucalyptus globulus, had an almost specific effect in protecting the neighborhood against malarial fever. The advantages of this particular tree have, however, been much exaggerated. Malarial fever never orig- inates at sea. Those cases which have been reported date their infection, unquestionably, to some period before the voyage. There is much to suggest that the soil has some intimate connection with the development of the coutagium of paludism. Variations ix Distribution. — One of the most striking character- istics of malarial fever is the manner in which it leaves one region in which it has existed for some time, to appear in another which may, for a con- siderable period, have been quite free from any manifestations of the disease. This change in the distribution of the disease is in great part due to the activity of man. On the one hand, an outbreak may follow the abandonment or neglect of richly cultivated areas which have been well drained and taken care of, as, for instance, the Roman Campagna in the time of Augustus, while, again, in other regions the turning up of the soil may bring about an outbreak where it is least expected. But this explanation does not answer all cases. The appearance of malarial fevers in the New England States during the past fifteen years, after a long period of almost entire quiescence, is a striking example of these inexplicable changes in location. Again, in districts where malaria is permanently endemic there are often cycles in the severity of the disease which are impossible to explain. Climate. — Heat and moisture are important for the development of the fever. In malarious districts a very dry season is usually more 80 ■ MALARIA. healthy. Laverau ^ states that in Algeria the rainy years show a more severe endemic than the dry, while the first " rains of the autumn give rise, almost always, in Algeria to a recrudescence of the fever." Season. — In tropical countries malaria exists usually throughout the year, but it is almost always most severe in the summer and fall. As one approaches the temperate climate the cases in winter and spring become very rare. Along the eastern coast of the United States, just as in Rome, the cases in the winter are very few, while with the spring a certain number of infections begin to appear. It is, however, not until July that the real malarial season begins. The height of the malarial season is reached in the months of August, September, and October. The following table, showing the number of cases of malarial fever treated at the Johns Hopkins Hospital between January 1, 1890, and January 1, 1894, gives a good idea of the variations in the occurrence of the disease to the seasons of the year : Jan. Feb. Mar. Apr. May. June. July. Aug. Sept. Oct. Nov.' Dec. Total. 9 8 8 17 21 18 38 66 122 120 38 25 490 The earliest cases show also the mildest types of infection. Thus, in the spring the first cases are usually tertian or quartan infections. As the season advances double tertian infections become more frequent, while at the height of the malarial season the majority of cases are of the sestivo-autumual type, the most severe form of malaria. Thus, out of 542 cases analyzed by Hewetsou and the author,^ there were — First half year. Second half year. Regularly intermittent fevers 113 230 -iEstivo-autumnal fevers 5 183 Combined infections 3 8 "m 42r=542 At the height of the malarial season, during the months of September and October, there were — Regularly intermittent fevers 109 jEstivo-autumnal fevers 120 Combined infections 5 This observation concerning the variation of the types of the fever with the times of the year is as old as Hippocrates. It has long been popularly supposed that the early cases of fever in the winter and in the spring represent, in toto, relapses from infections of the preceding fall, the fevers of first invasion beginning only with the summer months. The analyses of our cases at the Johns Hopkins Hospital tend, hoAvever, to show that, while the proportion of fevers of first invasion is less in the spring than in the summer months, yet they do occur. Winds. — There is much which tends to suggest that the infective agent may be carried by the wind. It has been asserted, for instance, that along the banks of a stream in a malarious district the fevers are often more frequent and severe on the side toward which the prevailing winds blow. Again, in other instances it has appeared that strips of 1 Traite des Fievra palustres, Paris, 1884, p. 8. ^ "The Malarial Fevers of Baltimore," Johns Hopkins Hospital Reports, vol. v. ETIOLOGY. 81 forest land liavc an-cstcd the spread of" tlic disease, suf^gesting that some inteetioiis suhstanee may l)e filtered out by the trees. Thus, Laueisi believed that it was through the influence of the winds that the Roman Campagna became more unhealthy after the removal of the sacred groves. These, he believed, acted as a protection l)y filtering from the air infectious substances carried by the winils which i)lew over the Pontine marshes. Altitude. — It has been repeatedly observed that in malarious districts the dangers of infection are much greater close to the ground. Sleeping, upon the ground is particularly dangerous. The upper stories of a house are safer than the lower. Infection appears to take place more readily by night than by day. DiNXKixc; Water. — Many have laid, and still do lay, much stress upon drinking water as the source of the disease. The experiments, however, of Celli,' ^Nlarino,' and Zeri,^ who caused individuals to drink in large quantities water wdiich was obtained from the most malarious districts, without any bad effects, and of Grassi and Feletti,' who fed individuals upon dew collected from malarious regions, with similar negative results, are strong arguments against this idea. It should be remembered, however, that while these experiments are strong evidence that the malarial poison is not introduced through the drinking water, yet it is no proof that water may not contain the parasite, or, indeed, form an actual culture medium for some forms of the organism. We are wholly ignorant of the manner of entry of the parasite into the system, of the form in which it exists outside of the body, or of the changes which it may pursue in other media than the circulating blood. It is not impossible to imagine a body which might pursue a part of its development in water, reaching its truly infectious form only in a later stage and in some other medium. Grassi and Feletti have shown that the living parasite from the circulating blood does not, when ingested, cause fever. Thus, they caused an individual to drink the fresh blood of a malarial patient without result, while inoculation experiments with similar blood are almost always positive. (See page 34.) Race. — In many malarial districts the natives — negroes, Arabs, Indians, Tamils — appear to have a relative insusceptibility to the dis- ease, the degree of which varies in different localities and according to different authors. Our observations in Baltimore would tend to show that here the susceptibility of the negro is only about one third that of the white. OccuPATiox. — The occupation has much to do with susceptibility to the disease. Soldiers and tramps who sleep upon the ground in malarious districts are particularly susceptible. Fishermen in the bays and inlets along the southern coast of the United States, as well as farmers and berry pickers in the same regions, are particularly open to infection. Age has apparently no effect upon the susceptibility, excepting in so far as the very young and the very old are less likely to be exposed. 1 BhU. d. Soe. Lane. d. Roma, 1886, vi. 1, 39 (5 Dec, 1885). 2 Eifonnn Medica, 31 Oct., 1890, >'o. 251, 1502. » Bull. d. R. Ace. Med. di Roma, 1889-90, xvi. 2-44. * Centralblatt fur Backt., 1891, ix. 403, 429, 461. Vol. I.— 6 82 MALARIA. Predisposing Causes. — It is generally believed that in malarious districts almost anything which tends to diminish the vitality of the patient acts as a predisposing cause to malarial infection. It is often asserted that where a previous attack has existed injuries of various sorts are particularly likely to be followed by a relapse of the malaria. It has been asserted, for instance, that an injury to the spleen in a patient who has formerly had malarial fever may call forth a relapse. With regard to the effects of traumatism, the observation of nearly a thousand cases during the last five or six years has not given any posi- tive answer, while the complications of malaria with other acute diseases have been, perhaps, rather surprisingly infrequent. It seems reasonable that trauma or operation, by reducing the condition of the patient, should render him more susceptible to a fresh malarial infection or more liable to a recrudescence of an already existing process. The fact, however, that in nearly seven years not a single case of post-operative malaria has occurred in the Johns Hopkins Hospital has led us to believe that many of the chills occurring under these circumstances, generally supposed to be malarial, are probably, in reality, septic in origin. Manner of Infection. — The discoveries of Laveran have revealed to us the infectious agent in malaria, while its specific action has been abundantly demonstrated by clinical observation and inoculation experi- ments. And yet it must be confessed that we are wholly ignorant as to the manner in which the parasite exists outside of the body or how in- fection takes place. The most important points of entry into the system which have been suggested are — (1) The respiratory tract; (2) The digestive tract ; (3) The skin (insect bites, etc.). (1) There is a very general belief that infection may take place through the respiratory tract, though positive proof of its occurrence is as yet wanting. In favor of this view are the observations of Lancisi and others concerning the winds. (2) Many observers, as has been said, still believe that the parasite is introduced chiefly through the digestive tract. The observations, how- ever, of Celli, Marino, Zeri, Grassi and Feletti, already referred to, are very suggestive evidence against this idea. (3) The inoculation experiments referred to in the description of the parasites have given positive proof that infection may take place when the parasite is introduced beneath the skin. This renders more plausi- ble the old idea that insect bites may sometimes serve to convey the contagium. In this connection one may remember the remarkable observations of Theobald Smith,^ who has shown that the hsemocytozoon of Texas fever in cattle {Pyrosoma higeminum) is conveyed from animal to animal by means of the cattle tick (Boophilus bovis). Experimentally it has been shown that although infection through the alimentary tract is improbable, subcutaneous infection is possible, while clinical observation is strongly in favor of the view that infection through the respiratory tract may occur. ^ U. S. Dept. of Agriculture, Bureau of Animal Industry, Bull. No. 1, Washington, 1892. ' PATHOLOGICAL AXATOMY. 83 In Saiimuiri/. — The malarial fuver.s lluuri.-li in low, moist, hot regions, the borders of rivers and marshes, places where the water is brackish being particularly dangerous. High, dry, sandy, or rocky regions are rarely malarious. In a malarious district there is greater danger of in- fection near the ground, by night than by day. There is suggestive evidence that the contagium may be carried In' the winds. Age has no marked influence on the susceptibility. The negro is relatively much more insusceptible than the white. The manner of existence of the parasite outside the body and the manner in which the infection takes place are still wholly unknown. Pathological Anatomy. (1) Anatomical Changes in Acute Malarial Infections ; (2) Changes folloaving Eepeated or Chronic Infections. Cases of the regularly intermittent fevers are so rarely met with upon the autopsy table that our knowledge of the pathological changes present in the internal organs are largely based upon a study of the cases of pernicious sestivo-autumnal fever. Our knowledge of the pathology of the malarial fevers has been greatly increased in late years by the investigations made since the discovery of the parasite by Laveran, Councilman and Abbott, Guarnieri, Dock, Bignami, Barker, and Monti. One of the most interesting points which at once strikes the careful observer is the extreme variation in the distribution of the malarial parasites in the body, and the anatomical changes produced by them in diiferent cases. This difference in the localization of the para- sites and in the seat of the important anatomical changes may bear, as has been pointed out in the description of the parasite, a direct relation to the symptoms which have existed during life. The most striking point in the appearance of the organs in malarial fevers is the melanosis which gives a characteristic slaty gray color to many of the organs. This results from the accumulation of the pigment produced by the parasites from the haemoglobin of the blood-corpuscles, and, while almost invariably present, its distribution, as in the case of the parasites, and the degree in which diiferent organs are aifected, varies considerably in different cases. The Brain. — The most striking changes in the brain are to be met with in the cases of comatose pernicious fever. The brain may be the seat of but few macroscopical changes. Melanosis may be entirely absent. At times, however, there may be a slight subpial oedema with hypereemia of the cerebral substance, and perhaps punctate hemor- rhages ; more commonly, however, the gray cortex shows a slats^ or chocolate color, which may be quite deep. The vessels are markedly injected, and in places, as has been said, punctate hemorrhages may be found. In these instances the microscopical appearances are most striking. The cerebral capillaries are crowded with parasites, which are, for the most part, within red corpuscles, and may form an actual comjjlete injection of many of the cerebral vessels. This is generally most striking in the gray substance. These parasites (usually of the sestivo-autumnal type) may be in all stages of development, though generally one of the stages is most marked. Sometimes in cases where 84 3IALAEIA. death has occurred during the paroxysm actual thrombi of segmenting organisms may exist. Sometimes the organisms may not be so numer- ous, but evidence of their previous existence is found in free clumps of pigment and swollen pigmented endothelial cells, as well as leucocytes containing pigment and red blood-corpuscles. There is usually decided granular and fatty degeneration, and often pigmentation of the endothe- lium of the vessels — a change upon which the punctate hemorrhages probably depend. Some endothelial cells may be greatly swollen, almost occluding the lumen of the vessels : these, as has been demonstrated, especially by Monti, may contain a considerable number of apparently well preserved parasites in various stages of development ; they may be within shrunken or brassy corpuscles or full grown and free. Occasion- ally large macrophages are seen almost occluding the capillary, which appear, according to Monti, to be endothelial cells which have broken loose and are free in the current. These lesions are particularly marked in the comatose form of per- nicious malaria. In some instances different parts of the central ner- vous system may be differently affected. In one case, for instance, studied by Marchiafava,^ where the patient died with symptoms of bulbar paralysis, a special localization of the changes was noted in the medulla. In other instances the cerebral lesions may be slight ; the collections of parasites in the capillaries, as well as the degenerative changes in the endothelium, are not to be made out. Monti ^ has recently studied the changes in the nerve cells in the gray cortex in pernicious malaria, according to Golgi's method, with interesting results. In some cases these elements Avere, so far as could be made out, quite normal, while in others interesting changes were noted : these cases were chiefly those showing grave nervous symptoms, such as coma, during life. The alterations were not uniformly diffused throughout the cortex, and never affected all the elements in a given zone. Usually cells more or less profoundly altered were found among other cells and fibres which were quite normal, although a tendency to a focal arrangement of these changes could be made out. The altera- tions affected chiefly the protoplasmic prolongations of the nervous cells of the cerebral cortex. Sometimes the prolongations appeared thinned and studded with fine nodes. Not infrequently these alterations were limited to the more delicate and distant branches, though it was not difficult to find cells of which all the dendrites presented the beaded appearance which is so well observed in the nerve cells of animals dead of inanition. In other points the alterations consisted of simple irregu- larities of contour in dendrites which were much thinned, extending from cells the bodies of which were sometimes normal, more often swollen, rarely thinned, shrunken, or atrophic. Coarser alterations were, however, not wanting. Cells were found whose dendrites showed coarse varicosities and very marked constrictions, so that they appeared as if formed of masses of protoplasmic matter connected only by the finest filaments of protoplasm. Similar changes were observed in the brains of animals in which embolisms were produced by the injection of lycopodium. 1 Lav. del. III. Cong. del. Soc. Ital. di Med. Int., Eoma, 1890, 142. 2 Bull. d. Soc. Med.-Chir. di Pavia, 1895. PATHOLOGICAL ANATOMY. 80 In most of Monti's cases the axis eyliiulers were well preserved ; the principal lesion u})peared to consist in alterations of the protoplasmic prolonular ])arasites show, usu- ally, all stages of development. The endothelium of the capillaries and small veins rarely contains pigment, in sharp contrast to the condition existing in the brain. It is striking that the areas of l)ronchopneu- monia, which are not infrequently found, contain only the ordinary polymorj)honuclcar leucocytes and alveolar epithelial cells, pigmented elements being very rarely present. The capillaries of the septa may, however, be filled with pigment and macrophages. Bignami suggests that this fact is due to the diminished vitality of the pigment bearing cells, which have, to a certain extent, lost their motile power and are thus less able to pass through the vessels. The Kidneys. — The changes in the kidneys in acute malaria are usually much less marked than in the liver and spleen. Their gross appearance varies but little from the normal. Evidences of pigmenta- tion are usually wanting on gross examination. The malarial parasites and phagocytes are usually present in smaller numbers, the quantity being disproportionately small in comparison to the alterations of the parenchyma which are sometimes to be found. The glomeruli, how- ever, are ordinarily considerably pigmented, the pigment at times being seen within large white cells within the vessels, sometimes in the glomerular endothelium. Endoglobular parasites are rarely seen in the capillaries of the glomeruli ; they are more common in the inter- tubular vessels, but are rare even there. The most important lesions consist in exfoliation and degeneration of the epithelium lining the capsules. Albuminous exudates within the glomeruli were found bv Bignami only in algid pernicious fever. At times, however, there may be marked alterations in the parenchyma — to wit, focal necroses of the epithelium, especially that of the convoluted tubules. The changes in the kidneys in cases of hsemoglobinuric fever have been described by Pellarin,^ Benoit,- Kiener, and Kelsch.'^ The kid- neys are somewhat increased in size, the color var^'ing from a deep reddish brown to a light yellowish brown coffee color in more ansemic individuals. When the color is pale, irregular pinhead points and blotches of a maroon color are to be seen upon the surface, some as large as several millimetres in area. They are also scattered through- out the cortex. These have been shown by Kelsch and Kiener to be due to pigment deposits ; they are not visible in more congested kid- neys. The pyramids are of a deep red color from intratubular hemor- rhages. The capsule is easily detached ; the consistency of the gland is normal. Microscopically, the epithelium of the convoluted tubules and of the large branches of Henle's loops are very opaque, the nuclei being scarcely visible. This is due to an infiltration of the protoplasm with a diffuse coloring matter and fine pigment granules which are rendered more evident by KOH. These granules are extremely small, and sepa- rately appear of a yellowish color, while en masse they have a brown shade. The epithelial cells are swollen and bulge into the lumen of the canal. Occasionally a cell shows a hyaline protrusion which seems on 1 Arch. deMed. nav., 1865. - Ibid. ^ Arch, de Phys., 1882. 88 MALARIA. the point of escaping. In some tubes the epithelial covering is repre- sented only by a thin protoplasmic layer with a homogeneous surface, appearing as if eroded down to the level of the nuclei. The lumen of the tubule is filled with clumps of amorphous material or casts mixed to a greater or less extent with this pigment. The brown specks and blotches seen macroscopically represent groups of tubules, the epithe- lium and lumina of which are crowded with similar masses of pigment ; but pigment may also be found in larger granules — granules nearly as large as a red blood-corpuscle, and more or less spherical ; they are refrac- tive, of a color varying from a yellow ochre to a deep brown, and are some- times accumulated in epithelial cells which bulge so as to almost occlude the lumen. Sometimes they occupy the lumen and form conglomerations, taking the shape of casts ; sometimes they are fused into a vitreoid mass. Between the opaque dark casts formed by the fine brown granulations and the almost vitreoid casts composed of the large orange colored granulations every intermediate stage may be seen in the same prepara- tion. Generally this pigment gives no reaction for iron, though Kelsch and Kiener have obtained this reaction from certain granules in one case. The finely granular substance is found, according to these authors, more particularly in cases where death has occurred in a pernicious paroxysm, while the larger forms of pigment are more frequent in cases of longer duration. In the glomeruli, as well as in the blood, Kelsch and Kiener have never seen the large variety of granules, though the finer granules are numerous. Between the glomerulus and capsule, usually near the mouth of the tubule, there is often quite a collection of granules, which are also found sometimes in epithelial cells, sometimes free. In the glomerulus itself one may see fine gran- ulations disseminated in its substance and apparently included in the cells of the capillary walls. More rarely granulations may be accumu- lated in a capillary loop. In some cases there are small interstitial hemorrhages. The pyramids show few changes. The same varieties of casts as noted above may be found, and the same pigment collections. The epithelium is usually intact, though sometimes protruding and vesicular cells suggest that they may take part in the formation of hyaline material. Almost invariably a number of the tubes are found filled with blood-corpuscles. The Gastro-intestinal Tract. — The stomach and intestines show, under ordinary circumstances, few changes beyond the melanosis. It is to be remembered, however, that the intestinal mucous membrane may be of a dark steel gray color in conditions other than malaria. Microscopically, one may see a considerable number of parasites, espe- cially of the full grown and segmenting varieties, in the capillaries of the mucous membrane, together with numerous pigmented cells and apparently few pigment clumps. In most cases, however, the gastro- intestinal mucous membrane is not particularly sought by the parasites. In other instances, as pointed out by Marchiafava and Bignami, this region may be the seat of the main localization of the afFection. Macroscopically, there may be intense hypersemia with punctate hemor- rhages in the gastro-intestinal mucosa. In one instance observed by the author there was a distinct dusky slaty tinge as well. Here the capil- laries throughout the gastro-intestinal tract may be crowded and blocked ' PATHOLOGICAL ANATOMY. 89 with parar^ites, free and cnntainod in the rod corpuscles or in phagocytes. As in the case of" tlie brain, actual tiironihoses may exist witli necrosis of the ejiithelial coverinu- and uh-eration. Cases of this nature are asso- ciatetl fre«(Ueutly witli niarUi-d gastro-intestinal syinj)tonis, some sliow- ing; a clinical picture very similar to that of Asiatic cholera. The Bone Marrow. — The marrow is generally of a dark slaty color ; it is often almost black. The small vessels are filled with endo- lilobular j)iuincute(l ])arasites, while numerous macrophages containing pigment and red blood-corpuscles may be found about the periphery of the lumina of the vessels. At times, between the corpuscles, Biguami ' found numerous ovt)id or round bodies which, from their size and stain- ing ])ropensities, he believed to be free spores. Not only in the vessels, but also outside of these, the pai'asites are to be found in greater or less number. The macrophages are, however, especially numerous, even in the })ulp. At times also free pigment clumps are apparently to be made out. The ADRENAL GLANDS may be the seat of pronounced alterations. There are irregular areas of vascular dilatation, parasites being numer- ous in the distended vessels. Macrophages with varying contents may be present in considerable numbers. The endothelial cells of the ves- .sels may be phagocytic, and malarial pigment and infected corpuscles may even be enclosed by true adrenal cells. In the other organs there is little that is characteristic. (2) Changes following Repeated or Chronic Infections. — Chronic Malarial Cachexia. While the above mentioned changes are found in the acutely fatal cases of malaria, interesting pathological changes may occur in various organs as the result of long continued or frequently repeated attacks. The most important of these changes occur in the spleen, the liver, the bone marrow, and the circulating blood. The Spleen. — The spleen is ahvays considerably enlarged ; it may be enormous, reaching beyond the umbilicus and as Ioav as the pubes. It is firm and hard ; the border is sharp. The capsule is usually much thickened, and white fibrous cartilaginoid plaques occur upon the surface. On section it has often a somewhat slaty color, while the trabecule are very prominent. The minute anatomy and development of the changes in the viscera, follow^ing repeated malarial attacks, has been followed w^ith particular care by Biguami,^ upon whose valuable work we shall largely trespass in the following description. The acute splenic tumor is caused chiefly by the aggregation in the pulp of the spleen of an enormous number of red corpuscles which have become either shrunken and brassy colored or decolorized, and are found included in the colorless elements of the spleen as brassy colored fragments or hyaline masses ; by the continuous aggregation of colorless elements containing pigment, red corpuscles, or parasites, which collect from all parts of the body, and many of Avhich are necrotic ; and, thirdly, by great numbers of red corpuscles contain- ing parasites, some of which apparently pass through the vessel walls 1 Atti d. R. Ace. Med. di Roma, Anno xvi. v., 1890. « Bull. d. R. Ace. Med. di Roma, 1893, Anno xix. f. 4, p. 186. 90 MALARIA. by diapedesis and seek the columns of the pulp, where they are for the most part enclosed by the epithelioid elements. While, as a result of this proceeding, a considerable number of the proper elements of the spleen become necrotic, others, as well in the pulp as in the follicles, undergo karyokinetic division, while all this is followed by a marked hypersemia and acute tumor of the splenic pulp. Thus the spleen is converted into a place for the deposit of cadavers, wdiile at the same time, during the same infection, processes of regeneration have begun to appear. When the actual infection is at an end and the acute hypersemia of the spleen has ceased, the tissues in the neighborhood of these collec- tions of necrotic elements, or those surrounding the necrotic areas of the splenic pulp, show certain changes which, on the one hand, tend to pro- duce permanent alterations, and on the other to lead to a partial repara- tion of the part. In those parts where a considerable portion of the splenic tissue becomes necrotic or disappears, being carried away by the lymphatics, the splenic vessels become considerably dilated, forming a network of venous lacunae which are separated by thin layers of pulp. This results in a tissue simulating that of an angioma. In those cases w^here a more marked destruction of the splenic tissue has occurred, and where every trace of the pulp is gone, parts become represented by extensive areas of tissue which consist of wide cavernous sinuses, the septa of which are composed of a very delicate connective tissue, rich in giant cells, similar to that of the bone marrow. Some of the follicles be- come necrotic and fibrous. While this occurs a process of regeneration yet more extensive takes place, starting for the most part from the fol- licles, but also sometimes from the splenic pulp. The follicles become hyperplastic, reaching sometimes three or four times their normal size. This new form of lymphoid tissue, starting from the follicles, may be sometimes seen to surround necrotic areas of splenic tissue Avhich be- come smaller and smaller and finally disappear. In the neighborhood of these hyperplastic follicles occurs a hyperplasia of the true elements of the pulp, while the reticulum becomes thickened so as to give rise, in preparations, to very beautiful and clear figures, such as are not to be seen in the normal spleen. The pigment and probably the greater part of the necrotic elements are carried on toward and collected about the periphery of the follicles, so that the diffuse melanosis of the pulp is followed by a perifollicular melanosis. The pigment then passes on into the lymphatic vessels of the sheaths of the arteries and of the con- nective tissue of the septa. This results, on the one hand, in thickening of the vascular sheaths and of the septa, and, on the other hand, in the appearance of single or multiple lymphatic cysts, giving sometimes the picture of a lymphangioma and resulting in chronic lymph stasis. When we consider that after each new infection fresh processes simi- lar to these must occur, it is easy to understand the gradual development of the enormous splenic tumors, in which, sometimes, it is dii!icult, even histologically, to recognize the original structure of the organ. The Livee. — The changes occurring in the liver in chronic malaria may in the same manner be traced from those occurring in the acute infection. In the acute infection an enormous number of phagocytes, pigmentiferous or globuliferous, coming in great part from the spleen, PATHOLOGICAL AX A TOM V. 91 invades the caj)illarv nctwctrk of tlic liver, wliile the parasites are gen- erally seanty. The eircuiatioii is slowed, tiie eapillary network heeomes dilated, while a eertain amount of" pigment is taken up l)y the endothe- lial eells of the vessels, and later by Kupffer's cells. The pigmented endothelium becomes swollen and in part necrotic. These vascular changes are followed by new areas of blood stasis. At the same time, as has been noted, many of the liver cells suffer alterations, either undergoing an acute atrophy from pressure or a coagulative necrosis. These areas are sometimes quite extensive. In other instances many cells are found to be filled with blocks of yellowish iron-containing pig- ment, resulting from the early death of many red corpuscles. At the same time a certain number of liver cells, Kupffer's cells, and endothe- lial eells multiply by karyokinesis. The result of all this is the acute hepatic tumor and the increase in functional activity — polycholia. But a small part of the great number of pigmented elements which enter the liver escape, passing through the branches of the supi'ahepatic veins. The greater part is taken up by endothelial and perivascular cells, so that the melansemia is followed by a melanosis of the vessels. The pigment then passes forward out of the capillary net^vork into the perivascular lymph channels, where it is collected in large blocks en- closed in white cells. These carry the pigment following the lymph channels to the periphery of the lobules, and perilobular melanosis follows thus the interlobular melanosis. This process then extends, and the masses of pigment are to be found three or four months after the end of the infection in large blocks, for the most part endocellular, in the perivascular lymphatic tissue of Glisson's capsule. AVhile this migration of pigment is going on in the lobule there occur, on the one hand, permanent alterations, and on the other hand regenerative processes. Where the dilatation of the lymph and blood- vessels and the degeneration and pigmentation of the vascular elements is most marked and extensive, no regeneration may follow the atrophy and necrosis of the endothelial and liver cells. The dilatation of the vessels increases and becomes permanent. The greater part of the re- maining liver elements disappears ; only a few remain in an atrophic condition, the tissue showing an angioma-like appearance consisting of ectatic vascular network, about which may be recognized a stroma consisting of Kupffer's cells. AVhere the dilatation of the lymph vessels is most marked there may occur small lymphatic cysts. In all parts of the liver, when the normal blood current has been restored after the disappearance of the pigment and the necrotic masses in general from the endothelial cells of the vessel walls, an active regen- eration of the tissue elements occurs about the atrophic or necrotic liver cells. The young hepatic cells become arranged with great regularity in long rows on both sides of the old elements. Thus, when the stroma remains intact, an interlobular regeneration may occur. These regene- rative processes are accompanied by the appearance of giant cells with budding nuclei, just such as are found in the embryonic liver. The regeneration never appears in parts of the liver that have not been entirely freed from the collections of pigment and parasites. The migration and collection of the pigment in the perilobular tissue is followed by a hyperplasia of tliis tissue, so that the surroundings of 92 MALARIA. the lobules are more distinct. These de- and regenerative changes result, then, in a marked increase in the size of some lobules and a diminution in size and an atrophy of others. As this process accompanies each acute infection, one can readily understand the chronic perilobular, mono- lobular hepatitis of malaria, which is characterized by the presence of zones of hyperplasia or of atrophy of the parenchyma, by chronic blood and lymph stasis, by the formation of areas of angiomatoid tissue, by lyniphectases and lymphatic cysts. In this manner the large liver tumors which are so well known, with smooth surface and lobules of irregular size, have their origin. Bignami divides the processes in the liver into four stages : (1) The liver appears congested, while the lobules are not sharply distinguishable and show in severe cases a decreased melanosis. The macroscopical characters are about the same as those of the liver in acute malarial infections. Microscopically, at this period, a little after the ter- mination of the acute infection, it may be noted that the parasites have disappeared from the capillaries of the liver, the pigmented endovascular macrophages have in great part gone, and the pigment is entirely col- lected in the endothelium and in Kupffer's cells. Those parts of the hepatic lobules in which necrosis or degeneration has occurred undergo a marked atrophy ; the necrotic and degenerate elements are carried away in the phagocytes, while the vascular network becomes dilated. (2) In a more advanced stage on gross examination the lobules are distinct. The melanosis continues to be diflFuse throughout the lobule, but is more marked at its periphery. The organ is still congested. The particular features of this stage are that, on the one hand, the hepatic lobule frees itself from the accumulation of pigment and the necrotic remains, which become collected toward the periphery of the lobule, while, on the other hand, an active process begins which tends toward a partial regeneration of the parenchyma. (3) In this stage the diffuse melanosis of the lobule, with the greater prevalence of pigment toward the periphery, is succeeded by an exclu- sively perilobular melanosis. The liver is enlarged, the consistency somewhat increased, the surface smooth. On section one may see that all the lobules are surrounded by a slate colored line, in the neighbor- hood of which the coloration of that part of the lobule is somewhat brown. In general, the slaty lines marking out each lobule form an exquisite network. The size of individual lobules varies greatly : some are two or three times the normal size, others are markedly diminished. Microscopically, it may be observed that the degenerative alterations of some lobules have led to the formation of false angiomata and of lacunae or cysts of lymphatic nature. Other lobules, by the process of regene- ration already described, have increased notably in volume. The pig- ment has become extravascular ; its transport through the capillaries and perilobular lymphatics is brought about by white mono- and poly- morphonuclear cells. (4) In cases in which the acute infection has passed for several months (in one case three months only) the pigmentation is greatly diminished and scarcely visible to the naked eye. The liver is notably enlarged and congested. The surface is smooth. On section one may see the lobules distinctly marked, surrounded by a most delicate red- PATHOLOGTCAL ANATOMY. 93 (lisli brown border; (he eonsi.stcnev is sonicwliat increased. Micro- scopical exaniiiiatioM shows tliat the inehiiiosis has Ix-coiiie exchisivelv perivascular. (5) Lastly, on(> arrives at the defiiiite terniiiiai ibrin of the cliroiiic malarial hepatic tumor. The macroscopical charactei-s are the tbllow- iuji,- : The liver is increased in size and in weight, sometimes enormously ; the surface is smooth, the capsuU' a little thickened. On section the appearance is finely granular, tiie lobules are distinct, a little prominent, and surrounded by a zone of slightly pinkish tissue. Microscopical ex- amination shows the disap]X'aranee of all malarial pigment. The altera- ticMis of the parenchyma are similar to those described in the last two stages. The lobules of varying size are surrounded by a hyperplastic perilobular connective tissue. The connective tissue of the larger septa is, on the other hand, of about normal volume. A notable dilatation of the capillaries, with stasis of the colorless corpuscles, persists. The hepatic cells are altered in form in the zones where the dilatation is most marked. There is considerable diiference in individual cases in the extent oi' these various lesions. There are cases, for example, in which, despite the enormous increase in the weight of the organ, there may be no very marked dilatation of the capillaries, nor are false angiomata or lymphatic cys1:s to be found, while, on the other hand, the hyperplasia of the perilobular connective tissue and the increase in vol- ume of many lobules may be more marked : there may be an evident hyperplasia of the parenchyma (hepatic cells with many nuclei and nuclei rich in chromatic substance). lu other cases, on the other hand, the cysts and false angiomata may be enormously developed, so as to constitute one of the chief factors in the enlargement of the liver. The Boxe jMaerow. — In individuals Avho have had numerous re- lapses of malarial fever the marrow of the long bones — for example, of the femur in the upper and louver fourths — is usually red and of a consistency greater than is generally seen in acute infections. The microscopical alterations are various ; generally the signs of an active proliferation of the proper elements of the marrow are present. This leads to an increase in the hematopoietic activity. There are factors, however, such as the degenerative and destructive alterations which take place in the bone marrow during acute infections, which injure, to a varying extent and through a varying length of time, the haematopoi- etic functions of the marrow. In other cases, very rare indeed, the bone marrow presents the macroscopical and microscopical features which exist in acute pernicious anaemia, particularly the presence of a consid- erable number of megaloblasts. Lastly, there may be cases in which the new formation of the hsematoblastic marrow is wanting or entirely insufficient. In these cases the post-malarial anaemia is of necessity progressive. The Blood. — Corresponding to the change in the bone marrow, Bignami and Dionisi ^ distinguish four types of post-malarial anjemia : (1) Ansemise in which the examination of the blood shows alterations similar to those observed in secondary ansemise, from which they differ only in that the leucocytes are diminished in number. The greater part 1 Cent./. Allg. Path. u. Path. Anat., 1894, V. No. 10, 422. 94 MALARIA. of these cases go on to recovery ; a few, without any further change in the hsematological condition, pursue a fatal course, (2) Ansemise in which the examination of the blood shows alterations similar to those seen in pernicious anaemia — presence of gigantoblasts (megaloblasts). These cases end fatally. (3) Ansemise which are progressive, as a result of lack of compen- sation by the marrow for losses brought about by the infection. At autopsy the marrow of the long bones is found to be wholly yellow, while the marrow of the flat bones is also poor in nucleated red corpuscles. (4) Chronic ansemise of the cachectic, which diifer from the above- mentioned types by clinical and anatomical characters in that the special symptoms of malarial cachexia prevail, while one observes post-mortem a sort of sclerosis of the bone marrow. The marrow of the long bones is red and of an increased consistency ; the giant cells are very numer- ous, and many are necrotic ; the nucleated red blood-corpuscles are very rare, and the colorless polymorphonuclear corpuscles are present in small numbers. The Kidneys. — The kidneys in chronic malaria show usually no great changes. Ki^ner, however, describes two forms of kidneys met with in chronic paludism : (1) the congested form, and (2) the atrophic form. (1) The engorged kidneys are voluminous, increased in weight ; the surface is smooth, the consistency firm, the color of a deep red. The congestion is especially marked in the pyramids. All the vessels are distended, and the congestion is sometimes so extreme that interstitial hemorrhages may result or hemorrhages into the interior of the tubules. The epithelium of the tubules is granular ; there is often desquamation, and hyaline casts may be found. (2) The atrophic kidneys are small and irregular in surface. The capsule is adherent, the consistency increased. The kidneys show a maroon or mahogany color or a blotchy appearance. Small cysts are often to be found. The microscope shows alterations as well in the connective tissue as in the epithelium of the tubules. Amyloid degeneration occasionally follows chronic malaria. This has been noted in the kidneys by Laveran ^ in two instances, but in both of them the malarial cachexia was complicated with chronic broncho- pneumonia and bronchiectasis. Frerichs^ describes three cases, while Marchiafava and Bignanii^ have carefully studied several instances. The clinical history of these cases showed that after a long period of febrile attacks (sestivo-autumnal or obstinate quartan) there followed the symptoms of nephritis and a rapid cachexia, in which the patients died in a few months. On autopsy the principal changes that were found were a grave anaemia, a marantic condition of the organs, a chronic nephritis, and a diffuse amyloid degeneration. The distribution of the amyloid substance in their cases was as follows : The degenera- tion was most prevalent in the kidneys, where not only the vessels of small and medium size and glomeruli were affected, but also, to a con- siderable extent, the walls of the renal tubules. The alteration of the ^ Traite des Fievres palustres, p. 94. ^ Lehrbuch der Leberkrankheiten. ^ m/orma Medica, 1891, vol. i. p. 571. MALARIAL CIRRHOSIS. 95 interstitial tissue and the degenerations of the renal parenchyma are very grave. After the kidneys the amyloid degeneration is most severe in the intcstineff and the upleen. In the intestine the degeneration aif'ects chiefly the vessels of the villi, but also the vessels of the submucosa, and to less extent those of the other intestinal coats. In the .yj/ecu the vas- cular network of the pt'rij)herv of the follicles is particidarly affected. Here one sees usually the deposition of great blocks of amyloid sub- stance, while in the trabecuhe of the pulp the process is in its beginning or is entirely wanting. In the liver there is a less extensive and diffuse deposition of amyloid substance than in the kidneys. The degeneration affects islands of hepatic tissue which are irregularly disseminated, so that, for example, one may see an island of the size of a lobule or larger from which the hepatic tissue has entirely disappeared, the vascular net- work showing a most grave amyloid degeneration, while about this the hepatic tissue has a normal apjDearance. The first small zones of degeneration, according to Bignami, seek by preference the periphery of the hepatic lobules, from whence the process spreads. Malarial Cirrhosis. — The Relation of Chronic or Repeated Malarial Infections to Cirrhotic Processes. For many years certain authors have associated cirrhosis of the liver, certain chronic renal changes, and, in some instances, chronic inflamma- tion of the lung, endocardium, and central nervous system, with malarial fever. Indeed, in almost all works upon medicine malarial fever is in- cluded as one of the etiological factors in ordinary atrophic cirrhosis of the liver. This statement has been based almost entirely upon rough clinical observation, no one having definitely traced the development of the cirrhosis from the changes following acute or chronic malaria. Frerichs ' noted the rarity of cirrhosis in patients dying with chronic malaria, though in five instances this was the only etiological cause which he could discover. Laveran^ in his considerable experience has seen but two cases of atrophic cirrhosis following malarial fever. Welch has seen but one case of atrophic cirrhosis which appeared to follow malaria. Kelsch and Ki§ner give a longer description of hepatitis in malaria, distinguishing three forms of chronic malarial hepatitis and two groups of malarial cirrhoses : (1) Insular cirrhosis with nodular hepatitis and insular cirrhosis with diffuse parenchymatous hepatitis ; (2) annular cirrhosis with nodular or diffuse parenchymatous hepatitis. The gen- eral appearance of the liver in these cases is that of ordinary atrophic cirrhosis. Bignami has recently discussed this subject in a very thorough man- ner. He concludes that there is little evidence to show that ordinary atrophic cirrhosis is a frequent follower of malarial fever. After describ- ing the development of the ordinary chronic hepatic tumor of malarial cachexia, he says : " It is easy to understand from this that it is not difficult to make a differential diagnosis between this form of chronic tumor — or of chronic hepatitis, as one might say — from the other forms ' Loc. cit. ^ Traite des Fievres palustres, p. 90. 96 3ialIria. of cirrhosis. There are not facts or reasons sufficient to cause us to believe that ordinary cirrhosis can follow a chronic tumor. The struc- ture in the two cases is absolutely different. In the one we have an extensive new formation of connective tissue, multilobular in nature, retracting about the included lobules ; in the other, a more scanty for- mation of perilobular connective tissue about a single lobule, not con- tracting, together with grave alterations of the lobules themselves, especially of their vascular and lymphatic system, not depending, as we have seen, upon the new formation of perilobular connective tissue, but due to lesions primarily local. Atrophic conditions of the liver exist in malaria, but are simple atrophies, and occur in patients who are exhausted, for example, by profuse diarrhoea, etc., or in cases which I have described as progressive post-malarial ansemia. They depend upon the complete want or almost complete absence of any process tending toward regeneration, resulting from grave and diffuse regressive alterations." Barker ^ has recently ably discussed the relation of malarial infections to cirrhotic processes, and has emphasized the fact that many conditions exist in the organs in malarial fever which might well be the starting- point for extensive growth of connective tissue. Flexner,^ after the injection of blood serum from one animal into another, has seen the development of characteristic cirrhosis of the liver and of the kidneys in rabbits, following focal necroses not dissimilar to those found in the liver in acute malarial infections. In conclusion, then, it may be said that secondary sclerotic processes of greater or less degree in the liver, spleen, and bone marrow are not uncommon after repeated malarial infections. The question of the possibility of the development of a true atrophic cin^hosis of the liver, of malarial origin, is not settled ; the development has never been actually traced and the condition, if it exist at all, is probably rare. The possibility of its occurrence cannot, however, be denied. Symptoms. Period of IxcuBATio:sr. — In the absence of definite knowledge as to how malaria is acquired, the ideas concerning the period of incuba- tion have varied very greatly. It has undoubtedly been observed that characteristic malarial fever may appear very shortly after exposure in a malarious district, many observers believing that this may occur with- in a shorter time than twenty-four hours. It is possible that the febrile attacks which occur sometimes immediately after exposure at night in damp, marshy, malarious districts may have some other cause than malarial infection. Thus, Plehn describes cases where, after exposure at night in very malarious districts in West Africa, there was an imme- diate paroxysm similar to a malarial attack, which, however, did not recur until the appearance, ten days later, of a true malarial fever, which doubtless dated its infection from the night of exposure. At the time of the first paroxysm the blood was negative, the parasite (sestivo- autumnal) not appearing until ten days later. The hypothesis of Plehn that the initial paroxysm was due to the absorption of some toxic sub- ^ Johns Sopkins Hospital Reports, vol. v. ^ The Medical Nev:s, Philad., Aug., 1894. SYMPTOMS. 97 stance pruduced, j)erluips, by the [)arasitc oiit.-^ide ol" the Ixjdy, i.s iiifreni- ous, but seems a little far-fetched. More commonly an interval of one or two weeks may be made out between the time of exj)o.-;ure and the time of tile breakinj; out of tlie disease. Maillot' considered the mean period of incubation to l)e from ten to twelve days, while Sorel '" esti- mated it at from seven to nine days. Hertz' states that the period of incubation is commonly reckoned at from six to twenty days, but be- lieves that the disease may appear immediately after the reception of the injurious influence. A number of instances of prolonged incubation have been reported, many of whicli are open to doubt. Some of these, however, are hard to explain. Such, for instance, is the case of Blaxall,^ where, after spending five days in the harbor of Port Louis, two of the crew of a man-of-war were attacked, at the end of, respectively, twelve and four- teen days, with quotidian intermittent fever, while two others developed tertian fever at the end of, respectively, forty-eight and one hundred and eighty-four days after em]>arkation. It is probaljle, in view of our present knowledge, that many cases of prolonged incubation represent relapses of earlier attacks, the manifestations of which have been pres- ent and would have been evident on more careful examination. Of recent years, since the discoveries of the malarial parasite and the inoculation experiments of Gerhardt,' Mariotti and Ciarrochi," Mar- chiafava and Celli/ Gualdi and Antolisei,* Angelini,^ Di Mattei,^'^ Calan- druccio," Bein,^- Baccelli,'" Sacharov,'* the suljject has been considered in a much more intelligent manner. The period of incubation in these cases where the blood of one malarial patient was introduced intravenously or h^qjodermically into a healthy individual, have varied greatly. In in- dividual cases there was a variance in the period of incubation of from six to eighteen days, while the average duration was from eleven to twelve days. Kecently, Bastianelli and Bignami ^'^ have contributed four new cases to this ILst and have made a careful study of this subject. In their words, the period of incubation in these cases of artificial inocu- lation represents " the time necessars' for the inoculated parasites to arrive, by multiplication, at the quantity necessary to determine the fever," . . . . " The period of incubation with a given variets" of para- sites varies inversely to the quantity of material inoculated." .... " The mean and minimum period of incubation under equal conditions varies with the various groups of the fever : it is least Avith aestival fevers, a little longer with tertian fever, and yet a little longer with quartan fever." They believe that they are justified in concluding that "' the period of incubation in experimental malarial infections is not a constant quantity, but varies in the same group of fevers and in differ- ent groups. In a given group of fevers it depends primarily upon the 1 Trailedes Fihre-s, p. 263. ^ j,,^/, ^^ Medecin milit., 1884, t. 3, p. 273. ^ Ziemssen's Cydopfjedia, vol. ii. p. 588. * Quoted from Hertz, loc. cit. '" Zeitsckr. f. klin. 3fed., 1884, 375. ^ Xo Sperimeniale, 1884, s. iv. t. liv. 263. ' ForUchritte d. Med., 1885, iii. Nos. 11 and 14. *i2i/. Mexl, 1889, Xos. 225, 264, 274. «i?(>: MeA., 1889, Nos. 226 and 227, pp. 1352, 1.358. ">/6(V/., 1891, p. 544, and Arch, fiir Hyr,., 1895, 191. '' Cf. Grassi and Feletti ; Cent, fiir Bach., 1891, ix. 403, 429, 461. '•■^ Charite Annalen, 1891, 181. " ^^ Deatsch. med. Wock., 1892, Xo. 32, 721. " Cent, fur Backt., 1894, xv. p. 158. ^ BuU. d. R. Ace. Med. di Bovia, 1893-94, Anno xv., v. xx. 151. Vol. I.— 7 ^linimum. Mean (days). (days). 11 13 6 10 2 3 98 MA LABIA. quantity of material inoculated. In different groups of fevers it varies with the rapidity of the cycle of development of the parasites and with the special capacity for reproduction of the parasitic variety." They have constructed the following table from an analysis of all cases of experimental malarial infection which they could collect : Period of Incubation. Maximum (days). Quartan fever 1-5 Tertian fever 12 Ji^stivo-autumnal fever 5 These researches, especially those of Bastianelli and Bignami proving that the incubation period in sestivo-autumnal fever may be as brief as two days, are of a great deal of interest. It is striking to see how well their conclusions agree with the deductions which have been drawn by other observers before the discovery of the malarial parasite. It is with the sestivo-autumnal variety of the parasite, that variety which is associated with the pernicious fevers, that the short periods of incuba- tion have been observed, while the older clinical observations of short periods of incubation relate usually to the same class of cases. We can- not, however, positively assume that these figures represent the period of incubation in infection as it ordinarily takes place, for we do not know how or in what form this occurs. The general results, however, of inoculations in tertian and quartan fevers agree quite closely with what might have been expected from clinical observation, while the demonstration that after small intra- venous inoculations in sestivo-autumnal fever the disease may appear in forty-eight hours makes it very easy for us to believe that, however the infection may occur, the true incubation period in some very malig- nant fevers may be extremely short. Plehn ^ advances an ingenious hypothesis to account for certain early manifestations of fever. He asserts, as has been stated above, that he has noticed in several instances a well marked febrile reaction occurring within a few hours after exposure in a malarious locality and simulat- ing a single malarial paroxysm. The examination of the blood was negative. From nine to twelve days later, however, characteristic mala- rial fever developed, the parasites being readily found in the blood. He suggests that by exposure in extremely malarious districts the individual may absorb a sufficient quantity of a pyrogenic toxine to cause imme- diately a single paroxysm days before the true incubation period has been passed through ; there is, however, little which can be advanced as proof of such an hypothesis. Basing our conclusions, then, upon the comparison between clinical deductions and the accurate observation of inoculation experiments, we may say that it seems likely that the ordinary period of incubation in tertian fever is about ten or twelve days, in quartan fever a little longer, while in sestivo-autumnal fever the period may range from twenty-four hours or even less to ten days or two weeks, averaging probably a some- what shorter time than in the case of tertian or quartan fever. Types of Fever. — The malarial fevers may be divided into two 1 Virch. Archiv, 1892, cxxix. 285. SYMPTOMS. 99 main classes : (1) The rc'i!:iilarly iiitcniiittont fevers, occurring throufrh- out the malarial season; (2) the more irregular, often more or less eon- tinned fevers, oecnrring in temperate climates, only at the height of the malarial season, the late summer and early fall. And under these two main classes one may sc])arate three distinct types of fever, dependinfr in turn upon infection with one of the three types of the malarial parasite which have been described ])reviously. Thus, the first class, the ret>:ularly intermittent fevers, includes («) ter- tian fever, with its combinations (double tertian fever), and (/>) quartan fever, with its combinations (double and triple quartan fever). The second class of fevers, that including the more irregular varieties, de- jK'uds upon infection with the third variety of parasite above described. (Occurring, as it does, at the height of the malarial season (August, Sep- tember, October), it justly deserves the name (c) cestivo-autumnal fever applied to it by the Italian observers. Tertian fever is common in almost all malarial regions. Quartan fever is, however, rare in many districts where the other forms of infec- tion are frequent. In the United States quartan fever appears to be rare ; in the last seven years, out of nearly a thousand cases observed at the Johns Hopkins Hospital, only nine cases of quartan fever have been seen. On the other hand, there are certain regions in which quar- tan fever is particularly common, as the neighborhood of Pavia in Italy and in certain parts of Sicily.^ These types of fever are the same wherever they exist. In tropical countries the severer types of 8esti^'o-autumnal fevers are in excess. As one passes aw^ay from the equator only the milder tertian and quartan fevers are to be seen in the earlier part of the malarial season, while the sestivo-autumnal fevers appear in the later summer and early autumn. Lastly, in districts where malaria is very uncommon the milder forms, tertian and quartan fever, alone prevail. Tertiax Feyee. — (1) Single Infections — Tertian Intermittent Fever ; (2) Double Infections — Quotidian Intermittent Fever. (1) Single Infections — Tertian Intermittent Fever. — This tvq^e of fever depends upon infection with the tertian parasite, an organism which, as has been described, possesses the remarkable characteristic of existing in the blood of the infected individual in great groups, all the members of which are approximately at the same stage of development and pass ^ The interesting fact that districts closely adjoining one another and presenting tlie same general physical conditions may be each the fof/er for a distinct t^-pe of malarial fever was noted by Trousseau some years before the discovery of the parasite. In dis- cussing the types of regularly intermittent fevers the great clinician says [Clinique niedi- cale, vol. iii. p. 42o, 2d. ed., 1S65): "The types seem to depend upon the nature of the miasm, and especially upon the locality which it infects, rather than upon con- ditions relative to the individual who is affected. Tours and Saumur, both situated on the left bank of the Loire, appear to me to present the same climatic and teHuric conditions, yet one observes at Tours only tertian fevers, while the several cases of quartan fever which I have met with there were individuals coming either from Saumur or Rochefort or from other regions where they had contracted it. One of the examples which has most impressed me in connection with the subject is the following : Fourteen soldiers imprisoned at Saumur came to Tours to testify before a court-martial. Tliey had been scarcely ten days in the last to\vn when nine of them were compelled to enter the hospital, affecied with quartan fever, the germ of which they liad evidently contracted at Saumur, since all the fevers which we observed with the inhabitants of Tours and the neighborhood were of the tertian type." 100 MALAEIA. through their cycle of existence together, all the organisms composing the group undergoing segmentation within a period of several hours ; it requires, as has been said, approximately forty-eight hours to complete its cycle of development. In infections, then, with a single group of parasites segmentation occurs at intervals approximately forty-eight hours apart. As Golgi so clearly showed, the febrile paroxysm is always associated with the segmentation of a group of malarial para- sites, and, as one might expect, the chief characteristic of this type of fever consists in intermittent febrile paroxysms occurring every other day. The regularity with which these paroxysms recur is truly remarkable, the onset sometimes taking place at almost exactly the same hour day after day. More frequently there are slight differences, generally, how- ever, of not more than two hours, between the time at which succeeding paroxysms recur. Our observations of nearly a thousand cases would lead us to believe that slight anticipation in the hour of onset is more common than retardation. The Paroxysm. — The paroxysm is usually divided into three clas- sical stages : (a) the chill ; (6) the fever ; (c) the defervescence or sweat- ing stage. (a) The Chill. — This may begin without any premonitory symptoms. More commonly, however, for a period of from a few minutes to half an hour the patient complains of uneasy sensations, a slight headache, or perhaps a little giddiness or fatigue. Not infrequently the onset is preceded by yawning. If the temperature is carefully noted during this period, it will usually be found that a slight elevation has already begun to appear. Immediately after this the patient begins to complain of chilly sensations, usually up and down the back ; these increase, the patient begins to shiver, and soon a general shaking chill follows. The chill is often extremely violent : the teeth chatter ; the whole body is thrown into so violent a tremor that the bed and often surrounding objects in the room are shaken. The skin is pale or often somewhat cyanotic and cool, though wholly disproportionately so in comparison to the intense feeling of cold complained of by the patient. It is often moist, while the erection of the hair follicles gives rise to the characteristic "goose flesh." The pupils are usually dilated. The patient complains often of headache, buzzing in the ears, vertigo, and sometimes of troubles of vision. The pulse is small and rapid and often of rather high tension. There may be nausea and vomiting. The duration of the chill varies materially in different cases ; it may last as long as an hour, though usually the period is considerably shorter — from ten minutes to half an hour. Not infrequently no actual shak- ing occurs, the patient complaining only of chilly sensations. Occa- sionally, though very rarely in this type of fever, the chill may be entirely absent. Thus out of 339 cases classified by Hewetson and the author at the Johns Hopkins Hospital, chills or chilly sensations were present in 95.5 per cent, of the cases. During the period of the chill the temperature of the patient rises rapidly, and at the end of the chilly sensations may have reached almost its height. Generally, almost the maximum point of temperature is reached within two hours after the onset of the paroxysm. (6) The Febrile Stage. — After a certain length of time the chilly sen- SYMPTOMS. 101 sations beconio less marked and are intcrriiiitt'd by flushes of heat, wliioh be- come more trefpient, and finally wholly replace the chill. Then begins the second or febrile stage of the ])aroxysm. The patient complains of an intense burning heat ; the skin is flushed, hot, and dry, the conjunetivre injected, the pulse becomes fuller, but remains rapid ; it may be dicrotic. The patient com- plains bitterly of headache and often of vertigo and buzzing in the ears. The coverings for which but a short time ago he had begged are now^ thrown aside. Often there is in- tense thirst. The patient is frequently restless, throw- incr himself from one side of the bed to the other. In some instances there is active delirium. A case ob- served by the author jumped from the window of the ward during the febrile stage of a double tertian paroxysm, killing himself by the fall. In other instances the pa- tient is dull, drowsy, and typhoidal in appearance, complaining upon inquiry only of intense headache and aching pains in the back and the extremities. Xot infrequently there is a slight cough. Sometimes there is vomiting or diar- rhoea. Bleeding from the nose occasionally occurs. On physical examination the face is flushed, the con- junctivae are injected ; the tongue is often dry and coated. There is often a dusky, yellowish-gray color m c Oc>COOOO2 II .1 ^ 1 1 ! . T ] 1 ■ . / 1 - > - y ■1 . ■ ■' ;, It '■' f ; L , 1- :■■• ! ' ■ . .■ > . 1 — -- j , 1 r— -^— -' f^ 1 ^:- . 13 90 v*'"^'*"^ / ■j'^. ■,• 20 70 V ^ V '■ 2U 72 r '■-',''' i 1 ^ i 20 72 =r- . l.._^ A. M . ■^ ! fcj A.M. IT 72 \ ■ ]"" 8 A.M. 1 1 \ \ 10^ A.M. IS 72 ' t 1 rsj N. 1 1 1 ! i 1 I '. 2 P.M. 13 72 l! 1 i ' 4 P. M . 1 IN ' ! :' ' 6 P. M. JiJJW i 1 8 P. M. 1 1 1 10 P. M. :■; '-3 ^ 12 M. / 2 A. M ^ 2- ■;, V 4 A. M . ^ b A. M- 16,72 ' w 8 A. M . j 1 ' 10 A. M. 21 1": : ■ ^ 12 1 1 • ^ — ■ 2 P. M. 24,S-J 4 p. M. h * 6 P. M. 20 60 [ 1 . ~ K 8 P. M. 1 > 10 P. M 20 61 1 1 : 1 V i 1 in 12 M. t 1 ^ ■ ! ' ' ! ' h : 2 A. ,V 20|64 :< , ; i i . j 4 A. M. 1 .,*» 1 1 1 6 A. M 20JfiS 1 ! ! 8 A. M 1 ■ 1 , • 10 A. M ts ' 12 N. 1 2 P. Mi / 4 P. M. i / 6 P. M. 2'l.K > / 8 P. M. r^l 10 P. M. 20 ■ n 12 M 1 \ \' ' 2 A. M. ^ 1? 00 1 ' V 1 1 , 4 A. M. A. M. ^ 6 IT 72 ^*^ II '8 A.M. i 1 ' , 10 A. M. ! > 12 N. 1 ill __•- " "^ 2 P. M 20 -JJ T^ 4 P. W . > 6 P. M. V 8 P. M . < 10 P. M. 70 / 12 M. y 2 A. M . IS 13 >J1 V 4 A. M . 1 > 6 A. M 13' « \ 3 A. M. > |0 A. M 13 72 12 N. < 2 P.M|. 1: -i ^ 4 P.M 6 P.M. 20 'JO i 8 P.M 10 P. M 20 •;! i 12 M- [ 2 A. M i li'.l K ' ^1 4 A. M. j ^, ; 6 A.M. 18 00 \ * 8 A.M. 1 1 ■ > 1 13 A.M. .6 7, ! , : / 12 N. 102 MALARIA. to the skin, while the lips and mucous membranes are pale. Herpes on the lips and nose is very common. Various cutaneous eruptions have been noted, usually erythematous in nature. In several instances the author has observed an extensive general urticaria. The respi- ration is not particularly accelerated, though the pulse is often rapid and sometimes dicrotic. The lungs are generally clear on auscul- tation and percussion, though, not infrequently, evidences of a general bronchitis — sonorous and sibillant rales — may be heard throughout the chest, more frecjuently in the back. The heart sounds are usually clear, though a soft systolic murmur may be heard over the body of the heart. The abdomen is generally natural in appearance. The area of hepatic dulness is often somewhat increased. There is frequently tenderness on pressure in the region of the spleen, while the area of the splenic dulness is almost invariably increased. In most cases the spleen is easily pal- pable. This has been the case in 73.4 per cent, of our cases in which notes were made. In fresh cases the border is rounded and soft ; in older cases, where there have been numerous previous attacks, the bor- der is often sharp and firm, reaching sometimes a considerable distance below the costal margin. The splenic tumor is particularly striking in children. The most marked splenic enlargements occur, however, in the more irregular sestivo-autumnal fevers. Massuriany^ noted the presence of a soft souffle over the splenic area, v.'hich Bouchard has compared to the uterine bruit. During this period the temperature reaches its maximum point. Temperatures as high as 108° F. have been noted. The duration of the febrile period is usually four or five hours, though, not infrequently, considerably longer. (c) The Sicecding Stage. — After the stage of fever has existed for four or five hours it is usually followed quite suddenly by the third or sweat- ing stage of the paroxysm. The patient begins to feel relief from the sensation of oppressive heat from which he has been suffering, and then, quite suddenly, breaks into a profuse sweat. The sweating is often excessive ; the night-clothes and bedding may be soaked. In asso- ciation with this the temperature falls, usually quite rapidly. The pulse, which has been rapid, becomes slow and full, and the patient often passes into a refreshing sleep. The temperature falls, almost in- variably to a subnormal point. The duration of the sweating stage varies considerably. The defervescence is generally somewhat longer than the rise of temperature, though it may be very short and sudden ; it commonly lasts from two to four hours, though often somewhat longer. The average length of the entire paroxysm from the time the tem- perature passed 99° F. until it reached this point again averaged, in 173 cases observed by the author, about eleven hours. The paroxysms occur more frequently during the day than during the night, the onset being, perhaps, more commonly noted between midnight and noon, though it may occur at any hour of the day or night ; indeed, jDaroxysms begin- ning in the afternoon are not at all uncommon. In children the paroxysm differs often from that observed in adults. Very commonly in young children both the first and third stages, the chill and the sweating, may be absent or abortive. The first stage is then generally represented by a slight restlessness. The face looks 1 St. Pet. med. WocL, 1884. SYMPTOMS. 103 pinched, the eyes aro sunken ; the fingor-tips and toes bocomo cyanotic and cold, while the child may yawn and stretcii itself. Nausea, vomit- in<2: and diarrlKca are particularly common. These may be the only manifestations of the lirst sta<>;e. Commonly, however, these sym[)toms are followeil by <>rave nervous phenomena. The chill in malaria, as in other acute diseases, is not infre(piently represented in the youn^ child by g;eneral convulsions. These begin usually with a slight spasmodic twitching of the eyelids or of the extremities, the spasm soon becoming general. The febrile stage and the whole paroxysm are often shorter in the child than in the adult. The sweating stage may be wholly absent. In many instances, besides a slight coldness of the hands and blueness of the finger-tips, and a somewhat pinched expression of the face in the first stage, the first and third stage of the paroxysm may be entirely lacking. The Intennifoiion. — In the period of intermission the patient often feels quite well, so much so that it is not uncommon for patients to pass through a number of paroxysms before consulting a physician, believing after each that the disease is at an end. The temperature after the sweating stage becomes almost invariably subnormal, and often remains so during the greater part of the next day. About forty-eight hours after the onset of the first paroxysm the fresh group of parasites proceeding from the segmentation of two days before having reached maturity and entered again upon segmentation, a fresh paroxysm begins. Often, as has been said, the time of onset of several successive paroxysms is almost exactly the same. More commonly, though, there are slight variations of an hour or two, anticipation or retardation. In these instances the parasite passes through its cycle of existence a little quicker or a little slower than in the typical forty-eight hours. Slightly anticipating paroxysms are very common, more so than retardation. The Blood. — The blood shows the presence of one group of the characteristic tertian parasites. These organisms are to be followed through all the stages of their development. They are most striking and most readily observed several hours before the paroxysm, when they are large and contain most pigment. At the time of the par- oxysm and immediately before this the picture may not be so striking, as many of the parasites which, earlier in development, are to be found w4th great frequency in the general peripheral circulation, become accumulated in certain of the internal organs, where they remain during the period of segmentation. Segmenting parasites are usually to be found in the peripheral circulation, the first being seen several hours before the onset of the paroxysm ; at times they may be present in large numbers. Large swollen forms of the organism with very active pigment granules, or deformed and vacuolated forms, are also common during this period. Often the fragmentation of these bodies may be seen, and numerous small pigmented extracellular forms resulting from this fragmentation may be found. These swollen vacuolated and frag- mented forms appear to be more common where recovery is taking place, and there is every reason to believe that they represent full- grown parasites which, failing to undergo segmentation, have become degenerate and sterile. During and just after the paroxysm the pro- cess of phagocytosis may often be observed under the microscope, and 104 MALARIA. pigmented leucocytes are always present. The elements taken up are for the most part the free pigment clumps from segmenting forms, the segmenting form itself, fragmented extracellular bodies, and flagellate forms. (2) Double Infections. — Quotidian Intermittent Fever. — Single tertian infections are among the mildest forms of malarial fever which are observed in temperate climates ; more commonly the individual shows an infection with two groups of the tertian parasite. These groups reach maturity on alternate days. Segmentation, then, of a group of parasites occurs every day, and, as one might expect, daily paroxysms, quotidian intey^mittent fever, result. The paroxysms in these instances are similar in every way to those of single tertian infections. The manner of onset and duration are the same, while during the periods of intermission the temperature is likewise almost always subnormal. It is common, however, for the paroxysms on successive days to show slight constant differences in their hours of onset, one group of para- sites arriving at maturity at an hour slightly different from that of the other. These differences are usually not great, though they may be considerable, one paroxysm beginning in the morning, that upon the following day in the afternoon. Very commonly one set of organisms is more numerous than the other, causing thus a more severe paroxysm. The chart then shows alternate mild and severe attacks. These facts alone might lead us to recognize the dependence of this quotidian fever upon a double infection without the confirmation obtained by examina- tion of the blood. The blood shows the presence of two groups of the tertian parasite in different stages of development. Thus at the time of the paroxysm, Fig. 2. Double tertian infection (quotidian fever). while one group is full grown and in the stage of segmentation, the other is represented by smaller, slightly pigmented, actively amoeboid bodies. The question of the origin of these double tertian infections is interesting and by no means wholly clear. Very commonly the first several paroxysms are tertian in nature, daily chills appearing only later on in the course. This may well be, and probably is due to the fact that at the time of the original infection there were two groups of SYMPTOMS. 105 parasites, one of which was so nmch sinaller than the other as to take materially lon^ 4-,^ ' -\ 3Wf- ■* ■"* 1 ■ ']' "1^ "i \ y~— L I ; I 6 p.M- ^ -^ "N" - M_p^ .J 5.^ H — - — — — — "-"i \ -r ; < - i 2 A. .1. / 4 A. «. — -t- £ 1 6 A.^.l. .' .'i S-; 8 A. [.1- ^^ 3 il i3 i ' ' ^ ■ 1 ^■^y|,.. ■ : K 1 ^, iir^i-- ~ c? =' ; > ^.^-I*'- < ~ 1 ; : _^ V 6, P.M. i; d ;r, 1 8 P. k ..-•^ lOP. |M. P V >• ■-^ 1 2 M . ^ — y 2 A. »1. ^ TT /•^ *f 6 A. M. g IS !^ SA.fvl. p N ~~^)i\ \.Sl. LPH. GRS. K 1 A: M . ,-. l! V 2-4 H. 2 :.. »j \ 2 P. [1I . , : ~ 'J, i i ; V^ -±M!L_ il < ill ■^ e P. M. ;| \ ! ! m — . : , , ■ : i OP. -1-: -^ 3u T-^T- 1 i ' ' / 2 M. o" ~ 1 : c 2..M. ' S' '* .„ , J / -^ 4 A. [.!• 1 ^i- < 6 A. iM . ! i 2. Cl 3 A. M. 1 "-;>• i iOA.M. . ^ 2i ' .V-. 1,1 '"■■■\ ! Of 1 :'■'. r 2 P. M. ! ~ ; S3 i ' i 4 P.M. ' 1 6P.J.1. 1 ^ 'QU ;,.SL LPH grs.t|t. 1 P' !^J1^ f 1 , it' 7 .> 4 M 1 1 1 i ' I2M.I -r 2A.f.. 1 < ' 4 A. A. \ 6 A. .1. V 8 A. VI. s 10 A. [^. ' : ; = ; 1 2 \ . ; l_^ -5 ~ 1 \ 2 P. .1. - " 1 4 P.M. ' j ;i 6 P.M. ' L _ ^r^ 0P.I.I. ill 1 _ — =_ j P. M ■1 ', ! 1 i 1 12 M. -ST 2 A. H. 1 '-^ " ~ ^^. 6 A. J\. iln+- 1 5 &3 1 ^, 8'a; 'I- li hi! 1 oxysms show, usually, a subnormal temperature. The periods of apy- rexia are, however, very brief, as one may readily conceive when he considers the length of the paroxysm, lasting, as it often does, tliirty-six hours or over. 110 MALAEIA. In those cases in which the paroxysms occur at intervals of approx- imately forty-eight hours, one from another, the irreg- ularity in the hour of onset of the paroxysms is partic- ularly striking. In some cases there is marked re- tardation, intervals of con- siderably more than forty- eight hours occurring be- tween the beginning of one paroxysm and that of its successor. More frequent- ly, however, there is antici- pation, the paroxysms re- curring at intervals of less than forty-eight hours. Now, if, as already stated, the individual paroxysm should last thirty-six hours or more, it may be readily seen how short the period of intermission in these cases would be. Often, then, there is an almost continu- ^ s |-|w | -jj | g ||||| | ii|.iMi. ij i irii I | | ||| ||| | | | | | | | ||| || P'"r'l > ^^^^ high temperature, with occasional remissions or in- termissions lasting, per- haps, less than an hour — " malarial remittent fever." In many instances the new paroxysm begins be- fore the previous one has finished, owing either to an excessive prolongation of the first paroxysm or to an anticipation of the succeed- ing one. In these cases the result is, of course, a eow- tinuous fever. Usually, the continuous fevers resulting from sestivo-autumnal in- fections, though the tem- perature may never reach the normal point, yet show indications of the parox- ysms and sometimes occa- sional abortive chills. In some instances, however, all evidence of paroxysms may be absent, the chart closely simulating that of typhoid fever. Such cases are probably often due to infections s W-h '" ■■■| EZ ■\n('d 8 ). ti Zl wa 9 '< V. zz ■_w;d Ho6t\ * \ 9i \z Z < 06 13 s, -.4^11111111111111111111111 H 65 •w •V 91 n ■in ■V R -• 91 K ■li, ■V h '^ 7,% i-z ■w-v * t 1 , A\ m n •wv Z " ::::::::::::_'. ' -c- ^^ es 95 o |W z 'l-t'OA'SlSiNNind^l! ; || |j n « ■wjj ..4. 58 65 •wa 8 L.l.--- 86 n •W|-d e 3-. 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MI S£ 1 i-M SI T _...?' ____ 001 5E n'd -^T"v ;;;;;;- Kl n W 'd i^i 1""""" OZI 01- w -d iNr^i"""" ON E NO ds a aijv 911 01 m-d v^ -^ \ -y-- 1 1 1 9!.l 3£ |Wi-d z 5^: We Nods a 3 1dV on 9E I'l?!^ z > T 1^^ II ' 1 fdi OE M 'A: 3N E NOdS d3idV oil 95 WfV R 1 ■■(' ON ONO s aaliiJvi W!-v 9 'IM"V *■! i ' ' ' ' ' 1 ■ y :::::::. MI 95 im-v si 1 1 :■ ' M V\ .T__t___^ i ■m S 1 1 1 < ■ ' ■III WI 65 ,W'd 01 ■ ~"^^^ 1 : :wd e' "~>L 1 1 ' ' +wrd 9' . ' ' , "^-^ ' 1 HI 'd t ' I , 1 1 . L '• '. ~~---». :jj 95 q; i'% o o 'o 'i S o 1 S S n CC SYMPTOMS. 1 1 1 with nu)iv than one oroup ot" pai'asites. It is [)r()hahly tiMic that the long duration of some of the paroxysms is accounted for by the fact tliat tlie sei2;inentation of a given group of jiarasites occurs through an appreciably greater length of time than iu the regularly intermittent fevers. The result of all this is that the chart of {estivo-autunuuil fever presents very connnouly somewhat the foll<»\\ing ])icture : At the onset there are several intermittent paroxysms occurring at intervals of from twentv-four to forty-eight hours or a little more. After a few of these attacks the fever becomes irregular or continued. This may occur, as has been said, in several ways : (1) Throuf/li iiiudlJicatioiif< of the carve in the iiulii-idKal paroxysni ; (2) bjj modification in HucceHnion of the paroxysms. (1) The important modifications of the curve are the following : (a) The lack of a sharp initial elevation, so that the curve rises in a slow and continuous manner ; (6) the occurrence of a pseudo-crisis, so that the attack tends to lose its individuality ; (c) the prolongation of the paroxysm, which is usually associated with an exaggeration of the thermic oscillations during the fastigium. (2) The modifications in the succession of the paroxysms may be («) the anticipation of the paroxysms ; (6) the retardation of the paroxysms ; (c) the prolongation of the paroxysms, by which apyrexia is made incomplete ; {d) the occurrence of slight oscillations in temperature during the period which ought to be one of apyrexia ; {e) the redupli- cation of the attack. Very often when the case first comes under observation it is already one of " remittent " or continued fever. The chills are frequently ab- sent ; the patient complains bitterly of headache and general pain in his back and extremities. He is usually dull, drowsy, and apathetic, though there may be marked delirium. The face is flushed, the con- junctivae are injected, the tongue dry and coated ; there is sordes upon the lips and teeth ; the patient remains continuously in a condition similar to that described in the febrile stage of the ordinary paroxysm. In these instances it is often absolutely impossible, without examination of the blood, to distinguish the case from one of typhoid fever. The writer has repeatedly seen patients with sestivo-autumnal malaria placed under treatment as cases of typhoid fever, the attention being first drawn to the true condition of things by a sudden fall of the tem- perature to normal, or by the discovery of the small amoeboid hyaline parasites within the red corpuscles. Grave cerebral or abdominal symp- toms develop, often early in the course of these subcontinuous fevers, which frequently tend to become pernicious. Careful observations may show that these symptoms are paroxysmal. Delirium, drowsiness, stupor, coma, grave cerebral symptoms, local spasms, general convul- sive seizures may occur, or perhaps profuse vomiting or a choleriform diarrhoea with collapse. In fact, any of the symptoms which will be discussed under the Pernicious Fevers may suddenly develop in the course of subcontinuous sestivo-autumnal infection. These instances of more or less continued fever are occasionally referred to as " malarial remittent fever. ^' They have been admirably described by Baccelli, who recognized their true malarial nature, under 112 MALARIA. "TTOir:::::::::::::::::: ■"■''■ -. - "3 ^ iw-flt ■ ' " m n ^ 3i'' - -__ - L ■w ■WiV. o^t . 1 ZL 02 ■ WiV 8, --- . -/ _ . - 'Wiv 91 :«j»lt :: ::: : ■j^t- --- .J fli 8Z J '' ZL 9£ _3p2i. :: ::::::::: :: •wid e - - - . S9 ot; •w'd 9 ~ 1 -., = ::?' "i zc ■W|d s .;; CO _ iSIl ___ . ... 3 08 t5 •Wi» 01 ' " - "" •W"|V 9 .. . 89 92 --'' J - ! _ _ 08 ZE •WiV Z .. '( \-Vt Z L •fl'"" . . f8 82 W |d 9 S>- - - .- ... W*|d t -_''s,_._ 88 K ■f'l"' 2 ,. - !l. _. " " w - lSy_ _.. _ _ ' _ _ . OS K t ■Wl'O . _ 08 n •W|V 1' - . J k, 26 82 'W|V z 1 "W Zl •W|d oy .^' ■fci t™ I'' « ... 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" " ^ ■- ' 001 t2 •w-vz| .c- ■J-'WBI ^ 2G t2 ■Wjd 01 F ^ZKJdjt, ... _ W 02 __^9t_ ___ __ m. __T!r5F^_ ___ _ _.._ 96 82 ■W ( 'f 2^f tOl 82 I ■W V si 1 96 82 ■W V 9| J •wvt 001 OS •wvz / J - JiiSL ... ... . --,?..- on 08 •W,dO. ,£,. ■Wd9 --,, f8 92 ■wjds i, ■Wjd . ^ ■■ = , ^ _ ^ - 801 98 3 w-jd s - T ---i 021-98 ^ ]_'N El NOISS WC V NO xysm is usually followed rapidly by a second, which generally ])roves tiital. Othhij Ckhebkal Manifestations. — In other instances most decideil cerebral symptoms of a different nature may occur. Delirium which may be maniacal may be observed. Active delusion.^ and halluci- iKifioiis are not uncommon, while in some instances tetanic convultiions have been noted. In a number of instances hemiplegia, has been associated with the paroxysm, disappearing after the attack. At times distinct symptoms of bulbar paralysis may occur. In one of these cases carefully studied by Marchiafava ^ the special localization Df the parasites in certain foci in the medulla was confirmed post- mortem. Hemorrhagic Type, — In some instances of pernicious fever grave hemorrhagic symptoms may occur — epistaxis, haemoptysis, extensive cutaneous hemorrhages. Several of these cases are described by Mar- chiafava and Bignami.^ Algid Type. — This is sometimes extremely insidious and fatal. After several paroxysms which are in no way remarkable the patient very suddenly passes into a condition of extreme collapse. This does not occur at the beginning of the paroxysm, but at the time when the stage of fever should exist. The temperature may be but slightly elevated ; indeed, in some instances it is subnormal. The condition is not unlike that in Asiatic cholera. The mind is clear, there is little suffering, ])ut extreme colla])se. The eyes are sunken ; the features drawn and jiinched ; the face expressionless ; the tongue dry ; the skin moist and covered with a cold sweat. The patient may be so quiet and uncom- plaining that it may be, as Laveran states, only through an accidental examination of the pulse that the true state of affairs may be discovered. The pulse is very rapid and feeble and thready, almost impalpable, be- coming imperceptible at the wrist before death. Physical examination of the thorax is negative excepting for the feeble action of the heart. The second sound at the base may be quite inaudible. The abdomen is usually retracted ; there is often tenderness on pressure in the region of the spleen, which is palpable. Sudoriferous Type. — A sudoriferous type of paroxysm has been •described, in which, during the last stage, the sweating becomes exces- sive and the patient passes into a condition of collapse with a thready pulse and cold extremities. Without vigorous interference the case may end fatally. Bilious Type. — A ty^Q of paroxysm has been described by cer- tain observers, the chief symptom of which is the vomiting of large quantities of bile-stained fluid ; this is usually associated with stools of a similar nature. Gastralgic and Cardialgic Types. — Severe gastralgic parox- ysms associated ^\i\^l profuse vomiting, and often with hsematemesis, ^ Lav. d. III. Cong. d. soc. It. d. Med. Int., Eoma, 1890, 142. ^ i^^. p,^_ 116 MALARIA. may occur without the existence of striking intestinal symptoms. An attack of this nature is well described by Laveran.^ Choleeiform Type. — In certain instances in which the chief localization of the parasite is in the stomach and intestines the patients present a clinical picture strongly resembling that of Asiatic cholera. These cases have been particularly studied by Marchiafava.^ The paroxysm usually begins with profuse vomiting and diarrhoea ; the dis- charges may resemble those of cholera. The skin is cold, moist, and clammy. There is cyanosis of the lips and extremities ; the pulse is rapid and thread-like. There may be cramps in the extremities. The condition closely resembles the algid stage of Asiatic cholera. If the paroxysm be not fatal, profuse sweating may follow, with an intermis- sion in the symptoms. Anatomically, the mucous membrane of the stomach and intestines is found to be filled with malarial parasites. These may produce actual thrombosis of the vessels of the mucous membrane with superficial necroses and ulceration. Pneumonic or Dyspnceic Type. — Baccelli^ and others have de- scribed a type of paroxysm the symptoms of which suggest strongly a pneumonia. This admirable observer, however, as long ago as 1866 recognized this condition to be distinct from a true complicating pneu- monia. There is intense thoracic pain, great dyspnoea, and a painful cough. There may be moderate dulness over the affected lung with coarse, sonorous, and sibilant and finer moist rales. Laveran * has seen a fairly abundant hsemoptysis following an acute dyspnoeic paroxysm. In other instances, despite the extreme dyspnoea, physical examination may be quite negative. The sputum is mixed with dark fluid and clotted blood. The condition is certainly not a pneumonia ; it is more probably an active congestion of the pulmonary vessels. In the absence of autopsy records in cases of this nature one can but suspect that they represent a special localization of the parasite in the pulmonary capil- laries. H^MOGLOBixuRic Type — " Malarial hcematuria." — Hsemoglobi- nuria is a not uncommon symptom in the graver fevers in cer- tain malarious districts. In temperate climates it is rarely seen. The ultimate cause of its production is not yet settled. A con- tinual destruction of the red blood-corpuscles is going on throughout every malarial infection. This occurs in various ways : (1) The para- sites, developing within the corpuscles, form the black pigment, melanin, at the expense of the corpuscles in which they grow, the corpuscles becoming gradually decolorized and destroyed. (2) In many instances the red blood-corpuscles containing the parasite undergo a pre- mature necrosis, becoming brassy colored and shrunken. (3) Sometimes the decolorization of the corpuscles containing the parasite occurs quite suddenly, the corpuscles bursting, as it were, and setting free their haemo- globin in the blood current. Thus, during an ordinary malarial attack there is always a certain amount of haemoglobin set free in the serum, but, as this amount does not pass beyond the limit of the quantity which can be disposed of by the liver, it does not appear in the urine. ^ Traite des Fievres -palui^tres, Obs. xxxviii. '' Gent. J. Allg. Path. u. Path. Anat., 1894, V. No. 10, 418. ^ Studien iiber Malaria, Berlin, 1895. * Traite des Fiewes palustres. sYJirroMS. 117 It is doubtless, in part, to this constant destruction of the red corpuscles, with the liberation of their luemoglobin, that the polycholia and slight jaundice so coninionly observed in malaria are due. Ponfick estimates that uj) to one sixth the total number of the red blood-corpuscles may be destroyed and disposed of in the economy without the haemoglobin appearing, as such, in the urine. If this destruction of the red blood- corpuscles becomes unusually great, and the quantity of haemoglobin separated from the disco-plasma of the red blood-corpuscles exceeds the amount which can be taken care of by the liver, hemoglobinuria will result. It is not, however, only the infected corpuscles which lose their lifemoglobin in these instances ; great numbers of their uninfected fel- lows are equally aifected, just as in the ordinary paroxysmal hsemoglo- binuria. Some substance excessively toxic to the disco-plasma of the red blood-corpuscles must be present in the circulation, or some change has taken place in the blood serum by which it has lost its isotonicity, but what these changes are and to what they are due are by no means clear. There is much which might lead us to believe with Baccelli that some toxic substance, produced perhaps by the parasite itself, may be at the bottom of these changes. Why, however, heemoglobinuria should be so common in certain regions — as, for instance, Greece and West Africa — and so infrequent in many other more malarious dis- tricts is quite inexplicable in the present state of our knowledge. Clinically, these cases are among the severest forms of malarial fever. The same condition is known in Western Africa as " black water feverJ' By many observers, particularly by the French, the term bilious hcenioglobinuric fever has been used. Not infrequently the term " hcematuric " is used, and, indeed, as the interesting researches of Joseph Jones show, actual heematuria often occurs. The hsemoglo- binuric attack is rarely the initial symptom of the infection. Usually the patient has had repeated attacks of malaria, the haemoglobinuria appearing suddenly with a relapse, or, if it be the first infection, the hsemoglobinuric attack is preceded by several intermittent paroxysms. In cases w^here either in a relapse or in a primary infection the hsemo- globinuria appears with the first actual paroxysm, there are often pro- dromal symptoms lasting for from several hours to sometimes several days. It is probable that these are associated with moderate fever and often represent abortive paroxysms. There are loss of appetite, head- ache, indefinite pains in the extremities and back. It may be remem- bered that in many paroxysms of the more ordinary types of sestivo- autumnal fever the gradual onset of the paroxysm without chill is fre- quent : this is not true in the case of the hsemoglobinuric paroxysm, which begins almost invariably with a severe shaking chill. This is followed by intense pain in the back, head, and extremities, and by pro- fuse vomiting ; the vomitus consists of a deeply bile-stained fluid. The face is flushed ; the conjunctivae are injected ; the pulse is rapid; the patient is usually in a condition of great anxiety and apprehension. There is a well marked icteric hue to the skin. There is usually profuse diarrhoea. The first urine that is passed, in the early stage of the paroxysm, has a somewhat rosy reddish hue. This, however, rapidly becomes deeper, and is finally an intense brownish black color with something of a greenish tinge, and a greenish yellow foam on shaking. The vomitus 118 31 A LABIA. becomes of a deeper color, at first yelloAV, then green, finally sometimes almost black. There may be diarrhoea, the dejecta being green or brown in color, while in other instances there is constipation. During the stage of fever the patient generally becomes jaundiced. There is usually little delirium, the patient being quite conscious and in a con- dition of great anxiety and agitation. He often complains of severe epigastric pain, which is possibly associated with repeated vomiting ; in other instances the pains in the loins may be extremely severe, bearing, possibly, as Kelsch and Kiener^ suggest, some relation to the intense renal congestion. The fever is often high, the temperature touching, in some instances, 41° C. (106° F.) or even higher. The urine at the height of the process is of a deep brownish black color, and deposits on standing an abundance of reddish brown sediment. The amount varies considerably in different instances, in some being extremely scanty, in others amounting to as much as 1000 or 1500 c.c. The specific gravity varies inversely to the amount of urine passed. As the amount is generally somewhat reduced, the specific gravity averages above normal. The reaction varies ; it is generally feebly acid. There is usually an abundance of albumin. In some instances a test for the biliary coloring matters may be obtained. Kelsch and Kiener assert that this is the rule at the height of the process, while Plehn^ in eight instances was unable to obtain this test. The sediment consists of mucus,, bladder epithelium, numerous granules and masses of pigment, renal epithelial cells, and, almost invariably, hyaline and granular casts with epithelial cells adherent. In many instances blood-corpuscles may also be found, actual hemorrhages taking place into the kidney. Often, however, besides the profuse sediment of a brownish granular material,, occasional epithelial cells, and casts, not a sign of a red corpuscle may be found, the condition being a true hsemoglobinuria. In the simplest and mildest attacks the temperature remains elevated nine or ten hours, and then falls quite suddenly to normal, the urine at the same time clearing up, excepting for a slight trace of albumin with occasional casts. In some instances a paroxysm of this nature is the last manifestation of the process, complete recovery following. In other instances there may be repeated intermittent hsemoglobinuric par- oxysms, ending perhaps in recovery. Very frequently, however, the condition is more severe. The fever lasts much longer ; the vomiting and diarrhoea continue ; the jaundice becomes more intense ; there are perhaps occasional slight intermissions, but in the main the attack is continuous. The urine, as well as the fever, may show occasional tem- porary changes for the better, but these are of short duration, fresh ex- acerbations rapidly following. The urine becomes often scanty and more albuminous ; the patient becomes emaciated and pale ; the eyes are sunken, the tongue is dry, the pulse rapid and feeble, and eventually a fatal result follows. In some instances, however, recovery may occur when the patient is a])parently almost beyond hope. Certain cases pursue an extremely rapid fatal course. The initial chill, fever, vomiting, and diarrhoea are associated with almost complete suppression of urine ; that which is passed, often but a few drops, is in- tensely bloody. There is great agitation, intense prostration, the patient 1 Maladies des Pays chauds. '^ Beulsch. nied. Woch., 1895, Nos. 25, 26, 27. SYMPTOMS. 119 lulling into a condition of profound c-olUipsc and dying witiiin several days. Nephritis almost invariably follows the hfenioglobinuric attack. In the milder cases it is transient and slight. In many more severe cases, however, the end of the paroxysm is followed by the symjjtoms of a well marked nej)hritis, lasting sometimes for weeks and j)ossiblv even for months. In a certain number of instances this condition pur- sues a rapidly fatal course. The albuminuria and casts persist ; the quantity of urine remains steadily below normal ; the jiatient becomes unemic ; and delirium, coma, and convulsions ensue with a fatal result. Malarial ha?moglobinuria does not occur in all malarious districts. In some regions where pernicious fevers are relatively conuiKjn luemo- globinuria is rarely seen. The cause for this is not apparent. In Rome, for instance, the disease is uncommon. It is not very frequent in most of the malarious districts of the United States. In Greece it seems to be unusually common, while in certain parts of Africa it is seen in its most fatal forms. The hlood generally shows the pestivo-autunnial parasite.^ Predispos- ing causes appear to be any over-exertion or exposure, indeed anything which reduces the vitality' of the individual. Extremely interesting is the widespread idea in certain regions that quinine, which has so specific an action upon the parasites, may yet have an unfavorable influence, indeed be the determining cause of the hsemoglobinuric paroxysm. In Joseph Jones' interesting memoirs- a number of assertions of this nature appear. More recently Plehn^ in a valuable article upon the black water fever of Cameroon records his belief that in that climate, at least, the development of haemoglobinuria is often l^rought about by the ad- ministration of quinine, while the records of his cases of hsemoglobinurie fever treated with and without the specific malarial remedy show that the more favorable course was pursued by those cases which v>-ere treated expectantly. This view, however, is not held by the majority' of ob- servers. The tendency toward spontaneoiLs recovery in many of these cases suggests, certainly, that the presence of the haemoglobinuria, de- pendent on whatever it may be, may have an injurious eifect upon the life of the parasite. The Blood ix the ^EsTivo-ArTUMXAL Fevers. — The blood in the sestivo-autumual fevers shows the presence of the small form of the para- site described first by Marchiafava and Celli (" Haematozoon falciparum," Welch). As already noted in the description of the parasite, only the earlier forms in its cycle of existence are generally found in the per- ipheral circulation. These are the ring-like or amoel^oid hyaline liodies, which are often quite free from pigment. As the later stages in the development of the organism are rarely found in the peripheral circu- lation, it is natural that the period shortly before and during the early part of the paroxysm should be that in Avhieh the smallest number of parasites is to be found on clinical examination of the blood ; and this ^ This has been the case in those instances observed bv the Roman authors, and the descriptions of Plehn and others seem to point in the same direction. Owing, however, to the remarkable distribution of these fevers, to which reference has been made above, we should perhaps bear in mind the possibility that there may be certain fine differences between the parasites of the ordinary irregular fevers and those of the haemoglobiniiric variety, which may be brought to light by furtlier study. ^ Medical and Surgical Memoirs, vol. ii., New Orleans, 1887. ^ Loc. cit. 120 MALARIA. is the case. There are cases of sestivo-autumnal fever where, at this period, a prolonged search must be made before parasites are to be found. Always, howev^er, in the experience of the writer, parasites are present after a few hours have passed by. And I believe that it may be emphatically stated that there are no dangerous forms of malaria in which the parasite is not to be found after reasonably care- ful search. After the infection has existed for a week or two the crescentic and ovoid pigmented forms of the organism are usually observable. Phago- cytosis is very commonly to be noted, and pigment-bearing leucocytes are to be found throughout almost ail periods of the fever. The period- icity in the phagocytic action is much less marked than in the ordinary intermittent fevers. This is due in part to the presence at all times of parasites in diiferent stages of development, and in part to the early necrosis of the red blood-corpuscles which is so common in these fevers the dead fragments are speedily engulfed and carried away by the color- less elements. Occasionally, true macrophages, such as are seen in the spleen, may be found in the peripheral circulation ; these may be enor- mous, ten times the size of an ordinary leucocyte. They sometimes contain coarse granules, much larger than any ordinarily seen in the blood, having somewhat the appearance of eosinophilic granules. These cells may contain not only parasites, but red corpuscles, usually shrunken and brassy colored, including a parasite, and also entire smaller phago- cytes with their included pigment or parasites or corpuscles. Fevees with Long Intervals. — From the earliest times there have been described, besides the ordinary quotidian, tertian, and quartan intermittent fevers, other fevers with intermissions considerably longer ; thus fevers with intervals of five, six, seven, eight, nine, ten, eleven, and twelve days, or even longer, have been believed to exist. Celsus, who distinguished quotidian, tertian, and quartan fevers, referred to the occasional occurrence of fevers with longer intervals, but noted their rarity.^ After Golgi's first researches concerning the life history of the quar- tan and tertian parasites, and after the fact became settled that a third variety of parasite existed, whose cycle, under some circumstances, lasted but twenty-four hours, the fever in every instance being definitely con- nected with the segmentation of a group of parasites, it is but natural that many observers should have suspected the existence of other varie- ties of parasites which in turn might be related to these rare fevers with longer intervals. And Golgi in 1889^ advanced the hypothesis that the crescentic bodies which we know to be connected with the sestivo- autumnal parasite might bear a definite relation to these forms of fever. He believed that they represented a form of parasite which underwent a long, slow development, lasting from seven to twelve days — that, finally, segmentation of the crescentic forms occurred and paroxysms followed, just as in the case of the regularly intermittent fevers. This variety of parasite, however, differed in the greater length and the irregularity of the cycle of development, while the paroxysms, in like manner, recurred at irregular intervals, from seven to twelve days apart ^ ' ' Tnterdum etiam longiore circuitu quaedam redeunt, sed id raro evenit." ^ Ziegler's Beitrdge, 1890, vii. 647. SY^Ml'TUMS. 121 or even more. Canalis ' lioliovcd that the festivo-autumnal parasite possessed two so])arate evclcs — a shorter, lastiii<;' from one to two days, and a longer, associated Avith the crescentic and ovoid bodies, lastin*;- an indetinite lengtli of time, three or four days at least. Antolisei and Ang;elini - also believed that this variety of parasite was associated with fevers with loni::er intervals. Clinically, however, one very rarely observes cases showing a regular recurrence of paroxysms at intervals lonoer than every fourth day. On the other hand, it is not so very unusual to meet with cases where a lunn- ber of paroxysms have recurred at intervals of, approximately, six to four- teen days. In all these instances one is generally compelled to depend largely upon the statements of the patient. An analysis of those cases which have been observed since the recognition of the parasite and its diU'erent varieties shows that these fevers with long intervals may be associated with any of the varieties of parasite which we now know. Golgi noted the existence of such paroxysms in patients whose blood showed the sestivo-autumnal parasite. Bignami^ and Pes* described eases occurring in connection with the tertian parasite, while Vincenzi ^ has shown that they may be associated with the presence of any of the varieties of parasites which we now know, alone or in combination. The manner in which these fevers arise was described first by Bignami. As stated in the description of the parasite, the mere presence of the organism in the circulating blood is not sufficient to produce subjective symptoms. These appear first only when, from steady multiplication, the number of parasites contained in the circu- lation has reached a certain necessary quantity. With every period of segmentation their number appreciably increases. Not every fresh segment, however, continues to develop. Were this the case, every in- fection would become pernicious within a short period. With each par- oxysm a very considerable number of young parasites is destroyed — so great a number, in fact, that many, indeed the majority, of cases of ter- tian and quartan fever tend toward spontaneous recovery, though, to be sure, relapses often occur. To what this destruction is due is as yet a matter of doubt. In how far it may depend upon the protective power of the blood serum or upon an active defensive phagocytosis on the part of the leucocytes, or, possibly, upon the deleterious effects of some toxic substance produced, perhaps, by the parasite itself at the time of segmentation, is as yet wholly a matter of speculation. It is, however, not an infrequent occurrence to see, more particularly in tertian or quartan infections, a severe paroxysm followed by a complete disap- pearance of the symptoms, while the blood shows a disappearance of the group of parasites. The author has previously published charts of this nature.*' In such instances, through some means or other, the greater part or an entire group of parasites is destroyed at the time of segmen- tation. In these cases the result is usually complete apyrexia for a certain length of time, from several days to two weeks or even more, and then, after, perhaps, a little warning, a repetition of the paroxysms. 1 Fortschritte d. Med., 1890, Nos. 8 and 9. ^ Eifonna Medica, 1890, 320, 326, 332. ^Ibid., 1891, No. 165, p. 169. * Ibid., 1893, vol. ii. p. 759. ^Bull. R. Ace. Med. di Roma, 1891-92, p. 631 ; Arch, per le Sc. Med., vol. xix. f. 3, p. 263. ^ The Malarial Fevers of Baltimore, loc. eit. 122 MALARIA. In some instances the first paroxysm may be followed by a period of apyrexia, lasting, as in one of the author's cases, eight days before the development of a second febrile attack, and that, in turn, by another intermission of approximately the same length of time, and so on, the chart thus showing an intermittent fever with intervals of, perhaps, eight or ten or twelve days. And yet the examination of the blood shows the characteristic parasites of tertian or of quartan fever. The explanation, then, of these fevers with long intervals is not to be found in a parasite whose cycle of development lasts an unusually great length of time, but in the fact that the first sharp paroxysm is followed by the destruction of so great a number of the parasites that a long period — sometimes practically that of the period of incubation of the disease — must be passed through before the group again reaches a size sufficient to produce symptoms. The recurrent attacks repre- sent, as Bignami pointed out, recrudescences from attacks from which complete recovery has not taken place. Single paroxysms with long intervals, or, more commonly, one or two paroxysms occurring to- gether with long intervals between them, may exist for a very consider- able length of time in tertian or quartan infections. Thus, the author has had occasion to observe an individual who for over two years had had occasional chills at irregular intervals of two or three weeks, more or less, due to an untreated tertian infection. One or two paroxysms were almost invariably followed by an apparent complete spontaneous recovery, only to be succeeded in the course of from two to four weeks by another relapse. In another class of cases the paroxysms with long intervals are due to imperfectly treated malarial fever. Many patients living in mala- rious districts are in the habit of taking large single doses of quinine immediately following any outbreak of fever. Thus in an instance observed by the author a lady asserted that she had had paroxysms at intervals of ten days. The third or fourth paroxysm occurred under his observation, the blood showing the characteristic tertian parasites. In this instance the patient, by taking a single dose of quinine after each paroxysm, had accomplished the same end which nature accom- plishes in the other class of cases — ^viz. the destruction of the greater part of the group of parasites ; and in each instance a relapse occurred about ten days after the previous attack. The same explanation is probably true in the cases occurring in sestivo-autumnal infections. There is no evidence to show that there is any such thing as a regular type of fever occurring at intervals longer than every fourth day. The paroxysms in these instances differ in no way from those in tertian, quartan, or sestivo-autumnal fevers according to the variety of infection. Combined Infections with Different Varieties of Parasites. Combined infections with two or more varieties of the malarial para- sites may occur, though they are rather uncommon. In 542 cases of malarial fever classified by He wetson and the author there were only 1 1 such instances. Clinically, these cases present usually the features of an ordinary tertian, quartan, or sestivo-autumnal infection, and without examination of the blood the presence of two varieties of parasites LXFECTIOXS WtTlI nfFFERKXT VAIIIKTIES OF PAIiASFfFS. 123 wcnild oftoii ivmtiin iiususjx'clcd. This is duo to the fact that the two (litlcTcnt varieties of tlie oroanisin are rarely present each in sufficient number to proihiee symptoms at the same time. One type of the para- site ahnost always predominates, and is responsible for the clinical symptoms. Certain cases have been noted where a distinct alternation of symptoms has occurred ; a period of quartan fever, for instance, beinji' followed by spontaneous recovery, and succeeded by a period of tertian fever, which, if untreated, pursues the same course, and crives way tinally to a relapse of the quartan infection ; the parasites of l)oth varieties are present at the same time. In rare instances complicated fever curves may arise from a combined infection. This is, however, very unusual. The commonest combination in this climate is sestivo- autumnal and tertian fever. The Urixe. — The urine in the malarial fevers has no special diag- nostic features. There are no constant changes in the amount or in the .specific gravitf/ of the twenty-four hours' urine. The color of the urine is somewhat increased, due probably to the increased quantity of urobilin which is derived from the haemoglobin of the red blood-corpuscles destroyed by the parasites. The amount of urea excreted during the paroxysms is increased, just as it is during any other acute febrile con- dition. Albumin is usually present in serious cases. Thus, out of 284 cases examined by Hewetson and the author, albumin was present in 133 instances, nearly one-half. In many of these instances casts of the renal tubules may be found. Actual acute nephritis may occur. Thus in 4 instances out of 335 of our cases evidences of a severe acute nephritis were present — a nephritis which, apparently, owed its origin directly to the malarial infection. In 3 of these instances the nephritis was hemorrhagic in nature ; in the other case, which resulted fatally, there was an extensive acute diffuse nephritis. Ehrlich's diazo reaction may be present; it was found in 5.5 per cent, of our cases. The Toxicity of Malarial Urine. — Extremely interesting researches have lately been made concerning the increased toxicity of the urine during malarial fever. Brousse,^ studying the effects following the injection of the urine of cases of malarial fever into animals, arrived at the following conclusions : " (1) The urotoxic coefficient calculated by Bouchard's formula, the mean coefficient being 0.464, rises during the paroxysm, and the physiological effects observed are those which usually follow^ the injection of urine — dyspnoea, myosis, falling of tem- perature, exophthalmos, and furthermore convulsions ; (2) this toxicity is diminished during the period of convalescence in intermittent fever, very much below that of the urine during the paroxysm, and moreover below that of the normal urine." ^ Roque and Lemoine ^ studied the urine in 3 cases of malarial fever — one a case of tertian fever and two cases of pernicious comatose mala- ria. Their conclusions were as follows : " (1) The pathogenic agents of paludism form, in the blood, a large quantity of toxic products, a great part of which is eliminated by the urine. This elimination is at its maximum immediately after the paroxysm, and lasts, generally, twenty- ^ Quoted from Laveran, Du Paludistne, etc., Paris, 1891. ^ Societe de Med. et de Chir. pratiques de 3fontpellier, 14 Mai, 1890. =* Bemie de Med., 1890, p. 926. 124 MALARIA. four hours, at least in the paroxysms of tertian fever. (2) Sulphate of quinine acts by favoring the increase of this elimination. (3) Certain pernicious fevers, showing a complete absence of toxicity in the urine, depend probably upon alterations in the kidneys and liver, and the return of the urinary toxicity should be considered a good prognostic sign, (4) Finally, it may be noted that in two cases recovery has fol- lowed a more increased elimination of toxines than that observed after the preceding paroxysms." In discussing this paper Lepine justly remarked that injections should be made not only with the pure urine, but also with a solution of the salts of the urine made after calcination. This alone can give a reliable idea of the toxicity of the urine dependent upon organic compounds. More recently Botazzi and Pensuti ^ have made an elaborate control research, and, while finding the same general results as Roque and Lemoine, dispute their conclusions. Their studies were carried out in ten cases. They collected urine during and after the febrile periods. They found that during the paroxysm the urine showed a less intense color than afterward. During the febrile periods examination of the urine with the ordinary reagents which are used in qualitative analysis showed always a diminished amount of alkaline and earthy phosphates, Avhile that voided after the paroxysm showed sometimes a considerable quantity. The specific gravity of the urine passed after the paroxysm was higher than that during the paroxysm. They state that under other conditions the urotoxic coefficient has been shown to run parallel to the elimination of the potassium salts, while the presence of peptones in the urine increases appreciably its toxicity. Both these substances they found present in increased quantities in the urine passed after the paroxysm. The urobilin, as already stated, is present in increased quantities in the urine of malarial fever, and especially so in that fol- lowing the paroxysm. The toxicity of this substance has been demon- strated by these authors, who found that the urine passed after the par- oxysm, when decolorized, lost half its toxicity. They assert, in opposition to Boque and Lemoine, that " there is no need to suppose the presence of special toxic substances of the nature of leucomaines to account for the toxicity of malarial urine " [after the paroxysm] ; " the potassium, the phosphoric acid, the peptones, the urinary pigments, and especially urobilin, which are found in this urine in markedly increased quantities relatively to the normal urine and to that of the febrile period, are of themselves a sufficient explanation." The cause of the increased presence of these substances is not difficult to appreciate. The potassium salts and the jDigments which they believe to be the chief cause of the hypertoxicity result from the destruction of the red blood-corpuscles, and the phos- phoric acid and peptones are doubtless due to the disintegration and com- bustion of the albumins and nucleins of the cellular elements of the tis- sues. They have not found evidence of a marked retention of toxic sub- stances owing to disease of the kidneys, as asserted by Roque and Lemoine. In conclusion, they state : " We think that we have demonstrated (1) that in the malarial fevers the febrile urine is' less toxic than that emitted during the apyretic stage ; (2) that the urine emitted during the period of apyrexia is more toxic than normal urine ; (3) that the ^ Lo Sperimentale, Firenze, 1894, xlviii. 232, 254. INFECTIONS Wrni DIFFERENT VARIETIES OF PARASITES. 125 toxicity of the urine of malarial i)atieiit.s aui>iiients constantly with the succession of febrile attacks, though in some cases this augmentation appears in the form of unex])eete(l and irregular exacerbations ; (4) that, as tiiere is nt)thing sj)eeitie in the course of the intoxications produced in rabbits with malarial urine, there is no need to suppose the ])resence of specific toxins or substances of the nature of leucomaines, for the salts of potassium, phosphoric acid, the urinary pigments, the peptones, all of which substances are eliminated in increased quantities, are a sufficient explanation ; (5) that the injection of febrile urine is followed by a slower intoxication, characterized by sopor, by increased diuresis, by diarrha?a, and mydriasis, while the apyretic urine produces a more acute effect, sometimes fulminating, characterized by clonic and tonic spasms and myosis, ' exhorbitisine,' spastic expiration ; (6) that to explain this different picture one may suppose that with febrile urine the polyuria and diarrhoea are due chiefly to the increased richness in the urea, while the peptones may contribute to the production of sopor. In the afebrile urines the salts of potassium, the phosphoric acid, the uri- nary pigments, and especially the urobilin, manifesting themselves as substances essentially convulsive, determine hypertoxicity. (7) Finally, besides the hsemocytolysis and the destruction of the cellular elements of the tissues, and the formation and elimination of toxic substances, there must exist intermediate factors wdiich account for the absence of increased toxicity after the first febrile paroxysms and the irregular ele- vation and diminution in the urotoxic coefficient in some other cases." Laveran speaks also conservatively concerning these experiments as a proof of the existence of a specific toxin. In conclusion, then, one may say that while a distinct increase in the toxicity of the urine has been shown to be present after malarial paroxysms, there is as yet no proof that this is dependent upon specific- products of the action of the malarial parasite. The Blood. — Besides the presence of the parasites, the examination of the blood in malarial fever reveals certain other changes which are at times valuable from a diagnostic point of view. {A) TJie Regularly Intermittent Fevers. — An actual ancemia always occurs in malarial fever. Kelsch/ Kalindero,^ Dionisi/ all noted that a considerable fall in the number of red blood -corpuscles to the cubic millimetre occurred after each paroxysm, while similar results were obtained by Dr. Kirkebride in some counts made under the author's observation in 1893. The fall in the number of red corpuscles may be quite considerable, though in tertian and quartan fever the restitution to normal is very rapid. Always, however, after several paroxysms have occurred there is a certain degree of anaemia, which, if the disease be allowed to continue, may become quite marked. The percentage of hcemoglobin falls with the number of corpuscles, but usuallvto a somewhat greater extent, while the return to the normal point, as noted by E,ossoni/ takes place more slowly than that of the- red corpuscles. 1 Arch, de Phys., 1876, ii. s., t. iii. 490. ■-' Jour, de Med. et de Pharm. d'Ah/erie, 1889, xiv. 123. ^ Lo Sperimentale, 1891, t. iii. and iv. 284. * Lav. d. Cong. d. Soc. Ital. d. med. Int., IF Congresso, Eoma, Oct., 1889, 121. 126 IIALABIA. The behavior of the colorless corpuscles in malarial fever has been noted especially by Kelsch/ Kalindero/ Bastianelli,^ and Billings.* It has been shown that the number of leucocytes in malarial fever is almost invariably subnormal. The smallest number of leucocytes is seen just after the paroxysm when the temperature is subnormal. From this time there is a gradual, slight increase, which becomes accentuated just before the paroxysm. A rapid diminution in number occurs again during the paroxysm. At no time is there leucocytosis. [B) The Estiva-autumnal Fevers. — The changes in the blood in the «stivo-autumnal fevers are very similar to those in the regularly inter- mittent forms, differing only in their intensity. The red corpuscles show a marked diminution ^vith each paroxysm. When the parasites are numerous this reduction amounts, sometimes, to as much as a million corpuscles during a single paroxysm. Between the attacks the corpus- cles do not show the same tendency to return to the normal number which is observed in the regularly intermittent fevers. The restitution is imperfect and incomplete. The number, however, rarely falls below one million to the cubic millimetre, although Kelsch has seen as small a number as five hundred thousand. The colorless corpuscles are almost invariably reduced in number. The changes in number follow the same course here as in the regularly intermittent fevers. There is a diminu- tion after the paroxysm, a slight rise just before the beginning of the succeeding attack, with a fall again later on. The hcemoglohin follows the same curve as do the red corpuscles, falling, however, generally to a slightly greater extent. In certain instances a well marked leucocytosis has been noted in pernicious paroxysms. Bignami has noted the unfavorable inferences that one may draw from this symptom. In some instances this, very possibly, depends upon a secondary mixed infection. In other instances, boAvever, it may occur where cultures from the organs are quite nega- tive. Thus, in one of the author's cases of the pernicious algid type the blood contained, one hour before death, sixty thousand leucocytes to the cubic millimetre. The leucocytes in malarial fever show certain other changes which are quite characteristic and interesting. Just as in the case of typhoid fever, where the number of leucocytes is ordinarily sub- normal, so in malarial fever, one finds upon a differential count a well marked reduction in the percentage of the polymorphonuclear neutro- philes, with a corresponding relative increase in the percentage of the large mononuclear forms. Thus the average numerical proportions of the various forms of leucocytes in sixteen cases analyzed in this clinic by Billings were as follows : — Small mononuclear 16.9 Large mononuclear 16.9 Polymorijhonuclear 65.04 Eosinophilic 0.96 In the pernicious case above referred to, observed by the author, the relative proportions of the different varieties of leucocytes, notwithstand- ing the leucocytosis, were as follows : 1 Arch, de Phys., 1876, ii. s., t. iii. 490. ^ j^g^^ ^^^^ 3 Bull. d. B. Ace. Med. d. Boma, 1890, Anno xviii., f. v. 297. * Johns Hopkins Hospital Bidleiin, 1894, No. 43, 105. SEQUELS AND COMPLICATIONS. 127 Small iiiiinoniu'lcar 23 per cent. Lar<;e numomu-k'ar and transitional tornis 18.4 " Polyniorithonuc'lear 58. G " The ohaiinc's in the l)loo(l in malarial luemoglobinuria have been alivatly ivt'cnvd to. Tlu' oravc aiijoniiio wliicli luay follow malarial fever will be eoii- sidered later among the sequelae. Sequels and Complications. There is no one point in the history of the development of our know- ledji'e eoncernino' the malarial fevers where so much confusion and mis- apprehension has existed as in the appreciation of the nature of the se(|uehe and complications. The relation of chronic cachexia and grave ansemia to malaria has long been recognized, as well as the existence of jui acute post-malarial nephritis. The grave cerebral, nervous, gastro- intestinal symptoms which may occur with acute malaria have been already referred to. Many observers, however, do, even today, ascribe to the malarial poison the capacity of producing of itself a considerable numl>er of other complicating processes ordinarily dependent on other t^pecitic causes. These observers have in particular described a charac- teristic " malarial pneumonia," " malarial dysentery," etc. That such misapprehension should have arisen is not remarkable when we consider the many ways in which the simple malarial process may be masked or complicated. Ascoli ^ states clearly the main possibilities in this direction as follows : " Finally, in conclusion, we may distinguish the following clinical forms : (1) INIalaria which simulates another pathological process. (2) A disease, the [ordinary] course of which is known, which, in an indi- vidual suifering with chronic malaria, progresses and develops anomalies in its course according to the stage of the cachexia.^ (3) A fresh malaria develops in a subject who is at that time in an apyretic stage of the disease or suifering from the remains of a former infection {combinata). (4) Different varieties of the hsematozoa exist in the blood of a patient suffering from malaria alone (mista). (5) Two febrile diseases exist together and contemporaneously (concomitanti) : («) exerting a recipro- cal influence detrimental to the organism { proporzionate) ; in certain of these cases the reciprocal influence is not manifest throughout the entire course ; (6) each preserving its more constant and common symptom- atology [cissociata). (6) The malaria may prepare the ground for the development of another acute infection, or it may follow after another infection has run itself out (consecutiva).'^ The sequelae and complications of malarial fever may be divided into — (1) Those sequelae or complications due directly to changes produced by the malarial parasites or their toxic products ; (2) true complications, mixed infections. 1. Sequelse and Complications due directly to Changes produced by the Malarial Parasites or their Toxic Products. — In the section upon the pernicious fevers the acute symptoms produced by the special 1 Bull. dellaSoc. Lane. d. Osp. di Boma, An. xii.,_1891-92, 103. ^ " Una malattia di processo morboso noto che, attacando un malarico chronico, assume andaniento e parvenze variabili secondo lo stadio della cachessia." 128 3IALABIA. localization of the parasites in the brain, Inngs, or gastro-intestinal tract have already been discussed. It is therefore unnecessary to refer again to the acute choleriform and comatose cases which might so readily sug- gest a mixed infection. Relapses. — The extreme frequency with which relapses are met in malarial fever has been referred to in the section on fevers with long intervals. Most cases, unless treatment be thoroughly carried out, show recrudescences in the course of one or two or three weeks. These are clearly proven to be due to the fact that all the parasites have not been destroyed by the treatment. The few which escape form a nucleus for the development of new groups, which in the course of a week or two arrive at a degree of development sufficient to result in a fresh outbreak of the symptoms. The recrudescences are, ordinarily, in every way simi- lar to the original attacks. There is, however, another variety of relapse which has been recognized for many years — viz. the reappearance of an infection many w^eks or months after all symptoms have disappeared. Undoubtedly, many such cases are fresh infections. There are, however, cases 'where a fresh infection can be definitely ruled out, while the malarial nature of the process is undoubted. An interesting example of the reappearance of fever after a long period of perfect health is the case of a friend of the author, a physician himself, wholly familiar with malarial fever, clinically and pathologically. During the fall of 1880 Dr. suffered from a prolonged attack of tertian fever which reduced him to rather a cachectic condition. Recovery followed full doses of c-[uinine. For twenty-one months after this the health was perfectly good, the patient living in non-malarious districts. On a hot afternoon of August, 1882, while making a pedestrian tour in the Tyrol, after a prolonged walk, during which the patient was subjected to great changes of temperature, there was a well defined characteristic malarial parox- ysm. The true nature of the attack was not suspected, but on the third day, at the same hour, while travelling in a railway-carriage, there was a second paroxysm. On the fifth day, again, at the same hour, a third characteristic paroxysm occurred. Convinced then of the malarial nature of the attacks, treatment with quinine was begun, which resulted in the immediate and permanent disappearance of the paroxysms. In the words of Dr. , " In this case there can be no question of a second infection. I had not been in a country where there was any malaria for two years, and for three weeks before the appearance of the first chill I had been in the mountains of the Tyrol." The absolute proof — the discovery of the parasite — is here wanting ; there can be little doubt, however, as to the nature of the case. The explanation of these cases is difficult. It is highly improbable that the parasite has remained present in the blood, passing through its ordinary cycle of development, and yet some form of the parasite must exist throughout this time. Bignami, as was noted in the description of the parasite, suggests that some form of the organism — which perhaps we have not yet been able to discover, possibly a non-staining spore — may persist in some of the internal organs, possibly within the protoplasm of some of the cellular elements. Cheoxic Malarial Cachexia. — The commonest sequel to mala- rial fever is that which is generally known as chronic malarial cachexia. SEQUELS AND COMI'LlCATIoyS. 129 111 malarious districts many patients allow an infection to continue for weelcs, months — nay, in some instances, even for years — without ever attemptiuii- a systematic or thorough treatment. Tlic result is, natu- rallv, a serious (.Irain upon the vital resources of tiie individual. The course of such a case is commonly as follows : The i)atient has several paroxvsms, and takes a few doses of quinine, which are followed by a disaj)pearance of the fever, or after a week or so of paroxysms which have been untreated the fever disappears spontaneously, Fre- tpient relapses occur which are improperly treated or allowed to take their own course. In some instances of iX'stivo-autumnal fever a j)atient may remain for a long- period of time with a slight, irregular fever, no sharp, definite, malarial paroxysms being observed. The first result of a continued process of this nature is the gradual development of an ansemia which usually becomes marked, and is sometimes extremely grave. The patient has a sallow, grayish yellow color ; the li[)s and mucous meral)ranes are blanched ; the tongue is often coated ; there is frequently oedema of the dependent parts. The spleen is usually greatly enlarged, sometimes reaching to the right of the median line. Indeed, some of the largest splenic tumors which occur may be seen in these cases. The hepatic flatness is increased in extent ; the border is often palpable, reaching sometimes a considerable distance below the costal margin. The patient suffers greatly from exhaustion, severe headache, pains in different regions of the body. Severe supraorbital neuralgia may exist. Sudden motion or exertion is followed by vertigo or faint- ing. The gait is tottering and unsteady ; there may be a marked general tremor. The examination of the blood during an afebrile stage mav be quite negative, excepting for the anaemia. More commonly occasional para- sites or pigmented leucoc}i:es may be found, while in £estivo-autmnnal infections the characteristic crescentic or ovoid j)igmented bodies are usually to be seen. Chronic cachexia may follow any variets' of infec- tion. In the majority of instances, however, it represents an untreated sestivo-autumnal infection, and in these instances the crescentic and ovoid forms of the parasite may be found. The same condition also follows frequently repeated attacks, even though the individual attack has been actively treated. The tendency toward dropsical transuda- tions is generally decided, and at times may give rise to confusion. Thus, in several instances the author has observed cases of moderate anaemia with quite marked oedema of the dependent parts and complete absence of fever, where, owing to an unsatisfactory history and the fail- ure to find parasites in the blood, the true nature of the process was wholly unsuspected until the appearance, within several weeks, of a re- lapse. Gastro-intestinal disturbances are verr common in malarial cachexia, and the grave anaemia, with diarrhoea, oedema of the dej^endent parts, the enormous splenic tumor, reduce the patient to a most distress- ing condition of marasmus, where he is an easy prey to complicating infections of all sorts. Chronic malarial cachexia is not uncommon in children, where, owing to the irregularity of the symptoms, the true nature of the pro- cess is often unsuspected. It may lead to the most intense grade of infantile atrophy. The child becomes greatly emaciated ; the sallow. Vol. I.— 9 130 MALARIA. grayish vello^v, parchment-like skin hangs in fokis ; the mucous mem- branes are blanched. There are occasionally slight febrile attacks, the child becoming cold and blue, or, perhaps, showing now and then a slight eclamptic attack. There are persistent gastro-intestinal disturb- ances, vomiting, diarrhoea, as well as, perhaps, diffuse bronchitis. The spleen is always enormously enlarged. PosT-^iALARiAL Ax^MiA. — The ausemia associated with malarial fever may assume various forms. Thus, Bignami and Dicmisi^ have distinguished four types of post-malarial anaemia. (1) Anaemia, in which the examination of the blood shows alterations similar to those observed in ordinary secondary ansemia, differing from these cases only in that the leucocytes are diminished in number. These cases often show well marked oligocythsemia ; oligochromsemia relatively greater ; more or less poikilocytosis ; nucleated red corpuscles (normo- blasts). The leucocytes, as already stated, are diminished in number, while the relative proportion of the large mononuclear forms is increased at the expense of the polymorphonuclear cells. The greater number of these cases go on to recovery ; a few, however without any change in the haematological condition, pursue a fatal course. (2) Anaemia in which the blood shows changes or alterations similar to those common in pernicious anaemia — /. e. marked oligocythsemia ; oligochromsemia relatively less ; marked poikilocytosis ; nucleated red corpuscles, for the most part gigantoblasts ; leucocytes, diminished in number with an increase often in the small mononuclear forms, and a diminution in the polymorphonuclear varieties. These cases end fatally. (3) Anaemia showing the ordinary characteristics of secondary anaemia, excepting for the complete absence of regenerative forms (nucleated red corj^uscles). These cases are progressive and fatal, the marrow, at autopsy, showing, as has already been stated, no evidence of regenerative activity. (4) Chronic secondary anaemiae occur in prolonged cases of malarial cachexia, and are remarkable for the small number of nucleated red corpuscles present and the marked reduction in the number of the leu- cocytes, particularly of the polymorphonuclear variety. There are, however, post-malarial anaemias which do show after the clearing up of the infection a leucocytosis similar to that in ordinary secondary anaemia. This is probably a favorable sign, pointing to a rapid regeneration. Malarial Xephritls. — The grave damage which the kidneys may suffer in certain acute malarial infections, either from the direct action of some toxin produced by the haematazoa or from the presence in the circulation of injurious substances, due indirectly to the action of the parasite, is most strikingly brought to one's notice in the intense acute nephritis which, as described in a previous section, may follow mala- rial haemoglobinuria. The kidney, however, rarely escapes a certain amount of damage in any severe malarial infection. Thus, out of 284 cases analyzed by Hewetson and the author, albumin was found in nearly one-half, while severe acute nephritis was present in 4 instances. The nephritis following malarial fever is usually a mild acute, diffuse process similar to that observed in any infectious disease. In some instances, as stated in the section on malarial haematuria, the course ^ Loc. cit. SEQUELAE Ay J) COMPLICATIONS. 131 may l)i' rapid and fatal ; in the majority, however, the projrnosis is favoral)le and eom|)K'te reeovery oeeurs. It is not impossihU' tliat, in some instances, a fatal chronic* dilfnse nephritis may owe its origin to the malarial poison ; however, detinite proof of this is as yet wanting;. There is nothing absolutely characteristic, clinically or pathologically, in these instances of malarial nephritis. Amyloid De(;knei{AT1()X. — Amyloid degeneration is an occasional .sequel to malarial fever. Two cases were reported by Frericlis,' and several others have recently been studied by Marchiafava and Dignami.- These eases have followed after a long series of febrile attacks, those which have been carefully studied having been aestivo-autumnal or obstinate quartan fever. The clinical symptoms are those of nephritis accompanied by an extremely ra])id cachexia, ending fatally, as a rule, within several months. The blood in these cases may show the condi- tion first notetl by Ehrlich as of grave portent — viz. complete absence of nucleated red corpuscles and eosinophilic cells, and reduction in the number of the leucocytes, with an excess of lymphocytes, while at autopsy the marrow of the long bones is found to be entirely fatty, showing no evidence of an attempt at proper regeneration. Atrophy of the Gastro-ixtestixal Mucosa. — Pensuti^ has reported a case of extensive atrophy of the gastro-intestinal mucosa fol- lowing, apparently, an acute malaria. Constant diarrhoea followed the attack, resulting in great exhaustion and death from broncho-pneumonia in three months. Though Baccelli was inclined to believe that the change was directly due to the action of some toxic substance connected with the malarial infection, the case cannot be said to be wholly convincing. Malarial Hepatitis ; Malaria and Cirrhotic Processes. — As has been stated in the section on Pathological Anatomy, many ob- servers insist upon the occurrence of a true atrophic cirrhosis of the liver as a sequel to malarial fever. There are many reasons which would lead us to believe that this may, in some instances, occur, but clinically, in this climate at least, such cases are rarely met with. In few instances does one meet with a true atropine cirrhosis of the liver in which other important etiological factors have not also been present. Xo.such case has come under observation in the Johns Hopkins Hos- pital in the seven years since its opening. On the other hand, chronic hepatitis, resulting usually in an increase in the size of the liver, is com- monly observed in malarial cachexia and following repeated malarial infections. Distinct clinical symptoms due to the hepatic changes do not apparently exist. Malarial Paraly^ses. — Cerebral Paralyses. — Various paralyses have been described in association with malaria. The diiFerent forms which may occur in acute pernicious malaria have already been referred to. They are usually transitory, disappearing under treatment, and are due probably to circulatory disturbances induced mechanically by the parasites : they are almost always cortical in nature. The nervous symptoms in acute malaria are more commonly irritative than paralytic. Occasionally s^nnptoms suggesting involvement of the spinal cord ^ Loc. cit. - Loc. cit. =• Qaz. Med. di Roma, 189B, xix. 12L 132 MALABTA. may occur. Several Italian observers have reported cases where the symptoms strongly suggested disseminated sclerosis. In all these in- stances the parasites were found in the circulating blood, and recovery followed treatment by quinine. In one of Torti's^ cases there was^ however, no fever, notwithstanding the presence of active parasites in the blood. In such instances it is easy to conceive that without exami- nation of the blood a diagnosis Avould be quite impossible. DaCosta ^ has also reported a case of paraplegia with intention tremor, severe headaches, bitemporal hemianopsia, and mental symptoms, where the blood showed the gestivo-autumnal parasites. Recovery occurred under quinine. The cases of "acute ataxia" reported by Kahler and Pick '^ were probably truly malarial. Bastianelli and Bignami ^ have reported a case show^ing symptoms of the so-called " electric chorea " or " Dubinins disease.^' This was associated with a continued fever, the nature of which was not, at first, determined. Examination of the blood later showed it to be due to an sestivo-autumnal malarial infection. Recovery occurred under quinine. They believed that the process was due ta " lesions secondary to the cerebral localization of the parasites." All of these processes coming on with acute malarial fever are essen- tially favorable in their course if treatment be begun in time. Accord- ing to Boinet and Salibert, however, permanent paralyses, both cerebral and spinal in nature, may follow malarial fever. Cases of peripheral neuritis following malarial fever have been, reported, though definite proof that they were malarial in origin has not been obtained. From what we know, however, of the pathogenesis of the disease, we may readily believe that malarial fever as well as other acute infectious diseases, may be followed by acute degenerative lesions in the peripheral nerves. Some observers have believed that there was some predisposing rela- tion between malarial fever and Raynaud's disease (symmetrical gan- grene), though this is by no means proven. Poncet has described a retinitis and a retino-ehoroiditis, due to emboli of melaniferous leuco- cytes in the capillaries. Mental Diseases. — Various mental affections may follow malarial fever, just as may be the case with any acute infection. There is nothing especially characteristic in these cases. Thus, one of our instances of tertian malaria was followed by an attack of paranoia last- ing for several months. True Complications and Mixed Infections. — Malaria, like any other acute disease, is subject to various complications, many of which are a result of mixed infections with other pathogenic agents. As stated before, many of the symptoms caused by mixed infections were believed by the older observers to be due directly to the malarial poison. Of late, however, with our increased facilities for study and appreciation of these conditions, it has been recognized that in the majority of instances the complication is dependent upon a true mixed infection. Pulmonary Complications. — Pneumonia. — As has been stated 1 Bull. d. Soc. Lane. d. Osp. d. Roma, 1891, xi. 217. ^ International Clinics, Philada., 1891, iii. 246. '^ Beitrdge z. Pathologie u. Pathologischen Anatomie des Centralnervensystem, Leipzig, 1879, * Bull. d. R. Aec. Med. di Roma, 1893-94, Anno xx. p. 221. SEQUELJE AND COMPLICATIONS. 133 in an earlier section, many observers have deseribeil pernicious levers M'hicli (luring the paroxysm showed well marked pulmonary symptoms, dys[)n(ca, pain, htcmoptysis. These symptoms, dependent probably u])on the special localization of the })arasites in the pulmonary ca])illaries, are to bo sharply distintiuished from true pneumonia, wiiich may, and not un- fre(piently does, complicate a malarial attack. ^Vgain, in certain instances an ordinary acute pneumonia may present an intermittent fever which simulates quite closely the chart of intermittent malarial fever. These eases, however, may be readily recognized by the absence of the ])arasite from the circulating blo( xl. Such cases have been descril)ed by Wunderlich, Jaccoud, Rcrtrand, and Andrew Clark, while Ascoli ' gives an excellent ciiart. True acute pneumonia and malarial fever may, however, coexist. In these instances the course of the pneumonia may be but little in- fluenced by the coexisting malarial fever, while in other instances the exacerbations and remissions of temperature may be quite marked. Here the ])ulmonary process is a genuine croupous pneumonia, due, as has been shown by Marchiafava and Guarnieri,- to infection with the diplococcus lanceolatus. Its course is quite uninfluenced by the admin- istration of quinine, and its connection with malarial fever is purely accidental, unless, as it may be in some instances, a preceding malaria has prepared the ground for the pneumococcus infection by reducing the vital forces of the individual. Pneumonia occurring in individuals suf- fering with chronic malarial cachexia appears to pursue an unusually malignant course, owing, doubtless, to the reduced condition of the patient. Retarded resolution and " organization " of the exudate are not uncommon in these instances (Ascoli). Broncho-pneumonia is also €ceasioually observed in association with malaria. The infection, how- ever, is purely secondary, in no way directly related to the malarial process. Pleurisy. — Certain observers have described symptoms in acute pernicious malaria suggesting pleural involvement where, on autopsy, nothing was to be found. In other instances pleurisy and malarial fever may coexist, although there is nothing whatever to show that this pleu- risy is not an entirely separate process from the malarial infection. There is nothing abnormal in the clinical or pathological course of such a pleurisy ; it is uninfluenced by the administration of quinine. These cases are not to be confounded with the pleural transudations which may occur in cachectics. Quinine has no influence upon the process. Typhoid Fever. — The relations between malarial fever and typhoid fever have been much discussed, and are today probably more generally misunderstood in this country than any one point in connection with the febrile diseases. Since the discovery of the malarial parasite, with our modern means of diagnosis, there is no reason for the existence of any such confusion at the present day. The great similarity' between the symptoms in certain cases of astivo-autumnal fever with typhoid fever has been pointed out in earlier sections. There is, however, no excuse whatever for the physician who today fails to recognize the malarial nature of such a fever after a few days' observation. The simple examination of the blood will invariably settle this question, the parasite being always present. ^ Loc. eit. ^ Bull. d. R. Ace. Med. di Roma, xv. 1888-89, 355. 134 MALARIA. Few are unfamiliar with the term so commonly employed, " typho- malarial fever." It was supposed that in malarious districts there ex- isted a continued fever which depended upon the combined action of two poisons, that of malaria and that of typhoid fever — true " pro- portio7iata/' in the sense of the old Italian observers. This fever was supposed to be markedly resistant to quinine and to betray its malarial nature by the frequency with which rigors occurred. We know today that " typho-malarial fever " as a distinct entity does not exist. Rigors occurring in the course of typhoid fever are by no means uncommon^ but are of themselves wholly insufficient evidence on which to base a diagnosis of malaria. We know, on the other hand, that there exist^ in this country at least, no malarial fevers which resist for more than three or four days the action of quinine. True complications of typhoid fever and malaria may occur, but they are rare, only one doubtful in- stance having been observed in seven years in the Johns Hopkins Hos- pital, where both typhoid fever and malaria are, unfortunately, very com- mon. Typhoid fever may be acquired by a patient suifering from acute or chronic malaria. A fresh malarial infection may break out or a slumber- ing infection may come to life again during the course of typhoid fever. But this condition is uncommon, and in no way justifies the term typho- malarial fever. There is little doubt that the enormous majority of cases referred to today as " typho-malarial " fever in this country and else- where are cases of typhoid fever, pure and simple. Too much stress cannot be laid upon this point, for the groundless assumption that there exists in this country a fever due to the combined action of typhoid and malarial poison, pursuing a fairly characteristic course and calling, from its malarial nature, for the continued use of quinine, has exercised in the past, and is exercising today, an extremely injurious influence upon the medical practice of this country. This influence cannot fail to be appreciated by the intelligent observer who has occasion to note the quantities of quinine which are systematically administered to many cases of uncomplicated typhoid fever in various districts of the United States. In the instances of true mixed infection of typhoid and malarial fever the picture may be most varied. If a fresh malarial attack or a relapse break out during the course of typhoid fever, well marked in- dications of the paroxysms, varying according to the type of parasite present, may be observed, as shown admirably by the charts recently published by Gilman Thompson. '^ In these instances the blood shows the presence of the parasites ; these, with the symptoms dependent upon them, disappear immediately after ordinary doses of quinine. If^ on the other hand, the typhoid fever develop in the course of latent or chronic malarial infection, the symptoms on the part of the malarial parasite may be almost absent. Intestinal Complications. — The occurrence of diarrhoea, partic- ularly in children, during acute paroxysms is well known. The changes produced by the malarial parasite in the intestine in certain acute per- nicious cases have already been considered ; the acute choleriform per- nicious paroxysm is truly malarial in nature. There is nothing, how- ever, to show that the more chronic dysenteries and diarrhoeas often 1 IVans. Ass. Am. Phys., 1894, 110. 9EQUELM AND COMPLICATIONS. 135 associated with cachexia arc in any way (Mrcctly coiuicctcd with the action of the malarial poison, exceptino- in so far as this may have pre- j)ared the oround. It is not impossible to conceive that severe infec- tions mii>ht follow directly npon an acute choleriform attack. I*artic- ularlv intercstino- are several cases noted in the medical clinic of the Johns Ho[)kins Hospital, where the Aina'ba coli has been found in the dejecta of ])atients sutfering' simultaneously with acute malaria and dysentery. In all of these instances the intestinal process might well have been directly ascribed to the malarial poison. The frequency \\itli which the Amcx'ba coli is associated with tropical dysenteries makes it exceedingly probable that many of these post-malarial intestinal affec- tions in tropical climates maybe in reality due to a mixed infection with the two protozoa, as in oiu' instances. Tuberculosis. — Numerous observers, and particularly Boudin,' have asserted that tuberculosis was directly antagonistic to malarial fever and the converse. Boudin pointed out that tuberculosis was rare in countries where malaria existed, and that where tuberculosis was common malaria was rare. This assumption has exerted a certain influence on the minds of many. Experience, however, has shown that it lacks foundation. In many of the districts where malaria is common it is true that tuber- culosis is unusual, owing to certain climatic influences. In the northern regions, where tuberculosis is more common, malaria, as is well known, is relatively infrecpient. In other regions we find malarial fever and tuberculosis side by side, intimately associated, occurring, by no means infrequently, in the same patient. Marchiafava,"' indeed, is inclined to believe from his observations that chronic malaria is not an unimportant predisposing cause to pulmonary tuberculosis. It is, how- ever, really interesting that among the 614 cases analyzed by Hewetson and the author in not a single instance was pulmonary tuberculosis present. Other Infections. — Infection with the other pathogenic organisms is not so very rare ; thus the author has observed furuncidosis, parotifis, toiisillitis, and acute rheumatism, while in one fatal case, admirably studied by Barker, there was a general infection with the Streptococcus pyogenes. Antolisei and Laveran have observed cases of variola comjilicated dur- ing convalescence by characteristic malarial fever, while Baccelli has observed the same in cases of other exanthemata. PosT-PARTUM AND PosT-oPERATiVE Malaria. — One hears not in- frequently of post-partum and post-operative malarial fever, and it is, alas ! only too common today to ascribe elevations of temperature during the first few days after operation and during the puerperium to malarial fever. This condition is probably rare. There are few such instances in literature where the malarial nature of post-partum paroxysms Avas def- initely proven. In the seven years since the opening of the Johns Hop- kins Hospital not a single case of post-operative malaria has occurred. Undoubtedly, the reduced condition of the patient during these periods might, and probably does, favor a recrudescence of the latent malarial infection. It is, on the other hand, probable that the majority of instances of supposed post-partum and post-operative malaria have no '■ Tmite des Fievres interraittentes, Paris, 1842. '' Bull. d. Soc. Lane. d. Osp. d. Boma, 1891, Anno xv. 180. 136 3i:alabia. connection whatever with true malarial fever, but represent simply a septic infection. This has been the case in every instance of suspected post-operative malaria which has come under the author's observation. IxsoLATiox. — The complication of an active or chronic malarial fever with insolation is probably not very uncommon. Bastianelli and Bignami '■ have recently demonstrated in an interesting manner the fre- quency with which such cases have, in Italy, been considered as essen- tially malarial in nature. The pernicious malarial fevers are particu- larly common at the hottest season of the year, while the individuals most subjected to malarial infection are also often those who work bareheaded in the fields, exposed directly to the sun's rays. These observers called attention to the fact that a number of instances of what has been considered pernicious comatose malaria have been reported in which, at autopsy, only cerebral hyperaemia, pulmonary hypostasis, and slight degenerative changes in other organs were observed. In some of these cases no malarial parasites were to be found ; in others, evidences of a recent infection ; in others, perhaps the evidence of a recent infec- tion with the presence of a small number of active parasites — far too few, however, to account under ordinary circumstances for such grave symptoms. Cases of this nature have led some observers to assume that a very small number of parasites might give rise to severe per- nicious symptoms, owing to their excessive malignancy. It is much more probable, as Bastianelli and Bignami state, that the process repre- sents a complication of malarial fever with insolation which might occur in an individual with active malarial fever or in one who has recently recovered from an attack. Indeed, it is not impossible that a preceding malarial infection, by reducing the strength of the individual, may render him more subject to such attacks. Diagnosis. (1) The Regulaely Inteemittext Fevers. — The diagnosis of the regularly intermittent, tertian, and quartan fevers is generally a rela- tively simple matter. The regular paroxysms with their three stages of chill, fever, and sweating are so characteristic as to leave little doubt in most instances concerning the nature of the process. The antemia and the enlarged spleen which are present in the vast majority of instances are also important from the point of view of difPerential diagnosis. Occa- sionally paroxysms very closely similar to the malarial access may occur from other infectious causes, and sometimes the regularit}^ with which the individual paroxysms may succeed one another may lead to errors in diagnosis. The paroxysms, however, in malaria diifer in certain respects from those occurring in most other acute infections. Thus, the average duration of the malarial j^aroxysm, if we estimate the course from the time the temperature passes 99° until it again falls below this point, is from ten to twelve hours, while in other infections the course is often materially shorter. There may, of course, be mild mala- rial paroxysms which last but four or six hours, but in these the tem- perature is correspondingly moderate. One rarely observes in malarial fever temperatures of 104°, 105°, or 106° in a paroxysm lasting as short i Bull. d. R. Ace. Med. d. Roma, 1893-94, Anno xx. p. lol. DIAGNOSIS. 137 a time as six hours or even less. The writer has seen cases of septic in- fection in which, for a considerable lent^th of time, chills closely simu- latinu' those of malarial fever occurred, while the amomia and enlart^ed spleen were also ])rescnt. The chief difierence to be noted was the marked diiference in the length of the paroxysms, which were some- times as short as four or live hours, the temperature reaching, perhaps, within this time a point as high as 106°. The same may be true of the chills which are not so infrequently seen during the course of typh(tid fever — chills caused, doubtless, by auto-intoxications as yet not under- stood. ^^'henever the temperature rises as high as 104° and the ])ar- oxysm lasts no longer than six hours, one is justified in the suspicion that the fever is not malarial in origin. At times, however, other infections may give rise to paroxysms most closely simulating those of malarial fever. Thus, in two instances the writer has observed typical quotidian paroxysms lasting from ten to twelve hours, and beginning nearly at the same hour on two successive days, which were considered to be malarial in nature, but which, upon examination, turned out to be due to acute otitis media (in one instance due to the diplococcus lanceolatus). The intermittent fever which is most commonly confused with mala- ria is that associated with jmbnonari/ tuberculosis. It is probably no exaggeration to say that the majority of cases of pulmonary tubercu- losis arising in the malarial districts of this country are, at some time in their course, mistaken for malarial fever. Intermittent fever, recur- ring often at fairly regular hours on succeeding days, is the rule at some stage, earlier or later, of pulmonary tuberculosis, while actual chills may occur. It is natural that the patient should ascribe such symp- toms to malaria ; there is, however, no excuse today for such error on the part of the physician. The sallow color, the anaemia, the enlarged spleen will serve to distinguish the malarial process from the tuberculo- sis, where, though the face be pale, the lips and mucous membranes show usually a good color, while splenic enlargement is rare. The examina- tion of the lungs, sputa, and blood will determine the diagnosis. The chills which often occur in the course of gonorrhoea or those folloAving catheterization or the passing of sounds may be confused with malarial fever. The urethra should always be examined in doubtful cases. In some cases of grave septicfemia following gonorrhoea there may be little or no evidence of an actual urethritis. Here the exami- nation of the blood will immediately settle the question. In the one instance ■ there is leucoc}i:osis without malarial parasites ; in the other, a normal or reduced number of leucocytes with the presence of the ma- larial organism. In all these cases the final decision must be arrived at from an examination of the blood. It is through this alone that a positive diagnosis of malarial fever can be made. Method of Examixatiox of the Blood. — For the satisfactory examination of the blood an oil-immersion lens is absolutely necessary. No physician today can consider himself equipped for practice without a good microscope and an oil-immersion lens. Though much valuable work has been done with dry lenses and lower powers, it is folly to attempt careful work without better means. The simplest and best method of studying the malarial parasite is in the fresh blood at the 138 IIALABIA. bedside or in the consulting room. The steps toward the preparation of the specimen are quite simj^le, though certain precautions must be rigidly adhered to. The cover-glasses and the slides must be carefully Avashed in alcohol or alcohol and ether in order to remove all fatty sub- stances ; they should always be washed immediately before use. The blood may be taken from any part of the patient's body, though the lobe of the ear is perhaps preferable, inasmuch as it is less sensitive and more readily approached than the finger-tip, while a smaller puncture w^ill draw more blood. This method is also more satisfactory than the puncture of the finger, in that the patient cannot so readily observe the proceeding — a point of considerable importance in nervous patients and in children. The ear is first thoroughly cleaned ; the lobe is then punctured with a small knife or lancet. For the most careful pro- cedures it is advisable to wash the ear with soap and water, and after- ward with the alcohol and ether. But, practically, it is often advisable to make as few preparations as possible, and unless the ear or finger be extremely dirty one may proceed at once. A pin or needle will, of course, answer the purpose, but it is well to remember that a stab made by a round blunt-pointed instrument is much more painful than that by a sharp cutting edge, while a considerably deeper stab is required to draw a given quantity of blood. If a very sharp spear-pointed lancet be used, and the lobe of the ear taken firmly between the fingers so that the skin is held tense, very slight pressure with the tip of the lance Avill cause an incision deep enough for all purposes. This process is almost without pain to the patient. By proceeding carefully blood may often be obtained in this manner from a sleeping infant without its awakening. After the first several drops of blood have been wiped away the freshly cleaned cover-glass is taken in a pair of forceps and allowed to touch the tip of a minute drop of blood. It is then placed imme- diately upon a perfectly clean slide. It is well, if a third person be present, to allow the slide to be vigorously rubbed with a clean linen cloth just before the application of the cover-glass. The spreading out of a drop of blood will be thus considerably facilitated. If the slide and cover be perfectly clean, the blood will immediately spread out between them, and, unless the drop of blood be too large, the corpus- cles may be seen lying side by side entirely unaltered in their main cha- racteristics. The drop of blood which is taken should be very small unless the patient be very anaemic, and care should also be exercised that the tip of the drop only touch the cover. If the cover be placed rudely against the drop and pressed perhaps also against the ear, the blood may so far spread out that the process of drying may have begun at the edge of the drop before the glass is laid upon the slide. If this be the case, the immediate spreading out of the blood between the slide and the cover does not occur. Xo pressure whatever should be exerted upon the cover, which should not be pushed or allowed to slide. The specimens will remain in good condition for a considerable length of time, an hour or more — long enough to be thoroughly examined. I^ one desire to observe the specimen for a greater length of time, the per- iphery of the glass may be surrounded by paraffin or vaseline. In this manner we may see the parasites living and in active motion, while DIAGNOSIS. 139 the most exquisite examples of phagocytosis may be observed. By enclosing the specimen in paraffin or vaseline the preparations may, iif' handled carefully, be carried from the residence of the patient to the consulting room and there examined, but under these circumstances one must generally rely upon dried and stained specimens. The preparation of specimens for staining is quite simple, re(piiring only a little experience and practice. Stained specimens are of especial assistance in the detection of the unpigmeuted hyaline bodies, particu- larly the pale tertian forms and those of the a^stivo-autumnal j)arasites. A small drop of blood flowing from the lobe of the ear or the finger-tip is collected upon a perfectly clean cover-glass, which is immediately placed upon another glass. The drop of blood, if the two covers be perfectly clean, spreads out immediately between the glasses. The cover-glasses are then drawn apart. If neither glass be lifted or tilted during this process, they will slide apart readily without sticking. If the glasses have remained together so long that they have begun to adhere, one may be sure that the specimen will be no longer perfect. The glasses, thus prepared, are allowed to dry in the air, which they do usually in the course of a few seconds, and may then be preserved for an almost indefinite length of time. To prepare them for staining the glasses should be heated upon a copper bar or in a thermostat at a temperature of 100° to 120° C. for two hours, according to the method of Ehrlich, or they may be placed in absolute alcohol and ether, equal quantities, for two hours or more (Xikiforov's method). The malarial parasite is readily stained by most of the basic nuclear dyes. The simplest method is perhaps to stain with a concentrated aqueous solution of methylene blue or Loflei^s methylene blue : Concentrated alcoholic solution of methylene blue, 30 c.c. Solution of caustic potash 1 : 10,000 100 " In either instance, the specimens should be stained for from thirtv seconds to a minute, washed in w^ater, dried between filter papers, and mounted in oil or balsam. The red corpuscles then will be un- stained, wdiile the nuclei of the leucocytes and parasites will be stained a clear blue. A contrast stain may be obtained by the following method : The cover-glass specimen, after fixing in absolute alcohol and ether from four to twenty-four hours, is placed for a few^ seconds (thirty seconds to five minutes) in a 0.5 per cent, solution of eosin in 60 per cent, alcohol, washed in water, dried between filter papers, and placed for from thirty seconds to two minutes in a concentrated aqueous solution of methylene blue, or in Loffler's methylene blue, washed in water, dried between filter j^apers, and mounted in Canada balsam. The red corpuscles and the eosinophilic granules are stained by the eosin, while the nuclei of the leucocytes and the parasites take a blue color. Admirable results may be obtained by a modification of JRomanov- shy's method. Two solutions are necessary — a saturated aqueous solu- tion of methylene blue and a 1 per cent, watery solution of eosin. The older the methylene blue solution the better the results. The staining mixture should be made just before it is to be used. To one part of the filtered methylene blue solution about two parts of the 140 ■ MALARIA. eosin solution are added. This is carefully stirred with a glass rod and poured into a watch-glass ; it should not be filtered after the mixture has been made. The cover-glasses, fixed according to the methods above described or by hardening in alcohol for from ten minutes up- ward, are allowed to float upon the top of this fluid. The specimens are covered by another inverted glass, and the whole by an inverted cylinder which is moistened on the inside. In from half an hour to three hours — best in two or three hours — good siDccimens are obtained. For quick work in the consulting room the simple stain with methy- lene blue alone is perfectly satisfactory, though the observer must of course have sufficient experience to be able to distinguish precipitates which may be present in the staining solution from parasites.^ The discovery of malarial parasites in the red blood-corpuscles is, of course, a positive sign of the malarial nature of the process. In some instances where the parasites may be very scanty or absent the presence or absence of a leucocytosis is an important diagnostic sign. As will be remembered, the leucocytes in malarial fever are normal or dimin- ished in number, whereas in almost all processes wdth which the acute intermittent malarial fever may be confounded there is a well marked leucocytosis. This is the case in all the septic infections which are most, likely to be confounded with tertian and quartan fever ; it is also true of tuberculosis, at least when accompanied by intermittent fever. The presence of a marked leucocytosis is strong presumptive evidence against the existence of malarial fever. In some instances where very few parasites are present the finding of pigment-bearing leucocytes may be an important aid in diagnosis. Tertian and quartan infections where multiple groups of parasites are present may occasionally be confounded with typhoid fever. Well marked remissions and, almost invariably, actual intermissions, usually occur, while the examination of the blood will readily clear up the diagnosis. The differential diagnosis between tertian and quartan infections may be readily made in the fresh specimen, less distinctly in the stained. The larger and more actively amoeboid, pale tertian para- site with fine brownish, actively dancing pigment granules may be readily distinguished from the smaller, less active, more refractive quar- tan parasite with its coarser, more slowly moving, darker granules. In the case of the tertian parasite the red corpuscles may be seen to become expanded and pale with the growth of the organism, while in the quar- tan parasite the corpuscle is shrunken and of a deeper, more brassy color. If the blood be examined just before or during the paroxysm, the more irregularly segmenting tertian organisms with their numerous (twelve to thirty) segments may be clearly distinguished from the smaller regular forms in quartan fever with their fewer (six to twelve) segments. The presence, in either instance, of one or more groups of parasites may usually be readily determined. Combined infections with quartan and tertian parasites — which, though very rare, do exist — may also be readily made out. In the stained specimen the size of the pigment and the parasite ^ The experienced observer may obtain sufficiently good specimens for diagnosis in many instances by rapid heating of the cover-glass over the flame for a few minutes ; the results, however, are uncertain. DLK.'XOSIS. 141 and the hcliavior of tlic red (•()r])uscl(', pale in nnv instance, taking- a doej) c'osin stain in the other, and the charaeteristies of" the se- of the administration of <|uinine. In the majttrity of instances of tertian infection in this climate all traces of fever disaj)j)ear within twenty-four hours. (2) Thk ^Estiyo-autumnal Fevers. — While the diajinosis in the regularly intermittent tertian and quartan fevers is a relatively sim])le matter, the same is not true of the more irregular sestivo-antumnal forms of malaria. In some instances, where the paroxysms are of shorter duration and occur at regular intervals, usually (juotidian, the diagnosis may be as self-evident as in the regularly intermittent fevers. The longer paroxysms, occurring at intervals of approxi- mately forty-eight hours one from another, with their less rapid rise, but with a complete intermission between them, are also generally easily recognized when vre take into consideration the aniemia, the en- larged spleen, and the herpes labialis which are so commonly present. When, however, from any of the varioiLs causes above mentioned the separate paroxysms become more or less complicated or merged one with another, so that at first but slight transient intermissions, then perhaps only irregular remissions, and finally a continued high fever, result, the diagnosis becomes often more difficult. Such a case often presents itself in the form termed by Baccelli ^' snhco)itunia fi/phoidea." The general clinical appearances are so similar to those of typhoid fever that a dis- tinction without examination of the blood may be quite impossible. In a certain number of instances vestiges of the paroxvsms still may be made out, a well marked acme in the fever being reached at approximately the same hour at quotidian or tertian intervals, though in other instances all traces of the individual paroxysms may have disappeared. Sometimes the history of several sharply intermittent paroxysms in the beginning of the illness may lead us to a correct diagnosis. Again, the prodromal symptoms are much less frequent and severe, as a rule, in malaria than in t}"phoid. Her])es is common in sestivo-autumnal malaria, unusual in typhoid fever. Delirium may appear quite early in a malarial attack ; it is rare during the first few days of a typhoid. Bronchitis is more common in typhoid than in continued malarial fever. Marked abdominal syni])- toms, though they may occur, are unusual in malaria ; the rule in typhoid fever. Certain ervthemata, and especially, urticaria, may be present in malarial fever, while the characteristic typhoid roseola does not occur. In both instances the spleen is usually enlarged. An important diag- nostic sign is the anaemia which is almost invariably present if the ma- larial fever has lasted more than a few davs, while in t^qjhoid fever anaemia during the first two weeks is rare. Another important sign is the slight icteric hue which is usually ]:)resent in malaria ; rare in typhoid. Ehrlich's diazo reaction is unusual in the urine in malarial fever ; it was found in but 6 per cent, of the cases classified by Hewetson and the author, while it is almost invariably present in typhoid. Here, however, as in all other forms of malaria, the final decision 142 MALABTA. is to be reached only by examination of the blood, where the small, amoeboid, and ring-shaped, hyaline sestivo-autumnal parasites are to be found. If the process has lasted a week or more, the pigmented ovoid and crescentic bodies are also usually present. In rare instances quite severe febrile symptoms may be present, while the peripheral circulation may at times show but a small number of parasites. Here the discovery of pigment-bearing leucocytes may often be of assistance. The dimin- ished number of leucocytes which one finds under these circumstances does not help us in the differential diagnosis from typhoid fever, where also the leucocytes are almost invariably subnormal in number. If the case occur in a neighborhood where it is impossible to obtain the aid of the microscope, the diagnosis may be definitely made by the therapeutic test. No malarial fever now known resists good doses of quinine for more than three or four days. It is generally safe to say that if the process be malarial the temperature will be practically normal by the fourth day. If quinine fails to influence the fever, we may rest assured that the process is either non-malarial or a mixed infection. The confusion with typhus fever might occur in some instances, but here, again, the examination of the blood will settle the question. As in the case of the regularly intermittent fevers, the process may be confounded with tuberculosis or other various septic infections. The one safe method of differential diagnosis is the examination of the blood. PERisricious Malaria. — The diagnosis in some pernicious paroxysms may be at times confusing. Comatose Pernicious Fever. — This type of fever must be distinguished from sunstroke, ursemia, cerebral hemorrhage. The differentiation of such an attack from sunstroke is by no means simple. As Bastianelli and Bignami have pointed out, individuals Avho are subjected to mala- rial infection are often those working in the fields and most exposed to the rays of the sun at the hottest season of the year, while the clinical symptoms of the two processes may be closely similar. It is interesting to note that the case of comatose pernicious fever referred to above as occurring in a tertian infection was at first mistaken for sunstroke. The slight jaundice, the anaemia, the enlarged spleen would serve to sug- gest the malarial nature of the process, while the examination of the blood gives a positive clue to the diagnosis. In the tetanic, meningeal, eclamptic, and hemiplegic types the same symptoms may lead to a cor- rect diagnosis. The Algid Type. — In this type of paroxysm, where the temperature may be normal or subnormal, and where often (from the actual conden- sation of the blood) the ansemia may not be as apparent, the diagnosis may be considerably in doubt. Here, however, icterus and enlarged spleen are suggestive, while examination of the blood will give posi- tive diagnosis. It is in cases of this nature that the physician who makes systematic blood examinations in all doubtful cases will be enabled at times to gain information which will save the life of his patient. The Hemorrhagic Type. — The diagnosis in some of the instances of this nature must be made between malarial and yellow fever. The early appearance of albumin and casts in yellow fever is suggestive, while the spleen is often but little enlarged in this affection. Tho examination of the blood may in some cases be the sole reliable niethotl of Jitlerentiation, Muhii'Ktl J[(riit<)(/f()hiiiiiri(i. — The diauiiosis here lies usuallv l)et\veen yellow fever, the ordinary paroxysmal Inemoo^lobiniiria, and aente nephritis from some other toxic orit^in. And here, again, tlie chief reliance must be placed upon the examination of the blood. Poiif-jMtrfum and Post-operative Malaria. — A diai- in IHHi), were afterward briefly referred to at the International Medical Congress in 1887, and phot()ii;ra])hs of ])ure eultures were exhibited at the l*an-Anieriean ^Medical Congress in 1893. Dr. Mcl^aiighlin states : " 1. Tliat he examined mieroscopieally the blood of twenty persons sutferiiii!; from dengue in its various stages, taking it directly from the veins, and found in all a peculiar staphyloeoceus. 2. Using necessary precautions to exclude alien germs and obtain chemical cleaidiness, he introduced upon the point of a sterilized platinum w'ire a small fraction of a drop of dengue blood into test-tubes containing sterilized culture jelly, and grew upon it the same micro-organisms which the blood con- tained. 3. Using requisite precautions against the introduction of any foreign element, he aspirated into a series of Liebig's potash bulbs the blood directly from the arm of a dengue patient. The bulbs were then hermetically sealed, and those micro-organisms which the blood con- tained allowed to grow upon the contents of the bulbs as a nutritive medium. The temperature was constantly maintained at 100° F. At the expiration of six months the contents of the first bulb Avas examined under high powder, with the result of finding the same micro-organism as was present in the blood drawn directly from the arm of the fever patient and that had been grown pure on the culture media." Dr. McLaughlin thus summarizes the results obtained from the preceding methods of examination : " I found a species of micrococcus, of un- usually small size, in the blood of all persons having dengue whom I examined, which has unique biological characteristics that distinguish this from all other species of pathogenic micrococci, and make it highly probable, at least, that this microbe is causative of dengue. The unique biological habit of this micro-organism is displayed by it in the group forms that occur when it is grown in artificial culture media. These are as follows : When a culture preparation of this micrococcus is suit- ably stained and examined wdth a high power (say a yV^^^ homogeneous immersion lens), the picture that is presented to the eye will be made up of (1) circular groupings of cocci around a larger coccus (arthrospore) that is located in the centre of the group ; (2) surrounding and imbed- ding the cocci wdll be seen a gelatinous substance — microprotein — of definite form and shape ; (3) these squares of microprotein in which the cocci are imbedded join similar squares, side to side, and thus form clear and distinct filaments. The separate segments of the filament, and the micrococci grouped around a larger, centrally located coccus in each segment, can all be distinctly seen in stained preparations when exam- ined with high-power objectives. " Not all the filaments that can usually be seen in the same micro- scopic picture are perfect in form like these described. Others will be seen that are undergoing a process of disintegration, the end of which is to liberate the cocci they contain, and filaments in all stages of disinte- gration, from the beginning of the process to its ending and the complete liberation of the cocci, will be observed. At the beginning of disinte- gration the filaments appear swollen, lose their distinct outline and the markings that differentiate their parts. Then the filaments fall away. 158 DENGUE. enlarge, and assume an imperfectly circular form, and finally coalesce and spread out, so that the picture they present (in stained preparations) is that of an irregular mosaic. The circular grouping of the cocci is still retained, while the microprotein which formed the principal mass of the segments retains sufficient of its outlines of these, at their points of coalescence, to jjroduce the mosaic. Finally, as disintegration con- tinues, all order in the grouping of the cocci disappears, and these bodies are seen scattered irregularly over the microscopic field. But it will now be observed for the first time that each coccus is surrounded by a capsule — a covering of microprotein which it brought with it from that of which the segments were composed. All the free micro- cocci that were seen, whether obtained directly from the blood or from artificial cultures, were encapsulated. Xo filaments were found in the blood that was obtained direct from the veins, and I cannot be sure they were in the blood cultures made of this micrococcus. I found many bodies having the outlines of filaments, but as I found no diiferentiating stain that the coccus would hold when it was washed out of the blood cells by the decolorizing washes, I cannot be sure that the bodies seen in the blood cultures were the filament-group form of this coccus ob- tained from other artificial cultures. " Blood as a culture medium for this micrococcus was obtained by aspirating it directly from a vein of a dengue patient into sterilized tubes and bulbs. These were then j^laced in a culture oven at 100° F. and examined microscopically at different periods. All contained large numbers of the micro-organisms." As dengue is a mild disease, it will be comparatively easy to confirm these observations of McLaughlin by inoculations upon the human sub- ject. The question will doubtless be determined upon the advent of another epidemic. COMMUNICABILITY. — The query as to the communicability of this disease has been so far unsettled. Its rapid and widespread diffusion seems to preclude its exclusive extension by contact of individuals. On the contrary, positive facts in evidence of its conveyance along routes of travel and from one person to another point to its being communicable. The evidence goes to show that the micro-organism which produces the disease may escape from the body of a person sick with dengue and infect another individual. Dr. Dickson states that immunity is conferred by previous attacks. He observed in Charleston that in 1850 only those escaped the disease who had suffered from it in 1828. Upon this point, however, there is no unanimity of oj)inion. Poggio expresses astonish- ment that one attack should protect so little from another. Thomas considers that once having had the disease a person is more liable to suffer from it than before, at least during an epidemic. The same author cites instances of patients who had dengue in Savannah in 1880 whom he had treated for the same disease previously. The truth appears to be that immunity from previous attacks is much less often conferred than in most other infectious diseases. Pathological Anatomy. — Dengue being, in the vast majority of cases, a non-fatal disease, no structural changes have been noted as characteristic. In the epidemic in Galveston of 1885 my colleague, Dr. Paine, observed a localization of inflammation upon the serous SYMPTOMS AND CLINICAL HISTORY. 159 membranes, especially the ])l('ura and peritoneum, hut these arc to be rey;ar(led as complications rather than as usual anatomical chaufjcs. Symptoms and Cijxical Histouy. — 'I'he |)crio(l of incubation varies from two to live days. The onset is usually sudden. The initial symp- toms are rigjors or chilly sensations, headache more or less intense, pains in the muscles of the limbs and l)ack or apparently deeper seated in the bones and joints. Coincidently there is a rise of temperature, which varies from 101° to 106° F. Anorexia is usually coni])lete ; nausea and vomitino- are common ; the tongue is moist and acquires a yellowish coat. The pulse and respiration are quickened in proportion to the extent of the fever, the former ranging from 95 to 120 per minute. In children convulsions may occur at the outset, and with a high tempera- ture they are frequently delirious. The face is turgid, the eyes red and watery. The urine is rather scanty and high colored, but is rarely albu- minous. Lassitude, weakness, and restlessness are usually present and proportionate to the severity of the attack. The joints are not only pain- ful and stitfened, but in many instances sM'ollen. These symptoms, after persisting several days, are followed in a considerable number of eases by an eruption which varies very much in appearance. Dickson describes the exanthem as appearing usually on the fifth or sixth day, and consist- ing of minute papulae, somewliat elevated, of a florid red color, distributed in irregular patches. It is noticed first in the face, then on the trunk iind thighs, gradually spreading to the extremities. AYhen fully devel- oped it is attended with some itching and burning, and generally dis- appears in two or three days with some desquamation. The eruption sometimes resembles urticaria or measles ; ordinarily it is scarlatinous in form, but is less diffused than that of either rubeola or scarlet fever. The exanthem, according to the writer's experience, is absent in many cases. In all probabilit}' it varies in frequency in different epi- demics. During the progress of these symptoms the fever continues, the temperature rising on the second or third day to 102°, 103°, or even 105° F. It then declines and returns to normal on the fifth day. According to the observations of D'Aquiu of Xew Orleans, "the tem- perature curves of dengue showed a continuous and steady rise until the highest point was reached on the first, second, or third day of the attack. Then comes a short stadium of a few hours, and then a remission, even to be followed by another rise of temperature, which, however, never reaches the maximum point of the first." The eruption generally ap- pears with the second access of fever, and simultaneously there is inflam- matory enlargement of the suboccipital, cervical, axillary, and inguinal l}Tnphatic glands. A disposition to hemorrhages from the mucous membranes has been noted in a considerable proportion of cases. Bleeding may take place from the nose, giuns, stomach, intestines, and uterus. Menorrhagia, metrorrhagia, abortions, and miscarriages are likely to occur. Convalescence is usually slow, and is characterized by an amount of prostration and weakness apparently out of proportion to the severity and gravity of the disease. The stomach is left in a weak and irritable condition ; there are anorexia, nausea, and vomiting. Xot infrequently one or two weeks elapse before a restoration to the normal vigor of mind and body is established. A better idea of the symptomatology of the dis- 160 DENGUE. ease will be obtained by a brief analysis of the more important clinical events. Tlie Muscular and Arthritic Pains. — Every author who has ever described dengue has called attention to the severity of these symp- toms ; especially is this the case if he himself has been the victim. The various names which have been given to the disease are significant as to the prominence of the rheumatoid manifestations. It is hardly necessary to remark that such events should be diiferentiated from true rheumatism. We have in dengue an exaggeration of what is observed in many other of the infectious diseases ; that is, a predilection upon the part of the specific pathogenic agent to affect the muscular structures. There are many of the milder cases where the pain is located in the muscles, chiefly of the neck and limbs, the joints not being especially involved. Course of the Fever. — The statement that there are two paroxysms of fever separated by an interval of complete apyrexia requires modi- fication. It was founded, doubtless, upon the accounts of the earlier writers before careful thermometric observations had been made, the period of decided remission being taken for complete intermission. Thus Eugene Foster states that out of 500 cases seen by him in the epidemic at Augusta, Georgia, in 1880, there was but one paroxysm, lasting from four to seven days. Confirming the statement of ^ Dr. D'Aquin, already quoted, that there was a continuous and steady rise of temperature until the highest point was reached, most frequently on the second day, then a short stadium of a few hours, then a remission, soon to be followed by another access of fever, which, however, never, reached the first maximum of heat. Dr. John Wortabet ^ in his descrip- tion of the epidemic of 1883 in Syria says that the fever was continuous from three to five days, ranging from 99.5° to 104.5° F., being higher in the forenoon than in the afternoon, and that the paroxysm occurring on the sixth day was very rarely observed in the Syrian epidemic. The observations of D'Aquin have since been confirmed by Vauvray, Avho studied the disease in Egypt, also by Dr. Brun, who observed the epi- demic which prevailed in 1888-89 in Beyrout, Syria. There are, doubt- less, however, some cases, as described by Martialis of India, Thomas of Savannah, and Holliday, where there is a distinct interruption of the fever, followed by a milder secondary thermic paroxysm. The Eruption. — During the first febrile paroxysm the initial rash is observed. In India this rash has been noted by Martialis and Charles as present in from one-half to two-thirds of the cases. It is usually transitory, lasting only during the first febrile period, and varies in appearance from a slight blush to a well marked erythema. The ter- minal rash is more constantly present than the primary one. It has no uniform appearance, and may be erythematous, miliarial, urticarial, or herpetic, and is indicative, should there be no relapses, of the decline of the disease. Upon its first manifestation there is often a slight rise of temperature ; sometimes there are successive crops, and desquamation is coincident with convalescence. The frequency with which any erup- tion at all occurs varies in different epidemics. Unquestionably there are many cases where it is entirely absent. ^ Transactions Ninth International Medical Congress, vol. iv. p. 467. 'SYMPTOMS AND CLINICAL HISTORY. 161 GJandalar KiiUvnjcinrnt.^. — Siiicf the lime of Dickson nearly all writers on den; of the faet that this epidemic did not differ from those which preceded it as regards the occurrence of this syni|)tom ; and, while it may not have been noticed in the praetice of several physicians, the observation of a large number of cases would show a certain propor- tion in Avhich it was found. Hemorrhages. — A disposition to bleed from various mucous mem- branes has been observed by a number of practitioners. My colleague, Dr. Paine,^ in speaking of the Texas epidemic in 1885, refers to " serious hemorrhages from the colon, stomach, vagina, and uterus," and states " that the two latter organs seemed to bear the brunt of this congestive action, as manifested by the frequent sanguineous exudations from these parts. It often happened that women menstruated out of their regular term, sometimes profusely, and suffered from menorrhagia when seized at a normal epoch. Old women long past the menopause w^ere known to lose blood from their genitalia. Miscarriages at every stage of preg- nancy occurred." Foster ^ mentions hemorrhages from the nose, gums, lungs, uterus, and bowels, one instance of the latter finally proving fatal. He also mentions two cases of black vomit similar to that seen in yellow fever. As to hsematemesis and intestinal fluxes, while there is no reason that bleeding should not occur from the stomach and bowels in a disease showing such decided hemorrhagic tendencies, the diagnosis of dengue should receive careful consideration under such circumstances. Refer- ence to this point will be made subsequently. Relapses. — The frequency of relapses is generally admitted as being one of the distinctive features of the clinical career of dengue. Baret and Mahe estimate the frequency of relapses at Reunion in 1869 as 15 per cent. By a relapse should be understood a recurrence of an attack after complete recovery. Relapses should not be confounded wath exacer- bations, which have been mentioned as occurring frequently after the remission. Varieties. — A consideration of the symptomatology of dengue would be incomplete without a description of the varied £orms which the disease assumes in the same and in different epidemics. It is on account of such differences that one writer will give prominence to one set of symptoms, and another, describing it as he observes it, will emphasize certain other phases. So far as a variety of forms is concerned, dengue does not depart in this respect from the rule observed by other infectious diseases. It is sufficiently descriptive to divide dengue into two classes : First, that mild form which runs a shorter course, two to three days, and in which such manifestations as high fever, arthritis, hemorrhages, glandular en- largements, etc. are absent ; and second, the more intense form, which will in the main conform to the description herein given. As to the ^ Transactions Ninth International Medical Congress, vol. iv. pp. 470, 471. '^ Reference Handbook of the Medical Sciences, vol. ii. p. .397. Vol. I.— 11 162 DENGUE. denguis maligna mentioned by Charles of Calcutta, I think it will be conceded that the term "malignant" as applied to dengue is a mis- nomer, since the disease is a remarkable one in respect to its mildness. The writer distinctly remembers his first impressions of dengue obtained from professional friends in the epidemic of 1873, that " it was a good epidemic — good for the doctor, making many people so sick that these were compelled to send for him, and at the same time causing no one to die." So universal is the benignancy of this fever that when mortality occurs there is strong ground to suspect the accuracy of the diagnosis. But this portion of the subject will receive further notice. Complications and Sequels. — Considering the amount of suffer- ing and discomfort incident to dengue fever, the comparative absence of serious complications and sequelae is somewhat unique, aside from those symptoms which have been mentioned, such as occasional convulsions in children, a disposition to abortion, uterine and other hemorrhages, rarely a pleurisy or peritonitis. The explanation of the fact lies in the non-affinity of the infection for such vital organs as the brain, lungs, heart, or kidneys. Convalescence is frequently characterized by anorexia, an irritable stomach, and an extent of muscular weakness and nervous depression apparently out of proportion to the duration and gravity of the disease. Diagnosis. — The ensemble of symptoms as above outlined ordi- narily renders the recognition of dengue an easy matter : especially is this the case during the progress of an epidemic ; but sporadic cases or epi- demics occurring coincidently with yellow fever, influenza, typhoid and malarial fevers are not so easily differentiated. Any one having practi- cal experience during the combined prevalence of these fevers can readily understand that they may be frequently confounded even by expert diagnosticians. Differential Diagnosis between Dengue and Yelloio Fever. — The idea that these two diseases are identical, or at least that dengue was a modi- fied yellow fever, was never tenable, but was nevertheless held by a number of reputable physicians who had studied the maladies at the bedside. The facts giving currency to this view are briefly as follows : Dengue often prevails concurrently with, precedes, or follows an epi- demic of yellow fever. The t^vo diseases have similar (though not identical) geographical distribution, follow like isothermal lines, and are affected by similar climatic and seasonal influences. The clinical events of mild cases of yellow fever may so closely resemble those of dengue as to justify Porcher ^ in this statement : " It is a significant fact that we have never been able to distinguish accurately between the two — to say of every case and at every stage of these two diseases, ' This is yellow fever, this only break-bone ;' yet the well marked examples of undeniable yellow fever were as different in every material aspect from lighter forms of break-bone coexisting with it as black is from Avhite." The following table, arranged from the presentation of the facts by Foster, will serve to accentuate the distinction between the two diseases, and at the same time, show the points wherein they resemble each other : in spite of their similiarity, the fact that dengue and yellow fever are entirely different diseases cannot be too strongly emphasized : ^ Transactions American Public Health Association, art. xxxviii. DIAGNOSIS. 163 Yellow Fever. Dengue. Arrested by severe frost. Arrested also by frost. One febrile paroxysm characterized by a Usually one paroxysm, but sometimes two ; steady rise and lasting about three days. a steady rise of temperature until the acme is reached ; a short stadium, fol- lowed by a remission, then a second rise. Duration, live to eight days. IStomac'li irritable, vomiting frequent. Vomiting not so frequent. Tongue, white centre, red edges, pointed. Tongue white, yellowish, rarely red edges. Pulse slows while tenqjerature rises. Pidse increases in rapidity with rise of temperature. Eruption rarely or never present. Eruption present in the majority of cases. Jaundice usually present. Jaundice extremely rare. Urine albuminous and often suppressed. Urine free from albumin and never sup- I^ressed. No involvement of lymphatic glands. Lymphatic glands involved in some cases. Hemorrhagic tendency frequent, alarming, Tendency to hemorrhage comparatively and terminal. rare, and, as a rule, insignificant. Often fatal. Proverbially non-fatal. Not protective against dengue. Not protective against yellow fever. Usually confers immunity against subse- Not generally protective against a second (pient attacks. attack. To illustrate the practical nature of this subject and of the close resemblance between dengue and yellow fever, it is Avorth mentioning that upon the report of an outbreak of dengue at Key West in August, 1893-94, it was thought by Dr. Swearingen, the Health Officer of Texas, to be sufficient reason to temporarily quarantine against that port ; which action led to some controversy with the health officials of Florida. Dr. Swearingen ^ based his procedure upon the grounds that " dengue, Avhile not generally regarded as a quarantinable disease, has been so often associated Avith yellow fever, by making its appearance sometimes just prior to that disease, and closely resembling it in certain mani- festations, and by its appearance in Key West concurrently with yellow fever in Havana, with which city Key West is in near proximity and close relations, that in the interests of public health in Texas it was thought best to take no risks until sufficient time had elapsed to demon- strate the safety of resuming intercourse." In all cases like this the public should have the benefit of the doubt, and the action of Dr. Swearingen was perfectly satisfactory, justifiable, and wise. Differential Diagnosis between Dengue and Influenza. — It would be interesting to draw a similar line of comparison between dengue and epidemic influenza. The points of resemblance are — the rapid and widespread diffi^ision, affecting all classes, all ages, and all conditions with indiscriminate violence ; the frequency of relapses and liability to repeated attacks ; the want of harmony between the apparent severity and small mortality of uncomplicated cases ; the sudden onset, the character and intensity of the pains, and the disproportionate mental and physical depression during the period of convalescence. The points of distinction are — the differences in geographical distribution, climatic and seasonal influences ; the absence of eruption in influenza except herpes ; the absence of remission or intermission of the fever in influ- enza ; the usual involvement of the air-passages in the latter and its non-occurrence in dengue ; the greater frequency and severity of com- ^ Texas Sanitarian, Austin, Dec. 24, 1894, p. 65. 164 DENGUE. plications and sequelae in influenza. It is easy to see, however, that the two diseases might readily be confounded. Typhoid Fever and Dengue. — At first thought one would hardly suppose that dengue and typhoid fever would ever be confused, the two disorders being so dissimilar ; yet that such confusion may occur when both are epidemic will readily appear. At the close of the epidemic of dengue in 1885 in Galveston numerous cases were reported by several physicians, denominated as typho-dengue. The clinical events narrated were fever of long duration (three to six weeks), intestinal hemorrhages, suppurative inflammation of the parotid glands, and in quite a number a fatal ending. The writer contended in a discussion of these cases before the Galveston County Medical Society that the term typho-dengue was a misnomer ; that the disease described was genuine typhoid fever ; and that it was proven to be such chiefly by its duration, the gravity of the symptoms, and its mortality. The confusion arose from the previous rarity of enteric fever, and the occurrence of a mild epidemic at the close of a more extensive one of dengue. Malaria and Dengue. — Dengue may also be confounded with malarial fever : especially is this so in regard to sporadic cases of the former or at the commencement of an epidemic of dengue when the latter is jDre- vailing. The differences in the febrile movement, the absence of erup- tions in malaria, the rapid supervention of anaemia, and the presence in the blood of the hsematozoon, suflice to establish the distinction, though the writer could relate cases where it was by no means easy to make a differential diagnosis. Prognosis. — The prognosis is almost invariably favorable. Atten- tion has been called to the fact that every author who has written upon the subject, perhaps without exception, has described dengue as a mild disease and without mortality except as the result of an intercurrent or rather accidental complication, such as convulsions in weakly children and septicaemia from a badly treated abortion. So when we hear of deaths from dengue as a result of intestinal hemorrhages or from black vomit, or any other causes, we should view the diagnosis with suspicion. The fact alone that the so-called dengue is attended by mortality is sufiicient cause to call in question the diagnosis. Treatment. — It is useless to discuss the old antiphlogistic plan of treatment — general bleeding, active emeto-cathartics, etc. — as it has very properly been discarded. The attempts to prevent attacks during an epidemic by the use of quinine have been proven to be entirely ineffect- ual. Quarantine measures, except when there is a suspicion of yellow fever, are not likely to be enforced at present, but the time may come when even this disease, though universally acknowledged to be non-fatal^ will be controlled in its march to a great extent by governmental author- ity. We do not as yet know to what extent this can be accomplished, but, judging by its method of dispersion, there is reason to believe in the probability of such restriction. Medicinal Treatment. — The disease being self-limited, the indications are to relieve the symptoms. If the stomach is full at the time of attack, a mild emetic would not be out of place. Apomorphia, one tenth of a grain hypodermically, will act with certainty and rapidity, or the older emetics, ipecacuanha, mustard, salt, and warm water, which are handy. TREATMENT. 16o may l)o u.sed. The bowels ordinarily re([uire attention, thougii excesrsive purgation is not desirable. Moderate doses of ealorael, five to six grains in a single dose, or the same (juantity divided into several smaller doses, has the etieet, when the bowels are moved, to relieve the nausea and headaehe by its revulsive and evaeuant action, as well as to favorably affect the alimentary canal for assimilation and absorption. Many prac- titioners prefer to prescribe a more rapidly acting purgative, as some of the salines, emulsions of castor oil, etc. To relieve the intense headache a hot mustard foot-bath at the outset is of decided service. The differ- ent coal-tar antipyretics are indicated for the relief of the rheumatoid pains, as well as to reduce excessive fever, and can be employed accord- ing to individual preferences. AVhile quinine cannot be depended upon as a prophylactic, it aids in controlling the pyrexia and pains, besides having a tonic effect. The salicylates are also useful analgesics. A very good combination at the outset would be the following for adults : R. Calomel, 6 grains ; Phenacetin, ^ drachm ; Quinine bisulphate, 15 grains. Mix and divide into ix capsules. Sig. Take three capsules every three hours. After the above, phenacetin with quinine, ten grains of the former to five grains of the latter, may be continued every four to six hours according to the temperature and severity of the pains. When the pain is unusually acute opiates may be required. Morphia and atropia given hypodermically afford the quickest relief. Salicylic acid or salicylate of sodium is objectionable on account of the disagreeable head symptoms and nausea frequently produced by either medicament. Salophen, how- ever, is free from these objections, and is a useful addition to the phen- acetin and quinine ; it may be given in doses of ten or fifteen grains according to the effects produced. Active hydrotherapy — that is, the use of cold baths — is ordinarily not required. AYarm baths, however, having the water at a comfortable temperature — say from 90° to 95° F. — allay nervous excitement and gen- erally add to the well-being of the patient. Cold applications to the head and sponging the body with tepid evaporating lotions, as of alcohol and water, assist in accomplishing the same results. Irritability of the stomach generally subsides when the bowels have been freely moved. If this symptom is obstinate, iced champagne, Yichy and Apollinaris waters, subnitrate of bismuth, dilute hydrocyanic acid, with sinapisms to the epigastrium, are remedies and measures which are indicated. Turpentine stupes and anodyne embrocations assist in relieving the rachialgia. The diet ordinarily should consist of milk, meat broths, and gruels. Lemonade and orangeade are gratefid to the taste. To relieve the depression of convalescence the moderate and careful use of alco- holic stimulants, with such reconstructives as the phosj)hates of iron, quinine, and strychnine, essence of calisaya, Ducros' elixir, etc., are often required and subserve a useful purpose. ENTERIC OR TYPHOID FEVER. By J. C. WILSON, M. D. Definition. — An acute, infectious disease, characterized clinically by a febrile movement varying in duration from twenty-one to twenty- eight days, by gastro-intestinal catarrh, marked prostration, rapid wast- ing, marked nervous symptoms, and a scanty eruption of isolated, slightly elevated, rose-colored spots, which disappear upon pressure and are de- veloped in successive crops ; anatomically by constant lesions of the lymph-follicles of the intestines, enlargement of the mesenteric glands and of the spleen, and parenchymatous degeneration of the viscera. Eberth's bacillus is present in the lesions. Synonyms. — To enteric fever many names have been applied. It is called by the Germans " typhus abdominalis " to differentiate it from true typhus — "typhus exanthematicus." Louis, in 1829, gave to the disease the name of " typhoid fever " (fievre typhoide), a designation that has since passed into almost universal use. To the name " typhoid," however, there are the same objections that apply to the " typhus abdom- inalis " of the Germans, as both terms would imply a relation to typhus fever which exists neither clinically nor anatomically. Although no longer in use, the term " slow nervous fever " of Huxham's day is finely descriptive. Other names still occasionally loosely used are "gastric fever," " intestinal fever," " ileo-typhus," and " infantile remittent fever." The last was at one time employed to designate the fever as it occurs in early childhood. The disease at this period of life is characterized by marked remissions in its temperature range, and Avas for a long time regarded as a distinct affection not in any way related to enteric fever, from which infants and young children were supposed to enjoy a high degree of immunity. Later investigations, however, proved the erroneous character of these views and established the identity of the so-called infantile remittent fever with enteric fever. " Enteric fever " seems the most appropriate name for the affection. It indicates at once the site of the constant and most important of the gross lesions, and by the use of the term " fever " coupled with the adjective, the infectious character of the process. For these reasons, and because it is not open to the objections that may be urged against " typhus abdominalis " and " typhoid," it is now extensively employed among English-speaking physicians, and especially in army and navy medical circles and in government reports. Etiology. — Enteric fever is due to the implantation in a susceptible organism of a specific infecting principle — the bacillus of Eberth. Predisposing Influences. — These constitute, first, all conditions which favor the development and accumulation of the infecting prin- 168 ENTERIC OR TYPHOID FEVER. ciple, and, second, those conditions Avliich increase the susceptibility of the individual to the cause of this particular fever and the liability of his exposure to it. The geographical distribution of enteric fever is wide. This disease prevails in all countries and in every climate. It is, however, especially prevalent in temperate climates. It is the great fever of the present historical epoch, just as the plague was in Europe the great fever of the Middle Ages and typhus the great fever of the seventeenth and eighteenth centuries. Enteric fever is endemic in the British Islands, in Continental Europe, and in ]S"orth America. Hirsch has reached the conclusion that the general prevalence of this disease in Europe and America dates no farther back than the second and third decades of the present centuiy ; that is, from the period which typhus {der Petechial Tfphus) ceased to prevail generally and in many localities disappeared altogether. In America enteric fever prevails from Hudson Bay to the Gulf of Mexico. In newly settled districts, where the land is being gradually brought under cultivation, the malarial fevers are common ; after a time, as populations increase, the malarial diseases and enteric fever prevail side by side ; finally, when the land has been generally taken up, drained, and tilled, and villages and cities abound, true agues and remittents largely disappear, while enteric fever becomes the usual endemic fever, common in proportion to the neglect of the sanitary measures by which alone it can be kept in check. Climate, not directly, but as determining the mode of life in commu- nities, has much influence upon the extent of the prevalence of enteric fever. The season of the year is a predisposing influence of great importance. About 50 per cent, of the cases occur during the months of August, September, and October. The number of cases decreases during Novem- ber and December, is lowest from February to May, again increasing in June. This fever is so much more common in the latter part of the year that it is known in some districts of the United States as " autum- nal " or " fall fever." The loeather, as regards dryness and moisture, exerts a decided in- fluence upon the prevalence of enteric fever. Its prevalence is greater during hot and dry seasons ; less during cool and wet summers. Out- breaks of enteric fever in localities supplied by surface water or shallow wells have frequently followed abundant rains. Age is of great importance among the predisposing causes. Enteric fever is especially a disease of adolescence and early adult life. The period of greatest susceptibility is between the ages of fifteen and thirt}', the liabilitv' diminishing progressively both above and below these limits. In 1864, Murchison demonstrated at the Pathological Society of London the intestines of an infant six months old who had been attacked at the same time with her mother. Cases in the first year of life are, however, exceedingly rare, but from the termination of this period the liabilit}' gradually increases through infancy and childhood. The explanation of the fact that the proportion of the cases occurring in infancy is smaller than that of childhood and adolescence is found in the greater exposure to the cause of the disease in the later periods. Enteric fever is not common in advanced life. I have, however, seen cases in the THE EXCITING CAUSE. 169 Fig. iifty-oii]jhth and sixty-ninth year. This ininiunity is to be accounted for hv the fact that a \wy^q projjortion of iiulividuals surviving to the hiter i)eriods of life have previously suffered from the disease. Si'x exerts no |)re(lisi)osiuij: influence. The disparity shown by sta- tistics is due to the fact that a ureater number of males than females sufferino- from acute disease are admitted to hospitals. Certain statis- tical series would ap])ear to show that the disease is more frequent in boys than in girls. These statistics fail to embody the fact that beyond the age of infancy girls are much less exposed to the infection than boys. The latter, in their outdoor sports — bathing, swimming, and the like — incur especial risk in drinking water directly defiled by sewage. The mode of life is without influence. Enteric fever is as apt to occur in the houses of the affluent as in the most crowded and destitute localities. The prevalence of enteric fever in the great centres of pop- ulation diminishes in proportion as protection of the water supply ad- vances and sewer systems are improved. In rural districts where sani- tarv regulations are ig-nored the dis- ease appears to be upon the increase. I have knowledge of several suburban localities in which enteric fever, for many years prevalent, has wholly dis- appeared within a short time after the introduction of artesian water and the abandonment of shallow wells. The Exciting- Cause. — The micro- organism described by Eberth, Koch, Gaff ky, and others, and known as the bcK-illus typhosus or baciUus typhi ab- dominalis, is at the present time gen- erally accepted as the cause of enteric fever. This organism is constantly present in the specific lesions of the disease. The bacilli are about one third the diameter of a red blood- corpuscle in length and about three times as long as broad — 2.5 by 0.8 //. They are blunt and rounded at the ends (Fig. 8), in one of which, sometimes in both, especially in cultures, there are areas of dense pro- toplasm that have been regarded as spores. They are motile. They can be readily grown in pure cultures on nutritive media of differ- ent kinds, and can be now differentiated from certain other bacteria with which they were formerly confounded, especially the bacterium coli commune. This bacillus completely fulfils two of the requirements of the law formulated by Koch in regard to the evidence that a disease is caused by a given micro-organism : it is present in every case of the disease and in such distribution as will explain the specific lesions, and it can be isolated in pure culture. The third requirement of the chain of evidence, that the disease must be reproduced by inoculation of the isolated organism, remains unfulfilled. The results of inoculation ex- periments have in most instances been due to the toxic rather than the infective properties of the inoculated substance. It has therefore been Typhoid bacilli in Peyer's patch before ulceration (Charcot). 170 ENTERIC OB TYPHOID FEVER. concluded that the lower animals are not susceptible to enteric fever. The fact that hyperplastic and ulcerative lesions of the lymph struc- tures of the intestines have followed such inoculations is not conclusive, since it has been shown that similar lesions may be caused by the bac- terium coli commune and other micro-organisms. Abbott in a number of experiments upon rabbits obtained a single positive result. In this case there was an ulcer in the ileum identical with those found in the intestines in the human subject, and typhoid bacilli were demonstrated in characteristic clumps in sections of the spleen and were obtained from that organ by culture methods. The difficulties regarding the subject are not insurmountable. Recent researches have shown that definite toxic and immunizing substances are produced by this bacillus. These results tend to support the view already almost universally accepted, that the organism in question is the specific cause of enteric fever. The bacilli have been found in the blood, especially in that drawn from the spleen and the rose-colored spots. They tend, however, to- colonize in clumps in the lymph-tissues of the intestines, in the mesen- teric glands, in the spleen, in the marrow of the bones, and in the liver. They have been found in the bile, in the urine, more abundantly when it is albuminous, and in the sweat. They have been isolated from en- docardial vegetations and from serous and purulent exudates in different parts of the body. They cannot be discovered in the stools until the tenth, sometimes not until as late as the sixteenth, day. In fatal cases cultures of the intestinal contents have frequently given negative re- sults. The most active existence of this organism is parasitic. It is, how- ever, a facultative saprophyte, and is capable of a prolonged existence under favorable circumstances both within the body of the patient who has suffered from enteric fever and outside of the human organism. Outside the body it retains its vitality for a variable period of time. The extreme duration of this period is not known. In ordinary water it is measured by weeks. Hochstetter found typhoid bacilli capable of growth after they had been for twelve days in a siphon of seltzer water. They survive longer in closed cisterns and reservoirs than when exposed to light, and Janowsky has shown that cultures cease to develop after some hours of exposure to sunlight. That they retain their vitality in running water has been shown by the history of many epidemics. Prudden found them capable of culture after having been frozen in ice for several months and after repeated freezing and thawing. Prudden and Ernst found them in the water-filters of houses in which cases of enteric fever had developed. Whether or not they increase in ordinary water remains unsettled. It is generally believed that some increase does take place. They grow luxuriantly in milk without causing coagu- lation or changing its appearance in any respect. They retain their vitality for months in fecal matter, and many local outbreaks have been traced to the disturbance of privy-vaults into which the stools of enteric- fever patients have been previously emptied. UfPelmann has shown that typhoid bacilli have a remarkable vitality and tenacity in dried fecal matter. They not only continue to live, but also grow and multi- ply, upon the surface of the soil, and where the ground is frequently THE EXCITING CAUSE. 171 moistened they penetrate to a consideral)lc depth, retaining their vitality. There is, however, no proof that typhoid bacilli are capable of an in- definite existence outside the body, much less of an iudcHnitelv \)yu- lonoed indej)endent and viu'orous non-j)anisitic o-rowth. On the con- trary, there is reason to bi'lieve that sunlight, dis[)ersion, the action of putri'factive bacteria (Karlinski), and unsuitable or insutlicient pabulum would ultimately lead to their extinction were it not for constant renewal by the infection of fresh cases. The iicrms find access to the body by way of various ingesta. If, as exceptionally aj)pears to have been the case, they are inhaled witii par- ticles of dust Hoatino- in the air, it is probable that they become en- tangled in the secretions of the mouth or pharynx and are swallowed. The common vehicle is drinking water which has been defiled by se\vage. The endemic prevalence of the disease in cities and many local epi- demics are to be attributed to this cause. Even water that has been recently boiled may take up germs from a contaminated filter or from contaminated ice. Many local epidemics have originated in the pollution of the water supply by a single patient. Among these none is more important than the well known epidemic at Plymouth, Pa., in 1865. A portion of the water supply of the town was derived from a reservoir filled from a mountain stream some distance above. A case of enteric fever occupied a house upon the banks of this stream during January, February, and March. The copious dejections of this patient w^ere thrown upon the ground, which was at that time frozen and covered with snow. Toward the end of March a thaw, accompanied by a rainfall, took place. About the 10th of April an epidemic of enteric fever developed in the town, chiefly among the inhabitants whose water supply came from the reser- voir. In a population of 8000 people 1200 cases occurred. The following personal observation illustrates a very common mode of the propagation of enteric fever : A physician developed the disease under the following circumstances : His house stood upon a small lot in a village at the time and for a long time previously free from enteric fever. Early in September the patient's brother came to his house ill with enteric fever. The dejections from this case, treated w'ith a small amount of a so-called commercial disinfectant, were thrown into the privy, an ordinary open vault such as is common in country places. The well from which the drinking water for the household was obtained was about twenty-five paces distant. Toward the close of September the physician fell ill with enteric fever, and within a few days three other cases occurred in his household. Infection is less common by the way of milk, in which the germs grow luxuriantly without altering its physical characteristics. A num- ber of epidemics have been traced to this cause. The infection in these cases cannot be traced to disease in the cow, but to an admix- ture of defiled water Avith the milk, either intentionally or as the result of its use in cleansing milk-cans. The transmission of the infecting principle by milk was definitely established by the investigations of Ballard during a local epidemic at Islington in 1871. The outbreak ■was shown to be due to the employment of water defiled by direct com- munication with drains for the purpose of washing the milk-cans. 172 ENTERIC OR TYPHOID FEVER. Circumscribed epidemics have occurred in which the most careful efforts to trace the source of the disease have been without positive result. In an outbreak a few years ago in a military academy in the neighborhood of Philadelphia this was the case. Among 132 students 14 cases developed in rapid succession. The infection was virulent, 5 of the 14 cases terminating fatally. One of the patients came under mv observation, and subsequently recovered in the German Hospital of Philadelphia. Painstaking investigations conducted by competent observers failed to reveal the source of infection. A theory that the first case was due to infected milk obtained at a shop in a neighboring city could not be established. The possibility that typhoid bacilli may be present on the surface of raw vegetables or other articles of food that have been washed with water containing them is not to be overlooked. Articles of food may be contaminated by the soiled fingers of the patient himself or of his attendants. The bacilli may be transported from the fecal discharges of a patient to articles of food by means of house-flies. Oysters " plumped " or freshened for market by exposure for a short time in the fresh water of streams defiled by the sewage of towns or cities may become infected. Conn has reported an epidemic at Middletown which he attributes to the eating of uncooked oysters infected in this way. Foote found in river ovsters a larger number of micro-organisms than in those from the sea. He shov/ed that the bacillus typhosus preserves its vitality in the brackish water in which oysters are laid down, and for a longer time in the oyster itself. It was at one time thought that the infecting principle of enteric fever was not immediately capable of giving rise to the disease, but that its pathogenic properties were acquired in the course of a short time in consequence of changes after leaving the body. In accordance with this view enteric fever was regarded as a contagious miasmatic disease. The theory of Pettenkofer that the poison is not eliminated in a con- dition capable of immediately giving rise to the disease, but that it acquires its pathogenic properties in consequence of changes in the soil, and that these changes are favored by the action of the ground Avater, is of a similar nature. These theories are no longer tenable. The doctrine of Murchison and his followers that the specific cause of this disease may be generated de novo in decomposing sewage in which the discharges of enteric fever patients are not present is like- wise untenable. It is true that filth, defective sewers, cesspools, and soils contaminated with fecal matter favor the accumulation of typhoid germs, and in some cases supply media for their growth, but these con- ditions cannot, in the absence of the specific infecting principle, give rise to enteric fever. There is no proof whatever that this disease in the absence of the germ referred to can be generated by the products of decay or decomposition, by sewer exhalations, by tainted food, or by the action of other bacteria. By far the largest proportion of the bacilli are without doubt destroyed within the body. The remainder find their way out in the stools, to a slight extent in the urine, very rarely in the vomited or expectorated matters or the perspiration. They are not eliminated by the expired ANATOMICAL CHANGES IN THE INTESTINES. \1'?> air. Enteric fever cannot therefore be regarded as contagious in the ordinary nieaninij: of tlie term. It is coniniunicable by the iiifcctiiitr principle contained in these matters, but chielly in the fecal discharges. This infecting prinei[)le is invariably derived cither diivctly (•!• indirectly from a previous case. Sporadic cases of enteric fever occasionally occur under circumstances that baliie explanation. This has sometimes been the case among small bodies of troops in practically uninhabited districts, as in border cam- paigns. The suggestion that the infection under these circumstances has taken place by means of typhoid bacilli in condensed milk or other articles of food, and that the innnunity of those who escape is to Ije ascribed to previous attacks of enteric fever, is plausible. The alter- nate suggestion that the infecting principle of enteric fever is a germ widely diffused in nature, and that it acquires pathogenic properties when developed in contact with decomposing fecal or other organic matter, has not met with general acceptance. Pathological Anatomy. — ;The typhoid bacilli, gaining access to the organism by way of the gastro-intestinal tract, enter the lymph structures of the intestines and there develop, elaborating toxic prin- ciples to which the constitutional phenomena are due. Brieger, Friinkel, and others have isolated from bouillon cultures of the bacilli a toxalbu- min to which the term typho-toxin has been applied. The fact that typhoid bacilli are not found in the fecal discharges in the early course of the disease, but first appear about the time of the necrosis of the lymph elements, justifies the assumption that the bacilli do not develop, as do those of cholera, within the lumen of the gut. The constant and characteristic gross anatomical changes of enteric fever are to be studied in the solitary and agminate glands of the intes- tines, especially at the lower end of the ileum, in the associated lymph- atic structures of the mesentery, and in the spleen. Anatomical Changes in the Intestines. — The anatomical changes in the intestines may be divided into four stages. 1. The Stage of Infiltration or Hyperplasia. — In this stage swelling of the solitary and agminate glands takes place, and is due to hyperplasia of their elements, the surrounding mucous membrane being intensely hypersemic. The agminate glands are distinctly elevated above the surrounding surface, and after the early hypersemia and congestion have disappeared become grayish white or opaque in appearance, with a slightly rough, irregularly mammillated surface. The solitary follicles are not invariably affected, but when affected they constitute shot-like projections from an eighth to a quarter of an inch in diameter. The hyperplasia of the lymph elements extends deeply into the submucous tissue, but at the borders it is limited, so that both the solitary and agminate lymph follicles are distinctly differentiated from the surround- ing mucous membrane by abrupt margins. The whitish or opaque appearance of the glands is due to the compression of the bloodvessels : nor is the infiltration limited to the glands, but may proceed deeper, involving the submucous, the muscular, and even the serous layers of the intestine. The infiltration attains its maximum development some time between the end of the first week and the tenth day of the disease. At this 174 ENTERIC OB TYPHOID FEVER. stage of the process the anatomical change may cease and resolution take place ; if, however, as is commonly the case, the bloodvessels have become so choked that repair is impossible, necrosis of the lymph struc- tures results. In children hyperplasia of the lymj)h follicles is not uncommon in intestinal diseases. It occurs also in scarlet fever, measles, and diph- theria. While, therefore, hyperplasia of the lymph follicles is not peculiar to enteric fever, a marked enlargement of these structures is rarely seen in adults in any other febrile affection. 2. The Stage of Necrosis. — The hyperplasia of the lymph follicles ad- vances. Resolution is no longer possible. Mechanical interference with the blood supply from the pressure of the infiltrated tissues, the growth of the bacilli, and the direct action of the concentrated toxic principles evolved at the seat of their activity are factors in bringing about rapid and more or less extensive necrosis in the affected glands. The swollen patches and discrete follicles undergo sloughing, which, on the one hand, may be superficial, involving only the epithelial and subepithelial struc- tures, and, on the other, may extend to and involve the peritoneal coat of the intestine. Between these extremes necrosis of varying depth occurs, the muscularis commonly, but by no means invariably, limiting the process. The infiltration and necrosis are jsrogressively more marked toward the lower end of the small intestine, and in severe cases the mucosa of the ileum for some inches above the ilio-csecal valve is extensively gangrenous. The attached sloughs are of a grayish- white color, or they may be stained yellowish brown or green by the intes- tinal contents, especially the bile ; sometimes, being infiltrated with blood, they are dark in color. The separation of the sloughs takes place during the latter half of the second and the course of the third week. 3. The Stage of Ulceration. — The sloughs are gradually detached, separation taking place first at the borders. Ulcers of varying depth and of a size and form corresponding to the necrotic tissue are thus formed. If an entire patch be involved, the resulting ulcer is elliptical, of considerable size, and situated opposite the mesentery, its long axis cor- responding to the long axis of the bowel. It is more common to find irregularly circular or ovoid forms which occupy a portion only of the Peyer's patch, or two or more irregularly bordered forms of ulceration separated by bands of mucosa. Very extensive ulceration is sometimes encountered just above the ileo-ceecal valve. The edges of the ulcers are usually abrupt, the surrounding tissues being thickened and often over- hanging. Their bases may be formed by the submucosa ; more com- monly they are formed by the muscularis, sometimes by the serosa, and in those instances in which the necrosis involves the peritoneum the wall of the gut may slough out through its entire thickness. Ulcers resulting from necrosis of the solitary follicles are usually small and round. "When death has occurred late in the course of the attack irregular, serpiginous ulceration is in some instances observed. 4. The Stage of Cicatrization. — The swelling in the edges of the ulcers gradually diminishes, the base becomes covered with a delicate layer of granulation tissue, and the mucosa extends over the healing surface, which is ultimately invested with epithelium. The gland structure is AXAT'OMICAL changes IX THE INTESTINES. 175 to some extent re-fonned. Tlic resulting scar is slightly depressed, usually pio-niented, smooth and less vascular than the surrounding mucosa. It has no tendency to contract or pucker or to narrow the lumen of the gut. AVhen cicatrization progresses in tiiis favorable manner the time occupied l)y the process of healing is j)rol)al)ly aljout a fortnight. Lesions are sometimes seen in which cicatrization is going on in one place while in another active ulceration is in progress. When death occurs during a relapse patches of active ulceration coexist with the nearly healed ulcers of the primary attack. The solitarv glands of the caecum and colon are involved in a con- siderable proportion of the cases. The appendix may also be the seat of ulceration. Perforation of the csecum is a rare event. The lesions of the lymph structures of the intestine do not in all instances go on to necrosis. It is probable that resolution without extensive necrosis takes place in the abortive cases and in many of the cases in childhood. This process results from fatty and granular changes in the cells which under- go destruction and are absorbed. There is associated with these lesions catarrhal inflammation of the large and small bowel, to which must be ascribed many of the intes- tinal symptoms, and in particular the diarrhoea. A limited number of cases have been reported in which the symp- toms of enteric fever have occurred, but upon section the intestinal lesions have not been found, although the mesenteric glands, spleen, and kidnevs have been enlarged and congested. The presence of the bacilli of Eberth in the affected organs is necessary to the diagnosis of enteric fever. Hemorrhage from the bowels occurs in about 5 per cent, of the cases. It occurs at the time of the separation of the sloughs. The frequent occurrence of large, even fatal, hemorrhages points to the implication of arterial twigs of some size in the necrotic process. Adherent clots may be found at the source of the bleeding. Oozing of blood may occur from the swollen borders of the ulcer. Intestinal perforation occurs with about equal frequency. The open- ing may be round or " punched out " or slit-like and linear. In the former case it results from the separation of a slough that has involved the wall of the gut throughout its entire thickness, including the peri- toneum ; in the latter from tearing of the base of an ulcer extending to the peritoneum in consequence of active peristaltic movement. Per- foration occurs more commonly about the time of the separation of the sloughs, but it may take place some weeks after the defervescence. In a majorit^^ of instances perforations are single, but two or more may be present. Their usual site is within ten or to'elve inches of the ileo- •csecal valve. Perforations of the caecum and of the appendix are less common. The escape of intestinal contents is followed by infection of the peritoneum and general peritonitis. The mesextePvIC glaxds show histological changes similar to those in the intestinal Ivmph structures. In the early stages they are Inqjertemic and enlarged; later they become pale, and not infrequently limited necrotic areas are found, especially in the central portion of the glands. In the majorit}^ of instances the lesions in the glands of the mesentery imdergo complete resolution. Occasionally they soften or undergo cheesy 176 ENTERIC OR TYPHOID FEVER. changes. They may ultimately be converted by the deposition of lime salts into hard, calcareous masses. In other instances softening of the mesenteric glands may result in the formation of pseudo-abscesses, the walls of which may rupture and give rise to fatal peritonitis. Other lymphatic glands may undergo enlargement, notably those in the fissure of the liver, the retroperitoneal glands, and the bronchial glands. The SPLEEN is enlarged in over 90 per cent, of the cases of enteric fever. Its structure shows changes analogous to those in the lymph follicles of the intestines in the earlier stages of the disease. It is soft, pulpy, and may be even difflu- FiG. 9. ent. Upon section the surface . is brownish red in color, and . *>- ..■^', '"' > " ' ,;, hemorrhagic infarcts are fre- ; . quently found. It is liable, when greatly softened, to be ■ . ",;n/\i '^ ' accidentally ruptured by palpa- ,-\ : - ^Vi ^J^i^ ^A-^'*" v* tion, or this accident may even ,. '"' :^-' ■iX^''t^'\>iy^-f'f'' '-^'3 • occur spontaneously. Rupture "^ ''^^^^4^'^^^^^th'^^'^ ^ of the spleen occurred in five -'''f^^^^^i'^oi'ii instances among two thousand "\'WmmW¥}W-: autopsies at the Munich Patho- 7 >{')r:Jv%A',f^V^i;^^V'^' ■ ■ The enlargement of the ,.-',■; '»^'^-^w! ' - spleen may be usually recog- ' ' ' nized toward the end of the " * ,;; first week. It reaches its max- ■ ' imum about the fourteenth day, Human spleen, tenth day of enteric fever (Charcot). when the Organ will be found tO be two or three times its normal size. During the fourth week or with the occurrence of defervescence involution rapidly takes place, and by the end of the fifth week the organ has returned to its normal dimensions. Persistent splenic enlargement after defervescence points to the possibility of a relapse. Enlargement of the spleen does not occur in many of the cases in advanced life : it may also be absent when the capsule has become thickened as the re- sult of previous inflammation, with the formation of firm adhesions to adjacent structures. The EiVER early in the course of the disease is hypersemic and slightly enlarged. Later it is somewhat pale and less consistent than normal. The minute changes are those of parenchymatous degeneration ; the liver cells are granular, crowded with fat, and the nuclei indistinct, often entirely absent. Very rarely the liver presents an appearance resembling that of acute yellow atrophy. Certain peculiar changes occurring in the liver have been described, notably by Wagner, who applied to them the term "lymphoid nodules," and Handford called attention to the existence, late in the disease, of small necrotic areas. Investigations recently conducted by Walter Reed in the pathological laboratory of the Johns Hopkins University ^ show that the lymphomata ^ Am. Journ. Med. Sciences, November, 1895. THE HEART AM) li LOO D VESSELS. 177 Human liver, tenth day of enteric fever ^Charcot). of \\';i»iiu'r are in reality areas ol' iieen»sis. As to whether tliey are duo to the direct action of the bacillus of Eberth or are caused by the action o^f toxalbuniins has not, as yet, been definitely determined. The latter ex- planation is ret;arded by Keed as the more prol)able, in view of the fact that Welch and Flexner ^ have produced in the liver of guinea-pigs well marked necrotic areas by the injection of the toxalbuniins of diphtheria. PillvphlcbitU with resulting abscess of the liver is an exceedingly rare c-om- plication. Lannois^ recently reported a case of enteric fever in which there occurred pylephlebitis and multiple hepatic abscesses, the presence of the bacillus of Eberth being demonstrated in the pus. As a result of his studies of this case and of the literature upon the subject the conclusion is reached that the complication is a rare one. Catarrhal or diphtheritic inflammation of the gall-bladder may be encountered. KiDXEYS. — Parenchymatous changes occur. They consist of cloudy swellino; with granular defeneration of the cells of the convoluted tubules. Acute nephritis is an occasional complication. Disseminated areas of round cell infiltration corresponding to the so called lymphomata of Wagner in the liver and sometimes proceeding to softening have been observed. When suppuration occurs the appearance is that presented by miliary abscesses. Typhoid bacilli have been found iu these minute collections of pus. Diphtheritic inflammation of the pelvis of the kid- ney is of rare occurrence. The bacilli have been found in the non- albuminous urine, more commonly when albumin is present and in cases of pyuria. Catarrh of the bladder is by no means infrequent. Diphtheritic cystitis is rare. Purulent cystitis is usually due to the use of uncleanly catheters. Epididymitis is more apt to occur in cases that have required catheterization. The Heart and Bloodvessels. — Endocarditis occasionally occurs. It is usually sliglit. Of two thousand post-mortem examinations at the Munich Pathological Institute^ it was present in eleven instances. Pericarditis is also a rare lesion in enteric fever, being found, according to the same statistics, in fourteen cases. The myocardium shares in the general wasting which accompanies the disease. The muscle of the heart is relaxed, flabby, and atrophic. When the organ is removed from the body and placed upon the post- mortem table it flattens out. Microscopically, there is found granular and fatty degeneration with small-celled infiltration ; the fibres are iu- 1 Johns Hopkins Hospital Bulletin, 1892, vol. iii. No. 20. 2 Revue de Medecine, 1895, No. 11, p. 909. ^ Miinehener medicinische Wochenschrift, Nos. 3 and 4, 1891. Vol. I.— 12 178 ENTERIC OR TYPHOID FEVER. distinctly striated or the striation is lost and they are translucent and granular. The arteries are frequently implicated in the pathological processes of enteric fever. Obliterating endarteritis occurs. It more commonly affects the vessels of the lower extremities. Endarteritis of the smaller vessels, especially of the coronary arteries, is not uncommon. Prolifer- ating endarteritis involving the smaller vessels was found by Dewevre in 3 of his series of 48 cases. Venous thrombi occur. They are relatively common in the femoral veins ; less so in the cerebral veins and sinuses. The voluntary muscles frequently show granular and fatty changes. These changes occur in other infectious febrile diseases and are not peculiar to enteric fever. Rupture of bundles of muscle fibres some- times takes place, giving rise to hemorrhage into the muscles, and, less frequently, to pseudo-abscesses. Salivary Glands and Pancreas. — The cells of the salivary glands and of the paiwreas frequently show granular degeneration, and it is stated that these structures become enlarged and firmer in consistence than normal early in the disease. A suppurative inflammation of the parotid glands — parotid bubo — sometimes occurs as a complication of the disease. The Respiratory Organs present various and important lesions. Ulcerative laryngitis not infrequently occurs. The situation of the ulcers may be in the posterior wall, upon the ary-epiglottidean folds, or at the base of the epiglottis. Acute laryngeal oedema occasionally results, and may necessitate the performance of tracheotomy. This operation was found necessary in 8 of the 20 cases noted in the statistics of the Pathological Institute of Munich. Bronchitis is common, and the bronchial tubes show those changes wdiich underlie the various forms of bronchial catarrh in other diseases. The lungs show changes refer- able to the twofold condition of an enfeebled circulation and a blunted condition of the nervous system. Broncho-pneumonia in enteric fever, as in other so-called typhoid conditions attended by an obtunded con- dition of the nervous system and impairment of the laryngeal reflex, is nearly always due to the entrance into the upper air passages and bronchial tubes of septic particles from the mouth and pharynx, either by inhalation or during the act of deglutition. Such infection causes bronchial catarrh, which by extension involves the finer tubes and air- vesicles. Hypostasis of the dependent portion of the lung and splenization are common. Many cases of so-called hypostatic congestion are regarded by Striimpell as being, in reality, instances of broncho-pneumonia. Other pulmonary lesions, more or less frequently encountered, are putrid bronchitis, gangrene, abscesses, and infarction. Croupous pneu- monia is a frequent complication due to secondary infection by the diploGOCCUs pneumonice, and is usually encountered after the course of the disease has become well established. Croupous pneumonia is, however, in some instances apparently due not to infection by the diplococcus pneumoniae, but to infection by the bacillus of Eberth. Under these circumstances it usually occurs early in the course of the attack, and has been attributed to localization of the specific process. The difference between the two forms, however, is rather a bacteriological than an ,s'>'.i//"/'o.i/,s' 179 anatomical one. la a rase ol" unnv in the Jc'Hcr.son Hospital, Ctjplin found Eberth'.s bacilli in the pnlnionary exndate. Involvement of the ])lenra is not very common. Fibrinons ])lenrisy and empyema occnr. The central nervous system rarely shows gross lesions. 8<^metimes sliii'lit adhesions of the dnra mater to the craninm are found. Increased vascularity of the pia with minute hemorrhages and vascular injection of the brain substance may occtir early. Wlien death takes place late in the course of the attack oedema and moderate distention of the ven- tricles are noted, and are to be attributed to wasting of the brain tissue. Very rarelv large hemorrhages or the signs of a purulent meningitis are found. The lesions of peripheral neuritis have been frequently observed. Symptom.s. — General Clinical Course. — The period of incubation of enteric fever is variable. In general it may be set down as from two to three weeks. The incubation period in some well-authenti- cated cases has not exceeded four or five days. In a case of my own in the Philadelphia Hospital it was, so far as could be determined, only four days. The onset is commonly so insidious that the patient is unable to designate the actual time of the beginning of the attack. Prodromal symptoms consist of general lassitude and languor, fatigue upon slight exertion, vertigo, headache, frontal, occipital, or general, but almost always aggravated toward evening ; slight nausea, loss of appetite, and in some cases fleeting colicky pains in the abdomen. A tendency to diarrhoea is often present in the prodromal stage, or, if absent, is easily induced by the administration of mild laxatives. The facies soon becomes dull, there is slight impairment of hearing, and the patient complains of aching of the back and limbs. The tongue is coated, and epistaxis, which may consist of only a few drops of blood, a mere stain upon the handkerchief, constitutes a sign of diagnostic importance at this period of the disease. These prodromal symptoms, not well defined in every case, continue for a varying period, and in some instances last for a week or more ; in others, however, where the infection is intense, characteristic symptoms of marked severity may develop within two or three days after the occurrence of the primary symptoms. In defeult of other definite cri- teria the actual onset of the disease is to be reckoned from the day the patient betakes himself to bed, but, as this event depends much upon individual temperament, some difficulty usually arises in estimating definitely the date of the beginning of the attack. The onset, however, is rarely abrupt, and is less frequently so in adults than in children ; it is seldom marked by a decided rigor, but is in some instances attended by chilly sensations. The first iceeh of the disease is characterized by a gradual rise in temperature, the subfebrile temperature of the prodromal stage grad- ually merging into the steadily increasing fever of the first week. The record of each evening's temperature exceeds that of the previous evening by a degree or a degree and a half of the Fahrenheit scale, until by the evening of the fifth day it reaches 1C3° or 104° F. About this time the temperature commonly attains the fastigium, the elevation which, in the absence of complications, it is to maintain during the course of the attack. 180 ENTERIC OB TYPHOID FEVER. The pulse is increased in frequency, and although the volume is full the tension is low; it after a time becomes dicrotic. The skin is usually hot and dry ; exceptionally even at this period it is moist and bathed in perspiration. The headache of the prodromal stage increases in severity, and epistaxis, which may or may not have occurred during the prodromal period, is often present during the first week ; it is usually slight, sometimes considerable. Muscular prostration is marked ; the patient's expression is already dull and apathetic, although upon being aroused his mind is clear and his memory good. Sleep is restless and often disturbed by disagreeable dreams, while toward the end of the first week slight transient delirium develops, especially upon awakening. The lips are parched and dry, and the tongue, usually at this period moist, is swollen and covered with a whitish fur, thin or thick and Fig. 11. BOWELS, NUMBEB 3 1 2 ! 1 ~ 1 1 _, ■" 1 1 r 1 1 ~ ~ r ' 1 1 F 106° 104° 103° 102° 101° Z s si i s 5 3 i-CL i i < i < S; i < i i\i < s < s s <- 5 s s : = i 5 s s <■ s <• s s s * s is < s i < <■ 5 <- s 5 < s 5 < s tt a < t 0; <■ Q.- s - - - — - — - - — -- -- s ^. ^ - — - - - — — — - h - - ^ ^ "1— - " nM i:: 1 2 r- 1 O) " — «a — CO " - " " - — — coo om oo ^ " 1 1 1 " 1 " " "" " ™ - ^ ^ — " !!; !i! - :! ^ ^ ^ t _ _ i s s i , ... = " — — — — 3 - — ^- p — — — — — -^ - — — — — — — — ^ ~ ~ — z- — — = E V z E E V - - 1 r I E -^ I — Z - - - ^: :fi t /-- 3 z\\ = I j = - E E E E E E - - 100° 99° _98° I ~ z E — J- ff } 1Z E )1 - E E [; 1 E = E E z Z \ 1 1 E n E E E - z _ _ - _ II- ^ p- — ^ — — — — — J — - - — - — - r — - -^ 4- — — )L j- - - i -- - - - - - - J — - - J n L_ r — , _ _ ,_ _ _ J L c _ -1 _ _ _ - , _ _ 97° — — - — ~ — — — — — S — ^ — -- — — — — — — — — ~ p ZTT — K- — ^ ki — ~ — — — — — — — — — — — - — — p- — — — — — ■». 5^ 1 ^ = = = - - - z - -- - - - r - - - ~ - - z - z ;- - - z - z - z z 4- z z -^- DAY OF DISEASE ~ " " 9 1 1 1 1 E i:: IT i.'i ir, TT 1 s" 1 9 20 -5 1 1 2 ~i J 1 1 "2 5 26 "2 7 3:: 28 ^ 30 31 "3 2 "3 3" PULSE RESP. 2 s S g 5 8 58 s 2 s f> s s ,- s » 3 8S ~ 5 2 g s s m r: S § Sg s o B s 8 s a i s g S 5 s S S s a 3 S ?S s S s S § s sis ^[s r,\-. ''r s|s g 2 s 3 J S ?, Z 3 S S! s ?i 3 c! S i S 3 •& S s Si £ S ?! 3 s s ?; S s 85 26 27 1 28 29 3'0 1 2 3 i 5 c 7 8| 9 10 ii 12 13 M| 15 if) 17 18 19 20 21 22 1 Enteric fever, single relapse (Pennsylvania Hospital). creamy, and limited to the dorsum, the margins and tip being bright red. Appetite is lost, and there is thirst ; diarrhoea continues, although in many cases the bowels are confined at the onset. Diarrhoea does not at this stage usually exceed four or five loose yellow stools in the course of twenty-four hours, fecal in character and unattended by pain. Diarrhoea may, however, be absent during the entire course of the dis- ease. Toward the end of the first week tympanites develops, and there is tenderness elicited by pressure in the ileo-csecal region or in the neighborhood of the umbilicus ; gurgling may also be developed by pressure in the right iliac region. Toward the end of the first week an increase in the area of splenic dulness may be detected, and the charac- teristic rash appears as rose colored spots. The urine is diminished in quantity, its urea increased, and the chlorides diminished, while fre- quently a trace of albumin is present. At this period a few scattered rales may be heard over both sides of the chest posteriorly, especially SYMPTOMS. 181 at the ba?^es, aiul sliiiht occasional cough may occur as a symptom of bronchitis ahnost from the very onset. Tliere is usually pallor of the face, with circuuiscrilx'd flushing of the checks ; the conjunctivse are pale and the pupils considerably dilated. In the f>eco)i(l ircck the symptoms are aggravated ; the fever remains high and is continuous or subcontinuous in type. The action of the heart is feeble and the first sound weak ; the pulse varies in frequency from 90 to 120, is less full than during the first week, and may become less dicrotic. The expression is duller, the flush upon the cheeks deepens, and in severe cases the face becomes slightly dusky. The headache now spontaneously diminishes. The patient becomes dull and somnolent, but has little or no sound sleep ; he is indifferent and apa- thetic, and the dulncss of hearing increases. When aroused and ques- tioned he commonly replies connectedly, but usually in monosyllables. Muscular movements are feeble and tremulous ; the tongue is dry, red, and fissured, often incrusted with sordes and protruded with difficulty. The patient lies upon his back, with his eyes half closed, listless, and making feeble, wandering movements with his hands. The delirium is usually wandering or muttering in character, and if the case be severe there may be involuntary discharges of the urine and faeces, or the urine may be retained. In other cases delirium is active, even maniacal, and this variety may develop suddenly from the wandering form. Tympanites, diarrhoea, and other abdominal symptoms are more marked ; fresh crops of the rash continue to make their appearance, and evidences of pulmonary congestion become decided. In favorable cases defervescence may now set in. In the third iceel: the symptoms are the same, but more grave. The loss of strength is extreme and the emaciation marked ; the muscles are flabby and the cheeks hollow. The pulse is feeble and accelerated, and sometimes running in character ; the rash continues to reappear in fresh crops ; free sweating is common and sudamina ajDpear, especially upon the abdomen and lower portion of the thorax. Muscular movements are tremulous and ataxic, and subsultus tendinum may occur. Bed- sores may noM* make their appearance, and there is danger of pul- monary complications and failure of the circulation. The heart's action is feeble, the impulse faint or imperceptible, and the first sound frequently inaudible. The temperature early in the third week usually conforms to the remittent type. With the fourth iceel: the temperature range becomes intermittent. This period may mark, even in grave attacks, the beginning of ccmvalescence. In that case the morning remissions of temperature for a few days often reach subnormal ranges. The symptoms ameliorate, gradual improve- ment takes place, the tongue cleans, constipation replaces diarrhoea, the area of splenic dulness decreases, the urine becomes clear and more abundant, and albumin, if present, disappears ; the skin is now bathed in perspiration • emaciation, however, does not stop until the tempera- ture -falls to normal ; a ravenous hunger now develops, and is charac- teristic of the period. Convalescence is tardy, and is apt to be protracted by complications, sequels, or relapses. The temperature is at this time extremely unstable, and recrudescences of fever are brought about by slight causes. 182 ENTERIC OR TYPHOID FEVER. Special Symptoms. — Temperature. — In uncomi^licated cases the temperature range may be divided into four periods, each of which has its special fever curve, the time covered by each period usually being one week, but often only five days, and exceptionally eight or nine days. This typical temperature curve is modified by comj^lications and treatment and prolonged by relapses and sequels. In the stage of onset or during the first week of the disease the temperature steadily rises until about the fifth or sixth day, the temperature of each evening being higher than that of the preceding evening, and the temperature of each morn- ing higher than that of the preceding morning : w^hile this step-like rise, as it has been called, occurs in many cases, it must not be regarded as invariable. In this way, by the end of the first week a temperature of 104° or 105° F. may be reached, and the height of the temperature range established. This fever range, the acme or fastigium, indicates the probable range of temperature in the absence of complications through- FiG. 12. M E ■W TJ r "m T m" — M E M E 'me' "m ~ M E m" - M E M E M E M E M E M E M E M E M E M E SOWELS NbMEER 1 1 1 1 2 2 1 2 3 1 1 1 1 I 1 1 1 1 1 2 1 1 105' —^ -^ — -^ -^ -^- -U — 1 — -;- —— -^ - -^- ~^- -^- -^- — - ■— ^? ■J- 3::: Tl 7^ 7^ - 1^ ^ ^^:^ F'S 7rj T,. -^ 2^ s^i s^s tT^ S''5' ~ ■ E J ^ ■^-' ■':■'' ' ' ■^ '- ^ ^ ■i\ % ^- ^ i ^ (f ^ <- 1 ± f; 1 fl- f: °- ^ 1 <- ^ 104' 103' 102° lOl' 100° 99' ^ t;; . 3 "^ ;. J. ^; ,^1 ~J_ *■* ^ a- o » (» o = o ■- <- < 0- < 0- < t •" - ■' - <.a •*— i ^.- h,- ^ o a> m »:■ ^• -^ OJ to «; , to lO to » ai -•x ■c r i'tr ^l— — — — - i— - — n — -^- A ^^- ^— -^— — ;— -Jf— _ l~ — i - z 2- ^ 1 ztz =P — fe - -^ i — — * A F -}— -"■- _L_ - ■ _ _ _ . ._ _ . E E E E ~ E E E E E E ^ 3. 7^ EE zrz EE - k- E - ztz = E - 1 £ 5 a;_ f\— ~_ z *iz z - - Z z z z z z z z z - z z z z z Z zjz 'V V 'l ; 97° = E EE E E E E E E E E E E E = E = = - Z — -j/ ]l i DAY OF 1 1 12 1 3 1 4 15 1 6 1 7 1 8 1 r 20 "tr ~~' Zi IT 4 au ^ PULSE lis s g g S s g g s s ■g ss s s g s f2 s » g g g .?: ;j s ,- ,T ga g RESP. S T, S S fi" s: T. ?, j; S ss SJ H s s s s s S s 2 s s S s ? 2 5S s DATE 24 25 26 27 28 29 30 31 1 2 3 4 5 7 8 Enteric fever, subnormal temperature after defervescence (Pennsylvania Hospital). sionally attended by a brief fall in temperature. Very high tempera- ture, so common in typhus fever, relapsing fever, and in other acute infectious diseases, observed as an early manifestation, is to be regarded as an evidence of intense infection or of the occurrence of an early complication. Hyperpyrexia may occur as a preagonistic phenomenon. During convalescence the temperature for the first few days fre- quently remains below normal. Its chief characteristic, however, at this period, is its instability, its liability to be disturbed by trifling causes. Thus, even after the temperature has been normal for a number of days rises may take place as the result of dietary errors, constipa- tion, the visits of friends, emotional disturbances, and like simple causes. Such recrudescences of fever commonly last some hours, very rarely more than a day or two. As recrudescences sometimes follow the first taking of solid food, this brief fever of convalescence has been called febris carnis. In other instances after the establishment of convalescence the temperature continues to range at subfebrile levels — SYMPTOMS. 185 100°-101° F. This l)0(l-fV'vor, ns it has I)o(mi tormod, is to bo ascrihcl to the influence U])()n an unstable teniperatiu-c of the retention witliiii the body of tlie pnxhiets of waste, the elimination of which has been interiered with by the inactivity of the skin and the constipation cha- racterizing early convalescence. So soon as the ])atient is allowed to be out of bed constipation usually ceases, the skin becomes more active, Fig. 15. 104° 103° 102 101 100= 99° NORMAL 98' 97- DAY OF DISEASE PULSE DATE M E M E M E M E M E M E M E M E M E M E M E M E M ? M E M F M E 1 1 1 II 1- = 1 1 1 1 1 1 = - 1 _ _ _ ^_ _^ _ _. ^ ^_ _,^_ ^_ _ i r — z z Zj H Z - ^ \~f\ ^ ^ =! p-; — ~ — — ] — — — — ^ v/ — Vt/ \i/ i 6 7 S 9 10 11 12 13 u 15 16 17 18 19 |l S| = 5 S 5|S = 1= s's '\~- ^¥ -|Si S|. U\i - - s|S ^ i!S ^1= 29 I 2 3 ] 5 c 7 8 'J 10 11 12 13 H Enteric fever, mild case : normal temperature 11th day ; recrudescence loth day, due to constipa- tion, and terminating after movement of bowels on the 17th day (German Hospital). and elimination in general more effective. Under these influences the subfebrile temperature rapidly falls to normal. Cases of enteric fever pursuing an afebrile course, although the disease possesses otherwise characteristic features, have been described. This must be regarded as a very rare form of the disease. Such cases are certainly almost unknown in this country. The temperature range of the relapse usually corresponds to that of the original attack ; the fastigium is, however, more quickly attained and defervescence occurs earlier. Circulatory System. — The pulse-frequency corresponds to the in- tensity of the fever, but not so closely as is usual in febrile diseases. Enteric fever is a fever of relatively slow pulse. Its frequency is ex- tremely susceptible to variations, and may be greatly modified by slight causes, such as change in posture or movements in bed. In severe eases it becomes irregular in rhythm and force — phenomena of unfavorable prognostic import. In the first week the volume of the pulse is full, but its tension low, and at this period the pulse is freqnentlv alreadv dicrotic. Dicrotism is important from a diagnostic standpoint ; it is rarer in childhood than in adult life. During the first week the pulse is usually though not invariably above 100, but later, in severe cases, it may become greatly accelerated and very weak. Coldness of the extremities and lividity of the surface are also indications of enfeebled circulation, and, as collapse may develop from this condition, are always to be regarded as symptoms of immediate gravity. With the onset of convalescence the pulse gradually returns to nor- 186 ENTERIC OR TYPHOID FEVER. mal. Its frequency is usually accelerated, but a slow pulse is not un- common, and instances of a fall so low as forty or even thirty beats to the minute are occasionally observed (bradycardia). The heart's action in mild cases and during the early period of the disease is but little disturbed, but in severe cases the force of the impulse progressively diminishes until, toward the close of the second week, it becomes extremely feeble or almost imperceptible, and the first sound very faint or inaudible. Occasionally there develops a faint systolic bruit at the apex. Pericarditis and endocarditis are of rare occurrence. Myocarditis, however, is more frequent, and the cardiac weakness shown in the feeble impulse and faint first sound is due in part at least to degenerative changes taking place in the myocardium, and in part to functional disturbance of the nervous system. Under these circumstances sudden death may take place as a result of car- diac failure. Slight oedema of the ankles, dependent upon cardiac weakness and anaemia, may occur in early convalescence. The blood has been carefully studied by Thayer,^ who found the number of red corpuscles at the beginning of the fever usually normal. During the first weeks the number of corpuscles falls gradually, but to a relatively slight extent. The fall is more rapid upon defervescence, reaching its lowest point about the first week of convalescence. Re- covery from this anaemia is gradual. As a rule, the decrease in the number of red corpuscles bears direct relation to the severity of the case, but grave anaemia may follow cases that appear to be mild. Severe post-typhoid anaemia may constitute a grave sequel of the attack. The haemoglobin diminishes with the red corpuscles and to a greater proportionate extent. Its return to the normal is less rapid. The leu- cocytes are at the beginning about normal, but their number gradually falls, reaching the lowest point about the end of defervescence. The diminution is slight ; the return to normal is gradual. The absence of leucocytosis may in a suspected case be of diagnostic value. Venous thrombosis, especially affecting the veins of the lower extremities, and most frequently a crural vein, occurs in about 1 per cent, of the cases. Its time of occurrence is usually late in the course of the disease or during convalescence. It is manifested by rapidly on- coming oedema of the extremity, with pain. The acute phenomena usually subside in the course of a few weeks ; permanent oedema with difficulty in walking often results. It sometimes happens that a portion of the thrombus becomes dislodged. The left crural vein is more fre- quently involved than the right. Respiratory System. — The frequency of the respiratory movements varies with the intensity of the febrile process. Pulmonary symptoms are among the most frequent and important manifestations accompany- ing enteric fever, although for the most part they are to be regarded as complications rather than as direct results of the specific infection. Bronchitis is very common. It is usually an early manifestation, and therefore may have diagnostic importance. Its existence is revealed by rales, usually at first dry and scattered. In cases of moderate sever- ity the bronchitis has no important bearing upon the course of the dis- ease ; in the graver cases it often extends to the finer tubes. ^ Johns Hopkins Hospital Reports, vol. iv. No. 1. DldESTI 1 7-; SYSTEM. 1 87 Bro)irlio-p)}eiimo))!(i may (Icvoloj) in I'literic fever, as in other diseases attended hy ui-eat jji-ostnitioii ot" the nervous system, as an inlialation or deglutition jjueuniouia. Ilypostatie congestion and o-dema in tlie Uit<'r periods of the disease are common, and are to be ascribed to enfeeble- ment of the circuhition and the lowered tone of the nervous system. Striimpcll is inclined to look upon many of the instances usually rejranled as cases of hypostatic congestion as in reality broncho-|)neu- monia. The physical signs are impairment of resonance at the bases posteriorly, feeble and distant respiratory murmur, and tine, moist rales, chiefly inspiratory. Croupous pneainonia may occur as a complication of enteric fever, usuallv in the second and third weeks. In the majority of instances it is to be regarded as a true complication dependent upon a secondary infection with the pncumococcus. It may be overlooked unless the chest be systematically examined, as the subjective symptoms are not marked. Croupous pneumonia may develop early, the onset of the affection being: abrupt, with a chill, and the pulmonary phenomena so dominating: the clinical picture as to obscure the signs of enteric fever. After the first week, however, intestinal phenomena, enlargement of the spleen, rose spots, and the subsidence of lung symptoms enable the diagnosis of enteric fever to be made. In such cases, known as pneumo-typhus, the pulmonary lesion is probably due not to infection by the pneumococcus, but to an early pulmonary localization of Eberth's bacillus. Pleurisy occasionally occurs as a complication of enteric fever. Catarrhal laryngitis is sometimes met with, and laryngeal perichon- dritis, with or without accompanying ulceration, may occur, the lesions usually involving the posterior wall or the base of the epiglottis, CEdema is liable to occur in association with ulceration or perichondritis, Epistaxis is a common symptom. It may appear in any period of the disease. It is commonly slight, but profuse, even serious, nose bleeding may occur. Striimpell mentions a case in which a fatal issue resulted. Very commonly during the period of prodromes, and often during the course of the disease, it amounts to nothing more than a stain upon the handkerchief caused by picking at the nostrils. Ulceration of the nasal mucous membrane is occasionally seen, and the fact that the nasal septum may be perforated or necrosis of the cartilages may follow with resulting deformities should be borne in mind, lest subsequently the lesions may in any case give rise to the suspicion that the patient has had s^i^hilis. Dig-estive System. — Marked disturbance of the digestive system occurs, and symptoms referable to the gastro-intestinal tract very often for a time dominate the clinical picture, while those dependent upon the general constitutional infection assume a subordinate role. Anorexia, as a rule, occurs early and is complete. It usually persists until defervescence. At this time, however, hunger is often urgent. Thirst is a prominent symptom, and even when the patient's mental condition becomes such that he fails to demand fluids, he drinks them with avidit}" when proffered. The tongue early in the course of the attack is moist, swollen, and usually covered with a whitish fiir ; later, the coating clears off from the 188 ENTERIC OR TYPHOID FEVER. edges and tip, which are often of a bright red color. The tongue may- remain moist throughout, but in severe cases it soon becomes dry and is covered with a dark brown coating with numerous cracks and fissures. Such a tongue may bleed, and this, together with oozing from the gums, leads to the accumulation upon the teeth, lips, and gums of a collection of material consisting of clotted blood, retained food, and cast-off epi- thelium, to which the name of sordes is given. This condition may be to a large extent averted by careful and systematic cleansing of the mouth. The tongue cleans off upon the occurrence of convalescence. The lips are cracked and dry, and the buccal mucous membrane dry and sticky. The pharynx is not infrequently the seat of a catarrhal inflammation. Membranous pharyngitis occurs in rare cases and is of serious import : the false membrane may extend into the oesophagus. Faucial angina, occurring coincidently with a diffused erythema upon the surface of the body, as happens in a small proportion of the cases, may give rise to a suspicion of scarlet fever. From the pharynx, by extension of the infection through the Eusta- chian tubes, the middle ear may become involved, and suppurative otitis media take place with perforation of the tympanum. This condition may, owing to the patient's mental condition, be overlooked. Not infre- quently, and usually in the third week of the disease, parotitis — parotid bubo — develops in consequence of infection by Avay of the duct of Steno. This, though usually unilateral, may involve both glands. Its usual termination is by suppuration, and its occurrence adds greatly to the gravity of the prognosis. Inflammation of the middle ear and of the parotid gland is the result of secondary infection. Nausea and vomiting occasionally occur early in the disease. They are much more common as manifestations of enteric fever during child- hood than during adult life. Repeated vomiting is a serious symptom and of unfavorable import, since it is, as a rule, to be ascribed to a complication, such as nephritis, a cerebral lesion, or developing peri- tonitis. Vomiting under these circumstances does not occur early, but is a late manifestation of the disease. In certain rare instances vomiting is so persistent that death from exhaustion may ensue, and in some of the cases ulceration of the stomach has been found after death. Symptoms referable to the intestinal tract are constant. In the early days of the disease constipation is the rule, and in not a few cases this condition continues throughout the entire course of the attack. The diarrhoea is usually proportionate to the severity of the attack and to the extent of the local intestinal lesions. This is not, however, inva- riably the case. Even extensive lesions of the glands of the small intes- tine may be present, while the colon contains solid fgeces. Diarrhoea is common toward the end of the first and during the course of the second week. It may not, however, occur until toward the close of the attack. It is to be ascribed in part to the local ulceration, but is chiefly due to the accompanying intestinal catarrh, especially to catarrh of the large intestine. The number of stools in the course of twenty- four hours varies from four or six to fifteen or twenty. They are usu- ally copious, in odor offensive, in consistency thin, in color yellowish or DIGESTIVE SYSTEM. 189 ochre yellow, soinctinies u;reenisii, in reacti(»ii alkaliiie, and arc V(»i(l(' i -forrT;- 2- s-j-s- pr ?J L^t^ fe 3? s sl-s^s-;-s-s-s i^i^i^i S ■i'-i S ■2 s E S S s -s ■k-i^ii^ S^*2-S- „ U :?- •5- !f4? ^^o EJ- ^n.-io 3--olo^o-o ?•?-?-? -£ r^.^ tf>. s+ 0.0 *S o .*-:*'.}- a < O 105° E »- °103° 102" 101° 100° 1- 5 89° S < S 98° 1- O ^ 3 97' < 1- * UJ a DAY OF DISEASE PULSE RESP. — -^ia 2121 ^ m4*- J.i<- o|~-|cJ- .■:\^^^im * ^ a>- o-.< v«- *- ['^ ■"-f'rS";:^- ' ; : ' ' 1 ! 1 1 I 1 1 ■ ■■, l.i ; i 1 A /\ A ~^ — 1 ! 1 M 1 ^-^— ^-^»^ -/\ ^^ -1— 1 — , - — — - - y\^ ' ' V ' : : i -^ :•; V"> \ ; ' — — ^ L - ^>b>i *r^ ^ A 1 / V ^ m. /\ / \ / • T N/ \ M r \ VI / V ' * • 7 \ \ / \ / A' / 1 ' i_i;\/ ^i \ ' / \ ' • 1 \/ ■s ,T \. ' 1 J , H ~ - 1 , ^ V- 1 ^' 2^2 — — ' -^ r^ — — — — — — — :;i^;z= o . o , o 1 V 1 1 1 ■ \ Il i 1 '■1:1 1 >? V J 1 ! 'T '*V. t *" 1 ^g' ': -"' 1 1 I ! 1 M I 1 1 ! [ 1 1 ! , : ( ! — -s-- -^-t^SttI — ^^ z- — s,_ .s,. - -_- z - f d 1 ^1 - ' — ^i-' - ^ z~Z i ^ -'i £ • i □•! -V 3, -■ T Q-! ,^ = ^ ~ l'itart of the ileum, but it may be in the caput coli or in the appendix. It is immediately followed by an acute septic peritonitis, almost always diffuse, although in rare instances localized by the imme- diate formation of adhesions to an adjacent loop of gut, or other viscus. Death may result immediately from shock. Usually the occurrence of perforation is manifested by intense pain in the abdomen, commenc- ing in the neighborhood of the right iliac fossa, and, as peritonitis develops, extending over the entire surface of the abdomen ; symp- toms of collapse, characterized by subnormal temperature, shallow, fee- ble breathing, cold clammy sweats, a feeble running pulse, great thirst, frequent vomiting, and partial suppression of urine. If death do not then occur, symptoms of peritonitis devolop ; the temperature again rises, the abdomen becomes extremely tympanitic, and the lower seg- ment of the liver dulness is effaced — a very important diagnostic sign as indicating the escape of the gases from the intestines, through the per- foration, into the abdominal cavity ; the abdominal walls become rigid, tenderness is extreme, and the legs are dra^Ti up ; vomiting sets in, the pulse becomes rapid, small, and thready, and the physiognomy that of intense suffering. Death takes place in the course of from two to four days, exceptionally later. Peritonitis, local or diffuse, may originate without actual perforation by extension of inflammation at the seat of ulceration from the mucous to the serous coat of the intestine, the latter structure remaining intact so far as perforation is concerned. It may also be caused by the rupture of a pseudo-abscess follo^ving soften- ing of a mesenteric gland, and occasionally as a result of the burst- ing of abscesses of other structures, as of the liver, gall bladder, spleen, or the abdominal wall. Splenic enlargement, according to Leube, occurs in over 90 per cent, of the cases of enteric fever : it is first detected toward the end of the first week, coincidently with the appearance of the rash, and continues to increase in size until about the fourteenth day. With the beginning of the fourth Aveek — i. e. with defervescence — a diminution of vol- ume takes place. Splenic enlargement persisting after the establish- ment of convalescence should be regarded with suspicion as indicating the possibility of a relapse. Usually the large spleen can be felt below the costal margin, but if the colon be greatly distended with gas it may be so pushed back that even the normal area of dulness cannot be made out for the sm-rounding t^'mpany. It should also be remembered that enteric fever in the aged is frequently unaccompanied by an increase in the size of the spleen. Accidental rupture of the organ, as from a 192 ENTERIC OR TYPHOID FEVER. blow or from undue force in efforts at palpation, has been observed ; spontaneous rupture is uncommon. Jaundice is not frequently present in enteric fever, and symptoms referable to the liver are uncommon. Occasionally the organ is some- what enlarged, but the parenchymatous degeneration gives rise to no clinical manifestations. Nervous System. — Morbid phenomena relating to the nervous system are very common and diverse in enteric fever. Not rarely they dominate the clinical picture. Headache is frequent, both in children and in adults ; it is an early symptom, appearing during the period of prodromes and may vary in intensity from a dull supraorbital pain to a severe neuralgic and per- sistent headache. It is usually most severe in the frontal region, and, at least early in the course of the disease, becomes aggravated toward evening. So intense may be the headache that it sometimes suggests meningitis, especially if, as sometimes happens, it is associated with vomiting, muscular twitchings, and retraction of the neck. It usually ceases spontaneously about the middle of the second week, and very often gives place to mild delirium. Headache may be associated with or alternate with somnolence and apathy. On the other hand, distressing Avakefulness may be present during the early course of the disease. In a majority of the cases, under expectant methods of treatment, the patient's mental condition as the attack advances is peculiar : he is drowsy, dull, and apathetic, and indifferent to his surroundings. The hebetude may be so marked that drink, though partaken of eagerly when offered, is not asked for during long periods. The patient pays little heed to his surroundings and rarely volunteers a remark. When aroused, however, he replies to questions intelligently, but slowly and in monosyllables, and almost immediately falls again into a somnolent state. An evidence of the extreme apathy of the patient's mental state is observed in the manner in which he responds to the request to put out his tongue : the organ is protruded slowly, and only in response to sev- eral sharp requests ; it is often not retracted at once, but held out until the order to put it in again is given. In some instances hebetude is present from the early days of the attack ; in others the mind remains clear throughout the whole course of the sickness. The latter condition is the rule in cases treated by systematic cold bathing, Avhich also favorably modifies delirium and other nervous symptoms. Delirium is present in a majority of the cases. As a rule, it does not commence before the middle of the second week, about the period when the headache subsides. In a small proportion of the cases it does not appear until late in the course of the disease, and lasts only a few days. In rare cases maniacal delirium occurs at the beginning of the attack, and may be the first symptom to attract the attention of the friends of the patient. The character of the delirium varies greatly. It is often slight and occasional, occurring chiefly in the night-time or on waking from sleep in patients who are at other times entirely rational. More commonly it is continuous, and usually of a quiet form. It may be — though this is not common — active and noisy, passing as prostration becomes more NERVOUS SYSTEM. 193 marked into the low, miittcriiiii" loi'in known as typho-niania, oi- into a waiulcrino-, fatuous state with treinWlinn- lilo t'oiiiid it (liiuiiiishcd. The iiiMc iicid is always increased. Diirinti,- the latter part ol' the attack, howes'er, the anumiit I'alls (<» iioniial, and diir- m^y convalescence it is less than in health. Copions deposits of the unites may occur at any time in the course of the disease. They are not critical and are without ]iro<>;nostic value. The chlorides are j:;reatly toms, to the arrange- ment of another <2:ronj) of cases as pncumo-fi/jjIiKs, with pleurisy as yjfea- ro-fi/phnx, and where profuse sweat- ing has occurred to the .siulora/ form. Others have sought to distinguish ataxic forms and adynamic forms and varieties based upon the promi- nence of particular symptoms. Such nosoloo-ical arranoenients are neither scientific nor convenient. Without attempting a closer analysis of the forms, the cases may be divided into typical and atypical. The former present the coniplexus of symptoms already described as constituting the clinical history of the disease, and further illustrated in the analysis of the symptoms and in the considera- tion of the complications and se- quels. The atypical or imperfect forms constitute in most epidemics a large proportion of the cases. The following special forms require sep- arate consideration : 1. The Mild Form, Typhus Levis- simus. — The symptoms are those of the typical disease modified as re- spects intensity, and in particular as to the febrile movement, which is of lower intensity. The commence- ment of the attack is usually grad- ual. There are prodromes ; chilly sensations occur ; there are headache, diarrhoea, epistaxis, and a scanty or well-marked eruption of rose spots. On the fourth or fifth day the tem- perature reaches 103° F., but rarely exceeds that level. The deferves- cence is by lysis, and may occur at the end of the second or during the course of the third week. 2. The Latent or Ambulatory Form, Walking Typhoid. — All the symp- toms are mild. There is general ma- laise, prostration, and elevation of temperature, slight diarrhoea. The patient i and does not regard himself as certain -- ~ ^ O / f II \ (" -' \ 7 - -- ^ — / Y- / - - / \ 1 i f "" -. n ■^ ^^ ^ O -- ^ ;: > :3 g < i^ c ^ o ■* -^ ^ — — — 3 = ..^ »• = '^ ■~ -I 2= — ■:^ 3 u = 3i ■^ ^ c \» c ^ i 5^ ^ •= n : ^ vT ■^• *■ — ■^ <: ■n — — — ra ,-— ' ^ < .!- c "™ ~ - -• ■< 1 __ _ . _ - ::». 5- ?^ z : = = - ■2. C ^ I o- 2 :» H <. f ^ =! '^ -" = . I" s ^ s 75 o S ^- — — 2. 3' "^ p — • J — n - (^ _ ^ M — p k Zl. 5' <' ■^ _^ "~ > ^ <; ■^ -. ^ _ ^ -4 • ^ —■ f n 'Z ^ — — — ^ n r* >:;■ — — " ■1 -Z - ^ • > ni. :;. "" ,. ^ • s; — _ >. ■< ■ : ; ^ i *■ > ^ - — -' -: =» » - rf' Z, ■^« * ~ s n H" >: r ■— • ^ -5 ^■^ ^• 3 -L^ _L ■ s; 1 about, attends to his work, ufficientlv ill to o^o to bed. The attack 200 ENTERIC OB TYPHOID FEVER. extends over three or four weeks, and the intestinal lesions proceed to sloughing and ulceration. Herein lies the danger of this form of the Fig. 18. 4THvyEEK . Cold tub-baths. Abundant malarial organisms. Dr. W. Oilman Thompson's second case of malarial fever associated with enteric fever. disease. Hemorrhage or symptoms of perforation may at length reveal the true nature of the attack, or sudden maniacal delirium may occur. .avwttK Fig. 19. •*l".WEtIV STI-WEEK 3ST" DAV 41»'D«V ins" ,| IE oT 104 J_^ _ -. o-tS- 1 103° r1 I o y- f - 3 T ~ :S 102° i_ Q ^ r tt/- -r T -.-^ -^ T tr 5 T R 2 t: 101 d X-> \ ^ Lit + " u u \\ \t - XCI^ L t ^ it it ^^ 2^s:5,i2K=.QLiJt — ^v>.^> Cold tub-baths. Pigment found in blood-corpuscles, C. C. = chills. but no germs. Same as Figure 18. Third case. 3. Tlie Abortive Form. — Prodromes are of short duration or absent altogether. The attack begins abruptly with rigors or a chill. The temperature rapidly attains its maximum. By the evening of the third or fourth day it may reach 104° or 105° F. Rose spots appear as early as the second or third day. At the end of the first or early in the second week defervescence takes place by lysis, often being completed in from twenty-four to seventy-two hours, the fall of temperature being accom- panied bv profuse sweating. Convalescence is rapid, but relapses may occur. This form of enteric fever appears to be not uncommon in Europe. In this country it is certainly rare. 4. Hemorrhagic typhoid — a very rare form, commonly fatal, charac- terized by hemorrhages into the skin and from mucous surfaces. This form corresponds to the hemorrhagic forms of variola, measles, and other infectious diseases, and is not to be confounded with ordinary cases of enteric fever in which hemorrhage from the bowels occurs. 5. Afebrile Typhoid Fever. — Dr. Cayley states that many cases and even epidemics of typhoid have been met with in which the temperature has been normal or subnormal throughout the whole course of the dis- ease. He cites an epidemic observed by Strube at the siege of Paris. The symptoms are those of ordinary enteric fever. The duration of the attack was short. Of 23 fatal cases, death took place in 20 during the \'.u!Ii:tii:s. 201 ooiirso of tlu' lii'st fourteen dny.-. The alxloiiiiual symptoms were slight, but the lesions were found upon post-mortem examination. 6. Infantile Remittent Fever. — This term lias heen applied to enteric fever as it occurs in children, for the reason that the pyrexia often assumes a distinctly remittent type throuulioiit (lie whole course of the Fk;. 'JO. M E M E M t M E M E M E M E M E M E M E M E M E M L M E M E M E M E 103 102 J 4--- r 1 ■ ;■ ■: ■ ■ - - -E 100 99 98' 97' ~ — M -/ TTT iiil 1 T iiiBiii Cii Or :>:SIKI ^ ^ 1" 1 1 1:; 1:; H 1.-. 10 1; K^ 19 -^o 21 -2-2 ■-':; 24 Enteric fever in child asred nine vears. attack. The disease is rare in the first year of life, but not infrequent during later infancy and childhood. The symptoms and complications are modified by the age of the patient. Nose-bleeding is not common ; the rise of temperature to the fastigium is abrupt ; nervous symptoms are prominent ; diarrhoea is uncommon. Other abdominal symptoms are, Fig. 21. M E M E MIE M E M E M E M E M E M E N E M E M E M E M E M E M E M E M E 104 103 102 101° 100° — — — — — — — ' — — — — — _ _ _i _;• JL _ _ _ _ 1 _] _ _ — — in ~TE 7T ~ — —J — —1 — — — — — - ~ Z ZI _ |z: viz - T -1 ^ V^ : ~ I - z = - - Z 99° 98° - ZZ d Z - -; i_ H _ : r t r - - r z L _ _ ,. _ _ w. Ii , f\ _ 97° — — — — — — — — — l— - ^^^ — — ♦ — -V — — V — — — — _ _ _ * — — — ' — — — — — — — — — — — — -t- — 0A» JF - 9 10 11 12 y-i 14 1^1 10 17 18 19 20 21 22 2a ^ Enteric fever in child aged four years, remittent type. as a rule, less prominent than at later periods of life. On the whole, the reaction to the infection is less marked. Nevertheless, grave cases occur. Exceptionally, fatal hemorrhage and perforation have been noted. Fatal intestinal hemorrhage occurred in a child twenty-two months old, in which, upon post-mortem examination, the characteristic lesions of 202 ENTERIC OB TYPHOID FEVER. Ph m T T -O O s 1 ' '■I '^ 09 02 •' u r. vwaga i 5, PJ "2 .» s ° 29 n " LU „ OS 02 ^ s "^ 9C 02 " al « Vl\l3N^ r'" o W 02 t. S ^J '"^ 06 02 ^' 111 , --' Ci OS 02 ,v, E ■" 05 02 " 111 n- v;\3N3 (» 0» 02 rt 2 '■: -' '" 8C f2 ^' UJ "l w «8 (IZ o S i >-^ ■" U 02 ■' u " vniaNa 3= ' o 09 02 ci E s: '" 21 02 "^ UJ o 09 02 oo s "::::::^:; : •=■ 09 n ^ UJ ^ VW3N3 ,-:=' f SL SZ r. E ---,.. '" !iOI 02 " UJ „ m 92 „ S IS —' '" 001 92 " UJ " VW3N3 Z' CI 001 02 ,„ E !■=: '^ 021 92 "^ UJ Z^i' rt 211 92 ^ s ...j^; ' "■' 90! OS " l:> : o 001 02 M E " '" m 02 ■" UJ ' ° J o "" OZ M s <<:_ -^ ns 22 -^ UJ -"I VW3N3 ;;5'"" 1 «0<.I02 „ S 'C ' SC f2 " UJ ,- sll fZ o 5 "*• 911 93 ^ UJ ^ VW3N3 o 9B OZ ^ E «;_ '^ 06 f3 UJ '"--.• o 8R ''2 S «;' '*' SS 22 UJ VW3J3 ; » -„ 96 02 S i::.-'™^^ UJ ; -, 001 ^2 ^ E E (-4=f--- " " ■ " 901 82 : ;::=- T 1-90I9EO S -■ ^ KII 82 UJ >< o ■■"'I S£ ci E f' •' 001 f2 ^* UJ - mm T o i-oi ze o) s ^ " 101 2E " UJ ^5 1 ^ ee 92 ,- E -I- ""' " h)I 2E °' UJ Vl^3Nb ^k. ^ 96 J'S u> E *; "96 fZ " UJ ^ > ' 51 001 82 ,n s <' ■' mi 82 "^ UJ - Vl^3N3 'l s r^ 001 82 ^ E Ji "^001 2S " '' o "01 82 m E "■ ran 82 •' ■uj -■ VW3N3' "" 'i Ov S«l fS (M E ^^"1 'X3j_ ^' <^" "' '■' --'" OT ft" fz ^ E ' i, ^' 001 1-2 "' UJ \ ^ 101 re o E ^ "' ^ol[^^ '•' UJ ~;sA o inijzt: o E :g: ^' 26 n UJ rt YW3N3 ~ '1 ^ 06 82 CO . -.,d-- -- _ " 96 02 " .? 1 <. 96 02 ^ E 1 ^:;:: ::::: " tS iZ '^ :?- ^ 88 OC -J, S — -^--- =' 96 91 '^ UJ . „ 88 lb- ^ --i^ r ■=' "01 82 " ' p«t ' „ 96 82 ^, S " ts re '^ + =' + -, 021 02 n E ::=L ^' noi ^^ ^ UJ r-. c 96 re „ E . ^= = " '^ 001 re '^ UJ < a, »2[ 9E rt 5 :>[::::::::: '-' 821 82 " UJ » - - '' ^ SO! 2E c3 E '■:;"" '^ 96 2C '-' UJ ^ "^ I. ,-, 00! 02 ^ E := -^ 901 OS UJ ^ -r- ,„ 02! 82 E :;::::::::::::: ^ t ' ' VARIF/riES. 203 enteric lever were Ibiind. lleiioeh lias re])urted a ea^e in wliieli lieiuor- rliage occurred in a girl ten years old in the course of a relapse whicli took })lace in tlie third week. There was at first an insignificant hh.'ed- ing, which was followed u])()n the next day hy a very copious hemorrhage with fatal ct)llapse, Henocii observed perforation in a boy aged eleven in tlie fifth week after convalescence had been apparently established. Statistics present a wide range of variation in regard to the frecpiency of perforation in children. Among 232 cases, according to Barthez and Killiet, it occurred in 3 only ; among 73 persons in whom this accident was noted, Murchison found 14 to be inider fifteen years of age. Certain secpiels appear more frequently in cliildren than in adults. Among these are noma, lesions of the bones, and aphasia. The death- rate in children in the first year is high, especially among the new-born. The mortality in childhood after the first year is decidedly lower than in adults. 7. Enteric Fever in the Aged. — In the advanced periods of life enteric fever runs a modified course. Its onset is insidious ; the febrile move- ment is less intense, and during convalescence the temperature falls to markedly subnormal ranges. The eruption is frequently absent and diarrhoea is less common. Perforation rarely occurs. Murchison en- countered it twice in patients over forty years of age, and I saw it in the body of a man aged fifty-three. Complications are frequent and grave. Broncho-pneumonia and croupous pneumonia occur, and there is especial danger of collapse from cardiac asthenia. The mortality of enteric fever after the fortieth year of life is high. 8. Enteric Fever in Pregnancy. — Pregnant women seem to enjoy a relative immunity. This immunity would appear to be greater during the last than during the first half of the pregnancy. Of women who in this condition contract enteric fever, more than 50 per cent, abort, this accident occurring usually in the second week of the attack. The foetus has been found to be infected, and successful cultures of the bacillus of Eberth have been made from the viscera. Relapse. — The relapse of enteric fever is the manifestation of rein- fection. It is attended by a repetition, with some modifications, of the fever and associated phenomena, a new eruption of rose spots, fresh glandular infiltration, and enlargement of the spleen. The relapse is, as a rule, of more abrupt onset and of shorter duration than the primary attack. It is commonly separated from the latter by an interval of some days, during which the temperature range is subnormal or normal. During this period in cases in which relapse occurs the spleen remains enlarged. The relapse is not invariably separated from the primary attack by an interval of apyrexia, but may develop during its course. It is then termed an intercurrent relajjse, and to intercurrent relapse must be ascribed many of the cases of unusual prolongation in the absence of com})lications. Two or more relapses may occur. As many as five relapses have been reported (DaCosta). I have observed four well characterized relapses in a young adult. The frequency of relapse is variable. It ranges from 3 per cent. (Murchison) to 15 or 18 per cent. (Immerman). In 284 cases under fifteen years of age observed in the Boston City Hospital from 1882 to 204 ENTERIC OR TYPHOID FEVER. 1895 and analyzed by Morse relapse occurred in 11 per cent. A large proportion of the cases of enteric fever in infancy and childhood are of mild intensity. The statistics of hospital and private practice with reference to this disease in the earlier periods of life are at variance. In private practice relapse appears to be much less common in child- FiG. 23. 'o¥"ilVE"«%"fs' 1 3 II -' ■'• W -2 ■: -2 2 2 ] 3 3 3 3 ',i 1 • L' In 11 uRiNE^ 5^ ^ g f,' ^ ];; 51 5: S ?. ^ s ^ S t; S s fj ;.-: -,-, L; a ;?,' :; -sssssss^s^isr^s^ssssisssssissss^s'ssss s's s 5 s s sis sjs s|s s s s;s s's s's s s ss s- 1Q^^ q:< QJ <^,cc<-CL < cl !' »' ■^,^. ■» ^JL PULSE is=¥^^,jii i|3;,.z,g^,j;-;'o;ip' :--p zisjs :^'',:i ^i? ?,' -i^^k - ?' -;-?.' ',5 ',- i,'- ^-=' -.,* i's i"" akiT Intercurrent relapse following mild primary attack (Philadelphia Hospital). hood than in adult life. This discrepancy is to some extent due to dif- ference of opinion among practitioners as to what constitutes a relapse. Relapse has been confounded with recrudescences of fever occurring during convalescence. Such rises of temperature are usually brief, not lasting more than a day or two. Occasionally they are of longer dura- tion, and are due to infectious or inflammatory sequels. Under these circumstances careful investigation will usually reveal the nature of the pathological process. Elevation of temperature during convalescence, unattended by rose spots, enlargement of the spleen, intestinal symptoms, and of brief duration on the one hand or protracted duration on the other, should not be regarded as constituting true relapse. The relapse declares itself by a step-like rise in temperature. Sometimes the rise is abrupt and progressive ; at others morning remissions occur, but usually the maximum is attained in the course of from three to five days. The subsequent course of the fever corresponds very closely to a primary attack, except that it is, as a rule, of shorter duration. Of 53 cases noted by Murchison, the mean duration of the primary attack was about twenty-six days, of the interval about eleven, and of the relapse about fifteen days. There is danger of the fatal issue from the stress of the disease when the attack is protracted by relapse or repeated relapses, but death may occur in consequence of any of the events which bring it about in primary attacks. Post-mortem examination of the bodies of those who have died in relapse of enteric fever has revealed the lesions of the primary disease. The individual intestinal lesions are less numerous, for the reason that only those glands and SECOND ATTACKS. "-iO.j patches ot" l^cyer arc involved that escaped during tlic first attack. Tlie ulceration is tlicrelore higher ii[) in the ileum and coexists with the recent cicatrices of the j)riniary attack, which are most numerous and extensive just above the ileo-ciecal valve. Relapse is due to reinfection from within the body of the patient. It is, in fact, a repetiticui of the primary attack. To the (piestion why the primary attack confers immunitv in a luajority of instances, fails to confer a lasting immunity in a few, and rentiers the patient liable to prompt reinfection in from o to 15 ])er cent., no satisfactory reply has yet been made. Second A.ttacks. — The attack of enteric fever in a great majority of instances confers complete innii unity against subsequent attacks. To this rule there are, however, exceptions. Many cases have been recorded in which a second or even a third well authenticated attack of enteric fever has occurred in consequence of remote independent infection in the same individual. I have personal knowledge of a case in which the patient suffered from three attacks of enteric fever at intervals of some years, the third proving fatal. To the immunity acquired in infancy and childhood must be attributed the insuscepti- bility of many adults upon exposure. Diagnosis. — AVell developed cases of enteric fever after the first week may be usually recognized without difficulty. During the first week it is, however, often impossible to form a positive diagnosis, but even then the nature of the disease may be suspected if there be febrile movement with nocturnal exacerbations, each night attaining a higher temperature, and especially if there be headache, epistaxis, diarrhcea, either sponta- neous or readily produced by laxatives, progressive asthenia, and, toward the end of this period, appreciable enlargement of the spleen. The direct diagnosis of the developed disease finds its support in the continuance of the febrile movement and the appearance of abdominal s%Tnptoms — namely, diarrhoea, pain, enlarged spleen, moderate tympany, and len- ticular rose spots. In doubtful cases the coincident occurrence of ca.ses in the same house or locality is of diagnostic importance. The differential diagnosis from certain other acute febrile disorders is sometimes attended with difficulty. The diseases with which enteric fever is liable to be conf(junded may be divided into two groups — first, those which resemble it in the first week of its course, and, second, those which resemble it in its more advanced stages. To the first group belong febricula, influenza, and in children certain of the exanthemata in the pre-emptive stage. Differences in the mode of onset, the short duration of febricula, the epidemic prevalence of influenza, are facts of importance in diagnosis. The prominence of coryza and bronchial catarrah A^ould suggest the possibility of measles, and erythematous angina would lead us to suspect scarlet fever, while intense headache and the presence of lumbar pains would serve to distinguish variola from enteric fever. To the second group belong certain forms of malarial fever, acute miliary tuberculosis, appendicitis, peritonitis, trichinosis, and, in children, entero-colitis. Jlalarial fever and enteric fever, as has been demonstrated by W. Gilman Thompson,' may coexist in the same patient. This association ^ Trans. Assoc. Amer. Phys., 1894 206 ENTERIC OR TYPHOID FEVER. is unquestionably rare, and cannot be regarded as establishing the exist- ence of such a nosological entity as typho-malarial fever. Some forms of malarial fever closely resemble enteric fever, especially when the marked abdominal symptoms are present. Vomiting, diarrhoea, splenic enlargement, cerebral symptoms, and the condition known as the typhoid state may occur in both diseases. The more important points of dis- tinction are to be sought in the presence of the eruption and the discovery of malarial bodies upon examination of the blood. The absence of the characteristic rash of enteric fever is without positive diagnostic value in doubtful cases, since in a small proportion of the cases the eruption does not show itself during the whole course of the attack. Acute tuberculosis presents in some instances a close resemblance to enteric fever. In the latter disease, however, the temperature in a majority of instances conforms more or less closely to a definite type, whereas that of tuberculosis is extremely irregular. In enteric fever diarrhoea and tympany are common ; in tuberculosis, diarrhoea when present is of a different character and the abdomen is flat, often scaphoid. In enteric fever nose-bleeding and enlargement of the spleen occur ; in tuberculous processes these symptoms are rare or absent altogether. The headache of enteric fever is usually dull ; that of tuberculous meningitis is acute and frequently associated with intolerance of light and sound. In enteric fever vomiting is much less common than in tuberculous menin- gitis. Convulsions are likewise rare in enteric fever, and the headache usually disappears upon the occurrence of delirium, whereas in tubercu- lous meningitis headache and delirium may alternate from the beginning. In this connection it is important to emphasize the fact that in rare cases of the so-called cerebro-spinal form of enteric fever the onset of the attack is abrupt, with intense headache, photophobia, painful retraction of the muscles of the back of the neck, twitching, delirium, and vomit- ing. Under these circumstances the diagnosis of enteric fever cannot be made until about the end of the first week, when the appearance of ab- dominal symptoms and rose spots, very often coincidently with subsi- dence of the cerebro-spinal symptoms, declares the true nature of the infective process. Croupous pneumonia may also occur early in the course of the attack, or pulmonary localization may cause enteric fever to simulate pneumonia. In certain cases it is not possible to determine whether the pulmonary phenomena are the results of an intercurrent process or of an early localization of the enteric fever infection. A^jpendicitis in rare instances may simulate enteric fever. The course of the temperature, the absence of splenic enlargement, the localization of the abdominal phenomena in the right iliac region are of diagnostic importance. Peritonitis due to other causes than perforation is to be discriminated from that occurring in the course of enteric fever, by the antecedent his- tory of the case. If the patient, however, does not come under obser- vation until after the appearance of the symptoms, it may be impossible to determine whether they are due to perforation or not. The presence of the rose spots would be of importance in the decision of this question. Trichinosis is attended with pyrexia, vomiting, and diarrhoea. Epis- taxis and splenic enlargement are rare ; rose spots do not occur. On ri'j )(! SdSlS—TREATMEyT. 2( )7 the other hand, ihc .-yiuptunir- oi' the myositis and the h»eal and general anlenia, so freijiient in trichinosis, are absent in enterie lever. Entero-voliti.s may in chikh'en be confounded with enteric fever. The fever and constitutional disturbances are symptomatic of the local trouble. The spleen is not commonly enlar^red, abdominal pain is con- spicuous and severe, and rose spots are absent. Prognosis. — The death-rate is much influenced by treatment. It ranges inider ordinary c<»nditions from about 7 per cent, under system- atic cold bathing to about 15 per cent, under expectant symptomatic treatment. Murchison found in 27,051 cases collected from various sources a death-rate of 17.45 per cent. ; Jaccoud, in a collection of 80,140 cases treated on the expectant plan, a mortality of 19,23 per cent. ; 17,000 cases in Vienna showed a mortality of 22.5 per cent. According to Caylev, the principal Continental hospitals have a mortal- itv varving between 16 and 25 per cent. Some years ago Delafield col- lected from the records of the New York hospitals, extending over a period of about five years, 1305 cases, with a mortality, estimated by years, varving between a minimum of 20.1 per cent, in 1879 and a maximum of 30 per cent, in 1880. The available statistics of recent vears unquestionably show a reduction under various plans of treat- ment. The mortality in childhood, taking all the cases together, is decidedly lower than in adults. Enteric fever, like all the acute infectious diseases, shows an extremely variable intensitv^ in children, the severe cases, however, being the exception rather than the rule. The prognosis in individual cases must be guarded, since it not infrequently happens that in cases running an apparently favorable course death occurs toward the end of the third or during the fourth week from some unforeseen accident or complication. The prognosis is unfavorable in cases in which the intensity of the infection is manifested by the rapid development of severe symptoms — intense p}Texia, cardiac asthenia, ataxic phenomena, and the occiu*rence of multiple cases in the .same house or in the immediate locality ; it becomes unfavorable like- wise upon the development of intestinal symptoms of high grade, such as copious diarrhoea, abdominal pain, or meteorism. Recurrent vomiting has also an unfavorable prognostic import. Finally, intestinal hemor- rhage, perforation, and such complications as ulcerative endocarditis, meningitis, diphtheria, large pleural effusions, and in children the exan- themata arising as intercurrent or consecutive affections, render the prognosis extremely grave. Sudden death may occur about the time of defervescence or in early convalescence in consequence of extreme cardiac asthenia. Corpulent persons bear enteric fever badly. Those whose habits have been intemperate and those who suffer from disease of the kidney and the gouty are especially liable to the gravest accidents of the disease. The death-rate is slightly greater in women than in men. Treatment. — («) Prophylaxis. — Enteric fever is theoretically a preventable disease. The objects of prophylaxis are (1) to prevent any case of the disease from becoming a focus of infection, and (2) to correct such faulty sanitary arrangements as lead to the pollution by fecal matter of water used for drinking and domestic purposes. The success- 208 ENTERIC OR TYPHOID FEVER. ful pursuit of these objects wherever the disease prevails would certainly be followed immediately by a notable decrease in the morbidity. Rational preventive measures, even though imperfectly carried into eifect, have been followed by remarkable results. Their general adop- tion and rigid execution would be followed by a very gi'eat reduction in the prevalence of the disease. The first measure of prophylaxis — namely, the prevention of the spread of the disease from any patient as a focus of infection — consti- tutes an important duty of the physician in attendance. The typhoid bacilli in the fecal discharges can be at once and absolutely destroyed upon the spot. They do not appear in the stools until some time after the period at which under ordinary circumstances the patient comes under the care of the physician. It follows from the facts now estab- lished in regard to the transmission of the disease that any given case may be prevented from becoming not only a source of infection to those in his immediate vicinity, but also to those at a distance. Upon those in immediate attendance devolves the duty of protecting alike persons in the vicinity of the patient and those to whom the disease may be conveyed by the contamination of running streams or other sources of water supply or in cities by way of sewer systems transmitting the in- fecting principle. To this end the fecal discharges of every case and the urine should be at once and effectually disinfected. For this purpose a solution of chlorinated lime of the best quality, containing at least 25 per cent, of available chlorine, of the strength of 6 ounces (192.) to the gallon (4 litres), may be employed. Commercial sulphuric or hydrochloric acid and water in equal parts will disinfect a stool in two hours. A solution of mercuric chloride, 1 : 500, acidulated with tartaric or hydrochloric acid, will disinfect an enteric fever stool in six hours. Carbolic acid in 5 per cent, solution is less efficient and requires twenty-four hours. Milk of lime, prepared by slaking freshly burned quicklime and stir- ring up the powder with twice its volume of water, is an efficient and rapid disinfectant for enteric fever stools. This preparation should be freshly made and added to the stool in equal bulk. When the bed-pan is to be used, it should contain one half pint (250 c.c.) of the solution employed. Directly after the movement of the bowels a pint (500 c.c), or as much as a quart (1000 c.c), of the solution, according to the amount of the dejection, should be poured over it. The contents of the pan should then be thoroughly mixed by agitation of the vessel, and solid masses should be broken up with a glass rod, which can be thoroughly disinfected. If a stick is used, it should be forthwith burned. The pan should then stand two or three hours before it is emptied into the water closet or privy vault. The nurse should be made to understand that prolonged exposure is necessary to complete disinfection. Clear solutions like that of the mercuric chloride should be colored by the addition of potassium permanganate, and the disinfectants employed must be kept in a place by themselves and conspicuously labelled " Poison." Commercial preparations placed upon the market under various names for the purpose of household and sick-room disin- fection are not to be prescribed. They are of unknown and doubtless inconstant composition, and unduly expensive. When acid disinfect- TREATMENT. 209 ants arc emplovod tlio water closet is to he tiiished for some minutes several times diiriiio- the »hiy to (hminish their action upon the tittinnsc(]Uence of tiie c()nsunij)ti()n of oysters taken from waters jjolluted bv the sewaiic of cities is most imjiortant. It is therefore obvions that the immediate and efficient disinfection of all the stools in every ease of enteric fever in the sick-room is an imperative measure of prophylaxis. (/>) The General Management of the Patient. — The result of the treatment in enteric fever is laruely influenced Ijy the details given to the general managi'nient and nursing of the case. The patient should not be exj)osed t(j continued infection. Obvious faults connected with the water supply or milk supply should be immediately corrected. Under these circumstances it is necessary to remove the patient to more favor- able surroundings. In hospitals enteric fever patients have usually been treated in the ward side by side with other patients. This prac- tice is without danger if precautionary measures are taken to secure the immediate disinfection and removal of the dejections and the cleanliness of the patient's person and bedding. It is, however, at present consid- ered better to place enteric fever patients together in separate wards. In general practice patients, as a rule, come under observation during the period of prodromes or early in the first stage of the disease. If the symptoms are such as to give rise to a suspicion that the disease is enteric fever, the patient should be ordered at once to bed. In the event of the malady not being enteric fever, the patient's interests do not suffer. If, however, the symptoms be those of developing enteric fever, rest in bed \\\\\ favorably influence the later progress of the attack. The general course of cases treated from the beginning of the attack is more favor- able than that of those coming under medical care after the disease has made some progress. Persons who struggle against the early symptoms of the attack, or who continue to go about until the intensity of the febrile movement, diarrhoea, or sheer prostration obliges them to betake themselves to bed, constitute the worst cases of the disease. The fatigue of long journeys undertaken to reach home after the development of the symptoms has frequently exerted an unfavorable influence upon the sub- sequent course of the attack. Rest in bed from the beginning of the sickness is important. Patients treated upon the expectant or expectant- symptomatic plan shoidd not be allowed to rise until some days after defervescence has been completed. The urinal and bed-pan must be regularly used. Many patients who declare that it is impossible to empri' the bowel in the recumbent pos- ture find upon trial that it is less difiicult than they supposed. Strict rules in regard to rest in bed and the employment of the bed-pan and urinal cannot always be carried out in the case of young children. The room should be large, well ventilated, and, if practicable, have a southern exposure. All curtains, hangings, and pictures shoidd be at once removed. Only such simple furniture as is necessary for the attend- ants should be retained. An open fireplace is advantageous. Free ven- tilation is necessary. Drafts are to be avoided, but the fever patient is with ordinary care little liable to take cold. In grave cases the patient mav be with advantage removed at intervals from one to the other of communicating rooms. In cities a back room removed from street noises is desirable. When the weather permits the patient may with advantage be removed during the day for a few hours to a porch or gallery in the 212 ENTERIC OR TYPHOID FEVER. open air and sunshine. A narrow single bed, not too high, greatly light- ens the labor of nursing. The mattress must be smooth, firm, and elastic. A rubber cloth or mackintosh must be placed under the sheet. The covering should be light and varied from time to time according to the sensations of the patient. Bedding or bed-clothing soiled by the invol- untary evacuation of urine or faeces should be immediately changed and disinfected. In very severe cases it is desirable to use two beds, placed side by side, from one to the other of which the patient when necessary may be lifted. The wants of the patient are to be attended to quietly, noiselessly, without conversation or comment. During convalescence the visits of friends are to be restricted in number and should be very brief. At this period tact and caution in the communication of details of business aifairs and matters of annoyance are most important. Patients who have been delirious must under no circumstances, though at the moment apparently rational, be left alone until convales- cence has been fully established. Suicidal impulses may develop, and many patients have destroyed themselves during the momentary absence of the attendant. Good nursing is of the highest importance. It means to the physician accurate and systematic information at his visits, alertness and responsibility in his absence. To the patient it means quietude, gentleness, neatness, diminished suffering. To both the physician and patient it means the best use of the resources of medicine. The free administration of fluid is necessary. Many patients, apparently fully conscious, fail to obtain the necessary amount of drink. Fluid, therefore, should be offered in small amounts at short intervals. A judicious nurse, administering fluid in small amounts at a time, is- not likely to give in the aggregate too much. Pure cold water is the best drink for fever patients. The aerated mineral waters afford an agreeable change. The diet throughout the attack should be nutritious, easy of diges- tion, and liquid. Definite and explicit directions as to kind, quantity, and the intervals of administration are necessary. The details must be systematically recorded. General directions on the part of the physician and general reports on the part of the nurse are inadmissible. The amount is to be regulated by the requirements of individual cases. Indigestion and an aggravation of the symptoms of intestinal catarrh result from over-feeding. On the other hand, under-feeding increases the asthenia and prolongs convalescence. As a rule, the mental condi- tion is such that the patient takes without objection whatever is prof- fered in the way of food or medicine. Enteric fever patients are usually rather over-fed than under-fed. The signs of gastric indiges- tion, increased diarrhoea, and the presence of milk curds in the stools will call the attention of the physician to the fact that the patient is receiving too great an amount of food. Despite theoretical considera- tions, milk holds the first place among fever foods. It supplies the liquid required for the chemical processes of nutrition ; it is in most cases readily digestible ; it is diuretic ; it may in a majority of the cases constitute the sole diet or at all events the basis of the diet. Used alone, milk should not much exceed in daily amount for an adult 3 pints (1500 c.c.) during the first period of the disease, or 2 quarts TREATMENT. 213 (2 litres) subsequently. This quantity must l>c given in divided ])or- tions at intervals during the twenty-four hours. Milk as a fever food may be raw or boiled, warm, cold, or iced, or now and then given coagulated into soft curds by nieans of rennet. It may be diluted with lime-water in tlie proportion of 1 ])art to 5, or mingled with one-third its vohnne of Viehy water. The repugnance evinced by some ])atients to a milk diet may be overcome in jxirt l)y the addition of coffee or spirit, such as brandy, whiskey, or rum ; the inability of others to digest it may be overcome by partial peptonization or by its administration in the form of koumyss, kefir, or matzoon. Sterilized milk may be used for a time with advantage, but it-s continuous employment cannot be recommended. The occasional administration of buttermilk or wine "whey may vary an otherwise monotonous diet. A raw egg beaten up in the milk, ■with or without spirit, reinforces the diet, and in the German Hospital we frequently administer three or four raw eggs during the course of the twenty-four hours to cases under the bath treatment. If there be irritability of the stomach, the white only of the egg, mixed with an equal volume of water and flavored with a little brandy or sherry, is better borne. It is usually desirable to vary the diet, and in some cases it is impossible to administer milk continuously. We may then employ broths or soups prepared from beef, mutton, chicken, or veal flavored with vegetable juices and containing a little rice or barley. These should be, however, systematically strained. Consomm^, either hot or frozen according to the fancy of the patient, clam-juice, oyster soup, thin barley gruel, arrowroot, and the commercial malt foods, pep- tonoids, and the freshly expressed juice of partly broiled beef, may be included in the dietary. A cup of hot coffee or cocoa, well diluted with milk, may be given once in the twenty-four hours, preferably in the early part of the day. Food should be systematically administered every two or three hours during the day and at intervals of three or four hours at night. In grave cases, where the amount taken at a time is small or the prostration is extreme, these intervals must be shortened. A restless patient who has just fallen into a quiet sleep must not be disturbed for food. Patients who are very somnolent or soporous must, if possible, be roused before food is given, in order to diminish the danger of inhalation pneumonia. Solid food is not to be administered until the evening temperature has been normal for a week. The change even then must be tentative and gradual by way of milk toast, custards, light puddings, and similar articles of diet to the ordinary every-day food. The details of the diet in voung children must be regulated in accordance with the asje of the patient and the previous plan of feeding, no radical departure from the usual nourishment being necessary beyond the avoidance of every kind of solid food. Alcoholic stimulants constitute an essential element of the routine procedure in the treatment of enteric fever by systematic cold bathing, and their administration will be discussed in connection with that plan. In other forms of treatment the circumstances under which alcohol is to be administered demand careful consideration. Those who recall the method of its employment some years >ago agree that it was very often given as a matter of course when not required, and nearly always in un- 214 ENTERIC OR TYPHOID FEVER. necessarily large amounts. At the present time alcohol is frequently used too freely in the sick-room. In mild cases of enteric fever and in young persons of previously good health and habits it is, as a rule, not required. In persons of feeble constitution and those past middle life, and in all severe cases, alcohol should be systematically but cautiously administered. To those who have previously been accustomed to its use it should be given from the onset of the attack, and to a guarded extent in amounts suggested by the habits of the patient. It is important that alcoholic stimulants should be given in guarded amounts during the early period of the attack prior to the subsidence of the headache — an event that commonly occurs between the end of the first and the middle of the second week. After this time alcohol may be used more freely. Alcohol is clearly indicated in all cases in which there is great general prostration. Its administration is essential where there is weak- ness of the heart's action, as shown by a small, feeble, and irregular pulse, a feeble cardiac impulse, and a faint first sound. It should be administered with a free hand upon the development of delirium, tremor, or other ataxic symptoms. Its use is especially important when diarrhoea, tympanites, and great tenderness indicate extensive and deep ulceration. The administration of alcohol is imperatively demanded in all severe cases and upon the development of serious complications, such as bron- chitis of the smaller tubes, broncho-pneumonia, croupous pneumonia, pleurisy, or peritonitis. The amount must be regulated according to its influence upon the symptoms for which it has been prescribed in in- dividual cases. The character of the first sound of the heart and the pulse and the nervous symptoms constitute the best guide for the dose and the frequency of its administration. If the urine be albuminous, and particularly if it contain casts, alcohol is to be given cautiously, and its effect upon the amount and character of the renal excretion is to be studied from day to day. Under ordinary circumstances the administration of alcohol should begin with small quantities, to be increased according to the require- ments of particular cases. Four to eight ounces (125-250 c.c.) of spirit or from a pint to a pint and a half (500-750 c.c.) of claret, burgundy, or champagne in the course of twenty-four hours yield the best results. In serious cases much larger quantities may be required. Whiskey or brandy may be given with milk in the form of punch, or, if the patient prefer it, diluted with water. Where small amounts of alcohol are indicated wine whey constitutes an agreeable means for its administra- tion. (c) The Special Manag-ement of Individual Cases. — The milder cases do well without drugs. Rest in bed, skilled nursing, and a care- fully regulated dietary comprise all that is necessary in the management of the case. With moderate fever, a good heart, no signs of serious intestinal lesions, and the absence of pulmonary complications beyond a slight bronchitis, the administration of medicines is needless. The treatment may with advantage be commenced with laxative doses of castor oil or of calomel, which should be repeated at intervals of three or four days until the middle of the second week of the attack. Later than this constipation may be relieved by enemata of lukewarm water in which is dissolved common salt in the proportion of a teaspoonful to TREATMI'JXT. 215 the pint, or by soapsuds or by tliin ^riK-l. In tlu' event of" constipation not being thus relieved, euenuita of glycerin and water or glycerin sup- positories may be employed. These measures to secure the action of tiie lower bowel do not require repetition at intervals shorter than every third dav. There are those who upon theoretical grounds regard the svstematic washing out of the lower bowel by large enemata of normal salt solution once or twice in the course of twenty-four hours as of advantage. Cases treated with so-called fever mixtures or with small doses of quinine, the mineral acids, turpentine, silver nitrate, or other drugs that have no effect upon the course of the disease must be regarded as man- aged in accordance with the expectant method. Fortunately, such medicaments are usually well tolerated by the patient. The great varia- tion in the intensity of the attack in different cases must put us on our guard against ascribing to therapeutic measures results that are really to be attributed to the course of the disease in individual cases. (d) Treatment of Special Symptoms and Complications. — The headache of the period of onset requires, as a rule, but little treatment ; it disappears spontaneously between the end of the first and the middle of the second week. Quietude, the exclusion of light, compresses to the head wet with cold or hot water according to the sensations of the patients, are very often sufficient to control the headache. Applications of Cologne water, of spirit of camphor, of menthol, or of chloroform are sometimes acceptable. If headache, however, persists, or is, despite the foregoing measures, distressing, antipyrine, acetanilid, or pheuacetin given in small doses repeated at short intervals are efficacious. Drugs of this class are, however, to be used in enteric fever with caution. Sleejjlessness may become a troublesome symptom in the early course of enteric fever. It very often diminishes during the course of the second week. It may, however, be persistent and exhausting. The insomnia of the early course of the attack may be usually readily con- trolled by appropriate doses of sodium bromide or chloral, used either separately or in combination. Sulphonal, trional, urethan, and chloral- amide are hypnotics of inferior value. Opium and its derivatives must be regarded as objectionable in the early stage of the disease by reason of their unfavorable influence upon the digestion and the secretions, and their liability to be followed by disagreeable after-effects, such as nausea, vertigo, and the intensification of headache. Later in the course of the disease opiiun becomes at once the most efficient and safest means of controlling insomnia and excitability, its effect upon the secretions being less unfavorable than early in the attack, while its disagreeable after- effects are less marked. Somnolence, stupor, and delirium must be treated by stimulants and external antipyretics. Among stimulants alcohol takes the first place and stands almost alone ; the spirit of chloroform and caniphor prove, however, useful in emergencies. The latter may be administered h}-]30- dermically in 5 per cent, solution in ether, 10 minims (0.6), being repeated once or twice at intervals of several hours. Ether alone in 10-minim doses, given hypodermically, is of advantage. Ammonium carbonate and the aromatic spirit of ammonia are of inferior value. They are, however, frequently employed in the treatment of pulmonary 216 ENTERIC OB TYPHOID FEVER. complications. Pure Siberian musk is a powerful stimulant in condi- tions of nervous depression. Administered in pill or suppository in single doses of from 5 to 10 grains (0.32-0.65), it sometimes produces decided effects. The difficulty of obtaining it, its great cost, and the uncertainty of its eifects preclude its general employment. Hyoscine hydrobromate, codeine, and asafoetida are also useful in the treatment of active delirium, while delirium suggestive of hysteria is often favorably influenced by full doses of valerian, alone or in combination with the bromides. Such external antipyretics as the ice-cap or the cold douche are indicated where delirium is marked and persistent or there is stupor tending to coma. Applications of cold must be transient and not too frequently repeated, lest they be followed by depression and collapse. It is a good practice to accompany them by warm applications to the feet and legs and sinapisms to the prsecordium and epigastrium. The tepid or warm bath or the warm bath gradually lowered exerts a favor- able influence upon this group of nervous symptoms. The delirium of enteric fever is, as a rule, manageable. Physical restraint is rarely required, though it occasionally happens, especially in hospitals where the nurses have a number of cases to look after, that it is necessary to confine the patient by a sheet passed over the lower part of his chest and fastened under the bed. Good nursing is indispensable. The enteric fever patient who has become delirious should never for an instant be left alone. Tremor, out of proportion to the other signs of nervous prostration, has been regarded by Sir William Jenner as a sign of deep ulceration of the intestine. In any case supervention of tremor is to be regarded as an indication for the administration of alcohol in full doses. Other nervous symptoms occurring during enteric fever do not call for special treatment. Those that persist after the subsidence of the febrile move- ment are to be treated in accordance with general rules. Dryness of the tongue and the accumulation of sordes upon the teeth and gums demand the frequent administration of water in small amounts, washing of the mouth with pure water or water containing borax, claret, or small amounts of tincture of myrrh, or the use of a cotton mop wet with a saturated solution of boric acid. Fissures at the nostrils or at the angle of the mouth or upon the lips may be treated by the occasional application of a soft ointment contain- ing 20 grains (1.3) of boric acid to the ounce (31.). Vomiting is not a common symptom in enteric fever. Occurring at the onset of the disease, it is usually an indication of profound infection or of extreme gastric irritability. Under these circumstances nourish- ment by the mouth should be temporarily withheld, while fractional doses of calomel at short intervals or full doses of chemically pure cerium oxalate or of dilute hydrochloric acid or cocaine hydrochlorate, gr. ^ (0.01), may be given. At the same time sinapisms may be applied to the epigastrium and iced dry champagne administered in small amounts. In some instances vomiting is due to antecedent lesions of the stomach. When vomiting occurs late in the course of the attack it is very often due to uraemia, and is then associated with other evidences of nephritis. TREATMENT. 217 In all cast's the in-inc sliouhl he, IVoiii the hcjrinniii^ of the attack, systematically cxamiiuHl at intervals <>i' two or three days. A ti'ace of albnniin witliont casts or with a cast here and there — febrile albuminuria — is not in itself of great clinical importance, but a large percentage of albumin M'ith many casts, and es]x>cially epithelial or blood casts, indi- cates the develoj)ment of an intercurrent acute nepin-itis. (hnxiipdfion late in the course of the attack may be due to the con- tinued use of a diet that is at once concentrated and leaves a minimum of unabsorbed residuum. It may, however, result from torpidity of the large intestine. In the latter case the fecal matter accumulates in the form of scybalae. This condition may set up a sort of secondary diarrhoea, due to the irritation of the lower boAvel and attended with a feeling of tenesmus and local distress promptly relieved by the' removal of the cause. Prolonged constipation is not necessarily a sign of mild intestinal lesions. On the contrary, deep ulceration of a single Peyer's patch may arrest peristalsis and thus produce constipation. It is there- fore important to avoid the administration of laxative drugs after the middle of the second week. Nor are large enemata, especially if administered with some energy, without danger. Diarrhoea requires no especial treatment so long as the stools are of moderate amount and do not exceed three or four in the course of twenty-four hours. This symptom is frequently due to the use of improper food or excessive amounts of food, particularly milk, the strong animal broths, or beef- tea. The substitution of a suitable diet is followed by relief. In other cases the prejiarations of bismuth, as the subcarbonate, subnitrate, salicylate, or subgallate, administered by the mouth in full doses, con- -stitute an efficient medication. When necessary small doses of opium may be employed in addition. The so-called intestinal antiseptics, such as naphtalin, thymol, resorcin, and the like, are less useful. The administration of astringents, such as alum, plumbic acetate, silver nitrate, tannic acid, catechu, and kino, in the present state of knowledge lacks the support alike of theoretical basis and empirical result. If the stools be highly fetid or ammoniacal, creasote, salol, or salophen may be given or animal charcoal may be administered in broth. Tympanites is a very common symptom. When excessive it consti- tutes an urgent indication for the administration of alcoholic stimulants or for their increase if already employed. Turpentine or camphor in addition to guarded doses of opium must be added to the treatment, and active preparations of pepsin or peptenzyme, alone or together with hydrochloric acid, should be administered with the food. Compresses wrung out of iced water or turpentine stupes should be applied, and very cautious light massage of the abdomen may be useful. Small enemata of iced w ater and enemata of cold water containing turpentine in emulsion are sometimes followed by good results. The careful intro- duction of a long intestinal tube will sometimes relieve the distention of the loAver bowel. The puncture of the distended gut with a hypo- dermic needle through the bowel 'svall is an unwarrantable procedure. The systematic administration of laxative doses of calomel or castor oil every third or fourth day during the first week or ten days tends to obviate to a great extent excessive intestinal disturbance, whether con- stipation, diarrhoea, or tympanites. 218 ENTERIC OB TYPHOID FEVER. Intestinal hemorrhage is to be treated by the temporary diminution, or even the complete withdrawal, of food for a time, and by the adminis- tration of opium, either by the mouth or by suppository. For the time being even water is to be administered in small amounts. To relieve thirst it is better to permit small pieces of ice to be dissolved in the mouth. The action of the bowels is to be controlled by the further administration of full doses of bismuth. If the loss of blood be exces- sive, there is imminent danger to life and more active measures are required. An ice-bag should be applied to the abdomen in the region of the right iliac fossa. Opium is to be gradually increased until drow- siness and contraction of the pupils follow. Ergotin may be adminis- tered hypodermically at short intervals. Enemata of iced water, not exceeding 4 ounces (120) at a time, may be repeated at short intervals. The astringent preparations of iron either by the mouth or by the rec- tum, and the employment of gallic acid, turpentine, alum, or lead ace- tate, are not likely to be followed by direct results. The pillows are ta be removed and the foot of the bed elevated upon blocks. Sterilized normal salt solution in amounts of from 4 to 6 ounces (120-180) should in grave cases be introduced by hypodermoclysis at from two to four diflPerent points and repeated as required. Fluid restored to the body in this manner is both safer and more effective than intravenous injec- tions. The transfusion of blood is attended with serious risk, and is scarcely to be considered under these circumstances. The fall of tem- perature and improvement in the mental condition of the patient which follow intestinal hemorrhage are usually transitory ; exceptionally, how- ever, they mark the beginning of convalescence. An abrupt fall of tem- perature of several degrees to the normal or below it, occurring in the mid-course of the attack, will justify the suspicion that hemorrhage has taken place, even though no blood may have yet appeared in the stools. This suspicion will be confirmed by the discovery of local dulness upon percussion in the abdomen, usually tympanitic. After intestinal hemor- rhage the diet must for a time be restricted to a minimum, and no effort should be made to move the bowels for a period of at least ten days. Spontaneous evacuations are apt, however, to occur in the course of six, or eight days. Peritomtis calls for the free administration of opium. This drug is to be given in the form of the deodorized tincture in doses of 10 minims (0.62) at intervals of an hour until evidences of its physiological effects show themselves. If opium be not well borne by the stomach, morphia is to be administered hypodermically. No nourishment is to be given except concentrated meat juice, a teaspoonful at a time, together with equal parts of brandy and water in the same amounts. Ice-bags should be applied to the abdomen. Should the patient rally, it is of the utmost importance that the bowels be confined as long as possible. An action will usually occur at the end of several days, even under the continued use of opium. If not, at the end of a week or ten days small lukewarm enemata of water containing glycerin or glycerin suppositories may be cautiously employed. Peritonitis in a small proportion of the cases arises in consequence of infection through the base of an ulcer without perforation ; in other instances the sloughing out of the base of an ulcer that causes perforation is preceded by local adhesive peritonitis forming TREATMENT. 210 attai'hnuMits with an adjacent visciis or coil of intestines, thus pi'eventin<;- general peritoneal infection. Under these eircnnistances in exce})tional cases rccovcrv may occur. As a rule, suddenly developing peritonitis is due to perforation of the gut, permitting the intestinal contents to escape into the general cavity of the peritoneum. The occurrence of this acci- dent at the close of defervescence or (hiring convalescence, when ai)pctite is retiuMiini", the nutrition improving, and the strength of the })atient augmenting, raises the question as to the propriety of cadiotomy in order to suture the lesion, resect the bowel at the point of perforation, establish an anastomosis between uninvolved portions of the intestine, or form an artificial anus, and to carry into effect the proper treatment of the infected peritoneum. In selected cases the hopelessness of ordinary methods of treatment justifies surgical procedure, and this opinion finds support in the fact that a small proportion of favorable results have been reported. Ferf oration of the intestine is usually single. Murchison's record showed one perforation in 28, two in 5, and three in 4 cases. R. H. Fitz found in 167 eases of intestinal perforation collected from various sources 138 single perforations and 29 multiple perforations. During the course of enteric fever palpation of the abdomen is to be practised with great caution by reason of the danger of exciting peri- tonitis, causing perforations or rupturing the spleen. Collapse attending intestinal hemorrhage or perforation or sudden heart failure is to be treated by absolute quiet, elevating the foot of the bed, the application of external heat, hypodermic injection of suitable doses of strychnia, atropine, ether, or solutions of camphor in ether. Epistaxis occurring early in the course of the disease is usually slight, often a mere stain upon the handkerchief, and of diagnostic significance only. Later in the course of the attack it is frequently abundant, but rarely attended w^ith danger. The application of ice to the brow or the instillation of very hot water into the nostril is useful. Persistent epistaxis may render plugging of the nostrils necessary. The adminis- tration of ergot, turpentine, and the preparations of iron is frequently employed. Retention of urine is liable to occur in severe cases. A routine examination of the suprapubic region is important. When necessary the catheter is to be employed : a soft-rubber instrument in the case of the male, a glass catheter in the case of the female, is preferable. The instrument should be thoroughly sterilized ; immediately before its introduction the parts about the meatus should be invariably bathed with corrosive sublimate solution, 1 : 2000. The chest complications of enteric fever are frequently attended with insignificant subjective symptoms. For this reason systematic exam- ination by means of the methods of physical diagnosis is necessary at short intervals. Dicrotism diminishes, or in some cases wholly ceases, upon the administration of proper doses of alcohol. Cardiac asthenia demands alcohol and strychnia. Caffeine citrate is also useful. When the fiiilure of the circulation is extreme the pillows are to be removed, the foot of the bed elevated by blocks, and absolute rest in the recumbent posture maintained. Cases of sudden death have 220 ENTERIC OB TYPHOID FEVER. occurred as a result of the patient's abruptly assuming the erect posture. In the feeble heart of enteric fever digitalis in small doses is of ques- tionable advantage ; in larger doses harmful. The nitrites, and espe- cially amyl nitrite and nitroglycerin, are of service. The hypodermic administration of ether or camphor in ether in 10 per cent, solution is useful. So also is the application of sinapisms or turpentine stupes to the prsecordia and epigastrium. Hypostatic congestion may be to some extent prevented by the sys- tematic employment of measures to maintain the forces of the circula- tion. The patient's position must from time to time be changed from the dorsal to the lateral decubitus. Bronchitis when slight requires no special treatment. AVhen severe it must be managed in accordance with general principles. Dry cups, oxygen inhalations, the administration of ammonium carbonate and increased doses of alcohol, are indicated in the graver forms. The dangers of inhalation bronchitis and secondary broncho-pneumonia may be to some extent reduced by thoroughly rousing the patient before the administration of nourishment. The formation of heel-sores may be anticipated, and to a great extent prevented, by proper nursing. Frequent change of posture, the removal of pressure by means of Avater-bags or air-cushions, scrupulous cleanli- ness, and attention to the bed must be practised in all cases. Erosions are to be immediately treated upon general surgical jjrincijDles. The water-bed may become necessary. The fever requires when moderate no special treatment. This is especially the case when the morning remissions are considerable, amounting to 1.5°-2° F. (.8°-l.l° C). Higher temperatures and slight morning remissions call for the use of external antipyretics. In a fever of so prolonged duration as enteric fever a very high and unbroken temperature must be regarded as a grave symptom, and yet cases marked by such temperatures frequently terminate in recovery. On the other hand, cases in which the temperature at no time rises above 103° F. (39° C.) occasionally prove fatal. The height of the fever is not so much an absolute gauge of the intensity of the infection as it is a manifestation of the reaction on the part of the organism to the toxaemia. The rapid and extensive depression of temperature following the administration of full doses of antipyrine, acetanilid, phenacetin, and similar pharmaceutical preparations is transient and associated with unfavorable symptoms, such as excessive sweating, cardiac depression, and a tendency to collapse. Furthermore, the eifect of these drugs upon the general course of the disease is far from favorable. Their use as antipyretics is to be emphatically discountenanced in the treatment of enteric fever. The same is to be said of the internal and external application of guaiacol. External antipyretic treatment by means of cold sponging, cold compresses, the application of ice, the cold pack, cold or gradually cooled baths, cold aifusidn, iced-water enemata, and the use of Leiter's coils is equally efficient in reducing temperature and unattended by the hazardous perturbations of the functions of the body that follow the use of the so-called internal antipyretics. Such applica- tions produce an effect in children greater than in adults in proportion TREATMENT. 221 as the extent of surface to whicli the application is made is rehitivelv greater as compared with tlie vohinie to he (-(Kdcd. The effect is more prompt and decided, tlie disturbances of circuhition are greater, and reaction is more tardy. Tlie employment of cold in the treatment <»f enteric fever in childhood demands, therefore, a degree of caution. Convalescence is slow. In many cases months elapse before the patient regains his previous bodily and mental vigor. Exce[>tionally the patient never regains his full strength and powers (»f endurance. Dur- ing the week following defervescence the temperature is labile and affected by slight causes. Recrudescences of fever occurring during this period are abrupt and transient. Constipation may cause a slight rise of temperature, which immediately falls upon movement of the bowels. Similar rises of temperature occasionally occur after the first taking of solid food, upon undue exertion, after the visits of friends, or conversa- tions upon matters of business. Patients, therefore, should be assidu- ously cared for several days after the temperature has reached the normal. During this period temperature observations should be taken in the morning and evening, and the diet should be for at least a week restricted to milk, eggs, custards, light farinaceous foods, animal broths, and jellies. If the case progress favorably, at the end of a week ordinary light diet may be gradually resumed, but the seedy fruits and other hard substances liable to pass through the intestines unchanged are to be avoided. Durino: the earlv convalescence the cravino- for food is often such that patients complain bitterly both of the quantit}' and qualit}^ of their sick-room fare. If during convalescence diarrhrea per- sist, the diet is to be carefully regulated, and the preparations of bismuth, together with small doses of opium, may be administered. Xot rarely there is a tendency to constipation which yields to simple salt-and-water enemata or glycerin suppositories. General asthenia is often marked and persistent. Under these cir- cumstances the patient's activities must be kept well ^nthin the limit of fatigue. If cardiac asthenia be pronounced, as shown by feeble, rapid, or irregular pulse and faintness, and dyspnoea upon exertion, carefully regulated rest, alternating with gentle, systematic exercise supervised with equal care, an abundant, nutritious dietary, together with strychnia, arsenic, and iron, prove useful. Alcohol is also indicated. These measures constitute also the proper treatment of the associated antTemia. Early change of surroundings and climate is of advantage. ThefalUng of the hair that takes place during couvalescence is in the majority of instances followed by a new growth. Experience has shown that it is undesirable to subject the patient to the annoyance of shaving the head, though the hair shoidd be cropped close to the scalp. Under favorable conditions the convalescent from enteric fever rapidly gains in weight ; he gains strength more slowly. The furunculosis of convalescence is to be treated by the prompt evacuation of the pus, the application of antiseptic dressings, and in persistent cases the internal administration of calcium sulphide. Periostitis occasionally occurs. Exceptionally the inflammation undergoes resolution without the formation of pus ; more commonly suppuration occurs and extensive necrosis may take place. Early sur- gical treatment is indicated. 222 ENTERIC OR TYPHOID FEVER. Peripheral neuritis, which affects more frequently the lower extrem- ities, is to be treated by rest, massage, and electricity, together with the use of cod-liver oil, iron, and minute doses of arsenic. Persistent rhachialgia and other spinal symptoms are best treated by rest, massage, and the occasional application of the Paquelin cautery. In some of the reported cases suggestion appears to have played an im- portant part in the rapid amelioration of the symptoms. Thrombosis of the femoral vein should be treated by the application of a flannel bandage from the toes to the groin, the elevation of the foot and leg upon a pillow, and the control of the early pain by h}^odermic injections of morphia. After a sufficient time for the complete organ- ization of the thrombus has elapsed the establishment of a collateral circulation may be favored by daily massage. When pain and tender- ness have disappeared and the patient is sufficiently convalescent to leave his bed, an elastic stocking should be worn. (e) Specific or Etiolog-ical Plans of Treatment. — Quinine, calomel, iodine, carbolic acid, sulphurous acid, chlorine, salol, boric acid, turpen- tine, oil of eucalyptus, thymol, camphor, the naphtols and naphtalin, bismuth salicylate, guaiacol, and many other drugs have been adminis- tered on theoretical grounds to patients suffering from enteric fever. The temporary administration of certain drugs of this class may have in some instances exerted a favorable symptomatic influence upon the gastro-intestinal derangements of the disease. There is, however, no adequate evidence to show that any of them or any combination of them, persistently administered throughout the course of the attack, is capable of any definite favorable modification of the toxaemia or of uni- formly abridging the duration of the attack or notably reducing the death-rate in large series of cases. None of these drugs can be said to have stood the test of time in the treatment of enteric fever or to have been generally adopted by the profession. Intestinal antisepsis, in so far as the pathogenic organisms of enteric fever are concerned, is directed against specific germs not present in the bowel prior to the breaking down of the intestinal lymph elements, and is therefore largely inoperative ; general antisepsis, if by that we are to understand a germicidal influence upon bacteriological forms diffusely implanted in the lymph tissues throughout the organism, is a vain fancy, wholly unsupported by facts. The parasite is more resistant to such influences than the host. Clinical and pathological considerations are alike opposed to the whole subject of the antiseptic treatment of enteric fever. (/) The Method of Hydrotherapy . — Curry at Liverpool, at the close of the last century, and Nathan Smith of Yale College, about the same time, advocated the use of cold water in the treatment of the more serious symptoms of the fevers. The methods consisted principally in cold affusion, though sponging was also employed. The teachings of these physicians were not generally accepted. It is true that during the past century hydrotherapeutic methods have been employed in the treatment of the fevers, and especially in combating high temperature. Nevertheless, it remained for Ernst Brand of Stettin to formulate a definite procedure for the treatment of enteric fever by systematic cold bathing. Brand's first publication upon this subject appeared in 1861. TREATMENT. 223 The lUL'tliod attracted little attention, however, until ahont the time of the close of the Franco-Prussian War in 1871. It was subseciuently practised in the hospitals at Lyons by the French military surgeons, who as prisoners of war had had the opportunity of observing its eifects at Stettin. Its ])raetice has slowly but steadily extended, until it is now extensively employed in hospitals and to some extent also in families. The method of ]>rand has been eontinucnisly used in the (jrerman Hos- pital of Philadelphia since I introduced it in my service there on the 1st of February, 1890. All patients suffering from this disease have been submitted to it except very rare cases in which the axillary tem- perature has not reached 101.5° F. (38.6° C), some of those admitted late in the course of the attack — that is, during or after the third week — and those brought in moribund. The details of the method, which except in some minor particulars is that formulated by Brand, are as follows : The patient receives a full bath at about the temperature of the ward every three hours when the thermometer placed in the rectum registers 102.2° F. (39° C.) or over. When axillary temperatures are taken the bath is administered at the end of the third hour if the temperature exceed 101.5° F. (38.6° C). The temperature of the bath standing in the ward varies between 65° and 70° F. (18.3°-21.1° C.) ; if in very warm weather it be found higher than 70° F. (21.1° C), it is cooled to that point by ice or the addition of freshly drawn water. Shortly after the patient has fully reacted, usually in half or three quarters of an hour, his temperature is frequently taken again in order to determine the effect of the individual bath. This is not, however, necessary, and is very often omitted, especially if the patient be already asleep. The patient remains in the bath, as a rule, fifteen minutes, during which time he is systematically rubbed by the attendants and encouraged to rub himself. For this purpose the nurses use their bare hands or bath-gloves. These frictions stimulate the peripheral circulation, constantly change the water in contact with particular points of the surface, moderate the sensation of cold, and, as Glenard has remarked, help to pass the time. If the pyrexia be high, the temperature before the bath exceeding 104° F. (40° C.) or rising very rapidly after the bath, or if it be but little in- fluenced by the bath, the immersion is prolonged to twenty or, in unusual cases, to twenty-one or twenty-two minutes. The tub, which is upon wheels, is placed at the side of the bed and parallel to it at the distance of about a yard. Both are surrounded by ward screens of white muslin upon iron frames, leaving sufficient room for the attendants. The patient's night-dress is removed under the bed- covering, his body is covered with a sheet or a large folded napkin is placed about the loins, and he is lifted from the bed into the bath. Many of the patients in whom the treatment is instituted early in the attack, or in whom for other reasons the symptoms are comparatively mild, prefer to rise and step into the tub with the assistance of the attendants, and no harm has ever been observed to result from per- mitting them to do so. If the patient be asleep, he is not immediately bathed, but fifteen or twenty minutes are permitted to elapse after he is aroused. If he be sweating, his skin is thoroughly dried before the bath. The tub is lined with planished copper, perfectly smooth. There 224 ENTERIC OB TYPHOID FEVER. is a sloping support for the shoulders and head of the patient, which, however, rest upon a rubber air-cushion. The water, usually about thirty gallons for the adult, is sufficient to cover the patient to the neck. Upon entering the bath he receives an ounce of spirit well diluted or half a glass of red wine, or either of these may be administered in divided amounts during the bath. His head and face are immediately and repeatedly bathed with cold water, and a compress wet with the same is applied to his forehead ; a basin and pitcher of cold water are at hand for this purpose. In cases with high temperature or marked nervous symptoms the cold water is very often from time to time poured over the head and face from the height of a few inches. Upon entering the bath the respirations are suddenly deepened. After the first shock the sensations for a time are not disagreeable, but in five or six minutes the patient begins to be restless and complains of cold. In ten or twelve minutes shivering takes place. About the same time the extremities and face become slightly cyanotic. While the patient is in the bath his bed is covered with a rubber sheet, this with a blanket, and over both is laid an ordinary ward sheet. The patient is lifted out, laid upon the bed thus arranged, closely tucked in the sheet, and covered with the blanket. In the course of ten or fifteen minutes he is thoroughly dried and his night-dress is replaced. About this time reaction is usually established, the patient receives nourish- ment in the form of milk or broth, and quickly falls into a gentle sleep. When there is marked cardiac asthenia or if for any other cause reac- tion is retarded, the patient should be at once dried beneath the blanket, receive a hot toddy, and have a hot water bag placed in contact with his feet. The condition of the patient is carefully watched during the bath, and its duration is shortened if its immediate effects, as manifested by shivering, cyanosis, and restlessness, are too pronounced. The German Hospital has a wheeled tub for each of the small wards set apart for the enteric fever cases. Several forms of portable tubs are supplied by dealers. An ordinary tub may be placed upon a low truck or platform upon wheels. In private practice the portable tub of Dr. Batt is convenient for immediate use.^ There is no difficulty, however, in procuring an ordinary tub from a plumber, which may remain per- manently by the bedside of the patient, being noiselessly and with but little trouble filled by means of rubber tubing from the faucet in the neighboring bath-room, and emptied by the same tube used as a siphon out at the window or into a basin connecting with the drainage system of the house upon the floor below. In the fever wards of the German Hospital the tubs are filled directly from a tap of sufficient length extending from the wall at a proper height, and they are emptied at the same point directly into a waste-way in the floor, the wall and floor being lined with slate or tiling. ^ Dimensions of tub when ready for use : length, 6 feet 3 inches ; width, 22 inches ; depth, IS inches. Dimensions of tub when folded for carrying: length, 2 feet 9 inches ; thickness, 9 inches. Dimensions of box containing frame : length, 3 feet 3 inches ; width, 8 inches ; depth, 3 inches. The tub part is composed of heavy canvas covered with rubber, is seamless, and has a tensile strength of 350 pounds. The tub is supported by hooks inserted through the canvas before the rubber is applied. The frame is composed of brass pipe nickel plated. Both tub and frame can be rendered aseptic by boiling. TREATMENT. 225 For a single ])ationt, as occurs usually in private practice, the water should 1)0 chanoi'd once in twenty-four hours. In hospital ])ractice, especially when a number of cases are being treated, it bec-onies neces- sary to bathe several patients in the same water. After the sixth bath the water should be changed. The patients void urine always immedi- ately before the bath, and I have never known an instance in which fecal incontinence occurred during the bath. It is desiral)le to have two attendants for the administration of the bath, though under ordinary circumstances, when the patients are in a condition to assist themselves, the bath may be administered by a single attendant. AVhen there are a large number of cases in hospital wards, as frequently occurs at the time of the epidemic prevalence of the disease, the administration of the baths becomes very laborious and a correspondingly large staff of nurses is required. During the bath the temperature of the water is slightly raised, the change amounting to from 2° to 3° F. (1.1° to Fig. 24. 106°' 105= 104' 103' 102' 101' 100' 99 NORMAL 98^ 97' MlE M E M E M E M E rwT E M E M E M E M E M E M E M E M E M E M E M E M E M E M E M E ^ ^ r 1 i ^ ^: ^ - + = = E i -=_ E E E E E E E 1 1 1 i 1 = = \ J^ M 1 S ^ w j 5 E 1 1 1 1 E E 1 1 — =: E = = E = 1 1 = 1 g = 1 1 E S ^ t 1 E 1 i =: 1 1 1 1 i 'M ^;e - ^ = i 1 1 1 ^ i ^ E = E E E 1 E i 1 1 1 E 1 H M 1 1 s s s i — 1 — -^ — = t=: =^ =r ^ = ^ — =: =: = ^ = =. = =: = rH = = — = OAV OF DISEASE 8 1 1 1 12 13 11 1 5 16 1 7 1 8 19 2 21 2 2 23 21 25 20 27 28 1 PULSE 55 = 5 2 2 § £ 5 = 2 = sis '^ ?, ?i a 2 s R 2 2 s S S 1 s a g ?! s g S S ? n \v, S f f! s STOOL 1 = 1— — 1 — — T 1 — 1 II 1 II 1 \\ II _J DATE 3 i 5 G 7 8 9 10 11 12 13 14 15 IB 17 18 19 20 21 22 231 Case bathed from ninth day. The black line shows a. m. and p. m. temperatures ; the red line the third hour temperature taken immediately before the baths (German Hospital). 1.6° C). The frequency of the bath is determined by the eifect upon the patient's temperature. If at the end of three hours the temperature remains below 101.5° F. (38.6° C.) in the axilla or 102.2° F. (39° C.) in the rectum, the patient is not disturbed until his temperature is again taken at the end of another period of three hours. If, however, during the second period of three hours nervous symptoms arise or manifest increase of fever is present, the temperature is taken sooner and the bath administered at once according to rule. Milder cases and those with declining temperature may require only two or three baths in the course of the twenty-four hours. Early cases and those Avith high tem- perature are subjected to the bath every third hour, alike during the day and night, and it sometimes happens that these frequent baths are necessary for several days in succession. Patients admitted prior to the tenth day of the attack receive one or more laxative doses of calomel. Other drug's are ordinarilv not admiu- VoL. I.— 15 226 ENTERIC OR TYPHOID FEVER. istered, and a majority of the patients reach convalescence without a single further dose of medicine. The maxim that the patient rather than the disease is to be treated is, however, constantly borne in mind, and when the indications have arisen I have not hesitated to administer increased doses of alcohol and aromatic spirit of ammonia, strychnine, opium, etc. in full doses. The necessity for medication has, however, in my own service been very infrequent. The diet has been already detailed. It has not only been possible to give it in larger amounts than under the ordinary expectant method of treatment, but patients frequently crave and demand food throughout the attack. In such cases two or more raw eggs are added to the milk and broth ordinarily administered. During convalescence red wine and Fig. 25. aoWELS. NUH8ER OF MOVEMENTS 1 1 F „ 106 7j- sjs- s- s s s s- s- s-s s-s s- 2- s s- s- s- s ^-^ s s 5- s- s- s- s s s s s 5 2 J s- s- < s 2- < 2- s- 2i2^ 1^- n' Q. □. < < 0- f.-^'S.- n- 2 - s- ^- i?- i?" i?" :?" 0" J^ O' ° S "1 Stgj^ 0- .n *+■ ' ^ -i- CO o>_ o_ «■- oJ.- -m. m- -*- «-r^ co-'d-l 0, '^- ^ cl- ^ r^ 0- ^ 0: CO- ^ ^- ^■ ■°- -^- oj-l * ^ — *- m+d-;f- 104° 103° 102' 101° 100° 1- 5 99° 1- < tt 93° H O m 97: < h- > DAY OF DISEASE PULSE RESP. ^ 1 A /^ fl f V ^ T T -^s ' . '\ ' 1 1 t >v / / *^, / ^^^' \ ' / i ' 1 f 1 j ; ^ V7' ' «l ' T / ' / \ ^-^n ■ r /' 1 ^ t f f 1 ^ 1 i 1 I / 1 1 U f H — r [ 1 I 1 1/ 1 / / 1 1/ f 11 / I J_ III — U ly-^h L--— :- — — — — — — ^— — — l— — — — — — — — — — — ^- ^ _ _ c -j - ^— ^ -U — — — — — — — — — — — — — — — — — — — V~ - — ■■ u J u ... 1 7" * — — ' — — ^ „ i.. ^ rr n- fy. ^ rr fr -\-- ^ '}--- - "H ~^ j- - - f- - - h" - - [^ " ], - [7 - f7 " < < n < < _< ? ~ -^ "ij- "i -f- c' \- -d ~x ^S 'ifr ^ ^ ^ -d 'X - fr •f- -s- "X -^ ;S Ix z - - lu i '^ IS t o_ -li 'n o_ 1 1 — :!_ = .m 24 --.m. s. = ^ri- = - = - - = = 25 = - = - - - = - - - -m^ 26 - -co - - i ¥ 3 ?, g I = 1 g s S 3 1 2 1 = 1 E = § § " ^ S s a g s = 1 = a s 1 5 2 s a % s g s 1 1 s 1 s s s SS S 5 s s 7, s s § § s s s s ?3 ^ S s ^ ?. S a S g g s i s S g s § S s £ s i s s i i 1 s Cold baths : 15 minutes. Cold sponging. Enteric fever, showing immediate effects of individual baths upon the temperature, and rapid rise to the fastigium; also slight effects of cold sponging (Pennsylvania Hospital). preparations of iron, especially Basham's mixture of iron and ammonium acetate, are administered. No solid food is given until the evening tem- perature has been normal for a week. Brand has shown that the mortality is reduced to a minimum where the treatment is instituted prior to the fifth day. A diagnosis of enteric fever can rarely be made in civil practice so early as this. The regular daily system of personal inspection and reports in military practice ren- der a probable diagnosis practicable thus early. In hospital practice a small proportion only of the cases are admitted during the first week. In the service of the German Hospital a provisional diagnosis of enteric fever is regarded as an indication for the employment of the baths upon admission. Under this practice occasional errors have led us to bathe TREATMKXT. 227 patients mIio have suhsiMjtU'iitly proved to bo .sutl'cring iVom iiiHiienza or other acute febrile disease. As a rule, the bej^inninp; of the attack can only be approximately fixed. The clerks are instructed in taking the histories to date the bi'tiinninii' of the attack from the day on wliieh the patient re7 to be *2J)..'>-'i years, " wliicli is about tlii'ee years above tlie mean a^c of the total ])o|)ulation." Oi' 18,1.')8 eases rej)orted l)y the same autiior, 1(1.10 per cent, of the eases were between fifteen and nineteen years of af^o ; 12.() per (;ent. were between ten and fourteen years of age ; 13.25 per cent, of tlie cases were between twenty and twenty-four : these are the three largest ])ereentages of tliis table. A study of the tables taken from the Kiverside and Reception Ilospitals will show a marked diilerence in the trecpieney of ty[)hus fever at different ages. These, liowev(!r, will be more in harmony with each other when it is understood that during the epidemics of 1881-82 and 1892-93 in the city of New York the disease very early in the epidemic invaded the cheap lodging houses of this city. As these are filled entirely by males, and chiefly by men of ages ranging between twenty and sixty years, with very few l)oys, it will l)e apjireeiatcd that the cases taken from these places must necessarily be drawn from persons over twenty years of age ; whereas in the statistics given from the London Fever Hospital the patients were removed from the cheaper class of tenement houses and residences, where every member of the family was subjected to the same infection. It will be seen, however, that under ten and over sixty-five years of age the disease is infrequent. As already stated, typhus fever is usually mild and rarely fatal under ten years of age. Other Influences. — Pursuits which involve confinement in close and badly ventilated apartments, or those which entail continued mental ex- citement or nervous depression, are predisposing agents. Fear is regarded l)y the laity as a potent predisposing cause. The importance of this is exaggerated, and it probably acts as a predisposing cause only when it impairs the appetite and general health and renders the person extremely nervous. I have met with one well marked instance where fear might be regarded as playing an important part in the production of the disease. It is as follows : An engineer employed on one of the islands under the jurisdiction of the Commissioners of Charities and Correction in New York City became very much frightened when it was announced that typhus fever had appeared in an adjoining building Math which he offici- ally had no communication. The man kept religiously away from every one who was in communication with the case, and practically remained in his own apartment when not at work. On the third or fourth day of the outbreak he completely broke down, became violently agitated, and remained in bed, declaring that he knew that he had the fever. The liberal use of bromide, with the assurance that he would not have the disease, put him on his feet again. His work was resumed, but he con- tinued to worry, though physically in good health. During the follow- ing week he Avas taken abruptly ill with typhus fever, and died. While I do not believe that fear can be regarded as an important predisposing cause, I am sure that it militates against recovery if it is well marked, and tends to make a very unfavorable prognosis. It has been claimed that the typhus germ is lighter than the air : this, however, cannot be accepted as true, and should not be taken into con- sideration in selecting the apartment for confinement of patients affected with this disease. 238 TYPHUS FEVER. Direct contact is not necessary to cause typhus fever. The germ is transmitted by emanations from the body, air-passages, and possibly by discharges from the intestinal tract. Air and fomites act as media in communicating the contagium. Walls and ceilings of apartments be- come infected. (See Ventilation, page 235.) It cannot be estimated how long the contagium remains active under various conditions, and therefore the fact that a long period of time has elapsed since the occurrence of a case cannot, as far as the clothing, bedding, etc. is concerned, be taken in lieu of proper and careful disinfection. It is generally regarded as a fact that the poison must be highly concen- trated to be transmitted by fomites. This may be true in the main, but there has been sufficient evidence presented from time to time to prove that a person visiting a t^^hus case may be the medium by which the disease is carried to other individuals. Sailors have been known to carry the disease to their own ship by having visited infected vessels. A case under my observation in 1893 well illustrates this point : A man liv- ing on street had died of what afterward proved to be typhus fever. He had before death been removed to the hospital. His apartment in one of the poorer tenement houses had not been disinfected ; his wife, desiring to comply with the ordinary custom in these cases, although the body was not present, invited some friends to visit her ; among them was a woman, Mrs. M , living on the Boulevard, who brought with her a friend who lived out of town ; the husband of Mrs. M was unable to accompany them. After having made a protracted call at the residence of the deceased, they returned home. Within two weeks Mrs. M and her husband were removed to the Reception Hospital with typhus fever. The latter, as stated above, did not visit the infected apartment ; the germ, it is fair to suppose, was conveyed to the husband by Mrs. M and her friend. The latter did not contract the disease. Attempts have been made to estimate the distance to which the germ may be transmitted ; it has been given in feet : this, of course, cannot be entitled to any very serious consideration, as such estimates cannot safely be used in a practical way, since the danger of infection is not dependent alone on the close proximity of the patient. The mixture of plenty of fresh air, which neutralizes the poison by dilution, is an ele- ment which is far more important to consider. It is fair to assume that a case of typhus fever in a large and well ventilated apartment will not, as a rule, propagate the disease if a reasonable amount of care is exercised. It is a well known fact that a nurse caring for a case of typhus fever in a private apartment where there is sufficient ventilation runs but little risk of contracting the disease, compared with a nurse who is caring for cases of this kind in the wards of a hospital. Murchison and Levy believed that tj^phus is not infectious during the very early period of the disease, probably not until the end of the first week. This belief appears to be rather generally accepted, and I can add that as the result of my personal observation during the epi- demics which during the last fifteen years have occurred in New York City I am inclined to endorse this statement. Where patients were re- moved during the first three or four days of the disease and the apart- ment was properly disinfected, secondary cases did not, as a rule, occur. Where subsequent cases did occur it is possible and probable that the / '. I THO 1. ( ! ICA L A NA TOM Y. 2-\\) iiit"r('ti(»ii CMMU' IVoiu sonu' t)tlicr sourt-c. Cases arc cited, howcxci', wliciv it is (|Mitt' clear that the disease may iuive been contracted during; tlie first davs of the disease, and it would be manifestly unsafe to re<2:ard this point as in any way settled, as it would necessarily tend to relax our efforts in the j)ronii)t I'enioval of cases from tenement houses to other a|)art- ments prejKired for their reception. It would also interfere with disin- fection, the value of which cannot be overestimated. Dr. Mooi'e I'efers to the opinion of the late Dr. Perry of Glasgow, who believed that the most infectious period of typhus fever is during convalescence. Al- thouiih this belief is shared by others, I reoard its accejitance as dan- oerous and opposed to the proper ])rotecti()n of the ])ublic. It has not as yet been satisfactorily determined whether or not the dead body is capable of propagathig typhus : thus far, there seem to be no well authenticated cases ^vhere infection has taken place from this source. Murchison believed that he contracted the disease in the dis- secting-room. This, however, could not be substantiated, as an ei)i- demic of typhus fever existed in Edinburgh at the time, and it is but fair to assume that he was brought more or less directly in contact with the disease, and that he was infected in this manner ; besides, the cloth- ing which envelops the dead body may be the source of infection. How- ever, as no sufficient reason has been presented why this should not occur, it W'Ould be unwnse to regard this point as settled. The question of idiosyncrasy is somewdiat obscure, and has about the same relation to this disease as to others. There are some wdio seem immune to typhus fever and are proof against infection, W' hile others are readily susceptible and may have the disease twice or three times. Dr. Murchison was an example of the latter class, he having had typhus fever twice. What this peculiar susceptibility or immunity consists of is unknown, and cannot be anticipated by an examination of a person. Does one wdio is constantly dealing with infectious diseases become immune is a question which is of peculiar interest, but w^hich is seldom referred to. There are those who believe that this is actual, and refer to the small number of cases occurring among health department officials and quarantine officers, wdio are constantly dealing w'ith this class of disease. It ^vould at least appear to be more than a coincidence. One attack of typhus fever, as a rule, confers immunity against a subsequent one. Ho w^ ever, a second or third attack sometimes occurs. Pathological Anatomy. — The anatomical changes found after death from typhus fever are not specifically characteristic, but are similar to those present in other acute infectious diseases. The organs present lesions that often occur in various conditions attended Avith fever, and the most noticeable feature at the autojjsy table is the presence of the changes unaccompanied by well marked and specific alterations. The findings at the post-mortem examination, if taken by themselves, apart from a clinical history or a probable exposure to typhus fever, are usually not sufficient to establish the diagnosis. The skin frequently retains traces of the petechial rash. The blood is generally dark and fluid, and the body tends to early decomposition. The muscles are dark red in color, and may be the seat of granular or waxy changes, and occasionally of hemorrhages. The heart is soft and flabby. The liver is large and soft. The spleen is almost always much 240 TYPHUS FEVER. enlarged and soft. The kidneys are usually swollen and congested, and the parenchymatous degeneration is more advanced in them than in the other viscera. The intestines are often normal, but have a rosy color. The Peyer's patches not infrequently present the " shaven beard " appearance, but are never ulcerated as in typhoid fever. Apart froru the parenchymatous degenerations of the organs already mentioned, the most constant complicating lesions are found in the respiratory tract. Acute bronchitis, and pulmonary hypostatic con- gestion, and oedema are common. Laryngitis and lobular or lobar pneumonia and gangrene of the lungs are sometimes met with. Inflammations of the serous membranes are very unusual. IncubatiojST. — This period generally ranges from eight to twelve days, usually the latter. There is some diversity of opinion among writers regarding this stage. Hutchison refers to a case where the incu- bation was thirty-one days. Huss at Stockholm speaks of this stage as one, two, or three days, sometimes ten, or in some cases only a few hours. Lebut in his article on typhus in Von Ziemssen's Encyclopedia places it at five to seven days. Where a clear history could be obtained in the cases of typhus fever occurring in the city of New York during 1881- 82 and 1892-93 the period of incubation was found to be about twelve days. This, I believe, w^ill prove to be about the duration in most cases if the histories are carefully investigated. I can account for the state- ments that the usual period of incubation is from three to seven days only on the assumption that the histories of the individual cases were not carefully and fully obtained. While there are very few instances in which the period of incubation exceeds twelv^e days, there are some Avhere the time is much shorter. Well authenticated cases are even cited in which the period of incubation was hardly appreciated, the stage of invasion occurring almost immediately after the exposure. This may be attributed to a peculiar susceptibility of the individual or to concentration of the poison to such an extent that its effect upon the system was almost immediate. After examining a number of cases of typhus fever I have frequently experienced a headache w^hich has lasted for a portion of the day. This experience has been shared by my col- leagues. Symptoms. — Invasion. — One of the marked characteristic signs of typhus fever is the abruptness of its invasion. This can be relied upon as one of the most valuable aids in making an early diagnosis, and is in marked contrast with the slow invasion of typhoid fever. The period of invasion usually lasts from one to three days, during which the patient suffers from a slight chill or chilly sensations (a decided or well marked chill is unusual) : this symptom is accom- panied by general malaise, which soon amounts to great and indescrib- able prostration, accompanied by headache, vertigo, loss of appetite, and soreness about the body ; pains in back and limbs, particularly the thighs and calves of the legs. The tongue has a white coating at first, and is usually large and pale. The coating subsequently becomes darker in color. The uniform and well marked congestion of the conjunctivae peculiar to this disease may be very early recognized, and is a strong diagnostic point in favor of typhus. The dusky appearance of the face SYMI'TOMS. 241 is vorv iioticcahlc. Considerable tremor in the hands is nsnally present. The urine is iuLili colored, scanty, and may have a siK-citic oravity as high as lO.'jO. There are no special abdominal sym])toms ; the bowels are usually constipated. There is sometimes nausea, but seldom vom- iting. The mental condition becomes rapidly blunted and confused, and the patient is listless and suffers from insomnia. The prostration be- comes more marked as the disease i)asses into the eruptive stage. Dur- ing the stage of invasion the pulse is increased in frequency and is com- pressible, and the temperature usually reaches 102° or lO;]"^ F., or sometimes even higher. Eruption. — Usually on the fourth day, rarely after the sixth, the eruption peculiar to typhus fever appears. At first it does not show its true characteristics, but develops as a rash which frequently resembles that of measles and is often mistaken for it. The spots are irregular in form and slightly raised, varying in size from that of a large pea to the point of a pencil. The spots may be isolated or grouped in patches similar to those of measles ; they do not at this time present the dusky appearance which is subsequently shown, but have a dark pink color and disappear on pressure. The eruption appears at first on the chest, abdomen, and then on the arms and thighs. The upper and anterior part of the shoulder and the anterior aspect of the forearm have always appeared to me to offer the best aspect for study. At these sites the skin is cleaner and whiter, and the eruption is usually well marked. Some writers lay great stress on the appearance of the eruption on the back of the hand : I do not regard this site as so favorable for study, as this part of the hand, particularly in the subjects who are affected with typhus, is usually hardened and discolored by work and exposure to the weather, and the eruption is not always easily distinguished. The eruption is not often apparent on the face and neck. Dr. Moore believes this to be due to two reasons : first, because these parts are very vascular and the hyperemia due to the fever conceals the spots ; second, because the rash develops less thoroughly in parts exposed to the air. This explanation appears to be reasonably consistent with the facts as far as it is ascribed to hypersemia, which in this disease is usually in- tense. The second reason can hardly be accepted, as in other eruptive diseases, such as measles and smallpox, the eruption on the face is more intense than elsewhere. In addition to the early measly rash referred to, there is often a mottled condition of the skin which is due to a sub- cuticular eruption. This has the appearance of being deep seated, and, although it can be recognized, it is paler and not as distinct as the former. The " mulberry rash " of Sir William Jenner represents the combination of the two eruptions just described. The mottling is per- haps best seen when standing three or four feet away from the patient. If possible a suspected case of typhus should always be examined in the daylight. The measly or morbilliform eruption gradually changes its charac- ter : the slight elevation disappears, and the dusky pink color becomes much darker, and does not disappear on pressure. This change is con- stant, and is a very important point in the diagnosis. It is due to capillary hemorrhage followed by the formation of pigment, which takes the place of the very early hypersemia : this change is fully Vol. I.— 16 242 TYPHUS FEVER. apparent on the fifth or sixth day, and may be considered the typical and permanent eruption of typhus fever. Another element is to be added to this eruption before its description is complete : I refer to the appearance of true petechise, which may be found on the eighth or tenth day in the centre of the dusky spots, constituting the permanent eruption already referred to ; they are of a bluish tint and their borders are not abrupt, but grade into the dusky color of the typhus rash ; they may invoh^e but a minute portion of the typhus spot or they may almost entirely obscure it. These petechial points repre- sent subcutaneous ecchymoses. The petechise alone frequently occur in other diseases ; they constitute an extremely important diagnostic sign only when they occur in combination with the dusky rash just described. Credit is given by Murchison to Staberoh, Stewart, and Jenner for the description of the conversion of the permanent typhus eruption into petechise. The petechise of typhus are, as a rule, confined to adult patients. About the time that the rash is fully formed the subcutaneous eruption or mottling commonly disappears. As might be expected from the description just given of the permanent eruption, it can be recog- nized after death, provided dissolution does not occur late in the course of the disease from some sequelse. The eruption generally disappears when about eight or ten days old. The rash would probably not be present if death occurred on the first or second day of the eruption, while it is due to simple hypersemia. I know of no statistics regarding this point, as a fatal result rarely occurs at this stage. As already stated, the typhus eruption never appears in successive crops, as in typhoid fever ; a day or two may elapse before the entire eruption presents itself, but when fully out it remains until it all grad- ually disappears. This is in marked contrast with t^-phoid fever. In some cases where the measly or early eruption has been quite prominent a slight desquamation may subsequently take place. This, however, is not very common. The eruption is almost always present in typhus fever, and without it a diagnosis of this disease can rarely be made. It certainly cannot be made in isolated cases. I have seen but one case where the diao;nosis of t^^Dhus fever without an eruption was in a measure justified. During the last epidemic in Xew York City (1892-93) a suspicious case was re- ported at Mt. Sinai Hospital. The patient, a man, had been removed from a vicinity where t\^3hus fever was prevalent ; his temperature and general symptoms were characteristic, but there was an entke absence of an eruption or mottling, the skin presenting a particularly clear and wliite appearance. The temperature dropped about the end of the second week, convalescence ensued, and the patient was discharged. I saw the case in consultation with Drs. Janeway and Jacobi. The general symptoms, particularly those referable to the nervous system, were characteristic of typhus, and, as there was nothing to account for them, the case was regarded as probable t}^hus without an erup- tion. I regard this as justifiable when well marked cases of typhus fever exist in the same place or vicinity. JMurchison's statistics of ad- missions into the London Fever Hospital, which cover a period of twenty-three years, show that out of 18,268 cases of typhus fever the SYMPTOMS. 243 eruption was present in 17,02.'>, or Do. 2 per cent. He admits that in some eases the eruption may have been overlooked, and states that in 1864 unusual eare was taken at the London Fever Hospital to ascertain if the eruption was present : during tliis time it was found in 97.77 per cent, of the eases. The class of people usually affected with typhus are those who pay absolutely no attention to personal hygiene or cleanliness, and a slight eruption is easily overlooked, particularly as the examina- tion of the eases is often superficial, the task l)eing as a rule an unsavory one. The eruption is more often absent in children than in adults. The eruption does not ahvays follow the course above described ; it may not pass beyond the first or second stage. In children it usually does not become petechial, and the disease is frequently mistaken for measles. In mild cases the eruption may begin to fade on the third or fourth day. In some few cases the true typhus eruption may be preceded by a preliminary eru])tion or roseola, "which may cover considerable portions of the body and may be confounded with scarlatina. This roseola is transient and gradually fades as the regular eruption appears. It is well to bear this in mind, as a diagnosis of scarlet fever might cause considerable embarrassment and dangerous infection. Dr. Wilks refers to a case where a preliminary eruption covered the whole body, and was undoubtedly promptly diagnosticated as scarlet fever. The appearance of the eruption is not followed by a fall in the temperature, as in the case of smallpox. Temperature. — There appears to be a uniformity of opinion re- garding the character of the temperature in typhus fever. The disease is ushered in with a comparatively sudden rise, which reaches the maxi- mum during the first week or possibly later. It may reach 103° F. on the evening of the first day, rarely rising higher. Murchison had the record of a case which reached 104.9° F. on the first day, as cited by Griesinger. The maximum when reached is generally no higher than 105° F. and a fraction. In children it may reach or exceed the maxi- mum just given without indicating a grave prognosis. A remission usually occurs during the early part of the second week, and in uncom- plicated cases a gradual decline takes place until about the fourteenth day, when there is usually a sudden descent of from three to five degrees, to or below normal, commonly the latter. This rapid decline may be immediately preceded by an exacerbation. The sudden decline which occurs on or about the fourteenth day may be looked upon as peculiar to typhus fever : it represents the crisis, and is an exceedingly important diagnostic point. An absence of the remission during the early j^art of the second week renders the prognosis unfavorable. An increase in the temperature during the second week usually indicates the presence of some complication which is generally referable to the lungs. A low temperature should not afford one a sense of security, as in many fatal cases the temperature does not exceed 103° F. This condition is found where there is a great depression of the vital powders. The peculiar manifestation of the temperature of typhus fever which is in marked contrast with that of typhoid fever is the slight variation in the daily range. This may be looked upon as the rule, and is ex- ceedingly important in the differential diagnosis. A slight increase in temperature usually occurs in the evening, although in some cases it 244 TYPHUS FEVER. may be highest in the morning. During the early part of convalescence it frequently remains subnormal. During this period (convalescence) a temporary rise of temperature may occur without apparent cause and without special significance. The following temperature charts, taken from the records of the Riverside Hospital, illustrate the range of temperature in what may be regarded as typical cases : Fig. 26. 105° 104° 103° 102° 101° 100° 99' 98' 3 4 5 i m 7 8 10 11 12 13 14 15 Ki 17 18 I i i S5 i m i? Case I. — Temperature chart. Case I. (recovery). — H. M , male, aged thirty-two years, was an orderly in the typhus ward of the hospital during the epidemic in New York City in 1881. The chart therefore records the range of temper- ature from the beginning of the disease. Fig. 27. 106° 105° 104° 103° 102° 101° 100' 99' 98' 97' ■ I i 8 9 10 11 12 13 14 15 10 17 18 19 i B i: 2i «; i^i? 30 Case II.— Temperature chart. SiMJ'TOMS. 24/5 Case I J. (recoverv).— J. D , male, :isew Y(>ri< City wlu-rc an outbreak of typhus occurred in Noveniher, ISSI. The j)atieiit was at once removed to the Riverside Hospital. Case J J J. (recovery). — G. S , male aged twenty-six years, River- side Hospital, February, l«9;j. The temperature chart in this case indi- Fm. 28. o'isEWE 4 5 c, r 8 '.) ]0 11 i-.> ]:; 11 ].-, It; ; ; ; ■ ■ ,.-.-- — 106' i-m. t- 1-^-1 M "A 1 j't -1 M □ J ~^ \- - - -A 1 — i— w.^-- J ] 1 — Y ■" L' \ inn' ^r^ lUU 1 / 1 t t yj ; Case III. — Temperature chart. cates the range from the fourth day of the disease. A record of the preceding days was unfortunately not kept, the patient not being under observation. It will be seen by the al)ove charts that the crisis in these cases occurred about the fourteenth dav. Fig. 29. 106 105' 104' 103' 102' 101' 100' 5 6 7 8 lu 11 12 1.3 11 g ffl Case IV.— Temperature chart. 246 TYPHUS FEVER. Case IV. (death). — J, C , male, aged forty-eight years, Riverside Hospital, April, 1893. This patient was an orderly at the Reception Hospital and was addicted to the use of liquor. His death occurred about the fourteenth day of the disease. Pulse. — The pulse of typhus has certain peculiarities which are gen- erally present in severe and well marked adult cases. In the begin- ning of the disease it ranges from 100 to 120 or 130. The latter is usually reached on the second or third day. Of 90 cases cited by Murchison, in only 15 did the pulse go above 120. Of 13 cases re- ported by this author as occurring in the service of Dr. Henderson where the pulse exceeded 134, 5 died. In a group of 26 cases at the Riverside Hosjjital during 1892-93 between the ages of twenty-one and sixty-five (mean age thirty-seven), there were 10 deaths, in 8 of which the pulse went above 120 ; of the 16 which recovered, the pulse was above 120 in 6 cases. These patients were inmates of lodging houses, and among them the mortality was high. Dr. Murchison un- doubtedly refers to adult cases in speaking of pulse frequency, as it is common to find the pulse above this point (134) in children. In Xovember, 1881, an outbreak of typhus fever occurred among the chil- dren who were inmates of an institution in New York City ; there were 19 children affected, all under twelve years of age. The records of these cases show that in 10 the pulse was above 130, in 6 it was above 140, and in 3 it was above 150; all of these cases recovered. In the class of severe cases the pulse becomes progressively weaker and the cardiac impulse is finally lost. Subsequently the first sound of the heart becomes weaker and may disappear. The second sound may also be affected in a similar manner. It is very unusual for the pulse to remain firm and strong throughout the first week of the disease. In 90 young and robust patients Murchison found but 4 cases where the heart remained in this condition. During the second week the pulse is usually dicrotic, irregular, or intermittent. During the early part of the disease the pulse rate may be very low, with a subsequent rise. In a case reported by Barallier (Murchison) of a man fifty years of age the pulse remained at 28 for three days. A very low pulse generally denotes extreme prostration. A stethoscope should be used in ascertaining the condition of the heart and circulation. The radial pulse cannot be depended upon to indicate the number of cardiac contractions, as the heart may beat twice to one wave of the radial pulse. This difference is not only due to feebleness of the circulation, but to a want of muscular tone. In favor- able cases the heart becomes somewhat stronger about the tenth or eleventh day. The silence of the heart, as the name implies, means that the pulsations cannot be detected, and almost invariably indicates approaching death. During this period of weakness and rapidity of the heart the daily variation in the number of pulsations is small, a slight increase usually occurring at night. After the first day of the disease there is very little relationship between the temperature and pulse ; that is, the temperature may be high when the pulse is slow, and vice versa. During the early part of convalescence the pulse may be slower than normal. Respiraiory System. — The increase in the respiratory action is de- SYMPTOMS. 247 pendent in a great measure on pulmonary complications ; nujre or less hypostatic conocstion is present in nearly all cases. During the first week the respirations do not, as a rule, exceed 25 ; however, with a high pulse and temperature they may become more rapid. On admission to the hospital of the grou]) of 20 cases above referred to, the nnm])er of respirations exceeded 25 in all but 2 cases. The following table indicates the highest and lowest respiratory range in the 10 fatal cases belonging to this group : Age. On admission. at ■ at- • V- ^ ry ■ ,• Maximum. Mmimum. 1 eare. Kespiration. 21 32 48 28 54 32 56 30 25 44 44 20 42 36 38 22 33 28 34 28 65 30 48 20 35 32 44 26 38 30 54 28 39 26 30 24 55 28 32 18 In the fatal class the mean number of respirations was 43 ; in the cases which recovered the mean number was 36. The pulmonary con- gestion usually present may end in oedema of the lungs, which is denoted by hurried and embarrassed respiration ; coarse rales at first, then fine crackling rales, and frothy expectoration tinged with blood. This con- dition usually ends fatally. In cases of great prostration the respira- tions may be subnormal in frequency and not exceed 8 or 10. In this class of cases the temperature is usually low. In severe cases the respi- ration may be sighing or irregular. Where great cerebral irrital^ility exists the respirations are jerky and spasmodic. This is regarded by Murchison as an unfavorable sign. The nervous or cerebral breathing of Sir Dominic Corrigan, which is of a blowing or hissing character, and Cheyne-Stokes respiration, are sometimes present. Epistaxis does not usually occur. In 7000 uncomplicated cases Murchison found it but 12 times. The records of the Riverside Hos- pital also show that epistaxis is uncommon. Dic/estive Trad. — During the first week the tongue becomes very dry and rough. This constitutes a strong diagnostic point in favor of typhus fever, and is present in three fourths of the cases. The whitish fur that is first noticeable changes to a dark brown color, and is gener- ally confined to the centre of the tongue, while the edges and point are pale. This condition continues until convalescence approaches, when the coating gradually disappears and the tongue becomes moist. There is a loss of appetite, and sometimes nausea, but vomiting is uncommon. The iliac meteorism and gurgling which are so often present in ts^phoid fever are wanting in typhus. Pain or tenderness may be found in the hepatic region, or sometimes in other parts of the abdomen, but it has no particular significance. Constipation is usually present. Diarrhoea sometimes appears at about the time of the crisis. Urine. — In the early part of the disease the urine is high colored, and may continue so until convalescence is established. It then be- comes lighter in color. At first the specific gravity may reach 1030 ; 248 TYPHUS FEVER. this afterward becomes diminished, and is apt to be subnormal after the crisis. The amount of urine at first is notably diminished, even when a large amount of fluid is taken. At this time it usually has an acid reaction. During convalescence the amount is generally equal to or above the normal. Suppression sometimes occurs as the result of an acute nephritis. The chlorides in the urine are markedly diminished, and may disappear as in pneumonia. Investigations by Parke, Mur- chison, Buchannan, and others show that the urea is at first increased. In a case cited by Buchannan the quantity of urea passed on the fifth day was 851 grains; that passed on the twelfth day was 1011 grains. As a rule, however, the quantity diminishes during the second week, and may fall below the normal register. An increase is also shown in the amount of uric acid. Albumin is probably found in one half or more of the cases. This does not usually indicate previous organic disease of the kidneys, but generally is due to simple hypersemia or some acute affection of these organs induced by typhus fever. The presence of albumin is frequently accompanied by mucus, epithelium, and casts of the uriniferous tubes. Organic disease of the kidneys renders the prognosis very unfavorable, inasmuch as it favors the occurrence of uraemia and ursemic convulsions. Nervous System. — Pain in the back and limbs and frontal headache, particularly over the temples, are constant symptoms and are well marked during the first week. The headache was present in almost every case received at the Riverside Hospital during 1881—82 and 1892-93. In 251 cases observed by Murchison and Henderson head- ache was present in 236. The pain in the different parts referred to varies in intensity, and usually subsides about the seventh or eighth day. At this period deafness, which occurs in a large percentage of the cases, is noticed. This, as a rule, disappears during convalescence or soon afterward, although in a few cases it remains permanent. Typhus fever is associated with early and great impairment of the mental faculties. Well marked delirium generally occurs during the latter part of the first week, although from the first there is obstinate wakefulness associated with general dulness, the patient being unable to converse intelligently. The delirium occurs at first during the night, but later there is no interval of lucidity. The delirium ranges from a low muttering form, which is so commonly found in older subjects, to that of acute mania, where the patient can only be controlled by force. In alcoholic cases it very frequently assumes the character of delirium tremens. This I have repeatedly noticed in patients removed from lodging houses, these people, as a rule, being alcoholic subjects. A suicidal tendency is not infrequent. The prognosis is in a great measure governed by the degree of delirium ; when the latter is profound the prognosis is correspondingly unfavorable. The pupils are usually contracted, sometimes to an intense degree, producing what is known as the pinhole pupil. The latter condition constitutes a very unfavorable sign. Complications and Sequelae. — Although numerous complications and sequelae may occur in typhus fever, it is necessary to refer to but a few of them. Of these bronchitis stands at the head. This is so con- stant and prominent that it may be regarded rather as a symptom than COMPLICATIONS AND SEQUELJE— DIAGNOSIS. 249 a complic-ation. It may (generally be expected to occur. Among those complications which are infrequent may be mentioned lobar pneumonia, larvnii'itis, iicncnil convulsions, pytemia, plilco:masia dolens, thrombosis, embolism, mcnini;itis, and intestinal hemorrhage. General convulsions which are ura?mic in origin constitute an exceedingly dangerous com- plication ; they occur late in the disease, during the latter i)art of the second week. The attack is generally preceded by a greatly diminished amount of urine, at times amounting to suppression. The mental con- dition is also notably atfected at this time, the stupor or delirium being intensified. The convulsions are usually followed by coma and death, the latter occurring within twenty-four hours. Diagnosis. — Typhoid fever is frequently mistaken for typhus, even by those having wide experience. Some of the essential points to be borne in mind in deciding between these diseases are as follows : Typhus fever has a very short and rather abrupt period of invasion. It usually commences with a slight chill or chilly sensation and a rapid rise of temperature, pronounced headache, and pain in the back and limbs. On the third or fourth day, rarely after the fifth or sixth, the character- istic eruption appears. In typhoid fever there is notably a long period of incubation and invasion. The patient has been suffering for days with general malaise (which is frequently regarded as due to malaria or general debility), and it is only after ten or fifteen days, when the symp- toms have gradually become more pronounced, that he is obliged to go to bed and remain there. I regard this as one of the most important points in the differential diagnosis, and it can almost always be relied upon. This cannot l^e said of the diarrhcea and epistaxis, which are erroneously believed by some to be present in all cases of typhoid fever. When epistaxis is present it suggests at once t^-phoid fever. Murchison found it in but 12 out of 7000 cases of uncomplicated cases of t}73hus fever. Diarrhoea is likewise a very uncommon symptom of t^-phus fever, par- ticularly before the crisis. Abdominal pain, tenderness, and tympanites, which are so constant in typhoid fever, are, as a rule, absent or only feebly marked in t}^3hus. The characteristic eruptions of these diseases are markedly different. When t^-pical, that of typhus appears on or before the fifth day and is found over the greater jjart of the body. When it is fully formed it is dusky in color, does not disappear on pres- sure, and there are no successive crops, as in typhoid. The eruption in this disease is not short lived, as in typhoid, but remains distinct for several davs, and is usually present when death occurs in uncomplicated cases. In typhoid the eruption does not appear until the beginning of the second week. It is confined principally to the abdomen, back, and chest, and consists of small rose colored papules which disappear on pressure. Successive crops occur. It is in those cases in which the typhus eruption is slight or the typhoid eruption is profuse that errors are apt to occur. I cannot speak too strongly on this point. Numer- ous cases of tvphoid have come under my observation which have been positively declared to be typhus fever on account of the accompanying general eruption. In some cases it was a profuse typhoid eruption ; in others it was a septic eruption or an accidental one. It must be borne in mind that a profuse typhoid exanthem follows the ordinary course of the eruption in that disease ; that is, in two or three days the first crop 250 TYPHUS FEVER. disappears and is succeeded by a second, or the first crop disappears and a much smaller crop follows. In other words, there are successive crops instead of a permanent eruption. Accidental eruptions Avhich sometimes accompany typhoid are, as a rule, short lived, and disappear on pressure or become indistinct in two or three days. A general eruption sometimes follows a high tempera- ture. I have seen numerous cases where the history of the invasion and the early symptoms w^ere clearly indicative of a typical case of typhoid fever ; still, on account of a profuse eruption, either typhoid or foreign to the disease, the diagnosis of typhoid fever would not be accepted until corroborated by the autopsy. Even if the history of the eruption alone were carefully studied, it would, as a rule, help to clear up whatever doubt might exist as to the diagnosis, I wish to repeat that the early history of the case, particularly the period of invasion, should always be carefully taken into consideration before a decision is made. In considering the diiferential diagnosis between measles and typhus fever, it should be remembered that measles is essentially a disease of children, while typhus affects adult life. The high temperature and pulse and early acute catarrhal symptoms affecting the eyes as well as the respiratory tract point toward measles. The bronchial or catarrhal svmptoms accompanying typhus are not as acute or as early. The erup- tion of measles, although it may in a w^ay be confounded with the early eruption of typhus, is particularly prominent on the face, where the eruption of typhus is absent. If measles occurs in an adult, the mental dulness and subsequent delirium which are marked in typhus are wanting. Special care should be taken to ascertain if there have been other cases of measles in the family or vicinity. It is Avell to remember that the eruption of two distinct diseases may be present at the same time. I have the notes of a well marked case of typhoid fever in the beginning of the second week which I saw in consultation at the New York Hospital in 1893. The typical eruption of typhoid fever was present on the abdomen. At this stage the temperature suddenly became higher and pronounced coryza and other catarrhal symptoms appeared. In two or three days the characteristic eruption of measles appeared on the face and chest. An investigation disclosed the fact that the patient, a young man, had attended his sister's children who were suffering from measles, shortly before he was removed to the hospital. If the patient is closely observed and the present and previous his- tory is carefully studied, malarial fevers can hardly be confounded with typhus. The periodicity which is usually prominent in malarial fevers, the controlling effect of quinine and other remedies, the history of the patient being at the tune present in a malarial district or having previously lived in one, the absence of an eruption, the evidence of an enlarged firm spleen, etc., should exclude typhus fever. A differential diagnosis between cerebral meningitis and typhus fever is not always easy at first. As a rule, however, in meningitis the cerebral symptoms occur earlier and are more marked, the headache is more intense, and the hearing is abnormally acute ; there are also present photophobia and acute delirium. In meningitis symptoms of irritation or compression are very early noticeable, such as vomiting, ptosis, strabismus, unequal or contracted pupils, muscular rigidity, rno(.;yosis. 251 tremor or paralysis, etc., whicli arc uncommon in typhus. Vomiting, wliich is a very common and constant sym})tom in meningitis, is very nirelv seen in uncomplicated cases ot"tyj)hus lever. (Jf course the pres- ence of a well marked typhus eruption would decide between the diseases referred to. This, however, may not appear for two or three days. Epidemic cerebro-spinal meningitis may be mistaken for typhus fever, but only in exceptional cases. Although the invasion of typhus is rapid, that of cerebro-spinal meningitis is luarkedly abrupt, and almost always occurs during the night with really no premonitory stage. Cerebro-spinal meningitis usually affects children before the tenth year, while typhus is a disease of adult life. In the latter the critical period occurs late in the disease. In cerebro-spinal meningitis death may take place within twenty four or forty eight hours, and the cerebral symptoms, such as intense headache, photophobia, phonopholjia, and delirium, become at once prominent. In this disease, also, vomiting is almost always present, while it is rare in typhus. In cerebro-spinal meningitis the pain is marked over the nape of the neck and down the back over the region of the spine. On the third or fourth day contrac- tions of the muscles of the neck and back are present. Retraction of the head and opisthotonos are more or less pronounced. The retraction of the head is a sign which is generally understood by the family, and constitutes a very important point in the diagnosis. The s^nnptoms just referred to belong to cerebro-spinal meningitis, and are not found in tvphus fever. An herpetic eruption is very commonly found about the lips, ears, and cheeks in cerebro-spinal meningitis, and only occasionally presents itself in typhus. The eruption of cerebro-spinal meningitis is irregular, has no definite form, and does not by any means always appear. It is usually found in certain parts where the temperature is supposed to be reduced, and is not spread uniformly over the body, as in typhus. I can hardly believe that a case of cerebro-spinal meningitis could exist where the diagnosis could not be made if the history and symptoms were carefully studied without the question of the eruption being taken into consideration, particularly after the lapse of tsvo or three days. Pneumonia is sometimes mistaken for typhus fever, and vice versa. However, a thorough physical examination of the chest, with a careftil investigation as to the history of the case, ought after a day or so to clear up whatever doubt may exist. Acute yellow atrophy of the liver and malignant endocarditis have also been mistaken for tx'jDhus fever. Peogxosis. — Among the more important signs and symptoms which indicate an unfavorable prognosis are — advanced age, intemperate habits, a pulse in an adult of over 120, marked and persistent nervous symptoms, such as delirium, a dark and abundant eruption, great mental depres- sion, disease of the kidneys or other organs, rapid respiration, insom- nia which cannot be relieved, Ursemic convulsions and pronounced coma vigil almost always indicate a fatal termination. A pinhole pupil is also regarded as an extremely unfavorable sign ; early relaxation of the sphincters, continued high temperature, particularly in adults, and also the advent of the different complications, tend to make an unfavor- able diagnosis. It must be remembered, however, that although some 252 TYPHUS FEVER. of the signs above enumerated are almost invariably followed by a fatal termination, recoveries have taken place after their appearance ; and every effort should be made to sustain life as long as possible. Prophylaxis. — Well directed and practical efforts toward the pre- vention of typhus fever in a community are far more important than the treatment of this disease ; this fact, unfortunately, is too often over- looked. It can confidently be said that if the proper preventive means are employed an outbreak of typhus will soon be under control. It is of the utmost importance that cases of typhus fever should be early recognized, and that suspected cases should receive the most careful attention and care until they are proven not to be typhus. If in a private residence or small house, the patient should be placed in a well ventilated room on the top floor, everything in the apartment having been previously removed which is not absolutely needed for the patient, particularly upholstered articles. After removal, the clothing, bedding, etc. and the room previously occupied by the patient should be sub- mitted to a rigid disinfection, as will be hereafter described. No one should enter the infected room except the nurses and physicians. This regulation should be particularly enforced, and food should be carried to the floor by an attendant and taken to the room by the nurse. The dishes should be placed in boiling water or a solution of bichloride of mercury, 1 : 2000, before being returned. Nurses leaving the apart- ment should remove all the clothing worn in the infected chamber be- fore going outside, should have a bath and have the hair thoroughly washed ; all linen, etc. when soiled should be put in tubs of boiling water, and afterward placed in a solution of bichloride of mercury, 1 : 2000. Worthless articles should be destroyed at once, preferably by burning. When the patient is able to leave the room he should be care- fully and thoroughly bathed, rubbed, and dressed in fresh clean clothes, and removed to another room. The windows, doors, and all openings into the infected apartment should be sealed by pasting Avith strips of paper. The apartment should then be disinfected by sulphur dioxide, at least four pounds of sulphur to each 1000 cubic feet of air space ; at the same time the air of the room should be rendered moist. The doors and windows and other openings should be kept closed for at least eight or ten hours, and longer if possible. The most effective means of all for disinfection is heat. If a disin- fection apparatus where a high degree of heat can be secured, such as is used by the Health Departments of different cities, is available, the clothing, mattresses, pillows, comfortables, and other material of this character which have already been subjected to the above fumigation and which cannot be washed, should by all means be heated in this manner or otherwise should be burned. Sulphur dioxide cannot be de- pended upon as a safe disinfectant in this instance, as it has very little penetrative power, and is only effective where bare surfaces are exposed. After fumigation the woodwork and wooden parts of furniture, beds, etc. should be carefully wiped with a solution of bichloride of mercury, 1 : 2000. I have referred above to a case occurring in a private resi- dence. Cases originating in tenement or apartment houses and hotels should always be removed to a hospital or place prepared for the recep- tion of such cases. Neither should cases of typhus fever be cared for in TREAT^rKST. 253 institutions unless a scpanitt' or distinct l)uil(lin- the body of typhus patients the bedelothin<»- or clothinh and the hath is contrainchcated ; it is at least a sale remedy. This, however, cannot he said oi" antipyrine, phenaeetin, and remedies ol" this class. AVhile they rechice the tenn)eratiire, they are a})t to cause con- siderable depression, which should be avoided. I believe this to Ik* tlie feeling of the majority of those who have had experience in tlie treat- ment of tyj^hns fever. Stimuhmts are particularly indicated in this disease; their vahie is conspicuously apparent in the later stage, particularly in alcoholic sub- jects. Digitalis is used as a heart tonic and diuretic. Nitroglycerin and strychnine particularly may be also recommended as heart stimu- lants. Morjihine, although objected to by some, is unquestionably valuable in the insomnia accompanying the disease when judiciously ad- ministered, and in comparatively small doses is certainly a cardiac stimulant. Innumerable remedies, such as sulphonal, trional, bromide, chloral, etc., have been used to relieve the insomnia Avith varying suc- cess, and may be given a trial. The fluid extract of guarana was a favorite remedy at Riverside Hospital, New York, during the epidemic of 1881-82 for the headache which is present in typhus fever. It is strongly recommended by Dr. Frank Chapin, who was in charge of the above hospital during the epidemic above referred to. One or two drachms of the fluid extract should be occasionally given. Sinakoski says that for over two years he treated typhus by every known method, and as a result he feels satisfied that the calomel treatment is superior to all others, and if begun early greatly diminishes the severity or aborts the disease. I cannot but feel that this writer is over confident regard- ing this form of treatment. I certainly do not believe that the disease can be aborted. Mr. H. T. Webster regards Echinacea am/usftfolia as a valuable antizymotic, and reports that he has used it with success in typhus fever. Schleschumizen reports good results from the internal use of creolin in doses of f grain in distilled w^ater four or six times daily. Under this treatment the disease w^as more submissive and pur- sued a milder course with a lower temperature. Dr. A^ance of Sonoma, California, recommends that leeches be applied to the temple in young and robust patients. It will thus be seen that innumerable remedies and plans of treatment have from time to time been suggested, but I believe the method which I have already recommended, of treating the difier- ent symptoms and complications as they present themselves, is the most practical and valuable. RELAPSING FEVER By warren COLEMAN, M. D. Definition. — Relapsing fever is an acute infectious disease caused by a spirillum, the Spirochoita Obermeierl, and characterized by a febrile paroxysm, by a period of intermission, and by one or more relapses. Etiology. — The discovery of the spirochseta of relapsing fever by Obermeier was made known in 1873, though the organism had been seen by this observer as early as 1868. It is a delicate spirally twisted filament of homogeneous ^ appearance, varying in length from 16-40 //, or, approximately, from two to six times the diameter of a red blood cell, and is always in active motion when seen in fresh cover-glass preparations. Its movements are a combined rotation on its long axis, propelling the organism backward and forward, and a shortening or lengthening of its spirals, a portion of the organism straightening out at times and thrashing around among the corpuscles in whip- like fashion. The spirochseta should be ex- amined in an ordinary cover-glass preparation of blood and without the addition of any reagents, since it is extremely sensitive to them. Von Jaksch states that the mere addition of distilled water causes the organisms to disappear. Or- dinarily they may be easily de- tected through the disturbance they create among the red blood cells. They occur singly or in groups, and may be seen with a ^ inch (Leitz) objective, though it is desirable to use a Y^2 i^ch homogeneous oil immersion lens and Abbe's condenser. The spirochsetse are found in the blood only during a paroxysm of fever, and disappear shortly before the end of the paroxysm. As a rule, they do not appear during the first two or three days after the onset of the disease. They may be present in great numbers in each field of the microscope, or there may be difficulty in finding a single organism. What becomes of the organisms during the period of inter- mission has not been determined. The small number of cases in which absence of the spirochsetse from the blood has been reported may be disregarded in the face of the over- ^ A beaded appearance of the protoplasm lias been noted by one or two observers. Vol. I.— 17 257 Blood of relapsing fever, showing Spirochaeta Obermeieri among the red corpuscles ; mag- nified 1150 times (Eichhorst). 258 BELAPSINO FEVER. whelmingly positive results in the majority of cases. It is a notable fact that the number of spirochsetse varies at diiferent times in the same individual during the same paroxysm, and Heydenreich, who made a careful study of the blood during an epidemic in St. Petersburg, set forth the opinion that fresh broods of the organism were probably pro- duced several times during a paroxysm. This opinion was based upon the finding of only a few spirochsetse in the blood of a patient at one examination, yet a specimen taken a few hours later revealed their pres- ence in large numbers. The same observer established a further inter- esting fact, that the spirochaetse after removal from the body survived but a short time at the body temperature, though if kept at a tempera- ture from 60° to 70° F. they remained alive much longer. This would seem to show that the very pyrexia produced by the organism is in the end the means by which the paroxysm is brought to a close. Sarnow and V. Jaksch have observed in the blood between the paroxysms highly refractive bodies resembling diplococci, which they suggest may be spores. V. Jaksch states that at times he has seen these coccus-like bodies grow out into short rods. Nothing is known of the habitat or life history of the spirochsetse, and up to the present time all attempts at artificial cultivation have failed. A review of the epidemics which have occurred since Rutty de- scribed relapsing fever in 1770 leads to the conclusion that there are certain endemic centres (e. g. Ireland), and that when epidemics occur in other places infection has been carried to them by persons or fomites. The formerly-considered autochthonous origin of relapsing fever is evidence that the disease is at first endemic. All authorities are agreed that relapsing fever is communicable by personal contact, and the more intimate the contact the greater the likelihood of infection. Thus in crowded tenements the disease spreads rapidly ; nurses and orderlies are more likely to contract it than hospital internes, and the internes than the attending physicians. When a person sleeps in a bed not yet cleansed which has been occupied by a relapsing fever patient, infection almost certainly follows. As regards the transmission of relapsing fever by fomites, there seems to be some difference of opinion. Wyss and Bock, Cormack and Parry, have recorded instances where the disease was thus conveyed, while Loomis, on the other hand, states that in the epidemic in ^ew York City in 1870 he found no evidence that the fever was conveyed by clothing, and that not a single person who was brought into imme- diate contact with the clothing contracted the disease. It was thought formerly that relapsing fever originated in destitution and filth, hence the names " famine fever " and " hunger-pest," but it is known now that these exert simply a predisposing influence. There has been much discussion as to the manner in which relapsing fever is transmitted from person to person. The expired air and the exhalations from the skin both have been accounted responsible for the spread of the disease. But we know nothing as yet concerning the channel through which the organism leaves the body or the form in which it leaves it, and until these facts can be ascertained opinion must be held in abeyance. The spirochseta is not present in the bronchial PATirOLOaif'AL .l.V.l'/'OJ/}'. 259 secretion, in the c()njuni'ti\;il secretion, or in the scrum of the herpetic or sudaminal vesicles wliieh occur in certain cases, and is found in the urine and matters vomited only when they contain blood. Heydenreich states that it does not leave the body in the ftcees. We are equally in doubt as to the maiuiei" in which the spirochseta etfects entrance into the body. It has been thought that it jiassed in with the inspired air. But such a theory presupposes the formation of spores and their drying outside of the body, and appears to be contra- dicted by the readiness with which the disease is transmitted. From studies during the Breslau epidemic Litten concluded that the spiro- chfetcie were not contained in the drinking water, and the oi-ganisms found bv Carter in water from a tank in Bombay, though similar in form, were larger than those seen in the blood of relapsing fever })atients. A manner of infection which has not received attention, and which seems upon a priori grounds not unlikely, is the introduction of the organism or its spores into the mouth by unclean fingers. The rapid dissemina- tion of the disease in filthy, overcrowded apartments lends weight to this supposition. But, whatever may be the channel of infection, the important fact remains that relapsing fever is directly communicable from person to person. MotschutkofFsky has shown that relapsing fever may be reproduced in man by inoculation Avith the blood of a patient ill with the disease, and several instances are recorded where infection followed wounding the hands at autopsies. Koch and Carter have produced relapsing fever experimentally in monkeys by inoculation. Relapsing fever may occur at any age, though the greater niunber of cases have been met with between the ages of fifteen and twenty- five. Neither sex nor season has any influence upon the development of the disease. That more males are attacked than females may be ac- counted for by the fact that males constitute by far the greater proportion of tramps and vagrants. One attack does not afford immunity against the disease. Pathological Anatomy. — The pathological changes caused by re- lapsing fever are in the main those of acute infectious diseases generally. The spleen is enlarged during the active periods of the disease, some- times enormously, and is dark and soft. Not infrequently it is the seat of anaemic infarctions and focal necrosis. According to Nikiforoff (Ziegler), microscopic examination reveals extensive degeneration of the pulp cells, amounting in places to actual necrosis, and the formation of fibrin in the veins of the pulp. The spirochsetse are found in consider- able numbers in the areas which are not entirely necrotic. Hyperplasia of the spleen pulp occurs in other places. Abscesses occasionally form, and may give rise to peritonitis. Rupture of the spleen has occurred in some cases, followed by rapidly fatal syncope. The kidneys are swollen, especially their cortical portion, lighter in color than normal from a granulo-fatty change in the epithelial cells, and streaked with the red, congested bloodvessels. Not infrequently the cut surface shows minute hemorrhages into the kidney substance. The heart muscle undergoes parenchymatous degeneration. The fibres lose their striation and their nuclei may show fragmentation. 260 RELAPSING FEVER. The liver is enlarged and congested, and its cells present parenchym- atous changes. The stomach and intestines may present a moderate grade of inflam- mation, as evidenced by injection of their vessels and minute extravasa- tions of blood in their mucous membranes. The lymph nodes are often infiltrated and swollen, but are rarely ulcerated. Symptoms. — Incubation. — The period of incubation in relapsing fever varies. Cases have been recorded in which the disease apparently followed Avithin a day or two of exposure (Murchison), and others where the symptoms did not present themselves for tAvelve or fourteen days. The average period of incubation appears to be five to seven days. After experimental inoculation of apes with the blood of relapsing fever patients the disease does not appear until several days have elapsed, and in the case of experimental inoculation in the human subject by MotschutkoiFsky symptoms did not follow for seven days. Prodromata. — Relapsing fever is rarely preceded by prodromal symptoms. If they occur, they last only a day or two, cluring which time the patient suffers from anorexia, lassitude, slight headache, or vertigo. Generally, the disease is ushered in abruptly by rigors or a chill of moderate severity. Invasion. — The attack usually begins during the day. Patients often can tell the exact hour of invasion, and not infrequently are seized while at work. Following the chill, there is a rapid rise of temperature^ the thermometer registering 104° to 106° F. by the evening of the first or second day. In many cases there is a rise of 2° F. or more during the chill. Hyperpyrexia in relapsing fever, however, is not dangerous. Accompanying the rise in temperature, the pulse speedily becomes ac- celerated, reaching 110, 120, or even a greater frequency. It is full and strong at first, and in the average case continues good throughout the paroxysm, but may become feeble, compressible, and even dicrotic. Early in the disease the patient suffers from extreme giddiness, so that he is unable to walk or even stand, and often takes to his bed from this cause. Headache of a most intense nature soon appears, and distress- ing pains occur in the muscles of the trunk and extremities, especially severe in the calves of the legs. The severity of the pains sometimes increases as the paroxysm progresses. Muscular hypersesthesia, particu- larly marked over the gastrocnemii, adds to the suffering of the patient. Cutaneous hyperaesthesia may be present, especially in women. Pains occur also in and about the joints, though, as a rule, the joints are not swollen. Patients sometimes come into the hospital under the im- pression that they are suffering from acute articular rheumatism. Nausea and vomiting usher in a certain proportion of cases. At first the contents of the stomach are expelled, and later mucus and regur- gitated bile. The face is flushed, but not dusky. The tongue is moist and coated with a whitish fur. Thirst is intense. There may be anorexia or the appetite may be increased. The skin becomes slightly jaundiced during the first few days, and in certain cases the color deepens. The jaundice is thought to be due to catarrh of the bile ducts. The bowels may be free or constipated. There is tenderness in the hypochondriac regions. SYMPTOMS. 261 aiul upon percussion the liver is found eularg^ed. The spleen increases rapidly and markedly in size, extending well below the free border of the ribs. It increases in size so rapidly that the enlargement may be noted from morning to evening of the same day. A petechial eruption occurs in about 10 per cent, of the cases (Mur- chison). Herpes labialis and sudaminal vesicles are met with in some cases. The urine presents the characters common to febrile conditions. It is diminished in amount, of dark color, and of higher specific gravity than normal, and it not infrequently contains albumin. Blood may be pres- ent. AVheu the jaundice is marked the urine contains bile pigment. The headache often diminishes, but the pains continue, sometimes with increasing severity as the disease advances. The suffering occa- sioned by moving causes the patients to lie perfectly still, but they are not apathetic. They are sleepless, but only because of the pains. Cerebral symptoms are not marked even w^hen there is hyperpyrexia. Occasionally, however, there is delirium. The temperature remains at about the height it reached on the first or second day, with a diurnal variation of 2'^ F. or more. The time at which the remission occurs varies in different individuals. The pulse retains its frequency or is increased somewhat. Crisis, — AVhen these symptoms have continued about a week, and with apparently alarming severity, the crisis comes. It may occur as early as the fifth or be delayed until the fourteenth day. There is a sudden fall of temperature ordinarily of from 5.4° to 10.8° F. (Lebert) to the normal or below" it. There is no disease in which the temperature falls so suddenly. Lebert has recorded a case in Avhich the fall amounted to 12.6° F., and Murchison another in which it amounted to 14.4° F. in twelve hours. The pulse rate diminishes correspondingly, dropping from 120 to 70. Occasionally it falls as low as 52 or 48 (Lebert). The headache and pains disappear, the tongue becomes clean, and the patient passes into a fairly comfortable state. The crisis occurs most frequently in the night or early morning. On the evening of the last day of the paroxysm the temperature may rise suddenly as much as 4° F. Profuse sweating, diarrhoea, epistaxis, or the menstrual flow not infrequently occurs at the crisis, or the patient may become wildly delirious imme- diately before the crisis, and be perfectly rational after it has passed. As a rule, the pulse continues a little above the normal, and is espe- cially likely to be accelerated if the patient attempts to get out of bed, but the appetite returns and he improves rapidly, feeling perfectly well in a short time. If he is in an hospital, he may insist upon returning to work. But his apparent recovery is of short duration. Relapse. — A relapse is sure to follow except in a limited number of cases^. It usually occurs on the seventh day and at night. It may occur earlier, even as early as the second or third day. The symptoms return with all their severity. The temperature rises to about the height it attained during the first paroxysm, the pulse becomes acceler- ated, and again the patient suffers from the headache and muscular pains. The duration of the relapse is variable, the average being from three to five days, after which a second crisis comes. At times when the first paroxysm is mild in character the relapse is 262 ' RELAPSING FEVER. severe, and vice versa. In the majority of cases convalescence is estab- lished after the relapse, but two, three, or even more relapses may- occur. Sudden collapse, occurring without any apparent cause, is a danger- ous and usually fatal symptom in a limited number of cases. The attack may have been mild and have been progressing favorably, when suddenly symptoms of cardiac failure come on. These may occur at any period of the disease, but are most likely to manifest themselves at the first or second crisis. The pulse becomes small, rapid, and feeble, the skin is bathed in a cold clammy sweat, and the patient passes into a state of unconsciousness, to be rapidly followed by death. In some cases the pulse gives evidence of the impending cardiac failure a day or so before the crisis, but in others there may be no indication of the danger until it arrives. Murchison found the heart fatty and dilated in three cases where it was examined jDost-mortem. In other cases a sudden effort, such as getting out of bed, induces cardiac failure. Occasionally there is a pseudo-crisis toward the end of the first paroxysm. The temperature falls suddenly, perhaps below the normal, and the distressing symptoms abate. But about twenty-four hours after- ward the temperature rises to 104° F., the headache and the pains return, and the actual crisis is delayed for twenty-four or forty-eight hours longer. According to Carter, the blood during these attacks shows the presence of the spirochsetse. Duration. — The average duration of relapsing fever is from eighteen to twenty days. After an attack patients regain their health slowly. Convalescence is long and tedious. Even when the disease ends with a single relapse it is often six weeks before patients can resume work, whereas if they have more than one relajDse the return to health is much longer delayed. Abortive cases occur in relapsing fever as in many other specific infectious diseases. Convalescence may be established after a light first paroxysm, or there may be a relapse of short duration. In either case patients recover their health quickly. Griesinger introduced the term bilious typhoid to include what he considered a distinct type of fever attended by jaundice and by a typhoid condition. There is some doubt, however, as to what disease he was describing. Since there is a form of relapsing fever, proved to be such by the presence of the spirocheetse in the blood, and attended by jaundice and a continuance of the pyrexia between the paroxysms, Murchison concluded that all the cases described by Griesinger were of this nature. Equally eminent authorities, however, contend that bilious typhoid is the disease now known as acute infectious jaundice. (See Weil's Disease, page 945.) Complications and Sequels. — Lobar pneumonia is the most com- mon of the serious complications of relapsing fever, though the fre- quency with which it occurs varies greatly in different epidemics. It develops, as a rule, during the paroxysm or the relapse, and is especially likely to involve both lungs. Persons of intemperate habits are most often affected. The cases may be mild or severe. Pulmonary gangrene follows the pneumonia in a small proportion of cases. In many epi- demics this complication has increased the mortality rate perceptibly. DIAGyOSTS. 263 Bronchitis is perhaps tho most fVeqiicnt complication of relapsing fever. Generally it is mild in character. Abscesses may form in the spleen and render convalescence slow and tedious, or may lead to a fatal termination through peritonitis or meta- static pvooenic processes in other parts of the body. Jlnpture af the sph'oi, without abscess formation, has occurred, accompanied by sudden and intense pain in the splenic region and followed by a ra])idly fatal syncope. Dysentery is a dangerous and oftentimes fatal complication in certain epidemics. Meschede states t\vA.t purulent otitis occurs in about 10 per cent, of the cases. One or both ears may be affected. Parotiditis is rare. When it does occur the inflammation usually proceeds to suppuration and delays convalescence. Epistaxis may be a dangerous complication. Though the urine in relapsing fever not infrequently contains traces of albumin, symptoms of kidney disease rarely occur. When symptoms of ursemia do appear in the course of the disease, they usually depend upon a pre-existent nephritis. Pregnant women always abort or have premature labor when at- tacked with relapsing fever. In the majority of instances the mother survives, but the child dies, even though viable when born. Among the more important of the sequelae of relapsing fever is a post-febrile ophthalmia, which occurs in two stages — an amaurotic and an inflammatory stage. The inflammation may involve the iris alone or the iris and choroid coat, and is accompanied by intense intraorbital pain. Optic neuritis occasionally occurs. As a rule, only one eye is affected. Loss of vision not infrequently follows. At times the head- ache and muscular pains persist after the paroxysms subside, and render convalescence long aud tedious. Diagnosis. — Difliculty in recognizing relapsing fever can occur only during the first few days of the disease, and before the spirochsetae have appeared in the blood. In its mode of onset it is not unlike typhus fever, yellow fever, and smallpox. But with the exception of tA^Dhus fever, fully developed cases present little difficulty. Epidemics of relaps- ing fever and typhus fever have prevailed at the same time, and under these circumstances it may be impossible to decide which disease one has to deal with until positive eviclence of the one or the other presents itself. There is the same absence of prodromal symptoms in both diseases, the same abruptness of invasion, the same rapid rise of tem- perature. In both diseases headache and muscular pains are prominent early symptoms. But in typhus fever prostration, in relapsing fever giddiness, compels the patient to seek his bed. In typhus fever the face is dusky — in relapsing fever, flushed. In typhus fever dulness of mtel- lect accompanies the headache — in relapsing fever the mind remains clear. And by the third day, often earlier, the spirochaetse may be found in the blood in relapsing fever. Peogxosis. — Relapsing fever is not a dangerous disease, despite the severity of its symptoms, and is not often a cause of death in itself. A fatal termination rarely occurs except from sudden collapse or some complication. The extreme limits of the mortality rate in the epidemics 264 RELAPSING FEVER. which have occurred are 2 and 11 per cent. The higher of these per- centages has occurred when complications were frequent. Pneumonia is the complication to be most feared, with the exception of pygemia fol- lowing splenic abscesses and dysentery. Eupture of the spleen may be regarded as an accident, and needs scarcely be taken into consideration in forming a prognosis. Even though pneumonia occurs, the case may terminate^ favorably. Eelapsing fever is more serious in chronic alco- holic subjects and in old people. Cardiac thrombosis is stated to be a cause of death in some cases, especially in persons whose previous health has been bad or in those of intemperate habits. The cardiac thrombosis is probably, however, only a concomitant of death, the actual cause being a degenerated myo- cardium. Treatment. — The treatment of relapsing fever is wholly expectant. The use of various drugs has been proposed with a view to abort or modify the course of the disease, but all alike have proved unsuccessful. We are powerless to do more than combat the symptoms as they arise. Quinine is of no avail. The headache which is such a pronounced feature at the onset of the disease may be relieved or diminished in intensity by the application of an ice-bag to the head. If this fails, morphine should be employed in sufficient quantity to relieve the headache and enable the patient to sleep. For relief of the muscular pains Lebert recommends rubbing with a mixture of equal parts of oil and spirit of chloroform. The bowels should be moved at the commencement of the attack with a single dose of calomel and sodium bicarbonate, or Avith small doses of calomel repeated every half hour until a grain and a half or two grains have been given, and followed by a saline in the morning. Later in the disease hydragogue cathartics may be administered to keep the bowels open, but care should be taken not to push their action too far. If there is diarrhoea, it should be stoj)ped by the use of opium, bismuth sub- nitrate, and astringents. The diet should consist of nutritious and easily digested foods. Further than this, no special precautions need be taken in the majority of cases. Should the j)atient's appetite be voracious, there is no objec- tion to gratifying it within reasonable limits. Patients who are badly nourished and ill fed should be placed ujjon a generous diet imme- diately. Sponging the body with tepid or cold water or the use of the cold bath is the best means of controlling the temperature. Internal anti- pyretics are not to be recommended, because of their depressing action on the heart. If delirium is present, the bromides and chloral should be used to control it. Symptoms of uraemia demand the active employment of measures to promote the excretion of urea. Murchison advises that one or two drachms of potassium nitrate, one drachm of dilute nitric acid, and half a drachm of the tincture of digitalis be taken in divided doses dur- ing the twenty-four hours. The infusion of digitalis, combined with potassium acetate, potassium citrate, or sweet spirits of nitre, will be useful for this purpose. Water should be taken freely, and copious perspiration should be induced by means of hot-air or vapor baths. TREATMENT. 265 Hv(lragot>ue cathartics may be used to cause a vicarious excretion of urea by the intestines. In old and otherwise debilitated subjects stimulation with alcohol should be commenced at the first indication of enfeebled heart action. Sudden collapse demands the free hypodermic use of stimulants, such as ether, nitroglycerin, strychnine, and camphorated oil (camphor 1 part, olive oil 8 parts). During the intermission the patient must be watched for fear that some complication may develop. It may not be necessary to confine him to bed, but it is advisable that he should remain indoors. If com- plications arise, they must receive appropriate treatment. Parotiditis should be treated with hot or cold applications, whichever is the more agreeable to the patient. As soon as suppuration is detected a free incision must be made, the pus evacuted, and the wound dressed antiseptically. The treatment during convalescence may be summed up as follows : a generous diet, tonics, and a moderate amount of alcohol with meals. Bitter tonics before meals, ale, porter or port wine with meals, and iron after meals will hasten the recovery of the patient. YELLOW FEVER. By GEORGE M. STERNBERG, M. D., LL.D. Definition. — Yellow fever is a specific infectious disease in which one attack, as a rule, protects from subsequent attacks. The febrile paroxysm inaugurating an attack usually lasts from two to five days, and is followed by a period of great depression of the vital powers, during which there is a tendency to suppression of urine and to passive hemorrhage from mucous membranes. The urine contains albumin, the skin has a more or less pronounced icteric hue, and in fatal cases "black vomit" is usually ejected before death. Etiology. — Yellow fever is not a contagious disease in the strict sense of the word — ^. e. it is not usually contracted by contact with the sick — but, as in cholera and in typhoid fever, the infectious element multiplies in the body of the sick, and epidemics usually extend from foci of infection originating from the introduction of cases of the disease into localities previously free from it. Although not definitely demon- strated, it seems extremely probable that this occurs in the same way as in the diseases mentioned — viz. through the excreta. This is indicated by the fact that while contact with the sick as nurse or physician does not lead to infection, the soiled clothing and bedding of yellow fever patients may induce an attack in those who handle them, and may orig- inate an epidemic when transported, without having been disinfected, to another locality. When yellow fever prevails as an epidemic, physi- cians and nurses are very liable to contract the disease because they are necessarily exposed in the infected localities, not because they come in contact with sick. This is an important fact which is established by abundant evidence, and yet it is denied by many physicians living in cities where the disease is endemic, who insist that the disease is trans- mitted by personal contagion. This opinion no doubt arises from the mistaken assumption that successive cases in the same house or neigh- borhood are directly connected in their etiology one with another, as commonly occurs in the strictly contagious diseases — e. g. smallpox or measles. On the contrary, they all contract the disease from a common and external source — the infected locality. It is well known that cer- tain local and climatic conditions are essential for the development of the infectious agent (" germ ") outside of the human body, and the con- sequent establishment of an external focus of infection and the epidemic prevalence of the disease. On the contrary, we have numerous obser- vations which show that the introduction of cases or of fomites into localities where conditions are not favorable for the external multipli- cation of the infectious agent does not result in the occurrence of other 267 268 YELLOW FEVER. cases in the vicinity, as would follow if the disease was propagated by personal contact. This is well illustrated in the city of Mexico, and at Petropolis, a health resort in the mountains a few hours' journey from Rio de Janeiro. Yellow fever is endemic at the sea-coast city of Vera Cruz, and during the summer months persons from the interior who visit this infected locality are very likely to contract yellow fever. Persons coming from the city of Mexico for a short visit on business or pleasure frequently fall sick with the disease after their return to their homes, but they never communicate it to those associated with them, and no focus of infection is developed as a result of their pres- ence in the crowded and rather dirty capital city, which is located at an elevation above that at which the infectious agent is able to propagate itself outside of the body of the sick. The same is true as regards Petropolis, which is a health resort during the epidemic season for unacclimated persons residing in Rio de Janeiro. Communication between the two places is unrestricted, and individuals exposed in Rio not infrequently fall sick in Petropolis, but they never communicate the disease to others. This is also the experience of physicians in charge of hospitals located in healthy suburbs of infected towns. So long as the hospital and its vicinity remain uninfected, cases do not originate in its wards as a result of the admission of yellow fever cases, although these may be cared for by susceptible attendants and treated in the same wards with patients suffering from other diseases. " In his report upon the camps established near Memphis in the epidemics of 1878 and 1879, Colonel Cameron makes the following statement : ' It was found necessary that the officer in authority should set an example of constant indifference to attack in order to appease, as far as possible, the constant anxiety of the population under his charge. Especially was this true in 1878, as depopulation went on slowly that year, and infected people poured daily into the camps from the more pestilential portions of the city. Very many reached camp Avith the fever on them, so that as many as seventeen persons fell victims in one night, not a few in their tents. In no instance, however, did they com- municate the disease to their families or bed-fellows, as far as could be traced.' " In the same epidemic (1878), Dr. Minor reports that over thirty cases were discovered among refugees in Cincinnati, O., and says : ' No physician or nurse contracted the disease, and in no instance did it exhibit any tendency to spread.' The same was true in Nashville the same year ; twenty imported cases occurred in different parts of the city without any local cases resulting from them. Evidence of this kind could be extended to fill a volume ; but sufficient has been pre- sented to establish the statement made, and the reader may be referred to the ' proofs of non-contagion ' in the second volume of the classical work of La Roche (pp. 236-566.)" ' Formerly many of those who denied that yellow fever could be transmitted by personal contagion assumed that it could not be trans- mitted, and ascribed outbreaks to local insanitary conditions, together with the favorable meteorological conditions recognized as essential for ^Quoted from the writei-'s article on Yellow Fever in Wood's Mefereiice Handbook of the Medical Sciences, vol. viii. p. 55. ETIOLOGY. 269 the development of an epidemie. These l)elievers in the " loeal oritrin " of the disease denied the neeessity for isolation of the siek and qnaran- tine restrictions, while the " contagionists " insisted upon the exotic origin of the disease and its transmissibility by ships, persons, and fomites. That this latter view is correct is beyond question, although, as we have shown, the disease is not usually communicated by personal contact, and favorable external conditions are as essential for the devel- opment of an epidemic as is the introduction of the specific infectious agent. As heretofore suggested, the yellow fever patient, like the patient with cholera or typhoid fever, probably carries " germs " in his intes- tine which are capable of abundant development outside of the body when loeal conditions are favorable. As to the specific germ, we have no exact information, inasmuch as all attempts to demonstrate its jDi'es- ence in the bodies of the sick or to isolate it from the excreta have been unsuccessful. But the conditions favorable for its development are well established. Yellow fever is endemic at certain places upon the sea-coast of Xorth and South America and the islands in the Gulf of Mexico, and from these places it is disseminated by human intercourse. Epidemics com- monly develop as a result of the arrival from an infected locality of an individual who has been taken sick en route or after his arrival. But they may originate from the introduction of infected articles, independ- ently of any imported case. The origin of several epidemics has been traced, with great probability, to the unloading of earth ballast from the vicinity of an infected city upon the wharves of a healthy seaport during the season favorable for the development of the disease. As a rule, some time elapses after the introduction of a case or of " fomites " before the outbreak of a local epidemic. This interval varies according; as local conditions are favorable or otherwise for the development of the infectious agent. Yellow fever is essentially a disease of the sea-coast, and especially of large cities in an unsanitary condition, but when circumstances are favorable it may extend into the interior, following routes of travel, and especially navigable rivers. It is, however, confined to the lower levels even in tropical or sub- tropical regions. In the Antilles the disease rarely prevails at an alti- tude above 700 feet. In Mexico the cities of Orizaba, Jalapa, and Puebla, which are more than 3000 feet above the sea level, have never suffered from the disease, although they have unrestricted communication with the infected seaport. Vera Cruz. In Spain, where several severe epidemics have occurred, the disease has rarely prevailed at an altitude above 1000 feet. The epidemic at Madrid (altitude 2000 feet), which occurred in 1878, was, how^ever, an exception to this rule. In the United States a severe epidemic occurred at Chattanooga, Tenn., in 1878. This town has an altitude of 745 feet, which is the highest point at which the disease has prevailed in this country. Temperature is an essential factor in determining the prevalence of yellow fever in those places where it is endemic and in the establish- ing of new centres of infection. Although the disease prevails to some extent throughout the year in the cities of Havana, Vera Cruz, and 270 YELLOW FEVER. Rio de Janeiro, it is especially prevalent during the hot season in these cities, and its epidemic extension occurs only in the summer months. The seasonal prevalence in the city of Havana is shown in the follow- ing table, compiled by Chaille : ^ Mortality from Yellow Fever in the City of Havana for Ten Years, 1870 to 1879, inclusive {^Chaille). Month. January February- March . April May . . June . . July . . August . September October . November December 1870. 4 4 6 14 66 112 201 91 77 49 35 18 23 12 34 91 201 234 138 72 55 51 42 1872. 1873. 32 23 27 37 127 378 416 127 35 28 5 Total I 665 991 515 1244 1425 1001 il619 1374 1559 11444 1874. 7 4 18 22 85 172 361 416 186 91 42 21 1875. 16 16 32 34 1876. 32 103 142 1 292 187 675 144' 250 102 97 109 105 82 1877. 9 11 8 16 143 249 285 234 185 150 76 1878. 26 13 5 28 33 184 304 374 179 106 33 34 1879. 11 13 6 13 40 237 475 417 148 44 31 In places which have a mean winter temperature below 65° F. the disease, when introduced, cannot establish itself as an endemic. The development of an epidemic requires a temperature of 75° to 80° F., maintained for some time, and upon the approach of cool weather the progress of the disease is checked. When the temperature falls below the freezing point it is usually completely arrested, and, as a rule, the disease does not recur during the succeeding summer unless it is again introduced. Epidemics may terminate before the occurrence of cold weather simply because all susceptible persons in the infected area have suffered an attack of the disease. Under these circumstances the con- tinued activity of the morbific element (" germ ") is shown when " un- acclimated " persons venture to visit the infected locality ; and many lives have been sacrificed by the premature return of refugees to their homes in the belief that they could safely do so, as no new cases had recently occurred in the pest-stricken town. Atmospheric moisture and precipitation influence the development of yellow fever epidemics, and in arid, desert regions the disease is unknown. But while a certain amount of atmospheric humidity and soil moisture is essential, the disease has sometimes committed its greatest ravages during unusually dry seasons. Heavy rains by puri- fying the atmosphere and washing away accumulations of filth may exercise a favorable influence upon the progress of an epidemic. The trade winds of the tropics, and strong sea-breezes in general, are bene- ficial from a sanitary point of view, and places exposed to their con- tinuous action rarely suifer from the disease under consideration. They dilute and carry away the poisonous emanations from insanitary places, and refresh and invigorate those who inhabit localities exposed to their action. ^ Report to the National Board of Health, Washington, 1880. SANITARY CONDITIONS— BACTERIOLOGY. 271 The wind has little to do with the dissemination of the disease. This is shown by the faet that vessels which anchor some distance from the shore in the vicinity of infected places do not suffer i'rom the disease so long- as they are kept in a good sanitary condition and unacclimatized members of the crew are not permitted to go on shore, while vessels lying at the wharves are very liable to become infected. The board of experts appointed by Congress to investigate the epi- demic of 1878 arrived at the following conclusion : "We know of no instance, either from our own observations or from i\\Q published records of yellow fever, in which it has been established that the disease has been carried to any considerable distance by atmospheric currents or by any modes or vehicles of conveyance other than those connected with human traffic and travel." Sanitary Conditions. — When the infectious agent is introduced by the sick or by means of fomites to localities in the " yellow fever zone " during the season favorable for the epidemic prevalence of the disease, its propagation without doubt depends largely upon local insan- itary conditions, and it is doubtful whether it could effect a lodgement in a clean and well paved city. Its epidemic prevalence in New York and Philadelphia during the latter part of the last and the early part of the present century was during a period when these cities were for the most part unpaved, unsewered, and unclean. And it is in similar localities in the cities now most subject to invasion that it usually first appears and most persistently remains. In Havana, Rio de Janeiro, and other endemic foci of the disease it is especially prevalent in low- lying, filthy districts with unpaved streets. Organic matter of animal origin in a state of decomposition appears to afford a favorable nidus for the germ, and the accumulation of fecal matter in exposed situations is favorable to the development of an epidemic. Reasons have already been given for the view that the excreta of the sick contain the specific infectious agent. Dr. Parkes, the English hygienist, maintained the fecal origin of the disease. He says : " To use a convenient phrase, yellow fever, like cholera and typhoid fever, is a fecal disease. And here we find the explanation of its localization in the West India bar- racks in the olden time. Round every barrack there were cesspits, often open to sun and air. Every evacuation of healthy and sick men was thrown into, perhaps, the same places." One method by which infectious material may be transported from such exposed filth-beds to the stomach of individuals living in the vicinity has recently attracted considerable attention in connection with the propagation of cholera. This is through the agency of flies, which may come directly from a cesspool to the kitchen or dining-room, and there contaminate articles used for food or drink. In this connection, however, it is well to call attention to the fact that the epidemic preva- lence of the disease has never been shown to depend upon the use of a contaminated water supply, as is the case in cholera and typhoid fever. In cities having a common water supply the disease is not generally diffused at the outset of an epidemic, but it extends rather slowly from certain infected foci to which it has been introduced in the first instance or subsequently. Bacteriology. — We have seen that the development of a yellow 272 YELLOW FEVER. fever epidemic depends upon conditions external to the human body- relating to temperature, filth accumulation, etc., and in the present state of science we are justified in the inference that the specific infectious agent which multiplies in presence of such conditions is a living micro- organism of some kind. But the morphological and biological charac- ters of this hypothetical germ have not yet been demonstrated. This assertion is based upon the personal investigations of the writer made in Brazil, in Cuba, in Mexico, and in the United States in accordance with an act of Congress (1887) authorizing such an investigation. In my report^ of these investigations I have formulated my conclusions as follows : " The most approved bacteriological methods fail to demonstrate the constant presence of any particular micro-organism in the blood and tissues of yellow fever cadavers. "The micro-organisms which are sometimes obtained in cultures from the blood and tissues " (immediately after death) " are present in comparatively small numbers, and the one most frequently found (Bacillus coli communis) is present in the intestine of healthy indi- viduals ; consequently its occasional presence cannot have any etiolog- ical import " Having failed to demonstrate the presence of a specific germ in the blood and tissues, it seems probable that it is to be found in the alimentary canal, as is the case in cholera. But the extended researches made, and recorded in the present report, show that the contents of the intestine of yellow fever cases contain a great variety of bacilli, and not a nearly pure culture of a single species, as is the case in recent and typical cases of cholera. " Comparatively few liquefying bacilli are found in the faeces dis- charged during life or in the intestinal contents collected soon after death from yellow fever cadavers " Some of the micro-organisms present in the dejecta of yellow fever patients, as shown by stained smear preparations, have not developed in the cultures made, either aerobic or anaerobic. One extremely slender, filiform bacillus, which can only be seen with high powers, and which is quite abundant in some of my preparations, has never been obtained in the cultures made, and no doubt there are others in the same cate- gory. " That the yellow fever germ is strictly anerobic, or that it will only grow in a special nidus, may be inferred from certain facts relating to the extension of epidemics." It may eventually be found that the micro-organism which produces this disease belongs to an entirely different group from the bacteria : we are disposed to believe, however, that it is an anaerobic bacillus which multiplies in the intestines or in fecal accumulations outside the body, and which produces a deadly toxin (toxalbumin ?) to which the phe- nomena of the disease are due. In view of the facts heretofore recorded and the conclusions reached as a result of experimental investigations it is evident that the dejecta of yellow fever patients should be regarded as infectious material, and 1 Report on the Etiology and Prevention oj Yellow Fever, Government Printing OiEce, Washington, 1890. SUSCEPTIBILITY AM) IMMUMTY. 273 should never be thrown into privy vaults or u]ion tiic soil until they have been completely disiufeoted. SlTSCEPTlBiLiTY AND IMMUNITY. — When vellow fcver prevails as an epidemic all persons exposed \vithiu the int'eeted area who have not previously suflt'ered an attack are liable to contract the disease. But there is considerable diti'erence in the susceptibility of individuals, and the negro race is generally believed to be less susceptible than the white. This is manifested, however, by the comparatively mild character of the attack rather than by an immunity from the disease. According to La Roche, the mortality among the whites on the island of Jamaica was 102 per 1000, and among the blacks 8 per 1000 ; in the Bahamas the mor- tality of the whites was 59 per 1000, that of the blacks 5.6 per 1000. In the great epidemic of 1878 the negroes appear to have furnished a considerable proportion of the cases, and in certain localities the mortal- ity among them was considerable. Thus at Brownsville (Tenn.) 162 cases with 21 deaths occurred among the colored population ; at Chatta- nooga, in a total of 685 cases, 429 were colored and 256 white, while the mortality among the blacks was 46 and among the whites, 118 ; at Decatur (Ala.) 64 cases and 28 deaths occurred among the whites, and 186 cases with 21 deaths among the blacks. The natives of northern latitudes are generally believed to be more susceptible than those born in tropical or subtropical countries, and the mortality among the fair- skinned natives of the North is higher than among natives of Southern Europe. Blair, as a result of observations made in Guiana, says : " The lower the winter temperature in the native country of those attacked, the more severe w^as their sickness ; so that, wdiile the mor- tality among West Indians amounted to only 6.9 per cent, of the sick, it rose to 17.1 among the Italians and French, 19.3 among the English, 20.2 among the Germans and Dutch, and 27.7 among the Scandinavians and Russians." The mortality among the indigenous races of the West Indies and of those parts of North and South America in which the disease pre- vails occasionally or habitually, and of Mongolians living in these regions, is also less than among the whites ; but none of these races have an immunity from attack. A single attack of yellow fever usually protects from subsequent at- tacks, especially if the individual continues to reside in one of the endemic foci of the disease. While second attacks are comparatively rare, and some authors of experience have asserted in positive terms (Blair and others) that they never occur, there is ample evidence that one attack is not always protective. Thus, "Dr. Jackson states that in Spain, during the epidemic of 1820, 20 Avell authenticated instances came within his knowledge of persons being attacked Mdio had had the dis- ease before." Dr. Wragg, speaking of the epidemic in Charleston in 1854, says : " Six of these w^ere so well proved as to admit of no doubt on the subject. Some of the patients were identified as having gone through the fever in this (the Roper) hospital in 1852, throwing up black vomit on both occasions " (La Roche). Dr. Rush also observed second attacks in Philadelphia in persons who had suffered a compara- tively mild first attack. In localities such as Havana and Rio de Janeiro, w^here yellow Vol. I.— 18 274 YELLOW FEVER. fever has established itself as an endemic disease, the adult native pop- ulation enjoys an immunity which is almost absolute, and has been supposed to be hereditary. This view, until recently, was generally accepted by physicians residing in these endemic foci of the disease. There is, however, accumulating evidence that the immunity enjoyed by "Creoles" is not inherited, but results from a mild and usually unrecog- nized attack during infancy or childhood. Dowler, writing of the epi- demic of 1853 in New Orleans, says : " Many creole children had, during the epidemic of 1853, a fever, a slight fever — yellow fever, if vou please, known as such rather by the coexistence of the epidemic than from any severe symptoms among these children — a slight fever never yet described, having generally but one paroxysm, lasting from six hours to one, two, or three days, scarcely ever requiring medication. That a few of these cases acquired an alarming violence, and even proved fatal, is most true, most deplorable." Hinemann writes with reference to Vera Cruz : " Until lately the phvsicians and people of Vera Cruz supported with fanaticism the dogma that natives were absolutely exempt from yellow fever. But the fearful epidemics of recent years (1875, 1877, 1878) have worked a change, for so many native children and adults suffered that the truth could no longer be denied that these do not enjoy an absolute immunity." In Cuba the dogma that Creoles are exempt from yellow fever did not withstand the searching investigation made by the Havana yellow fever commission of 1879. In the epidemic of 1887 at Key West the children of " acclimated " Cubans, natives of Havana, born since the arrival of their parents at Kev West, showed the same susceptibility to the disease as other chil- dren. The recent investigations of Guiteras also give strong support to the view that the immunity of adult Creoles results from an unrecog- nized attack occurring during childhood. Blair, speaking of the epi- demic in British Guiana (1851-54), says : " Infancy was one of the most favoring causes of the action of the yellow fever poison. The constitution of the new-born or young white creole was highly suscepti- ble. He or she was truly in the category of new-comers." The great susceptibility of new-comers who without previous " ac- climatization " are exposed during the prevalence of an epidemic is generally recognized in those places where the disease is endemic ; and, on the other hand, persons who have resided for some time in an infected locality seem to acquire a certain degree of immunity independently of an attack of the disease. The fact that foreigners may remain for years in Havana, in Rio de Janeiro, and other endemic foci of the disease without suffering an attack is well established. But those who have escaped for several years are liable to be attacked during a season of unusual epidemic prevalence. The disease is, hoAvever, less fatal in such cases than among unacclimatized strangers. Owing to the immunity acquired in childhood or by long residence in the infected area, yellow fever is a disease of minor importance among the native population in cities where it is endemic. This is shown by the following figures : In the citv'- of Rio Janeiro, which has a popu- lation of 400,000, the mortality from some of the principal causes of PATHOLOGICAL ANATOMY. 275 death in the year 1886, an ejiiiU-niic year so far as yellow fever is con- eerned, was — from tubercnlosis, 2077 ; diseases of the circulatory appa- ratus, 1458 ; diseases of the cerebro-spinal system, 1345 ; diseases of the dig-estive apparatus, 1097; malarial diseases, 1086; yellow fever, 1015. In the same year (1886) more than twice as many deaths among; the civil population of Havana resulted from tuberculosis as from yellow fever. That the immunity enjoyed by the poj)ulation of the infected cities mentioned is not due to climate, j)er se, is shown by the fact that country people living in the same latitude readily contract yellow fever when they visit these cities during the epidemic season ; also by the fact that when the disease w'as first introduced to Rio JTinciro in 1849 the native population gave no evidence of immunity, and for several years the mortality among them was considerable. The susceptibility of males and females probably does not difi'er materially, although a larger mortality occurs among males, because they more frequently and often recklessly visit infected localities, and because of the intemperate habits of some of those who fall victims to the disease — e. g. sailors and soldiers. A recent debauch is generally recognized as a predisposing cause. Pathological Anatomy. — An inspection of the exterior of the body of an individual who has recently succumbed to yellow fever fur- nishes indications which should at once arouse suspicion as to the nature of the disease, especially in localities where it is known to prevail. The integument presents an icteric hue which differs from the saffron yellow color of jaundice and is due to blood pigment. It resembles the color which is seen to follow a bruise causing an effusion of blood into the tissues, and is less intense and less uniformly distributed than the yellow produced by bile pigments. Moreover the depending portions of the body, as a result of hypostatic congestion and pressure, have a deeper coloration and are more or less livid and mottled. That this appearance is due to pressure and position is shown by the fact that "when the body is placed upon the side or abdomen soon after death, the most dependent part still shows this livid and marbled appearance. The face often has a livid and turgescent appearance, like that of a person recently drow^ned, or the face and hands may appear cyanosed. The lips or gums are often soiled with dark blood as a result of passive hemorrhage during the last hours of life, and a little stream of black fluid may frequently be seen trickling from the corners of the mouth or nostrils. This is the so-called " black vomit," which flows from the distended stomach or is forced out by an accumulation of gas in the intestine. Cadaveric rigidity is established soon after death. In the warm latitudes where the disease habitually prevails putrefactive decomposition quickly occurs, and unless the autopsy is made within a few hours after the fatal termination of a case, postmortem changes are likely to complicate the pathological appearances resulting from the disease. The blood in yellow fever presents no changes which can be recog- nized by a microscopical examination during the progress of the case or immediately after death, but there is a certain degree of disorganization of the red corpuscles in severe and fatal cases, as is shown by the yellow color of the serum from the presence of free haemoglobin. This may 276 YELLOW FEVER. be observed in blood drawn as early as the third or fourth day, but is much more pronounced in that obtained from the large vessels and cavities of the heart after death. The serum obtained from blisters in advanced cases also has a yellow color. That this is not due to bile pigments is shown by the chemical researches of Cunisset and others. Blood drawn during life does not coagulate readily, or the coagulum is soft and loose, and the blood in the heart and large vessels after death is usually fluid and dark colored. The cavities of the right side of the heart may, however, contain soft coagula, and the right ventricle sometimes contains a more or less decolorized flbrinous clot. The " disorganized " and diffluent condition of the blood has been supposed by some to account for the passive hemorrhages which are so charac- teristic of the disease. But it is evident that if the capillaries and larger vessels were intact no escape of blood could occur as a result of its loss of coagulability. The hemorrhagic tendency is rather to be ascribed to changes in the walls of the small vessels and capillaries which weaken their resistance to pressure ; and several competent observers agree that the walls of these vessels undergo a fatty degen- eration. Upon removing the calvarium the brain and its meninges are usually found to give evidence of congestion. The pons and medulla are espe- cially hypersemic. The surface of the brain often presents little hem- orrhagic points and its substance is tinted yellow. There is usually some effusion into the ventricles and in the subarachnoid space, the fluid being of yellow color and sometimes turbid. Schmidt of New Orleans has described certain changes in the sympathetic ganglia tO' which he attaches importance. These consist in a disappearance of the nuclei from most of the ganglion cells, and in a " peculiar fatty lustre"" which they presented, even in specimens mounted in balsam. The lungs occasionally contain hemorrhagic infarctions, and are hypersemic, otherwise they present no evidence of pathological change. The heart has been described by some authors as soft and friable. I have not observed this, and no evidence of fatty degeneration was found in slides mounted by Guiteras (1879), whose autopsies were made very promptly after death. On the other hand, Schmidt and Riddel believe that the muscular fibres undergo a fatty degeneration. The pericardium frequently contains a considerable quantity of yellow serum. Upon opening the ca^'ity of the abdomen the most important and characteristic pathological appearances will be found. The stomach almost always contains a considerable quantity of a grumous black fluid similar to that commonly ejected during the last hours of life — " black vomit." There is no mystery as to the nature of the pigment in this black fluid. It is undoubtedly blood pigment more or less changed by the acid secretions of the stomach. The writer has repeat- edly verified the presence of numerous decolorized blood corpuscles by microscopical examination. These are often massed together in little clumps, and brownish pigment granules are seen attached to these masses or in their vicinity. The pigment is not dissolved in the fluid, but is present in the form of granules which are insoluble in water ; consequently, the spectroscope fails to demonstrate the presence of PATHOLOGICAL ANATOMY. 277 blood pi>iniont. But wIk-ii the black matter is dissolved in aeidified aleoliol a positive result may be obtained. Freire and others have imagined that this blaek pigment is a product of the vital atttivities of some micro-organism. But this view is entirely without scientific foundation. By adding some drops of hydrochloric acid to blood diluted with water a dark fluid is obtained which does not differ in appearance from the black vomit ejected l)y yellow fever patients (Dantes). The mucous membrane of the stomach shows patches of congestion, and occasionally small red spots resemljling ecchymoses, which, according to Schmidt, consist of "an unbroken network of minute vessels congested with blood and identical with the network of large capillaries which surrounds the aperture of the gastric glands." The congested patches present no uniformity, the number and extent differing in different cases. Some authors have supposed that the most important pathological changes in yellow fever occur in the stomach, iind that the disease is essentially an infectious gastritis. Crevaux thinks that the most important lesion consists in a fatty degeneration of the cells which line the gastric glands and of the capillaries of the mncous membrane. In specimens obtained at some of my own autop- sies in Havana, placed in alcohol very soon after death, there is evi- dence of inflammation in a certain proportion of the cases. This is shown by the presence of collections of leucocytes in the submucous coat. But this appears to be rather exceptional than otherwise. The small intestine, and especially the ileum, often contains a blaek fluid similar to that found in the stomach or, more frequently, a grumous, black material which consists of mucus and blood pigment and is smeared over the mucous coat of the gut. This usually comes from the stomach, but in some cases is due to a passive hemorrhage from the mucous membrane of the intestine itself, which is sometimes uniformly red as a result of hypersemia or may present arborescent patches of congestion similar to those seen in the stomach. The large intestine occasionally shows a like appearance, but is usually normal. The liver presents the most constant and characteristic pathological changes. As a rule, it is of a pale yellow or brownish yellow color, like that of new leather in its various shades, and contains comparatively little blood. But it is sometimes livid and gorged with blood, present- ing a dark blue or purple color. This is especially apt to be the case when death occurs after a very brief illness — two or three days. As the victims of chronic alcoholism are especially apt to succumb to an attack of yellow fever, evidence of interstitial hepatitis is not infre- quently found associated with the lesions characteristic of yellow fever. The dimensions of the liver, except in comparatively rare cases in which it is gorged with blood, do not differ materially from the normal. The parenchyma is more or less friable and easily torn, owing to the fatty change in the cells. On section the liver tissue is found to be drier than normal and to present the " boxwood " or " new leather " color characteristic of the disease, unless death has occurred during the stage of hypersemia, which probably usually precedes that of anemia and fatty degeneration. The cells are not uniformly changed, but areas of greater or less extent are seen in which they are infiltrated with fat globules. These are of vart-ing dimensions, and one or several may be 278 YELLOW FEVER. contained in a single cell. The nuclei often remain intact in these cells infiltrated with fat, but, according to Schmidt, '' a great number of nuclei may also undergo fatty degeneration." Not infrequently the central vein is surrounded by normal cells, while those cells about the periphery of the lobule contain many fat globules. In two of the livers brought back from Havana by the Yellow Fever Commission of 1879, in which there were evidence of cirrhosis, Woodward found that, in addition to the fatty change described, " an abundant infiltration of leucocytes was observed, not merely in the abnormally developed interlobular connective tissue, but also in the parenchyma of the lobules." I have also found a rather extensive infiltration of leucocytes in two cases, and in one of these a veritable necrosis of the cells had occurred in limited areas in the vicinity of the infiltration. Councilman, who made a careful study of material ob- tained at my autopsies in Havana (1888, 1889) discovered a form of necrosis in the interior of the cells not previously described. He says : " The most interesting results were obtained from the examination of the liver. It has long been held that fatty degeneration of this organ was one of the most characteristic lesions of yellow fever, and it was found to a greater or less extent in all of the sections examined. It varied greatly in intensity in the diiferent cases ; in some comparatively large areas of liver tissue, which showed very little degeneration, were found ; in others only here and there a few normal liver cells were seen. This lesion, however, does not seem to me to be the most important one of the organ. When sections of the liver are deeply stained with eosin and subsequently with a nuclear stain, either hsemotoxylin or methylene blue, a very peculiar appearance results. When such sections are examined with a low power the liver cells are found to be stained a faint reddish blue or purple color, the nuclei being a deep blue or purple. Among the liver cells or in place of them a great number of bodies stained intensely red with the eosin are found when examined with a high power. These bodies are found to differ entirely from the liver cells. They are sharply circumscribed, are highly refractive, and are composed of a perfectly hyaline mass containing numerous vacuoles. Their size varies greatly ; in some cases they are no larger than a leucocyte, in others as large as two liver cells. They are found enclosed in liver cells otherwise perfectly normal, and in some cases they entirely take the place of these in the liver beam-work between the capillaries. In some cases examined they apparently made up the mass of the tissue, only here and there a portion of a liver cell or a nucleus of such being seen. Sometimes, especially where the liver tissue was most scanty, along with these definite circumscribed masses more or less granular material was found which stained in the same way. These bodies were generally round or more or less irregular in form. In some of the liver cells small hyaline masses staining in the same way were found which were not so sharply circumscribed as the larger bodies. They were found most abundantly in the cases where the fatty degeneration was most extreme, but the most striking pictures were obtained where the liver was least altered. " In a few instances liver cells were found which only differed from the normal in being more coarsely granular, the granules staining with PATIIOLOaiCAL ANATOMY. 279 eosin, but not so distinctly as the cosin-stainino- bodies, and the nucleus stained more faintly blue than the nuclei of the surrounding liver cells. In most cases these bodies were without any nucleus ; in others a nucleus was present. This always was at the periphery, and fjenerally took the lono- irregular form of the nucleus of a wandering- leucocyte. Polynuclear leucocytes Avere numerous in all the livers examined. In some cases there were well-defined groups of them in the capillaries and in the liver beam-work between, and as it seemed often in the red- stained bodies. In several specimens there were hemorrhages in the liver, large areas being occupied by red blood corpuscles, between which the red bodies were often seen. This peculiar condition of the liver is possibly made more clear by staining the sections deeply with picrocarmine. In sections so treated these bodies stain an intense bright yellow with the picro-acid. Concerning the nature of these bodies there can be little question. When first seen it was thought that they were probably some form of lower organism, possibly amoebse, but a more extended study showed that this could not be so. Bodies in all respects similar to them were found in rapidly advancing cases of cirrhosis of the liver, in phosphorus-poisoning, and in other cases of rapid fatty degeneration, but they are particularly found in cases of acute yellow atrophy of the liver. Areas were found in sections from this which were very similar to the advanced cases of yellow fever liver. It must be considered that in yellow fever, along with the fatty degen- eration, there is a necrosis of the liver cells which sometimes affects only portions of the cells, at others the entire cell. Almost every change leading up to the formation of these bodies could be seen. The exact relation of the fatty degeneration to the necrosis could not be determined. The necrotic masses were found both in intact liver cells and in those which had undergone fatty degeneration. In the latter cases it seemed probable that the necrosis preceded, or at least accompa- nied, the degeneration. If it only represented a necrosis of the small remnant of cell protoplasm between the fat drops, it is difficult to see how so large a body could be formed from this. When the necrotic masses were found in the liver cells they were nearly always at the periphery of the cell next to the capillary." ^ The changes in the kidneys are those produced by an acute paren- chymatous nephritis. The macroscopic examination does not reveal any marked variation from the normal appearance, except that when a fatal termination has occurred after a very brief illness they may be found hypersemic and of a deep red color. The observations of Cre- vaux, Schmidt, and others indicate that there is always a brief period of congestion in advance of the changes in the renal epithelium. Small hemorrhagic foci are not infrequently seen beneath the capsule or in the cortical substance, and little globular hemorrhagic points have been observed on section which proved to be the distended capsules of the glomeruli. In thin sections, properly prepared, the renal epithelium is found to have undergone degenerative changes to a greater or less extent, and in places complete degeneration has occurred. Sometimes whole bundles ^Quoted from the writer' s Report upon the Etiology and Prevention of Yellow Fever, "Washington, 1890, p. 152. 280 YELLOW FEVER. of tubes are denuded of their epithelium and are empty. These changes are most marked in the tubules of the labyrinth. Councilman describes the changes in the cells as follows : " The cells often contained larger and smaller fat drops, shown by the clear spaces remaining after they were dissolved out by the alcohol, but the principal change was a hyaline degeneration of the cells. The cells contained an immense number of clear hyaline granules which stained more brightly with eosin. In the dilated tubules there were large and smaller, generally round, masses of similar hyaline material." Besides these hyaline masses there are also granular infarctions of the tubules, and others in which there is a mixture of granular debris and hyaline material. These correspond with the granular and hyaline tube casts found in the urine of yellow fever patients. Again, there are infarctions of another kind which attracted the writer's attention early in his investigations, but the exact nature of which has not been determined. The peculiarity of these consists in their form and in the fact that they are deeply stained by the aniline colors. They are made up of disk-shaped masses, irregular lobate clumps, or amorphous fragments. Councilman speaks of this as " colloid material," and says it is found in the loops of Henle and the collecting tubules. The writer has elsewhere suggested that these infarc- tions, which are stained by the nuclear staining agents, may be made up of the nuclei of cells which have undergone the hyaline degenera- tion described by Councilman. Another unexplained object which is not infrequently seen in sections of the kidney has a crystalline appear- ance and an irregularly circular or lobate outline. These bodies are highly refractive, and are marked by lines of fracture radiating from the centre to the periphery. They do not stain with any of the re- agents used in the preparation of sections for microscopical examination. Occasionally a considerable number of leucocytes may be seen in the tubules, and sometimes they contain red blood corpuscles. Councilman concludes his report of the examination of a series of sections which I submitted to him for examination, as follows : " The changes in both the liver and kidney appear to be due to a general toxaemia rather than to the local presence of infectious agents. They are diifuse, affecting the whole of the organs, and not small areas." We have heretofore suggested that the phenomena of the disease are due to the action of a deadly toxin formed, probably, in the intestine. My experiments in Havana (1889) show that "the material obtained from the small intestine of yellow fever patients at autopsies made soon after death is very virulent when injected beneath the skin of guinea- pigs." ^ The examination of the liver and kidney for micro-organmns has given results which correspond with those obtained by the method of cultivation. In those cases in which my cultures made from blood or liver tissue, obtained as soon as possible after death, gave a positive result, I have usually found the same micro-organisms in thin sections of the same material. In my report, heretofore referred to, I say : " A summary of these results shows that I have obtained micro-organisms in my aerobic cultures as follows : In blood from the heart, 4 times in 19 cases ; in the liver or kidney, or both, 13 times in 43 cases." Dr. Councilman, who carefully examined a series of thin sections ^ Report on Etiology and Prevention of Yellow Fever, Washington, 1890, p. 131. INCUBA TION.—S YMPTOMS. 281 j^ubmittod to him by n\v, says : " Bactoria of some sort were found in 28 of the 130 seetions examined; of these, IS were seetions of the liver, 8 of the kidney, and 1 eaeh of stomaeh and lymj)h ^land. There was notliinir in their form or rehition to the tissue that would lead one to suppose that tlu'ir presenee was otlier than aeeidental. In no ease <'Ouhl anv eonnection he shown between their presence and the essential lesions of the disease. In no case was there any lesion in the surround- ing tissue which could be attributed to their presence. Among the bacilli were some Avhicli agreed in form witli the colon bacillus." Intubation. — The period of incubation is comparatively short, iind probably never exceeds five days. Instances of attacks occurring inside of twenty-four hours after exposure are well authenticated. Several authors have insisted that the period of incubation may be prolonged to two weeks or more, but we believe this to be an error based upon a misinterpretation of the facts observed. Thus w^hen a <'ase develops on a shij) some time after leaving port, it does not follow that it resulted from exposure while on shore. On the contrary, such a •case is usually quickly followed by others, and is evidence that the ship is infected. Symptoms. — There are no constant or well defined premonitory .<. 61. 284 YELLOW FEVER. At the outset of the attack the face is flushed or congested and swollen ; sometimes in plethoric subjects it may be of a dusky violet color : this, with the deep red suifusion of the eyes which is commonly present in severe cases, together with the absence of any eruption, forms a striking feature of the first period of the disease. The countenance may be expressive of anxiety and pain, but is often dull and apathetic in appearance. Later, in fatal cases, the eyes often become sunken, the •eyelids ecchymosed, the brows contracted, and the features shrunken, or the face may be bloated and flabby. In mild cases the hypersemia of the conjunctivae and flushing of the face are of brief duration ; in more severe cases they often last through the febrile stage of the disease ; in rapidly fatal cases the eyes may remain deeply injected throughout. A faint yellowish tinge of the conjunctivae may usually be recognized by the third or fourth day ; this becomes more intense as the disease pro- gresses, and often lasts after convalescence is fairly established. The skin is sometimes hot and dry throughout the febrile stage ; more frequently it soon becomes moist, and free perspiration is readily induced by warm drinks and covering with blankets. During the sec- ond stage the skin is usually cool and moist, and when death occurs during this period of depression it is often preceded by a clammy sweat and coldness of the general surface of the body. In exceptional cases the skin remains hot and dry, and the temperature elevated up to the time of the fatal termination, which may be less than forty-eight hours from the inauguration of the attack. A peculiar odor given off" from the surface of yellow fever patients has been recognized by numerous physicians who have had experience in the treatment of this disease, but attempts to describe it have not been very successful. Kush compared it to the "washings from a gun," and Jackson says it is " sickly and faint, and not unlike the smell of a fish-market." The yellow color of the skin which has given the disease the name by which it is generally known among English-speaking people is not always present, or may be so slight as to be recognized with difficulty. In severe cases, however, it is usually seen toward the end of the febrile stage, and becomes more intense during the " stage of calm," lasting until convalescence is fully established and even longer. The color of the skin varies from a faint yellow tint to a deep orange or saffron yellow, or it may occasionally be a bronze or mahogany color. This yellow color is developed at a time when the urine is albuminous and free from bile, and without doubt is due to the presence of blood pigment in the liquor sanguinis and not to bile pigments. But in certain cases jaundice from bile pigments is developed at the end of the second period or during convalescence, and is accompanied by the presence of an abundance of bile pigments in the urine. In these cases the yellow color of the skin is more intense and lasts longer. The characteristic yellow discolor- ation, which coincides with the period during which hemorrhages are likely to occur, may first be recognized by a slight yellow tinge of the conjunctivae, of the face, and of the skin over the superficial blood- vessels. In fatal cases the cadaver presents a well marked yellow dis- coloration, especially the dependent portions subject to pressure, even when this was not noticeable during the last hours of life. .^Y^fPTO^fs. 285 Bereno;er-Fc'ran(l has noticed an crytlicniatons eruption about tlic scrotum in yellow lever })atients whieli he believes to be a cliurueteristic feature of the disease. Other eruptions mentioned by various authors as occasionally observed are erythematous patches about the knees and elbows, pustules about the mouth and elsewhere, petechite, furuncles, etc. The uritic is scanty even during the first period of the disease, and in fatal cases complete suppression occurs some time before death. The presence of albumin is so constant a symptom as to be ])roperly con- sidered a pathognomonic feature of the disease. In mild cases only a trace may be found during a brief period, but when frequent and care- ful tests are made it will seldom, if ever, prove to be entirely absent. In cases of moderate severity it is usually present in considerable quantity, especially during the second stage of the disease, when the amount of urine secreted falls to a minimum. In severe cases the coagulated albumin precipitated by heat or nitric acid frequently occu- pies one half the contents of the test-tube or even more than this. The deposit is usually sufficiently abundant after the second day to leave no doubt as to its character, and increases in quantity during the second period of the disease. The amount present is to some extent an index of the gravity of the attack. In a series of 16 non-fatal cases in which the writer (1875) made careful observations upon the quantity and specific gravity of the urine the following averages were obtained : Fluidounces. Spec. gray. First day 1023 Second dav 11.5 1025 Third day' 16 1028 Fourth dav 18 1022 Fifth day" 19 1022 Sixth dav 20 1022 Seventhday 22 1021 Eighth day 22 1019 Ninth dav ■ • • -23 1016 Tenth day 28 1013 Eleventh day 37 1011 Twelfth day 41 1013 It will be noticed that the amount of urine secreted gradually increased and the specific gravity diminished after the third day. When these two factors are considered together, it will be seen that the total solids excreted were about the same from the third to the eleventh day. The amount of urea eliminated by the kidneys is in inverse proportion to the severity of the attack, and corresponds closely with the quantity of urine. This is always considerably less than normal, and in severe non-fatal cases often falls to a few ounces in the twenty-four hours, while in fatal cases complete suppression usually occurs in from a few hours to twenty- four hours before death. According to Cuniset, the amount of uric acid, although reduced, is not diminished to the same extent as the urea. The urine, as a rule, has a decidedly acid reaction. Occasionally it contains blood as a result of renal or vesical hemorrhage. In non-fatal cases bile pigments commonly make their appearance in the urine about the time that convalescence is established. There is usually complete anorexia during the febrile stage, and in 286 YELLOW FEVER. severe cases this may last through the following period of depression ; but in mild cases the appetite usually returns with the disappearance of the fever, and the patient often at once enters upon convalescence. In cases of moderate severity, although the desire for food may return, the stomach is not able to retain anything but the simplest forms of liquid nourishment, and any indulgence of the appetite is likely to cause vom- iting and to lead to serious consequences. Thirst is constant during the febrile stage, and in a less degree during the succeeding period of depression, especially when there is copious and frequent vomiting. Voraiting frequently occurs during the febrile period, the vomited matters consisting for the most part of fluids ingested, containing in suspension flocculi of mucus from the stomach ; occasionally the fluid ejected at the outset of an attack has a yellow color from the presence of bile. The vomited matters almost always have an acid reaction. In cases which run a favorable course vomiting ceases, with the other dis- tressing symptoms, at the termination of the febrile paroxysm ; but in severe and fatal cases it is likely to return after an interval of twenty- four hours or more, during which the patient complains of a feeling of weight and discomfort in the epigastric region. This gastric distress may be slightly relieved for a brief period after the act of vomiting, although often nothing is thrown up but a few spoonfuls of a clear acid fluid. In other cases the amount of fluid ejected is considerable ; in severe and fatal cases this presents, in a more or less marked degree, the characters of "black vomit." At first the black pigment is usually seen in the form of a few little flocculi suspended in a transparent fluid ; in severe and fatal cases the number of these flocculi increases, and the vomited matters may present the appearance known as " cofiee-ground vomit," or they may be so numerous as to give the fluid a uniformly black color when first ejected. But upon standing this black vomit usually separates into two portions, the lower containing the black matter in suspension, while above this a transparent liquid is seen. Under the microscope the little pigmented masses are seen, by trans- mitted light, to have a yellowish brown color, and a careful examination shows that they contain decolorized blood corpuscles and granular leuco- cytes as well as the brownish pigment granules. In short, there is no doubt that the appearance of black vomit depends upon the escape of blood from the gastric mucous membrane into the cavity of the stomach. Occasionally there is a more active hemorrhage and the patient throws up pure blood. Recovery sometimes occurs after the characteristic black vomit has been ejected, although this is generally recognized as a very grave symptom, presaging death. The name " vomito " given to the disease in Spanish- American countries has reference to the dreaded black vomit, but is scarcely appropriate, inasmuch as a majority of the cases ending in recovery do not present this symptom. That the gastric mucous membrane is seriously implicated in the dis- ease under consideration is shown by a marked tenderness on pressure over the epigastrium, by the constant feeling of discomfort and pain in the epigastric region in severe cases, and by the tendency to passive hemorrhage above referred to. The bowels at the outset of an attack are apt to be somewhat consti- IJIA(;\0STS. 287 patcd ; later thov ofton romaiii t()r|)i:e from the mucous membrane of the small intestine. Occasionally there is more active iiemorrhaue and a (liseharj>:e of pure blood from the bowels. Hemor- rhag'es may also occur from the mouth, nose, bladder, or uterus, or even from the eyes and ears in rare cases. Epistaxis and oozing of blood from the gums, tongue, or lips is the most frequent form of hemorrhage after that from the gastric mucous membrane. The symptoms connected with the nervous system arc those which might be expected in a disease characterized by a febrile paroxysm and sui)se- quent stage of depression. At the outset, "when the fever is at its height, there is usually severe frontal headache and rhachalgia ; the patient is apt to be wakeful throughout the first stage, or his sleep is fitful and disturbed by distressing dreams ; his mind is in a state of tension, and he is anxious, watchful, and easily excited ; but, as a rule, there is no active delirium. Certain cases are characterized by sluggishness of mental action, apathy, and indiiference ; in others there are hallucina- tions and more or less incoherency of ideas ; occasionally there is active delirium, which may call for restraint in order to keep the patient in bed, but the intellect often remains unclouded throughout even in severe and fatal cases ; more frequently the fatal termination is preceded by a torpid condition of the mind with a disposition to somnolence, gradu- ally passing into complete coma. Occasionally death is preceded by convulsions, and tetanic rigidity of a more or less complete character has been noted as a rare occurrence. There is frequently great restless- ness, with deep sighing res])iration, often spasmodic in character. The respiration is accelerated during the febrile stage, but the respiratory apparatus is not implicated in this disease. In severe cases convalescence is often slow, and may be complicated by the occurrence of parotitis, abscesses, furuncles, hepatitis, or diar- rihoea. In mild cases, on the contrary, the patient frequently is out of bed and ready to resume his usual occupations within a day or two after the termination of the febrile paroxysm. Army experience shows that those attacked are rarely able to resume their duties in a less time than ten days or a fortnight from the date of attack, and that a consid- erable number must be retained in hospital a month or more, on account of the debility following a severe attack. Relapses are not infrequent as a result of some indiscretion com- mitted during the early period of apparent convalescence or during the second stage of the disease. Relapses are said to occur occasionally as late as from two to four weeks after the termination of the primary febrile paroxysm. Diagnosis. — A prompt diagnosis, especially of the first cases in an epidemic, is often a matter of very great importance. But notwith- standing the well marked clinical features of the disease and its charac- teristic pathological lesions, the diagnosis of early cases has often been a matter of dispute, even after the autopsy. This may be due to inex- 288 YELLOW FEVER. perience on the part of physicians encountering it for the first time, or to mistaken ideas as to the nature of the disease among those who have seen much of it, but have failed to recognize its specific character and to differentiate it from certain fevers of malarial origin encountered in tropical or subtropical regions. When a case of yellow fever is im- properly diagnosed as " bilious fever " or " remittent fever," and after the administration of several full doses of quinine at the end of three or four days the temperature falls to the normal, the diagnosis is sup- posed to be confirmed, and this defervescence, which is a characteristic feature of the disease, is supposed to have resulted from appropriate medication. If the case results fatally, the prejudice which so often goes with a positive but mistaken diagnosis sometimes leads to the asser- tion that the case was one of " pernicious malarial fever." Formerly a considerable number of the physicians in our Southern seaport cities maintained that yellow fever and the malarial fevers are closely allied if not identical diseases, and under this idea the milder cases in an epidemic were often called " malarial fever," and only those in which black vomit and a yellow discoloration of the skin completed the clinical picture of a severe case were recognized as yellow fever. Simi- lar mistakes in diagnosis occur not infrequently at the present day in some of the Spanish -American seaports where this disease is most prevalent. The fact that the early cases in an epidemic are sometimes of a mild character has led to much confusion in attempts to trace the origin of certain outbreaks. These early cases having been called by some other name, it is not until a typical severe or fatal case occurs that a diagnosis of yellow fever is made : this being considered the first case, the origin of the epidemic which follows remains a mystery, or it is supposed to have originated de novo as a result of insanitary conditions which it is not difficult to discover. There is nothing in the symptoms at the outset of an attack of yellow fever which will justify a positive diagnosis in the absence of a prevail- ing epidemic. The chill followed by fever, with flushed face, injected conjunctivae, full pulse, frontal headache, and lumbar pains, might mean smallpox or some other eruptive fever or an attack of one of the malarial fevers. But the eruptive fevers will soon be ruled out by the absence of an eruption ; intermittent fever, by the brief duration of the paroxysm and speedy return to a nearly normal state of health ; remittent fever after two or three days, by the difference in the temperature curve and the absence of albumin from the urine. It is true that in certain severe forms of malarial fever the urine may contain albumin, but this is not an early symptom in these cases, and does not greatly detract from the diagnostic value of this symptom. In yellow fever, even when the attack is of a mild character, a distinct deposit of albumin will usually be obtained by the third or fourth day, and in cases of moderate severity the precipitate will be so abundant as to justify a positive diagnosis as early as this (third or fourth day) when this symptom is considered in connection with the temperature, the pulse, etc. Or if doubt still exists, the symptoms which characterize the second stage of the disease will serve to differentiate it from those forms of malarial fever for which it has most often been mistaken. As an aid to diagnosis I introduce here nfA(;y(MSis. 289 scvt'i-al ti'iupcratuiv charts of typical cases which show tlie characteristic features of the febrile paroxysm : ] Kk i. 3 1. a! S liJ 1- DAY OF DISEASE I 2 3 4 5 6 7 8 9 10 11 12 13 14 1 2 3 4 5 6 7 8 9 10 11 12 13 14 103 \ V 102 \ \ 101 \ 1 100 Ce se 1 \ Case 2 99 \ u - 98 104 103 / [l L 102 \ V Ca se 3 / ■»«, Ca se 4 101 A V 1 1 1 100 ^ 1 \ / V I > 1 A A i 99 \ y.Kh J U \m WYl 98 ^ J V ^ V Y V y 1 105 ^ ■*! / ■/ 104 / ;V, 103 Cc se 5 W Ca se 6 102 / ' 101 \ \ \ \ 100 ^ iA \ / i. jT *> r \ 98 V !\ \ 105 A 104' r V\a y /^ \ 103' y I Ca se 7 1 Cc se 8 102' 1 \ri A K >» A 101 / V \ ,v V ^ looi V \ A / ^ 7 99 \ / / 4 ^ ^ 98 1 Cases Represented by Temperature Chaiis. Xo. 1. ^lild case of brief duration ; boy, aged three vears (Xew Orleans, 1873) ; reported by Dr. T. C. Faget. Xo. 2. Mild case of brief duration ; young female (Xew Orleans, 1873) ; reported by Dr. Touatre. Vol. I.— 19 290 YELLOW FEVER. No. 3. Protracted mild case ; male, aged twenty-seven years (Fort Barrancas, Fla., 1873) ; reported by Dr. Sternberg. No. 4. Typical case of moderate severity ; male, aged thirty-one years (Fort Barrancas, Fla., 1873) ; reported by Dr. Sternberg. No. 5. Typical severe case ; male, aged twenty-seven (Fort Barran- cas, Fla., 1873) ; reported by Dr. Sternberg. No. 6. Typical severe case ; male, aged twenty-seven years (New Orleans, 1873) ; reported by Dr. Layton. No. 7. Protracted severe case ending in recovery ; reported by Berenger-Feraud (French Antilles). No. 8. Fatal case ; death on ninth day ; male, aged twenty-eight (Fort Barrancas, Fla., 1873) ; reported by Dr. Sternberg. It is true that certain cases of malarial fever exhibit a temperature curve which presents considerable similarity to that of yellow fever, but as a rule "remittent fever" has a series of febrile paroxysms separated by more or less complete remissions, instead of a single paroxysm of several days' duration ending in defervescence, complete or nearly so. As regards the presence of albumin in the urine, the following obser- vations by Donnet, made during an epidemic in Jamaica, are of interest : In 61 cases, carefully studied, albumin was found for the first time on the first day in 2 ; on the second day in 11 ; on the third day in 19 ; on the fourth day in 14 ; on the fifth day in 6 ; on the sixth day in 4 ; on the seventh day in 4; on the eighth day in 1. The desquamative nephritis to which the presence of albumin is due is also shown by the presence of numerous granular casts in the urine, which may usually be found as early as the third or fourth day. If a diagnosis has not been made before, the symptoms which charac- terize the second period of the disease should serve to diiferentiate it from all forms of " malarial fever," properly so called. The cool and usually moist skin, the abnormally slow, soft pulse, the gastric distress and pain or pressure in the epigastrium, the yellow tinge of the conjunc- tivae, and the albuminous urine in a patient whose temperature is normal or subnormal, following a febrile paroxysm such as is represented by our temperature charts, certainly furnish a clinical picture which should be recognized. But experience shows that it frequently is not recognized, and cases which present the additional feature of black vomit have been called " hemorrhagic malarial fever," " pernicious fever," etc. It is true that severe cases do not always present the typical course which we have described : the temperature may remain a degree or two above the normal during the stage of depression ; the skin may be dry, and a reactionary fever of a remittent character may quickly follow the initial paroxysm ; but we still have the albuminous urine, the abnor- mally slow pulse, the yellow tinge of the conjunctivse, and in certain cases the hemorrhages so common in this disease — black vomit, etc. In addition to this there are other difPerences in symptoms which have more or less value. The tongue in yellow fever is usually narrow and pointed, with red margins, and is apt to be tremulous ; it is often com- paratively clean at the outset, and rarely presents the thick yellowish or brownish coating seen in remittent fever. The tongue in the mala- rial fevers is usually broad and flabby, and marked upon its margins by indentations made by the teeth. The yellow color of the skin in bilious DIAdSOSIS. 291 remittent fever is due to ii .stainin<>; by liilc pigments, and does not differ from that of simple jaundice ; it is more intense in color and more j)er- sistent than the yellowish tint seen in yellow fever : it should be remem- bered, however, that a true biliary jaundice maybe developed in xunx- fatal eases of yellow fever durinu- tlie jx-riod of convalescence. The spleen is not involved in yellow fever, while in the malarial fevers it is more or less swollen and tender. Vomiting of bili(»iis matter is a common symptom in severe forms of malarial fever ; in yellow fever it is rare, and only occurs, if at all, at the outset of the attack ; the vomited matters later are transparent and colorless. In yellow fever the amount of uric acid excreted is diminished, Avhile, according' to La Hoche, it is notably increased in remittent fever. Suppression of urine is a common feature in fatal cases of yellow fever ; it rarely occurs in bilious remittent fever. That form of fever which the French denominate jievre bilieuse meloiwrique, and which has been called " hemorrhagic malarial fever" by certain American authors, presents features which differ essentially from th(^se of yellow fever. These are well stated by Berenger-Feraud, as follows : " Prolonged residence in a malarial country is the most powerful, and, indeed, indispensable, predisposing cause. *' The disease is always preceded by numerous attacks of malarial fever, simple at first, then more and more complicated, and taking on in general more and more of a bilious aspect, producing a very decided anaemia. " Icterus appears at the outset of the attack, and is never wanting ; it gives from the commencement and throughout the attack a uniform yellow color to the patient, varying from greenish yellow to a decided yellow ochre. " The march is intermittent or remittent from the first, and the pulse, urine, and vomiting follow very exactly the variations of temper- ature. " The vomiting is bilious, of a decided green color ; it is a constant symptom at the outset of an attack, and is arrested with the termina- tion of one attack to reappear with the next. " After the first, or febrile, period the vomiting continues, but pre- serves the same characters ; it stains linen a bright green, and when collected in a basin it appears transparent and is of a beautiful emerald green or olive color. " The tongue is moist, broad, covered at first with a heavy white fur, which soon receives a greenish tint from the vomited matters. The tongue is not red, either upon its tip or edges ; it remains broad, heavily coated, and moist to the end of the malady. " The urine is black from the commencement, and its color is cha- racteristic, so that the patient himself is struck with it. It is usually abundant and frequently passed, and only has the melanuric aspect dur- ing the attack." Dengue, as regards its epidemic prevalence, somewhat resembles yellow fever. It is an acute, infectious disease, which prevails in those latitudes which are most subject to invasion by yellow fever during the season most favorable for the epidemic extension of this disease. It, 292 YELLOW FEVER. also, is characterized by a febrile stage of comparatively short duration, but the characteristic features of yellow fever are absent — albuminous urine, stage of depression, hemorrhages, etc. — and it is accompanied by severe arthritic and muscular pains which have led to its being called " breakbone fever." Moreover, there is usually a well marked eruption, resembling that of scarlet fever and commencing on the third day, and after the termination of the initial febrile paroxysm a second commonly occurs, accom])anied by a rubeoloid eruption which often ends in des- quamation of the cuticle. There is a wide difference also in the com- parative fatality of the two diseases. Dengue, although the most dis- tressing to the patient, is by far the least serious in its results, and rarely is the cause of death. Certain circumstances connected with the personal history of the patient will aid greatly in establishing an early diagnosis. A stranger in Havana or Rio de Janeiro during the epidemic season, who has an attack of fever presenting the symptoms described as attending the febrile stage of this disease, and whose urine is found at the end of two or three days to be albuminous, is sent without hesitation to the yellow fever hospital. And a person arriving at one of our seaports from an infected locality, presenting similar symptoms, would be isolated and placed under careful observation, even if the diagnosis was not at once established. But in a similar case, with no history of exposure in an infected locality, there is often doubt as to the diagnosis or an absolute denial of the possibility that the disease is yellow fever. When we hear of the prevalence of a " malignant form of malarial fever" in a seaport city located within the limits of yellow fever inva- sion, we are always justified in suspecting that the disease is in fact yellow fever. For malignant and fatal forms of malarial fever belong to the country rather than to the city, and cases of this kind do not occur in groups among the residents of a restricted area within the limits of a city. Even when a localized epidemic does not appear to be "malignant" in character, especially when it occurs among a native Creole or negro population, the fact of its prevalence in a large town or city is opposed to the view that it is of malarial origin — properly so called — and it is more likely to be yellow fever than anything else, unless, indeed, it should prove to be dengue. Prognosis. — Yellow fever is an extremely fatal disease, and even in apparently mild cases a guarded prognosis should be made, as they may suddenly assume a serious character. The prognosis is especially unfa- vorable in the case of plethoric persons and in those of intemperate habits. It is more favorable in women and children than in men — more favorable in the case of native Creoles and negroes, in warm lati- tudes where the disease prevails, than for recently arrived strangers from more northern latitudes. The writer's personal observations and studies have led him to attach great value to the temperature observations made during the first two or three days of the attack as a guide in prognosis. When the temperature of the body, as shown by a clinical thermometer placed in the mouth or axilla, does not go above 103° to 103^° F. during the first forty-eight hours, a favorable result may usually be anticipated. If, on the contrary, the temperature reaches 105° or more, the case must be viO(J^'(),sh^. 293 considered a severe one and the prognosis is orave. This is shown by tlie foll»)\vin«i- table, ('onij)iled by the writer some years since from u series of 2(j!) cases recorded by various authoi's, in which careful tem- perature observations had been made : Cases in w iiii-h ilio teiuperaturo was 107° and above U)0°-1U7° 105°-] 0G° 104°-10r)° 103"-104° 102°-103° 10r-102° Total No. of cases. 13 36 80 87 29 15 269 No. of deaths. 13 9 22 24 6 74 I'cTcc'iitaKo >- the first twentv-four hours, and often induces a free ])ers])iration, with relief of the headaclie au(l other distrcssiuii" sym})t(>ms which occur at this time. The usual j)ro- cedure is to have the j)atient sit \\\)im the edge of his bed with a blanket wrapped around him and his feet and legs immersed in a bucket of Avater as hot as he can bear and containing- a liberal quantity of mustard flour. Berenger-Feraud recommends the use of large enemata of cold water as an antipyretic measure. These may be frecpiently repeated, and are said to be (piite harmless. Cold enemata have also been recommended for the relief of the congested and inflamed kidneys. The knowledge that exposure to cool currents of air or a sudden fall in the external temperature is dangerous for yellow fever patients on accounl of the visceral congestions which are likely to be induced by such exposure — especially of the kidneys — has led many ])hysicians to refrain from the use of cold lotions to the surface as an antipyretic measure, and by some the use of cold drinks is denied. This we believe to be a mistake, and the excessive use of blankets and hot drinks to induce perspiration may cause great discomfort to the poor patient with- out any corresponding benefit. AVhen the febrile stage is ap})roaching its termination, and during the stage of depression which follows, ex- posure to cold currents of air or a sudden fall in the external tem])era- ture, not compensated by artificial heat or a sufficient supply of bed- covering, may be fatal. But when there is considerable fever the patient should be lightly covered, care being taken, however, to protect him from draughts. If the skin is hot and dry, warm aromatic drinks may be given to promote perspiration, but it is a mistake to suppose that the course of the disease can be arrested or the deadly poison eliminated by maintaining a free perspiration ; aiid when the patient is loaded dow^n with blankets, the profuse perspiration which is often induced by this treatment does not materially reduce the body heat. Antipyrine has been given f(U' its sedative and anti]iyretic effect, and is considered useful by some of those physicians who have had an opportunity to test its value. AVe should be disposed to administer it with caution and during the acme of febrile heat only — prefera1)lv at night, with a view to securing rest. The use of arterial sedatives in small but repeated doses is approved by many experienced physicians : they may reduce the febrile action to some extent. Aconite mav be given in combination with some mild diaphoretic during the first day or tAvo ; later, (JIf/ifalis will be prefer- able on account of the tendency to heart failure, Bemiss says : " We have seen digitalis produce unquestionably good effect in mitigating fever, and have often administered it in doses of thirty to sixty drops of the tincture every third or fourth hour. It is best to give it in solu- tions of acetate of ammonia or potash." AVe should prefer to give it, in proper doses, with a solution of sodium bicarbonate in ice-cold Avater, administered as recommended by the Avriter in 1887. Bicarbonate of soda has frequently been prescribed as an occasional 298 YELLOW FEVEB. dose to neutralize the acid secretions of the stomach and to allay vom- iting, but in the treatment above referred to the writer proposed, by the systematic administration of this salt, to neutralize the acid secretions from the outset, and thus to prevent, if possible, the nausea and vomit- ing which are so frequently distressing features of the disease. An alkaline treatment seemed to be indicated also by the highly acid condi- tion of the urine, and it was hoped that it might have a favorable action on the kidneys. And on theoretical grounds it was thought that it might be well to administer at the same time the powerful antiseptic, mercuric chloride, in a minute and perfectly safe dose. Accordingly the following prescription was made : I^. Bicarbonate of soda, 10. (150 gr.). Bichloride of mercury, 0.02 (^ gr.). Pure water, 1000. (1 qt.). M. Sig. 50 cc. (3 tablespoonfuls) every hour ; to be given ice-cold. Another object in view was to give a moderate quantity of ice-cold water at regular intervals, as this would be less likely to induce vomit- ing than larger amounts taken at the patient's option, and if absorbed would quench thirst better than larger quantities quickly rejected. I have had no personal experience in the treatment of yellow fever since this plan was suggested, but have received very favorable reports as to its value from various sources. The treatment referred to has been tested by a number of physicians in the United States, in Cuba, and in Brazil, and I have had reports of 374 cases treated by ten physicians. - Of these, 301 were whites, with a mortality of 7.3 per cent, and 73 cases blacks, with no mortality. During the last epidemic at Jacksonville, Florida (1888), Sollace Mitchell treated 106 cases in the " Sand Hills Hospital " with 5 deaths — a mortality of 4.7 per cent. Of the 106 cases, 79 were whites, and of this number 73 were adult males. All of the deaths occurred among these, and the mortality among this class, considered separately, was 6.8 per cent. La Guardia and Martinez in 1889 treated 44 cases in the Mer- cedes Hospital, Havana, with a mortality of 15.9 per cent. They say : " We have observed the following facts : The patients have offered a notable gastric tolerance during the medication ; when treated from the first day vomiting has rarely occurred. The secretion of urine has always been considerable ; even in the grave cases, when death occurred, they did not die anuric." Whether this treatment is still in use in the Mercedes Hospital and elsewhere in the city of Havana I am not in- formed, but the evidence published is certainly sufficient to justify a more extended trial. To what extent the small amount of mercuric chloride added to the formula is concerned in the favorable results reported I am unable to determine. This salt remains in solution in presence of sodium bicarbonate, but would be precipitated by potassium carbonate, which salt is also contraindicated in a disease in which there is a tendency to ursemic poisoning. The addition of tincture of digitalis in suitable doses to the formula given might prove to be an advantage, but this can only be determined TRKATMKXT. 299 bv earottilly condnotccl clinical experiments. The administration of the ice-cokl alkaline mixture at regular intervals, with or without the addition of one of the agents mentioned, appears to us to be a rational feature in the symptomatic treatment of tiie disease, and, as stated, is supported by favorable clinical evidence. It is very desirable to ])revent vomiting, inasmuch as the attempt to arrest it by medicini's administered per os is usually a failure. Morphia given hypodermieally suggests itself, but ex])erience shows that this is a dangerous remedy, and only very minute doses are tolerated. Blair has seen stupor, prostration, and complete narcotism follow the admin- istrati- the headache there is no decided pain anywhere. The ex- pression becomes unnatural, evidencing dread, and the complexion is pallid. The pulse may be slightly quickened, but there is nothing dis- tinctive in the character of either pulse, respiration, or temperature in this stage. The premonitory stage may last for one or two days, and if promptly treated may end in immediate recovery. Otherwise it will merge into the second stage of serous diarrhoea, and, as stated before, it may be abbreviated even to a few hours or it may be absent altogether. II. The SECOND STAGE presents one of the most alarming condi- tions ever recognized in any of the infectious diseases, excepting, per- haps, yellow fever. The stools become more and more frequent, finally almost continuous. They are still alkaline, and they become more and more watery until they finally consist only of water, in which flakes of w^hitish mucus and epithelium float about, giving rise to the character- istic appearance familiarly known as " rice water." The bowels having been thoroughly evacuated of all fecal matter and bile by previous pas- sages, the stools become purely sero-mucous and odorless, though there is a distinct meaty smell. They are frothy and exceedingly copious ; as much as two quarts of fluid may be almost instantaneously evacuated with considerable force. If left standing, a sediment is deposited which, when examined^ is found to consist principally of desquamated intestinal epithelium, granular debris, bacteria, and possibly a little mucus. The stools, although described as resembling rice water, are in reality much more transparent (Milles). In some cases they are stained with blood pigment, and, according to Flint, the specific gravity of the evacuation is 1005 to 1013. They contain sodium chloride and also ammonium carbonate, which latter imparts the alkaline reaction. There is at first a notable absence of tormina and tenesmus ; in fact, patients are often temporarily relieved by the evacuations. When the stools become typical they are found to contain fewer varieties of bac- teria than are present normally, and, in fact, the comma bacillus may be the only one present. This germ, however, is not found in any con- siderable quantity until the evacuations are thoroughly watery. The quantity of fluid drained from the system by this means is enormous, and far exceeds that which is ingested. It should be remem- bered that about 70 per cent, of the normal body weight is composed of water, and while the evacuations continue much of this Avater is drained from the more fluid tissues, such as the muscles and viscera, and is withheld from the digestive organs, and is reabsorbed from the serous surfaces. Hence all the latter become dry or coated with a sticky, thick, slimy secretion, and the soft tissues generally diminish in volume. Brunton considers the transudation of serum into the intes- tine as due to paralysis of the intestinal nerves. The facies are typical in this stage. The rapid emaciation, showing prominently in the face, gives the individual a wizened aspect. The conjunctivae are red and congested, the pupils are contracted, and the orbits are hollow and are generally surrounded by dusky rings. The eyes have a vacant, staring, 316 CHOLERA. cadaveric, expressionless look. The face is flushed, the nose is pinched, the mouth is drawn, the cheeks are sunken, the abdomen is depressed and " boat-shaped," the skin becomes inelastic, loose, and wrinkled, and the muscles lose in volume. A few hours will make a previously healthy-looking young adult appear like a withered octogenarian. The tongue is dry, covered with a thick, yellowish white coat in the centre, but red at the edges and tip, somewhat resembling the tongue of typhoid fever, but with less prominent papillae. The whole mouth is very dry and thirst is extreme. The desire for fresh water and for acidulated drinks is insatiable. Patients drink eagerly, and never seem to get enough water. Among other subjective sensations complained of are headache and a feeling of oppression or of suffocation in the chest. Restlessness gives way to quiet and apathy. The mental condition of the patient is characteristic. The mind is dull, listless, apathetic, but consciousness may remain until death super- venes, and the patient can often be aroused to answer questions intelli- gently, although he volunteers nothing, but moans and rests with the eyes half closed. When aroused from this semi-conscious condition the voice is feeble, cerebration is slow, and speech is difficult. If asked how he feels, the patient may reply that he is well, but asks at once for more water. Vomiting usually characterizes this stage, and it comes on suddenly or is preceded by nausea. It is difficult to control, and is often accom- panied by considerable straining and consequent epigastric pain and soreness. The stomach is at first emptied of whatever food it may con- tain ; then bile is vomited, and finally the ejecta consist of watery fluid, become colorless, almost odorless, alkaline in reaction, and resemble the choleraic stools. The urine, like the other secretions in the body, is withheld, and suppression may become complete, or, if this is not the case, it is dark-colored, of high specific gravity, containing an exces- sive percentage of urea, some albumin, and hyaline, granular, and fatty casts. The anuria is not wholly due to lack of water in the blood, but in great part to inability of the kidneys to perform their functions. The scrotum is retracted. The pulse, owing to the small volume of blood contained in the arteries and the feeble heart action, becomes very thread-like and compressible. It is quickened, at first to 100, later it may rise to 115 or 120. Arterial tension is diminished. The respi- ration becomes feeble and shallow. It is mainly thoracic, and may be irregular in rhythm. It may be increased to 30 or 40. The perspira- tion is often profuse, being the only secretion which is not checked. The surface of the body becomes livid, and feels cold and cadaveric to the touch, although the internal temperature may register one or two degrees above the normal when carefully taken by a long-stemmed thermometer placed in the rectum. It is often stated that cholera is a disease of subnormal temperature, but this is not strictly correct, as pointed out by De Renzi, Guterbock, and others. Although the tem- perature in the mouth has been recorded as low as 79° F. and that in the axilla at 75° F., the internal temperature is elevated, and the patient complains of a subjective sensation of fever. The fever is described as being of a remittent type with exacerbations. This temperature is SYMPTOMS. 317 commonly overlooked on account of the frequency of the stools and the difficulty of takings the temperature correctly in any other place than the rectum. The freshly voided urine may show an elevation of tem- perature. The muscular cram])s may aifeet the dia])hrao;m, giving rise to more and more tlitticult respiration, or, occurring s[)asmodically, cause hiccough. The stage of serous diarrhoea lasts from one to two or three hours or more, and the patient usually passes into the stage of collapse. More rarely recovery takes place at the end of the second stage. Naturally, the more violent the symptoms of this stage the briefer it becomes. One important fact should be borne in mind — namely, that tlie quantity of the evacuations is not an infallible guide for prognosis. A very fatal form of cholera is sometimes observed in which diarrhoea is slight, although the other symptoms are all present. This is described as " drv cholera," or " cholera sicca." Such are often cases in whicli the patient is suddenly seized with great prostration and faintness with- out any premonitory symptoms. Death occurs in two or three hours, and examination of the intestines shows them to be enormously dis- tended with serous fluid which failed to escape in diarrhoeal stools, apparently because intestinal paralysis has been complete. The stage of collapse cannot be distinctly separated from the stage of serous diarrhoea, for they gradually merge one into the other. In this algid stage the heart action becomes so feeble on account of the lack of blood pressure, the difficulty of propelling the thickened blood through the capillaries, and the lack of nutrition of the organ itself, that stimulation is urgently needed. Owing to the excessive loss of water by osmosis into the intestine the blood becomes thick and tarry. The bloodvessels are comparatively empty, and the velocity of the blood stream is reduced by the weakness of the heart. The red corpuscles do not circulate readily through the pulmonarv capillaries, and the normal respiratory function is greatly impeded. There is deficient oxidation, and carbonic acid accumulates in the blood. Cyanosis results, and this becomes especially marked about the nose, lips, and in the extremities. As a further consequence of the rapid loss of fluid from the system the muscles become dry and pass into tonic spasms, in which they are hard and board-like. Severe and frequent cramps ensue in them. The abdominal recti are usually first affected, and subsequently the calves of the legs, and finally nearly all the larger muscles of the extremities and trunk, may be involved, including those of the arms and neck. The cramps are persistent, and give rise to intense, agonizing pain, especially in the abdomen and legs. The arms and legs are distorted. Pain is also referred to the sternum and other parts of the chest. The patient's general condition is pitiful. The skin is dry, pinched, and wrinkled, the face is expressionless, the half-closed eyes have a vacant stare ; the mouth is drawn and set ; the cheek-bones protrude as if they would burst through the skin ; there is sudden increase in vom- iting and diarrhoea, which is followed by further fall in the surface tem- perature (Shakespeare), although the deep internal temperature may continue elevated by one or two degrees. The patient's mouth is so diy and he is so feeble that he is unable to articulate, although he can 318 CHOLERA. be aroused to evident consciousness. The muscular cramps continue, and the abdominal walls are sunken, but rigid. The emaciated fingers and toes are flexed or drawn into unusual positions by the contractures. The respirations become more and more feeble and irregular, and the exhaled breath is cold. The patient often suffers greatly from a sense of suifocation. The tears, saliva, and bile are all suppressed, and so is the menstrual function. The conjunctivae become so dry that exposure to the air may make them inflamed (Stille), The urine continues highly albuminous or else is totally suppressed. It sometimes contains sugar. The rapidity of the pulse is not excessive. It often remains between 100 and 120, and it finally becomes imperceptible at the wrist. The second sound of the heart is quite inaudible. The duration of this stage varies from a few hours to as much as one or two days, ending either in the stage of reaction or in a typhoid state in which the patient may linger for a week or more before death, or, as is frequently the case, it terminates early and the patient dies of asthenia. Death sometimes occurs from sudden heart failure, and the patients who have not presented the most severe symptoms have been known to escape from bed, take a few steps, and drop dead. Usually, however, death occurs so gradually that it may be difficult to fix the exact moment at which the heart action finally ceases. Just before death and for some time thereafter the temperature begins to rise, and within an hour or two after death it may reach 106° F. In the asphyxiated cases, caused by stagnation in the flow of the thickened blood, the temperature may even reach as high as 108° F. Not infrequently rigor mortis sets in while the patient's facial muscles and those of the extremities are so contracted as to produce fixed grimaces and contortions, which add much to the horror of the disease. TV. Stage of reactiOjS^. — This stage follows gradually upon that of collapse. The diarrhoea and vomiting, which have ceased toward the end of the previous stage, either from exhaustion or from lack of fluid to be voided, do not return. By slow degrees the pulse becomes again perceptible, and the internal temperature begins to rise, in the majority of cases for two or three or more degrees. The patient's expression becomes more intelligent, and muscular contractures cease. The res- piration becomes deeper and more regular, and slowly the external warmth of the body is restored. The patient ceases to experience thirst, and there is gradual evidence of the recovery of the different secretory functions which have been suppressed. The urine increases in volume and improves in character, and the stools, which are now infrequent, by slow degrees take on a solid character (after nourishment has been given), and show some evidence of bile pigmentation, although if there has been excessive denuding of the epithelial surface of the intestine they may continue to have a hemorrhagic character. Recovery is sometimes prompt, but, as might be expected from such a severe disease, it is often protracted by continued anaemia and pro- nounced irritability and feebleness of the stomach, bowels, and nervous system in general. Such symptoms as severe frontal headache, dizzi- ness, and fainting may recur from time to time. In other cases septic material is apparently absorbed from the denuded intestinal surfaces, and the patient passes into a condition of septicaemia or a typhoid state. COMPLICATIONS AND SEQVELjK. 319 in which he may linger for a week or two before deatli. Tliis condition is characterized bv continued liit>h fever (104° to 105° F.), a dry fissured tongue, continued diarrhioa, delirium, and coma. Sometimes there are cutaneous eruptions of differeut kinds, luiviuij:: no constant type, how- ever. Other cases, again, owing to the continued sup])ression of urine, pass into a unomic condition, with a preponderance of nervous symp- toms, such as delirium and convulsions. In still other cases the intes- tines have been so much weakened that they are long in regaining their natural tone, and protracted diarrhoea maintains the exhaustion of the patient. Relapses sometimes result from overexertion, too hasty resumption of normal diet, or occasionally without any assignable cause. In the disease called " cholerine," which has been mentioned as often preceding or accompanying widespread epidemics of cholera, and which some Avriters regard as a mild form of the latter disease, the symptoms are much less severe, and, although the diarrhoea is exhaustive, asphyxia, muscular cramps, and total suppression of the urine are not common. This disease, however, is often fatal. DuEATiox. — The cases which are fatal commonly terminate in two or three days. Death has been known to take place within two hours after the passage of the first typical stools, the patient going into the algid state at once. Ordinary cases, ending in recovery, may last from a week to several weeks according to the severity of the disease and the supervention of complications. Epidemics do not long prevail in any one locality. They do not often remain longer than three or four weeks in one place, but, being migratory, pass on to new localities, and are thus sometimes prolonged throughout an entire season. They may be temporarily checked by cold weather and be resumed in the sj^ring. Complications axd Sequelae. — Owing to the conditions under which cholera develops, especially those of the presence of a damp soil, putrefying organic material, and bad water, other diseases are apt to prevail in the same locality and at the same time in which cholera is active. Such diseases are simple diarrhoea, gastro-enteritis, dysentery, and the more severe forms of malarial fevers. A variety of symptoms have been recorded in different epidemics as complicating or following cholera, but none of them are distinctive or constant. Such are the different exanthemata, as roseola, urticaria, etc. The emaciation predisposes to bedsores, ulceration, and furunculosis. Perspiration may continue and become excessive, the sweat containing urea. Painful swelling of the parotid glands has been recorded. Occa- sionally a condition resembling tetanus obtains, and the muscles remain rigid and contracted for several days. Still rarer sequelae are gangrene, peritonitis, and ulcer of the cornea. Very commonly considerable irri- tation of the gastro-intestinal tract persists after many days or weeks, which naturally postpones convalescence. The circulation may remain feeble for a long time, so that the patient suffers from coldness of the extremities, wakefulness, dizziness, and other symptoms. Persistent albmuinuria may remain, and there is sometimes cerebral congestion. In many cases, and in children especially, broncho-pneumonia is a somewhat common complication. Diagnosis. — The immense importance of an early diagnosis of Asi- 320 CHOLERA. atic cholera is self-evident, for not only is the clinician materially aided by being thus enabled to apply the proper treatment at the onset, but the sanitarian can more easily control an impending epidemic by prompt recognition of the first cases. The diagnosis is, however, beset with difficulties even during the prevalence of an epidemic, for, on the one hand, a number of very mild cases escape detection — which for this reason are apt to spread the scourge in its worst form — and, on the other, there are undoubtedly many cases of severe acute gastro-intestinal dis- ease which so closely simulate Asiatic cholera as to be neither clinically nor anatomically distinguishable from it. These cases are due to other bacteria than the comma bacillus, which are endowed with either per- manent or temporary specific virulence. Fortunately, in the recognition of the spirillum of Asiatic cholera discovered by Koch we have a means of diagnosis which is today admitted by the great majority of author- ities to be absolute. Hence in all suspected cases early bacteriological examination is imperative, and whenever the spirillum is found the case is at once to be regarded as one of true Asiatic cholera. Upon the negative side it must be admitted that there are cases of true cholera in which the spirillum cannot be found, but these are far fewer of late years since the bacteriological technique has made such rapid advances and the examinations are made more promptly. The causes of failure to find the bacillus in such cases are chiefly the following : 1. Imper- fect technique. 2. Examination conducted after the intestines have been already irrigated with acid injections. 3. Examination made at the wrong stage of the disease, when the bacilli are absent or greatly reduced in number. 4. Some few extremely virulent cases, occurring especially in young children, in which death results before there has been time for the development of many germs. The panic caused by Asiatic cholera, no matter in what community or class of people it may appear, is only to be judged by those who have an opportunity of being witness to such scenes. The most formidable barrier the sanitarian meets with in his endeavors to check an epidemic is the fear possessed by the masses. People imagine that the authorities are hunting for the sick, not to help them in their distress, but to exter- minate them by any means. When a patient is taken to a lazaretto his relatives and friends are often convinced that he will be poisoned at once and hurried into an unknown grave. Consequently in hospitals one very seldom sees cases of cholera in the first stages of the disease. This experience was repeated during my stay in the New York Quaran- tine in 1892 and 1893. There are three symptoms which are present at the outset of the disease, the observation of which has aided me and others connected with the quarantine in diagnosing suspected cases at a very early stage. These symptoms are as follows : 1. Expression of the face. The face appears pale, with slightly flushed cheeks, a bluish hue of the lips, slight congestion of the conjunctivae, and a peculiar, rather stupid look in the eyes. 2. Moderate rapidity of the pulse. This symptom is most important, and is one of the earliest to appear. The pulse is compressible, and beats about 108 to 120 a minute without accompanying elevation of temperature. DIAGNOSIS. 321 3. Appearance of the toiufue. This is thickly coated in the centre and red at the edges, sometimes moist, in otiier cases drv. The sul)iective symptoms cannot he (Icpciidcd upon :it all in the pro- dromal staye. It is oidy in the jjrenionltory stage or before the recognition of an epidemic of cholera that the disease is apt to be mistaken for any other. Typical cases are absolutely unique, and the diagnosis is easily estab- lished by the rice-water stools, the rapid emaciation, suppression of secretions, prostration, and algid condition. Nevertheless, errors have been made, and those diseases and conditions which have from time to time been mistaken for cholera, or for which cholera has been mistaken, are septicaemia, cholera morbus or cholera nostras, severe gastro-enteric fever, typhoid fever, pernicious malarial fever wdth gastro-intestinal symptoms, and ptomaine or other forms of poisoning. Asphyxia from coal-gas (CO) poisoning may resemble the stage of choleraic asphyxia, but the absence of the rice-water stools will not long leave the diagnosis in doubt. In the typhoid or septic condition into which cholera patients some- times pass during the reaction stage the disease sometimes resembles typhoid fever, but the latter can be differentiated by the type of the fever, the abdominal eruption, the less rapid emaciation, and the fact that the stools, if diarrhoeal, are much less watery than in cholera. In cases of severe septicsemia the invasion is less acute, the temperature is higher, there may be chills and sweating, and the history of the case is wholly different. Exceptionally, intensely acute cases of cholera mor- bus prove fatal in a day or two, and very closely resemble Asiatic cholera, although usually complete suppression of urine, cyanosis, and prolonged muscular cramps are wanting in the former disease. The bacterial diagnosis can be made within a few hours. The stools, while loose and watery, are not so clear as the t^'pical rice-water evacuations of Asiatic cholera. The cases are almost always isolated, non-epidemic, and recovery is more frequent. In pernicious malarial fever of the gastro-enteric t}^e the onset of the disease is often acute, and for a few hours it may resemble cholera, but the temperature is much higher, reaching 106° or 107° ; free pigment is found in the blood, with some- times malarial organisms. Ptomaine poisoning produces great prostration, violent watery diar- rhoea, cramps, thirst, etc., but the histoiy of the case and the non- appearance of typical rice-w^ater stools will enable the diagnosis to be made. There are some cases of acute arsenical poisoning which may resemble the first stage of cholera from the collapse, cramps, suppression of urine, and thirst which may occur ; but in these cases there is decided epigastric pain and burning, with constriction in the throat and oesoph- agus. In all doubtful cases thorough bacteriological examination should be at once made. Peognosis. — The prognosis of cholera depends mainly upon the severity of a given epidemic and the promptness with which individual patients are treated. Other conditions which affect it are the general sanitary condition of environment and the patient's previous state of health. The prognosis is worse along the sea-coast than inland, and is always bad in overcrowded camps and tenements. In Asia, such are Vol. I.— 21 322 CHOLERA. the habits of the people, so largely influenced by ignorance, supersti- tion, and certain religious customs, that no progress has of late years been made in reducing the mortality from cholera, excepting where the British government has been able to improve the water supply and drainage in some localities, notably in Calcutta. By these means the mortality of foreign soldiers serving in India has been reduced to one sixth of the rate of thirty years ago, when it varied between 18 and 20 per 1000. In various epidemics the mortality has varied chiefly between 20 and 80 per cent., and it has sometimes been as high as 90 per cent. The mortality is greatest at the extremes of age when individuals are regarded, but in general the total mortality is greater in early adult or middle life, because more victims are taken during this period. Some extensive epidemics have had comparatively slight mortality, while others, less widespread, have been exceedingly fatal. From 21 cases of cholera diagnosed by myself bacteriologically, and 1 clinically, only 4 deaths resulted : 3 died directly from the effects of the disease ; the fourth, after becoming convalescent, contracted lobar pneumonia, to which he succumbed. Judging from these results, in which there is a mortality of less than 14 per cent., Asiatic cholera should not be considered such an excessively dangerous disease ; in fact, it is an easy enemy to vanquish if one is well prepared for it and is forewarned of its presence. Prophylaxis. — Unquestionably, the greatest drawback to the total extirpation of cholera, which is theoretically quite possible if a sanitary millennium could be attained, is the ignorance, superstition, and fanaticism prevailing among different races and tribes of semi- civilized Eastern people. In the past few years many lives have been lost through riots originating in efforts on behalf of the people to pre- vent the enforcement of ordinary commonsense hygienic rules. Officers in authority in their attempts to use disinfectants, and even physicians making humane efforts to treat the disease, have been brutally mobbed. It will be long before this condition can be overcome, and such is the religious superstition prevailing in India in regard to bathing in the sacred pools and other religious rites, that it is doubtful whether the disease can ever be wholly controlled as it should be. It is possible, however, for civilized countries to protect themselves against invasion by the adoption and enforcement of simple sanitary regulations which have been thoroughly proven abundantly adequate to check absolutely the further spread of the disease. Cleanliness. — In all epidemics of cholera a careful study of the modes of transmission of the disease emphasizes the fact that personal cleanliness and absolute cleanliness of all clothing are distinctly pro- phylactic. Upon guarded steamships, unless they have contracted the disease from foul water on shore, it never spreads among the well cared- for cabin passengers, but affects particularly emigrants of the low classes, whose filthy habits, combined with overcrowding, make them ready sub- jects to the infection. Among other prophylactic agencies are the examination and disin- fection of all emigrants coming from a region infected with cholera, their detention, by suitable quarantine regulations, on their arrival at a new port, their promjjt treatment, isolation^ and disinfection when sus- rnoriiYLAxis. 323 picious cases oociir, and liiially tlic eiiliiilitcimu'iit of" the fj:eneral ])ul)li{r as to the real nature of the disease and tlie iinjjossihility of infection by any other means than throtiiih the agency of the mouth, because eitlier contaminated food or drink is the agent necessary to originate an epi- demic. When an invasion of chok'ra is threatened, all cities liable to be invaded, especially seaboard towns, should l)e put in the best ])ossible sanitary conditit)n. The streets shonld be thoroughly cleaned ; all sew- ers, cesspools, or receptacles for excreta or manure should undergo a most thorough cleansing and disinfecting. The water snpply shonld be immediately investigated, and every source of contamination with it ."^ihould be guarded, if necessary, by sanitary police. Through printed circulars and the public press the public should be warned to use no water for either cooking, drinking, or washing purposes (or brushing the teeth) which has not been iirst subjected to thorough and prolonged boiling, Avhicli will render it absolutely innocuous. The local government should appoint special medical inspectors whose duty shall be to allay the fears of the people and disseminate knowledge in regard to the importance of obeying sanitary rules and caring for personal hygiene. They should make house-to-house visits iind see that all cases of diarrhoea or dyspepsia from any cause are promptly treated. Large assemblies of people should be forbidden, especially at public funerals of those who have died from the disease. Baw Food. — The eating of all forms of raw food shonld be discour- aged, for undoubted cases of infection from this source are numerous. If necessary, the civic authorities of the town should take measures to prevent temporarily the sale of all fruits and such vegetables as are apt to be eaten raw. This was done in Hamburg during the last epidemic there. The reason for such action is obvious. The fruits and vegeta- bles are often cleansed by w^ashing them in foul water, and undoubtedly' not only cholera, but typhoid fever germs, may be conveyed into the human body by eating raw food which has been thus contaminated. Moreover, it has been clearly proved that flies are active agents in spreading cholera bacilli abroad. Their filthy habits, in the exercise of which they alight on decomposing offal and excreta, cause the con- tamination of their feet and bodies with the germs of disease, Avhich are thus easily conveyed by them to any articles of raw food, such as sweet, overripe fruits, etc., which are exposed on public sale. This is not mere theory, but the observation of scientific bacteriological research. Much discussion has been occasioned in regard to the possibility of infection from beet sugar prepared in an affected locality, the idea being that the coarse sacks in which the sugar is shipped for commerce become saturated with saccharine material, affording a good culture medium for cholera germs ; but Sternberg has proved that cholera bacilli do not grow in a moist beet sugar medium in the absence of nitrogenous material, and beet sugar alone does not nourish the spirillum. Disinfection of Stools, Clothing, etc. — Physicians, nurses, and attend- ants are no more liable to contract cholera than they are in attend- ing cases of typhoid fever to acquire that disease, and identical precautions must be observed. In both cases infection is con- A'eyed through the stools, and absolute personal cleanliness after 324 CHOLERA. handling the patients or their evacuations cannot be too strictly- insisted upon. In cholera the stools are so copious, and occur with such frequency and violence, that it is often difficult to keep the patients and their bedding clean, and the hands of the attend- ants must necessarily come more or less in contact with the evac- uations. Unless they thoroughly disinfect themselves by washing the hands in soap and water, alcohol, and finally corrosive sublimate, a, 1 : 500 solution, or 1 : 20 carbolic acid solution, they may convey the germs to their own food at their next meal, and thus become infected. Great care should be exercised by such attendants not to spatter any fluid into their own mouths while bathing cholera patients or washing utensils, bed-pans, etc. All clothing and bed-clothing of patients, if they cannot be burned, should be placed in disinfecting solutions before they are washed ; otherwise there is the same danger of infection for those who- handle them by spattering the contaminated water about or immersing their hands in it. It is claimed that greatly debilitated patients wha have been crowded in rooms or hospital wards with cholera patients, and who have been obliged to inhale effluvia from their evacuations, have contracted the disease, but under these conditions it is difficult to dis- prove the possibility of other sources of infection, such as those before described, and the poison must certainly be very concentrated to enter the system in any such manner. All dejections must be received in china bed-pans containing either a 1 : 500 corrosive sublimate solution or a 5 : 100 carbolic acid solution. The volume of solution should be at least half of that of the stool to secure thorough disinfection, and it should remain in contact with it for an hour or two before being thrown away. Schauz and others advise the addition to the disinfectant of a solution prepared by adding lOO- grammes of crude sulphuric acid to a litre of water. This is to be 'added to the stool in the proportion of one sixth of its volume. Other disinfectants are made more efficacious by the addition of this acid. The practical objection to this method is that the acid is ruinous ta metallic drain-pipes, and to overcome this difficulty Stills suggests that the dejecta after disinfection be either mixed with sawdust and burned or buried in a trench. Quarantine. — When a vessel sails from a port in which cholera pre- vails or in which, during an ejiidemic elsewhere, suspicious cases of gastro-intestinal disorders have been reported, she should, on arrival,, be held at quarantine until thorough bacteriological examination can be made, which is possible within twenty-four hours. If the result of the examination establishes the presence of cholera infection on board, all the passengers should be removed at once, and carefully separated into groups of the sick, the well, and suspected cases. Authorities differ as to the length of time which they should be detained, and many eminent sanitarians (especially in England) are disposed to ignore the necessity of quarantine for the well, believing that the disease can be readily stamped out in any situation in which it may occur. Others claim that all persons from the infected vessel should be held for from seven to ten days. In any event, their baggage should be disinfected by steam, and the vessel must undergo thorough disinfection by being- flooded Avith steam and washed down with a 1 : 500 solution of bi- TREATMENT. 325 t'hloi'idc of mercury. Elmiiirants who are susjHH'tcd should he f^ivon au autisoptic bath, and their personal elothinti; and l)a<^^age should be disinfected in steam sterilizers under pressure. Since the disease is often s})read bv foul clothino-, the importation of raj>;s from infected ports should be absolutely prohibited durino; the prevalence of the disease. The International Sanitary Conference, which met at Konie in 1885, adopted the view that a disinfection of the mails and of clean dry mer- chandise was M'holly unnecessary. During: the prevalence of cholera epidemics on board ship it is impossible for the ship's surgeon to take the time or sup])ly the facil- ities for bacteriological research, even were he competent to do the work of an expert. There is a strong tendency on the part of shipowners to conceal, for obvious reasons, the possibility of deaths from cholera occur- ring upon their vessels ; hence it is that the doubtful cases are usually recorded as " gastro-enteritis." The fatal cases are promptly buried at sea, and all their effects are thrown overbroad. This greatly embar- rasses the health officers in their work at quarantine, for it is often impossible upon the ship's entry into port to obtain a single article of personal clothing or of bedding which belonged to a fatal case, much less to obtain any of the excreta, for examination. It should be the duty of the ship's surgeon to preserve specimens of the dejecta in sealed receptacles for bacteriological examination, for it would thus be possible for the health officers to determine with greater certainty whether or not the ship has been infected with cholera. During the last epidemic of cholera in this country much time and anxiety might have been saved upon the ship's entering New York harbor had this precaution been taken. Treatment. — There is as yet no specific treatment for cholera, although it is not impossible that an antitoxin or an immunizing serum may be before long discovered which will affi^rd a means of checking this much-dreaded plague.^ The rational treatment of the disease is based upon the principles now established which govern the treatment of similar infectious diseases having a definite focus of operation for the activity of the ^ The prophecy here made by Dr. Byron is possibly approaching verification since his untimely death. Dr. Haffkine, a former pupil of Pasteur, has for several years been experimenting with preventive inoculations against cholera. The inoculations are first made witli a mild culture of cholera germs, and five days later with a stronger one. Five days later, still, immunity is reported to follow. Dr. Simpson, health officer of Calcutta, was authorized in the spring of 1894 to expend 20,000 rupees (approximately §5000) in research with the inoculations. His report to the Municipal Commissioners of tliat city, lately issued, covers a series of 7690 persons, chiefly Hindoos, who received the treatment. Of this number many were exposed to the disease before the lapse of five days after the second inoculation, but some of these escaped infection, or, being infected, escaped death. Of a smaller series of 269 persons inoculated five days or more before exposure, a few — Dr. Simpson does not give the exact number — became infected, but only 1 died. He claims that the chances of death among inoculated subjects are "22.62 times smaller" than they otherwise would be. Dr. Haffkine himself, experi- menting in India, claims similarly favorable results. Judgment of the value of this treatment must be suspended until more extensive reports are received. As in the early days of the diphtheria antitoxine inoculations, much opposition is being made by some of the British physicians in India to the treatment, but it is to be hoped, as Dr. Bvron has said, that success in this or a similar method may be attained when the technique of its application is fully understood. — Editor. 326 CHOLERA. pathogenic germs, from which poisonous materials or toxalbumins are developed to be absorbed by the agency of the lymphatic or blood- vessels, and thus cause general systemic intoxication. In the case of cholera the focus of the disease is a single one, very definitely located in the intestines. The appearance and nature of the germ is definitely known, as are also those remedies which are capable of destroying it. The problem of treatment is, then, a twofold one : first, to either destroy or limit the development and activity of the germs in loco, and, second, to combat the eifects on the system of the highly poisonous substances which may have been already absorbed, and aid the process of elimina- tion and reparation. Such is the extraordinary virulence of this disease that the former method offers more hope of successful accomplishment than the latter, although both methods are to be simultaneously em- ployed. The treatment above outlined will be conveniently described under the headings of 1. Internal antiseptic treatment; 2. Systematic treatment. 1. Internal Antiseptic Treatment. — Many remedies have, in times past^ been strongly advocated for the purpose of limiting the local action of the cholera bacilli, and such remedies were, in fact, employed before the germ theory was established, but modern research and experience have reduced this number to a very restricted basis. Calomel is strongly recommended by Von Ziemssen and others. It is distinctly serviceable in the premonitory stage and in mild cases as an evacuant of the poison from the intestine, and its probable partial conversion in the alimentary canal into a more strongly antiseptic form of mercury no doubt enables it to exert some slight disinfectant or germicidal action. I have, however, found it worse than useless in severe cases. Mercuric bichloride is used by Ivert and others. He employed it in Tonquin, and claims a reduction in mortality from 66 to 20 per cent. Iodoform has been recommended by Bouchard,- and other remedies of the so-called intestinal antiseptic series which have been extensively tried are naphthol, naphthalin, salicylate of bismuth, salol, etc. All the above remedies possess the common disadvantage of being administered per os. There is usually persistent vomiting, which is intensified by all stomach medication. Moreover, most of these remedies are so altered in their transit to the real focus of the disease that they cannot be depended upon. Owing to their poisonous nature in large doses, it is unjustifiable to give them in strength sufficient to prove effective germicides against so active a bacillus as that of cholera. 2, Systematic Treatment. — The systematic treatment which follows is most strongly recommended from the results of my personal experi- ence with cholera at quarantine. It will be conveniently divided to correspond with the natural stages of the disease. (a) Premonitory Stage. — In the premonitory stage the patient should be kept in bed after receiving a warm bath, and must be carefully protected from cold. Ten grains of calomel may be administered, and intestinal irrigation should be at once begun after the manner de- scribed below (Enteroclysis, p. 329). The food must be very simple, and it is best given in small doses at two-hour intervals. Such articles as boiled milk, thoroughly cooked TREATMENT. 327 rice, milk tOcast, and plain broths sIiduUI be given. It is often best to pancrcatinize the milk, and, as the gastric juice is feeble and intestinal digestion is disordered, it is well to give fifteen or twenty minims of dilute hydrochloric acid with five grains of pepsin after taking animal food. The acid destroys the cholera bacillus and ])rcvcnts the develop- ment of its |)oison, besides being the natm-al acid of the gastric juice. It has the further effect of tending to slightly diminish the i)atient's thirst. These are the ordinary precautions to be taken in dealing with the premonitory stage, but every case of cholera, in whatever stage it may be first seen, should be subjected at once to intestinal irrigation. The premonitory stage is often very brief, and is often unre(;ognized by either patient or physician, and in a majority of cases the physician is not called or does not reach the patient until the evacuant or collapse stage has developed. Those cases seen at Swinburne Island were of such an exceedingly virulent type that the premonitory diarrhoea was very slight and often passed unnoticed. The administration of preparations of opium in the early stage of cholera to control the diarrhoea is to be condemned, for it may cause re- tention of the intestinal contents, and thereby counteract nature's only method of eliminating the poison of the disease by watery evacuations. Given later, it is usually ineffectual in controlling the discharges from the bowels, and it merely adds a dangerous narcotic to the system. Morphine may be required hypodermically, however, to relieve the cramps when in the later stages they become intolerable. The treatment of the second stage, or stage of serous diarrhoea, does not differ essentially from that of the stage of collapse, and it will there- fore be detailed under that heading. (b) Stage of Collapse. — In this stage the most active and prompt treat- ment is an absolute necessity if the patient's life is to be saved. The main indication for treatment in this stage is to restore by every possible means the water which has been drawn from the blood in copious alvine evacuations. During two epidemics I have obtained the most encouraging results from what I may call the surgical treatment of this stage — /. e. the injec- tion of fluids into the body through the skin and rectum, as descriljed below (Hypodermoclysis, Enteroclysis, p. 329). This method of treat- ment, resorted to at Swinburne Island, differs from all others, inasmuch as the internal administration of drugs is avoided. I first used this treatment in 1892, and, encouraged by the results obtained, I again used it in 1893 with still better effect, though it should be stated that the last epidemic was not of such a virulent character as that of 1892, and that most cases were treated at an earlier stage of the disease. In former epidemics the attempt has been made to transfuse salt solution, defibrinated blood, etc. into the veins as a means of restoring the balance of circulation more promptly than in any other way, but the practical difficulties in the way of this procedure are considerable, owing to the fact that all the veins are collapsed, and are, consequently, difficult to find. It is often impossible to secure one large enough for transfusion without performing a formal operation to reach a deep- seated vein. Especially is this true in children, and the time lost in the procedure may be even greater than that required for the absorption 328 CHOLERA. of fluids administered in other ways, and the operation adds to the dis- comfort, if not the terror, of the patient. Practically, the method has proved an emphatic disappointment, and it is now rarely practised. Hypodermoclysis. — This name is applied to the simple process of the free subcutaneous injection of a normal salt solution ; that is, 0.6 per cent, of sodium chloride in distilled water, or, practically, two small teaspoonfuls of pure common salt to the quart of warm water, distilled and sterilized. It is often well to add an ounce of brandy, as stimula- tion is much needed. The operation of injecting this fluid was first suggested and used by Cantani of Naples in the cholera epidemic of 1865, and he has since then employed it repeatedly ^\\i\\ great success. Its recommendations are its simplicity and the promptness with which it can be performed. To give the injections an ordinary rubber douche- bag is utilized, such as that commonly employed for vaginal irrigation. To the rubber tube leading from this bag a small-sized aspirating needle is attached. The bag is filled with the salt solution at a temperature of 110° F., which is reduced to 105° F. in its passage through the appa- ratus. A large fold of skin is grasped between the thumb and fore- finger, and lifted so that the needle can be introduced deeply into the loose cellular tissue of the subcutaneous space. The skin, as well as the hands of the operator and needle, should all be first sterilized. The skin should be first washed with soap and water, and afterward cleansed with alcohol and ether and a 1 : 500 solution of bichloride of mercury. The needle should be boiled for at least half an hour. The point of selection for administering the injection should be preferably on either side of the abdominal wall between the inferior ribs and the iliac crest. In extreme cases the injection can be made into the peritoneal cavity. The inner surface of the thighs can also be utilized, but the region of the neck should be avoided, as two cases of laryngeal oedema are known to have occurred after the injections. When all these precautions are conscientiously observed no untoward results occur. I have known of but one accident — the development of an abscess — which was distinctly due to a careless observation of the above rules. The quantity of fluid injected for the first time by hypodermoclvsis should be, for an adult, from one to two quarts ; for an adolescent, one or two pints ; and for an infant, one half pint. In critical cases the injection should be pushed as much as possible, and repeated again in an hour or two. The liquid enters by hydrostatic pressure, and the reservoir may be gradually raised or lowered to regulate it. i^bout half an hour should be con- sumed in injecting a quart of fluid. The injections are not so painful as might be supposed. At all events, the patients are so ill that they submit to the treatment without much complaint, and, as the saving of time is an important object, the use of cocaine is not desirable, espe- cially as it is decidedly depressant to the heart action in the doses which would be required to cover the ground of the injection. As an imme- diate result of the entrance of the fluid a large tumor forms which may reach the size of an orange, but it is not advisable to attempt to dispel it by massage. If the hypodermoclysis is successful, the tumor will soon be naturally absorbed, and in favorable cases its disappearance will be complete in from twenty to forty-five minutes. I regard the rate of absorption as of considerable prognostic value, for if absorption is TREATMENT. 329 delayed for three or ioiir lioiii's, it is an indication that the lymphatic and liioniic circulations are botii very feeble and that death is likely to soon occur. More ]'aj)id al)sorption, on the other iiand, with iniprove- nient in the volume of the pulse, is an ex(H'e(liii<;ly favorable sign. The introduction of the salt solution has a twofold l)eneticial action : First, by restoring; the proper volume and normal density of the blood the i'irculation is benefited and the inhibited renal function is re-estab- lished ; secondly, it acts favorably as a diluent of the ])tomaines which have been absorbed from the intestines, and aids in their elimination from the system. In favorable cases the effects of the injections are truly astonishing in their rapidity of action and in the change in the appearance of the patient. This method of treatment is indicated just as soon as there is the slightest appearance of the approaching stage of collapse, and it should be repeated according to symptoms until permanent restoration of the balance of the circulation and respiration has been established. Among those who commend this treatment as a result of personal trial are, notably, Cantani, Nothnagel, Kaeler, Rumpf, Von Ziemssen, and Stofella. E)it('rocIysis. — To fulfil the second important indication for treat- ment it is necessary to reach the focus of the disease by intestinal irri- gation. There is the more hope of benefit from this procedure from the fact that comma bacilli affect the superficial layers of the intestinal mucous membrane, and are, consequently, within reach. The difficulty or impossibility of oral medication has been already discussed, and it remains to be proven that fluids introduced in large volume per rectum <.'an be made to flood the whole intestine. This fact is often denied, for it is claimed that the anatomical structure of the ileo-csecal valve com- pletely prevents regurgitation from the large into the small intestine. That this is ordinarily true under normal conditions there can be no doubt, but it is, nevertheless, also true that under moderate hydrostatic pressure fluids may be made to pass this valve. The conditions for its successful passage are the use of a long and properly introduced rectal tube, a large volume of fluid, a hydrostatic pressure of about five feet, a horizontal or partially inverted position of the patient, and the per- formance of gentle massage, commencing in the right iliac region and passing in the direction of the ascending colon. To test the possibility of the passage of the fluid beyond the ileo-csecal valve I have made experiments on a number of cadavers, and have been able to fill not only the entire intestine, but even the stomach, in the manner described. These results are confirmed by Cantani, Simon, Hofmolk, and Hegar, and they are further confirmed by the fact that in several instances where I have used tannic acid injections for cholera patients some of the acid has been ejected by vomiting. In some experiments upon cadavers I have even succeeded in forcing the passage of liquids from the rectum out through the mouth and nose by means of no harder pressure than that which is justifiable in the clinical treatment of cholera. There are undoubtedly some cases in which, owing to a twist in the large intestine, old adhesions, disproportion in the size of the valve, or other conditions, it may be impossible to reach the small intes- tine, but even in these cases the large intestine can almost always be 330 CHOLERA. completely flooded. The rapid emaciation of the patient and the con- sequent thinness of the boat-shaped abdominal walls makes it compara- tively easy to manipulate the intestine by massage. Method of Giving the Injections. — The ordinary fountain rubber douche-bag is employed, or, in an emergency, a quart bottle may be fitted with a piece of rubber tubing, and when the bottom is knocked oiF it may be suspended inverted and used as a reservoir. The rubber tubing is connected with a long rectal tube which should have a blunt extremity and one or two large perforations situated from one to two inches behind the blind end. Such tubes as those employed for stomach washing are of suitable size and stiffness. If too stiff, they do not readily follow the curves of the rectum, and if too limp, they bend or twist, which makes their introduction difficult. Such a tube can always be passed in for a distance of seven or eight inches, and occasionally^ with good luck, it can be made to pass beyond the sigmoid flexure. All the apparatus employed is to be sterilized, and the water used for the injection should be distilled and sterilized. The tube is well oiled and carefully passed into the rectum. Sometimes its further passage can be facilitated by allowing some of the fluid to flow while the tube is pressed inward. The object of the injections is a threefold one : First, to flush the intestine and wash out such poisonous material as may be within reach ; secondly, to supply a medium fatal to the comma bacillus ; thirdly, the fluid being hot, local warmth is applied to the deeper portions of the body, which is serviceable in arousing the patient from collapse. These indications are met by the use of a 2 per cent, solution of tannic acid in water, heated in the reservoir to 110° F. A lowering of about five degrees in this temperature occurs as the fluid flows through the rubber tubing-. It is well to warm the rectal tube in hot water before its inser- tion. When the tube is in place the injection should be allowed to flow at first very slowly, and fully ten or fifteen minutes should be occupied in giving a quart or more of fluid. After the fluid has been injected, several minutes more should elapse before the withdrawal of the tube, while gentle pressure is maintained on the perineum, and the patient is to be encouraged to make every effort to retain the injection. The tube is then very slowly and carefully withdrawn. By means of these precautions it may be possible to secure the retention of the injection for some time. This will check the growth of the bacillus, and much of the fluid may be absorbed by the lymphatics. The quantity of fluid to be employed should be from one to two quarts, and in severe cases it is to be used as often as once every hour. Other remedies which have been used by rectal injection are solu- tions of subacetate of lead, solutions of creolin (2 per cent.), and diluted laudanum. With regard to the efficacy of the treatment by hypodermoclysis and enteroclysis the following data are instructive, but it should be borne in mind that the patients treated at Swinburne Island were many of them brought off the vessel in an almost moribund state. There were in all 72 cases treated in the epidemic of 1892 at Swinburne Island, with 20 deaths, giving a mortality of 27 per cent. ; or, if 46 suspects are in- cluded who had distinct prodromic symptoms of cholera, the mortality TREATMENT. 331 is rcdiu'od to 17 per cent. On the other hand, amont^ the patients attacked at sea upon the vessels which reached our quarantine the mor- tality varied from 50 to 98 per cent., and the general mortality of this epidemic in liamlnirii" ^vas hetween 50 and 60 per cent. I'ndouhtedlv, the mortality at Swiuhurue Island Wduld have been even lower l)ut for the fact that uiany of the patients attacked were under-fed Russian emi- grants, already anannic or diseased. Many of them were marasmic young children, so that the premonitory stage of the disease was often absent. Application of Wannfli. — In the stage of collapse the external surface of the body is always cold, and the external temperature may be six or eight degrees below the normal. To restore the natural warmth and aid in the re-establishment of the normal circulatory functions external heat must be energetically applied. In many cases this is best accomplished by the use of a hot plunge bath, which has the further advantage of diminishing the tendency to cramps. While in bed the patient should be kept warm by the use of hot water bags, hot sand bags, or hot bricks packed about the extremities, or hot air may be applied beneath the bed- clothes. The latter should consist of two woollen blankets and a coun- terpane. As before indicated, heat is also supplied in some degree by the warm subcutaneous and rectal injections given. If perspiration occurs, the sweat should be immediately dried. Belief of Pain and Cramp. — "When the cramps are unbearable they should be relieved by inhalation of chloroform to the point of primary anaesthesia. Moderate cramps are sometimes relieved by the rubbing of the muscles with mustard water, by the application to the abdomen and legs of hot water bottles or of turpentine stupes. Placing the patient in a bath of 108° F. for twenty minutes will sometimes give great relief. Care is of course to be exercised in moving the patient, and he should be lifted so as to be subjected to as little exertion as possible. When the patient's general condition is one of great suifering, small hypodermic injections of morphine (one sixth of a grain), combined with one one-hundreth of a grain of atropine, should be given locally in the muscles chiefly aifected. It is noticeable that in cases of cholera treated by subcutaneous and rectal injections the frequency of pains and muscular cramps is greatly diminished. This is a further proof of the belief that the cramps are directly due to the drying of the muscles and nerves which follows the loss of water from the intestines. Relief of Vomiting. — When the vomiting is excessive it may be some- times relieved by hypodermic injections of morphine, and h\ a mustard paste or turpentine stupes applied over the region of the stomach. The aerated waters, small doses of iced champagne, or iced fresh lime juice are sometimes grateful for relieving thirst and to some extent controlling the vomiting ; but, as a rule, throughout the entire stage of collapse, if there is any nausea or tendency to vomiting, it is best to make no attempt to give anything at all by the mouth. The mechanism of vomiting only excites further intestinal movements in a reflex manner, and is weakening and injurious. When vomiting is persistent and the ejecta are copious, it is desirable to wash out the stomach by lavage. For this purpose a hot 2 per cent, tannic acid solution is to be employed, like that recommended for enteroclvsis. The removal of the cholera 332 CHOLEBA. liquid from the stomach will check further vomiting and straining, and will add much to the patient's comfort. Stimulation. — While the stomach remains irritable stimulation is to be given in connection with the hypodermoclysis or by separate hypo- dermic injections of brandy. The ordinary hypodermic syringe, holding half a drachm, may be filled with good brandy, which is to be deeply injected in the outer side of the arms or thighs. Several such injections should be given, at least once an hour. For an infant five or ten minims may be used. The entire stage of collapse is to be combated by vigorous hypoder- mic stimulation, for which purpose such remedies are to be used, in addition to brandy, as sulphuric ether, strychnine, gr. one thirtieth, citrated caifeine, gr. j, and morphine, gr. one sixth. Efforts to stimu- late by the mouth do more harm than good. In this stage, especially when dyspnoea is prominent, the free inhalation of oxygen gas is often beneficial, or at least it relieves the subjective sensations of the patient. Nitrite of amyl inhalation is also of occasional benefit. (c) Stage of Reaction. — Should the suppression of the urine continue into this stage, the rectal and subcutaneous injections should be con- tinued two or three times a day, but it is undesirable to use tannic acid. If the temperature becomes normal, the external application of heat is discontinued, and should a reactionary fever occur the patient's woollen undergarments and heavy bedclothes should be removed. As the symptoms begin to abate and slight improvement is mani- fested, a little fluid nourishment may be cautiously given per os. Aerated waters may be freely given. For this purpose may be used one of the meat extracts, pancreatinized milk, or koumyss. The milk is often better borne if diluted with equal parts of Vichy or carbonic water. Iced champagne in tablespoonful doses is also to be recom- mended. Throughout convalescence the patient must be carefully watched, and the return to solid food must be very gradually made, attention being given to the condition of the bowels and gastric digestion. The stomach often remains very weak for many days, and the patient must be kept upon a diet of predigested milk, beef peptonoids, nutritious broths, and gruels, egg albumen with sherry, milk punch, or egg-nog. Later, such articles may be given as cream toast, junket, well boiled rice, lightly cooked eggs, custards, meat broths thickened with rice or macaroni, etc. As soon as more food is given, it is best to resume the administration of dilute hydrochloric acid and pepsin, which may be given every three or four hours. Strychnine may be given as a tonic, at first hypodermically two or three times a day, and then by the stomach in doses of one fiftieth of a grain. Later the simple bitters and preparations of malt may be useful, and three grains of quinine may be given as a tonic after each meal. The urine should be frequently examined until all albuminuria has disappeared. If the kidneys are slow in resuming their normal activity, mild saline diuretics and effervescing mineral waters are to be prescribed. The patients at Swinburne Island were compelled to take a daily sun bath, which proved of great benefit. TREATMEyT. 333 I (][Uot(> in full tlie details of three eases from my eoiitrihiition to the livport of ILcdlih Ofiiccr, Port of New York, 18i)3, whieii are seleeted from the cliiiieal notes of Dr. Jndson Daland, who volunteered us assist- ant during the late ej)idemie at Swinburne Island. They will be found to present an instruetive elinieal })ieture of the symptoms and a resume of the treatment eni[)loyed : Ca8E J. — " Male, twenty-nine years ; passeng'er on boai'd S. S. Kara- mania ; in perfect health until the 3d of Auj»;ust, 1893, when he beiran to have a moderate diarrluea and nausea. Not considering his illness serious, he did not report his condition until the afternoon of the 6th, when his symptoms became alarming. When examined by me the same day I found him in collapse, with the following- sym])t()ms : Pulse rapid, filiform, and compressible ; temperature subnormal, features pinched, eyes sunken, injected, and expressionless ; lips, eyelids, and extremities cyanosed ; cold, clammy perspiration ; husky voice ; complete indiffer- ence to all surroundings ; intelligence unimpaired. Patient complains of excessive thirst and a choking sensation, which he describes as if having a heavy weight upon the chest. Vomiting and rice-water dis- charges abundant and repeated at short intervals. " Examination of dejecta showed comma forms mixed with other bacteria ; cultures on bouillon and gelatin revealed the bacilli of Asiatic cholera. Patient was transferred to the hospital and subjected to the following treatment : Hourly rectal injections of the hot 2 per cent, tannic acid solution ; subcutaneous injections of brandy, preceded by a single injection of y^ grain of nitroglycerin. The condition of the patient grew rapidly worse. At midnight his temperature (rectal) was 96° F. ; pulse only perceptible at the brachial artery ; profound collapse. Three quarts of sterilized salt solution (salt 1 part, water 1000) were injected into the peritoneal cavity after proper disinfection of the skin and instruments. Rectal injections were also continued. From this time symptoms began to improve. Six hours later all the fluid had been .absorbed from the peritoneal cavity, the radial pulse could be perceived, the respiration was easier. A second intraperitoneal injection of two quarts of warm salt solution was injected, and the rest of the treatment continued. " August 7. — Improvement continued. As vomiting had ceased, the patient was allowed to take some beef tea and milk and seltzer. Rectal injections continued ; hypodermic stimulation suspended. Diet care- fully increased until the morning of August 10th, when all treatment was suspended and the patient was taken out for a sun bath. Recovery. Duration of disease from first symptoms to convalescence, six days." Case II. — " The second case well illustrates an ordinary attack of Asiatic cholera. A Russian, aged seven years, was admitted from the steamship Bohemia, September 26, 1892, at 8 p.m., with a temperature of 96.2° F., pulse 106, respirations 22, and the surface of the body extremely cold and cyanotic. The face was pinched, especially in the nasal region ; it was markedly cyanotic, and the eyes were deeply sunken and surrounded by dark circles. The pulse was feeble and small, and was counted witli difficulty. She at once received a w^arm plunge bath, and her stomach was then washed out with one pint of a 1 per cent, solution of tannic acid at the temperature of the body. Shortly 334 CHOLERA. afterward she vomited twenty-three ounces of fluid. She remained in about the same condition during the night, but the passage of a moderate amount of urine encouraged us to hope for a favorable issue. On Sep- tember 27th her pulse was 104, temperature 97.4° F., and respirations 18. The cyanosis persisted ; there was no further vomiting, but she had frequent copious discharges from the bowels, composed chiefly of the tannic acid solution which had been injected j^er anum. Later in the day improvement began ; the temperature varied between 100.2° and 100.4° F. ; a large semi-solid stool was passed. She slept moderately well during the night, but complained greatly of thirst. A sufficient quantity of urine was excreted, and the liquid from the bowels was composed chiefly of the tannic acid solution that had been given by injection. She became very restless, but the following day was much brighter and began to notice her surroundings. The dejecta changed in character, becoming greenish in color and somewhat frothy. On Sep- tember 29th she slept well ; her bowels were moved only after giving the intestinal injection of tannic acid solution. In the afternoon her improvement was so marked that it was decided to suspend these injec- tions. Her temperature varied from 97.8° to 99.4° F., the pulse be- tween 96 and 120, and the respiration from 22 to 24. On September 30th she was able to take nourishment and stimulants by the mouth, but the stools continued brownish and thin, and when an attempt was made to administer beef tea or any food by the mouth vomiting occurred. The cyanosis disappeared, but she was still shrunken and emaciated. She continued to improve, and on the fourth day after admission was carried into the open air, where she received a sun bath for two hours. " The following is a summary of the treatment : Upon admission she received a hot plunge bath. The first enteroclysis or intestinal in- jection was retained for three minutes, and afterward these injections were repeated every two hours. A subcutaneous injection of one pint of a 0.6 per cent, solution of sodium chloride was given the day after admission. At first whiskey was administered by the mouth, but after- ward 10 minims were given hypodermically every four hours. The total duration of the patient's illness was five days, and her convalescence was extremely rapid and uninterrupted." Case III. — " I will narrate the history of a third case, the most in- teresting of all observed, in which we were fortunately able to note minutely every change that took place from the beginning to the end. This patient exhibited nearly all the symptoms of a typical malignant case of Asiatic cholera, illustrating also, in an equally striking manner, the results obtained by treatment. " This patient, a male, aged twenty-four years, a native of Germany, was admitted to the Swinburne Island Hospital on September 27, 1892, at 11 A. M. His muscular and osseous systems Avere unusually well developed, and it was reported that he was perfectly well on the morning of September 27th until 4 a. m., when he first complained of pain in the abdomen, which was followed by two loose stools. He con- tinued feeling well until we saw him at 10 A. m., when, in'view of the diarrhoea, it was deemed wisest to remove him to the hospital, although his general condition did not indicate that he was suffering from cholera. He objected strongly to his removal, and said that he felt TREA TMENT. 335 pertbotly well, lie walked i'roni hi.^ brrtli to the side ui" the .ship and down a rope ladder to the quarantine tug-boat. He arrived at Swin- burne Island, and reiterated his statement that he felt perfeetlv well, and walked iVoni the (juarantine boat to the door of the hcjspital, when suddenly lie eoni])lained of weakness in the knees and fell to the oroimd in a state of eolh'.pse. He was earried to the ward in a condition of partial stupor, from wliieh he w'as easily aroused. He responded to all (/ic((l Injiuvnce^. — Changes in the weather and temperature undoubtedly act as predisponents with regard to dysentery. Thus, it has been observed tliat sudden reduction of the temperature in the night, as is of common occurrence in the autumn season, or exposure to rain or heavy dews, will be followed by an increase in tlie number of dysentery cases. Unhygienic infuence.s, such as have heretofore prevailed in armies, fleets, and prisons. Dysentery has followed the track of all the great armies which have traversed Europe during the continental wars of the past two hundred years. It helped to destroy the British army in Hol- land in 1748. It decimated the French, Prussian, and Austrian armies in 1792. It was the chief cause of death in the ill-fated Walcheren expedition in 1809. It cut down the garrison of Mantua in 1811-12. It was the most fatal disease in the Peninsula campaign, and disastrous to the British troops in the Crimea in 1854. It is the disease of fam- ished garrisons in besieged towns, of barren encampments, of starving prisoners, and of fleets navigating tropical seas. Dysentery and diarrhoea w-ere of enormous frequency in the Federal and Confederate armies during the Civil War in America from 1861- 65. As stated by Woodward : " These disorders occurred with more frequency and produced more sickness and mortality than any other form of disease. They made their appearance in the very beginning of the war, not infrequently prevailing in new regiments before their organization Avas complete, and although, as a rule, comparatively mild at first, were not long in acquiring a formidable character. Soon no army could move without leaving behind it a host of victims. Thev crowded the ambulance trains, the railroad cars, the steamboats. In the general hospitals they were often more numerous than the sick from all other diseases. They abounded in the convalescent camps, and formed a large proportion of those discharged from the service for dis- ability. Many of the prisoners upon both sides suifered and died from dysentery. For many months after the war was over and most of the troops had returned to their homes deaths from chronic diarrhoea and dysentery contracted in the service continued to be of frequent occur- rence among them." What explanation can be given of this excessive morbidity and mortality from intestinal fluxes in army life ? The replv must be that it lies in the infraction of almost every item of sanitarv law which is incidental to, and so far has appeared to be inevitable in, times of war. The lowering of vital resistance from overcrowding, irregular habits, exposure to bad weather, forced marches, want of rest, intemperate eat- ing and drinking, bad cooking, and imperfect quality of the food, by producing intestinal catarrh provide a suitable soil for the growth and development of pathogenic organisms, which in the opinion of the writer are most apt to gain an entrance through contaminated drinking water, such polluted water supply being specially apt to occur in camps and armies. Before discussing the methods of water infection mention should be made of other causes which are mainly predisposing. 342 DYSENTERY. Errors of diet have been regarded from time immemorial as potent factors in the production of dysentery. Articles which have been con- sidered as most obnoxious are unripe fruit, decomposing vegetables, tainted meat, canned fish, meat, and vegetables. Such articles are more liable to cause diarrhoea, nature thus getting rid of the irritant sub- stances. Occasionally, however, such dietetic errors result in a catarrhal proctitis, which ra]:)idly subsides when the oifending cause is removed. Dysentery is not likely to result unless the error is frequently repeated, but the catarrhal condition ensuing upon dietary faults will undoubtedly predispose to the worst forms of the disease. The idea that fresh fruits and vegetables are dangerous has been proven to be a mistake ; on the contrary, army experience has demonstrated that by warding off scurvy and maintaining a better state of general health dysentery is actually prevented when such articles are freely consumed. Constipation, and Retention in the Bowels of Fermentative Irritant Compounds. — ^Virchow and others have attached great importance to such conditions as causes of dysentery. Several circumstances show that this view is true of a certain class of cases, or at least that such influences predispose to dysentery — viz. the catarrhal and diphtheritic inflammation, ulceration, sloughing, and perforation of the mucous mem- brane in contact with fecal masses which accumulate above the point of obstruction in cases of stricture, and the fact that constipation often pre- cedes the occurrence of dysentery, are significant in this direction. Constitutional Condition of those Exposed. — Various writers on dis- eases of camps and armies have called attention to the effects of exhaus- tion from fatigue, over-exertion, loss of sleep during long marches, sieges, battles of several days' duration, as predisposing to dysentery. In a like manner, any severe constitutional disorder producing gen- eral debility favors the development of dysentery among those exposed to its exciting causes. Thus, Finger, in describing the Prague epidemic, calls attention to the frequency with which the disease attacks patients already the victims of tuberculosis, cancer, typhus fever, syphilis, and Bright's disease. AVoodward confirms these observations, and adds that in the American Civil War the diseases in which dysentery occurred principally as a secondary affection were tuberculosis, typhoid fever, malarial fever, and scurvy, and that in tuberculosis and typhoid fever there was not only the intestinal ulceration peculiar to these diseases, but in many instances acute catarrhal and diphtheritic dysentery devel- oped as the terminal event. As regards malaria and the scorbutic taint, the evidence is conclusive that the cachectic condition produced by these diseases is especially favorable for the development of dyseiiterv. Drinking Wcder. — In regard to contamination of drinking water as a source of infection, it has been conclusively proven that the infectious micro-organisms of cholera and typhoid fever (intestinal diseases) also are largely conveyed by means of impure water. It will be shown that there is at least a strong probability for such an origin in many cases of dysentery. When we consider the large quantity of water consumed by every individual, the extreme likelihood of its contamination with path- ogenic organisms, and that, unlike the food, it usually is taken without any previous preparation by which such infectious agents might be ETIOLOGY. 343 destrovod, wc can appreciate the infliicnce a poisoned water supply might have as an excitant of tliis disease. From the earliest times the use of impure drinking water has been considered as a cause of intestinal fluxes. Hippocrates discussed the question at length, and attributed the occurrence of such disorders among those wlio live in marshy districts to drinking the stagnant water of lakes and ponds. This opinion was quoted by Galen, who pointed out the methods of purifying water by filtration and boiling. It is unnecessary to discuss at length the various ingredients of water which have been supposed to exercise a causative influence in the pro- duction of dysentery. Evil effects have been ascribed to inorganic sub- stances in suspension and such substances in solution as sulphate and carbonate of lime, salts of soda, potash, and magnesia. The evidence upon this subject appears to be that, while such waters may often have a purgative effect, especially upon those unaccustomed to their use, and may be deleterious in other ways, there is no proof to show that these chemical ingredients will cause dysentery. Facts appearing to offer such demonstration — e. g. where in an epidemic of dysentery only those who drank limestone water were affected, those who used cistern water being entirely exempt — do not prove that the carbonate of lime was the morbific agent, but only that such water, being supplied by surface drainage, was liable to other contamination. The presence of decomposing matters of vegetable origin in the water used for drink has been regarded as a cause of intestinal flux, but so far the evidence from either custom or experiment has been inconclusive as to the evil effects of such substances. Pathogenic Micro-organisms in Drinhing Water. — Since the facts as regards this source of infection have been established as to typhoid fever and cholera, the probability of a similar origin of dysentery has been greatly strengthened, and in the opinion of the writer ample confirma- tion will be offered when similar methods of investigation have been applied to dysentery ; and here, also, fecal contamination is the most probable source of infection. I will cite but a few of the facts which go to supjDort this view. Read relates that in August and September, 1870, one of two regi- ments lodged in the barracks at Metz suffered greatly from dysentery, while the other had but few cases. On inquiry it was found that the former obtained its drinking water from two wells which were proved to have been contaminated with fecal matter filtered from neighboring latrines, while the latter drank from two wells not having such connec- tion. The impure wells were closed and the disease at once subsided. Oaks traced an outbreak of dysentery at Cape Coast Castle, on the west coast of Africa, to the passage of sewage from a cesspool into one of the tanks supplying drinking water. One of the most conclusive instances upon record of water infection is that mentioned by Fagge in regard to the prevalence of dysentery in the Millbank prison. It appears that this disease had prevailed ex- tensively and for a long time in this prison. Fagge says : " In the year 1854 the prisoners ceased to be liable to dysentery, and during the next eighteen years (up to 1872) one death only occurred from that dis- ease or from diarrhoea ; indeed, so far as I am aware, the immunity has 344 DYSENTERY. continued down to the present time. Now one, and only one, change in its hygienic arrangement has coincided in time with this improvement in the sanitary state of the prison. Formerly the water which the con- victs drank was taken directly from the Thames as it ebbed and flowed beneath the walls. But on August 10, 1854, the artesian well in Tra- falgar Square was made the source of supply to the prison ; this has since continued. The change was effected in the midst of the cholera epidemic ; six days afterward the disease suddenly ceased. Typhoid fever too no longer attacks the convicts, and the death rate has declined to an extraordinary extent. It is, I think, impossible to avoid the con- clusion that the exciting cause of dysentery in Millbank prison was the Thames water, and in all probability the noxious ingredient was derived from the sewage contained in it." Fecal contamination is undoubtedly the explanation of the excessive prevalence of dysentery in military camps in times of war. The notorious difficulty is a proper disposal of the excrement of large bodies of men ; its indiscriminate deposit upon the ground from whence it could be washed by every rain into the shallow wells, springs, and creeks which afforded the water supply fur- nishes the key to the situation. Contagium. — The question of the contagiousness of dysentery is one which has been extensively discussed. It would be useless to quote authorities or recapitulate the reasons they give for their opinions upon this subject. We can understand the wide differences which prevail when we consider the various standpoints from which the disease is viewed, and the want of unanimity as to what constitutes contagious- ness. If we accept the modern definition of contagion — that is to say, when the micro-organism which causes a disease may under the ordi- nary conditions of life be freed from the body of the diseased person and by whatever means conveyed to the body of another in a condition capable of lighting up the disease anew — then we must conclude that dysentery is contagious, the evidence going to show that the contagium is in the dejecta, and is likely to reproduce the disease in other victims chiefly through the drinking water. It is probable that in the future we must recognize a number of different organisms as the cause of the various forms of dysentery, for it is impossible that conditions so vary- ing in both their anatomical and clinical aspects as are the various forms of dysentery can be due to a single organism or even a single group of organisms. TJie Amoeba Dysenterica. — Although earlier observers had discovered certain organisms belonging to the protozoa in the stools, the first ac- count given of the presence of amoebae in the intestinal contents was given by Lambl in 1859. Losch was the first author who gave an accu- rate description of a species of amoebae which he found in the stools of a dysenteric patient, together with a careful clinical history and account of the autopsy. The first case studied by L5sch was received in the clinic of Prof. Eichwald in St. Petersburg in November, 1873. The amoebae found in the stools were oval, pear-shaped or irregular in form, five to eight times the size of a red blood corpuscle. They were formed of an outer hyaline or faintly granular material enclosing a more gran- ular mass. They were often so abundant that a single field of the microscope contained sixty or seventy. They changed their form fre- ETIOLOGY. 345 quently with j^reat rapidity, tlirusting out blunt processes which were at times quickly withdrawn ; at others the granular interior slowlv flowed into thcni and a change of place resulted. Tlu; nucleus was pale, of delicate contour, and (litHcult to make out. It alwavs contained a nucleolus of variable size. In the resting amcebte the nucleus was always in the midst of the granular interior. Refractive vacuoles of various sizes which under- went some change of form were very numerous in the central mass. Foreign substances, such as bacteria, fragments of cells, and red blood corpuscles, were frequently seen in the anifjebte. Cunningham, the only observer who has rejjorted on the subject irom India, states that he has found amabas in the intestinal canal of healthy persons, as well as in those alfected with cholera and other diseases. He thinks the conditions which especially favor their presence are fluidity of the stools and an alkaline reaction. He found them also in the dung of horses and cows, and discovered bodies which he regarded as their spores. In the cholera report of Koch an account is given of autopsies made on 5 cases of dysentery in Egypt. In the colon of most of the cases there were oedema and extensive ulceration of the mucous membrane; amoebae were found at the base of the ulcers and in the material cover- ing them in all ])ut one case, and in that the ulcers were healed. Amoebse have been found in the intestinal contents by four Italian observers — Grassi, Perroncito, Calandruccio, and Blanchard. Their reports have reference only to the presence of the organisms. Next in importance to the paper of Losch on the amcebae were the observations published in a series of papers by Kartulis of Alexandria, Egypt, on dysentery and abscess of the liver in 1887, 1889, 1890, 1891. In his first publication he gives a description of the amoebfe not diiFer- ing materially from that of Losch, except as to the size of the organ- ism. The second paper, published in Virchoic's Archiv, is devoted to the study of the relation of the amcebse to abscess of the liver, and of his attempts to secure pure cultures. In another article he calls atten- tion to the wider distribution of the amcebse, and cites cases in which they were found in Greece. In his last article he gives details of his experiments in the cultivation of the amceba, and bespeaks for this organism as the cause of dysentery a greater recognition among pathol- ogists than it has hitherto had. The culture medium found most suitable was an alkaline straw infu- sion, to which was added either contents of liver abscess or stools con- taining amoebae. In twenty-four to forty-eight hours a thin membrane formed on the surface which consisted of bacteria and young amoebae. Studied in drop cultures, the amoebae were much smaller than those in the stools ; their movements in the swarm form were very active, but they did not send out pseudopodia. Among the actively moving amoebae were found round inactive bodies with a nucleus and finely granular protoplasm about the size of a white blood corpuscle ; these were thought to be spores. Pure cultures were difficult to obtain : success was secured only in one case, where the material was obtained from a liver abscess free from bacteria. With both pure and impure cultures inoculations were made 346 DYSENTERY. in cats with positive results, by injecting the cultures into the rectum and tying the anus. Feeding the animals with amoebae gave negative results. Hlava, in 1887, investigated the dysentery prevalent in Prague, and found amoebse in 60 cases of partly endemic and partly sporadic dys- entery. His description of them agrees fully with that of Kartulis. Hlava also injected stools containing the organisms into the rectum of dogs and cats, with positive results. Kartulis remarks that dogs in Egypt were spontaneously affected with dysentery, and the same amoebse were found in the stools as in man. Osier, in 1890, was the first in America to discover amoebse, finding them in the contents of a liver abscess in a patient operated on by Dr. Tiffany of Baltimore. They were present in large numbers in the pus, and subsequently faund in the stools. The patient had contracted chronic dysentery in Panama. The organism, as described by Osier, conforms in every respect to the description of Kartulis except in being a little larger. In 1890, Mus- ser and Stengel each reported 3 cases of dysentery in which amoebse were found. In April, 1891, Dock gave a resume of the subject, and reported 12 cases of amoebic dysentery occurring in Galveston, Texas. In 4 of these there Avas abscess of the liver, and in 4 this disease was only recognized at the autopsy, symptoms of dysentery not being pres- ent during life, the lesions in these cases involving only the csecum. Dock's description of the organisms is in accord with that of Kartulis and others. In 1891 ^ Councilman and Lafleur reviewed the literature of amoebic dysentery, and gave the results of a careful analysis and study of 15 cases occurring in Baltimore, and a comparison of the symptoms ob- served in the catarrhal and diphtheritic forms with those of amoebic dys- entery. As more than half of these cases were fatal, they were able to make many valuable additions to our knowledge of the pathological anatomy of this disease. In the remarks here given I have freely drawn upon the excellent summary of the subject as presented by these authors. In September, 1893, the writer reported 7 cases of dysentery treated in the John Sealy Hospital, Galveston, Texas, during the previous year, in which the amoebse were found. The symptoms in these cases were uniform and characteristic : as they all recovered or were dis- charged uncured, no autopsies were made. In 1 case the discovery of amoebse in the pus from a liver abscess led to the diagnosis, the intesti- nal symptoms being very obscure. The organisms in these cases pre- sented the features as recorded by other observers. Baumgarten, speaking of the opinion expressed by Kartulis that the amoebse are the cause of dysentery, says : " We regard it is improbable that the amoebse can produce the entire series of changes which con- stitute the dysenteric process. Anatomically, dysentery consists in a combination of diphtheritic and purulent inflammation, which rapidly produces deep ulcerations of the parts affected ; there is no analogy to make us believe that amoebse can be the cause of the ulceration. We think it more probable that pyogenic micro-organisms play an import- ant part with the amoebse in the production of tropical dysentery." ^ Johns Hopkins Hospital Reports, vol. ii. Nos. 7-9. ACUTE CATARRHAL DYSENTERY. 347 Coimcilman and LatltMir, after an exhaustive study of the subject, state, as a jxirt of thcii- coiichisions, "that the anuebic is a form of dys- entery M'hich etiolotiically, clinically, and anatondcally should be re- garded as a distinct tlisease, and that the amceba has been shown to be the causative agent from its constant presence in the stools and the ana- tomical lesions, and from the inoculation experiments of Kartulis." While I am strongly inclined to believe in the (;orrectness of this conclusion, yet, on account of the difficulty of obtaining pure cultures of the amnebiC, and the uncertainty of the inoculation ex])eriments of Kartulis, the pathogenic influence of these organisms must be considered as lacking that complete and stringent proof requisite to identify its positive causative influence. 1. Acute Catarrhal Dysentery. Pathological Axatomy. — Since acute catarrhal dysentery most frequently ends in recovery, opportunities for post-mortem examinations are rare in uncomplicated cases. The colon, and more particularly the csecum, hepatic, splenic, and sigmoid flexures, and rectum, are the parts chiefly involved, though sometimes the ileum is also aifected. Areas of mucous membrane are congested, red, swollen, and more or less covered with tenacious, yellow- ish or brownish red mucus, with some admixture of pus. Punctate or diifiised extravasations of blood are usually visible. The solitary glands are generally enlarged, and project as grayish white elevations, from the size of a pinhead to that of a pea. The submucous tissue is swollen from congestion and serous infiltration. If the case is prolonged, follic- ular ulceration or diphtheritic inflammation may ensue. The following is a synopsis of changes as found in the intestines of a typical case reported by Coimcilman and Lafleur : " The patient, aged sixty-three, had dysentery two weeks before death. He had severe pain : the stools were fluid, but contained no blood. Xumerous ulcers were found in the colon, especially the descending portion, and the rectum. The ulcers were usually superficial, and many confined to the mucous membrane ; others were deeper, but none extended to the muscular coat. Some of the ulcers were round ; others of irregular shaj^e from the union of adjacent ones. The edges were smooth and were undermined. The intestine was not thickened, except about the largest and deej^est ulcers. The mucous membrane generally was pale and soft. The tis- sues, after hardening in alcohol and submission to microscopic examina- tion, showed decided changes. The superficial portions of the mucous membrane near the ulcers was broken down into a granular looking mass, in which only the remains of cells were found. Deeper down there was a diffuse infiltration with pus cells, most .marked just above the muscularis mucosa. Lieberkiihn's glands showed various stages of disorganization. In some instances they were dilated into thin-walled cysts, filled with pus cells ; in others the cells were separated from each other, forming irregular masses of epithelium ; the cells were generally swollen and with indistinct outlines. The lymphoid cells were increased and the solitary follicles slightly enlarged. " In the mucous membrane corresponding to the wdiitish areas there DESCEIPTION OF PLATE III. Fig. 1 : A transverse section of colon near the cfecum in a case of secondary diph- theritic dysentery following the amoebic form, complicated by an extensive abscess of the right lobe of the liver. Following is a brief history of the case : Aug. Schmidt, aged forty- three, native of Germany, laborer, admitted to Sealy Hospital, Galveston, Oct. 23, 1895. Lived in Galveston fifteen years ; previous health good, with exception of an attack of diarrhoea fifteen years ago. Gave a history of diarrhoea alternating with constipation, lasting about three weeks prior to admission. Stools varied in number from four to ten daily ; contained mucus, but no blood. There had been some abdominal pain, but na tenesmus. Condition on admission : anorexia, tongue thickly coated and brown, slight tenderness over right hypochondrium. Bowels obstinately constipated from Oct. 23d until Dec. 3d ; stools averaged one daily. Under the use of repeated la,xatives during the succeeding three weeks the number averaged two daily ; enemata and purgatives were required to keep the bowels active during this time. Dec. 27th a severe uncontrollable diarrhoea ensued, the number of stools varying from three to twenty-three daily; the dejections were large, thin, and watery, containing mucus, small particles of fecal matter, and undigested food, chiefly casein ; examination for amoebse negative. Diarrhoea lasted until the patient died, Jan. 8, 1895. During the first four weeks the temperature varied from normal to 100.4° F. ; the following three weeks it was higher, ranging from 100° to 102°, once reaching 103° F. ; on Nov. 30th and Dec. 3d it was subnormal (97°). On Dec. 11th there was a severe rigor, followed by a temperature of 106.8 F. ; similar rigors and high temperature occurred on the 14th, 19th, 25th, and subsequently. During this period the patient complained of severe pain in the hepatic region. Abscess of the liver was sus- pected, and an operation arranged for, but being postponed for some reason and the con- dition becoming hopeless, incision was abandoned. The autopsy revealed extensive ulceration throughout the large intestine, as shown by photograph. The drawing, by Prof. W. Keiler, made shortly after death, shows the dark discoloration, the oval-shaped ulcers, crowded together and mostly covered by a closely adherent diphtheritic exudation, extending in depth to the muscular coat, and having their long diameter across the gut. The drawing is life-size and the coloring true. The ulcers were situated mainly upon the crests of the folds of the mucosa, the grayish, dark green discolorations corresponding to the depressions between the folds. The entire colon was thickened and softened ; the latter probably was a post-mortem change. The small intestines were normal. The entire right lobe of the liver was occupied by an abscess, in the contents of Avhicli amoebae were found ; there were no other important lesions. The case is one of great interest, as showing the insidious nature of amoebic dysentery — that unhealed ulcers may exist with obstinate constipation, and death finally occur from hepatic abscess or the intervention of an acute secondary diphtheritic ulceration of the intestine of such an extent and severity as to preclude the possibility of recovery. Fig. 2 : a, amoebse coli of various sizes and shapes ; a', amoeba coli, with especially delicate and numerous pseudopodia ; b, elastic tissue remnants ; c, crystals of hsematoidin ;: d, phosphoric crystals ; e, bismuth crystals ; /, crystals of the fatty acids in combination with magnesium and calcium ; g, spiral ducts of plant ; h, spindle shaped trochid of plant ; i, red blood cells ; j, mucus not stained by bile ; k, various epithelial cells of a yellow hue from bile ; I, pus corpuscles stained by bile ; m, various masses of mucus and animal debris stained by bile ; n, partially disintegrated muscle fibres from meat diet. The granular matter forming the bulk of the stool consists of animal and vegetable debris and bacteria, oil globules, etc. 348 PLATE III. Fig. I. Fig. 2. Fig. I. Transverse Section of Colon near the Cscum, in a Case of Secondary Dysentery following the Amoebic Form. Fig. 2. Amoebse Coli of various sizes and shapes. (Drawing by Prof. A. J. Smith, University of Texas, Galveston.) IJII'IITIIEUITKJ DYSENTERY. 349 was a (lifFiiso suppiiraticjii of the tissues. The grlands were broken down, their oontines lost, and tliev were represented by irreguhir masses of" epithelium surrounded l)y pus cells. The ulceration extended througii the nuiscularis mucosa, sometimes in only very small areas ; at others the entire ulcer was seated in the submucosa. In such instances the submucous tissue was somewhat thickened, and the edjje of the ulcer marked by granulation and pus cells. The pus cells extended deeply into the submucous tissue, sometimes diifusely infiltrating it, at others collecting in groups. " Around the vessels everywhere there were dense accimiulations of cells, swollen connective tissue corpuscles, and pus cells. A marked feature was the very great swelling of the connective tissue cells near the ulcers. They were converted into large, irregularly shaped masses, with a large vesicular nucleus. Scattered through the swollen con- nective tissue were numerous masses of fibrin. The vessels showed an increase in number and swelling of the endothelial cells ; their walls were thickened and contained numerous pus cells, as did also the lumen." As shown from this description, the lesions in catarrhal dysentery consist essentially in a suppurative inflammation of the mucous mem- brane, whence it is liable to extend into the deeper tissues. 2. Diphtheritic Dysentery. Pathological Axatomy. — It is stated by AVoodward that the majority of fatal cases of acute dysentery in which autopsies were made during the American Civil War were those in which diphtheritic in- flammation was the characteristic morbid process. Similar lesions have been described by English writers in India, the French in Algeria, by English, German, and Irish observers in those countries, as by Wood- ward and others in America (Fig. 35 and Plate III. Fig. 1). Fig. 35. Photo^aph of colon (description of Case, page 548). It appears to be certain that the lesions of most of the epidemics of dysentery' are those of diphtheritic colitis, and, while diphtheritic inflammation may complicate the catarrhal and amcebic varieties, it is to 350 DYSENTERY. be regarded as a distinct form. In fact, most cases of diphtheritic dysentery are found to be associated with catarrhal inflammation of other portions of the intestines, and this catarrhal inflammation is some- times limited to the colon, but more frequently involves the lower por- tion of the ileum or may appear in detached patches higher up in the small intestines. The diphtheritic process, which in most instances is to be regarded as having supervened upon the catarrhal inflammation, varies greatly in extent and as to the firmness and tenacity of the exudation depend- ing upon the stage of the process in which death occurred. The exu- dation is sometimes limited to the descending colon and rectum, or to the latter alone ; sometimes it involves other portions of the large in- testine, or the whole of it, extending in some instances into the small intestine ; the exudation is in some cases quite superficial, lying as a separable layer upon the mucous membrane, involving the outer epi- thelium and filling the follicles of Lieberkiihn. Usually, however, in portions of the affected area a part or even the whole of the submucosa is also involved. The exudation presents under the microscope the characteristics of any other croupous exudation, showing a finely granular or indistinct fibrillated appearance, which coagulates with various degrees of firm- ness, and entangles in the coagulum a variable number of white blood corpuscles. The parts embraced in the exudation promptly undergo coagulation necrosis, the depth of the slough depending upon the depth of the previous inflammation. The exudation and resulting sloughs are primarily whitish or yellow- ish in color, or are often reddened by hemorrhage or colored greenish or black by subsequent changes in the blood. The loss of substance pro- duced by separation of diphtheritic sloughs constitutes a form of dysen- teric ulceration. The ulcers are of different sizes, and vary from mere abrasions to deep excavations that expose or even invade the muscular coat. Death often ensues before sloughing is completed, the ulcers present- ing no indications of the separation process : when the area destroyed is not too extensive, the ulcers may cicatrize and recovery take place, or more frequently remain in an indolent condition, a chronic flux per- sisting, which after a variable period proves ultimately fatal. In some instances the ulcers may perforate the serous coat, death rapidly resulting from peritonitis. It is an important pathological fact of great significance in connection with the prognosis that very exten- sive ulcers from diphtheritic sloughing may completely cicatrize and recovery occur. The cicatrices are more or less puckered, and in rare cases stricture of the bowel may result from this circumstance. In the early stages of the diphtheritic process the changes observed in perpendicular sections do not materially differ from those in catarrhal inflammation, except that the surface of the affected part is coated with a thin diphtheritic layer. This layer consists essentially of the blood fibrin, which begins to transude as soon as the inflammation is sufficiently intense. The behavior of the fibrin varies in accordance with its quality and the activity with which it is poured out. It may present almost any degree of firmness, from a jelly-like layer of very slight cohesion AMLEUIC DYSKyTERY. 351 to a toiio;!!, firmly adlioront mass, wliicli ran be strictly called a ])scu(l<>- inembranc, eiitan<;l('(l in the substance of wliicli are variously lvmj)lioi(l elements (white l)lood corpuscles, j)us corpuscles, and red bl<»od cells): the latter especially are prone to accumulate near the mucous surface. This fibrinous layer not only forms a coating of variable thickness u])on the surface of the mucous membrane, but distends the glands of Lieberkiilin, and there is an increased number of lymphoid elements in the adenoid tissue of the mucosa, the closed follicles, and the submucous connective tissue, thus ensuring more or less thickening of tlie intestinal wall. In the graver forms of the diphtheritic process the capillaries of the mucosa are distended with blood, and hemorrhagic areas of considerable size are noted upon the superficial })arts of the mucous memljrane and in the deeper parts of the diphtheritic layer. In projiortion to the increasing severity of the case the lymphoid elements infiltrate the sub- mucous tissue, and a granular material similar to the surface exudation makes its appearance in the lymph spaces. Sooner or later during the progress of these alterations sloughing sets in, just as it does in diph- theria of the pharynx. The stage at which sloughing begins varies in different cases : in some the tissues retain their vitality until the mucous surface is coated with a dense yellow pseudo-membrane ; in others at an early period the affected parts are swollen by a rich albuminous exudation containing only a moderate amount of fibrin and cell elements, in which sloughing may occur with great rapidity and destructiveness. This necrosis is rapidly followed by putrefactive changes in the dead parts, which condition is favored by the moisture and high temperature of the interior of the body. Putrefaction is manifested microscopically by a granular metamor- phosis of all the tissue elements involved into an unrecognizable mass of molecular debris. If the patient survives" the occurrence of tissue necrosis, the sloughs separate by the ordinary suppurative process taking place adjacent to the boundaries of the necrosed portions. The depth of the primary diphtheritic ulcer depends upon the depth of the diphtheritic infiltration. The original ulcer may, how^ever, extend both in area and depth, either by secondary sloughing or a true ulcerative process, the cell elements floating off as pus corpuscles ; thus the muscular coat may be gradually involved and perforation rapidly take place by rupture of the thin tissue forming the floor of the ulcer. 3. Amcebic Dysentery. Pathological Anatomy. — The large intestine is chiefly involved, for the reason that here the amoebae find favorable conditions for their development ; the small intestine seems to be affected only when there is an enormous number in the colon, from whence they pass into the ileum. The most striking characteristic noticeable in all cases of this special anatomical form of dysentery is the great thickening of the intestine. In some cases thickening involves all the coats ; in all cases it is more marked in the submucous coat, and in some confined in the latter. There is not only a general thickening due to oedema, but cir- cumscribed thickenings are present, containing small ca^^ties filled with 352 DYSENTERY. gelatinous pus. These cavities communicate with the mucous membrane by a small opening. There are also various tracts communicating with neighboring cavities. (Plates IV. and V.) The elevated nodules vary in size : the openings often are no larger than a pinhead, or so large that the cavity is freely exposed ; even then the surrounding mucous membrane is deeply undermined, and there are often sinuses in the submucosa leading off from the ulcers. The latter contain the same gelatinous looking material as the cavities, which, ex- amined under the microscope fresh, show numbers of amcebse, large round cells, red corpuscles, and pus cells. Moving amoebse are almost always found if the examination is made soon enough after death. The undermined ulcer in connection with the formation of cavities and various tracts in the submucosa appears to be the variety oftenest observed, though other forms of ulcers may be present in the same intestine — e. g. Avhen the undermined edges have sloughed away, leaving the edges smooth in places and in others only slightly undermined. These ulcers are most frequently met with in the last portion of the transverse and descending colon. The submucous coat is the one chiefly affected ; it is infiltrated and oedematous, not only at the site of the ulcers, but elsewhere. The ulcers increase by gradual infiltration and softening of the tis- sues, with subsequent necrosis of the overlying structures. The roof covering in the more or less closed ulcer, the softening continues at the sides, and an ulcer with undermined ragged edges is found. The base of such ulcers is usually clean and is formed by the muscular coat ; the latter, while it offers a barrier to molecular disintegration, may also become necrotic by gradual infiltration along the connective tissue septa until the subserous coat is reached. During the continuance of this process the peritoneum becomes greatly thickened and involved in a similar destruction. The mucous membrane seems to suffer least, or rather the lesions in this coat are secondary to those of the submucosa, the process consisting essentially of advancing infiltration and softening in the submucous and intermuscular tissue, with subsequent necrosis of the overlying tissue. Reaction on the part of the tissue is shown in the formation of granu- lation tissue rather than of pus. When suppuration is a prominent fea- ture in the process, it is due not to the action of the amcebse, but to the pus organisms which enter the tissues. The amoebae can extend in the tissue a considerable distance, which latter softens and breaks down, resulting in the formation of the large ulcers with soft undermined edges. Sometimes there is great undermining before breaking down of the overlying tissues, large sloughs thus resulting. In other cases the amoebse are cast off with the softened tissue, leaving an ulcer with smooth sides and base, or the suppuration of the tissues produced by bacteria may get the upper hand and an ordinary suppurating ulcer result, the amoebse being either cast out by the purulent softening or possibly destroyed by pus products or bacteria, there appearing to be an antagonism between the amoebae and the suppuration process. Councilman and Lafleur (to whose excellent description of the lesions of this form of dysentery the writer is indebted, and the reader is re- ferred for fuller details) state that, while the lesions of amoebic dysen- PLATE IV. ^'^. # « ^^; ^^r^l 'Ju:y^^ 4. Dysenteric AmoebEe. Figs. 1, 2, and 3, amccba; from a section of intestine hardened in alcohol and stained with methyleiie-blue. In Figs. 1 and 2 the granulation is very distinct. In Fig. a tlie dark staining at one end is seen, which frequently shows as a crescent under a lower power. Figs. 4, 5. G, 7, 8, and 1."., amwba.- from sections of intestine and abscess of liver hardened in stron? Muller's fluid and stained with hamotoxylin and eosm. In Figs. 4. 6, and 8 the nucleus. V, is very evident. In Fig. ."i there is a large vacuole, possibly resulting from a rupture of several vacuoles. Figs. 7 and 15 are examples of amcebte much smaller than the others. (Councilman and Lafieur, Johns Hopkins Hospital Reports, vol. ii. Plate VII.) PLATE V. 12 ^ v^\ 10. 13. 15. 11. i4. Dysenteric Amoeba. Figs. 9, 10, 11, 12, 13, and 14 are from various tissues hardened in Flemming's solution In Figs. 9, 11, and 12 tlie central mass lias shranken from the peripherv. In Fi<^ li and 12 nuclear detritus in the form of small brightly staining rods is seen. In Fi-s 13 and 14 are the radiate-like structures described in the text. In Figs. 10 and 13 are portions of the nuclei of included cells. In Fig. lo there are included blood-corpuscles. (Councilman and Lalieur. Johns Hopkins Hospital Reports, vol. ii. Plate VU.) . 1 Ma:n ic d \ 'setter \ : 353 terv conform most closely to the (loscri|)tion which lias been given of follicular colitis, they found the follicles involved in only one out of ei_i>;ht cases, and then it was a passixc process and in no case originating in the follicles. Abscess of the Liver. — As illustrating the frequency of this lesion in amoebic dysentery, the following facts are significant : Of the 12 cases reported by Dock, 5 tlied, and in 4 there was abscess of the liver ; in Councilman and Lafleur's series of 15 cases 8 died, and of these were com[)licated by hepatic abscess; of the 7 reported by the writer, none of which were fatal, 1 had abscess of the liver. Thus, out of 34 cases 11 were subject to this complication, and of 13 fatal cases 10 had abscess of the liver. These figures are confirmatory of the opinion that the amoebic is the prevalent form of tropical dysentery, for we find (not quoting authorities or details) that in India, Cochin China, Algeria, and Egypt hepatic abscess is discovered in 1 out of about 4 fatal cases ; also that in Cuba, Brazil, Chili, Venezuela, and Mexico liver abscess is of great frequency in connection with dysentery. Not discussing here the causes or modus operandi of liver complica- tions, we proceed with the anatomical changes found in this organ. The commonest seat of abscess is the right lobe and its lower border, corre- sponding to the hepatic flexure of the colon or the upper surface close to the suspensory ligament. In the last situation the abscess usually ex- tends through the diaphragm into the lung. The forms of liver abscess can be divided into («) the small very acute variety, (b) the larger one with partially fibrous walls, and (c) the chronic abscess with hard, dense fibrous walls. The microscopic character of the abscess contents varies. The smaller contains a viscid translucent liquid with a few pus or lymphoid cells, fatty granular material, fragments of distorted liver cells, a few red blood corpus- cles, and numerous amoebse in active motion. In the large abscess the fluid is not so clear ; its opacity is not due to pus cells, but to fat, frag- ments of tissue, and broken-down liver cells. The fluid cannot properly be called pus, as there is a remarkable absence of well preserved cells. Amoebae are found scattered abundantly through the contents of the abscess, especially at its periphery and in the included portal tissue. At the edges they are found chiefly in the capillaries, and usually do not extend in the tissues beyond the area of necrosis. Some abscesses are of microscopic size, and are not connected with the larger ones : in these we find the same process of destruction and extension as in the larger ones. Abscess formation is not the only change, for there is found also a more or less extensive necrosis of liver cells around the centre veins which does not appear to be due to the presence of amoebse. These organisms invade the already necrotic tissue, and appear to influence its breaking down and liquefaction. While the more chronic abscesses differ from the acute in many respects, they have most features in common, and the differences can be explained probably by the smaller number and less intense action of the amoebae and a minor degree of diffuse necrosis of the tissues. There are certain abscesses showing a combination between those with fibrous walls and the small ones of recent formation. In these, por- tions of the walls are distinctly fibrous and other portions are formed Vol. I.— 23 354 DYSENTERY. by necrotic tissue, which extends also into the surrounding liver tissue. Occasionally in the vicinity are small necrotic foci with central softening which are isolated from the large abscesses, but become con- nected with it by a gradual increase in size and continuation of the softening process in both directions. Thus the chronic abscesses increase in size in two ways — first, by gradual extension with a continual new formation of fibrous tissues, and secondly, by formation of separate small abscesses which soon become a part of the larger. The smaller peripheral foci may meet, and in this way cut off larger or smaller areas of tissue. The irregularity in the walls of the large abscesses is produced in this way. The amoebae are not relatively so numerous in the large as in the small abscesses ; often in large sections they are not found at all. They are usually to be seen in the necrotic edges of the abscess and in the small foci adjoining. Summing up the changes in the liver it appears that there are two classes of lesions : First, extensive necrosis of tissue which does not appear to be due to the direct action of the amoebse, for the organisms are not found in them, and they are too regular in situation and extent for such production. These necrotic lesions seem to be due to the action of the soluble chemical products of the amoebse absorbed from the in- testinal ulcers. Second, abscess formations which we are justified in believing are due to the direct action of the amoebse for the following reasons : They are invariably found in every abscess ; they are most numerous in the smallest and most recent, and in the situations where the abscess was extending ; no other organisms are found in the smaller abscesses ; the few bacteria found in the large ones do not appear to have any causal connection ; none of the pus-producing organisms are found ; and, finally, the lesions are of a different character from those produced by bacteria. Abscess of the Lungs. — Abscess in these organs secondary to ab- scess on the upper surface of the liver was found in 3 out of 6 cases by Councilman and Lafleur, who observed the following : Abscesses of the lung resembling those of the liver in several particulars. They were lined with opaque, ragged necrotic material, which in places projected in large masses into the cavity. There were also projec- tions from the abscess into the surrounding pulmonary tissues, and by union of these large masses of tissue were cut off, as in large hepatic abscesses. In a few places the abscess wall was comparatively smooth and formed of dense connective tissue. In other places there was no definite boundary between the necrotic tissue lining the abscess and the surrounding lung tissue. These abscesses were usually empty. Ex- amination microscopically of the contents clinging to the wall showed granular detritus, round lymphoid cells, a few pus cells, numbers of red blood corpuscles, fat globules, and amoebse ; also elastic fibres of pul- monary tissue. The lung tissue in the vicinity of the abscess showed the alveoli to be small, and an enormous increase of the interstitial connective tissue was noted. The bronchi were also altered : their walls were thickened, con- taining great numbers of round cells ; some were filled with fibrin and pus cells, while in nearly all of them a similar condition to that of the alveoli was found in the projection of masses of connective tissue from the wall. SECONDARV DYSENTERY. 355 Tlio amoeba} varied in niunbers in different cases and in different parts of the same abscess ; they were especially nnmerous in places where the abscess was rapidly advancing, and where there was no dis- tinct wall ; they were also numerous in the tissues around the abscess, decreasinu- as the distance from the abscess increased. They were also found in the wall, epithelium, and lumen of the bronchi near the abscess. In the production of both \\\w^ and liver abscess the action of the amoeba" is similar : they act by causing a necrosis and liquefaction of the tissue ; the peculiarity of their action and the difference which dis- tinguishes these effects from those of bacteria consist in the general absence of acute inflammatory reaction on the part of the surrounding tissues. In all cases, in the intestines, liver, and lungs, unless there is a complication in the presence of pus-producing bacteria, there is an absence of suppuration. The extension of the lung abscess into the sur- rounding tissue is probably due to the entry of the amoebae by means of bronchi bordering on the abscess. It is highly probable that the amoebae reach the large intestine chiefly through the drinking water : food is less likely to be the source of infection, as the organisms Avould be destroyed in the process of cooking. No action is exerted by them upon the stomach or small in- testine, as they do not find here suitable conditions for their increase, but in the colon, finding a favorable soil, they multiply rapidly, and, aside from the production of definite ulceration, we have evidence of their causing a superficial necrosis and softening of the epithelium, an increased secretion of mucus from the epithelial cells, and cysts of the mucous membrane from the dilatation of glands whose mouths have been plugged from the accumulation of mucus. The question arises as to the routes by Avhich hepatic and pulmonary metastases take place. The evidence seems to show that in most instances the amoebae reach the liver by passing through the intestine, entering the organ directly from the hepatic flexure of the colon, or, wandering along the upper surface of the liver in the abdominal cavity beneath the diaphragm they may cause peritonitis, or, as is more likely, produce no effect upon the peritoneum. There may be infection through the bloodvessels also, as shown in cases where there is formation of small multiple abscesses both on the surface and through the liver tissue. •Abscess of the lung appears to result from a direct extension through the diaphragm from the liver, as it is usually found in that portion of the lower lobe of the right lung which is in contact with the diaphragm. 4. Secondary Dysentery. Pathological Anatomy. — The lesions of this form of dysentery are usually those of diphtheritic colitis, previously described. In some cases there may be only a thin superficial infiltration of the upper laver of the mucosa in localized regions, especially along the ridges and folds of the colon, often extending into the ileum. In severe forms the entire mucosa may be involved and necrotic, often having a rough granular appearance. In that form which occurs in connection with pneumonia the exudation may consist of a firm white pellicle which seems to lie upon, and not within, the mucous membrane. 356 DYSENTERY. Follicular Ulceration. — A great deal has been written, especially by older authorities, upon the subject of follicular dysentery, A careful study of the results of autopsies and comparison of the clinical histories will'show that the lesions in a majority of these cases correspond to the description of amoebic dysentery as herein given. In the cases cited by Woodward as acute or " Chickahominy diarrhoea " he thus describes the lesions : " In some of the fatal cases of acute diarrhoea the only intestinal lesion observable with the naked eye was a reddish discoloration of the mucous membrane, which for the most part occurred in patches of various dimensions from a few inches to several feet in length. Such patches were observed in all parts of the intestinal canal, but were more common in the ileum than in the jejunum, and were still more frequent in the colon, where they particu- larly affected the ceecum and sigmoid flexure. Microscopical examina- tions of these reddened patches showed their color to be due either ta an engorgement of the small vessels with blood, to transudation of its coloring matter, or to actual hemorrhage into the mucous or submucous layer, or to a combination of these conditions. In the majority of cases the solitary follicles situated in the reddened patches were more or less enlarged ; the most common condition being that in which they had attained the size of pinheads and appeared as whitish or yellowish elevations surrounded by a circlet of increased vascularity. In the colon these minute elevations were generally sessile ; in the small intes- tine they often had constricted necks and projected from the surface of the mucous membrane. The question arises, How many of these cases in which there is follicular inflammation proceed to ulceration, and how many which have been described as follicular ulceration are really such? It is natural,, upon seeing enlarged follicles in certain cases and in others small nodular ulcers, to regard the latter as coming by gradual transition from the former. But, as we have seen in the amoebic form, ulceration does not begin in the follicles, and when they are afiected it is only in common with the other tissues in the submucous coat. POST-MOETEM APPEARANCES IN ChRONIC DySENTERY. — Wood- ward divides the lesions of those dying from chronic fluxes into three groups, which may exist either singly or variously combined : (1) Chronic inflammation of the mucous and submucous coats of the intestines, especially of the colon without ulceration. (2) Chronic inflammation accompanied by follicular or other ulcers,, especially in the large intestine ; in these cases the pathological picture is often complicated by the development, just before the fatal issue, of diphtheritic inflammation between the ulcers. (3) Extensive ulceration of the large intestine, the result of slough- ing during a previous attack of acute diphtheritic dysentery. To these three groups may be added a fourth — viz. (4) Catarrhal dysentery, becoming chronic and attended by a form of ulceration- differing from the amoebic and diphtheritic. (1) In the first group, chronic inflammation without ulceration, we find that the bright red discolorations of acute inflammation are replaced by mahogany red, brown, green, slate color, ash color, or other neutral tints of various hues. Black, bluish, or brownish deposits of pigment ACUTE CATARRHAL DYSESTERY. 357 are observed in llie closed follicles or in patches scattered over the mucous membrane of both large and small intestines, and in the apices of the villi of the latter, especially of the ileum. With these modifica- tions of color enlargement of the solitary follich's, and more or less thickening of the mucous membrane and sul)mucous connective tissue, especially of the large intestine, are associated. The degree of this thickening varies witii the duration and severity of the case. (2) The second group of cases, including those of chronic inflamma- tion accompanied by follicular or other ulcers, can be properly classitied with the ain(el)ic form. Confirmatory of this view, Councilman and Lafleur stati' that they examined the colon specimens in the Army Medical Museum at Washington, many of the specimens represented among the illustrations in Woodward's book, picking out those which seemed to represent the amoeba forms, and on consulting the histories of the cases found in each a clinical history corresponding to amcebic dysentery. The writer, who has had under observation a larger or smaller num- ber of cases of chronic dysentery for the past twenty years in the hos- pitals of Galveston, is confident in the light of present knowledge that most of such cases belong to the amoebic variety. (3) The third group of lesions in chronic dysentery are those where there is extensive ulceration of the large intestine succeedino^ an attack of the acute diphtheritic form. As a description of the morbid anat- omy of such cases has already been given, it will be unnecessary to repeat it here. (4) Ulceration follo^ving acute catarrhal dysentery has also been described. In these last two groups the patient is gradually exhausted by a long process of suppuration taking place from the unhealed ulcers, or is rapidly carried off by the supervention of an acute diphtheritic in- flammation of the large intestine. 1. Acute Catarrhal Dysentery. Symptoms axd Clixical CorESE. — This form of dysentery often occurs during the progress of an ordinary acute diarrhcea after the latter has lasted a few days or weeks, or it begins as an independent affection, frequently coming on after more or less protracted constipation. In the latter event it is usually preceded by a sense of malaise, with uneasiness in the abdomen, resembling the sensations incident to indigestion. These are succeeded by abdominal griping, accompanied by a desire to go to stool. The dejections are at first feculent and copious, though not infrequently they are scanty, mucous, and without fecal admixture from the beginning. It is only in rare cases that this mild form of the dis- ease begins Avith a rigor followed by fever, as is common in the diph- theritic form. When catarrhal dysentery supervenes upon diarrhoea the stools sometimes suddenly acquire the dysenteric characters ; usually, however, the latter ai-e gradually developed. These characteristics are as follows : At intervals griping abdominal pains occur, generally in the umbilical region, but often extending along the course of the ascending and descending colon, and accompanied by a dull pain in the loins. The pains resemble those of acute diarrhoea, but are usually more severe. 358 DYSENTERY. They are accompanied or followed by an urgent desire to expel the con- tents of the bowels, but the spasmodic efforts that ensue are only suc- cessful in expelling, after prolonged straining, a little mucus or muco- pus, which may or may not be mixed with blood. This scanty dis- charge is not followed by the sense of relief which is noted after the discharge in acute diarrhoea, but painful sensations remain in the rectum and anus even after a lull has taken place in the repeated expulsive efforts. The term tormina has been long in use to describe the griping abdominal pains ; the painful expulsive efforts are called tenesmus. The paroxysms of tormina and tenesmus vary in frequency according to the severity of the attack, from half-hourly, hourly, or longer intervals to every few minutes. In some instances they occur so often that the patient is hardly able to leave the closet. Notwithstanding the violence of these local symptoms, there is usually at first but little constitutional disturbance. The appetite is fair ; there is no complaint of thirst ; the pulse is but slightly increased in frequency ; the temperature is normal ; but usually there is a sense of weakness, causing the patient to prefer the recumbent posture. After a few days, however, there is more or less complete anorexia, coated tongue, nausea, sometimes vomiting and slight fever, the temperature rarely exceeding 100—101° F. The par- oxysms of tormina and tenesmus are usually not so frequent in the morning hours, but increase in number during the afternoon and through the night. The pain and loss of sleep produce debility, rest- lessness, and other evidences of nervous disorders. The disease now may take one of these directions : (a) The symptoms may moderate and convalescence ensues ; (6) they may become aggravated, and the case assumes the character of diphtheritic dysentery ; or (c) they may persist with fluctuations of intensity and gradually pass into a chronic flux. In the milder cases, which constitute the majority, convalescence begins about a week from the time the stools become distinctly dysen- teric. As the case progresses toward recovery the paroxysms of tor- mina and tenesmus become less frequent and painful : the surest sign of approaching convalescence is the reappearance in the stools of fecal matter. The passage of hard fecal lumps (scybala) is not infre- quent in the early stages, or they may occur subsequently from having been collected in the pouches of the colon without being of favorable import, but when the muco-purulent and bloody stools are replaced by those of a semifluid fecal character, we may expect a speedy recovery. In the American Journal of the lledical Sciences for July, 1875, Austin Flint published an important contribution upon the natural his- tory of acute dysentery, consisting of a report of 10 cases observed with- out medicinal treatment. From the analysis of these he concludes : (1) " The disease in a temperate latitude tends, without treatment, to recov- ery ; (2) it is a self-limited disease, and its duration is but little, if at all, abridged by methods of treatment now and heretofore in vogue ; (3) convalescence is as rapid when active measures of treatment have not been employed as in cases actively treated ; (4) relapses do not occur in cases in which the disease has been allowed to pursue its own course without active treatment ; (5) sporadic dysentery in a temperate climate DIPHTHERITIC DYSENTERY. 359 does not eventuate in a chronit- I'urni ul" llu- disease." All of tiie 1(J cases ended in recovery. The most protracted one lasted twenty-one days, of which fourteen were occu])ied by the prcliininary diarrhd'a. The shortest ease lasted six days, 'riic averai>;e duration, excliKlin^- the one with prcliniinaiy diarrh(ea, was about ten days. While these observations of Flint are of ^reat value as slinwin^ the course of the disease when uninfluenced by treatment, and while it is doubtless true, as stated by George B. Wood, that in the vast majority of eases the disease takes this favorable turn, yet when a larger nund)er of cases are observed it will be found that some, after run- ning the course as above outlined for one or two weeks, pass into the diphtheritic form. Others without the latter complication are accompanied by severe symptoms of constitutional disturbance, from impaired digestion, rapid emaciation, exhaustion, and possibly death. Still other cases mav gradually assume the characters of a chronic flux. Vesical tenesmus and prolapsus ani may accompany simple catarrhal dysentery, but are less frequent and intense than in the diphtheritic form. Proctitis. — Cases are not infrequent which present many of the symptoms as above outlined where the inflammatory process is limited to the rectum. Proctitis, as this condition is called, may be acute or chronic, and may depend upon a multitude of causes. The acute forms, as pre- viously mentioned, may be due to dietetic errors. There are some persons in whom the rectum appears to be the pars minoris resistentke. Dysen- teric symptoms in such individuals may follow the ingestion of articles of food which in others would be entirely innocuous, or irritant foods, which in most persons would be follow^ed by a simple diarrhcea, in them produces a proctitis. Traumatic influences of various kinds play an important role. Among the more common of such causes are the pres- ence of foreign bodies, impaction of fecal masses, intestinal parasites, abnormal sexual intercourse, careless use of instruments, etc. The con- dition is also often consecutive to other abnormal processes of the rec- tum and neighboring organs — e. g. hemorrhoids, polypoid growths, pro- lapsus, cancer, stricture, gonorrhoea, uterine and periuterine inflammation. The long continuance of any of these factors may result in chronic inflammation and ulceration of the rectum, as well as of suppuration in the perirectal tissues. The enumeration of these causes emphasizes the necessity in all cases, when the symptoms point to the rectum as the seat of the disease, of making a careful physical examination by touch and speculum, as a removal of the cause constitutes the most important indi- cation for treatment, and is alone in many instances sufiicient to eflect a cure. As proctitis is fully described in special treatises, it is not neces- sary to enlarge upon the subject here. 2. Diphtheritic Dysentery. Symptoms and Clinical, Course. — This form may begin in four different ways : 1. It may have been preceded by the symptoms as above described of a simple inflammatory dysentery. 2. In numerous cases it may be abruptly developed during the process of a chronic flux. 3. A 360 DYSENTERY. primary diphtheritic dysentery may occur without having been preceded by any preliminary catarrhal stages. 4. It may occur in a secondary form after various acute and chronic diseases, mth an absence of bowel symptoms or a diarrhoea consisting of three or four large movements during the day or perhaps the joassage of a little blood and mucus. Those cases beginning as an acute catarrhal dysentery, instead of pursu- ing the ordinary course toward recovery, as above outlined, exhibit a more or less gradual aggravation of all of the symptoms. The patient grows more emaciated, becomes very weak, and eventually sinks into a condition of collapse, with cool surface and extremities and greatly enfeebled heart action. As the disease progresses the tongue becomes brown and dry or smooth, red, and dry, sometimes fissured ; the anorexia and thirst become extreme ; the abdomen tender to the touch and often distended with flatus ; the skin is sallow or slightly jaundiced ; the expression is anxious ; the eyes appear sunken and acquire a vacant expression. Pari jmssu with these symptoms there is a change in the character of the stools, which at first consist of stringy mucus, more or less mingled with blood and pus, but now contain a quantity of yellowish or reddish masses of various sizes, which upon microscopic examination are seen to be necrosed particles of the diphtheritic exudation. The mucus or muco-pus of the stools is now mingled with a thin reddish serum, which sometimes entirely replaces it. In this fluid the pieces of necrosed membrane float, giving the passages the appearance of raw meat minced and mixed with bloody Avater. The stools have a charac- teristic cadaveric odor. About this time the skin around the anus is apt to become excoriated ; prolapsus ani is likely to occur from the extreme tenesmus. The patient also complains of strangury and vesical tenes- mus. The urine is generally decreased in amount, is of high color and specific gravity, and is occasionally albuminous. Notwithstanding the extreme exhaustion, the patient often survives till the end of the second, third, or even fourth week from the com- mencement of the dysenteric symptoms. Death in the third or fourth week is apt to be the result in cases presenting the above-mentioned characteristics. Usually a few days before the fatal ending the stools become brownish or black and of a very offensive putrid odor; they also often contain larger fragments than before of necrosed mucous membrane, though this is not uniformly the case. Those cases which are not preceded by diarrhoea, but begin as dysentery from the first, pur- sue a similar course to that above sketched. Not infrequently they begin with a chill, followed by fever and the onset of the abdominal symptoms ; the temperature is usually higher than in the type just descriljcd. Pro- nounced nervous symptoms are not unusual — headache, delirium, flushed dusky face, and subsultus tendinum. The fever passes into a typhoid form, with sordes upon the teeth, a rapid weak pulse, 110—140, and a continued high temperature. Those cases which begin with an active fever frequently pass into a condition of collapse, with slight elevation of temperature, cool surface, and a pulse which, though full, is but little accelerated or slower than usual. When diphtheritic dysentery is developed during the progress of a chronic flux, it is apt to occur suddenly and prove rapidly fatal, the patient being already exhausted from the chronic disorder, and probably AMCEBIC DYSENTERY. 361 in tv state of excessive cmaciiition. After some exposure to cold, intein- jHTance in eatinji; or (Irinkinj:;, and often without any assilla[)sc. In the mng continned agne or after remittent fever had been first deveh)j)ed. In still other cases malaria was manifested by chronic poisoning ; the resnlting cachexia, whether existing l)y itself or associated with mild scorbntic taint, was so widely spread as to favor the development of ilysentcry as well as diarrluea. The subjects of this cachexia seemed less able to resist the causes of the disease than healthy men, and, once developed in them, dysentery, even in its simple or catarrhal form, was more a])t to become chronic and to prove fatal. Not only were the ordi- nary forms of intermittent and remittent fevers observed, but occasion- allv paroxysms of pernicious malarial fever. Though the paroxvsms were otten ol)stinate and prone to recur, yet quinine was essential to control them, and its power in this reg-ard was strong proof of the malarial nature of the complication. Notwithstanding the general con- sensus of opinion as furnished by army surgeons npon this subject, the diagnosis is beset with difficulties, and has doubtless often been made upon insufficient grounds. Osier mentions the fact that with but one exception the cases of dysentery he has seen associated ^snth intermittent pyrexia were due to suppuration. This observation is in accord with the winter's own expe- rience in a hospital drawing its material from an extensive malarial country. I cannot recall a single instance of undoubted association of malarial fever with dysentery. It would thus appear that the malarial element is not so likely to be associated with dysentery in civil as in army practice. W. C Maclean gives these symptoms of malarious dys- entery : " Such cases will be recognized by the periodicity^ of the febrile paroxsyms, the presence of gastric irritability, such as we see in remit- tent fevers, and by the peculiar nature of the evacuations, which from the first are serous and contain but little blood, but have the character- istic dysenteric odor." Other writers mention the periodicity in the frequency of the stools, while the occurrence of chills is regarded as significant of malaria. Such evidence is not conclusive, for fever of remittent or intermittent type, marked gastric symptoms, diarrha?al rather than dysenteric stools, and periodical exacerbations of the intestinal flux are symptoms recog- nized in dysentery when malaria can be excluded, while rigors with intermittent pyrexia and sweating are frequently indicative of suppura- tive processes in the liver or elsewhere. These facts should guard us against the hasty assumption of malarial infection, which can be diag- nosticated with certaintv bv the discovery in the blood of the haematozoa mala rite. Ti/phoid and Typhus Fever. — The combination of adynamic fevers with dysentery has been long recognized, and no doubt a tendency has existed to over-estimate their frequency by confounding the typhoid febrile symptoms which, as we have seen, are not infrequently developed in connection with certain forms of dysentery with true typhoid or typhus fever — an error which has been favored by the peculiar charac- ters assumed by dysentery in certain epidemics. ^Nlany writers of the last century went so far as to describe dysentery as merely one of the varieties of typhus, giving it the name of " colotj'phus," and looking 372 DYSENTERY. upon it as the local manifestation of the typhus contagium ; but since the anatomical test has been applied it was found that in many of the so-called cases of typhoid dysentery there was an entire absence of the characteristic lesions of typhoid fever, leading Rokitansky to express the belief that the coexistence of dysentery with typhoid fever is excessively rare. But that this complication does occur, and not infrequently, has since been shown by numerous observers — first by Trousseau and Par- mentier in 1826; since by Parkes in India, by Baily at the Millbank Penitentiary, London, by Finger during an epidemic in the hospital at Prague, and by Lyons during the Crimean War. These observations were confirmed during the American Civil War, not merely by clinical observation, but by autopsy and preservation of the specimens in the Army Medical Museum. Woodward states it was so common to find the characteristic lesions of typhoid fever in the ileum and of dysentery in the colon that he was led to believe that the combination was likely to occur in every army where typhoid was the prevailing fever. The complication supervenes much in the same way as in malarial fever ; that is, the continued fever and dysentery run their course simultane- ously, or either appears as the primary disorder, to which the other was subsequently superadded. With reference to the coincidence of typhus fever and dysentery, aside from the brief statement that it does occur mentioned by several authorities, I find no details. My friend. Dr. C. Warfield, who has had an extensive experience with typhus fever in Northern Mexico, states that diarrhoea occurred in about 20 per cent, of the cases, and that occasionally dysenteric symptoms were present. The lesions of dysentery, however, were not confirmed by autopsies. Dysenteric Arthropathies. Since Sydenham mentioned the occurrence of joint symptoms in an epidemic of dysentery in 1672, they have been met with in numerous epi- demics, as that of 1765, described by Lepecq de la Cloture and Zimmer- mann; 1776-77, described by Stoll ; 1835, described by Thomas; and that of 1854 occurring in the canton of Montargis in France, described by Huette. In the American Civil War the pains in the limbs and back which were common in connection with both acute and chronic dysentery were in most instances, according to Woodward, rather due to malarial and scorbutic neuralgia than to rheumatism. Dewevre has recently made an interesting report upon this subject, giving the results of this complication in 65 cases, 15 of which occurred among 445 cases of dysentery Under his care in the military hospital at Lyons, France, during the summer of 1885. He found the onset of articular symptoms to begin at variable periods of the dysenteric attack. Out of 60 obser- vations in which the date of invasion was mentioned, in 9 it fell in the first week, in 7 in the second, and 44 in the first days of convalescence or several weeks later. Occasionally the development of the arthropathy is preceded by a sudden arrest of the intestinal symptoms, or the course of the joint lesion is interrupted by reappearance of the flux. In one case the alternation of articular and intestinal symptoms recurred three times in the same individual. The invasion is always sudden, and at first affects but a single joint. Of the 63 cases, the attack began in the DY^EyTERIC rARALYSES. 373 knees 25 times, in the ankles 16 times, in the shonldors 9 times, in the elbow 4 times, in the hip once, in the ritrht middle finfrer once, in the toe once, in the tempiu-o-niaxillary articulation once, and once in the sterno-clavicular articulation. The SYMPTOMS are of slight intensity. There is bnt little pain, and either no fever or a slight and temporary rise of temperature, and no other disturbance of the general health. The patient usually first notices trouble with the joint upon making some slight mo\'ement. The ligamentous attachments are tender, with some swelling of the periarticular tissues ; usually there is no effusion into the joint and no redness of the overlying skiii. Hydrarthrosis may, however, occur, ])articularly in the knee, when it may distend the capsule and render movement difficult. Limitation to a single joint is exceptional, occur- ring in only about 8 per cent, of the cases. After a few hours or days other joints are implicated, but with less intensity, the last joint to recover being the one primarily attacked. All the joints may be attacked successively, but usually the number is limited to three or four. In cases of hydrarthrosis absorption is slow. Restoration of the functions of the joints involved, although sometimes requiring only a week, is usually protracted to a month or several months, and is most obstinate when the smaller joints are affected. Neither ill health producing the dysentery nor a severe course of the disease seems to predispose to the arthropathies. On the contrary, they are more frequent in robust subjects, who have been but little weakened by the dysentery, than in the weak and cachectic, and in the mild rather than in the severe cases. Exposure to cold or over-exertion was not observed as a possible causal factor. Various explanations have been offered to account for the connection between dysentery and arthritic troubles, but none of them are entirely satisfactory. Stoll and his followers, looking upon dysentery- as a rheu- matic affection, found a ready explanation in a simple metastasis to the joints. Others based the occurrence of arthropathies upon the exist- ence of a " reflex relation " between the articular and intestinal lesions. Some of the observers regard the rheumatoid symptoms as the manifes- tation of a mild pysemic infection. The most probable solution of the question appears to be that the joint affection bears the same relation to dysentery as it does to other infectious diseases — e. g. scarlet fever, typhoid fever, cerebro-spinal meningitis, dengue, etc. ; that is to say, it is not a genuine rheumatism, from which it differs in many essential particulars, but it is the localization of the infectious agent or its prod- ucts acting upon the joints through the circulation. Dysenteric Paralyses. The most important contributions to the study of the paralytic com- plications of dysenterv have been made during the latter half of the present century. Cases have been reported and the pathology discussed by various writers, notably Delioux de Savignac, Leyden, Barie, Weir Mitchell, "Woodward, and Pugibet. The latter in 1888 gave a most valuable resume of the subject, from which the details here given are mainly derived. Paralysis may occur in both the acute and chronic 374 DYSENTERY. forms of dysentery, sometimes during the course of the attack, but usually as a sequel. By far the most common form is paraplegia. The upper extremities may be also involved ; hemiplegic and monoplegic cases have been reported, and diffused general paralysis has also been observed. In some cases the onset is sudden, developing within twenty- four to forty-eight hours, and lasting but a short time — three to twenty- eight days. In other instances the paralysis has a gradual development, this appearing to be the usual history of the paraplegic form. Paralysis of the vesical and anal sphincters and girdle sensations are usually ab- sent. The paralysis is rarely complete in all of the muscles of the limb or in muscular groups elsewhere. Among muscles innervated by the same plexus some may be affected and others not. Sensory dis- turbances are usually not prominent, but in some cases neuralgic pains, tingling sensations, cramps, and limited anaesthesia were observed. In an analysis of 17 cases reported by Pugibet, including his ow^n and those of several other observers, in 13 the paralysis lasted four months, in 4 it was stationary at the time of the report, in 2 death resulted from the paralytic lesions, and in 4 it was independent of them. In speaking of the cases of palsy connected with dysentery. Weir Mitchell states that in nearly every instance there had been many possible causes, as long marches, bad diet, malapa, or spinal injuries, the latter being so common that almost any soldier long in the service had some to relate. It was thus difficult to fix upon any single factor as essential, as it was likely that several contributed to influence the result. The pathologi- cal condition underlying dysenteric palsies has not been satisfactorily studied, and the views which have been presented to explain their origin are largely theoretical : some of the reported cases were due to central lesions, and others were cases of multiple neuritis. Sequels of Dysenteey. — Among the more important sequels© especially of chronic dysentery are prolapsus ani, anal fistula from peri- neal abscess, and hemorrhoids, these conditions being largely the result of mechanical causes. Indigestion, irritability of the bowels, or obsti- nate constipation are not infrequent. Intestinal strictures resulting from cicatricial contraction after the healing of dysenteric ulceration, according to Woodward, are exceedingly rare. Profuse intestinal hem- orrhage after subsidence of the dysenteric flux is a sequel mentioned by my colleague. Dr. Clopton, as occurring not infrequently in his expe- rience. It is not, apparently, due to ulceration, but rather to a dis- eased condition of the walls of the intestinal bloodvessels and to the morbid state of the blood itself. Diagnosis of Dysenteey. — The recognition of the catarrhal form of dysentery is usually easy, the frequency of the stools, the presence in them of blood and mucus, the tormina and tenesmus producing a characteristic clinical picture. Local affections of the rectum, syphilitic and chancroidal ulceration, cancer, strictures, the presence of foreign bodies, and intussusception, especially in children, may produce straining and the passage of mucoid and bloody dejections. A careful physical examination in such cases will generally with- out difficulty determine the diagnosis. The acute diphtheritic form with its rapid and intense onset and severe constitutional symptoms may readily be mistaken for enteric fever. The higher temperature PROGNOSIS. 375 of dysentorv, the aggravated intestinal symptoms, the presence in the stools in the early stages of blood and mucus, and later of di|)h- theritic sloughs, the absence of enlarged spleen, and the charac- teristic rose eruption of typhoid fever, shoiihl guide to a correct dif- ferentiation. The aincebic form can be recognized by a careful miero- seo})lc exaniinatit)n of the stools, which should be made in every case where, with a deterioration of the general health, aiuemia, and impaired nutrition, there exists a disposition to looseness of the bowels. The irregular and chronic course of these cases should be borne in mind. A j)aticnt may not be bedridden, and even be in a fairly good con- dition, with well formed stools and very insignificant intestintd disturb- ance, and yet in the adherent particles of mucus in the fjeces the amcjebae can be discovered. In such a patient an intense relapse is liable to occur at any time or a complication with liver or lung abscess. Cases are not rare in which the intestinal symptoms are either entirely in abeyance or so slight as to attract no attention until the occurrence of hepatic abscess, which may be detected during life by the presence of the symptoms heretofore detailed, or when rupture has taken place into a bronchus by finding the amoebse in the sputum. In other instances the existence of amoebic dysentery and subsequent abscess of the liver is not recognized until revealed by the autopsy. With regard to the diagnosis of secondary dysentery, attention has already been called to the fact that the absence of characteristic dysen- teric symptoms is the rule in these cases, and that the intestinal compli- cation is but rarely suspected during life. The knowledge that an extensive colitis, and perhaps ulceration, may be manifested only by a slight diarrhoea when it occurs during the terminal stages of some severe adynamic disease should not be lost sight of, as the prognosis in the presence of such a complication will be materially aifected. The necessity of careful physical examination by touch and speculum in chronic cases, and where the rectum appears to be involved, has been previously mentioned. Prognosis of Dysentery. — The prognosis in sporadic dysen- tery in adults is favorable both as to the certainty and speed of recovery, though it is to be borne in mind that a certain propor- tion may eventuate in the diphtheritic form, ultimately proving fatal, or others become chronic and pursue an indefinitely prolonged course. On the contrary, there is hardly any disease in wliich the mortality is more frightful than epidemic or diphtheritic dysentery. The circumstances upon which the epidemicity depends contribute very greatly to increase the mortality. It is unnecessary here to recapitulate these influences in detail : it suffices to say that impair- ment of constitutional vitality from long continued infraction of hygienic laws, over-exertion, loss of sleep, exposure, improper and badly cooked food, overcrowding, filthy surroundings, impure water, are the conditions associated with epidemics of this disease. When we take into consideration the further fact that it frequently attacks those whose powers are already enfeebled by the existence of some other severe disease, and when we consider the extent and severity of the intestinal lesions, we can understand that the death rate may vary from 50 to 80 per cent. The outcome of individual cases can be judged by 376 DYSENTERY. the severity of the symptoms. Rapid emaciation and debility, dysen- teric collapse, cool surface and extremities, dry, brown tongue, heart failure, anorexia and excessive thirst, tenderness of the abdomen, anxious countenance, shrunken features, sero-sanguinolent stools con- taining masses of necrotic tissue having a cadaveric odor, a putrid scent from the body, and persistent singultus, are symptoms of extensive intestinal sloughing and forebode a fatal ending. When diphtheritic dys- entery supervenes during the progress of the chronic form, or occurs secondary to some severe acute or chronic disease, the patient, being already exhausted and emaciated, is apt to succumb in a few days. Less severe cases may assume a subacute type, often lasting a month and a half to two months, and may end in recovery or pass into a chronic flux of indefinite duration. It should not be forgotten that even extensive ulceration is not incompatible with cicatrization and cure. The prognosis in children will be governed by the constitution and surroundings of the child, the ability of parents to execute proper measures of treatment, the season of the year when the attack begins, and the occurrence of complications. It goes without saying that the prognosis is more unfavorable when the child is already the victim of malnutrition from tuberculosis, rickets, or syphilis. The chances for recovery are worse in crowded centres of population, among the poor, in teeming tenement houses, where a change of air and proper alimenta- tion cannot be secured. Cases beginning in the early summer are less hopeful than those occurring later. The prognosis is worse in children prematurely weaned and improperly fed or who have suffered with pre- vious attacks of diarrhoea. Persistent fever, vomiting, rapid wasting, and severe nervous symptoms are of ill omen. "The form of stool which is of worst augury is that composed of greenish matter like chopped spinach in dirty brown, stinking fluid, and mixed with puru- lent mucus and blood ;" the thicker and more homogeneous the motions become, although they may still be intensely offensive, the more favor- able is the prognosis. Continuance of normal dentition, the appearance of tears, and, according to Eustace Smith, the occurrence of an eruption unconnected with the exanthemata, are signs of favorable import. Re- covery is possible even in cases in which the symptoms are violent. Under no circumstances are the recuperative powers of nature in chil- dren more wonderfully exhibited than sometimes in aggravated cases of dysentery. I have seen restoration to health wiien high fever, vomit- ing, excessive purging, bloody and mucoid stools, rapid emaciation, and exhaustion would have seemed to render such a favorable ending hope- less. The prognosis in amoebic forms, whether gangrenous, chronic, or of moderate severity, is always uncertain ; the gravity of the disease lies in its tendency to persist : the latter is inherent, depending upon the nature of the lesions and the fact that they are so refractory to thera- peutical measures. The frequency of hepatic complications, the con- stant tendency to chronicity in cases not rapidly proving fatal, are fac- tors rendering it very difficult to foretell the result. A duration of two to four or six months in recovered cases and an average mortality of 33|- per cent, are about what can be expected. Treatiment of Dysentery in General. — Prophylaxis. — It is PROPHYLAXIS. 377 a truthful sayinji^ and worthy of" universal acceptation with rop^ard to erous, so that after an extensive but brief popidarity it fell into tlisuse. Sueh has been the fate of many other so-called specifics. Ipecac is the remedy which has attained a f^reatcr reputation than any other as a spccilic for dysentery. Its use in this disease was made known by Piso in 1G48; he described it as a "sacred anchor, as the most exquisite gift of nature," claiming that it not only evacuated the morbid humors by purging as well as by vomiting, but produced revul- sion from the diseased intestine, and that an astringent effect succeeded its primary action. It was forgotten for a time until reintroduced by Adrian Helvetius as an antidysenteric nostrum. The secret was bought by Louis XIV. and given to the profession of the time, by whom it was regarded as a specific for dysenteric fluxes ; but the belief gradually died out. Broussais used his influence against it, though it still c;on- tinued to be prescribed by a few until in 1851 it was made the subject of a special essay by Savignac, who ascribed its beneficial results to not only its emetic and purgative action, but to its diaphoretic, sedative, and alterative influence. The article of Savignac did not attract much attention. In 1858, Docker, who had successfully employed ipecac on the island of Mauritius in the treatment of dysentery, called renewed attention to the subject. His plan of administration (the one still used) was, having put the patient to bed, to give a drachm of laudanum, apply a sinapism over the stomach, half an liour later to give from thirty to ninety grains of powdered ipecac, usually in a bolus ; if this was vomited, he repeated the dose until it was retained. A single dose often sufficed for a cure, the pains promptly subsided, and the stools ceased. He gave it to patients of various constitutions and in all stages of the disease with equal benefit — out of 50 cases he lost but 1 . The pub- lication of Docker's results was followed by the rapid and successful introduction of his method in India, where it was advocated by Donald- son, Cunningham, Ewart, and others. In England it received the sup- port of Waring, Maclean, and Aitken. During the American Civil War the ipecac treatment was not very thoroughly tested ; its trial, however, at the Ecklington Hospital, AVashington, D. C, and in an epidemic at Columbia, S. C, was not favorable. Better results have been reported at various times in medical journals of the United States by the non-emetic use of the drug in sporadic dysentery and also in chronic fluxes. It has been used to a certain extent on the continent of Europe, and, it is stated, with fair success during the late Franco- Prussian War. Maclean has been a most enthusiastic advocate of the ipecac treatment. He says in 1868, "a decade after the introduction of this treatment into India, that it is now almost invariably followed ; it has reduced the former mortality by from 25 to 75 per cent. ; it is, in his opinion, the most simple, the most successful, the most conservative treatment he has ever seen used in dysentery. Year by year under its use the number of chronic cases is becoming smaller and hepatic abscess less frequently seen." Joseph Ewart in 1883 speaks of it with the same enthusiasm. Numerous other writers in India corroborate these vie-^vs. Recently, however, there has been a modification of opinion 380 DYSENTERY. upon this subject. Dobie ^ says that the treatment by large doses of ipecac has fallen into disfavor. Chowdhovry says that both in civil hospitals and private practice it has been found unbearable in many cases. While neither of these writers have lost faith in the ipecac treatment, they advocate its use in much smaller doses. Upon this subject Woodward judiciously remarks : " It will be observed that in the most modern times the use of ipecacuanha in the treatment of the fluxes has re-established the reputation it enjoyed in the seventeenth century, and is regarded in many quarters with a confidence as blind as that reposed in it by Piso or Helvetius. Nevertheless, a little reflec- tion must show the absurdity of expecting benefit from such a remedy in acute diphtheritic dysentery after the formation of the diphtheritic layer, in the chronic fluxes after extensive ulceration has already occurred, or in those cases which owe their virulence to the co-existence of a scorbutic or some other constitutional taint. It is easy to recog- nize, by the details of the majority of the successful cases recorded in which the virtues of ipecac are most lauded, that they were sporadic, for the most part mild acute forms, and against the small number of chronic cases reported to have been successfully treated must be offset the contrary results of the larger clinical experience of the Ecklington and Dreadnought hospitals." While the above is perfectly true, and while the ipecac treatment, in spite of oft-repeated trials, has never gained a foothold in this country, w^e must concede that in tropical and certain severe cases of catarrhal dysentery it is a remedy of great value : the number of those who testify upon this point and their reliability leaves us no room for doubt. It is possible, as suggested by Ball, that the discrepancy of results as obtained in America and India may be due to the fact that ipecac possesses especially curative powers in the amoebic form ; if so, such results must follow only in the earliest stages, for it is only necessary to reflect upon the nature of the lesions to be convinced that we cannot rationally expect any immediate cure from ipecac or any other remedy after the intestinal ulceration has fairly commenced. As regards the use of this drug in much smaller doses, one to three grains every two to three hours, while this method has received the sanction of some of the highest authorities, the writer must express his skepticivSm, for the reason that, so far as he knows, there has been no systematic experimentation with this remedy alone : the exigen- cies are such that other remedies are generally prescribed at the same time, leaving the effects of the ipecac in doubt. Careful clinical obser- vation only will settle these questions. Opium. — The history of the use of this remedy in the treatment of intestinal fluxes is exceedingly interesting. Its unique and incompar- able therapeutic powers have caused its administration to enter more or less into every plan of treatment of these diseases from prehistoric times down to the present day. It was of the effect of opium in dysentery that Sydenham wrote his celebrated eulogy beginning, " And here I can- not but break out in praise of the great God, the Giver of all good things, who hath granted to the human race, as a comfort in their afflic- tions, no medicine of the value of opium, either in regard to the num- ber of diseases it can control or its efficacy in extirpating them." ' London Lancet, 1888. MEDICIXAL 'J'JUJATMJ'JNT. 881 TIk' position of o])iuin us a ivmcdy for dysontoric affections is a peculiar one. It has hei'U used by tliose who abuse it, and abused by those who use it. The controversy as to its proj)cr phice and ])o\vers, which has been of very long standing, is still unsettled. \\'itliout attempting to enter fully into the history and merits of the dis[)utation between the extremists (»n the one hand, who claim that opium is a sov- ereign remedv in all forms and stages of dysenti-rv and has peculiar anti])iiiogistic powers, and those, on the contrary, wh(» hold that it is procluctive of more harm than good, I shall endeavor to deline its true place and powers in the treatment of dysenteric disorders. The fact that it has maintained its position for centuries in spite of the very strong opposition to its use and the excellent reasons for the same is very good evidence that opium is possessed of j)eculiar and positive virtues. As an analgesic it is unsurpassed. In a disease where pain, excessiv^e intestinal peristalsis, loss of sleep, and ofttimes both primary and secondary nervous depression, play such an important part it is diffi- cult to dispense with opium in some form or at some time, no agent hav- ing yet been found to equal it for the relief of these symptoms. The objection which has been strongly and truthfully urged against its use is that it produces anorexia, nausea, arrest of secretion, indigestion, ner- vous depression, constipation, and retention of acrid irritant contents of the intestine. While freely admitting these evils, the practical conservative thera- peutist still finds in opium a remedy difficult to dispense with. The ground taken by George B. Wood, Stille, Flint, and a host of the fol- lowers of these great leaders of medical thought in this country, that opium exercises some special power in controlling the inflammatory process of the intestines, is not now regarded as tenable, for, as Ball pertinently asks, " What reason is there to suppose that in croupous and amoebic inflammations of the colon Opium exercises any more of an antiphlogistic power than it does in typhoid infection of the small intes- tine or in diphtheria of the throat ? For my own part," he says, " ex- perience has taught me more and more to distrust the fallacious effects of opium in dysenteric diseases, and I am quite sure that this conclusion is in accord with most recent anthorities." Accepting this warning, as well as that of Galen, who wrote, sixteen centuries ago, that '' those who resort to anodyne remedies at improper times or immoderately jugulate the sick along with their pains," we still find an indispensable place for opium : especially is this true in severe cases of the catarrhal and diph- theritic forms, obviating its acknowledged e\'il effects by proper doses and judicious combination and alternation with other medicines. Not expecting any specific effect upon the inflammatory or ulcerative pro- cess, we give it to ease the pain, to reduce the excessive frequency of the actions, to control morbid peristalsis, to relieve the agonizing tenesmus, to afford needed rest, and to overcome the profound nervous shock inci- dental to the diseases we are dealing with. It is for these reasons that those who have urged the strongest objections against the prescription of opium have themselves employed it while abusing it, and, having most excellent grounds for so doing, they are nevertheless compelled to use it. Until some remedy is found which possesses the therapeutical powers of opium without its objectionable features it will still occupy a 382 DYSENTERY. prominent place in the list of remedies for the treatment of dysenteric diseases. Purgatives, — Mild purgation for the purpose of evacuating the ali- mentary canal of the peccant humors, being in accordance with the humoral pathology, has been resorted to in the treatment of intestinal fluxes from the earliest times. It was generally admitted that drastic cathartics were objectionable, on account of their irritant effects ; hence the milder laxatives, especially those having an after astringent effect, were preferred. According to modern views, purgatives are used in the treatment of dysentery to fulfil the following indications : (a) To cleanse the alimentary canal of various irritants, as undigested food, hardened fecal masses, and decomposing secretions ; (6) to increase and modify intestinal and other glandular secretion, thus aiding absorption and assimilation ; (c) by increased secretion to favorably influence congestive and inflammatory processes of the intestines. The remedies which have been most extensively used to accomplish these ends are rhubarb, castor oil, calomel, and the salines ; of the latter especially the sulphates of soda and magnesia. As to rhubarb, while its secondary effect may render its use occasionally advisable in mild cases or in children with irritant intestinal accumulations, its tardy, uncertain, and painful action ren- ders it generally objectionable. Castor oil, on account of its certain, rapid, and generally unirritant action, has been extensively used, especially in England and the United States. Illustrative of the extent of its consumption. Woodward states that nearly a quarter of a million of quarts were purchased by the pur- veying department of the army during the four years of the American Oivil War, and either alone or combined with laudanum or turpentine it was the favorite purgative in dysentery. It is not now very often prescribed for adults on account of its nauseous taste, and the fact that it is a simple evacuant ; it is, however, quite frequently given with advantage in the mild fluxes of children, as well as of adults, in the form of emulsion and in combination with opiates to obviate any griping effects. Calomel appears to have been first used in the treatment of dysentery early in the seventeenth century. It was very extensively employed, and an immense amount of harm done with it during the first half of the present century. It was used not only for its effects upon the intes- tinal canal, but in conjunction with mercurial inunctions and opium in order to produce salivation. The extent to which it was misused is almost incomprehensible. Cunningham in 1805 gave it in twenty-grain doses repeated two or three times a day, one of his patients taking in this way three hundred and sixty grains. In ordinary dysenteries John- son was content to give daily twenty -four to forty-eight grains of calo- mel with two to four grains of opium and ten to fifteen of antimonial powder or ipecac. The enormous mortality necessarily resulting from such heroic medication did not appear to disabuse the minds of those who resorted to it : it was not until 1844 that this practice ceased in India, but calomel continued to be used in more moderate doses until 1860, when it was displaced almost entirely by the ipecac treatment. The abuse of this medicine in Europe and in the United States was notable, but not so great as in the tropics. MFA)icL\. 1 L rn /■;. i tmext. 383 Diirino; the Aniorican Civil War calonu'l Avas cxtciisivclv used in tlio troatnuMit ofdyscntcrv. It was misused to siicli an extent, in the opin- ion of the yni-o-eon (Jeneral, that he issued an order directing that it he struck from the suj)|)ly table of the army, and that no further re(|uisi- tion for this medicine should be approved by Medical Directors. \Vhile this ]>iece of official despotism -svas denounced by the American Medical Association as "an unjust charg-e of Avholesale inalj)ractiee a<;ainst the army suroeons, and as unwise and unnecessary," it illustrat<'s the change of oj)inion upon this subject, for, though it was so extensively used twenty years ago, Ball comments upon the fact that Osier does not even mention calomel as a remedy for dysentery in his recent work upon the Practice of Medicine. In spite of the terrible abuse of this remedy in the past, and the fact that it has been negatively placed upon the black list by such a high authority as Osier, the writer is of the opinion that calomel judici- ously and carefully used fulfils some important indications in the treat- ment of dysentery : especially is this the case in the presence of malarial complications. Here and in similar conditions, where there is a morbid condition in the processes of absorption and secretion of the alimentary glandular organs, calomel exerts a unique beneficial influence. It should not be used as a purgative, for we have those which are milder and more rapid, but solely for its alterative effect, which can be obtained by small doses and without harmful results. Saline Purgatives. — The salines have long sustained a well deserved reputation in the treatment of dysentery. In many respects they are superior to any other purgative. As cleansing agents their rapid action, the increased secretion produced by them, their mildness and certainty, are special advantages ; in addition to which they are acceptable to the stomach, deplete the intestinal bloodvessels, and, it is claimed by some, increase the secretion of bile. Rapidly following their use the bloody and mucous stools are replaced by free liquid fecal dejections ; the tormina and tenesmus are relieved ; many cases of the sporadic form require no other treatment than a free saline purge. The sulphate of magnesia or sulphate of soda are to be preferred. Details as to methods of admin- istration and dosage will be hereafter mentioned. Vegetable and 3Iineral Astringents, — Remedies of this class adminis- tered by the stomach have been more or less extensively used in the treatment of intestinal fluxes for centuries. It will only be necessary to speak of a few of them as representative of the class. They are advised for the supposed effect of checking excessive and abnormal secre- tion and of stimulating to healthy action an inflamed or ulcerated mucous membrane. Tannic or gallic acid will doubtless represent all the virtues of the vegetable astringents ; of the minerals, the salts of iron, lead, copper, and silver are typical. Most of the members of this group have very properly been discarded in the treatment of dysentery. Nitrate of silver, however, still has the sanction of high authority, especially in chronic cases. In its administration the question alw^ays arises. How can we rationally expect a half grain of this easily altered salt to run the gaunt- let of chemical change from stomach to colon, and then produce any material effect upon the extensive surface of the latter, as it is generally 384 DYSENTERY. given in combination with other remedies ? The verdict upon its use by most clinicians will be " utility doubtful." Antiseptics. — The most important agents of this class are bichloride of mercury, the salts of bismuth, creasote, carbolic acid, salol, naphtha- lin, resorcin, creolin, tricresol, etc. These remedies have been advised for use per os upon the germicidal theory, and prescribed with varied success in dysentery and kindred aifections. Without stopping to dis- cuss the merits of this theory, or how far it is practicable to reach from above and destroy infectious organisms in the colon, let us view them from a clinical standpoint. Corrosive sublimate was recommended by Kopp in 1827, subsequently by Eisenmann and Parkes, more recently by Ringer ; the latter claims that in the acute fluxes with frequent bloody, slimy stools rapid relief is effected by hourly doses of yro **^ T2"o^ grain. It perhaps may do good in some cases, but its virtues have not been generally substantiated. Subnitrate, Subcarbonate, SubgaUate, and Salicylate of Bismuth. — These salts of bismuth produce very similar results, and the consensus of opinion is decidedly favorable as to their beneficial action, more espe- cially in the chronic fluxes. Exactly the modus operandi of bismuth is not known positively : judging by its local effects, we conclude that it is slightly astringent, antiseptic, and protective. When perfectly pure it can be given in such large doses (thirty to sixty grains) as to ensure its passage through the colon. It subserves its best purpose after the acute stage has passed and the intestine has been emptied of all irritant con- tents. In chronic cases it aids in the healing process and decreases the frequency of the stools. Creasote and Carbolic Acid. — The well known antiseptic and anti- putrescent power of these drugs commend them for trial in dysentery. The difficulty to overcome in their use is to introduce them in suf- ficiently large quantities to produce an antiseptic effect upon the intes- tine without poisoning the patient. So far, this objection as to carbolic acid has proven to be insuperable. Recently creasote has been given in much larger doses in the treatment of tuberculosis than was formerly thought possible ; though it has been warmly praised in some quarters, its positive value in dysentery has not been established. NaphthcUin, resorcin, salol, and numerous other members of the phenol group have been advised and, especially the latter, extensively used in dysentery and kindred affections upon the ground that effectual intestinal antisepsis could be produced by them without danger of toxic effects. Good results have been claimed for naphthalin given in five- grain doses three or four times daily. I can speak of the value of salol from quite an extensive experience in the acute diarrhoeas and dysenteries of both children and adults, as well as in the obstinate looseness of the bowels in the amoebic form. Combined with large doses of bismuth, it appears to exercise better control over this obstinate diarrhoea than any other remedy. It can be given in large doses (twenty grains to an adult) and kept up for days without harmful results. Tricresol. — A combination of ortho-, para-, and metacresols, con- stituting tricresol, now obtained in a pure state from coal tar, has recently been the subject of studious investigation by chemists, bacteri- ologists, and surgeons in Germany and elsewhere. This new claimant TREATMENT OF CATARRHAL DYSENTERY. 385 for antiseptic honors is siiid to possess deeideil advunta^^es over its older competitors — viz. that it will act in the presence of albumin, and that, beinij; five times as powerful as carbolic acid, it will ])ro(hice intestinal antisepsis without dauo-er. II. Kolch rej)orts 12 cases of tyj)ln>iivin*>- it in doses of one and one half grains dissolved in oUve oil by means of potash soap in capsule three times daily after milk. The result was rapid convalescence in thirteen to eighteen days and an absence of all severe symptoms. If these favorable reports are confirmed, the remedy commends itself in the treatment of dysentery, both by the stomach and by injecticjn of a solution in the bowel. Medicatio)i by the Rectum. — The plan of treating inflammatory dis- eases of the lower bowel by direct medication through the rectum is not new : on account, however, of various difficulties it did not grow into general favor until in recent years. The objections to rectal medi- cation which have been urged are the pain incident to the introduction of the tubes in the anus, the irritability of the I'ectmn causing expulsion of the injection, and the uncertainty of the amount of the drug absorbed. The advantages, however, of local treatment are so positive as to warrant the eiforts which have been made to overcome the objec- tions, and ])robably the greatest advance made in the treatment of dysenteric diseases has been in the extensive use of local means. The indications fulfilled by rectal treatment are (a) by thorough irrigation with simple warm or cold water to cleanse the rectum of all irritant contents ; (6) by astringent and alterative remedies to stimulate healthy action of the inflamed or ulcerated mucous membrane and control excessive serous exudation ; (c) by the use of antiseptics to destroy infective organisms ; {d) by the local action of anodynes to produce a more rapid and powerful effect than when the remedy is introduced by the stomach. Rectal tenesmus and premature expulsion of the enemata can best be overcome by the previous injection of a cocaine solution or by throwing into the bowel half a drachm of laudanum in half an ounce of warm starch-water. To thoroughly irrigate the colon one and a half to two quarts are necessary. A large sized Nelaton's catheter or a rubber tube made for the purpose, having been gently introduced eight or ten inches, should be connected with a fountain syringe or funnel, with the patient in the knee-elbow position or with the hips elevated on a pillow. The injection should be allowed to flow very gradually into the bowel, the connecting tube being compressed occa- sionally and the abdominal wall gently kneaded in the direction of the colon from below upward, to allow the intestine to adapt itself to the distending process and prevent a possible rupture. Very happy results have followed simple irrigation with boiled water, the griping pains and frequency of the stools being rapidly reduced. In other cases a solution of common salt or borax, about two drachms to the pint of water, has a better effect. The use of medicated injections will be mentioned in connection with the special treatment. Treatment of Catarrhal Dysextery. — Confinement to bed is necessary in all cases ; the attempt to be up and to take exercise of any kind is prejudicial. The diet should be carefully regulated ; no splid food should' be taken ; milk, chicken, and meat broths, and light farina- VoL. I.— 25 386 DYSENTERY. ceous articles, should constitute the nourishment. The bowels should be cleared out by a saline, half an ounce of Epsom, Glauber's, or Rochelle salt ; if one dose should not act freely, it may be repeated ; the occur- rence of free watery stools is usually followed by a relief of the symptoms. If there is a disposition to excessive peristalsis, the salts can be followed by an opiate with bismuth or salol combined with the latter, as in the following prescription : ^. Bismuthi subnitratis, Siij ; Salol, 3j ; Pulveris opii, gr. vj. Misce et in chartulas No. vj dividenda. Sig. Take one powder every three or four hours according to frequency of the stools. In two or three days it may be necessary to repeat the saline. Or the case can be treated from the beginning by giving small doses of salts, one to two drachms, in combination with four to five drops of tincture of opium, taken three or four times daily. The milder cases may be relieved by simply washing out the colon with three to four pints of warm water. Treatment of Diphtheritic Dysentery. — The problem of treatment here is not so simple. The lesions are so severe that many cases will die in spite of everything that can be done. The indica- tions are to (a) sustain the patient's powers by nutritious, unirritating food, and by the free use of stimulants, alcohol and strychnine ; (6) to counteract malarial complications by the use of quinine, and scurvy by fresh vegetable diet ; (e) to relieve pains, obviate nervous depres- sion, produce sleep, and hold in check the excessive frequency of the stools, for which purpose opium in some form is demanded ; (<:?) to cleanse the intestine by the occasional and moderate use of salines ; (e) to produce a healing, protective, and antiseptic effect upon the bowels by the use of such remedies internally as bismuth, salol, creasote, turpentine, tricresol, naphthalin ; (/) to cleanse the bowel by irrigation and to medicate it by injections of antiseptic and astrin- gent remedies. In a disease characterized by such profound constitutional depression the careful selection and administration of food become a matter of great moment. The digestive powers are impaired ; hence peptonized milk, milk with lime or Vichy water, koumyss, or matzoon, liquid pep- tonoids, chicken broth, beef juice, should be prescribed — in other words, concentrated nutritious food that will be largely absorbed and leave no irritant debris. Alcoholic stimulants in the form of good whiskey, brandy, and champagne are necessary as soon as adynamic symptoms are noticed, or even to anticipate them when we are sure of the diagnosis. Strychnine is useful, not only for its stimulant effect upon the heart, but for its tonic effect upon the muscular coat of the intestine. Quinine is required whenever a malarial factor is present : it should be given in antiperiodic doses, fifteen to thirty grains daily, until the malarial element is eliminated. Small doses of calomel may also be required in the presence of this complication. If a scorbutic TREATMENT OF AMCEBIC DYSENTERY. 387 taint is suspected, lemon or lime jiiiee, onions, wateivresses, and other fresh unirritant vegetables are recpiired and produce rapid improvement. It is difficult to dispense with opium in this form of dysentery ; it may be given by injection into the bowel, thirty or forty drops of the tincture with half an ounce of warm starch water, repeated often enough to control the excessive frequency of the stools, the violent tenesmus, and counteract the nervous depression. Its tendency to cause retention of the irritant intestinal contents may be obviated by an occasional saline or irrigation with hot water. If the rectum is too irritable to retain an enema of laudanum, morphine may be given hypodermically, or powdered opium by the stomach, the latter in doses of one to two grains every three or four or six hours, according to effects. A combination of opium with large doses of bismuth and salol or creasote is an excellent one in severe cases, as in the following pre- scription : 1^. Bismuthi subnitratis, 3vj ; Tincturse opii deodoratse, giij ; Creasoti, gtt. xxiv ; AqujB menthae piperitse, 5vj. — M. Sig. Take one tablespoonful every three or four hours. Cocaine given internally often has a happy effect in obviating tenesmus ; it mav be given in doses of one to two grains everv four or six hours. Cleansing enemata can be followed by antiseptic injections, as of creolin or tricresol, 3ij— siv, in a quart of warm water. Injections of carbolic acid or corrosive sublimate are dangerous, because if used in sufficient quantities to avail as germicides they are apt to produce toxic effects. Ordinary astringent injections, as of alum, tannic acid, acetate of lead, or nitrate of silver, may be of service when the stools are large and serous. Treatment of A^necebic Dysentery. — In the early stages, before the ulcerative processes have fairly commenced, the ipecac treatment finds its application. It is possible that the remedy may have some destructive effect upon the organisms ; at any rate, the testimony, as previously related by those who have tried it in tropical dysentery, is conclusive as to its value. It is necessary to take precautions that the ipecac should be retained : the nauseant or emetic effects are not desired ; the stomach should be quieted by the pre%'ious administra- tion of thirty drops of laudanum or by hypodermic injection of one quarter grain of morphine. It should be empty : no liquid should be allowed. A large mustard plaster is applied to the epigastrium, and half an hour after the opiate thirty grains of ipecac given in a bolus ; the dose may be repeated the second or third time, or it may be given in smaller quantities, five to ten grains in repeated doses. The diet in this form of the disease is a matter of great import- ance. Upon this point Ball quotes from Graves's Clinical Lectures, in which he says : " I have found several cases Avhich had obstinately resisted the most varied remedies assiduously employed get well rapidly after a liberal allowance of meat was given ; and at present, when called on to treat a case of dysentery of long standing, the first thing I 388 DYSEXTERY. do is to put my patient on full meat diet." I can add my testimony as to the value of this suggestion. The ordinary dietetic rules are not applicable in amcebic dysentery or in any chronic form. There is hardly any disease characterized by such rapid anaemia and wasting : it is nothing unusual to find patients taking the ordinary diet of milk and slops to lose in weight a pound daily, or to find them gain rapidly when placed on a full diet of nitrogenous food, as scraped meat, raw or slightly cooked, soft-boiled eggs, broiled fish, nutritious soups, or cooked tender meats when the patient will chew them thoroughly. A moderate amount of toasted bread can be allowed under the same restrictions. Rectal injections of a solution of quinine from 1 : 5000 to 1 : 1000 have been recommended by Osier, Councilman and Lafleur, and others, from a suggestion by Losch, who found that the amcebse were killed by such solutions outside of the body. The beneficial result of this treatment is subjudice. My personal experience was not satisfactory ; the matter will have to be determined l^y further trial. There can be no question, however, as to the value of nitrate of silver injections : the bowel ha^'ing been first washed out by a large enema of warm water (two quarts), introduced gently and slowly, as previously suggested, is to be followed by the silver injection, 30 grains to the quart. This should be retained as long as possible and given twice daily. Strong injections of small quantities do no good, as they fail to reach the ulcerated surfaces. Other astringents are useful, as sulphate of copper, alum, and acetate of lead, but generally are inferior to the silver salt. Injections of corrosive sublimate have been recommended by some high authorities. I have already mentioned the objections to this agent : if used in small quantities, it will not reach the extensive surface of the colon ; if in large quantities, it is likely to be absorbed and produce serious poisonous effects. The same objection applies to carbolic acid. Xext to nitrate of silver, I have found creolin to pro- duce the best results ; it can be used in the proportion of half an ounce to the quart of warm water. Iodoform is inapplicable, on account of its insolubility and the large quantity required. Tricresol is an anti- septic which is likely to jDrove of value. Opiates are not usually indicated in this form of dysentery, except perhaps in the gangrenous form to restrain excessive peristalsis and give the patient rest. Large doses of bismuth (thirty to forty grains) and salol in ten- to twenty-grain doses are of distinct value for the arrest of obstinate diarrhoea. The above suggestions are also applicable to non-amoebic forms of chronic dysentery. A change of climate or a sea voyage ^vill sometimes effect a cure when other means fail. The min- eral acids, preparations of pepsin, iron, quinine, arsenic, and strychnine are of servuce in promoting nutrition and as aids to counteract anaemia. Reference has been made to the necessity of requiring patients ^^dth dysentery to assmne the recumbent position. This is a matter of such importance in all forms of the disease that reiterated attention is called to it. Except in very chronic cases, where the intestinal symp- toms are to a great extent in abeyance, and where gentle exercise may be permitted, the patients should persistently remain in bed ; they should not be allowed to get up for any purpose : the sitting posture which many patients insist upon while at stool favors very decidedly both the TREATMENT. 389 pain and the frocjuency of the dejections. They shonld also be taught to restrain ;is niueli as j)ossihle the desire to empty the bowel. Some remarkable cures have recently been re])orted of chronic dys- entery by the use of an infusion or fluid extract of a plant growing in Mexico and Southwestern Texas known as the chapparro amargrm). R. T. Knox of Gonzales, Texas, reports the cure of a long-continued and most obstinate attack of chronic (probably amccl)ie) dysentery, of which he was himself the victim, by the use of this remedy when all other means faithfully tried had failed. Similar good results have been recorded by J. W. Nixon and others. The remedy is not narcotic, but excessively bitter and astringent. In doses of one half to two drachms of the fluid extract it produces no disagreeable effects. The reported cases are too few to predicate any basis for a positive opinion as to the virtues of this drug, but chronic dysentery is a disease so difficult to manage that any agent offering a prospect of doing good is worthy of trial. The fluid extract can be used in the doses mentioned, and can be prescribed in connection wdth the other treatment suggested. The management of non-amoebic forms of chronic dysentery is prac- tically the same as herein given. I have now under observation in my wards four cases of dysentery, ranging in duration from six w'eeks to six years. A trial is being made with chapparro in very much larger doses than as above mentioned, one of these patients taking an ounce of the fluid extract every four hours, the average dose being half an ounce every four to six hours. In two cases various other methods of treatment had been used with- out any decided benefit. In order more thoroughly to test the vir- tues of the remedy, every other medicine w^as discontinued, and only the ordinary precautions as to diet and quietude are enforced. While I am not able to pronounce absolutely as to the final result, the symptoms have been rapidly ameliorated : one case is apparently cured, the others decidedly improved. The effects w^ere more pronounced from the fact that when the supply of the drug w^as exhausted the patients relapsed, and again improved w^hen the medicine was resumed. The compound tincture of benzoin, in doses of half a drachm, re- peated every three or four hours, is an excellent remedy for the relief of intestinal hemorrhage, pre\dously mentioned as an occasional com- plication. THE PLAGUE. By WILLIAM M. WELCH, M. D. Synonyms. — English : The Bubo Plague, The Pest ; Latin : Pestis, Pestilentia, Pestis Inguinaria ; French : La Peste ; German : Die Pest, Beulenpest. Definition. — The plague is an infectious febrile disease which has prevailed epidemically at different times in various countries, and is characterized by buboes or swelling of the inguinal or other lymphatic glands. It is frequently attended by carbuncles, petechise, or purpuric spots distributed over different parts of the body. History. — During the Middle Ages, and even at a later period, almost every variety of pestilential disease that prevailed in epidemic form and was attended by great mortality was included under the term " plague." It is believed that Galen was largely responsible for this confusion by reason of a definition given by him, as follows : " When a disease attacks a number of persons in one place, it is an epidemic ; and when many are destroyed, it is a plague." But a gradually increasing knowledge of diseases has resulted in a differentiation so distinct and definite that confusion of terms no longer exists : those terms which formerly applied to a large group of diseases have either been limited to certain maladies or discarded altogether, while new names have been found for the others. The term " plague " is now restricted, as the definition indicates, to a contagious febrile disease presenting certain definite symptoms and pathological processes, most prominent among which are the formation of buboes. No very reliable account of the plague is to be found previous to the sixth century, although it is believed to have existed in Egypt, Libya, and Syria before the Christian era. The first extensive epidemic of the disease in Europe occurred in Constantinople in the year 542 a. d., dur- ing the reign of Justinian, and hence has frequently been spoken of as the Justinian plague. From that time until the latter part of the seventeenth century plague epidemics frequently occurred in Europe : so frequently, indeed, that this disease was more dreaded than any other that prevailed. It was especially rife and fatal during the Middle Ages, and even continued in various countries as a devastating scourge for a few centuries later. In the seventeenth century there were, according to Sir Gilbert Blane, no less than forty-five epidemics of the plague in various parts of Europe. Fourteen of these occurred in Holland, where the disease was introduced by the Dutch engaged in the Levant trade. From Hol- land the infection was conveyed to England, and in that country as many as tw^elve epidemics occurred. The most notable epidemics in both of these countries were in 1665. This has often been termed 391 392 THE PLAGUE. the year of the " Great Plague." The disease spread with such great rapidity and manifested so much virulence that, it is said, 7165 deaths occurred in a single week, and no less than 68,526 in one year, in the city of London and its suburbs. When we consider the population of London at that time, it is evident that this was a very large mortality rate. After a long interval of comparative absence of the plague, it reap- peared in the early part of the eighteenth century. It was met with most frequently in the Turkish dominions. During this century no less than nineteen epidemics occurred in Egypt and nine in Turkey. Epi- demics occurred also in Germany, Russia, Spain, Poland, Greece, Italy, Sweden, and France. An epidemic most notable for its severity visited Marseilles in 1720-21. Within the present century the disease has pre- vailed at different times in Egypt, Turkey, Greece, and Russia. It has also visited Germany, Syria, Italy, Persia, and some other countries. In 1844 the disease disappeared from Europe and Asia, but reappeared with great virulence in Arabia in 1853, and somewhat later was seen in North Africa, Persia, and Hindostan. During the period from 1873 to 1877 the pestilence prevailed with unusual severity in almost every part of Arabia. In 1878-79 it committed great ravages in Astrakhan. The most recent epidemic of the plague occurred in China in 1894. It pre- vailed in Hong-Kong, Canton, and some other districts. Owing to the ignorance and superstition of the Chinese, no reliable statistics could be collected, but it is known that the epidemic was very severe and fatal. Fortunately, this pestilential disease has never visited America, or, if it has been seen at all, it has never prevailed in epidemic form. Etiology. — All modern authors concur in the belief that the plague owes its origin to a specific contagium. While the disease has always been confined to the Eastern Hemisphere, yet it is universally admitted that the contagium is not indigenous to any country or soil. There is no doubt, however, that certain circumstances may combine to favor the propagation and action of the infecting principle — such, for example, as poverty^ overcrowding, personal uncleanliness, improper or insufficient food, and the like. All observers agree that the physical and social wretchedness resulting from poverty is, except the contagium itself, the most potent factor in the spread of the disease. While this fact has been noticed in all epidemics, it was so conspicuous in the great epidemic of London in 1665 that the writers who described the disease at that time termed it " the plague of the poor.'' Certain local conditions are also known to be favorable to the spread of the plague. In the Eastern countries, where the disease prevailed in past ages with such great virulence, the state of civilization was wretch- edly low, and a large proportion of the inhabitants were not only insuf- ficiently fed or forced to subsist on the most unwholesome food, but lived in crowded dwellings that were poorly constructed and badly ventilated. No regard whatever was paid to sanitary laws. Improper drainage existed in all cities, towns, and villages ; masses of decompos- ing animal and vegetable matter, including human dejecta, were allowed to accumulate ; human corpses were commonly kept too long before burial, and even then they were interred at an insufficient depth ; the dwelling-houses had simply an earth floor, and not infrequently a ETIOLOGY. 393 horrible (xlor was cinittod from the (lecoinposiiijr dead Ixxlies of some previous oeeiipaiits who liad been buried oiilv a few feet beneath. AVlien sueh a deplorabh' condition exists, it is not snrprisin^ that the phigue, onee introduced, should lini^er and commit great ravages. After the introduction of better sanitary regulations in Egypt and Turkey, in 1844 the plague disappeared, but it returned again ten years later, when these regulations were disregarded. The importance of sanitary meas- ures was fully realized in China during the recent epidemic. A com- mittee of the Sanitary Board has emphatically expressed the o[)inion that the speedy stamping out of the plague in that country in 1894 was due to thorough cleansing and disinfection of the houses in which cases had existed. AVhatevcr the local conditions or the habits of the people of any countiy may be, the plague never originates autochthonously, as was formerly sup- posed, but is always introduced by a previous case and commiuiicated from one person to another. The theory that the disease is spread by infection has, it is true, often been assailed, and evidence to prove its non-con- tiigious nature presented, but all modern authors agree that the pre- ponderance of testimony is to be found on the affirmative side of the question. Even the Turks, who are not very familiar with the theories taught in more enlightened countries, have gradually arrived at the conclusion that the plague is infectious. It would appear, however, that in order for an epidemic to arise and continue with great severity -certain favorable local conditions must be present — such, for example, as have already been described. So also moderately warm weather and dampness or a marshy conformation of soil, such as exists at the mouths of rivers, are favorable to the development and spread of the disease. Individual predisposition to the plague varies, as in most other con- tagious diseases. Some persons appear to be entirely immune, while others take the disease after the slightest exposure. Sex exerts no influence whatever over the predisposition. Intemperance and all habits that depress the vital forces, if they do not render the individual more susceptible, are sure to predispose him, if attacked, to a severe form of the disease. Age appears to exert some influence over the predisposi- tion, as it has been observed that persons over fifty years of age are seldom attacked. The plague differs from most other infectious diseases in that one attack does not confer immunity against subsequent attacks. Although bacteriology has not brought to light any specific micro- organism to explain the infectious nature of the plague, yet such a pathogenic germ is believed to exist. That the disease is really infec- tious has been demonstrated in various ways. Many instances are recorded of the contagium having been conveyed from one city or locality to another by means of infected individuals. On the other hand, it has never been known to originate in any district or island which has had no communication with an infected locality, but, like infectious diseases in general, it follows the line of travel. The disease has often been con- fined to an infected area by means of a rigid quarantine. Transmission of the contagium has occurred through the bedding, clothing, and other effects of patients. The corpses of persons who had died of the plague have been known to transmit the infection, even when a long time had elapsed after death. This fact was recognized ages ago in some of the 394 THE PLAGUE. Eastern countries, and consequently the reopening of graves of persons who had died of the plague was made a penal oifence. " Such grave- yards were therefore frequently surrounded with walls, upon which notices were posted to the effect that the reopening of a grave would be punished as a capital oifence." ^ It would seem that the poison of the plague is capable of remaining for a long time in an active state outside of the body, as epidemics not infrequently break out anew after a long interval and without any fresh importation of the infection. The contagium of the plague is believed to enter the system usually through the lungs. A few instances are recorded showing that it is possible to produce the disease by inoculation. The presence of the infection in the circulation is first manifested in the lymphatic system, causing swelling and inflammation of the glands. The stage of incubation is short, being usually from two to five days. It may, however, be as long as seven or eight days, but rarely longer. Pathological Anatomy. — The gross pathological changes are not numerous : no careful examination has ever been made of the blood. Swelling and inflammation of the lymphatic glands are the only constant abnormal changes found after death. The inflammation is not always limited to the glands, but extends more or less to the contiguous tissue, in which extravasation of blood is often found. More often the inguinal glands are the ones involved, although it is not unusual to find glandular swellings in the axilla, the neck, and other external portions of the body. The deep seated lymphatic glands, and even those within the cavities of the body, are also not infrequently enlarged. The external glands, especially those in the inguinal region, are very liable to undergo sup- puration. When those in the axilla are severely involved the inflamma- tion sometimes extends to the pleura. Petechise, ecchymoses, and carbuncles are frequently found in the skin. The carbuncles often present large sloughs, surrounded, of course,^ by an inflammatory process. Ecchymoses are sometimes found in the mucous and serous membranes. Parenchymatous degeneration has been noticed in the various internal organs of the body : the spleen, especially, is said to be almost always hypertrophied, soft, and of dark color (Liebermeister). Symptoms. — In studying the symptoms of the plague it is found most convenient to divide the disease into four stages : First, the pro- dromal or invasive stage ; second, the febrile stage ; third, the stage of the local manifestations ; fourth, the stage of convalescence. First Stage. — The disease usually begins somewhat suddenly by feelings of lassitude, loss of strength, general uneasiness, and mental anxiety. Headache is commonly present, together with vertigo and a sense of fulness in the head. The face is generally pale, the eyes, languid, the intellectual faculties impaired, and the gait unsteady or staggering, resembling that of an intoxicated person. It is not unusual to find nausea and vomiting, and even diarrhoea, at this stage. These early symptoms may be either very mild or very severe, and may con- tinue from a few hours to two or three days. During this period there is usually but little if any fever. The second stage is ushered in by chilliness or rigors, followed by ' Liebermeister, v. Ziemssen's Cydopcedia. SYMPTOMS. ;iy;j i'ebrile reaction. Thoiv is a continuance of most of tlio synij^toins already mentioned, some of wiiieli may assume still greater prominence — such as the languor, debility, headache, dizziness, and the irritability of the stomach. Precordial uneasiness is very commonly complained of. The fever often becomes very intense. It is not innisiial to Hnd the temperature of the body rise as high as 104° F., but more fretjuently it ranges between 101° and 104° F. There are present also the usual concomitant symptoms of high fever, such as a hot and dry skin, uncpiencliable thirst, furred tongue, and accelerated respirations. The pulse is not only frequent, but feeble, and sometimes irregular or inter- mittent. In severe cases it may vary from 120 to 150. The tongue at first is somewhat swollen, moist, and covered with a white fur, but later it becomes brown or almost black, and sometimes fissured, while dark sordes collects on the teeth and lips. The eyes are injected, the face flushed or livid, and the countenance is greatly changed. At first the bowels are constipated, but toward the end are relaxed, the passages becoming dark, oflFensive, and sometimes bloody. A dark grumous or bloody vomit is not uncommon. The urine also is often tinged with blood. When these symptoms are present the patient soon sinks into a typhoid condition ; delirium, stupor, or profound coma supervene, and death often results about the time the lymphatic glands begin to enlarge. In the most malignant cases the fatal blow appears to be given at the very commencement of the disease. Such cases are characterized by severe nervous symptoms and extreme prostration, from which the vital forces never rally, and death often results in less than twenty-four hours without any development whatever of the local manifestations. Usually the febrile symptoms are not of uniform violence through- out the twenty-four hours, but there are remissions and exacerbations. The reinissions occur in the morning and toward evening, the exacer- bations in the middle of the day and at night. The morning remission and the nocturnal exacerbation are most marked. The remission is often so great as to lead the patient to hope that convalescence has begun. The subsidence of the fever is not infrequently attended with free perspiration, and when this occurs on the third or fifth day of the disease it is regarded as a favorable indication. After the febrile symp- toms have continued for two or three days the inguinal lymphatic glands enlarge and become sensitive to pressure. The intensity of the fever now diminishes, although the temperature often fluctuates considerably throughout the succeeding stage. The third stage is characterized by the development of the local lesions. Usually the earliest evidence of localization of the disease is found in the inguinal region, and consists of inflammation and swelling of the lymphatic glands. This symptom is often preceded by a shoot- ing pain in the part. Next to this region, the glands in the axilla are most frequently affected. Those in the neck, and even in other parts of the body, are often attacked in severe cases. The swellings vary very considerably in size. Sometimes they are so small as to be difficult of detection ; in other cases they become as large as a hen's egg or even much larger. In the neck the swelling has been known to attain enor- mous dimensions within a few hours, becoming so large, indeed, as to cause asphyxiation from pressure. The swelling, however, is apt to be 396 THE PLAGUE. greatest in the inguinal region, and the glands which are attacked are usually those lower down on the thigh than in the case of venereal buboes. Suppuration may occur, or the inflammation may disappear by resolution. The former is thought to be the more favorable mode of termination. The suppurative process is apt to be slow, continuing often as long as two or three weeks before the pus is discharged. After this the abscess slowly heals, leaving a permanent scar. Carbuncles, which are less frequent than buboes, usually make their appearance at a later period. They may appear upon any part of the body, but are more often found on the lower extremities, the buttocks, and the back of the neck. Sometimes there is but one or there are very few, and at other times they are quite numerous. They may be either small or large. In favorable cases, instead of gangrene developing, which is often the case, the slough separates early by suppuration. Petechise, vibices, or extensive ecchymoses are often seen in the last stage of fatal cases. Aubert regarded these symptoms as almost a certain sign of death. It should be stated that it is not possible in ever\' case of the plague to find clearly marked the three stages just described. Sometimes the first symptom that attracts attention is a so called " boil," which has made its appearance without premonition. Occasionally the disease is so mild that the patient is not obhged to go to bed. Such cases may be seen in mild epidemics or toward the close of severe ones. On the other hand, in the most severe form of the disease cases have been known to terminate fatally within a few hours, without any appreciable prelimi- nary symptoms. In this class of cases death results from shock pro- duced by the ^^rulence of the poison. More frequently, however, in the fatal cases death takes place betvs-een the third and fifth days. After the eighth or ninth day, or even after the seventh according to Lieber- meister, the dangerous period of the disease is past, yet death may result from sequelae. The subsidence of the fever on the third or fifth day, with profuse perspiration, as already mentioned, is regarded by most observers as favorable. Fourth Stage. — In most of the cases which terminate favorably con- valescence begins from the sixth to the tenth day, but, on account of the suppuration and a large number of discharging sinuses, is often very slow. During this stage certain sequelse are liable to arise, among which may be mentioned furuncles, secondary' abscesses, parotitis, dropsy, partial paralysis, and mental disturbances. Pneumonia, attended by a typhoid condition, is sometimes seen, and when it occurs is always very fatal. In pregnant women abortion is apt to take place, and this com- plication is almost always followed by death. A genuine relapse has been known to occur when convalescence seemed fully established. DiAG-xosiS. — It is difficult to distinguish the plague only at the beginning of an epidemic or in cases which are atypical. When the disease is known to be prevalent the diagnosis in well marked cases is usually easy enough. Some doubt might exist in the mind of the diag- nostician during the first day or two of the illness, but the early appearance of shooting pain in the inguinal region, rapidly followed by tenderness and swelling of the glands and the formation of buboes, is calculated to reveal the true nature of the disease ; but if anv doubt should still imOGNOSLS—TREA TMENT. 897 exist, it would soon bo removod by tlie nij)icl spread of tlio mulady, the development of carbuncles and petechia', and the friirhtful in(jr- tality. The diseases with which the plaiiue is most liable to be ('(diibunded are lvnn)hadenitis, scrofulous or syphilitic alfections associated with fever, malignant typhus, pernicious j)aludal fever, and malignant pus- tule. But a reasonable familiarity with the symptoms of these diseases will usuallv enable tiie diagnostician to exclude then\ when considering the ditfevential diagnosis l)ctwcen them and the plague. Prognosis. — As the i)laguc is an exceedingly fatal disease, the |)rog- nosis in well marked cases should be guarded. Some idea of the great fatality of the disease may be formed by considering the results of cer- tain epidemics. For example, it was estimated that in Marseilles in 1720, out of a population of 90,000, 80,000 suffered from the disease, and of this number 40,000 perished. Likewise, in Toulon in 1721, out of a population of 26,000, about 20,000 took the disease, and of these 16,000 died. Also, in Moscow in 1770-71, nearly one-half of the entire population perished. In various epidemics the death rate among persons attacked has ranged from 50 to 90 per cent. In individual cases the unfavorable symptoms may be enumerated as follows : sudden and extreme prostration at the onset ; a tendency to syncope, stupor, or coma ; injected eyes, stammering speech, unsteadi- ness of gait, and a drunken expression ; a low muttering delirium ; ex- cessive oppression of breathing, and an irregular or intermittent pulse ; a dry, black tongue ; hiccough, severe precordial pain, and vomiting of dark grumous material ; the appearance of petechise, vibices, and large ecchymoses. On the other hand, the favorable symptoms are early and decided remissions in the fever, and its subsidence on the third or fifth day, with moderate perspiration ; a limited involvement of the lymphatic glands ; the development of buboes, advancing rapidly to suppuration ; no great loss of strength ; the cessation of the nervous symptoms ; and a return of the natural expression of the countenance. Treatment. — It is sometimes easier to prevent than to cure a dis- ease, and this is particularly true of the plague ; for it is certain that a great deal may be accomplished in the way of prophylaxis by suitable measures energetically applied, while it seems impossible to change the course of the disease after symptoms have appeared. Some of the severest epidemics of this disease have not only been limited in their spread, but were conquered by quarantine and hygienic measures. The history of the latest epidemics in Egypt is very instructive as showing what may be accomplished by a rigid quarantine system. The importance of this measure was also very forcibly demonstrated at Noja, Italy, when the plague prevailed there in 1815. The city was surrounded by three separate military cordons, one outside of the other, thus preventing absolutely any person from either entering or leaving the infected locality, and, as a result, the disease was confined within the limits of this cordon sanitaire. It is reasonably believed that by this severe measure Lower Italy, and even Europe, were spared from the decimating ravages of the scourge. So also in the province of Astrakhan in 1878-79 the plague was prevented from spreading by the same rigid restrictions. 398 THE PLAGUE. A writer^ who is thoroughly familiar with the history of this disease says : " The extinction of the plague was a gradual process, and kept pace in great measure with the development and perfection of the quar- antine system as carried out, not only with reference to the East, but also between neighboring countries of Europe. Indeed, I cannot understand how any one pretending to criticise facts in an unprejudiced manner, and with some regard to the condition of the plague in the East, can for a moment hesitate to attribute the chief cause of the dis- appearance of the plague from European soil to the development of a well regulated quarantine system." Under the head of Etiology (page 392) attention has been directed to the fact that poverty, overcrowding, bad ventilation, unwholesome or insuf- ficient food, and unhealthy surroundings are important factors favoring the propagation and dissemination of the infection. It is evident, there- fore, that in the administration of sanitary laws these conditions should receive attention. Exposed persons should not only be properly fed and have their dwelling rooms well ventilated, but they should bathe regularly and avoid intemperate and all other depressing habits. It is clearly the duty of the state or municipality in which the disease exists to correct all bad hygienic conditions or unsanitary surroundings. The polluted soil should be saturated, if possible, with some active disin- fectant ; all articles of clothing, bedding, etc. which have been in con- tact with the sick should be promptly disinfected, as well as the dwell- ing in which the patient resided. The bodies of persons having died of the plague should be buried in accordance with strict sanitary regu- lations, or, preferably, reduced to ashes speedily by the process of incineration. Clinically considered, there is no special form of treatment for the plague : all that can be done is to treat the symptoms as they arise. The fever may be mitigated by febrifuge mixtures or some of the least depressing antipyretics of the coal-tar products. Cold sponging, or even cold baths, may prove of great service when the temperature is high. As suppuration of the buboes is thought to be desirable, this process should be encouraged by warm poultices, and as soon as pus has formed it should be evacuated and the parts treated in accordance with antiseptic principles. The danger of collapse in the early stage of the disease may be lessened by confining the patient to bed and insti- tuting at once a supporting plan of treatment. As death is generally caused by cardiac paralysis, strychnine and alcohol should be given in large doses. A Kberal amount of suitable nourishment is required. ^Hirsch, quoted by Liebenneister, loe. cit. INFLUENZA. By JAMES C. WILSON, M. D. Definition. — An acute infectious disease occurring in widely ex- tended epidemics, characterized by catarrh of the mucous membranes of the respiratory tract, less frequently of the digestive tract, by quickly oncoming debility, and by nervous symptoms. There is a strong tend- ency to complications, especially pneumonia. Uncomplicated cases are rarely fatal except in feeble or aged persons. The attack does not con- fer subsequent immunity. Synonyms. — Epidemic catarrhal fever ; la Grippe. This disease has an extensive literature and innumerable synonyms. Many of these terms are the outcome of efforts on the part of the profession to give it descriptive designations ; others are of popular origin, suggested by its sudden occurrence, certain of its symptoms, or its widespread prevalence. The Russians have called it Chinese catarrh ; the Germans and Italians, the Russian disease ; the French, Italian fever or Spanish fever. In two instances the popular name has found its w^ay widely into medicine and medical literature almost to the exclusion of the studied terms l)y which science has sought to designate it. These are influenza and la grippe. The derivation of la grippe is obscure. It has been traced to the Polish chri/pka (raucedo) ; others have derived it from agripper (to snatch). The term influenza is of Italian origin. It is said that the disease received this name because its sudden outbreak and wide prev- alence were attributed to some influence of the stars, or, according to others, from a secondary signification of the word indicating something fluid, transient, or fashionable. History. — Influenza is distinctly an epidemic disease. It has pre- vailed since the beginning of the sixteenth century in great pandemics. Many of the accounts of epidemic diseases of earlier date doubtless refer to influenza, but they are not sufiiciently exact to warrant us in inferring its undoubted existence. According to Parks, it is men- tioned in the Avritings of Hippocrates, who, however, gives no exact description. Several epidemics of catarrhal fever, Italian fever, and the like, which were probably influenza, occurred in the ninth century. In the year 827 a. d. a cough which spread like the plague was re- corded. In 876 there appeared in Italy a similar epidemic which spread with great rapidity all over Europe. In 1173 a widespread malady, of which the symptoms were chiefly catarrhal, raged throughout Europe, and epidemics of a like character occurred during the following century (1239-99). There are to be found records of six similar epidemics in the fourteenth century, and seven great \'isitations of influenza occurred 399 400 INFLUENZA. in the fifteenth century. Aitken ^ speaks of a very fatal prevalence of influenza throughout France in 1311, and of an epidemic in 1403 in which the mortality was so great that the courts of law in Paris were closed in consequence of the deaths. The earliest accurately described epidemic of the British islands is that of the year 1510. The disease apparently started from Malta, in- vaded Sicily, then Italy, Spain, and Portugal, then crossed the Alps into Hungary and Germany, extending westward into France and Britain. Its track widened over all Europe from the southeast to the extreme northwest, and it is said that not a single family and scarce a person escaped it. It was attended by "a grievous pain "in the head, heaviness, difficulty of breathing, hoarseness, loss of strength and appetite, rest- lessness, retchings from a terrible tearing cough. Presently succeeded a chilliness and so violent a cough that many were in danger of suffoca- tion. The first day it was without spitting, but about the seventh or eighth day much viscid phlegm was spit up. Others (though fewer) spat only water and froth. When they began to spit, cough and short- ness of breath were easier. None died except some children. In some it went off with a looseness, in others by sweating. Bleeding and purg- ing did hurt" (Thomas Short). The epidemic of 1557, starting westward from Asia, spread over Europe, and then crossed the Atlantic to America. The malady broke out in England in the month of September. " Presently after were many catarrhs, quickly followed by a more severe cough, pain of the side, difficulty of breathing, and a fever. The pain was neither violent nor pricking, but mild. The third day they expectorated freely Some, but very few, had continued fevers along with it; many had double tertians ; others simply slight intermittent. All were worse by night than by day ; such as recovered were long valetudinary, had a weak stomach and hypped." Gravid women either aborted or died. This epidemic spread with frightful rapidity. Thousands were attacked at the same time. The entire population of Nismes, with scarcely an exception, fell ill with it upon the same day. It was extremely fatal. The disease raged in some parts until the middle of the following year (1558), and carried off in Delft alone five thousand of the poor. In all cases mild treatment was called for, with warm broths and speedy im- mersals, " to recall the appetite and keep the vessels of the throat open." About a quarter of a century later, in 1580, a great epidemic of influenza spread from the southeast toward the northwest, over Asia, Africa, and Europe from Constantinople and Venice, and extended over Hungary and Germany to the farthest regions of Norway, Sweden, and Russia. It prevailed in England, and was described by Dr. Short. In Italy it was rife during August and September, in England from the middle of August to the end of September, and in Spain during the whole summer. In most places its duration was about six weeks. The termi- nation was, as a rule, favorable. In the account of Dr. Short it is stated that " few died except those that were let blood of or had unsound viscera." In some districts, on the contrary, the course of the disease was very severe. In Rome two thousand died of it, according to the author ^ Practice of Medicine. HISTORY. lol just cited, but Zut'1/.cr states tluit victiuis of tlie epulemie in the Ktonial City numbered not less tiian nine thousand, and adds that Madrid must have been alm(»st de|)<)j)uhited l)y it. This hitih mortality has been attril)utetoms are similar to those of tlie previous epidemies, with great shortness of breath, which continued in many eases some time after the tlisappearanee of the catarrhal troul)le. Influenza reappeared in Germany in 1 •")!»]. An epidemic extending- from Holland throuuh France and into Italy occuri-ed in l.">!);5. In IGIO catarrh prevailed throughout Europe. In 1G26-27 epidemic catarrhal fevi'r made its ap])earance in Italy and France; in l(j42— 4o, in Holland ; in 1(J47, in S[)ain and the colonies of the \\'estei-n Wdrld ; and again in IGoo in North Anierica. Noah Webster, in his work entitled ^I Brief Hi.sfori/ of Epidemic and Pestilenti(d iJi.srd.sc-i, ])ub- lished in Loudon in 1800, states that the outbreak of 1647 was the first epidemic of catarrh mentioned in American annals. Epidemic catarrh revisited Austria, Germany, and England in 1658 and again in 1675. The first of these two epidemics is described by Willis, the second by Sydenham, as they occurred in England, and the accounts arc to be found in the Annals of Influenza. About this time the disease began to be known as influenza, and it is interesting to note that the influence of the stars suggested itself in connection with its sudden appearance and Avide prevalence. Willis writes that "about the end of April (1658) suddenly a distemper arose as if sent by some blast of the stars, which laid hold of very many together — that in some tOAvns in the space of a week above a thousand people fell sick together." Epidemics occurred in Great Britain and Europe in 1688, 1693, and in 1709. Epidemic catarrh spread in 1712 widely over Euro])e from Denmark to Italy. In 1729-30 a great epidemic swept over Europe. In five months the disease overspread Russia, Poland, Germany, Sweden, and Denmark. In Vienna sixty thousand persons fell ill of it. In the autumn it reached France and Switzerland and extended to England ; it extended to Italy, thence to Spain, from which country it found its May to Mexico. The symptoms were those already described as characteriz- ing the attack in previous epidemics. The attack began with pains in the limbs, and fever, hoarseness, catarrh, dyspncea, and cough followed. Delirium, drowsiness, and faintness occurred in some cases. Turbid urine, copious sweating, looseness of the bowels, and nosebleeding were common. In Switzerland only children and old persons died. In this pandemic the disease was not very fatal. Influenza invaded Saxony and Poland two years later, and, s]n'ead- ing through Germany, Switzerland, and Holland, reached Great Britain in December, 1732. Thence, toward the end of January, it spread to France, Italy, Spain, and westward to North America, passing on to the islands of the West Indies and to South America. The dis- ease in this epidemic ran a favorable c0, 17SM), and anionression arc, however, the same. Finallv, cases occur in which there is but little of the usual tendency to localiziition of the infectious process; the patient suffers from fever of varying intensity, with great depression and simultaneous and equal implication of the respiratory, circulatory, nervous, and gastro-intes- tinal organs. Herpes occurs in a considerable proportion of the cases. Urticaria is less common. Diifuse erythematous rashes and instances of purpura have been observed. Attempts have been made to arrange the foregoing forms of influenza into different categories, and in theory a thoracic, cardiac, gastro-intes- FiG. 36. F. 105 104° 103' 102° lOl' 100° 99° 98° 97 DAY OF DISEASE M E M E M E M E M E WI E M E |l \\ \ \ \ 1 \ \ \ \ I \ / ' / A /\ / 1 / \ K \ \ l/ \, \j \ / \/ Y 1 2 3 4 5 G 7 c. —40 — 38 Temperature in Influenza— Critical Defervescence. tinal, and nervous variety may be recognized. In practice, however, the various described types merge so gradually into each other, and are so modified by the indi\'idual peculiarities of the sick and by the com- 410 INFL UENZA. plications which arise in the course of the attack, that there is, as a rule, but little advantage in referring particular cases to theoretical categories. The DURATION of the milder forms of influenza is from two to three days. In well developed cases without complications convalescence sets in between the fourth and seventh days. Severe cases with complica- tions may be protracted for several weeks. Relapses occur in about 10 per cent, of the cases. Analysis of the Principal Symptoms. — The Fever. — In un- complicated cases the temperature rises rapidly to 101-105° F. in the Fig. 37. F 106' 105° 104° 103° 102° 101° 100° 99' 98° 97° DAY OF DISEASE IVl E M E ^ 1 E M E M E M E IVl E / f\ / V / / I h ' 1 • n A / / \ r\ 1 \ / V / 1 2 3 4 5 6 7 c. ^-41° -40 —39 Temperature in Influenza— Interrupted Crisis. first twenty-four or thirty-six hours. From this point it falls by a defervescence usually critical ; sometimes by an interrupted crisis ; sometimes by rapid lysis. The temperature reaches the normal usually in the course of from one to four days ; less commonly secondary rises of temperature occur after an afebrile period of one or two days — inter- mittent form ; or, again, the fall of temperature does not reach the nor- mal, and is succeeded by a series of rises, defervescence occurring some time before the close of the first week — remittent form. The accom- ANALYSfS OF THE PnrXCfl'AL SYMrTOMS. 411 panying- clKU'ts represent the more eoimiion loriiis ot" the tornjx'rattire curve. One reealls the statement of the ehroiiieh'r of an early epicU'mie : "Some had continual fevers alon^- witii it; many had double tertians; others simply slioht intcrmittont." There is no constant relation be- tween the heijiht to which the temperature rises and the severity of the other symptoms ; subjective distress may be moderate in patients show- ing a temperature of 104-105° F., while other patients in whom the thermometer marks a fever of 101-102° F. may suffer agonizing pain F 105 104 103' 102° 101° 100° 99° 98 97° DAY OF DISEASE M( E M E M E ME M E M E M,E I \ A / \ A ' \ / / \ 1 \ 1 Y A / \ \ ^ \ \ \ , l\ V 1 \ \ \ J \ V 1 I i » / \ 'A / 1 \/ v/ V V 1 2 3 ■1 5 !J - 1 * 1 —38 Influenza— Rapid Lysis. in the head, back, and limbs. The temperature rises early in the course of the disease, and may subside before other characteristic phenomena show themselves ; or, again, the temperature may be still high when the headache, pains, or even the catarrhal symptoms, have subsided. If the fever continue beyond the seventh or eighth day, it will usually be found, upon careful examination, to be due to some complication, as a rule involving the respiratory tract. The temperature curve, due to the influenza infection, not infrequently merges into that of a complicating bronchitis, broncho-pneumonia, or croupous pneumonia. The pulse has no constant characteristics. Its frequency is mode- rately increased ; very often with high temperature the pulse does not exceed 100. It is less forcible than in health ; compressible even when full ; often irregular, changing in character in the course of a few hours. In some cases the pulse is slow. The urine is usually diminished, sometimes temporarily suppressed. 412 INFLUENZA. Fifi. 39. F 105' 104° 103' 102' 101' 100° 99' 98° 97' DAY OF dlSEASE M E M E M E M E M E W! E IVl ^ I \ \ 1 j 1 J 1 A \/ ]/ 1 2 3 i 6 7 Influenza— Intermittent Type. Fig. 40. F 104' 103° 102° 101° 100' 99° 98° 97° DAY OF DISEASE M E IVl E M E M E M E M E M E II \ 1 \ A 1 \ / \ 1 ' 1 I 1 / 1 j I I \ I A \ • \ \/ \ 1 / \ / \ A 1 ^ 1 \ 1 \ / V u 1 3 3 i 5 7 c. r— 40° —38 Influenza— Remittent Type. AyALy:sis uF Tin-: vniyciVAL HYMrroMs. 41 ;3 As a rule, it shows little clianiio, and is not commonly, as in other febrile diseases, coneentnited and hi«;h cdjored. It deposits on coolinti; a sedi- ment of urates, whieh toward the end of the fever is often very abun- dant. Deferveseenee is in many instances attended by a eoi)ious excre- tion of urine. Albuminuria occasionally occurs, especially in compli- cated cases. Griffiths and Ladell isolated from the urine in influenza a toxic fever-producing ptomaine which causes death in animals in eight hours. The substance was found to be a whitish crystalline body hav- ing- the formula C,,H,,NO„ soluble in water of slightly alkaline reaction. The skin in some cases is hot and dry during the febrile movement ; more commonly there is sweating from the onset, often continued through the course of the illness, and frequently being very marked during convalescence. Sudamina occur. The face is often flushed, and there are irregular erytiieniatous niottlings of the skin, especially upon the neck and chest. Other forms of erythema, and especially erythema n(xlosum, have been frequently observed. Labial herpes is often seen in cases not complicated by pneumonia. Urticaria is not uncommon. Disturbances of the digestive tract are more or less prominent in almost all cases. In many instances they are such as are usually seen in febrile disorders — namely, loss of appetite, thirst, impaired taste, pasty tongue, tenderness in the epigastrium, and constipation. Xausea and vomiting sometimes usher in the attack, and in some cases vomiting continues for several days. In the so-called abdominal form of influ- enza these symptoms are more severe, and diarrhoea frequently consti- tutes an urgent svmptom. In some of the epidemics the intestinal catarrh has shown a tendency to run into dysentery. The countenance expresses anxiety and depression. There is pallor, together \\dth injection of the conjunctivae, puffiness of the eyelids, and redness of the tissues of the nostril. The facies is sometimes slightly flushed and may suggest that of enteric fever. Catarrh. — A more or less extensive hypertemia of the mucous mem- brane of the respiratory tract is invariably present, and may be said to be characteristic of the disease. There is eoryza, often severe. The eyelids may be swollen and reddened ; there is lachrymation ; sneezing is frequent, and in many cases there is an abundant discharge from the nostrils. Epistaxis is not rare. Erythematous angina, with tickling sensations and difficulty of swallowing, is frequent. In many cases the catarrhal symptoms are restricted to the upper air-passages. Implica- tion of the larynx is shown by huskiness or loss of voice. Hoarseness is common. Cough is a prominent symptom. It is commonly frequent and dis- tressing, sometimes paroxysmal from the beginning of the attack, almost always so at some period of its course. The spasmodic character of the cough in some of the older epidemics led to a confusion of diagnosis between influenza and whooping cough. The cough is apt to be Avorse toward evening and at night. In some cases it leads to vomiting, and by its violence and persistence gives rise to myalgia in the muscles of respiration and occasionally to hernia. It is at first dry or attended Avith a scanty muco-serous expectoration ; later the sputa become muco- purulent, and they are sometimes streaked or mingled with blood. Toward the close of the attack the cough becomes less urgent and loses 414 INFLUENZA. its spasmodic character. In some of the epidemics cough has not been a prominent symptom, and cases may be encountered in most epidemics in which well developed influenza runs its course w^ith little or no cough. Various rales may be detected during the course of the attack as in ordi- nary acute bronchitis. In other cases rales are absent and the ausculta- tory signs are negative. Dyspncea is not infrequent. It may occur in cases where none of the objective signs of any pulmonary lesion can be discovered. In this case it may be of nervous origin, and a direct disturbance of the function of the vagus has been invoked in explanation of it. This view is rendered plausible by the fact that the dyspnoea is occasionally intermittent and paroxysmal. In some of the epidemics orthopnoea and suffocative attacks have been common. Stitches in the side and substernal pain occur without appreciable physical signs. Haemoptysis may occur in patients who present no physical signs of lung disease. Nervous System. — Marked lowering of muscular strength is a very early symptom and constitutes one of the most remarkable features of the disease. Patients are extremely weak from the onset of the attack and exhausted by slight bodily effort. The ordinary strength is not regained until convalescence is far advanced. Headache is a constant symptom. In addition to the general head- ache which marks the onset of the specific fevers, severe pain across the brows and in the orbits is scarcely ever absent. These pains are referred to the region of the frontal sinuses and nasal ducts, sometimes to the region of the antrum of Highmore or to the Eustachian tube and the middle ear. They are often most intense. They last commonly until the end of the attack, and in many cases persist as sequels. The head pains increase in severity toward evening. In some instances the occur- rence of epistaxis has afforded temporary relief. The headache may be limited to one orbit, one side of the forehead, or one side of the face. Neuralgia in the distribution of the branches of the fifth pair is not infrequent. Hypersesthesia of the surface of the head and neck and painful stiffness of the muscles of the neck are encountered. Among the more constant symptoms of influenza are the very severe pains in the back and limbs already referred to. There are sensations of sore- ness and bruising, such as follow severe and unaccustomed muscular effort ; dull tearing and burning pains may be felt in particular mus- cles or tendons, and are very common in the calves of the legs. These pains are neither relieved nor aggravated by gentle movement or by moderate pressure. Restlessness, insomnia, and anxiety occur in most of the severe attacks. Dizziness and faintness are not uncommon. Mild delirium is frequent; the more intense forms of delirium are occasionally ob- served. Somnolent states may also occur. Hebetude and torpor have characterized some epidemics. In grave cases painful cramps, subsultus tendinum, twitchings, and trembling of the hands occur. The mental power is enfeebled. Special Senses. — The acuteness of the special senses is diminished. The sense of smell is frequently entirely lost, and that of taste greatly impaired. Many patients complain of a disagreeable coppery or metallic taste. The hearing is somewhat blunted. Severe earache is not COMPLICATIONS AND'SEQUELJE. 41 o uucoiuiiion. Siip})iiratiuii ot" tin- inirMk' car and pedoratioii ot" the meinbraiio occur in a considerable proportion ot" the cases. Complications and 8EQri:L.E. — The most important complications are those connected with tiie respiratory tract, Tiie liypenemia and bronchitis which occur in the severer cases cannot be projK'rly looked upon as complications. In many instances, liowever, the bronchitis becomes intense, imj)licating the large and small tubes and giving rise to a prolonged symptomatic fever, which may even be accompanied by delirium. Broncho-pneumonia is not infrequent in children and aged persons, and may lead to a fatal result from progressive restriction of the respiratory surface or cardiac failure. This complication develops insidiously usually about the fourth or fifth day, but it may set in as early as the second day, or later during convalescence. The symptoms are frequently at first obscure, and extensive involvement of the lung may take place without great rise of temperature. Croupous pneumonia is less common. It is a late complication, occurring toward the close of the attack or when the patient is beginning to get aljout. It jn'esents the usual physical signs of pneumonia, and does not commonly differ in other respects from croupous pneumonia of the ordinary form. Both lungs are frequently involved. The crisis may occur late or deferves- cence may take place by lysis. In some cases, however, the pneumonia occurring after grippe is afebrile. Great feebleness of respiration and a tendency to cardiac asthenia characterize this form of pneumonia. Low muttering is apt to occur, and there is frequently jaundice with slight intestinal hemorrhage. Abscess or gangrene of the lung may follow the pneumonia of grippe. Pleurisy is not an uncommon complication, and empyema may occur. Purulent pericarditis may occur in connection with pneumonia or inde- pendently of that complication. In aged persons serous eifusion into the pleural sacs is now and then encountered. Parotitis is a rare complication of influenza. The infecting principle of grippe exerts a powerful depressing influ- ence upon the heart, both during and after the attack. The nutrition of the cardiac muscle is impaired and its innervation is deranged and enfeebled. Cardiac asthenia, often of a high grade, results. I have not personally seen either endo- or pericarditis occur. The murmurs which I have noted have been endocardial and either dynamic or litem ic. Among the complications relating to the nervous system cerebro- spinal meningitis is to be mentioned. It is fortunately of compai"atively rare occurrence. The cases may run an acute course like that of epidemic cerebro-spinal fever, with intense headache, convulsions, delirium, stupor, and opisthotonos, or the symptoms may be of moderate intensity and terminate in slow recovery. Abscess of the brain may occur as a complication. Cases have been reported by Bristowe, Sharkey, and others. Peripheral neuritis not infrequently develops during the course of the attack. General asthenia constitutes the chief and most constant sequel. The profound nutritive derangements of the acute process are at once followed by manifest loss of strength of varying grade and duration. 416 'INFLUENZA. It is, however, often extreme — altogether out of proportion to the intensity of the symptoms and their duration — and frequently lasts for weeks or months. It is important in this connection to note that this post-influenzal asthenia bears no constant relation to the original severity of the, case, many apparently light attacks being followed by profound and prolonged loss of strength, while cases of great intensity often ter- minate in comparatively early and complete recovery. Xor is this dif- ference in many instances merely accidental. The manifest explanation is to be found in the fact that in severe cases the patients are obliged to keep the bed and receive perforce necessary care during the active period of the attack, while those whose symptoms are slight remain up and are neglected. 1. Sequelae relating to the Respiratoey Tract. — 1. Bron- chitis. — It is not to be wondered at that an acute affection characterized by active catarrhal processes aflFecting the mucous membrane of the re- spiratory tract should, in a considerable proportion of the cases, be fol- lowed by a lasting and troublesome bronchitis. This is the sequel that more than all others attracted the attention of physicians in the earlier epidemics. I have noted two principal forms : (a) Subacute bronchitis, with little constitutional disturbance, but marked physical signs, and an abundant tenacious, muco-purulent expectoration. This condition lasts for several weeks and terminates in complete recovery. (6) A bronchitis which resists ordinary treatment, and, with varying ameliorations and exacerbations, gradually establishes itself as chronic. In other words, the attack of influenza proves the starting-point of a bronchitis which is chronic from the outset. 2. Broncho-pneumonia has been observed in a large proportion of the cases, not only as a complication, but also as a sequel — a fact for which the catarrhal inflammation of the respiratory mucous membrane and the acute prostration sufficiently account. 3. Croupous Pneumonia. — All practitioners have been impressed with the frequency with which croupous pneumonia develops in the course of influenza or during convalescence. The association of these two diseases has much to do with the high death rate of influenza in certain epidemics — more, perhaps, than has generally been ascribed to it, for the reason that the symptoms of influenza may, in cases of unusual severity, mask those of the intercurrent affection. Nor is it remarkable that pneumonia, so often intercurrent in acute diseases, should arise as a complication. Occurring as a sequel of influenza, pneumonia fre- quently involves the upper lobe — apex pneumonia. It occasionally runs a very protracted course, and under these circumstances often assumes the guise of tuberculosis — pneumonic phthisis or phthisis florida. I have encountered several cases in which the differential diagnosis presented great difficulty, was rendered hopeful only by the absence of tubercle bacilli from the sputum, and finally confirmed by recovery. In these cases high and irregular temperature, continuing for several weeks, with copious muco-purulent expectoration, rapid wasting, sweating, apex dulness, with diffuse subcrepitant rales, especially when there is a marked family predisposition to pulmonary tuberculosis, render the clinical picture alarmingly like that of a galloping consump- SFQUEL.E RELATING TO THE RESPIRATORY TRACT. 417 tion. All the cases of this nature that 1 have seen terminated in com- plete recovery. 4. Pill 1)10 nari/ Co)tstuiipt)oi>. — Far more numerous, however, have been the eases in ^hich influenza has been the point of departure for actual ])ulnu)n;irv eonsuni])tion. TJie patients have been persons in whom the hereditary j)redisposition was marked or who were living under conditions, such as association with consumptives, which singu- larly exposed them to infection. Under these circumstances the symp- toms of influenza have passed away, leaving, usually, merely debility with slight cough and expectoration, such as attend an ordinary bron- chitis. But these symptoms have persisted, not yielding to treatment, and after a time, npon examination, tubercle bacilli and localized dul- ness have been found. 5. Pleurisy. — Whether or not the infecting principle of influenza directly causes pleurisy cannot in the present state of knowledge be positively affirmed. Plastic pleurisy constantly, pleurisy with effusion occasionally, arise in connection with croupous pneumonia and tubercu- losis occurring as sequels of influenza. The stitch in the side of influ- enza is probably in most cases pleurodynia, as it is unaccompanied by friction sounds and as a rule quickly passes away. Intercostal neural- gia is not rare, even with herpes zoster, in the course of or as a sequel of influenza, and may sometimes mislead ; but it is certain that second- ary infections, to which the lesions of the bronchial mucous membrane expose patients suffering from the grippe, sometimes toward the close of the attack, and often during convalescence, may reach the pleura and give rise to inflammation of that structure. The pleurisy arising under these circumstances may be plastic or it may be accompanied by serous or purulent effusion, and does not diifer from that caused by similar in- fections under ordinary circumstances. To this general statement there must, however, be noted an exception. In a number of instances in persons previously in good health I have seen influenza followed by pleurisy of an unusual form. The symptoms have been acute and very severe. Among them the following were especially marked : Great pain, limited to the region of the apex, irregular high temperature, often reaching 104-105° F., coarse, rubbing friction sounds, slowly increasing dulness, with feeble distant breath sound, no bronchial res- piration ; cough has been slight or absent, and there has been little or no expectoration ; constitutional disturbance has been great ; the physi- cal signs at the base and upon the opposite side have been without significance. These phenomena have warranted the diagnosis of a rapidly developing apex pleurisy with great thickening — a diagnosis confirmed in my experience by a single post-mortem examination. In other instances recovery has slowly taken place with retraction, re- stricted movement, and permanent impairment of resonance, though the general health of the patients has remained good, and it has been im- possible to find in their occasional scanty morning sputa tubercle bacilli. 6. Asthma. — In neurotic individuals asthma has occurred as an accompaniment of bronchitis following influenza. 7. Otitis media constitutes one of the more distressing complications and sequels of influenza. It is more likely to arise in cases in which nasopharyngeal lesions are prominent or persistent. The superficial Vol. I.— 27 418 INFLUENZA. layer of the mucous membrane of the nasopharynx in the acute stage rapidly undergoes patchy necrosis, and there is an abundant irritating discharge. The ear trouble may occasionally arise without great pain, but, as a rule, the suffering is severe and tends to recur after perforation of the tympanic membrane as the thick discharge and necrotic tissue accumulate. Rapid disorganization of the structures of the middle ear sometimes occurs, with permanent deafness as a result. In many cases the suppuration yields stubbornly to treatment and persists for weekg or months. II. Sequelae relating to the Circulatory System. — 1. Cardiac Disorders. — Hearts impaired by previous disease of the valves or wall often undergo additional damage and pre-existing symptoms are aggravated. But it is not always the damaged heart that suffers. Many of the worst cases occur in persons of previous good health. Robust, self-reliant men who scarcely know what sickness is become feeble, hypochondriacal, and valetudinarian. It has been a pitiable sight to witness the sufferings, partly physical, largely mental, of some of these patients. The actual cardiac symptoms are heart conscious- ness, sometimes distress, sometimes actual precordial pain, usually paroxysmal, occasionally suggestive of angina pectoris, breathlessness and faintness upon effort, unsatisfactory sleep, disturbed by dreams and startings, headache, and great languor and malaise. The physical signs are simply those of enfeebled and irregular heart action. They consist of weak impulse, faint first sound, and now and then an indistinct soft systolic murmur. The pulse is small, feeble, arhythmic, and intermit- tent. Much more distressing to the patient and his friends are the men- tal symptoms. To his general feeling of depression and disability are added tormenting fears of permanent invalidism or sudden heart failure. The condition is always distressing, sometimes alarming. Fortunately, however, experience has shown that the prognosis is favorable. These cases, even after they have lasted a year or two, quickly recover under proper treatment. In another group of cases the nutrition of the heart muscle is fairly well maintained, its innervation being chiefly affected. Here we have the intermittent heart. At regular or irregular intervals the heart drops a beat. If the patient is aware of this fact, either from feeling his own pulse or from the disagreeable precordial sensation which sometimes occurs, he is apt for a time to be much distressed by it. Presently, however, with returning health the heart dropping ceases to annoy him. In a small proportion of cases it continues to be a lasting cause of distress and valetudinarianism. Cardiac intermittence does not always yield readily to treatment, and once fully established becomes in a small proportion of the cases a permanent symptom. Precordial pain, arhythmia, tachycardia, and bradycardia are com- mon after influenza. 2. Simple ancemia may occur after grippe as after other acute diseases. It is neither constant nor intense, the brunt of the infection, save in ex- ceptional cases, falling rather upon the nervous system than the blood. There is nothing especial in the anaemia of convalescence from influenza. It usually yields to treatment and terminates in recovery. 3. Pernieious Ancemia. — In four instances, however, I have seen that form of anaemia called pernicious follow grippe. One of these DIAGNOSIS. 419 cases WHS of peculiar interest as an illustration of the tendency of the infection to select in its attack the tissue of least resistance — the weak spot in the oroanisni. A oc'iitleiuan at>;e(l fifty nine, su])pose(l to he iu full health, had mild influenza in the spring of 1891. lie kept about, but was for several days feverish and depressed. Catarrhal symptoms were slight. From this time he suddenly grew pale, and died in eight- een months, having presented all the symptoms and blood conditions of pernicious aniemia. This patient's father died at an advanced age of diabetes mellitus. His only son died at the age of thirty seven of malignant hemorrhagic measles, and a grandson, the child of the last, had benign hemorrhagic measles. III. SeQIHOL.E KIOLATINU TO THE GaSTRO-INTESTINAL TrACT. These present little that is peculiar, and as a rule are not persistent. Occasionally a tendency to diarrhoea persists, and I have seen mem- branous enteritis follow the gastro-intestinal form of grippe in several instances. The suggestion tliat catarrhal appendicitis may arise as a late result of gastro-intestinal influenza is worthy of serious considera- tion. IV. Sequelae relating to the Nervous System. — Headache, insomnia, and neuralgia are common sequelae. The nervous derange- ments which follow grippe may consist of mere general loss of tone — neurasthenia with gastric, cardiac, or spinal symptoms predominating, or they may assume the definite aspect of substantive aflPections, such as hysteria or chorea ; again, various motor and sensory palsies, manifesta- tions of peripheral neuritis, may arise ; finally, psychic disorders, as melancholia and the insanities of malnutrition, may occur. The nature of the nervous trouble is doubtless determined by hereditary or pre- viously acquired predisposition on the part of the individual, and its course is not different from that of similar affections arising under other circumstances, and especially after the other acute infections, as, for example, enteric fever. The prognosis is in the main favorable. With reference to insanity following influenza, so far as I can learn its fre- quency has been greatly overestimated, and it is probable that persistent insanity arising as a sequel of this affection is in point of fact rare, and that it occurs chiefly, if not solely, in those already strongly predis- posed to mental disorder, in whom the attack acts as an exciting cause, not specifically, but in the same way as any other powerful perturbating agent. Diagnosis. — The direct diagnosis of influenza is under ordinary cir- cumstances unattended with difficulty. The progress of the outbreak, the number of individuals attacked nearly at the same time or in quick succession, the rapidly developing asthenia, and the prominence of the nervous symptoms serve to distinguish it from other epidemic diseases. The bacteriological diagnosis can be sometimes made by an examination of the bronchial sputum, and can be verified in doubtful cases by cultures. The differential diagnosis between influenza and non-specific catarrhal affections attended by fever, malaise, weakness, severe headache, and pains in the limbs may be made by due regard to the causative relations of the two affections. Outbreaks of simple catarrh occur as the result of sudden changes in the weather, and are for that reason most frequent in 420 INFLUENZA. changeable seasons, and especially at the end of winter and in the early spring. Influenza, on the other hand, is not in any way dependent upon the vicissitudes of the season, and may occur, as has been shown, indifferently at all times of the year, in wet or dry, mild or cold seasons, and in every variety of climate. No difficulty attends the difFerential diagnosis between influenza and ordinary sporadic catarrhal fevers, which lack the characteristic depression, neuralgic and rheumatoid pains, and the irritating cough and dyspnoea. Some of the cases of influenza bear a strong resemblance to enteric fever in the first week. Malaise, headache, obtunded hearing, mental depression, fever, epistaxis, coated tongue, tender belly, and diarrhoea are observed in both affections. The temperature curves are, however, unlike, and the acute attack of influenza in uncomplicated cases runs its course ere the period at which splenic tumor and rose spots establish the diagnosis of enteric fever. Anders has called attention to the occur- rence of influenza during the period of incubation of enteric fever. This accidental association of the two diseases may sometimes occasion difficulty in diagnosis. Cerebro-spinal fever has sometimes prevailed during epidemics of influenza. The occasional occurrence of cases of influenza with marked nervous symptoms, intense head pains, pain- ful retraction of the muscles of the back of the neck, and vomiting, renders the differential diagnosis between these two affections extremely difficult and in some instances impossible. Whether the infecting prineij)le of influenza is capable of directly giving rise to infection of the meninges or not remains to be determined. Dengue, or breakbone fever, closely resembles influenza. Each of these diseases prevails in pandemics, developing suddenly, advancing rapidly, affecting almost all the inhabitants of regions invaded. They resemble each other in the frequency of relapses and the liability to repeated attacks during the same outbreak ; in the fact that they are not self-protective ; in the want of accord between the gravity of the symp- toms and the low death rate of uncomplicated cases ; in the suddenness of the attack, intensity of the pains, and high degree of mental and physical depression. Influenza lacks, however, the cutaneous mani- festations, the remission in the course of the fever, and the tend- ency to arthritis which are seen in dengue. It differs from dengue also in the liability to serious complications and in prevailing in all climates. Prognosis and Mortality. — Death scarcely ever occurs in un- complicated cases except at the extremes of life. The very young bear influenza badly ; the aged bear it worse still. Pre-existing disease often modifies the course of influenza unfavorably. Individuals suffer- ing from chronic bronchitis, emphysema, fatty heart, and nephritis offer poor resistance to the depression of grippe. Phthisis and other ex- hausting diseases increase the danger of the attack. Cases attended by very severe symptoms usually recover, unless the patients be very young or very old or the subjects of some complicating malady. The prog- nosis in individual cases is greatly modified by the character of the pre- vailing epidemic. In some of the epidemics the death rate has been low and the mortality from other diseases not greatly increased. More commonly the death rate of endemic affections is much increased, and THE ATM EST. 421 in sonu' of the older cpidcinics influcnzn apjx'urs to have been attciidcd bv a hi<2;h direct (U'atli rate. Tlie deaths from inHiienza reported in I*aris, Deeeniher, 1H80, and flannarv, 1890, nnnibered oidy 'Jl.'>, whik' the general mortality ex- ceeded the average by 5500. Trkatment. — PrnpJii/Id.vis. — Ett'eetive preventive measures are as yet unknown. Unfavorable sanitary conditions, overcrowding, damp unhealthy dwellings a])pear to increase the prevalence and severity of the disease ; the opposite conditions of living do not, however, secure immunity. During an epidemic the aged, those enfeebled by chronic diseases, those subject to bronchitis, consumption, emphysema, degenera- tive disease of the muscles of the heart, and nephritis, should be cared for with solicitude, since they constitute the ckiss especially prone to the graver complications of the disease and contribute a large contingent of the fatal cases. During an epidemic the isolation of a patient who has developed the symptoms of the disease, either in his home or in a hospital or other public institution, does not secure, as in certain of the other contagious diseases, protection for those about him — a fact to be explained by the activity of the infecting principle and the intense susceptibility of individuals in all classes of society. The segregation of the patients and their attendants and the disinfection of the belongings of the patient and the apartments are not neces- sary. The nasal and bronchial discharges should, however, be disin- fected. Every case, however mild, should be regarded as likely to be serious, and the patient should be confined to the bed or to the couch for some days. Prophylaxis against the attack is theoretical and to a great extent impracticable ; prophylaxis against sequels is in the highest degree prac- tical and useful. The Management of Cases. — The treatment of influenza is expectant and supporting. i!^ot only are epidemics self-limited, tending to rapidly exhaust the susceptibility of a community, but the individual attack is also of definite duration and self- limited, tending to run its course in from three to four or at most, in the absence of complications, in from seven to ten, days. Where the duration of the attack is prolonged beyond the period indicated, complications are almost invariably present. In all epidemics the majority of the cases are of mild intensity. The management of this group of cases should be for the most part hygienic. Patients are uncomfortable and anxious, easily fatigued, and unfitted for their usual avocations. It is only exceptionally that they consult the physician. It is unfortunate, however, that this is the case, since those who continue their avocations and duties and expose themselves to un- favorable influences during the attack not infrequently manifest at a later period the most serious results of the disease. In point of fact, the patient should even in the milder cases abandon for the time being his ordinary avocation. He should remain within doors, preferably upon a couch, for at least two days, and only gradually resume his accustomed duties. The diet should be restricted to the ordinary fever foods. Milk is especially indicated, and may be given in doses of from one litre to a litre and a half during twenty-four hours in divided doses. Egg 422 INFLUENZA. albumen stirred into water, flavored with a little brandy or wine, or eggnog, milk punch, or gruel, may occasionally with advantage re- place the ordinary allowance of milk. Hot beef tea or concentrated meat extracts are to be avoided. They very frequently increase the headache and languor. Cold drinks in moderate quantity are usually acceptable to the patients. Weak wine whey, a mixture of equal parts of seltzer water and milk iced, koumyss, matzoon, and similar pre- parations, enable the nurse to furnish the necessary changes where the stomach is irritable. The administration of alcoholic stimulants must be regulated in part according to the previous habits of the patient, in j^art according to his immediate condition. Abstemious persons may not need them, but those who have been in the habit of taking alcohol, the aged, and those debilitated from previous sickness are benefited by the judicious use of alcoholic beverages. Early in the course of the attack a laxative may be necessary. This may consist of some form of saline or a laxative dose of calomel, or the latter administered at night, followed by the former in the morning. Caution is, however, necessary in the use of purgatives in influenza, since in a very considerable proportion of the cases gastro-intestinal symptoms with diarrhoea occur, and in some instances are difficult of control. The analgesic antipyretics are to be used cautiously in view of the tendency to general, and especially to cardiac, asthenia. Nevertheless, the guarded administration of antipyrin, phenacetin, migranin, and other members of this drug group are often necessary to relieve the agonizing pain of influenza. Small doses of phenacetin and sodium salicylate, administered in powder or capsule at short intervals, very often exert a powerful influence in mitigating the suiferings of the patient. Small doses of Dover's powder repeated at intervals of two or three hours are likewise of benefit. I cannot say that I have seen any advantage from the use of warm baths, foot baths, or diaphoretic drinks, the patients usually preferring to remain undisturbed. Advantage sometimes follows the administration of small doses of morphine, with which, in the case of extreme sweating, minute quantities of atropin may be added. If there be great restlessness and jactitation, the hypoder- mic injection of morphine, together mth hyoscin hydrobromate, proves useful. Quinine in small doses is mthout eifect. In large doses it simply augments the sufferings of the patient. There is no adequate evidence to show that quinine in any dose favorably modifies the course of the attack or aborts its duration. During convalescence iron and bark, and in particular strychnine in full doses, are to be administered. In the milder cases the catarrhal symptoms call for no special meas- ures of treatment. When intense the corvza, tonsillitis, laryngitis, and bronchitis are to be treated upon general therapeutic plans. Inunctions of fatty substances about the brow and over the bridge of the nose are sometimes useful in relieving the distress of the coryza. Animal fats, such as washed lard, cold cream, and the like, are preferable to the min- eral fats — cosmoline and vaseline. A 2 per cent, solution of morphine and cherry-laurel water may be snuffed into the nostrils. The pains TREATMENT. 423 associated witli the coryza and tlie iiciivalfjic pains arc to sonic extent mitigated bv a flannel nightcap or silk iuindUerciiief' tied about the head. Tickling cougli may be relieved by steam inhalations and the application of sinapisms over the manubrium. In the graver eavSes prominent indications for treatment are to be found in the fever, the catarrhal i)roeess, the asthenia, and the pain and sleeplessness. It is especially important that the failure of the powers of tiie circulation whicli arc cliaracteristic of the disease should be anticipated by efficient supporting treatment. This is particularly urgent in the case of influ- enza affecting infants, the very old, and those previously debilitated from any cause. The febrile movement is not usually excessive, almost always transi- ent. A fever regimen should be adopted. The disinclination to take food is often so great that a sufficient quantity can scarcely be adminis- tered, especially in the early days of the attack. Small amounts of nourishment must be given at regular hours. As convalescence begins patients should be urged to take food. The quantity taken at one time should be increased and the intervals between feedings pro- longed. At least enough fluid should be taken to assuage thirst. The ingestion of simple beverages exerts a favorable action upon the skin and kidneys. The frequency of spontaneous sweating and the readiness with which free perspiration may be induced must be looked upon as a contraindication to the use of diaphoretic drugs. General and local bloodletting, emetics, uauseants, and drastic purga- tives are to be avoided in the treatment of influenza. For the relief of the distressing cough no drugs are more effectual than opium and its derivatives, especially morphine and codeine. It is important to observe the same caution in administering this group of medicines to infants and aged persons in influenza that is necessary under other circumstances. The influence of carbolic acid in restraining cough makes it a useful adjuvant. The bromides, paraldehyde, chloralamide, trional, and chloral may be used for the relief of jactitation and in- somnia. Chloral should be used with great caution. Gastro-intestinal symptoms must be managed in accordance with general principles. If of moderate intensity, they require no special treatment. Complica- tions are to be treated in accordance ^\\ih. general therapeutic indica- tions, especial attention being directed to the asthenia which is so prominent and disastrous a tendency in grippe. The treatment of influenza demands the most careful attention of the physician, who must be on guard to detect the inflammatory lung com- plications, which so often lead up to a fatal issue, as early as possible. The circumstances of the indi^ddual case, the age of the patient, the nature of the complications, and the effect of remedies must be carefully taken into account. All measures that tend to depress the general ner- vous system, the functional activity of the respiration, or the heart power are to be carefully avoided. During the convalescence the patient should be treated with equal, even more, care than those convalescing from other acute infectious dis- eases. Rest in bed, a systematic diet of high nutritive value, strychnine, iron, and later change of climate, are important. The patient should be instructed as to the liability of pulmonary disorders, which may become 424 INFLUENZA. chronic, and in regard to the necessity of limiting for a time the appli- cations of his energy. The convalescence is often slow and trying, alto- gether out of proportion to the severity of the primary attack. Influ- enza is a distressing affection even in the milder cases, and so often dangerous in its after effects that it cannot, though a disease of short duration, be looked upon as a trifling malady. EPIDEMIC CEREBROSPINAL MENINGITIS. By THOMAS S. LATIMER, M. D. Synonyms. — Cereljro-spinal fever ; Spotted fever ; Lepto-meningitis. Definition. — A s^pecitic infectious disease of microbic origin, but little if at all contagious, characterized by inflammation of the lepto- meniuges, with disturbance of function of the whole cerebro-spinal axis, motorial, sensory, and psychical, with strong tendency to a speedily fatal issue. History. — Epidemic cerebro-spinal meningitis has been known from the earliest years of the present century, but was first accurately described by Viesseux in Geneva in 1805. It appeared in the United States in 1806, and continued with l)ut little interruption for ten years During this time it also made its appearance in Spain, Germany, Italy, Algeria, and Denmark. In 1854 it broke out in Sweden with severity, causing 4000 deaths. Slight epidemics occurred in Germany in 1822 but it was not until 1863 that it was there of frequent occurrence V. Ziemssen, writing: in 1874, savs that it had then become domesticated in Germany. Since then Striimpell says there have been more or less ex- tensive epidemics every year. It broke out in the workhouses of Ireland in 1846, and appeared in severe form in Dublin in 1866-68. In Fagge's Practice of Medicine, published in 1886, it is stated that Scot- land and England had been almost exempt up to that time. It was first observed in this country at Medfield, Mass., in 1806. After this scattered epidemics of moderate severity appeared in various parts of the United States up to 1816, when the disease disappeared, to recur in Middletown, Conn., in 1822-23. Since then it has been of frequent recurrence in various parts of the country. At Carbondale, Pa., 400 persons died from this cause out of a population of 6000. In Pepper's Aiiierican Text-booh,^ a tabulated statement, begun by Stille in 1863 and carried on to 1883, and completed by Pepper up to 1892, shows that it prevailed continuously during this period in Philadelphia ; the smallest mortality for any one year was 23 in the year 1891. The total mortality' reported in this city for this period was 2575. Numerous cases occurred in both armies in the late American war, but it cannot be said to have had any widespread prevalence in either. Etiology'. — The essential cause of epidemic cerebro-spinal menin- gitis is not yet definitely determined, though a large body of evidence tends to establish such a relation with the micrococcus lanceokdus encap- sulatus. This organism is found almost invariably in the exudates, meningeal and cerebral, and in the lungs in cases complicated with pneumonia. Eberth first isolated it in 1880 in a case of meningitis secondary to pneumonia ; Bozzolo and Leyden in 1883 ; Weischelbaum ^ ^Iti American Text-book of the Theory and Practice of Medicine, Pepper, vol. i. p. 163. 425 426 EPIDEMIC CEREBROSPINAL MENINGITIS. in 1886 ; Netter in the same year ; Goldschmidt in 1887 ; Ortman, Foa, and Bordoni-Uifreduzzi in 1888 ; Banti in 1889 ; and Bonome in 1890. Mirto obtained it from the exudates in 1891, and inoculated rabbits with it, producing septicaemia. Klippel in 1891 and Ribbert in 1892 found it in sporadic cases. In Welch's laboratory in Baltimore in 3 recent cases the same organism was found (Flexner and Barker). Other organisms, however, have been frequently found associated with cerebro-spinal meningitis ; thus, according to Flexner and Barker, in 1889 Netter found the Friedlander bacillus in a case of meningitis following otitis media. Mills, in a case of pneumonia associated with meningitis, thought he had discovered the same organism. Monti in a case of pleuritis with arthritis obtained the micrococcus^ kmceolatus in 1889. Adenot in the same year and Kainen in 1890 each isolated a bacillus which they supposed to be the typhoid bacillus. Debove, in a case associated with peritonitis, obtained a pneumococcus. Hanot and Luzet isolated streptococci from the exudate from the meninges in a case of general infection resulting from puerperal fever. The staphylococcus pyogenes aureus was found in a case associated with otitis, broncho- pneumonia, and arthritis by Le Gendre and Beaussenat in 1892, Klip- pel in 1892, in a demented individual who died of acute meningitis, observed the micrococcus kmceolatus over an area of brain softening where the exudate was most abundant. Boulay and Courtois-Suffit in 1890 isolated the mici^ococcus kmceo- latus from a case of combined meningitis and peritonitis without pneu- monia ; and Bonome found the same organism — pneumococcus — in a case of combined pericarditis and meningitis. Zorkendorfer, from Chiari's laboratory, reports a case of purulent meningitis associated with inflammation of the ethmoidal cavity and suppuration in the sphenoidal sinuses, in which diplococci were found in the pus taken from the sinuses and from the meninges. Pure cultures of these caused fatal septicaemia in rabbits, in whose blood organisms were found not distinguishable from the micrococcus lanceolatus. Drs. Flexner and Barker — to whom I am indebted for most of the historical facts here mentioned — found the micrococcus lanceolatus in a case of traumatic meningitis with no other focus of infection. Prudden likewise isolated it in a case of traumatic meningitis, a patient of Holt's. Streptococci and staphylococci have also been found by various observers, and by Roux a bacillus resembling that of typhoid fever ; by Mircoli, the bacillus pyogenes foetidus. Netter clearly traced meningitis to the pneumococcus in 16 out of 30 cases in which no pneumonia had existed. The number of cases examined is as yet too small to warrant the statement that the pneumococcus lanceolatus is the single and only cause, but the facts recited above go far to show that, although other organisms are often found and the pneumococcus has not invariably been shown to be present, it is, however, so much more frequently present than any other pathogenic microbe that it may fairly be consid- ered the causative agent in a large proportion of cases. If, however, it is admitted that this organism is the specific cause of epidemic cerebro-spinal meningitis, the frequency with which it is found in sporadic and traumatic cases makes it impossible to distin- guish the epidemic from other forms of meningitis. It is generally ETIOLOUY. 427 julniittod that tlio clinicnl ])henomona arc nol widely dissimilar in the various tbrnis of nu'iii ileitis, and if this etiological lactor is not pecu- liar to the ei)ideinic form, then all meiiin<;'e:d intlammations are essen- tially the same, and any tranmatie or sj)oradie ease may be a [)oint of departure in epidemics of this disease. The frequency with which the inicrococca.s lancco/dtu.s is found in the mouths of healthy individuals (;h the stomach into the circulation, and, ac<[nii-int;- a virulence not before possessed, "ive rise to meningeal and other intiammations, thus becoming truly auto-infec- tive. Such an origin of course does away with the necessity for conta- gion or th(> introduction of the microbe with food or drink. It is almost uniformly present in health, and requires only some alteration in the condition of the host to invest it with virulence. If so, \vc must seek an explanation of its epidemic prevalence in the environment of the individual. The atmosj^heric conditions, character of the water and food supply, season, shelter, clothing, occupation, and any of the many conditions affecting the general health, are without special bias until the entrance of a specific organism or a newly acquired virulence gives it. Of these predisposing causes — predisposing to epidemic prevalence — w^e have comparatively little definite or positive information. It may be said in general terms that extreme cold of long continuance ; bad food, especially if in process of decomposition ; drinking water containing' abundant organic impurities ; breathing the foul air of crowded tene- ment-houses ; insufficient and uncleanly clothing, — may all be conditions so impairing the vigor of the individual, while favoring the multiplica- tion of the organisms and determining greater virulence, as to cause epidemic outbreaks where otherwise a sporadic case or two only would be found. These conclusions, however, which seem reasonable enough, cannot readily be sustained by any positive evidence at our disposal. In the winter and spring of 1893 an extensive epidemic of cerebro- spinal meningitis prevailed in the vicinity of Lonaconing, a mountain village of about 5000 inhabitants in the coal-mining region of Mary- land, wdiich was carefully studied by Drs. Simon Flexner and Lew^ellyn F. Barker of the Johns JEIopkins University staff in the Department of Pathology. The well-known ability of these gentlemen and the pains- taking manner in which this study was conducted, make their report one of the most (if not the most) valuable recent contributions to the study of this disease. It will be understood in what follow^s that w^hen- ever reference is made to the Lonaconing epidemic it is done on the author- ity of their report and that of R. L. Randolph, assistant ophthalmic and aural surgeon of the Johns Hopkins Hospital, whose report is limited to the ophthalmological phenomena observed in this epidemic. The village of Lonaconing is situated in a deep gulch in the Alle- gheny Mountains, through which a muddy creek of considerable size runs. All the streams in this vicinity are subject to speedy rise after a heavy rainfall of even brief duration. The houses are situated in terraces on the side of the valley and mountain through which the stream runs. Tier above tier rise on the side of the mountain the houses occupied by the miners, while in the valley are situated the 428 EPIDEMIC CEREBROSPINAL MENINGITIS. business and professional houses. Above the level of the dwellings are placed the privies, which must constantly pollute the soil about them, and after rainfall, as indeed at all times, foul the stream running through the town. The stables are quite close to the dwellings. On the arrival of Drs. Flexner and Barker the snow which had recently fallen had already begun to melt with the effect thus described : " The water streamed down the mountain sides, carrying with it the general refuse from the yards, the material from the cow stables, and the excreta from the outhouses of the upper tiers, through the yards, past the dw^ellings situated below, and finally entering the creek, which acts as a huge sewer winding through the centre of the town. On their way these polluted surface washings found no system of drains for their reception, and in places crossed the common roadway in little rivulets, through which the inhabitants of the town had to drive and walk." The water supply of the village is obtained from surface wells and from cisterns, and in many instances the surface water with its accom- panying filth was seen flowing directly into these wells, which are in constant use for drinking water. They may be further supposed to be contaminated by filtration of water from the creek, which is itself addi- tionally fouled by slaughter-houses built on its margin, from which the blood and other noxious matters find ready entrance into its waters. In many instances the houses of the miners are overcrowded ; in one house in which was a fatal case eleven persons slept in three bedrooms. The houses were generally very close together. Many, however, were commodious, well built, and not overcrowded ; these possessed no im- munity, and the majority of cases prevailed in the higher rows. One fatal case occurred in an isolated dwelling on a high hill a quarter of a mile distant from any other dwelling. A number of cases, however, occurred in the lower sections, and there were numerous sporadic cases more or less distant from the site of general prevalence. The earliest cases were in two young men, aged respectively twenty- one and twentv-two years, who in January, 1893, after a dance in which they were overheated, exposed themselves to extreme cold, so that " their hair, wet with perspiration, was frozen upon their heads." A long and cold drive to their homes followed, and on the next day they were attacked with cerebro-spinal meningitis. Immediately afterward the disease be- came epidemic at many different points in the same region, and prevailed continuously during the succeeding months up to the middle of May. Fresh cases occurred with every decided diminution of temperature ; and by the 1st of March 68 well marked cases and 40 classed as abor- tive had been recorded. No notable difference attributable to sex was observed, and though, as usual, children were most often attacked, it was by no means limited to them. An outbreak in the neighboring town of Frostburg ran the total number up to 200. In this epidemic it is noteworthy that such a condition existed as is favorable to the development and spread of infectious diseases in gen- eral, and that there was an actual prevalence at the same time of scar- latina, diphtheria, and other diseases of this class. It is also shown how close is the relation to season, and even to variations of temperature in the same season — a fact frequently observed before. ETIOLOGY. 429 That external variations in tcmpcratnrc should so dccidcdlv infliK'nce tho c'j)ideinii- pi'cvalonce ol" this disease is somewhat renKirkal)le, as it is of course attended with little or no alteration in the temperature of the medium in which the orer amount. The body of the cord was invaded in like manner, but to a greater extent than in front. That ])art of the cord at which the pos- terior roots enter was especially the site of cellular infiltration ; between the roots and the median fissures the cell infiltration was abundant, but a uniform layer of cells may be said to have extended from the ante- rior lateral to the posterior lateral fissure. The predominating cells resembled " lymphocytes or the mononuclear cells of granulation tissue." Changes in the ganglionic cells of the cord were not marked ; some variation was observed in the granulation of the cells and in the clear- ness of the nuclei and nucleoli, and especially in the sharpness of the cell outline. There were no well defined changes in the axis cylinders of the cord observed by Flexner and Barker, owing possibly to some difficulty in satisfactorily staining those parts. In the nerve roots, how^ever, swelling of axis cylinders and interstitial changes also were marked. In both anterior and posterior roots the axis cylinders were swollen in considerable nnmbers, though in the anterior roots a large number — the majority — were not affected. " The normal axis cylinders lie in a space which has apparently been formed either by the disappearance in part or the contraction of the myelin sheath, a faint line of myelin being still visible just inside Schwann's sheath ; in some instances the myelin entirely fills the space between the axis cylinder and the sheath of Schwann. On the other hand, the swollen cylinders, which occur singly or in groups, always fill the space inside the myelin sheath, being distinguished from the latter by their larger size and by their staining properties. It is worthy of note that in those nerves in which a cellular proliferation, especially around the veins, can be made out, more axis cylinders show this change than where the cellular increase is not so apparent." The vessels of the perineurium are engorged and hemorrhages occur between the bundles. Cell proliferation in the interstitial tissue is not abundant in the anterior roots, but in the posterior roots it is quite marked, and at times is so great in the peri- and epineurium as to obscure the fibres. Other organs are more or less affected, but not in a manner distinctive of the disease. Congestion of the kidney, liver, spleen, and lungs with oedema not infrequently occurs. Tiie lungs are at times engorged, oedematous, or solidified, and the pneumococcus is found in the exudate. The pleura and pericardium are now and then inflamed and ecchv- motic, and occasionally lined with purulent exudate. Endocarditis is 436 EPIDEMIC CEREBROSPINAL MENINGITIS. also occasionally present, v. Ziemssen has found the intestine present- ing conditions analogous to those occurring in dysentery. Eifusions into the joints, purulent or semi-purulent, are not infre- quent. Granular degeneration of voluntary muscles, especially of the spinal muscles, is of common occurrence. Symptoms. — The period of incubation is necessarily uncertain, if indeed there is any propriety in speaking of an incubative period in a disease supposed to have its origin in an organism almost uniformly present in the human body. Whether the organism begins to acquire virulent properties or the body ceases to be resistant to it cannot at present be stated, since we know so little of the circumstances effecting the change. Nevertheless, persons have been known to develop symp- toms after association with the infected or after exposure to contact with infected clothing within from eight to ten days. The symptoms are necessarily varied and complex, depending as they do on the degree of toxaemia, the extent and site of the inflammation, and the amount of inflammatory exudate, and this irrespective of the particular organism concerned in its production. Certain cases progress with such rapidity and violence as to over- whelm the system before the local changes can exert marked influence. Others present phenomena of the gravest character, which may be alto- gether ascribed to profuse exudation in and upon delicate structures within a circumscribed space surrounded by unyielding walls ; still others to the direct destructive metamorphosis of the inflamed tissues. To what extent any of the clinical features of the disease are due to the local action of the infecting organism cannot now be said, since but little is known of this branch of the subject. It may be stated, in general terms, that the psychical phenomena are most apparent in those cases in which the cortex is most implicated, the special sense disturb- ances where the base is most involved, and the muscular and general sensory disorderly manifestations when the spine is extensively in- vaded. The fact must not be lost siglit of that all the phenomena character- istic of this affection may occur without any inflammation of the meninges whatever — that decided inflammation of considerable extent and with abundant purulent exudation over convexity and base may be revealed post-mortem in cases where no clinical evidence of its existence had been present, as in a case related by L. Emmet Holt.^ Prodromata are exceptional, and when present not very characteris- tic. Occasional rigors, general malaise, headache, back-pain, vertigo, and loss of appetite furnish little if any indication of the nature of the impending trouble. No elaborate classification of the varieties of the affection is desir- able. It is sufficient to describe the ordinary form, and to note the particulars in which it may vary from this form, and as far as may be the condition causing or attending such variation. TJie Ordinary Form. — Prodromata are rare and slight, such as have already been referred to. It has been thought that cerebro-spinal meningitis is more likely to begin between the hours of midday and ^ Transactions of the American Pediatric Society, vol. v. p. 214. sYMP'roMs. 437 rai(lni;s to the ]»hlebitic form as distinjiuished from the marantic, which is seen only amonj:: elderly ])ersons. This writei- ealls attention to the im|)ortant fact that the eye phenomena may he deteeted ophthalmoscopically some time hefore there is snhjective evidence of such severity as to attract attention in the midst of the severe jicneral ^uft'er- ing. Of the 35 cases exainiiicd by Randolph, the fimdus was normal in but 7, and of these 7, " 1 ha sFj,)rr.LM 441 Till- urinary I'uiictidii i- comiiKiiily bill little di.stiirlx'd. Polyuria i.s present at times. All»iiinin may We present, and occasionally a ft'W casts are I'oiind. The urine is oi'teu of liirv exudaU's or to the stnu'lural cliaiiiics wroimlit in tin- iiilliinicd nervous clenu'iits by tho spreadinii' of the inHainiiiatinii inward, and not till' iiicrc |)r('ssure of" fluid ; but \vv cannot thiid< this tlu,' most coninutn cause of death, or, at any rate, that it liives sufficient warrant to tlie statiMuent that death is due to the h)cal intracranial mischief rather than to the infection per sc. Not a few eases must also die in conse- quence of complieations, such as pneumonia, superadding pulmonary <»bstruction to central respiratory labor. A few eases with nephritic com[)lications may have a fatal issue determined by addition of unemia to the other depressing influences. Fatal results sometimes occur many months after apparent recovery, or patients may continue ailing many, many months before death ensues. Hadden's ease lasted over fif- teen months, and Striimpell ' re[)orts a ease that died after three nuaiths' illness. Diagnosis. — Owing to the extremely varied clinical picture pre- sented by this disease, in sporadic cases it will often escape recognition, but during its epidemic prevalence, when it is in the thought ni' the observer, it can usually be readily diagnosed. A primary difficulty occurs in the fact that all the characteristic symjitoms may be present in the absence of any meningeal inflammation whatever, as in the case of middle-ear disease, and this difficulty is increased when it is remem- bered that middle-ear inflammations may excite meningitis or a primary meningitis may lead to suppurative otitis. Time and treatment of the aural affection can alone resolve the doubt in such cases. The positive indications of meningitis are sudden invasion, pain in head, cervical, dorsal, and lumbar regions, loins, and less often of the extremities ; intense general hyperaesthesia ; assumption of positions relaxing painful muscles ; great increase of pain on movement ; inability to effect extension of the legs in the sitting posture, which may be readily effected in the recumbent posture; petechise, purpuric spots, herpes labialis, vomiting, and intense photophobia with irregular move- ments of the globe. Ophthalmoscopic examination of the eye will almost always shoA\' some orbital lesion even in advance of subjective indications. Engorge- ment and congestion of the optic disks, venous thrombosis, tortuosity of veins, descending neuro-retinitis (von Graefe), are conditions fre- quently present and of great value in diagnosis, as are also intolerance of sound, delirium, stupor, irregularity of pulse ; and, finally, blind- ness, indifference to sound, paralysis, and coma. The disease is to be differentiated from typhoid fever, in which tlie cerebral symptoms are a prominent feature. Typhoid is more gradual in its invasion, the fever pursues a more definite course, the pulse is more regular and uniformly rapid, pain is less pronounced and more apt to be limited to the first stage, vomiting is much less frequent, bend- ing and rigidity of neck and liack are rare, sordes on tongue, lips, and teeth is more often present and usually in greater quantity. The rose spots of typhoid are distinctive when present. Ileo-caecal gurgling and tenderness, and after the first week looseness of the bowels, are more distinctive of typhoid. Epistaxis and intestinal hemorrhages are com- mon to typhoid. Delirium is less active usually, and stupor more con- ^ Pathological Societi/ Transaction.-^, 1885. 444 EPIDEMIC CEREBROSPINAL MENINGITIS. tinuous. When hypersesthesia is present in typhoid it is of brief dura- tion. Extreme photoj^hobia is rare in typhoid, as is also the great sensibility to sound. Typhus fever resembles epidemic meningitis in the abruptness of its invasion, the extreme headache and cervical pain, general hypersesthe- sia, and rapidly developing delirium and stupor. It diifers in the briefer duration and commonly milder character of the pain and mus- cular rigidity. The hypersesthesia is less : great photophobia is uncom- mon. The fever is more uniformly high in typhus and pursues a more regular course. Typhus in this country is more rare, is virulently con- tagious, and can commonly be readily traced to its origin. The roseo- lous eruption in typhus is tolerably constant to the fourth day, while the eruption of meningitis may occur on the first or second day. Herpes rarely if ever occurs in typhus. Kernig's sign, of which we have no personal knowledge, according to its discoverer serves to distinguish cerebro-spinal meningitis from all other aifections. Influenza has some points of resemblance to meningitis, more espe- cially the sudden invasion, the head and back pain, convulsions, and stupor ; Ijut the absence or mildness of muscular rigidity, the rarity of delirium and coma, the presence of catarrhs, the relative mildness of the special s'ense symptoms, and its cosmic prevalence serve sufficiently to distinguish it. The cerebral type of influenza which most closely resembles epidemic meningitis usually occurs as an occasional variety during the prevalence of other forms. . The presence of the grip organism may serve to establish the diag- nosis, or, rather, we should say, to establish the etiology of the particular case, for a true meningitis may exist differing in no important particular from that induced by any other cause. Gowers thinks that meningitis, especially the tubercular form, is not rarely confounded Avith hysteria, from which it may be distinguished in part by the previous history of the case. Hysterical attacks are rarely single and the individual symp- toms are seldom persistent. Hysteria commonly belongs to a later period of life, and more especially to the female. Strabismus in hysteria is always convergent, associated with contracted pupils, and varies from day to day. Strabismus due to organic disease is always divergent and connected with irregularity of pupils. Pyrexia and the existence of trophic disturbances of the skin make for meningitis. The presence of symptoms distinctive of organic disease, such as the ophthalmic conditions referred to, are of far more value in diagnosis than the history of previous attacks, and go much farther in favor of meningitis than a history of previous attacks goes in favor of hysteria. From other varieties of meningitis the epidemic form is not to be positively diagnosed by the symptoms alone. In all forms of menin- gitis the direct structural results of the inflammation are the same, and the pressure effects of the exudate are not different. So likewise in ordinary cases the toxic effects are not clinically distinguishable. It is only in fulminant cases, which may be said to be peculiar to the epi- demic type, that any marked clinical distinction exists, and this chiefly in the sudden and violent manner in which the symptoms develop. Just, however, as ordinary epidemic cerebro-spinal meningitis differs from the PROG X()S[.<— Tin:. 1 TMKST. 44o fulminant variety in the slowness ami relative mildness ot" its develnj)- ment, so does tnbercular meningitis nsually dift'er from ordinary epi- demic meningitis in the eomparative slowness of its ao unlikely to be mistaken for epidemic meningitis that it is scarcely neces- sary to consider them in detail. Pneumonia is at times primary and at times secondary to meningitis, but as it seems probable that they have a common origin it matters little which is the antecedent disease. There is of course no difficulty in distinguishing between the iuflammaticiu of the meninges and a pneumonitis. Tetanus might possibly be confused with sporadic cases of meningitis, but the diseases are readily distinguished by the history of injury in the former, the more violent muscular contractions and the consequent deformitv, the persistent presence of trismus, the greatly exaggerated reflexes, the diminished sensory disturbance, the absence of photopholna, and the freedom from mental disturbance. PROGNOSIS. — The progiKJsis is always grave, and, though many cases doubtless recover, of no case is it possible to anticipate recovery with any strong measure of proliability. The mortality varies in different epidemics, but is always high, ranging from 30 per cent, to 70 per cent., according to v. Ziemssen ; Hirsch places it at from 20 to To per cent. In the mild or abortive cases recovery may take place in five or six days. But in other forms it is the more protracted cases that do best : tliose that live past the first week have a moderately fair prospect of recovery, but as it cannot be said of any case, however mild in the beginning, that it will recover, so it cannot be said even in cases advanced to the stage of coma that they are quite hopeless. In all, however, in which the onset is sudden, the symptoms violent, the stupor persistent, the pupils dilated, the muscles paretic, the pulse feeble and irregular, the skin cya- notic, death may be confidently anticii^ated. Cases advanced to the stage of coma have recovered, but so rarely that this condition piay l)e taken as of fatal significance. Under five and over forty years are lui- fiivorable periods. All fulminant cases die, or the exceptions are so few they may practically be left out of consideration. Treatment. — There is no specific treatment fin* epidemic cerebro- spinal meningitis, and no very effective symptomatic treatment. In all cases the patient should be placed in a cool, darkened, and well ventilated room, from which all visitors and noises are to be rigidly excluded. The 446 EPIDEMIC CEREBROSPINAL MENINGITIS. liead should be shaved and the whole body thoroughly cleansed. As the possibility of contagion must be admitted, articles of dress worn by the patient and the bed linen should be disinfected before being sent to wash. Other prophylactic measures are of small value, although it is of course desirable, as in all other infectious diseases, to avoid all forms of unclean- liness, overcrowding, improper food, drinking foul water, and all things tending to impair bodily vigor. It is important to avoid exposure to extreme cold when overheated and exhausted by excessive exercise, especially on the part of those Avhose duties bring them into close association with the affected. In the early stage remedies supposed to lessen the circulation in the affected parts by producing vasomotor contraction of their bloodvessels, such as ergot and belladonna, have been thought effective. The use of mercury, both internally and externally, has had many advocates, but does not hold a very high place in the estimation of modern practitioners except in cases associated with syphilis. It is, I believe, more frequently used than openly advocated. It is still held to be of value, however, by competent observers, v. Ziemssen commends it, and Pepper thinks it of service in the treatment of sequelae. It may be doubted whether it has any proper place in the management of this affection. Bloodletting, both general and local, has been extensively practised and is still not without advocates. Striimpell thinks the local abstraction of blood of undeniable value, however difficult to explain. Pepper also thinks venesection may be useful in well selected cases of sthenic type, considerable pyrexia, and in the early stage in healthy adults. Even in delicate and young subjects he holds the local abstraction of blood or dry cupping at times advisable. Many others entertain similar views. The writer is inclined to the opinion that the abstraction of blood in any way or at any period of life is of more than doubtful utility in this disease : although it is better borne by the adult than in childhood, it is harmful at all periods of life, and the cases, if any, in which it may be useful are of such extreme rarity that its use as a therapeutic measure had better be abandoned. Of like value are blisters to the scalp and along the spine. Proba- bly of little or no real value, they undoubtedly add much to the suffer- ing of the patient. If useful at all, they can only be so in the first stage, before any extensive exudation or destructive structural meta- morphosis has occurred. Escharotics of all kinds are for similar rea- sons objectionable. They are capable of little good, they are directly painful, and unquestionably add to the hyperffisthesia and to the pain and muscular spasm produced by movements and manipulation. German authorities still recommend the antiphlogistic measures of the past — in fulminant cases blisters, mercurial inunctions, calomel by mouth, vene- section, leeches, and cups. In the opinion of the writer such measures are hurtful in by far the larger proj)ortion of cases, however judiciously selected. An occasional brisk cathartic, especially in the beginning of the dis- ease, is often serviceable, and at no time harmful if used with ordinary discretion. Xow and then a case, apparently in the last stage, may be profited by full catharsis, as in Cases 72 and 75 of Abercrombie's series of simple meningitis, where even after the induction of profound stupor TREA TMKNT. 447 severe niii'iiation was tnllnwcd Itv rcfoNcrv >rciiiiiiiil\' •''"' t<» the remcdv. SiU'li r(iiiark:il)U' ctt'octs, however, arc not to be anticipated, and tlie mea.-iire is nndonbtedly eai)able of harm in enfeebled snl)jeets. ("ahibar bean, recommended by N. S. Davis, is entitled to f'nrther trial ; as yet bnt little evidence of its efficiency is ottered. In a disease in which we know of no means of destroying the organism producing it, nor any of neutralizing its toxins, which runs a rapid course to a fatal issue in a large proportion of cases, it would seem most advisable to limit our efforts to the relief of symptoms, the maintenance of strength, and to those topical measures which are under other circumstances found to limit the amount of inflammatory transu- dation. All of these purposes are in a measure accomplished by anodynes, of which opium and its derivatives are best. The most troublesome symptoms are pain, hypertesthesia, muscular spasm, vomiting, sleepless- ness, and all of these are more effectually combated by the hypodermic iujeetittn of morphine than by any other means. In the later stages, ■when coma supervenes, neither this nor any other measure is likely to be of any use, and it is only at this period that there is danger in the discreet use of this agent. It is a conservator of strength, since nothing conduces to speedy exhaustion more than continuous suffering, loss of sleep, and inability to take and retain food. So far as any drug does, it lessens the amount of inliaramatorv exudate, and in those cases in which the jirogress of the case is uninfiueuced by it, it more than any other ay;ent solaces the last hours of the sufferer. Of equal or perhaps greater value is the coincident use of cold to the head and spine. To be useful it shoidd be thoroughly used, and the best results are to be had from the early and almost continuous applica- tion of ice to these parts. This measure likewise lessens pain, dimin- ishes transudation and the migration of leucocytes, overcomes muscular spasm, relieves vomiting, especially if ice is also kept in the mouth and occasionally swallowed, and conduces to sleep. This measure may be advantageously associated with the application of warmth to the extremi- ties ; and, since its good effect is probably largely due to the diminution of cereliral and spinal hyperj^mia, we may reasonably expect that coin- cident lowering of the general Ijlood pressure by the administration of such agents as nitroglycerin will materially favor this end. As the general temperature is not usually very high, and lifting or other manipulation of the patient is very painful and likely to produce muscular spasm, the use of cold bathing is contraindicated ; moreover, by inducing contraction of the cutaneous vascular area it would tend to heighten the blood pressure in internal organs. Applications of ice to the head and spine as directed are far less troublesome, less painful, more efficient, and probably unattended by the ill effect referred to. Cold douches to the head or the use of a Leiter's coil where ice can- not be had may be advantageously emjiloyed, but they are not of the same efficiency as the continued application of ice. Aufrecht ^ reports a case of cerebro-spinal meningitis with low tem- perature treated with hot baths, 40"^ C, with immediate remission of symptoms and subsequent recovery. His patient was a man twenty- ^ Die Therapie der Gegenuart, Jan., 1895. 448 EPIDEMIC CEREBROSPINAL MEXINGITIS. five years of age, in whom, at the end of the third week of illness, benumbed sensorium, constant delirium, and persistent opisthotonos existed. The pulse was rapid, but the fever had subsided. " After the somnolence had lasted ten days, in view of the frequent pulse and low temperature it was decided to use the hot baths. There were criven from the loth to 17th of April twelve baths at 40° C. of ten minutes' duration each. After the first baths improvement began. Graduallv the sensorium cleared up, pain and opisthotonos diminished, incontin- ence of urine and fseces disappeared, the abducens nerve assumed its normal function, and the power of speech returned. Upon discontinu- ing the treatment nocturnal headache and delirium reappeared, where- upon three more baths were given, after which all symptoms of disease vanished." ^ This very interesting case suggests a wider field of useful- ness for hot baths than within the clinical limitations mentioned. That hot baths may be useful in the absence of fever, with feeble pulse, clouded sensorium, and headache, need surprise no one ; but remembering the great hypersemia in all stages of this disease of the vessels of the brain and cord, the extent of the inflammatory exudate within the cranium and spinal column, and the not infrequent congestion of other internal organs, it would be perfectly rational to expect benefit in other cases in which the temperature was not very high, even, or perhaps most, in the early stage of this infection. Hyperj)yrexia rarely occurs in this disease except just before death. Indeed, high temperature is not a characteristic of cerebro-spinal meningitis, and may in many, if not most, cases be ignored if measures Avhich might add to the pyrexia tend to the relief of other more im- portant conditions ; and probably nothing is more important than the diversion of blood, if it can be effected, from the engorged cerebral and spinal vessels, and no measure seems better calculated to effect this than the measure under consideration. It may also be serviceable by favor- ing the elimination through the sweat glands of toxic agents ; and also, by lessening nephritic hyperemia, increase the functional activity of the kidneys with a like result. It would, moreover, in the judgment of the writer, be rational to associate this with the application of ice to the head and over the carotid arteries ; and, if the reasoning is just, these measures are especially applicable to the early stage of the affec- tion before injury, mechanical or other, is done to the important struc- tures implicated. Other remedies of anodyne and hypnotic properties, such as potas- sium bromide, chloral hydrate, sodium bromide, bromoform, phenacetin, and chloroform, are at times useful, but none of them are so potent for good as morphine in cases where it is well borne. The writer has seen phenacetin give the most marked relief to the painful symptoms and induce quiet and restful sleep in other forms of meningitis, and should be inclined to expect similar benefit in the epidemic form. Iodide of potassium has long enjoyed some repute as a sorbefacient in this affec- tion. In syphilitic cases and in subacute and chronic cases, after the subsidence of acute symptoms, it may be of some value, but in the career of the disease it can be of little service. Its value at any time when syphilis does not complicate the trouble has doubtless been exag- ^ Journal of Nervous and Mental Disease, March, 1895. TREA TMENT. 449 gerated. The use of (|iiiiiiii(' lias Ix'cii advocated, but it is of doiihtful advantage, nor is there any reason to snppose it more usefnl in tli<' inter- mittent oases than in others. To maintain tlic 8tren<;th of the })atient earefnl attention shonld be given to the food. It shonld always he licjnid, and shonld he adminis- tered at short intervals. If the vomiting makes it diffienlt to retain the food, advantage may be taken of an administration hyjxxlei'mieally of morphine to give a somewhat larger (jnantity than at other times. The use of ehloral hydrate by enemata will often I'elieve this symptom for a time and enable the patient to retain food, lleetal feeding may also be practised with advantage, in which case the food should always be pep- tonized. The writer is skeptical as to the benetit of forced feeding in troubles of this kind. The use of a stomach tube is very likely to in- duee efforts at vomitino-. The struyo'le necessarv for its introdnetion nuist add to the pain in head and back, produce severe muscular con- tracture, and in the young and timid convulsions may be excited. The free use of water at such temperature as best suits the patient, if it can be retained, is always desirable. With little children the white of an ogg may often be given mixed with water, slightly sweetened and acid- ulated with lemon, without exciting opposition, to the manifest advan- tage of the patient. Animal broths in all forms may alternate with milk and eggs. The administration of stimulants may become needful, especially when food is badly assimilated. At times a little champagne iced or brandy and ice will quiet the stomach, and enable food to be retained better than anything else. When they add to the excitement of the patient, increase the pain and delirium, or notably heighten the fever, it is best to omit them. Milk punch by stomach or bowel is a good form in which to give alcoholic stimulants. At all times when there is great depression and a feeble heart they may be tried, subject to the above conditions. In cases that recover convalescence is often j^rotracted and requires the careful supervision of the attendant. Stimidants may be required, but if food is taken in fair quantity and ajipears to be well digested and assimilated, alcohol may be advantageously dispensed with. Active exer- cise is commonly impracticable, but passive exercise in the open air and sunshine should be enjoined as soon as it can be borne without distress. Massage of paralyzed muscles and of stiff and painful joints will Ijc of service. With this electrical stimulation may be associated to advantage. Various drugs are recommended during this period, such as mercury and potassium iodide to favor absorption of inflammatory products, iron, cod-liver oil, bitter tonics, etc. Good food when it can be digested and assimilated is the only real tonic, and drugs of this class are only val- uable in so far as they favor these ends. It is to be feared that in the majority of instances they are more likely to disturb the stomach and impair digestion than to improve it. Perhaps a few drops, not above five or ten, of the muriated tincture of iron, with a slight excess of hydrochloric acid, especially in cases where this acid is shown to be deficient in the gastric secretion, taken directly after meals, will at times prove of value. But so far as drugs are concerned it may be said with- out reservation that no drug that disturbs the stomach can at this time be other than harmful, and no matter what the supposed indications for Vol. I.— 29 450 EPIDEMIC CEREBROSPINAL MENINGITIS. its use it should be withheld. With these may be classed even those peptonized and other artificially digested foods which offend the taste and nauseate the patient. Sapid foods that " make the mouth water " also excite the gastric secretion, and are, other things being equal, most easily digested. There can be little doubt that enjoyment of food has much to do with its proper digestion, or, at any rate, food that offends the taste or has merely lost its savor by reason of sameness is less likely to be promptly digested. As much variety should therefore be secured as is practicable. It is much to be feared that lack of suitable season- ing is too often a characteristic of sick-room diet. Insipidity in food with defective taste in the invalid is an unhappy conjuncture. As there is no local inflammatory trouble in the alimentary canal, in these cases there can be no reason why pungency in food should be objected to if it accords with the patient's taste. ERYSIPELAS. By GEORGE DOCK, M. D. Synoxyms : Rose, St. Anthony's fire ; f^rysipele (Frencli) ; Erv- sipel, Rothlauf (Gorman), etc. The etymology is uncertain. Definition. — Erysipelas is an acute infectious disease characterized by a peculiar inflammation of the skin, with fever and other general symptoms, and caused by the streptococcus of Fehleisen. EtioloCtY and PATHOLOCrY. — Formerly considered a so-called gen- eral disease caused by alterations in the body fluids, especially bile (Galen to writers of the nineteenth century^), with a local manifestation, we now know that erysipelas is of bacterial origin, beginning as a localized infection and producing general symptoms as the result of the local dis- ease. Very early in the history of bacteriology- bacteria were found in erysipelatous lesions, but their constant occurrence was first shown by Koch.^ About the same time, and independently, Fehleisen^ not only demonstrated the presence of the organisms, but by cultures and sub- sequent inoculations showed their causal relation. The inoculations included seven on human beings, the subjects of inoperable malignant disease, and justified by the clinical observation that erysipelas acquired in the ordinary way in such cases seemed sometimes to have exerted a favoral)le influence. The streptococcus of Fehleisen was supposed at first by its discoverer and others to be sid generis, and it was not until several years after the first announcement of Fehleisen, when the value of the independent researches of Rosenbach, Passet, and Garre on pyogenic streptococci could be realized, that the specific nature of Fehleisen's organism was seriously questioned. Since then, as the result of an enormous amount of experimental- and much clinical work, the belief has gained accept- ance that the streptococcus of erysipelas is identical with the strepto- coccus pyogenes of Rosenbach, and cannot be distinguished from the streptococci found in suppurative lesions of the most diverse kinds — e. g. phlegmon, puerperal peritonitis, certain anginas, etc. A discus-sion of the various observations and experiments for and against the specific nature of the erysipelas organism is quite outside the object of the present article. Much confusion has been thrown around ' E. (J., "There are a number of reasons which make it extremely probable that the connection between the skin and mucous membrane of the alimentary canal, between the perspiration and the secretion of bile, between the solar plexus and the cutaneous nerves, is effective in the production of erysipelas" (Reil, Fieherlehre, vol. ii., 1804). - Nepveu, Des Bacteries dans PErysipele, Paris, 1870; Hueter, Deutsche Zeitschrift fur Chirurgie, 1868, i. p. i. ; Cenlmlhlatt fur die med. Wissenschaften, 1868, Xo. 35. ^ "Zur Untersuchung von pathogenen Mikro-organismen," MittheUungen aus dem Kais. Gcsundheitsamf, 1881, Bd. i. S. 38. * Fehleisen, " Aetiologie des Erysipels," Berlin, 1883, Verhandlungen der Wiirzburger med. GeselUehaft, 1881. 451 452 ERYSIPELAS. the subject by failing to adhere closely to the generally admitted clinical and anatomical features of erysipelas. By ignoring these features yari- ous authors haye thought to haye produced erysipelas ^yith cultures of different species of micro-organisms, when in reality the change pro- duced was not erysipelas at all. The idea that erysipelas in man has in certain cases been produced by other organisms than the streptococcus of Fehleisen (staphylococci, typhoid bacilli, etc.) has two j^ossible sources of fallacy. One of these is that the supposititious erysipelas is not a real erysipelas. This was no doubt the case with the experimental bacillary erysipelas of rabbits described by Koch. The other souix-e of fallacy is the fact that the organisms cultiyated from erysipelatous lesions may have been recent arrivals there. The old idea that the erysipelas cocci can l^e recognized h\ the results of inoculations in animals has been almost entirely abandoned by all who have carefully examined the matter.^ Whatever the future may reveal in regard to the relation of the streptococci found in various dis- eases, we can at present assume that under ordinary conditions erysipe- las in man is always caused by streptococci morphologically similar to the common streptococci of suppuration. For obtaining these organisms in pure cultures various methods are used. The usual method, and the old one, is to remove a piece of affected skin with the most rigid antiseptic precaution and place it in sterilized bouillon. This is of course a method which cannot be used very frequently, and as a substitute that of Achalme ^ is preferable : After carefully disinfecting the skin a thin layer of collodion is rapidly dried over the part to be examined ; a sterilized lancet is then passed rapidly through the collodion into the deep layer of the skin. The first drops of blood are removed by the aid of a sterilized pipette. The skin is then squeezed so as to press out a dro}) or two of serum, which is received in a sterilized pipette. From this tuljes of nutrient media are inoculated. It is necessary- to use a good deal of serum, because even in that from the most active seat of the disease the microbes may be rare. Cultures from different cases of erysipelas, or from the same case in different media, give results which differ slightly, as can be seen from the descriptions of various observers. On the whole, grown under similar circumstances the cultures show unmistakable resemblances. In gelatin the colonies grown at the ordinaiy temperature become visible in from thirty-six to forty-eight hours. In the depths C)f the gelatin they appear as small, opaque, white specks, round and sharply circumscribed. Those on the surface are somewhat larger and almost hemispherical. Examined with a moderate power, the margins are seen to be slightly irregular. The centre of the colony is milk-white, the border somewhat translucent. From the fact that the gelatin is never liquefied, the streptococci can be distinguished from the vdiite staphylo- coccus which may grow in the culture as the result of contamination from the skin. In agar or serum at 35° C. the colonies grow more rapidly and are more translucent. Grown in bouillon, the medium becomes turbid in about twelve hours, ^ KMrih, Arheiten aus clem Kais. Gesundkeitsamt, 1891, vii. 389; Von Lingelsheiin, Zeitschrift fur Hyqiene, xii. .308. 2 Achalme, "'Sur I'Erysipele," Paris Thesh, 1892. ' ETIOLOGY AND PATHOLOGY. 45;5 but clears ii]> in three or loiir days, and tlie cocci ihcii loi'ni a j^ranidar sediiiieiit oil the hottom. J 11 milk the strej)t(>cucciis causes a local coagulation in the course of several days, followed more or less rapidly by complete coagulation and subse([uent retraction of the clot, leaving the serum clear. Examined alive in liquid, the streptococcus shows only Brownian movement. The sti'e|)tococcus of ervsij)elas stains readily with the usual aniline tlyes, and fiintly with carmine or litematoxylin. It is not decolorized by the methods of Gram and Weigert. The appearance of the organism differs slightly according to the soil in which it is grown, but in general it forms short chains of from six to eight cocci on solid media. In liquid media the chains may contain as many as thirty to forty cocci. They measure from .3 to .6 micromilli- metres in diameter. The chains often contain pairs in closer apposition (diplococcus forms). In old cidtures the cocci show considerable varia- tion in size, and also in intensity of staining. The stre])tococcus of erysipelas grows well in the air, but it also grows anaerobically. According to Achalme, it grows better without access of air. Lubinski ^ could see no difference in the appearance of the colonies grown under both conditions. Both observers say that vitality and virulence are well preserved in anaerobic cultures. Ac- cording to Achalnie, the streptococcus grown anaerobically shows more marked action than otherwise, so that he claims it is really a facultative aerol)c. The streptococcus grows best in alkaline media. It produces, how- ever, an acid reaction in the medium, which is, according to Achalme, less marked than that produced by streptococci from pus, although this observer also claims that attenuated cultures of erysipelas cocci produce an acid reaction more rapidly than virulent ones. The acidifying power varies much wdth the medium in which the organisms are cultivated. The nature of the acid formed is not known. The erysipelas coccus is sensitive to extremes of heat and cold and to variations in its culture soils, but wdth care in the selection of the cul- ture and the soil may be kept alive for long periods (" almost unlimited," Achalme). Both experiments in vitro and clinical observations go to show that the organisms may remain latent for long periods, and then as the result of some change in the environment which favors their activity, or in consequence perhaps of the disappearance of some substance which inter- feres with them, they may become active. In consequence of this quality certain auto-infeetions may be explained. The virulence of the streptococcus of erysipelas varies extremely — in fact, quite as much as that of the similar cocci found in other diseases. Cultures may be attenuated and their virulence restored, although the latter, or even the preservation of a fixed degree of virulence, is a matter of great difficulty. In experimenting with cultures of erysipelas cocci, rabbits oifer the best medium, and in them all the degrees of intensity of the reaction may be observed wdth cultures of different degrees of virulence. Thus ^ Cenlralhlatt fiir Bakteriologie unci Parasitenkunde, Bd. x\ri. No. 19, 189-t. 454 ERYSIPELAS. in the most severe cases there is a general sepsis without local lesion either from inoculation in a vein or in the skin. In the descending scale of virulence we have fatal sepsis following more or less severe local lesion ; localized erysipelas ; mild redness and swelling of the skin. Finally, cultures may be so attenuated as to produce no local alteration. According to numerous experiments, putrefaction is a powerful assist- ing source of virulence in a streptococcus culture — a fact which has an important bearing on puerperal erysipelatous infection. The symbiosis of the streptococci is doubtless of great importance. Roger made the interesting observation that injections of filtered cultures of micrococcus prodigiosus with very weak cultures of streptococcus produced a severe infection. Clinically, mixed infection of streptococcus and other bac- teria is not uncommon, but so far as erysipelas is concerned reliable data are scanty. The mode in which the organisms produce the phenomena of the dis- ease is by no means so definitely known in the case of erysipelas as in tetanus, diphtheria, and some other diseases. Manfredi and Traversa^ who were the first to experiment with soluble products of the cocci, were able to produce only transitory nervous symptoms. Achalme had a similar experience. Roger thought he obtained a soluble toxic substance from erysipelas cultures, the action of which was not in proportion to the dose employed. Roger asserted that by heating this substance at 110° C. it acquired vaccinating qualities. Courmont^ holds that the streptococcus produces a slowly acting predisposing substance, with last- ing eiFects, but one that acts indirectly. Brieger and Wassermann^ found the urine in a case of erysipelas with nephritis very fatal to mice. Stern ^ found that the serum of vesicles in cases at the height of the disease was much more fatal to mice than blood serum of normal subjects. Numerous experiments in the treatment of malignant disease by injections of erysipelas or streptococcus toxins have shown that the serums or filtrates usually produce the general symptoms of erysipelas. The experiments, however, have added little to our knowledge of the erysipelas poison. Although the streptococcus is the cause sine qua non of erysipelas, it is evident there must be other factors. First among these is individual predisposition, the real nature of w^hich, however, we do not yet under- stand. That the various causes of temporary or permanent weakness of the tissues favor the occurrence of the disease we can easily believe. So alcoholism, exposure, overwork, exhausting disease, even hunger and fatigue, come in play. A very important factor is the existence of a solution of continuity of the skin or a mucous membrane. Operations, wounds of all kinds, accidental lesions, injuries received at post-mortem examinations, acne and other skin diseases, sores or abrasions of the eye, mouth, nose, or pharynx, boring the lobe of the ear for earrings, operation wounds of the nose, throat, or mouth, cautery wounds, tracheotomy incisions, leech bites, the umbilical cord or stump, the uterus post-partum, may ^ Berne de Med., 1890, No. 10, p. 843. ^ Qhariie Annalen, Bd. xvii. ^ Congress fiir innere Med., xii. p. 286. ETIOLOGY AND PATHOLOGY. 455 i'lirnisli the jxtints oi" entrance of tlic ^cniis. The old division of ery- sipelas into traunititic or surgical and non-traninatic (" idio])atliic ") or medieul ery8ij)elas is i'ullinii; into deservetl disnse, or when used at all the terms are applied in a different sense from the original one. In the old sense idiopathic cases were due to an internal alteration becoming localized in the skin, surgical cases to the entrance of a " contagium." It is reasonable to sup[)ose in many cases that even if no wound can be seen there is nevertheless one present, however small, in the skin or a neighboring mucous membrane (throat, nose). We must, however, admit that diminished vitality of the covering epithelium may suffice for the entrance of the germ without solution of continuity, or that in certain circumstances infection may take place through physiological wounds, such as the tonsils. For such cases the term " cryptogenetic " is preferable to "medical" or "idiopathic." From what Ave now know of the bacteria of erysipelas we may suppose that the organisms are often present in or on the body, but lack the assisting causes necessary for the development of the process. Among these causes may be men- tioned putrefaction or the presence of certain micro-organisms as already mentioned. Disturbances of the circulation around the point of entry are im- portant assisting causes. This has long been known to clinicians and has been demonstrated experimentally. Roger ^ found that when strep- tococci were inoculated into both ears of rabbits and the superior cer- vical ganglion of one side destroyed, the local reaction was favored on that side. He also found that section of a sensitive nerve assisted the infection, Aprojws of this, Guinon^ raises the interesting question whether nervous affections, such as hysterical hemiansesthesia, ex- ophthalmic goitre, etc., have any effect on the course of erysipelas. Ochatin^ and Von Lingelsheim* varied these experiments, producing hypergemia by section of nerves, and also by the use of collodion or adhesive plaster and injecting cultures of erysipelas cocci. They found not only that the process was more severe in the hypersemic ear, but that even cultures of mild virulence could produce severe lesions. Filehne^ has shown that by raising the temperature of inoculated animals the infection runs a more rapid and more favorable course. Contagion, or the acquisition of the disease from another known case, does not occupy as important a position in regard to erysipelas as it did in the preantiseptic days. In fact, in surgical wards now the disease is hardly ever seen to spread, and when it does some error in technique can usually be discovered. It has been thought that erysipelas is contagious in the sense that it may be acquired " through the air." This is possibly only when the germs themselves are transported in that medium, and its actual occurrence is always doubtful. An interesting case of indirect contagion, which also illustrates the resistance of the organisms, is reported by Stumpf.*" A woman had a boy infant, born in 1888. He acquired erysipelas and died. In 1889 a girl child Avas born and remained healthy. In 1890 another boy was born. He was ^ Comptes rendus de la Societe de Bioloc/ie, 1890, p. 222. ^ Traite de Medecine, tome ii. ^ Arch, de Med. exper. et d'Anat. path., iv. 2. * Zeitschrift fib- Hygiene, xii. ^ Proc. Physiolog. Soc, Cambridge, Aug. 11, 1894. ^ Deutsche med. Woch., March 17, 1892, p. 231.' 456 ERYSIPELAS. washed, and tlie shirt worn by the first child, which had not been used in the mean time, was put on him. Thirteen days later he developed erysipelas, with a relapse and ultimate recovery. Erysipelas is influenced to a certain extent by atmospheric condi- tions. In this country it is most frequent in the early spring. Low temperature and moisture and rapid changes in temperature aid in its production. According to the investigations of Anders,^ the number of cases increases from August to April (in Philadelphia), and then decreases. One half of all the cases occur in February, March, April, and May. These relations are not always the same in other places and times. Erysipelas is most frequently observed in early middle life. Notwithstanding the greater exposure to wounds on the part of men, the temporary predisposition furnished by the puerperal condition makes the relative proportion of the sexes less unequal than might be supposed. Anders puts the proportion of men and women affected as three to two. Pathological Anatomy. — Even during life the lesion of ery- sipelas exhibits the cardinal signs of inflammation. After death the redness and swelling are diminished, especially the former. The micro- scopic alterations in the tissues have been carefully studied in pieces excised during life, controlled by the examination of experimental le- sions in animals. Our knowledge of the changes is due largely to the investigations of Vulpian, Volkmann and Steudener, Renaut, Till- manns, Ranvier, Cornil, and others, though the researches of Fehleisen have thrown a light on them which former investigators could not give. Recently Unna has published the results of his observations, which fill out important lacunee. Following Fehleisen, the lesions are described as in three zones. The outer zone is beyond the raised margin of the erysipelatous area. Microscopically, this zone shoAvs masses of cocci in the lymph spaces, but no alterations in the tissues. This zone passes into the middle one, corresponding to the advancing margin of inflam- mation. It is characterized by the evidences of inflammatory reaction in the tissues.^ The vicinity of the streptococcus colonies contains numerous small cells, and some of these cells contain cocci. In the third zone cocci are few or absent, but there are traces of inflammation in the stage of retrogression or absorption. According to Unna,^ the process affects the skin and subcutaneous tissue simultaneously, but heals more rapidly in the skin, and seldom reaches the height it does in the deeper tissue. In the subcutaneous tissue he finds that the cocci are not confined so especially to the outer zone as in the skin — a differ- ence which he suggests is due to more favorable conditions for the growth of the cocci in the deeper tissue. This corresponds to a more severe process in the subcutaneous tissue. In the inflammatory areas vascular changes are marked. The veins and capillaries are distended with blood. The leucocytes are not ^ Journal of the American Medical Association, July 22, 1893. ^ In erysipelas lymphangitis is jiart of the process, yet lymphangitis and erysipelas are not identical, either clinically, anatomically, or etiologically. Lymphangitis may be produced by various kinds of bacteria, as shown by the researches of Fischer and Levy (Deufsches Archivfilr C'hirurgie, xxxvi., 1893, H. 4 u. 5). ^ Hislopathologie der Hautkrankheiten, Berlin, 1894. VATlloLoaiCAL ANATOMY. 457 arranged especially aloii*;- the walls iA' the vessels, hut (»ften form small jii'oups in the vessels. Thev are distinetly increased in these parts. The caj)illariGs often contain rows of leucocytes, thouj^h according to Unna diiipedesis is not a constant occurrence. The arteries are dilated in some places, and ix'sides an increased ])ro])oition of lencocvtes contain much ('oaii'ulati'd tihrin. In other places the arteries are narrow, hut j)luuii('d with lihrinous thromhi, containiuii: leucocytes. In some of the veins (.-eutral thrombi are to be seen, evidently })ropagated from those in the arteries or capillaries. There is, then, a paralysis of the vessels, especially of the veins, with slowing of the current, adhesion of leuco- cytes, and intravascular formation of tibrin, es})ecially in the arteries. The Ivmph spaces and lymph vessels are distended with lymph con- taining streptococci in chains and masses. The leucocytes are found in greater numbers as the process advances. In many places in the lymph vessels there are firm white thrombi. The vascular changes are by no means the only ones of importance. The connective tissue breaks down and liquefies, or becomes fibrillated or converted into a pnlpy mass. The elastic tissue degenerates. The spindle cells of the skin break down and their nuclei disappear. The striped and smooth muscular fibres of the skin undergo a fate similar to the other tissues. The epithelial tissues suffer also. The swelling of the papillse loosens their connection with the overlying tissue. When the papilhe break down the epithelium follows, the nuclei lose their staining capacity, the protoplasm becomes indistinct and stains less readily. According to Unna, the epithelial cells do not swell, but the degenerated and partly necrotic epithelium is raised in tofo from the papillary layer, forming thus blebs or vesicles. In the contents of the vesicles cocci are rare in the beginning, but fibrin and leucocytes are always present. Later, bacteria of various kinds can be found in the vesicles. Sometimes the leucocytes are so abundant in the contents of the vesicles that the liquid is turbid or opaque, or, in other words, purulent. Occasionally vesicu- lar degeneration of the epithelial cells takes place, as described by Cor- nil, but this is not the cause of the gross vesicular lesions, which are due to the oedematous infiltration of the papillary layer of the skin already described. In contrast to the marked changes in the surface epithelium, that of the sweat glands and hair follicles is often little or not at all affected. In severe cases the hair follicles undergo changes similar to those in the surface epithelium. Erysipelatous inflammation of the skin may be described as a sero- fibrinous inflammatioM, but it may and sometimes does pass on into a suppurative or necrotic form. In the deep tissues erysipelas causes changes of a different kind, especially when the subcutaneous tissues are well developed. The lymph vessels and lymph spaces in the coats of the large vessels in the septa of the adipose tissue form the paths of the cocci, which are present in these parts in enormous numbers. Usually the cocci do not penetrate farther than the adventitiae of the vessels. The vessels themselves do not contain thrombi, as do those in the skin, but the fat lobules and their capillaries contain large masses of fibrin. There are also large 458 ERYSIPELAS. numbers of leucocytes which break down, forming pus in the septa of the fat tissue. This process often extends deep into the muscular tissue. The process in the deeper tissue is therefore a fibri no-purulent inflam- mation, although not recognizable clinically as purulent. In fact, in the majority of cases which seem to be su])erficial the deep-lving pus is absorbed without being discovered. It is when the pus makes itself known clinically that the term phlegmonous may be applied. (In addi- tion to this there is, of course, occasional phlegmon formation as the result of a complication to be mentioned later.) In the healing of erysipelas the cocci die, and they as well as the leuco- cytes and thrombi are removed from the areas in which they were. As blood begins to flow through the vessels the epithelium is renew^ed, forming a layer which desquamates at first, but ultimately becomes permanent. Finally the muscles, connective tissue, and elastic fibres are regenerated. As is well known, erysipelas is one of the diseases in which Metch- nikoff asserted the importance of phagocytosis. Perhaps most investi- gators, however, consider that in ervsipelas phagocytism in the manner originally described by Metchnikoff is not so important as the latter claimed. That the leucocytes frequently contain cocci, in different stages of degeneration very often, is admitted, but the general belief is that the cocci have been seriously affected before becoming the prey of the phagocytes. In the healing of erysi])elas macrophages, containing leucocytes, fibrin, cocci, and unrecognizable debris, can be seen. The earliest claims to the discovery of germs of erysipelas include accounts of bacteria in the blood. Later observers are unanimous in holding that as a general thing the cocci do not enter the blood circula- tion, notwithstanding the fact that they are frequently carried con- siderable distances in the lymph vessels. Even if they enter the blood by Avay of the lymphatics, they must do so so rarely and in such small numbers that they are disposed of in the blood without setting up other processes. That the cocci can, and in rare cases do, enter the general circulation was shown first by the observations of Von Noorden and PfuhL Sudakow ^ examined 5 cases of ervsipelas with reference to this point. He found cocci in 2 cases in both blood and sweat. In one case the blood, in another the SAveat only, contained the organisms. Aclialme " was unable to cultivate organisms from large quantities of l:)lood in 18 cases of ervsipelas of moderate severity. On the other hand^ in .3 fatal cases he was able to cultivate them from the blood (in the heart), and in 2 cases he found cocci in the urine. The probability of the cocci setting up metastatic processes by way of the blood depends partly on their virulence, partly no doubt on the numerous accidents to which they become exposed when they leave the lymph spaces, in the plasma or in the bodies of the leucocytes, and are carried toward the blood circulation. Here they are either disposed of or, under favorable circumstances, produce lesions which will be considered under Complications (p. 467). A diminution of the red blood corpuscles in the active stage of the disease was noticed by early investigators in ^ Centralblatf fiJ.r Bakteriologie u. Parasitenkimcle, 1893, ii. p. 817. ^ Loc. cit., p. 236. SYMPTOMS. 4-59 that field, but tloes not .scom to be constant. An increase of leucocytes, especially the polynuclear neutrophile eelLs, amounting to as much as two or three times the normal, is perhaps a constant occurrence. An increase of lihrin has l)een observed by many since it was first noticed by Andral and Gavarvet. Inflammation of the r('i;ionary lymphatic vessels and glands occurs in the course of erysipelas as part of the disease, but is marked only in cases of unusual severity or as a complication. Occasionally lymph glands some distance from the skin lesion are affected, sometimes very early in the disease. Other anatomical alterations play a subordinate part in erysipelas, and ^vill be considered under the head of Com- plications (p. 467). Symptoms. — The stage of incubation of erysipelas is either without symptoms or has those common to many other infectious diseases — malaise, anorexia, lassitude ; in some cases an indefinite feeling of exhilaration, perhaps from slight fever, can sometimes be recalled by the patient. The duration of this stage is variable. According to observations of Widal and ]S[etter and of Echalier^ in patients who acquired erysijjelas by exposure to other known cases the incubation was respectively two, six, ten, thirteen, and fourteen days. In Fehlei- sen's experiments on men the duration varied from fifteen to seventy- two hours, which corresponds to the period usual in animal inoculations (one to three days). Cases without a discoverable wound sometimes seem to have a longer period of incubation than others. The first striking symptom, which is rarely absent, is a chill. Usually the chill is sudden and severe, resembling the chill of malarial intermittent fever or of croupous pneumonia or the severe chills of septic infection, to which, indeed, the erysipelatous chill has a close affinity. It may last for only a few minutes or from one to two hours. The usual duration of the chill is less than half an hour, with cold skin, cyanosis of the lips and extremities, chattering of the teeth, and trembling. From the severity and the duration of the chill an idea of the severity of the disease may be formed. During the chill nausea and vomiting usually occur. The vomitus is not peculiar, but when vomiting is severe bile is often present, and so keeps up the tendency to perpetuate the term " bilious erysipelas." After the chill, or sometimes shortly before it, the temperature rises, usually rapidly, reaching 102° F. or more according to the severity of the case. The pulse is frequent in proportion to the rise of temperature, but full and strong. Nausea and a feeling of discomfort in the epigas- trium, with loss of appetite, continue. The tongue is slightly swollen, with a yellow coat. There is continued malaise. Headache is a common symptom. With some or all of these symptoms a day or more may elapse before the disease in the skin becomes visible. It was this period between the appearance of the general symptoms and those in the skin that seemed so convincing of the dyscrasic nature of the disease at a time M'hen the nature of infection was so much less understood than it is now. During this period the diagnosis is usually in doubt, or if there are marked cerebral symptoms the case may be considered one of typhoid 1 Paris Thesis, 1890. 460 ERYSIPELAS. fever. Occasionally careful examination or the jjatient's own account discloses tenderness or swelling of the lymphatic glands supplied by the part aifected. In some cases tenderness of the lymphatics, less fre- quently swelling, precedes the inflammation of the skin by several days. In cases beginning in the nose epistaxis often occurs, either spontan- eously or from blowing the nose. Before the inflammation appears the patient almost always has a .sensation of fulness or tension, sometimes a prickling or itching in the part aifected. When the infection takes place in the nose there may be an unusual sense of fulness and pain, beginning very soon after the chill and followed by the usual symptoms of coryza. When the inflam- mation begins in a visible w^ound the latter sometimes becomes paler before the special process appears. The characteristic erysipelatous lesion varies in color from a yellow^- ish pink to a bright or deep red color. In anaemic or cachectic persons the color is paler. Pressure causes the color to pale, showing a yellow- ish tint in the anaemic parts, but it immediately resumes its previous tint when the pressure is removed. The surface of the skin is usually shining, V>ut finely or coarsely granular according to the texture of the skin in the part affected. The appearance of the surface has been well compared to that of an orange. The characteristic feature of the ery- sipelatous patch is the abrupt margin by which it is sharply marked off from the sound skin. The distinctness of the margin and the elevation of the inflamed surface vary in different cases, depending partly on the thickness of the skin. The margin sometimes is regular, sometimes zig- zag, and again not at all distinct. This is especially so when erysipelas affects skin previously the seat of an ordinary inflammation or skin which is rugous, as that of the scrotum. Sometimes the margin can be recognized more easily by touch than by sight. An additional aid to its detection is that by examining the affected area through a glass plate with pressure. This method of examination, " diascopy " of Unna,^ €an be practised with a microscopic slide or a watch-glass, or by the more complicated method of Liebreich, called by him " phaneroscopy." The affected skin feels hard, brawny, like congealed skin or that of a cadaver. It cannot be pinched up in a fold except with difficulty. Pressure increases the pain. The inflamed part not only gives the sub- jective sensation of heat, but is actually warmer than the normal skin. On the surface of the inflamed area, except in the mildest cases, vesicles or bullae appear as the process reaches its height. By coales- cing these form large areas more or less elevated, filled with a fluid which is at first clear, later turbid. The epidermis over the vesicles easily becomes broken, and the serum, often mixed with blood or pus, dries on the surface. The erysipelatous patch enlarges by spreading in waves or irregular lines, " like an oil drop on paper." The extension is rarely symmetri- cal or even on all sides, but may spread on one side while remaining stationary or receding on others. The spreading takes place by stages. Sometimes it can be seen that the process is arrested tempor- arily w^here the skin is firmly attached to the deep tissues, as at the naso-labial fold, the margin of the hairy scalp, Poupart's ligament, etc. 1 Unna, Berliner klin. Wochenschr., No. 42, 1893. SYMl'TUMS. 4(U The swellini»: involves not only the skin, but also the subcutaneous tissue, thus adclint>; greatly to the detbnnity. Tlie ju'ocess is greatest where the skin is loosely attaelied, as in the eyelids, li])s, scrotiun, and external genitals. The (edematous swelling in these parts adds much to the distortion eharaeteristie of the (^lisease. Tile tenij)erature, which rises rapidly after the chill, reaching a height of 104° or 105°, remains elevated as long as the infianimatory process is active. The temperature is usually remittent, with a morning fall of one or more degrees. Usually the remissions are more marked in mild or favorable cases, and in these the temperature may be inter- mittent. (This has no necessary relationship with malarial infection, though it was formerly looked on as showing a malarial origin of the disease.) On the other hand, very severe cases may show marked remissions, as in one under my observation in Avhich the temperature showed a daily diiference on successive days of 3°, 3.4°, 5°, 5.5°, 4.2°, 4.6° F. Complications, especially internal complications, have a tendency to increase the temperature, and relapses are almost always preceded by a sadden rise. If death occurs in hyperpyrexia, the temperature some- times continues to rise post-mortem. In rare cases, sometimes otherwise severe, there is no elevation of temperature at all — afchrlle eri/sipcld^:. The pulse follows the course of the temperature during the height of the disease, with certain limitations. In cachectic persons it is rela- tively frequent. In cases with jaundice it has been observed to be relatively slow. The other symptoms are usually severe in proportion to the eruption and fever. Prostration, loss of appetite, coated tongue, and constipa- tion are almost always present. In severe cases delirium is common, usually of a mild kind. In others there is apathy, stupor, or even coma. In the most severe cases the typhoid condition comes on, with sordes on the lips and tongue — the latter being dry — trembling, delirimn and sometimes convulsions or coma. The urine usually contains albumin, hyaline casts, and increased numbers of leucocytes, and sometimes red corpuscles and renal epithe- lium. At the height of the disease the local symptoms are marked. As the redness and swelling invade new areas, with their characteristic sub- jective sensations of intolerable tension and itching, the parts earlier affected become pale and less tense, although subcutaneous inflammation and oedema cause the swelling to remain for some time. The duration of the swelling and redness in any one part varies much in ditferent cases. Sometimes the whole process is over in a few hours ; again, it may take a week or more to reach the stage of resolution, even without complications. In recovery the swelling subsides, the temperature falls, the pidse often becomes abnormally infrequent. The gastric symptoms subside, appetite improves, and convalescence is usually rapid in uncomplicated cases. The fall of temperature often precedes the other symptoms of recovery. It is nsually rapid and marked in cases which recover promptly, slow or irregular in others. Yet there are exceptions to this, and severe relapses or complications sometimes follow in cases with marked crises. The losses of epidermis from vesicles, scratching, or 462 ERYSIPELAS. treatment are restored. Desquamation, usually in fine scales, sometimes in patches, continues for some time. The affected skin, especially that of the nose and face, often remains hypersemic for a long time. The hair falls out when the scalp has been aifected, but soon grows again. The new hair is apt to be curled or darker than before, but soon resumes its former appearance. In parts where the skin is loose, as in the eye- lids, oedema is likely to persist for some time. Recurrences. — Erysipelas is one of the acute diseases in which recur- rence takes place — a fact which gave much trouble to those who sup- posed that infection always produced immunity, but at the same time wished to include erysipelas among the exanthemata. Relapses may occur in convalescence, beginning in the same point as the original dis- ease or elsewhere. They are usually not so severe nor of as long dura- tion as the primary attack, but they do not always become successively milder, as has been supposed. Attacks occurring after long intervals are also likely to be less severe than the first one, thus giving support to the idea that a sort of immunity is produced, but to this, too, there are exceptions. Some individuals seem extremely disposed to recurring erysipelas, as in the subjects of so-called menstrual erysipelas, first described by Hoff- mann in the last century. Hirtz and Widal ^ have reported the case of a woman of fifty who had erysipelas every month at the time the menses had usually occurred. As an example of the number of recurrences which can take place, the same observers report the case of a woman who for four years was free from the disease only two months. Admit- ted to hospital for nephritis, she had in the next three months twenty distinct attacks of erysipelas on the face and thighs. The latter began in a chronic eczema. Some of the attacks were afebrile ; in one the temperature was above 40.5° C. for a week. The blood contained viru- lent streptococci in both mild and severe attacks. Critzman ^ reports the case of a woman who from the age of thirty to thirty-five had ery- sipelas almost regularly at the time of menstruation. A piece of excised skin in one attack showed streptococci of Fehleisen. Recurrences may be explained by a retention of the germs in the body in a latent form, which, according to experiments in vitro, may last for long periods. The following observations show a not infrequent mode of recurring erysipelas : A man with an old wound of the right orbit was admitted to my wards with severe angina. On the fourth day, M'hen the angina had subsided and the temperature reached 99° F., the patient had a chill, with a rise of temperature, soon followed by severe erysipelas of the face, beginning around the orbital wound. The temperature reached 105° F. every day for four days, notwithstanding full doses of salol, and then fell slowly with disappearance of the ery- sipelas. A purulent discharge from the right frontal sinus was treated locally in the eye ward. Two days after complete disappearance ery- sipelas began again, but subsided rapidly under the use of ichthyol. Six days later another attack came on, beginning, as had the others, at the wound. This attack was quite severe and lasted a week. Ichthyol was used as before. I then had an opening made into the left frontal 1 La Bulletin medicale, 1891, No. 101, p. 1163. 2 Arch. gen. cle Med., 1892, Jan., p. 24. SYMPTOMS. 463 .sinus, with penuaueiit drainage and tlu)rou<;li irrigatioa, and tlie patient made a eomplete recovery. Varkitio)it< in the Cour,se of fhc Lord! LcHion. — The erysipelatous lesion varies much in its course, a|)pearance, and intensity in different cases. Various terms have been applied to those varieties, most of" which suffer from havint;' been used in different senses by different writers. I shall mention only the commonest. The term fixed erysipelas is given by some writers to mild cases which remain localized in the vicinity of the point of origin. Others applv the same term to an inflammation whi(;li occurs especially around chronic ulcers. This latter is not, as a rule, identical with true ery- sipelas. JIi(/r((ti)i;reater exposure to wounds and also to the miero- ori>anisnis. Corresponding:; to the most common seat of inoculation, the local lesion usually ap])ears first in or on the nose, from which it spreads in ditlerent directions, and often so symmetrically that at a certain stage the area of intitimmation has a shape somewhat resembling that of a butterHy with the wings spread. In mild cases it extends no farther than the middle of the cheeks and is limited to the skin. In other cases the disease passes down to the angles of the jaws, np to the scalp, and back to the ears. Often the progress is temporarily arrested where the skin is firmly attached to the deej^ tissues, as at the naso-hibial fold and the margin of the hairy scalp. For a similar reason the chin is sel(h)m affected as severely as other parts of the face. In all but the mildest cases the subcutaneous tissues are also affected. The eyelids soon become swollen, and so thickened that they cannot be opened. The nose is broad and shapeless ; the lips are swollen and their motion painful ; the ears form large swollen masses ; the nares are occluded ; the mouth and tongue are dry; the tongue is red or brown, sometimes fissured and l)lecding. Ill other cases the inflammation passes down the neck and surrounds it. In such cases the scalp is usually invaded from different directions. This is accompanied by the most severe pain, although, owing to its texture, the swelling is not so great as in other parts of the body. From the swelling of the skin, aided by that of the deep tissue, the vesiculation and scabbing, the swelling of the eyelids, between which purulent secre- tions trickle, the swelling of the nares, causing the patient to breathe through the thickened lips, the aspect of the patient is most repulsive. When the scalp is invaded the symptoms usually reach their acme. All the general symptoms of the disease are present, and headache, restless- ness, and delirium are rarely absent. The nervous symptoms are often so severe that meningitis is suspected. Formerly, in fact, it was thought that the inflammation often passed down the veins into the cranial cavity, but this rarely happens. The nervous symptoms are readily explained on the ground of intoxication, as held by Todd long ago, or fever, and are often as serious even when the scalp is not involved or when the local disease is at the opposite end of the body. The duration of erysipelas of the face varies as that in other parts, from a day to one or two weeks, usually lasting about a week. Uri/sipelas of the bodi/ and extremities occurs most frequently as a complication of surgical diseases. It does not require special consider- ation, as the general and local symptoms are similar to those already described. Erysipelas of the 3Iucoux Membranes. — Erysipelas affecting the mu- cous surfaces is sometimes called interna/ erysipelas. In these parts the disease may be primary or secondary. As the structure of many of the mucous membranes resembles closely that of the skin, it may be Vol. I.— 30 466 ERYSIPELAS. admitted that they offer favorable localities for the activity of the ery- sipelas coccus, but the real nature of many so-called primary cases of erysipelas of the mucous membranes may be questioned. The Nose, Mouth, and Pharynx. — Judging from the frequency with which erysipelas first appears on the nose, it would seem that the nasal mucous membrane is often the starting point of the disease. This is no doubt true, and yet it must be remembered that the infection may take place in the nose without setting up the characteristic lesion at the" point of entrance, just as infection may take place in a wound in the outer skin and the disease begin some distance from it. The disease usually begins like a coryza, with dryness followed by increased secretion, and is soon attended by unusual pain and the other symjDtoms of erysipelas. Very often erysipelas begins during an ordinary attack of coryza, the latter furnishing the necessary conditions, and the first suspicion of the existence of more severe disease is caused by the chill, followed by the other general, and finally the local, symptoms of erysipelas. The occurrence of erysipelas of the pharynx has been observed for a long time as an isolated affection and in epidemic form. It is usually supposed that the " black tongue " which attracted so much attention during the middle of this century was erysipelas. It seems much more likely that these were for the most part cases of dij)htheria, possibly streptococcus diphtheria. Erysipelas of the pharynx, including the tonsils, may be primary or secondary. Infection may take place in the latter by way of the mouth, nose, and lachrymal ducts, or even by the ear. In any case the diagnosis can only be made when erysipelas appears on the skin. AVithout that the most accurate term that could be given (in case of bacteriological examination) Avould be streptococcus angina. The local symptoms are those of an angina, varying from a mild catarrhal to a diphtheritic, phlegmonous, or gangrenous inflammation. Generally the lymphatic glands at the angle of the jaws are unusually swollen and tender. The other symptoms are those of erysipelas in other locations, but, as remarked above, it is only when cutaneous erysipelas is present that the diagnosis can be made. In any event, the throat affection should be treated as an angina after its kind in each case. Erysipelas of the mouth is much rarer than that of the pharynx. It is usually secondary and requires no special description. The stomatitis which develops in many cases of erysipelas hardly deserves the specific term. Chantemesse anclWidal claim that inflammation of the submaxillary glands (angina of Ludwig) is of erysi])elatous origin, having found streptococci in the exudate in that condition. I have seen Ludwig's angina as a complication of erysipelas. The Larynx. — Erysipelas of the larynx, which was described long ago by English physicians, may be primary or secondary. The latter is recognized by the appearance of the lesion elsewhere. The former is of more importance on account of the belief that many cases of so-called idiopathic oedema of the glottis are erysipelatous. It is also thought that many cases of phlegmon of the larynx are erysipelatous. Massei ^ ^ Das primdre Erysipel des Kehlkopfs, German translation by Yincenz Meyer, 1886- COMPLICATIONS AND SEQUKLM 467 and l)(.'la\an' drscrxe credit lor calliiii;- altciitinii to tlic .siil)j('('t. \'ir- cliow soon lifter predioted that many acute cases of (edema of the o;h)ttis would prove to be ervsipehitous, as tlie anatomical conditions in both diseases are similar. Biondi and others have found streptococci which could not be distini>-uished from those of Fehleisen. The ((Uestion of nosoloiiv need not be discussed here. Massei trives the fojlowini'- dis- . . . ^ tiniiuishiiii:- features of the disease: Marked swellinti; of the mucous membrane, developing almost constantly in the glandular tissue at the base of the tongue, soon spreading to the epiglottis and aryepiglottic folds ; rapid ]xissage of the swelling from one ])art to the other, witli sudden ajipearance and disappearance of dyspuwa ; high fever in the beginning. Ilerzfeld- calls attention to the phlyctente on the epiglottis, some of Avhich disappear, while others break down and form superficial ulcers. This condition, which Massei also describes, was noticed by Gottstein in primary oedema of the larynx. Herzfeld thinks these spots are due to a mild subepithelial exudate, and are not true vesicles. Pain in the prelaryngeal region is a marked symptom. Massei ascribes it to inflammation of the prelaryngeal ganglia. Erysipelas of the lower respiratory passages, the lungs, and pleura are important chiefly as complications. Many cases described under that name have been cases of streptococcus infection which are not definitely entitled to the term erysipelas. The (roiifal JIucous Membranes. — Although admitted as possible by some writers, erysipelas of the urethra of man must be exceedingly rare. Achalme could not cultivate the specific organisms in normal urine even w'hen made alkaline, and obtained no results from the injection of one c.c. of a virulent culture in the bladders of rabbits. In the female, on the contrary, erysipelas of the genitals is of great importance on account of its association with the puerperal state. As this subject does not belong to internal medicine, it cannot be further considered here. Traiisinission of ErysipelcLS from the Mother to the Foetus. — The possi- bility of this, which has no doubt occurred, depends on the circulation of the germs in the blood, a matter which has been mentioned in an earlier part of this article. Although abortion is not rare in pregnant women with erysipelas, such patients rarely have pyaemia, which would almost necessarily follow in case the organisms could reach the fcetus in a virulent condition. The abortion must therefore be due to other causes than fcetal erysipelas. Erysipelas of the newborn occasionally occurs by infection of the cord or stump, and begins on the abdominal wall. It also occurs in the newborn, as in later life, in accidental wounds, excoriations (nose, vulva in intertrigo), and skin diseases. It sometimes complicates circumcision Avhen performed without aseptic precautions. Many cases of so-called erysipelas of the newborn are really cases of sepsis, usually produced by streptococci, but often complicated by other organisms. Complications and Sequel.^:. — The complications of erysipelas are due either to unusual localization, or to unusual severity of the essen- tial disease, or to secondary infections. Many of them are almost con- 1 Neiv York Medical Journal, Sept. 12, 1885, p. 284. ^ Arch, fiir path. Anat., Bd. 133, p. 176. 468 ERYSIPELAS. stant, and might be considered as ordinary phenomena of the disease ; such is albuminuria. Others are rare. Erysipelas affecting the eyelids is sometimes followed by suppurative conjunctivitis, keratitis, iritis, detachment of the retina, and even destruction of the bulb. Glaucoma has been observed as a late sequel. In other cases inflammation aflFects the orbital connective tissue and pro- duces exophthalmos, thrombosis of the sinuses, infection of the men- inges, or, as a late complication, optic atrophy. The ear complications of erysipelas have been well described by Haug.^ The afPection is usually secondary. Primary erysipelas of the ear has followed boring the ear, itching diseases of the ear, or removal of impacted cerumen. Usually the internal ear is not affected, except by temporary hypersemia. In the external canal erysipelas causes swelling, with vesicles. Necrosis does not often occur, but suppuration sometimes does. Eczema may follow. Usually the disease does not pass the tympanic membrane, but in severe cases otitis media occurs, and even abscess of the mastoid antrum. Sometimes suppuration of the mastoid cells occurs without perforation of the tympanic membrane. Erysipelas rarely affects the ear by extension from the pharynx. Parotitis occurs in some cases in which the mouth or pharynx has been involved. It frequently goes on to suppuration. Empyema of the antrum of Highmore occasionally follows erysip- elas of the face. The coated tongue, vomiting, and other evidences of gastric disorder so common in erysipelas are usually explicable by the intoxication and fever. In rare cases inflammation, exudation, and ulceration of the mucous membrane of the duodenum occur, with streptococci in the lesions examined post-mortem. In other cases diarrhoea with bloody stools has been observed, leading to the supposition of an erysipelatous enteritis. In many cases it is probable the enteritis is septic, not neces- sarily due to specific organisms. Rendu has reported an interesting case "in which facial erysipelas spread into the mouth and pharynx, and after several days, during which the patient had severe gastro-intestinal symptoms, appeared at the anus. Ucke ^ has reported a case of secondary erysipelas of the stomach. Erysipelas is a comparatively common complication of wounds and ulcers in or near the anus. The liver is often enlarged, the 'seat of parenchymatous degeneration and sometimes of necrotic foci. The spleen undergoes similar changes, and an enlargement of that organ has been looked on as an important diagnostic sign. Frequently, however, the spleen cannot be felt. Albuminuria is an almost constant symptom in erysipelas, occurring in about two thirds of cases of all degrees of severity ._ Usually the albuminuria lasts but a short time in the height of the disease, and the amount of albumin is small. Hyaline casts, an increased number of colorless corpuscles, and red blood corpuscles occur at times in the urine even in mild cases. Usually the lesion causing these symptoms is due to intoxication, but some observers have found organisms in the urine 1 Prager medieinisehe Wochensehrift, 1893, No. 37. 2 Centralhlatt Jixr allg. Path, und path. Anat., p. 473, 1894. COMPLICATE L\S AND SEQUELAE. 469 similar to those in the skin. In nirc rases nephritis occurs, with large quantities of albumin, epithelial and blood easts, and free blood cor- puscles in considerable numbers. Salinger' has seen uriciiiia in such a case. A'arious lesions, such as diffuse nephritis, glonierulo-nejdiritis, and septic interstitial nephritis, have been observed. As a geneial thing, the ne})hritis ot" erysij)elas docs not become chronic. Nephritis is sometimes absent in the most severe cases of erysipelas. Pericarditis is comparatively rarely observed, though no doubt some- times overlooked, as it is in other diseases. It has been observed in different forms, from peric^arditis without effusion to suppurative inflam- mation with streptococci in the exudate. Endocarditis is much more frecpient, and usually occurs in the later stages of the disease. It usually affects the mitral valve. The symp- toms, physical signs, and outcome of erysipelatous endocarditis are like those of other cases of infective endocarditis. Accidental systolic mur- murs are comparatively frecpient. Mvocarditis has been observed in erysipelas as in other infectious diseases. The changes are both proliferative and degenerative. Endarteritis and degeneration of the intima and media of the arteries have an importance chiefly anatomical. Pleurisy and ])neumonia are rare C(^mplications of erysipelas, found most frequently in cases with general sejisis. Cases of pneumonia in which the local lesion seemed to vary during life, and in which the lesions post-mortem were irregular or serpiginous, have been called ery- sipelatous. The peculiarities mentioned, however, do not demonstrate the speciflc nature of the cases, as they are sometimes present in true croupous pneumonia, and there is no advantage in applying the term erysipelatous unless the clinical relationship is evident, and very little even in that case. Peritonitis occurs very rarely, either as part of general infection or by extension from the female genitals. Inflammation of the meninges or brain is rare in erysipelas. Occa- sionally the former occurs from the extension of inflammation from the orbit or along one of the cranial nerves. It is sometimes due to organ- isms other than the specific streptococcus. Peripheral neuritis is a very rare complication. Various affections of the joints occur in erysipelas. When the skin is involved over a joint an effusion in the latter sometimes occurs from the extension of inflammation to the serous membrane of the joint. Sometimes this serous effusion seems to be due to obstruction of the lymph circulation. In other cases suppuration takes place in the joint as part of a general septic condition. Occasionally there is a mon- arthritis from the localization of micro-organisms in a single joint. In some of these cases pure cultures of streptococci have been found. In an interesting case observed by Galliard,' in which the right knee became inflamed on the sixth day of a facial erysipelas, the pus in the joint contained both staphylococci and streptococci. As a rare occur- rence multiple arthritis with the characteristics of acute rheumatism has been observed. 1 Medical Xewff, .July 4, 1891. ^ CentrulblaU fur Bakteriologic unci Pavasiteiikunde, 1893, ii. p. 436. 470 ERYSIPELAS. Serous eiFusions and inflammations take place sometimes in the sheaths of tendons. One of the late sequels of erysipelas, especially that of the face and scalp, is seborrhoea. A not uncommon consequence of repeated attacks of erysipelas is chronic dermatitis. In some of these cases a chronic hyperplasia of the subcutaneous tissue takes place, with dilatations of lymphatics, which is spoken of as elephantiasis. As a rare sequel of recurrent erysipelas Tenneson and Darier have observed lymph varices of the cheeks and mucous membrane of the mouth. They explain the condition as due to obliteration of lymph vessels or sclerosis of lymphatic glands. Abscess of the superficial lymphatic glands is a common occurrence in erysipelas, and hardly needs detailed description. Diagnosis. — Difficult or usually impossible before the local lesion is developed, after that the diagnosis can almost always be made by inspection. When the general symptoms only are present, one should exclude as many other conditions as possible by the complete examina- tion, and withhold the diagnosis or simply make one covering the most distinct local condition. As in all other cases, the examination of the pharynx should never be neglected, and when the general symptoms are present, with pharyngitis, the possibility of erysipelas should not be forgotten. Whenever there is a known wound or abrasion, still more, exposure to other cases, the symptoms of the onset should at once excite the suspicion of erysipelas. This is true also of coryza, in which chill, fever, vomiting, etc. occur without signs of other infectious disease. The examination of the lymphatics of the head and neck should not be neglected. When the eruption has appeared, it is usually unmistakable, but there are enough anomalous cases to make a careful examination neces- sary always. The elevated redness, the increased consistence of the skin, the margin, which the patient often describes as spreading or which can be seen to spread from hour to hour, the fulness, itching, or tickling in the skin, the tenderness in the enlarged lymphatic glands in the vicinity, and the history of the onset, usually make matters clear. But sometimes some of these signs are absent or equivocal, and a dif- ferential diagnosis must be made. Usually a want of definiteness of the margin causes the greatest difficulty. This allows confusion be- tween erysipelas and numerous forms of erythema and dermatitis, such as those from exposure to the sun, from irritating drugs, or from pois- onous plants or animals. In most of these the redness is not so clearly outlined, the swelling if present is very superficial, the margin does not extend in so characteristic a manner. Finally, the general symptoms are absent. In the case of dermatitis from poisonous plants or animals a history can usually be obtained. The appearance in many of these cases is like that of erysipelas, but the swelling is not so deep. Lymphangitis and erysipelas have a close relationship, and in ery- sipelas it is often possible to make out distinctly the existence of inflamed lymph vessels. In lymphangitis without erysipelas the absence of the characteristic elevation with progressing boundaries is important. Red- ness over a considerable area may be present, but is likely to be irreg- ular in its outlines and uneven in intensity of tint, or even with areas PRoaxosfS. 471 of miuirt'c'tcd skin in it. In .simple lyni[)luingitis the temperature is not so high tis in erysipehis, and the symptoms of the onset are nsually not so (listinct, thmioh sometimes present. It is (lillieiilt to dislinii'iiish between ervsipelas and dill'iisc [thieaiiion of the skin. The latter mav have an abrupt. mar of the :ilcoh(tl ill tlic jircparatioii of iron iniivorsally used, but in iii<».ilical vein inflaniination. The embolisms will usually hv found in the hmgs at bifurcations of the pulmouarv artery, and are oenerally centres of infarction. As they involve the smaller arteries for the most part, they are peripheral, wedge- shaped, and are not always sharply defined. Infarction is less apt to follow than in simple embolism. In multiple infective embolism infarc- tion will be present at some centres, absent at others. Pulmonaiy metastatic abscesses are not often larger than a cherry, are usually situ- ated in the pulmonary periphery, and involve the plcune, whence a purulent pleurisy may have originated. They are at first grayish in color, firm and surrounded by an intense hypertemia ; later, they form purulent foci. They become infiltrated with inflammatory products, the inflammation having extended from the intima of the obstructed artery until the whole area of the infarction has become implicated. The in- filtration occurs by migration from the surrounding hypersemic zone which bounds the abscess. This abscess contains a central necrotic mass and abounds in micrococci. The embolic abscesses of other parts are usually smaller than those of the lungs. They differ in shape and ap- pearance. In the spleen they are small and often surrounded by a zone of inflamed tissue. They swarm with micrococci, and are of a dirty yellowish red color. Embolic abscesses of the liver, which, as involving ramifications of the hepatic artery, are most often a result of endocar- ditis ulcerosa, are small, yellow, wedge-shaped, and usually close to the capsule. Arising in the portal system, they are of larger size and few in number. The abscess is always separated from the surrounding hepatic structure bv a zone of enlarged yellow lobules. Colonies of micrococci are present in the interlobular vessel and fill the capillaries for a long distance (Orth). Very few corpuscles are seen, the infarct being largely made up of liver cells. In the kidneys the abscesses are rarely larger than mustard seed, and are generally situated in the cortex, arranged in small groups, rarely in the pyramids — in the middle and outer portions. They are of a pale yellow color, and do not undergo softening, as their contents are not purulent, but rather masses of fatty degeneration. Micrococci will be found in them always. In pysemic arthritis the inflammation begins in the synovial mem- brane, and the pus is often ichorous. The membrane is swollen, red- dened, and covered with pus. In the pleural, peritoneal, and pericardial ca\'ities the inflammation speedily causes the accumulation of pus. Embolic abscesses of other structures may also be encountered, as in the skin, subcutaneous tissue, and the lymphatic glands, the parotid gland, etc. When metastatic abscess has occurred without embolism the sup- purative inflammation will have originated in foci in the capillaries, where micrococci have invaded the epithelium damaged by the toxic substances in the blood, whence the inflammation has spread outwardly. Widespread coagulative necrosis will be found in pyoemia. The spleen is enlarged and softened, the heart flabby, and the mucosa of the intes- tines swollen and softened and the submucosa the site of numerous capillary hemorrhages. Purpuric spots will be observed upon the skin quite often, especially after ulcerative endocarditis. The brain and 484 PYJEMIA. spinal cord and their membranes are rarely the seats of inflammatory changes. Suppurative meningitis, embolic abscess, and hemorrhagic effusions are rarely found. In ulcerative endocarditis of septic type micrococci pervade the vegetations on the valves or heart wall. When the right side of the heart is implicated, the small detached fragments may have caused embolism and metastatic abscess in the lungs ; but from the left heart the embolisms involve the systemic circulation. Ulcerative endocarditis is often found without discoverable primary infective centre. As in infective osteomyelitis, the micro-organisms have found a habitat in the endothelia damaged and destroyed by coag- ulative necrosis. The secondary abscesses exist sometimes in great numbers ; at other times only one or two may be found ; again, ulcer- ative endocarditis may exist without embolism. The left heart is usually implicated in ulcerative endocarditis, though the right side is more often affected than in simple endocarditis. The endocardium as well as the valves may be affected. Vegetations, sometimes luxuriant, and ulcera- tions are the characteristic features. The vegetations are grayish yellow, very friable, and of varied conformation. They consist of fibrin and granular debris, cellular elements, blood cells, and micrococci. The ulcerations are irregular, may involve the myocardium, and even pene- trate to the pericardium, or the cardiac septum may be perforated (Bramwell). Small abscesses are found at the bases of the vegetations. in many cases. The organisms present are usually streptococci and staphylococci. The intestines are not so frequently the seat of lesions in pyaemia as^ in septicsemia. Submucous metastatic abscesses are occasionally present,, especially in the large intestine. These may open through the mucosa and form ulcers. Metastatic abscesses are often found in the muscular tissue, even in the walls of the heart, in the subcutaneous cellular tissue^ the skin, and in the medullary cavities of bones. Symptoms. — Following delivery or a wound or surgical opera- tion, pygemia cannot develop until suppuration has taken place. This is commonly some time during the second week after external sup- purative lesions, but after delivery during the latter part of the first week. Impending pyeemic infection is usually indicated by alteration in the appearance and behavior of the wound. The granulations will become pale, inactive, and unhealthy. The pus will lose its creamy character, and become thin and ichorous and scanty. The surrounding^ tissues will grow infiltrated and oedematous and somewhat livid. The lochia of the puerperal woman will become scanty and fetid or suj)- pressed, the external genitalia hot and dry, and intrapelvic pain and tenderness develop. The patient will suffer from general discomfort and anorexia. There will be slight headache, elevation of tem^Dcrature, and thirst. The tongue will have a thin, moist coating. The general symptoms will be ushered in by a chill more or less severe, and lasting^ from a few minutes to an hour or more. It may be limited to a chilly or " creepy " sensation, Thermometric observation will already show several degrees of elevation. In the great majority of cases the chill will occur in the daytime. The initial chill does not mark the occur- rence of suppuration. It is probably due to septic absorption or to the circulatory changes consequent upon the entrance of infective material SYMPTOMS. 485 into the l)legins in the veins at the placental site by bacterial invasion of the thrombi, the disorder may develop very insidiously from a slight endo- or para- metritis, usually during the first week of childbed. The svmptoras begin w4th a chill, which may be protracted and severe. Apart from the symptoms of intrapelvic inflammation, the course of the established disease is that of ordinary pyjemia. Peritonitis is generallv absent. Death usually occurs during the second or third week, but recovervmay follow after more or less prolonged illness in cases where metastasis has been slight and has not involved the more important organs (Lusk). Many of the milder forms of pyaemia, such as occur in typhoid fever, scarlet fever, etc., pursue very protracted courses. The occurrence of <"hills after the third week of typhoid fever more often than not signal- izes the engrafting of septicaemia or pysemic processes upon the original disease : and, although pure cultures of the typhoid bacillus have been obtained from suppurative foci in this disease (evidence that this bacillus is also a pus organism), commonly typhoid and post-typhoid parotiditis, femoral phlebitis, pylephlebitis, etc. are of distinctly pya?mic origin. Similarly, the suppurative joint inflammations, etc. after scarlet fever are evidences of secondary pyaemic infection. The milder pvaemic in- fections that arise in this manner usually pursue a favorable course, but, as a rule, even in chronic pyaemia the course is unfavorable. The patient finally becomes exhausted by the toxicity of the disease and the fever. He grows profoundly prostrated, emaciated, and anaemic ; bedsores, furuncles, and subcutaneous abscesses mav develop before death. Osteomyelrtis, which is generally an affection of childhood, or, occur- ring later in life, a recurrence from childhood and due to encapsulation of pyogenic organisms after the original attack, or, as is more probable, a reinfection in a locus mi nor is resistentice from the blood current, may exhibit only pain and the symptoms of acute septic infection and k rapidly fatal course. But it may also constitute one oif the phenomena of ordinary pyaemia, and, on the other hand, rarely it may serve as the centre for general pvaemic infection. Cases in which infection of several centres of the osseous system by pyogenic bacteria occurs are not so very uncommon. They are not, strictly speaking, truly pyaemic, and follow a much more favorable course. The more protracted cases of pyaemia are often very obscure. It is here that errors in- diagnosis are most often made, especially when the primary focus has escaped observation. Chronic forms of pyaemia mav 490 PYEMIA. originate in pyelo-nephritis, intestinal ulcerations, and various suppura- tive centres in internal parts of the body, and present symptoms closely resembling those of tyj^hoid fever, tuberculosis, etc. The most interesting form of chronic pyaemia, however, is malignant or ulcerative endocarditis. This may occur as a frank secondary symp- tom of pysemia, or it may be the primary lesion and infective focus. Though it may proceed to a fatal termination within a few days as part of an already disseminated pygemia, or even as a primary affection, its course is often prolonged for many weeks and even months. When secondary, following a wound, a surgical operation, or suppurative puer- peral lesion, no modification of the ordinary course of pyaemia may be observed. Should the life of the patient be prolonged, however, embol- isms from the endocardial surface, sometimes in countless numbers, may be swept into the circulation, and small metastatic abscesses evoked in the various organs and parts of the body. Its presence will usually, but not always, be recognized by the devel- opment of an endocardial murmur. In the great majority of cases the left side of the heart is implicated. In 209 cases referred to by Osier in his Gulstonian Lectures, the left valves were affected in 171 cases, the right valves in 34. In 9 cases the right heart alone was involved. Pysemic endocarditis usually arises in hearts that have already been dam- aged and aflPord a favorable nidus for the growth of pus organisms. It rarely begins as a primary endocarditis. The symptoms are often extremely vague and misleading. They may begin abruptly or insidi- ously, with chills, pyrexia, sweats, all of irregular and atypical charac- ter, and pass gradually into a typhoid state. As a rule, subjective cardiac symptoms are slight ; they may be altogether absent. Palpi- tation, prsecordial distress, and pain are occasionally present (Bramwell). Sometimes the symptoms are pronounced, and at once direct attention to the heart. The earlier general symptoms have often a close resemblance to those of malarial fever ; all phases may be closely simulated. In the absence of embolic symptoms they may be readily mistaken for typhoid fever. During the course of the affection great variability of the cardiac murmur will often be observed, and affords a significant aid to- diagnosis. These cases may be protracted for months. They may not exhibit symptoms of metastasis until near the end. More acute case& rarely run their course without metastasis. The absence of a heart mur- mur throughout is not so very uncommon. Then an early diagnosis i& quite impossible. Later, ulcerative endocarditis may be inferred by exclusion or determined by evidences of arterial metastatic inflamma- tion. Ulcerative endocarditis may endure days, weeks, or months,, gradually exhausting the patient with recurring rigors, pyrexia, and sweats, until he passes into a state of profound prostration, coma, and death. The temperature by rapid changes may pass from the normal to 105°, 106°, 107° F., or more. A continuous high temperature is some- times maintained. Nearly always, sooner or later, the symptoms will be modified by those of metastatic inflammations. Excepting when the right heart is involved these will develop in the systemic arterial circu- lation, justifying the term arterial pyaemia suggested by Wilks. The lungs are, naturally, much less frequently the seat of infarcts than in DIAGNOSIS. 491 ordinarv [)y;einia, hut pnciiinoiiia, |)lciirisy, and empyema are not unooinnion concomitants. Deliriuin, paralysis, coma will indicate cerebral and meningeal metastasis. Local and general symptoms will for the most part he those of general pyiemia. Multiple cutaneous and suhcutaiu'ous ahscesses, and often, toward the end, innumerahle cutane- ous JuMuorrhages forming purpuric spots, will not infrc(|ncntly develop heforc death. Sometimes gangrene of the extremities will indicate the occlusion of large arteries by emboli from the valvular vegetations. Parotiditis sometimes forms a symptom. With the establishment of some or all of these symptoms the con- dition of the patient becomes more grave. Chills, varying pyrexia, drenching sweats, diarrhtea, hebetude, delirium, coma, succeed until the patient finally succumbs, usually within four or five weeks. Practically, recovery never follows. All cases of ulcerative endocarditis in which pus organisms pervade the endocardial vegetations, and ulcerations and their resulting embolic inftircts, may fairly be considered pysemic, whether origmating with rheumatism, old endocardial disease, or otherwise. Diagnosis. — Pyajmia is very often mistaken for other affections ; most commonly for septicaemia, intermittent and remittent malarial fever, typhoid fever, acute miliary tuberculosis, and acute rheumatism. The diagnosis from septicsemia may at first be impossible. Indeed, progres- sive septicaemia may pass into pyaemia by the development of thrombosis and embolism, and, conversely, more or less septic intoxication and infection is present during the progress of pyaemia. Septic intoxica- tion generally develops within a few days after a wound or injury and after the beginning of gangrene, and is dependent upon putrefactive as well as suppurative foci. Pyaemia is due to suppuration, and usually does not occur earlier than the second week of the wound or injury or suppurative lesion. The course of septic intoxication is briefer, and is without local manifestations. In progressive septicaemia chills are not nearly so often observed as in pyaemia. Pyaemia runs a more protracted course, but differentiates itself by the establishment of thrombosis and embolism and metastatic abscesses. The fever of septic infection is more continuous and attains a higher degree within a few hours. Its duration is much briefer, and when it is prolonged a pyaemic condition is often established. Microscopic examination of the blood affords a ready method of distinguishing malarial fever from pyaemia. The presence of the Plasmodium malariae will establish the diagnosis. The distinctly inter- mittent and remittent character of the fever of pyaemia is the cause of ■ many mistakes. In the more acute forms of pyaemia doubt will be dis- pelled by the course and development of the essential symptoms of the disease. The diagnosis from symptoms alone is often very difficult in the more chronic forms ; but, apart from the microscopic diagnosis, the irregular development of chills, fever, and sweating, even without the secondary local manifestations, will not long justify hesitation between the two affections. Moreover, as Osier has well said, if a supposed case of malarial fever persists despite the full exhibition of quinine after several days, other causes than malaria must be sought for. Chronic cases may readily be mistaken for typhoid fever. Resemblance 492 PYJEMZA. may be heightened by abdominal symptoms — diarrhoea, tenderness in the right iliac fossa, splenic enlargement — delirium and the typhoid state that is so often observed, especially in malignant endocarditis. It is verv important to remember that frequently after the third week of typhoid fever a true pyaemia or septicaemia may be engrafted upon the original disorder. The occurrence of chills and the intensification of svmptoms during the latter period of typhoid fever is very often due to septic or pysemic absorption from the intestinal ulcerations. Post- typhoid parotiditis, phlebitis, etc. are usually pysemic. Except in pro- tracted cases of pyaemia the course of the fever will soon remove uncer- tainty from the diagnosis. In acute tuberculosis pyaemia is sometimes suspected at first. The course of the former aifection, while occasionally very rapid, is always more regular than that of pyaemia. The expec- toration, and often the discharges when present, will reveal the bacillus of tuberculosis. Acute rheumatism may be confounded with pyaemic arthritic inflammation. Post-scarlatinal and gonorrhoeal purulent arthri- tis are usually pyaemic, the latter inflammation sometimes due to meta- stasis of the gonocoGcus. When the primary suppurative focus has been apparent pyaemia is usually recognized without difficulty, but when this centre has escaped observation or has been beyond its reach, much obscurity often exists. Originating in osteomyelitis, pyelitis, pylehepatitis, or in any of the so called spontaneous manners, the keenest powers of observation will be necessary. In malignant endocarditis the diagnosis from typhoid fever may, for a time, be impossible. The purpuric eruptions of the endocarditic pyaemia have caused this disorder to be mistaken for typhus fever, cerebro-spinal meningitis, or malignant specific exanthematic fever. Hepatic intermittent fever — which, indeed, is probably a mild septic or at least fermentation fever — the fever of rapidly developing cancer, Hodgkin's disease, and the fever of local suppurations of what- ever nature may at times simulate pyaemia. Peogxosls. — The prognosis of pyaemia is unfavorable. Death will usually occur before the end of the second week, sometimes during the first. In chronic pyaemia the prognosis is less absolutely bad, though most cases end in death, sometimes after weeks and even months. The course of malignant endocarditis and of pyaemic cerebral suppuration is uniformly fatal ; of the former rarely later than three or four months, usually within as many weeks. Where the primary suppuration focus is within the reach of surgical treatment, and the metastatic abscesses are few in number and not situated in vital parts, recovery may take place, though slowly. It cannot be denied that a thrombo-phlebitis following a primary suppuration in its turn may be followed by symptoms of embolism in the lungs and elsewhere, limited, however, to one or two foci, and yet recovery eventually take place. In such cases it can only be presumed that the micro-organisms of the thrombus and of the embolus have been of feeble virulence, and have been destroyed by the bactericidal action of the blood and leucocytes. The prognosis is much more favorable when metastatic abscess affects a part within reach of the surgeon's knife, as in metastatic parotiditis. Teeatmext. — Prophylaxis. — The basis of modern surgery is in the avoidance of influences that permit the infection of wounds and the TREATMKyT. 49:i admission to the circulation ot" sc})tic and pyoircnic organisms and their toxic products. The most certain t^uarantee of protection to the individ- ual is the maintenance of a rigid asepsis in uninfected lesions and the antiseptic treatment of these when conditions of sepsis or supj)uration prevail. The prevention of suj)purati()n in a wotmd furnishes absolute protection aj2:ainst pyjemia (Senn). The details of necessary treatment to this end are strictly surgical, and need not be considered here. Aseptic and antisejitic treatment in internal medicine has a much more restricted field, and is limited to a more or less ineffectual clisinfection of the alimentarv canal. Some measure of success may be expected in se])tic and suppurative lesions of the mouth, nares, and fauces, as in diphthe- ritic and scarlatinal inflammations, but it is doubtful if antiseptics can be administered in sufficient and safe quantities to effectually disinfect the intestinal canal. To the mouth, throat, and nares applications of hvdrogen dioxide, corrosive sublimate, carbolic acid, sulphurous acid, and other bactericidal agents are universally employed, but no substance should ever be applied to these parts in such strength as to exercise a caustic action or in such a manner as to disturb mechanically the rela- tion of the parts, lest absorbing surfaces be laid bare and the entry of micro-organisms and their products to the circulation facilitated. Nu- merous plans for preventing general infection through ulcerating sur- faces in the intestinal canal, as from dysentery, typhoid fever, etc., have been proposed. It has been asserted that effective antiseptic treatment of this canal may be secured through salol, naphthalin, beta-naphthol, calomel, and other drugs. That some such influence may be brought to bear may be inferred from the positive deodorization of the stools that may be secured by these means, but there is little evi- dence of satisfactory antiseptic results. Salol in doses of from 60 to 80 grains daily, naphthalin in daily doses of from 1 to 2 drachms, beta- naphthol in 40-grain doses daily, have all been extolled for this purpose. Lately calomel has been recommended as an intestinal antiseptic, pos- siblv through its conversion into corrosive sublimate. It can hardlv be hoped, however, that an efficient antiseptic effect can be afforded by such measures. The Treatment of Pycenua. — The first objective point is the treat- ment of the primary suppurative focus and the destruction of its power for further evil. Pus should be set free, tension relieved, and drainage secured, if practicable, and thorough disinfection established. Early operative interference is indicated in acute osteomyelitis. Disinfection of the uterine cavity should be attempted in puerperal pyaemia. Ex- cision of thrombotic veins has been recommended by Klebs. To prevent detachment of infected thrombi absolute rest and the avoid- ance of disturbing manipulation should be insisted upon. Purely antipyretic drugs should never be given. The questionable advan- tage of the reduction of temperature is more than counterbalanced by the decided depression following their use. Agents that maintain the \'ital power should be administered. Quinine and iron seem to serve this purpose best. At the outset c^uinine should be given in full doses, 30 to 40 grains during the day, in divided doses. This dose may be repeated for one or two days, but after this not much advantage is to be obtained from such amounts, and the daily dose may 494 PYEMIA. be reduced to 10 or 12 grains. Large doses of iron seem to be very serviceable occasionally. From 15 to 30 minims of the tincture of the chloride, well diluted with water, may be given every fourth hour. This preparation of iron seems to possess advantages over the others. Salicylic acid, salol, sodium benzoate, and many other remedies have been urged, but their value is doubtful. Alcoholic stimulants will be indicated nearly always, and when the heart begins to fail strychnine is of undoubted value. As there is no specific treatment of pyaemia, the most important indication is the support of the powers of life by sys- tematic nourishment and stimulation. This holds especially in chronic pyaemia. The food should be the most assimilable possible. As the main reliance nothing is so good as milk. From three pints to a half- gallon during the day will be sufficient. Strong beef extracts, pepto- noids, and peptonized foods will prove useful adjuvants, thus supporting the patient until the infection has become exhausted. Whenever secondary infective inflammations are accessible they should be actively treated surgically. Unfortunately, in the cases usually coming under the care of the medical practitioner the infective centres are beyond reach in the internal parts of the body. The successful treatment of pyaemia is almost exclusively surgical. In the rare cases of recovery the result is usually due to the feebleness of the infection, and the merit of the physician depends upon his ability to supply to the sufferer support in the form of nourishment and stimulation that will strengthen him in his struggle against the morbific influences. SEPTICAEMIA. By I. E. ATKINSON, M. D. Definition. — Sopticfcmia (ar^-zixo::, putrid, and ahm, blood) is an acute febrile affection depending \\\)0\\ the presence in the blocjd and tissues of organic chemical substances, resembling alkaloids, which are formed bv minute organisms or bacteria which are also the causes of suppuration or putrefaction. These micro-organisms develop in foci in or upon the body, and excite in them suppurative or putrefactive pro- cesses and form poisonous chemical products. From causes that are not well understood these poisonous chemical substances, alone or along Avith the micro-organisms that produce them, gain admission to the circulation through lymphatics and bloodvessels, and produce morbid effects which are known as septic intoxication. Often this septic intoxi- cation is intensified and perpetuated by the continued activity and repro- duction of the accompanying micro-organisms within the body, whereby the supply of poisonous chemical products absorbed from the original focus is supplemented. The condition induced in this manner is known as septic infection or progressive septic infection. In pure septic intoxica- tion no lesions beyond the original soiu'ces of contamination are pro- duced ; but in progressive septic infection minute areas of inflammation and coagulation necrosis in the vascular system will be excited ; l^ut the disorder is characterized by the absence of gross suppurative or necrotic lesions. AYhen, however, death does not speedily terminate the infective processes, secondary centres of suppuration and necrosis sometimes develop. Septicaemia is then said to have become complicated with pvsemia, and the result has been called septico-pycemia. With these processes must be considered one in which symptoms are produced indistinguishable from those of ordinary septiccTemia, though milder and more transitory, which seem to depend upon toxic products of fermentations, possibly not bacterial in origin — the fermentative fever of Bergmann. Symptoraatically, no sharp line of demarkation separates the mildest forms of surgical or traumatic fever or the irritative fever following absorption of poisonous products of putrid food substances and the most pronounced forms of septicaemia. The stress of septicaemia is thrown chiefly upon the vascular and nervous systems and the blood, but the* range of its activity is by no means understood, and probably includes most parts of the body. Etiologt. — Although the secondary results of wounds and injuries and suppurative and putrefactive processes generally upon the system at large have attracted the attention of writers ever since Hippocrates, and in many instances have excited shrewd guesses as to their parasitic origin, a scientific basis for their elucidation did not exist until Van 495 496 SEPTICEMIA. Leeuwenhoek in 1675 by means of a simple microscope discovered and described minute organisms which we now know to have been bacteria. The wide diifusion of such organisms at once, and naturally, suggested the dependence of many morbid conditions upon them. Such concep- tions, however, were based solely upon speculation, and presently fell into disfavor, and were soon almost forgotten. Active interest in minute organisms as possible causative influences of disease was not again awakened until the present century had well advanced. Mean- while, however, much work had been done in the study of putrefactive and suppurative processes and their relation to secondary inflammatory and degenerative changes, but the results were of pathological and not of pathogenic interest. Among the eminent men engaged in this research may be mentioned John Hunter, Abernethy, Cruveilhier, Magendie, Haller, and Virchow. With the second half of the century renewed and scientific interest in minute organisms as pathogenic influences received a stimulus from Davaine's discovery in 1850 of the anthrax bacillus in the bodies of animals afl'ected with splenic fever, and the investigations in 1857 of Pasteur demonstrating the agency of bacteria in fermentative processes. In 1866, Rindfleisch described the presence of micro-organisms in local inflammatory deposits in the body. Von Recklinghausen, Waldeyer, Birch-Hirsehfeld, Hueter, and others fol- lowed immediately with important observations revealing the presence of bacteria in pysemic conditions. In 1870, Klebs described as micro- sporon septicum the bacterium which he had detected in the blood and tissues after wound infection, and diflerentiated septicaemia and pyaemia. The pathogenic influence of bacteria was now universally recognized^ and Koch's observations in 1870 established a scientific basis for bac- teriology in relation to pathological processes. Koch's experiments with septicaemia of mice showed that the animal surely died in from eight to sixty hours (depending upon the virulence of the injected fluid) after subcutaneous inoculation with putrefying fluids. The result depended upon the stage of putrefaction. Blood that had been putrefying five hours in five-drop doses killed in eight hours without producing macroscopic pathological changes and without the development of bacteria in the blood or tissues ; while blood taken from the auricle had no eifect if introduced under the skin of another healthy mouse. Smaller doses, one to two drops, of the putrid fluid caused death in from forty to sixty hours. He found that by injecting the blood of the mouse thus destroyed he could propagate the virus indefinitely and in undiminished virulence, even in doses as small as one tenth of a drop. Different varieties of bacteria were found in the blood of mice made ill by the injection, but when death resulted small bacilli alone could be found. Gross lesions were never found, but in capillary bloodvessels alterations were produced resulting in extensive blood extravasations (Senn's Principles of Surgery). Koch also succeeded in causing septicaemia in rabbits by injecting into their tissues putrid infusion of meat, whereby changes similar to those induced in septi- caemia of mice were brought about. The organism found was an oval micrococcus which invaded, and sometimes completely obstructed, capil- lary vessels. Cultures of this coccus introduced into another rabbit evoked similar symptoms. ETIOLOGY. 497 A variety of other niiero-orgtiuism.s have been proven eapal)h' ol' causinii' septicioiiiia in animals ; for example, laicrococcu.s /(incco/dtu.s, oriiiiiially cleseribed by .Sternberg, and often present in the months of healthy persons, but also found in croupous pneumonia, cerebro-spinal meninii'itis, otitis media, and other diseases, and micrococcus tetragcnnn of (nitVky from healthy saliva and the sputa of tuberculous patients. Pasteur in 1880 first cultivated xt rcptococcas from the organs of women dead of puerperal fever, and it is now well established that in the great majority of catjes of human sei)ticiemia this pyogenic micro- organism is the pathogenic factor. But it is also certain that a number of other pyogenic bacteria may determine the same results. First among these is sf(ij)!ii//ococcHs pi/of/eiiei^ aureus. These two bacteria will be found to be the causes of nearly all cases of septicaemia. Occasional causes of septic;emia are stapJnjlococcuti pyof/eneti albus, f/onococcu.s, mlcro- coccufi lrobal)ly produced by them. The conception of the action of poisonous chemical substances elaborated by bacteria upon the animal body received its im- petus from the discoveries of Pasteur regarding putrefaction and fer- mentation. Research has shown that charactetistic symptoms of sepsis may be evoked in animals by the injection of putrid fluid from which living organisms have been carefully excluded by sterilization, as well as of sterilized cultures of pyogenic organisms. Indeed, definite chem- ical substances which have been called ptomaines, toxic alkaloids, toxins, have been obtained from the putrid liquids, and have been proven to be capable of exerting poisonous influences over animals sub- jected to their action. Brieger and others have isolated a number of such products. Clinical observation appeared to justifv the conclusion that similar toxic effects are frequently produced in man, and that a dis- tinct form of septicaemia exists which is an intoxication produced bv the absorption of the chemical products of putrefaction and suppuration, and in Avhich no infective invasion of the blood itself bv putrefactive and pyogenic organisms occurs. Such septic intoxication is widely held to depend upon putrefactive processes alone, in which bacteria are not to be found in the blood, or, if so, are only accidentally present and are innocuous. They are saprophytic bacteria, and can only grow in necrotic and putrefying foci exposed to the air. The intoxication, being caused by toxins (ptomaines) formed in these foci and absorbed into the blood, results in death or recovery just as the dose has been great or small. If this be small and the supply restricted by the re- moval or destruction of the putrefactive centres, recovery will pmbablv follow ; but if it be large and the supply continuous, the patient will probably die. This form of septicaemia is more especially encountered in puerperal fever, where the toxic material has been derived from putre- VoL. I.— 32 498 SEPTICEMIA. factive changes in the cavity of the uterus following delivery. Its sup- posed origin in saprophytic bacteria suggested to Matthews Duncan the name sapnemia {aanpo:;, putrid, aiim, blood), by which it is widely known. There is some reason to believe, however, that septic intoxica- tion is not so constantly dependent upon the organism of putrefaction as this term would indicate, as in typical "saprsemia" Bumm, Von Franque, and others rarely failed to find in the toxic centres pyogenic bacteria.^ It is also significant that proteus vulgaris, a widely distrib- uted micro-organism of putrefaction, according to Flexner, "may be unassociated with other bacteria in abscesses and in peritonitis, and it may cause general infection by invading the blood and internal organs." ^ When pyogenic bacteria are the cause of septic intoxication, it is by no means certain that the circulation remains free from them, but for some unexplained reason they are incapable of growth and reproduction in the blood ; the suppurative centres furnish the toxins upon which the symptoms depend. Not only may a septic intoxication depend upon absorption of the toxic chemical products of pathogenic bacteria, but it is known that similar effects, though in much milder degree, may be caused by ferment substances not bacterial in origin. Thus a febrile reaction may be ex- cited by introducing into the blood of a living animal pepsin, trypsin, pancreatin, or a number of indifferent substances. The transitory fever that often follows within a few hours a wound, an injury, a surgical ope- ration, even when there may be no external lesion, but especially after more or less extravasation of blood, the stomach ingestion of various 'injurious food substances, as so often occurs in children, — all maybe supposed to be due to the absorj)tion of various aseptic substances which Worm-Muller believes to cause by their action upon the blood the gen- eration of fibrin ferment, which excites febrile reaction. This fever Bergmann denominates "fermentation fever ;" Volkmann, aseptic fever ; it is also known as irritative fever, resorption fever, etc. While it is quite possible, however, that this " fermentation fever " may be due to the absorption of " products of aseptic tissue necrosis," it is by no means certain that it may not ultimately come to be proven to depend upon a true septic intoxication of feeble potency. Septicemia in by far the greater number of cases is a sepdic infection. By this is understood a condition in which pyogenic bacteria gain ad- mission to the blood and tissues, and there pursue their pathogenic activity. The common source of septic infection (progressive septic infection) is streptococcus pyogenes. Staphylococcus pyogenes aureus is also a frequent cause, but indeed any of the pyogenic bacteria may determine septiceemia. The best type of the disorder in the lower ani- mals is anthrax, due to bacillus anthracis, in which the blood and tissues frequently swarm with the micro-organism. In septic infection the symptoms are due to toxins produced both at the original source of infection in the body and by the micro-organisms in the blood and tissues. The essential difference between a j)ure septic intoxication and septic infection consists in this, that the one cannot be inoculated upon another individual, while the other is freely inoculable. ^ Williams, American Journ. Med. Sciences, vol. cvi., 1893, p. 47. ^ Welch, A System of Surgery, Dennis, vol. i. p. 322. ETIOLoav. 499 Jn man, in s('j)tic infection tlu' mnnbcr of" micro-organisms is always limited, and often very small — iiardly ever so ahnndant that the simple meeiianieal I'tfects of tlu'ir presence can be considei'ed as a factor in the morbid resnlts. " We find them far more frequently in the blood at autopsies, even very fresh ones, than we are able to do durin'enic bacteria, only exceptionally are al)le to multiply in the circulating- blood of hmnan l)ein<;s. The greater frequency of their presence in demonstrid)le number at autopsy may be due in part to their multiplication after death, but this cannot be the sole explanation, as the cocci are found in autopsies made very early after death, more frequently than they are found during life. The explanation is jn'obably that during the last hours of life they often find suitable conditions for their multiplication in the blood." They " grow outside of the circulating blood, and often do not make their appearance in any considerable number in the circulation until shortly before death and after the manifestation of grave constitutional symptoms." ^ Exactly what determines the admission or exclusion of the organ- isms, or the mildness or severity of their eifects after they gain access to the circulation, is not understood : a mere scratch with infected material from a suppurating or erysipelatous centre or a dissection wound may be followed rapidly by fatal results after but little local reaction. On the other hand, the condition of the infected tissues un- doubtedly has great influence over the result, and if they permit the passage of only a few microbes, these may be destroyed without disas- trous consequences by their inherent germicidal properties. The devel- opment of pathogenic organisms within the body is undoubtedly facili- tated if their poisonous chemical products are absorbed at the same time with them. The septic intoxication that ensues impairs the power of resistance of the blood, bloodvessels, and tissues, and favorable oppor- tunities are afforded for the development and reproduction of micro- organisms at distant points. " If a large quantity of pus microbes is introduced into the peritoneal cavity or directly into the circulation, death results from sepsis before a sufficient length of time has elapsed for the pus microbes to produce the histological changes which are necessary for the production of pus " (Senn). But in septic infection the intoxication is intensified and perpetuated by the microbes which have gained access to the circulation and find conditions favorable to their growth and reproduction. Thus the patient is not only poisoned by toxins formed at centres of infection, but also by those formed within the body. Different conditions vary the activity of pathogenic organisms. Ex- perimentally, these variations have been shown to be brought about by many modifying influences ; clinically, widely different morbid results are observed to be produced by a single species of bacterium in propor- tion to its virulence — at one time intense septic infection, at another localized inflammation. Under inoculation pathogenic micro-organisms prove more virulent when derived from centres of infective inflamma- tion. AVelch points out the modifying influence of mixed infections upon pathological results — an influence that probably depends upon the ^ Welch, Dennises System of Surgery. 600 SEPTICEMIA. effects of the chemical products of one bacterium upon the vitality of another, and which may be exerted in diminishing or intensifying the morbid processes. " A bacterium of attenuated virulence may become augmented in virulence by inoculation in combination with another species which need not necessarily be itself pathogenic, or sometimes simply in combination with the chemical products of another species. These mixed infections very often occur in mau,'^ He also notes the frequency of secondary infections with pyogenic bacteria, especially streptococeus pyogenes, in various specific infectious diseases, such as typhoid fever, tuberculosis, diphtheria, scarlet fever, smallpox, and other affections, these increasing the conditions favorable to the de- velopment of the purely septic micro-organisms. ^ At present it is not possible to offer a scientific justification of the clinical definitions of the different forms of septicemia. Sharp limita- tions do not exist, and it is probable that purely saprophytic septicaemia occurs but rarely ; but for practical purposes it' has been found conveni- ent and advantageous to assign to septicaemia three types. These are — (1) A febrile reaction due to the presence in the blood of toxic sub- stances absorbed from putrefactive or suppurative foci, where they are produced by the vital activity of bacteria, which, however, remain re- stricted to the sites of their original production, and do not gain access to the blood, or, reaching this fluid in limited numbers, are incapable of growth and reproduction there (septic intoxication). (2) A febrile reaction due to the presence in the blood and tissues of toxic substances, together with the bacteria which produce them and which are jDyogenic. These are derived from original foci upon the body, and after their entrance into the circulation continue to grow and to be reproduced, and to generate their toxins (septic infection ; pro- gressive septic infection). To these may be conveniently added — (3) A febrile reaction due to foreign aseptic substances in the blood, which determine in it the presence of fibrin ferment, which is the excit- ing cause of the fever. This is mild in its course and transitory (fer- mentation fever). The sources of septic intoxication and septic infection are suppura- tive and putrefactive centres of all kinds upon the surface of tl>e body or the mucous membranes, as well as lesions and abrasion of any kind whereby an absorbing surface is exposed to the influence of the patho- genic organisms. It is doubtful that micro-organisms can gain the cir- culation through the unruptured epidermis, but it is possible that the mucous membrane does not offer an impassable barrier to them. It is, of course, impossible to say what channels for their admission may not be afforded by the mucous tract, and many eases of so called " sponta- neous septicaemia " originate in the infection of some undiscovered lesion. The occasional development of obscure septicaemic disorders Avithout previous recognized injury or lesion appears to justify the claim that in- fection may occur througli an intact membrane. Most bacteriologists at present, however, deny the occurrence of this spontaneous or crypto- genetic septicaemia. Pathological, Anatomy. — It is doubtful if any lesions of the tissues are produced by fermentation fever. Its course is always favorable, and the VATHOLUUICAL AS ATOMY. 501 alterations it causes, if any, are transitory and have not been recognized. The morbid changes rcsultinii- from septic intoxication are never such as can be seen by tiic naked eye. I liey are microscopic and never exten- sive. The coagulability of the blood is certainly diminished, and putre- faction sets in earlier than is usually the case. Rigor mortis is also established earlv. The blood will be free of micro-org-anisms and of dark color. In fatal septic intoxication the course is so acute that re- cognizable changes in the bloodvessels and tissues will not have had time to appear. Even in septic infection (progressive) there is a notable absence of gross lesions unless the course of the disease have been pro- tracted and septo-pvfemia have develo])ed. After death from progressive septic infection rigor mortis occurs early. The l)lood is dark and coagulates feebly or not at all. In it the micro-organisms of pus will be found often, sometimes in considerable numbers ; groups of micrococci may crowd tissues and capillaries. Only slight changes may be noted at the primary centres of infection, though lymphatic vessels leading from them may be found in a state of inflammation. Thrombosis and embolism are rarely present. There may be some cloudy swelling of internal organs from superficial coagu- lation necrosis. There will be widespread evidence of septic inflamma- tion of capillary vessels. A coagulation necrosis of these vessels caused by the toxins in the blood favors implantation of septic organisms, and their development and an extensive metastatic inflammation. Should the course of the septiciemia have been protracted, these foci of inflam- mati » / 1 1 • 1 Temperature record of septic intoxi cation. Septic intoxication usually develops from centres of considerable size, and should the dose of toxins not be repeated the symptoms attain their acme almost at once, within a day or two if the amount absorbed have been insuf- ficient to destroy life, or terminating in death within the same brief period should an overwhelming quantity have been re- ceived into the circulation. The disease may run a more protracted course, if the centre of absorption persist, from the re- peated admission of the toxin into the blood. In this event there will be no repetition of the chill, but recrudescence of the other symptoms may be expected, varying in intensity with the extent of the intoxication, generally tending toward a fatal termination. The course of septic intoxication is usually from two to four or five days. (See Fig. 43.) It rarely persists beyond the week, except in certain cases when the supply of toxin is limited and its source inaccessible, as in some examples of pul- monary gangrene, etc. Progress toward recovery is marked by a gradual subsidence of all the symptoms and the return of healthy action in the periphery of the putrefactive focus. A fatal termination is preceded by intensification of all symptoms. The essential failure is in the nervous system. The prostration becomes extreme, the heart action feeble and rapid, and the arterial tension gradually fails. The respiration grows more shallow and hurried. The intelligence becomes more blunted ; delirium supervenes and passes into coma. The eyes are sunken, the skin bathed in sweat. Death occurs from failure of the heart. (3) Se'ptic Infection (Progressive Septic Infection). — AVhile in septic intoxication the intensity depends largely upon the extent of the toxin- producing centres, this is not the case with septic infection. Here the micro-organisms are always pyogenic, more or less freely reproduced within the body, and continue to contaminate it with their freshly pro- duced toxins. Thus we very commonly see intense infection follow a very insignificant lesion, such as a dissection wound or the prick of an infected needle or scalpel. That general infection may occur it is not at all essential that the point of original infection be in a state of sujjpu- ration or putrefaction. It is impossible to ascertain what routes for the admission of bacteria may be offered by the parts of the mucous tract inaccessible to the eye. Internal sepsis is by no means rare. Thus, septicffimia may originate from intestinal ulceration, from pulmonary cavities and suppurative centres, from empyema, from purulent peri- carditis and peritonitis, from otitis media, from osteomyelitis, from pyelitis and pyelo-nephritis, and, in short, from any internal part of the body involved in suppurative inflammation. An intense and rapidly fatal sepsis follows septic peritonitis and acute multiple osteomyelitis. .';iyMrTOMS. 505 while the septic symptoms from ])iiriilent pleurisy and pericarditis will be much less severe, thoui;h often more })r<)traeted. It is reasonably certain that sei)ticaMnia may develop from an urethral stricture. While the so called spontaneous septic iniection cannot be allowed, the obscu- ritv of the source of vsome septicemias even su<2;gests the entrance of micro-orijanisms throuoh the intact mucous mend)rane. It is usuallv impossible to account for the origin of an osteomyelitis or of an ulcerative endocarditis in the absence of any demonstral)le lesit)n ; but at present it would be rash to assert that septic bacteria ean reach the circulation except through some lesion of continuity. The unruptured pulmonary mucous membrane, for example, is almost cer- tainly impervious to them, though intoxications from sewer gas by this route may readily take place. Without doubt, pyogenic organisms in limited numbers may enter the circulation, and, not finding conditions favorable to their development, perish, or at least remain quiescent so long as the blood and tissues maintain their normal powers of resist- ance. On the other hand, especial virulence may destroy life so speedily that time will not have been allowed for the production of anatomical changes ; but in other and more protracted instances the organisms may onlv find favorable opportunities for growth in special structures, such as the bones, the endocardium, etc. Again, the toxins absorbed from pri- marv centres of suppuration may so empoison the blood and the intima of bloodvessels that the powers of resistance of these is diminished to the degree that they come to aiford the conditions for bacterial devel- opment. It is thus that in ordinary cases of septic infection colonies of micro-organisms will be found in scattered foci of the capillary system, and when life has been sufficiently prolonged the results of Fig. 44. 103 102 M E M E ■ME m; e M E M E M E IV1,E M E A > ) /\ f A ,/ ' A- — — f \, V ' V J 1 / / , / / f 1 1 f 1 / f 1 / / i\ i\ /{ A / ! v \i ! [ j 1 1 ' 1 Temperature record of septic infection. their activity may even be thrombosis and embolism and pysemic abscess. The symptoms of septic infection rarely begin wathin tw^enty-four 506 SEPTICEMIA. hours, usually only after three or four days. There may be an initial chill ; more commonly there are only chilly or " creepy " sensations. Unlike septic intoxication, septic infection does not reach its maximum intensity immediately after the onset. (See Fig; 44.) The fever gathers force as the micro-organisms develop and produce their toxin. The course of the established disease is that of a septic intoxication. In some cases, even in those pursuing a rapidly fatal course, there may be but little elevation of temperature. Generally, however, the fever rapidly attains a height of 102°-104° F. The latter temperature is not often exceeded, even in fatal cases. Slight morning remissions are often observed. The pulse is notably of low tension, and may be very frequent, 120-140 or more to the minute. Microscopic examination of the blood rarely reveals the presence of bacteria, but will show sometimes marked leu- cocytosis with decided diminution in the number of red corpuscles. The nervous symptoms quickly appear, and the patient develops a remarkable indifference to his surroundings and his danger. Little or no agitation or jactitation will be exhibited. There is rather a profound depression of muscular activity. The mental indifference is often ac- companied by persistent somnolence and succeeded by low muttering delirium. The tongue, at first moist and coated, as the disease advances becomes reddened at the tip and border, but often dry and brown, almost black, at the centre. There are great thirst and complete loss of appetite. JSTausea and vomiting are frequent, as is diarrhoea. Later the stools may become bloody, and sometimes pronounced entero-colitis results. The skin assumes an earthy color. This often passes into a slight icteroid hue, which is attributable rather to liberation of blood pigment than to hepatogenous changes. Toward the conclusion of fatal cases it may be bathed in sweat. Sweating is frequent in all cases ; it may be intermittent. Various cutaneous eruptions are often observed. These are usually erythematous. They may be distinctly scarlatinoid in character. Most cases of so called surgical scarlatina are really septic. This eruption often begins in the vicinity of the original focus of infec- tion, but may show itself upon any part of the surface. It rarely shows the diffuse characters of true scarlet fever. The erythema may also be distinctly erysipeloid, but differs from erysipelas in being painless. Usually the erythema is in scattered patches. Vesicular and pustular eruptions are also occasionally observed. In fatal cases petechise, some- times in large numbers, and ecchymotic extravasations of blood, appear ujDon the skin. The urine is scanty, of high specific gravity, loaded with urates, but usually free from albumin. The primary seat of infection becomes dry and inactive, and in severe cases very foul. In puerperal septicaemia the lochia become offensive in odor, and are diminished or even sup- pressed. (In favorable cases the primary lesion gradually acquires a healthy appearance or a re-establishment of the lochia takes place.) The secretion of milk diminishes or is suppressed. During the course of the disease fresh absorption of infective material may be marked by recur- ring chills, but these are never so pronounced or frequent as in pyaemia, nor are the variations of temperature so decided as in this disease. In milder and favorable cases, though the temperature may be high, the pulse retains some volume, and its frequency may not exceed 80 to 90. sYMrro.y.s. 507 The Ivinpliatic system is always iiivolvi'd in s('|)tic infection. Upon tlic skin tlu' i)atli of invasion may often he traeed hy a red line e()n'esj)ond- ing to the inllamed lymphatics leadin<>; from the point of infection. Tlie lymphatic lilands nearest to the infective centre are often much enlaro-cd and very tender. A general adenopathy may .sometimes be developed. The spleen is always enlarged and its percussion area increased. 8t)metimes it may he discovered by palpation. Some cough may be present. It is generally dependent upon bronchitis. Pneumo- nia is not a common complication of septicsemia. Occasionally a con- siderable degree of hypostatic engorgement of the lungs will be encoun- tered. In favorable cases of septic infection improvement is first noted Fig. 45 TIME M E M E M E M E M E M E M E M E M E M E IVI E M E M E TEMP. F. 106 II l\ A 105 /\ , N / V / V y 104 J \ f\ l\ \/ 1 103 Y \ \ \ I 1 li 102 v ■ 1 / 1 lOf J'*' «j \ / 1 / 1 1 \ 100 v A v^ \ 1 1 99" V J > / L i U A / 98 f\ \/ \ J V y ^ \j 97 1 1 V. Temperature record of septic infection. in a lowering of the temperature and increased tension and diminished frequency of the pulse. In fatal cases death approaches as in septic intoxication, with increasing asthenia, failing heart, delirium, and coma, though a fair degree of intelligence may be preserved until near the end. It may occur within twenty-four hours ; usually it is not delayed beyond the week. Carbuncular inflammation is often a cause of even fatal septicaemia, probably of infective nature, but it is impossible to decide whether we should consider as septic infections or septic intoxications those milder febrile reactions that so often accompany the development of a furuncle or small abscess and similar processes. Usually the general symptoms promptly subside with the amelioration of the suppurative centres, but occasionally fatal septicaemia and even pyaemia result. 508 SEPTICEMIA. A most important consideration is the septic infection that so often forms a factor in the course of various specific disorders, such as scarlet fever with severe angina, smallpox in the maturation fever, typhoid fever, diphtheria, tuberculosis, etc. This is nearly always a streptococ- cus infection, occurring through the peculiar lesions of these diseases, and in many cases constituting the essential cause of death. Important as these secondary infections must be, it is most difficult for the physi- cian to determine the extent to which they are responsible for the results, as distinguished from those of the primary infections. It is reasonably certain that the enormous streptococcus invasion of the mature eruption of smallpox largely influences the outcome of this affec- tion. Similarly in scarlet fever and diphtheria the abundant presence of streptococci and staphylococci in the faucial membrane affords the fairest possible opportunity for the concurrent development of septicse- mia. In the former affection especially the suppurative complications and sequels even in remote parts of the body conclusively prove the admission of pyogenic organisms to the circulation. It is well known that the hectic fevers of advanced tuberculosis are principally due to septic intoxication following the invasion of softened tuberculous foci by pyogenic bacteria. Probably the most interesting secondary septi- caemias are those complicating and following typhoid fever. (Though the typhoid bacillus is itself pyogenic, and may be found occasionally as a pure culture in post-typhoid pus formation, it is likely that the great majority of these inflammations are dependent upon the commoner pus bacteria. After the third or fourth week of this fever typhoid bacilli are discovered only with difficulty, and the prevailing bacteria found in localized inflammations are streptococci.') It is not impossible that many unduly protracted cases of typhoid fever, and even of sup- posed relapse, are really septicemic. The most obscure septicaemias are those that have been called cryp- togenetic, from the supposed passage of pyogenic bacteria through a healthy or intact mucous membrane. Such cases, in fact, probably always originiate in some undiscovered primary focus : the root of a carious tooth, the middle ear, a nasal sinus, an urethral stricture, or any minute lesion of the mucous tract (Welch) may be the starting point These infections often result in a more chronic septicaemia, last- ing often several weeks, and often enough running a mild course. In chronic septiceemia there are often developed recognizable centres of local inflammation ; mild endocarditis, pleuritis, pericarditis may arise. There may be also pulmonary engorgement and oedema and pronounced enteritis. Apart from puerperal and ordinary surgical septic infection, there can be no doubt that many septicaemias of feeble intensity and of favorable course are encountered, especially by the physician, and are accountable for many unduly protracted and not understood febrile processes. Chronic septicaemia of greater potency may not only de- velop localized inflammations, as has been shown, but may result in pronounced pyaemia. The micro-organisms of septic infection and of pyaemia are the same. Diagnosis. — Fermentation fever ends at a time when septic intoxi- cation and septic infection begin : within a few hours after its exciting 1 Dunin, Archivfiir klin. Med., Bd. 39, S. 369. injcxosis. 509 cause it bogint^, and within a day or two it terminates. Its uniformly favorable course will serve to ilistinrin<^' from any of the manifestations of small])ox. It is said that Morgagne, Boerhaave, and Dienu'rbroek could boast of this peculiarity. Yet instances are recorded where persons have resisted the infection when received in the natural way, but have yielded to the disease late in life by inoculation. Gregory gives an example of this kind in the case of a lady who brought up a large family of cliildren, many of whom she nursed through small- pox Avithout receiving the infecjtion herself, but at the age of eighty- three she took the disease by inociulation. While but few are naturally insusceptible to smallpox, yet at the present day, through the agency ■of vaccination, individual susceptibility is greatly changed, and even iibsolute immunity is enjoyed by the greater part of the population. Sex. — The predisposition to smallpox is certainly not influenced by sex. Under the same conditions males and females are equally suscep- tible to the disease. Race. — As to whether race exerts any influence there is some differ- ence of opinion. Most authors, however, agree that the predisposition is more marked among the dark skinned races, particularly the negro race. There is no doubt that when smallpox prevails epidemically in this country the proportion of deaths to the cases is greater among the negro than the white race ; but this, I believe, is owing to the fact that there is greater neglect of vaccination by the former. In my expe- rience the uuvaccinated cases of each race have perished in about the «ame proportion. Age cannot be said to influence the predisposition to the disease, as it is naturally present at all periods of life from earliest infancy to ex- treme old age. If aged persons are found less susceptible at all, it is because of the prophylactic power of vaccination. While nursing infants under six months old commonly resist the infection of measles and scarlet fever, they are quite sure to yield to the infection of small- pox. Even the foetus in utero is not exempt from the danger of an attack when a pregnant woman suffers from the disease. The variolous process in such a patient is exceedingly liable to excite abortion or pre- mature delivery, and the foetus or child may show evidence of the disease in the form of local lesions. Such evidence has been observed as early as the fourth month of foetal life, and at various periods thereafter until the completion of gestation. I can recall in my experience at least one case in which the child was born at the eighth month with the variolous eruption just appearing. The eruption was confluent, and death oc- curred during the suppurative stage. In the majority of cases of infection of the foetus it is found that it does not pass through the disease coincidently with the mother, but at a somewhat later period. It would appear, therefore, that infection in its case does not occur until the mother manifests symptoms of the dis- ease, and that its case is marked by a distinct and separate incubation 516 SMALLPOX AND VARIOLOID. period. When we consider the close relationship of the blood of mother and fcetus, this seems remarkable, bnt not more so than the fact that the foetus frequently escapes infection altogether. Very often, indeed,, the pregnant Avoman passes through an attack of smallpox without abortion occurring, and when the child is born at full term it is found to have the usual susceptibility to variola or vaccinia. I have vacci- nated a considerable number of infants born under such circumstances, and have seldom if ever failed to produce in them the vaccine disease. Very exceptionally, however, a child survives an intra-uterine attack of variola : such a child when born may or may not show scars, but is,, of course, insusceptible to vaccinia. It is well known that a pregnant woman while personally immune from smallpox is liable to miscarry when exposed to the infection of the disease. In consequence of such exposure during the latter stage of pregnancy healthy mothers are said to have given birth to infants affected with variola. While the possibility of such an occurrence can- not be excluded, yet it seems to me that the more probable explanation in such cases is that the mother had suffered from variola sine exanthe- mata — a form of the disease most likely to pass unrecognized. A child thus infected in utero and recovering from the disease might be found at birth and ever afterward insusceptible to variola. It is not impossi- ble that some of those, like Diemerbroek and others, who claimed for themselves natural insusceptibility to the disease may have acquired immunity in this way. Infrequent instances are met with of apparently healthy persons resisting the infection of smallpox at one time and yielding to it at another. I will relate a case in point: In 1874 a colored man, aged thirty, came under my care suffering from confluent variola. He stated that vaccination had been performed at different times during his life,, but never successfully. In 1871 he belonged to the crew of a sailing vessel on which several cases of smallpox occurred, and his duties required him to come frequently in quite close contact with those who were ill, yet he did not take the disease. He was vaccinated at the time, but, as before, without result. When he fell ill with variola three years later he was unable to account for the source of the infection. The attack proved fatal. Not only cases like this, but those cited when considering the history of smallpox inoculation, show that susceptibility to the disease may occasionally, from some unknown cause, be tempo- rarily absent. Experience also shows that the susceptibility may at one time be diminished, and at another greatly increased. The existence of acute and chronic diseases is said by some to lessen temporarily the susceptibility to the infection of variola. Curschmann believes that it is very slight among patients while in the acute stage of scarlet fever, measles, or typhoid fever. Several patients of his while suffering from the latter disease were exposed to the contagium of smallpox, but infection, he thinks, did not occur in any case until the body temperature became permanently normal. He was led to this conclusion from the fact that the interval bet-ween the time when the temperature reached the normal point and the beginning of the initial stage of variola corresponded to the longest period of incubation of the disease that is met with — namely, fourteen to nineteen days. There is ETIOLOGY. 517 no doubt, however, tlmt variolyogenes aureus and staphylococcus alhus. The bacteriological study of the disease is therefore incomplete. But, while we are not yet positively informed as to the bacteriology of smallpox, there is no doubt that the disease is spread by means of a specific virus which is reproduced in every patient. That the infecting principle is contained in the pustules has been clearly proved by small- pox inoculation. It is also contained in the exhalations from the body, in the breath, and probably in the various secretions, although this has not been demonstrated. Ziilzer proved that it is contained in the blood by successfully inoculating a monkey with blood taken from a smallpox patient. The contagium emitted by a patient is most intense in his immediate vicinity, but it may be transported in an active state for some distance by the atmosphere. It is impossible to fix definitely the striking-dis- tance of the contagium, since this depends largely upon the number and severity of the cases collected together. If a susceptible person should enter a small apartment containing one or more severe cases of small- pox, infection would almost certainly occur, Avhile if the apartment be large and well ventilated and the cases few and mild, the risk of infec- tion M'Ould be greatly diminished, or if he should approach equally near the same cases in the open air, the risk would be still less. Smallpox is undoubtedly infectious in all stages characterized by symptoms. It is alleged by some that the disease is even infectious during the incubation period, but I think there is very little reason to believe that such is the case. It is not improbable, however, that the blood of a person in this stage of the disease might convey the infec- tion if it were introduced into the veins of a susceptible individual. An interesting case is reported by Schaper, showing that the infection ETIOIJKiY. 519 was transmitted during" this stage bv sicin-grai'ting. The small pieces of skin used for the purpose were taken from a person who several hours later began to manifest symptoms of smallpox, and the individual upon whom this skin was transplanted was attacked by the disease on the sixth day after the operation.' Excepting the incubation period, the disease is least infectious during the initial stage, and most highly so during the sup[)urative and early period of the desiccative stages. The scabs are unquestional)ly infec- tious, and as long as these remain on the skin the patient should l)e regarded as dangerous to the community. Even after death the body still retains the power of transmitting the contagium. This fact has been demonstrated more than once where public funerals have not been interdicted, and where the bodies of persons who have died from small- pox have by accident found their way into dissecting rooms. While the contagium of smallpox is perhaps more commonly con- veyed from person to person through the atmosphere, yet this is not the only medium of infection. The infecting germs become attached to all objects in the immediate vicinity of the patient and cling to them for a variable length of time. Objects which have a rough, shaggy surface, such as blankets, woollen clothing, etc., not only become more intensely infected, but hold the infection much longer, than smooth objects. AVoollen garments closely packed and excluded from the air as com- pletely as possible have been known to retain the infection for many months, and even years. If, however, such garments be freely exposed to the atmosphere and sunlight, the contagium will soon be destroyed. Of course it may be destroyed at once by disinfecting agents. Not only objects in the room of the patient, but also healthy persons whose duties require them to come in contact with the sick, may be the means of communicating the infection. The infection may adhere to the hands and other parts of the body of the attendants, but the chief dan- ger is from their clothing. Great caution should therefore be observed by physicians, nurses, and others in attendance upon smallpox patients. The manner in which the contagium enters the system is usually by absorption in the respiratory tract. When there is susceptibility to smallpox a single inspiration of air containing the germs of the disease is quite sufficient to ensure infection of the individual. While it is possible for the contagium to be absorbed by the mucous membrane in the upper part of the air passage, there is no doubt that absorption takes place principally through the lungs. It is well known that the contagium never enters the circulation through the skin, except by inoc- ulation. The older writers believed that it was possible for the virus to enter by the mucous membrane of the alimentary canal, especially by the stomach, but the comparatively recent experiments of Ziilzer on a monkey which was forced to swallow smallpox crusts were followed by negative results. Conditions seem to exist at times more favorable to the spread of smallpox than at others. For instance, at one time the disease is met with in isolated cases, and shows but little disposition to spread, or if it spreads and assumes the proportion of an epidemic, the epidemic is small and marked by unusual mildness. At another time the disease ' Carschmann in v. Ziemsaen's Cydopcedia of the Practice of Medicine. 520 SMALLPOX AND VARIOLOID. rapidly spreads from a single case, and speedily assumes the dimensions and fatality of an extensive and malignant epidemic. This variation in the behavior of the disease at different times has never been satisfac- torily explained. To say, as the earlier writers were wont to do, that it is owing to some peculiar condition of the atmosphere is no solution of the problem. Perhaps Diemerbroek was not far wrong when he ex- pressed the belief that " this is one of those mysteries which nature for ever intends to keep to herself." There is, however, one cause well understood which at the present day influences to a great extent the recurrence of epidemics, and that is the neglect of vaccination. During the prevalence of smallpox this important agent is freely employed and serves as a powerful factor in extinguishing the epidemic. But it is well known that in the course of a few years the susceptibility of very many of those previously pro- tected by vaccination becomes gradually re-established. If we consider the large numl^er of susceptible persons belonging to this class, together Avith the number of those who are apt to neglect vaccination, we can readily see how there is provided from time to time a suitable soil into which only a few smallpox germs need be introduced to give rise to an epidemic of the disease. Pathological Anatomy. — While it is generally conceded that the etiology of smallpox must be explained by the germ theory, yet nothing is known of the nature of the specific micro-organisms believed to be present in the disease, nor of their manner of attacking the blood and tissues of the body. The only bacteria described are those belonging to the cocci group, especially such as are peculiar to pus formation, but they can scarcely be said to bear a causative relation to the pathological processes of the disease. The Skin. — The earliest, and indeed the chief, anatomical changes met with are found in the skin. Usually on the third day of the disease the characteristic cutaneous lesions begin in the form of small red spots. These are produced by circumscribed hypersemia of the papilla? and extend deeply into the skin. Papulae are thus formed, and as they advance in their development the epithelial cells above the con- gested pa|)illse, through an increase of protoplasm, become enlarged and granular. This distinctly granular condition of the involved epithelia causes the papules to assume at quite an early stage a solid, dense character. The papulae are next converted into vesicles by an exudation of lymph from the papillary layer. As the lymph increases the altered cells over the engorged papillae are separated and changed, so as to form septa or partition walls, which give to each vesicle a reticulated or many celled cavity. AVhile the contents of the vesicles at first is principally lymph, together with coagulated fibrin and granular matter, eventually pus cor- puscles are formed, mainly by the transformation of epithelia. Quite early in the vesicular process a depression, known as " umbili- cation," is seen in the centre of very many of the vesicles. This is believed to be due either to the hair follicles or the excretory ducts of sweat glands, as in either case the epidermis dips downward and forms a part of their anatomical structure. If, for instance, a vesicle forms about a hair follicle, the centre of its epidermic covering will be held PA THOLOGICA L . 1 A . I T'>M V. 52 1 down bv the .sheath of" the tolliele, while the surrouiuHu^ portion will become more elevated. The (hicts of the .sweat glands have the .same relation to the epidermis and may act in the same way. It shoid«l be stated, however, that some authors do not aeeept this explanation, but believe that the eentre of" the vesicle is held down i>y a resistant portion of tissue from some other eau.>ie. According to Curschmann, Auspitz and Basel) teach that the j3eripherv of the vesicle swells more rapidly and thus l)ecomes more voluminous than its centre. When the vesicle has advanced to the pustular stage and the pock is fully di'V(lo])ed, the umbilication disap])ears. This results from accumu- lation of tile |)us corpuscles, which, by maceration and tension, causes the fibre of tissue holding down the centre of the pustule to give way. When desiccation commences it is not unusual to find that many of the pustules begin to dry in their centre, and thus assume again an umbil- icated appearance ; but the umbilication previously described is some- thing very different, both in its cause and appearance. In unmodified smallpox, sometimes also in varioloid, both the papilke and connective tissue beneath the pustules become involved in the iuflam- matory process, and, through the accumulation of pus corpu.scles in the papilhe, the bloodvessels are compressed, producing necrosis of the upper layers of the true skin. The extent of tliis necrotic action determines the size and shape tjf the cicatrices ; for wherever fibrous connective tissue is destroyed its place is supplied by cicatricial growth. Perma- nent scars may therefore be expected to follow the eruptive process. The vesicles in hemorrhagic variola differ from the ordinary vesicles in that they contain i)lood instead of lymph and pus. In the milder oases of this form of the disease there may be only a slight admixture of blood with the elements usually found ; in the severer cases not only do the vesicles literally fill with blood, but there is hemorrhagic infil- tration in all the layers of the cutis and even in the subjacent areolar tissue. This latter condition is often very extensive, covering almost the entire surface of the body. In such cases death usually occurs before there is time for the development of vesicles. Wagner's inves- tigation shows that the hemorrhagic extravasation is not the result of rupture of the bloodvessels, but is due to transudation of the altered blood through the relaxed and weakened vascular walls. Certainly no anatomical changes sufficient to account for this condition have yet been found in the walls of the vascular system. The iiiiicous membranes are not exempt from the eruptive process. The eruption on this membrane, however, rarely observes the same course as on the cutaneous surface. Instead of running through the distinct stages of papule, vesicle, and pustule, it is apt to assume the form of diffuse purulent infiltration of the layers of the epithelium, and may even become diphtheritic in character. The extent and intensity of the involvement of the mucous membrane usually bear a very direct rela- tion to the eruption on the skin. That part of the mucous surface which comes in immediate contact with the air is more apt to be attacked. Indeed, the mucous lining of the nose and mouth seldom escapes. The tongue, posterior nares, and pharynx are often severely attacked, even to the extent of interfering with deglutition. The eruption may occur in the larynx, trachea, and bron- 522 SMALLPOX AND VARIOLOID. chial tubes, even below the bifurcation, giving rise to various grades of catarrhal inflammation. Catarrhal pneumonia occurs not infrequently. The eruption has been found in the upper part of the oesoj^haguSy but it is doubtful whether it ever extends to the stomach and intestines. It has, however, been seen at the lower end of the rectum close to the anus. The vulva and outer portion of the vagina are often severely attacked, and I think there is good reason to believe that the cavity of the uterus is not infrequently involved. The eruption is found at the orifice of the urethra, but the urethra and urinary bladder seem to be exempt. The Viscera. — There are no pathological changes found in any inter- nal organ that can be regarded as peculiar to smallpox. The liver, kid- neys, and s^Dleen have been found sw^ollen and engorged with blood, and occasionally in a state of fatty degeneration. When the latter condition exists there is also apt to be degeneration of the walls of the heart. In the severer forms of hemorrhagic variola, where death occurs early, the heart, according to Ponfick, is contracted, firm, and of a brownish red color. In this class of cases the spleen also is small, dense, and very dark. Besides these changes hemorrhages are found in the viscera, the cavities of serous membranes, the loose connective tissue of the medias- tinum, and in various other parts of the body. The brain and spinal cord have been found congested and oedematous. Changes not well defined sometimes occur in the nervous system, giving rise to aphasia and certain forms of paralysis. Hemorrhages into the sheaths of nerves have been seen by Zlilzer. Abscesses and purulent collections in various serous cavities, as the result of septicsemia, not infrequently occur. I have several times seen large collections of pus in the pleural cavity, and also in the larger joints, especially the elbow joint. The eyes are often severely affected. Conjunctivitis and oedema of the lids are common. The cornea is frequently attacked by ulcerative action, resulting often in perforation and protrusion of the iris. Suppu- ration of the globe sometimes follows. Symptoms. — Incubation. — The period that intervenes between the reception of the variolous contagium into the system and the earliest manifestation of symptoms is known as the " period of incubation." The duration of this period generally does not vary very greatly. In the majority of cases in which I have had opportunities of observing it care- fully I have found it to be from ten to twelve days. It is seldom less than eight or more than fourteen days. The period can only be determined accurately when an individual is exposed to the contagium but once and for a short time. Where the exposure is frequent or extends over a long period it is not easy to determine the exact time when the con- tagium enters the system. When the disease prevails epidemically it is not impossible for an unknown exposure to precede the one of which the individual has knowledge, and in such case the period of incubation would appear to be unusually short. These facts may explain many eases in which this stage is believed to be either unusually long or short. When, however, infection takes place by inoculation, constitutional symptoms usually manifest themselves on the latter part of the seventh or beginning of the eighth day. SYMPTOMS. ry2^ Alter the ooutugium i.s received into the system certain unknown pro- cesses are doubtless set up, although rarely indeed are any symptoms observed during the incubation period. Some authors describe as occa- sionally present such symptoms as languor, gastric disturbance, pain in the head and back, and a peculiar pallor of the face, but I have never met with any of these except toward the close of this stage. Usually the individual appears to enjoy perfect healtli until the invasive symj> toms appear. Initial Sfaf/e. — After slight malaise, of short duration, the symp- toms of smallpox appear suddenly, and often with considerable violence. The earliest symptom is usually a distinct chill or repeated rigors ; high fever follows immediately, and continues unabated until the peculiar cutaneous lesions appear. This comprises a period of from two to four days, and is designated the stage of invasion, or initial stage, of smallpox. The chill which usually marks the beginning of the initial stage is sometimes severe, though more frequently it assumes the character of repeated rigors. While, as a rule, the latter are well pronounced, yet occasionally they are so mild as scarcely to attract attention. Synchron- ously with the chill or immediately folloNAnng it fever appears. The temperature on the first day often rises to 103° or 104° F., and on the second and third llays, with perhaps the exception of slight morning remissions, it rises still higher, frequently reaching 105°, and in some cases even 107° F. The elevation of the temperature is usually sud- den ; in but few diseases does it rise so quickly from the normal to a high degree. Even in varioloid the early symptoms are not infrequently equally severe, although occasionally they are so mild as to escape atten- tion, so that the first symptom noticed is the skin lesion. But the eruption of unmodified smallpox never appears without being preceded by a well marked invasive stage. While the fever continues the skin, of course, is hot and sometimes dry, though more frequently covered by a moderate perspiration. The pulse is full, tense, and rapid ; its rapidits* generally corresponds ^A^ith the temperature curve. In adults it may vary between 100 and 130, while in children it not infrequently reaches 160. The respirations are almost always increased in frequency, especially when the temperature is excessively high. Prostration is often extreme, being out of all pro- portion to the length of the illness. Strong and robust patients are frequently unable to stand without support, and when in the upright position soon become pale, languid, and liable to be attacked by vertigo or syncope. There is also thirst, the lips and tongue are parched and dry, and loss of appetite is manifest. Constipation is common. The tongue is usually coated with a thick yellowish covering, and the breath is heavy and offensive. According to some authors, the odor from the body of a patient at this stage of the disease is so peculiar and distinctive as to make it possible for the diagnosis of smallpox to be made by this symp- tom alone. I have heard of many curious instances of this kind, but I must confess that my olfactories have never acquired this degree of acuteness. Irritability of the stomach is a very frequent symptom at this stage. It is often verv obstinate, continuinsf for two or three davs or until the 524 SMALLPOX AND VARIOLOID. eruption appears, and is apt to be accompanied by marked tenderness of the epigastrium. The irritability usually ceases when the eruption ap- pears, but if it continues longer the case should be viewed with some solicitude. In hemorrhagic smallpox especially this symptom, together with epigastric pain, is not infrequently very prominent and distressing. Certain nervous symptoms are usually present. The most prominent is headache, which is scarcely ever entirely absent. Delirium is often seen, especially when the temperature is high. It may be mild in character, the patient simply talking incoherently, or so violent that forcible re- straint is necessary. The latter form is usually attended with great restlessness and insomnia. Coma is rare, although it may be met with in children. Convulsions are very common among children — more so, perhaps, in this disease than in any other of the exanthemata. Pain in the back is a symptom so commonly observed that it is believed to be of special diagnostic value. It is not so constant as some other symptoms, yet it occurs in more than half of the cases. Like headache, it begins at the onset of the disease and continues until the eruption has made its appearance. The lumbar and sacral regions are the parts to which the pain is usually referred, although it may extend to the dorsal region. As a rule, it is more severe in unmodified smallpox than in varioloid, yet this rule is subject to many exceptions. In heAiorrhagic cases the pain is often excruciating. Pain in the back is perhaps more constantly seen among female than male patients, owing to the fact that the menstrual function is very liable to be excited by the initial process of smallpox, causing the menses to appear out of their regular period. Pregnant females also are exceedingly liable to suffer from premature delivery or abortion. The pain in the back, therefore, resulting from these causes tends to give greater prominence to this symptom of smallpox in females. The urine is usually more or less diminished according to the degree of fever. The solid constituents are not out of their normal propor- tion, except the chlorides, which are considerably diminished. In severe cases, especially those about to assume the hemorrhagic type, albuminuria may be present. A high grade of fever might be respon- sible for a small quantity of albumin, but if it be present in great abundance, a malignant type of the disease should be suspected. Before giving an unfavorable prognosis, however, care should be taken to see that the albumin is not the result of some chronic disease of the kidneys. The sj)leen, according to Curschmann, whose attention has been especially directed to it in a large number of patients, is not rarely enlarged. He says he has never been able to detect any enlargement of this organ in the initial stage of varioloid, but has found this con- dition present, and often to a marked degree, in unmodified smallpox. In many severe and grave cases, however, the splenic tumor was absent. Therefore no great diagnostic value can as yet be attached to this symptom. A peculiar prodromal rash often makes its appearance during this stage. When it occurs it is usually seen on the second day of the invasive fever, and continues not longer than forty-eight hours or until the beginning of the true eruption. The frequency of this rash appears to vary in diiferent epidemics. During the widespread and malignant SYMPTOMS. 525 epicleiuic of 1871-72 it was very coiuiikmi. Some authors describe it as ])rt'sentiii^ an erythoinatous or scarlatiiiilonii a|)[)('araiice, but according to my observation it more nearly resembles the rash of measles. So close, indeed, is the reseml)lanee that the first time I met with it I fell into the error of sup])()sing the case to be one in which measles and smallpox coexisted. The name generally given to the rash — roaeula variolosa — conveys a very good idea of its appearance. This ])eculiar exanthem occurs quite as often in varioloid as in variola. In the absence of any exact data 1 venture the assertion tiiat I have met with it more frequently in the former. I am able to recall at this moment two cases of variolous disease in which it was tlie only eruption that occurred at all. In one of these, it is true, about half a dozen small papules appeared as the initial rash faded away, but they disappeai'ed in two or three days without becoming in the slightest degree vesicular. These belonged to the class of cases commonly desig- nated variola sine cnDttlioiiafa, the most benignant form of the disease that occurs, as well as the rarest. That such cases are encountered occasionally is evident from the writings of all authors, both ancient and modern. Perhaps in every epidemic patients are seen who give a history of exposure to the contagium of variola, and after the usual incubation period are suddenly seized with repeated rigors, followed by headache, fever, irritable stomach, prostration, and pain in the l)ack ; Avhich symptoms continue three or four days, and then subside without any cutaneous manifestations, except perhaps the rash just described. It is difficult to explain such cases on any other supposition than that the disease was smallpox without the eruption. While the initial stage may present the most varying phases, some symptoms may be entirely absent and others appear Avith great severity, yet there are usually no indications^, thus far, to justify the certain ex- pectation that the case will be mild or severe, modified or unmodified ; this can only be clearly determined when the eruption has made its appearance, which is not until the invasive stage has passed. The dura- tion of this stage is commonly forty-eight to seventy-t^vo hours ; it is rarely less, but it may be somewhat prolonged. There is, however, no decided remission in the fever until the second or third, and sometimes not until the fourth, day of the eruption. Stage of Eruption. — By observing carefully the early stage of the disease it will be found that the true eruption makes its appearance with remarkable regularity on the third day of the illness, counting the day on which the initial chill or rigors occurred as the first. The eruption almost always appears first on the forehead and temples near the edge of the hair, and on the wrists. Not infrequently it may be seen first on the upper lip or near the mouth. It rapidly spreads to the scalp, face, neck, ears, forearms, and hands, always showing a decided prefer- ence for the cutaneous surface habitually exposed to the atmosphere. In the course of twenty-four hours, sometimes somewhat earlier, it extends to the body and lower extremities. ISot simultaneously does it appear on these parts, but first on the back, arms, and breast, then on the legs and feet. Nor does the entire eruption make its appearance all at once on any one part, but it continues to multiply for two or three days before its definite limit is reached. A careful study of the eruption 526 SMALLPOX AND VARIOLOID. has shown that the lesions are exceedingly apt to locate themselves around the hair follicles and orifices of the glands of the skin. Another notable feature of the lesions is that they show a remarkable predilection for all irritated or abraded surfaces, and hence collect in dense clusters around an ulcer or any localized inflammation of the skin. Even the redness produced by a sinapism predisposes that part to an intensely confluent form of the eruption. But while the lesions may thus be increased on certain areas, they do not seem to be thereby diminished on other parts of the body. As the outbreak of the eruption is gradual, so also is its develop- ment. It usually appears in the form of minute red points, some of which may be so small as to be scarcely visible, and others as large as a mustard seed. These gradually increase in size and number, becom- ing more and more prominent, so that in twenty four hours they assume the form of elevated papules, characteristically indurated, and convey to the touch a sensation similar to what would be expected if grains of shot were buried in the skin. The papules at first are always discrete, but they may rapidly increase in number and become confluent, even before the vesicular stage is reached. At first the small red spots give rise to no subjective symptoms, but as they advance to the papular stage there is a slight pricking or painful sensation, and this increases as the lesions become more prominent. On the third day of the eruption, or fifth day of the disease, very many of the lesions which made their appearance first will be found to contain a little clear serum. By the fourth or fifth day all the lesions are transformed into vesicles with cloudy and milky contents (Fig. 46). These continue to enlarge, attaining their maximum size about the seventh or eighth day. As soon as the vesicles form there can be seen in very many of them a central depression, which deepens as they enlarge, giving them the peculiar umbilicated appearance which has been described in a previous section. Umbilication of the vesicles is a very important diagnostic symptom in variola, since the vesicular erup- tion of no other disease presents exactly the same appearance. A close examination of the vesicles shows that their interior is divided into many partitions or cells. This is evident from the fact that if a simple puncture be made into the epidermic covering of a vesicle only a small part of its contents will escape through the opening, while the principal part remains undisturbed. ^^tage of Suppuration. — The contents of the vesicles gradually grow more and more turbid by the constant accumulation of pus corpuscles until it becomes distinctly purulent. This condition is usually reached in unmodified smallpox about the sixth day of the eruption, and marks the beginning of the stage of suppuration. The pustules now in good part become large and globular, losing to a great extent their umbili- cated character. The efflorescence or areola which at first surrounded them becomes broader and more intense, causing the skin in their imme- diate vicinity to present an inflamed and tumefied appearance. On parts of the body where the pustules are thickly set, particularly on the face and head, the redness and tumefaction are extreme, often distorting the features to such an extent as to make the patient unrecognizable. The eyelids are frequently so oedematous that they cannot be opened, and n -0 r- > H m m to" D m n r- > H m sYMrroMs. 527 iniiciL- or piiritonu secretions collect at tlieir margins ; the lips, nose, and cars are greatly swollen ; and the scalp is often so swollen and ])ainful that pressnre from the ])illow is scarcely endurable. Fig. 46. Discrete variola ou the sixth day of eruption. As the eruption on the body and lower extremities is later in making its appearance, so also is it later in reaching maturity. About the eighth H m VAhllF.TIKS OF SMALLI'OX, 533 o > -1 X •D C 0) is 0>DO OO OOO Ot », «, 0„ — ^ KJ^ lu^ •f'.j ~ ■" S - 24:90 "- ! <, m 24 ! 92 ^_ 1 1 1 > [ S 20 , 90 . -*— — m l« -*>2|„. ♦«=: 2[ ~— ~~^ s 24 j 90 [ 1 m 34! 104 CT - - " < s w- 24 112 ~'^ m 2" 108 03 »= =• 1 s 24 120 fn K. !112 ^I < >♦ - S ■ 20 ;iio - m 1 10 : 00 Ci 1 — -i • 'J-. 1 24 |108| ^ .Mil S m 20 [1081 1 -^ ^,>, s -' 2.! 110-^ 1 m X 24 112 ^ t j ►== S 24 110 - ~^ M m 24 112 - , , 1 . 1 - -c:^ 2 ~ 2^ ll'-. PH NACETIN GR.TTfS kj 2 AND . P. ^\ _jj =i ■ m ,__, 24 1 108 n 1 j ■=r=?lT "i 1 1 1 2 o 24 110 i 1 1 1 T rL- ^ 2 •^ 28 ,110 ! 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S4 iO •< — — 1 1 2 ct 90 ~ ■"^p* II I I m :>•) 82 M 1 K 'III 1 1 I 2 38 1 i U: ::;! 1 M ^ m 84 i •= ; 1 , M 111 i 2 ■- 1 64 ^ : III 1 rn 162 zi Lr^ M ' 2 " j88 > m ;84!*- ^ i 1 1 i 2 > ; m 82 ^ v^ 2 84 1 M ' ; 1 m 534 SMALLPOX AND VARIOLOID. irritation and extensive suppuration is, at this time, extreme, and gen- erally constitutes the chief source of danger. At this stage, also, com- plications are liable to occur, such as ulcer of the cornea, purulent forms of keratitis, pneumonia, pleurisy, empyema, suppuration of the joints, and gangrene of portions of the cutaneous integument, especially of the scrotum. An uncontrollable diarrhoea frequently sets in and aids in diminishing the vital forces. The mortality from confluent variola is, of course, very great. If death does not occur from exhaustion, it is liable to result from septicsemia, pyaemia, or some one of the other complications just named. When this form of the disease terminates in recovery it is only after a long and tedious illness and a tardy convalescence. During desicca- tion the inflammation and swelling of the skin and mucous membrane subside, and the patient is able to take nourishment more freely. The scabs form into large coherent masses, and some of them remain for a long time firmly adherent, especially those on the face. After they have fallen ofi* the skin is very red and spotted, and left permanently disfigured by unsightly scars. During the period of falling of the crusts various sequelae are liable to appear, among which furuncles are most common. Large abscesses also may form on various parts of the cutaneous surface ; the cellular tissue beneath the scalp seems to be peculiarly liable to this process. Petechial, Purpuric, and Hemorrhagic Variola. — These names are applied to the different phases presented by malignant or hemorrhagic smallpox. In certain epidemics a petechial eruption is frequently seen at the close of the initial stage of the disease or about the time the true eruption appears, or should appear if it is not delayed, and is generally the precursor of a train of symptoms indicating great malignancy. This eruption is often quickly followed by the purpuric or hemorrhagic vari- ety, and the disease rapidly runs its course to a fatal termination. At other times petechise and ecchymoses appear between the papules or vesicles, and as the latter develop many of them fill with a sanguino- purulent fluid, while others fill with distinctly purulent matter ; thus a great diversity is sometimes manifested in the eruption of a single case. While such cases usually result fatally, yet, if the dyscrasia is not too great, they may terminate in recovery. There is no doubt that in all cases of hemorrhagic variola the blood is greatly altered, and even in most cases so completely devitalized as to be incapable of maintaining the vital functions. Therefore recovery from this form of the disease, especially when well marked, is quite exceptional. The causes leading to the hemorrhagic type of smallpox are, as yet, unknown. There is no doubt that such cases result from the or- dinary variolous infection, and that the infection derived from them may in turn give to the disease its typical aspect. It is knoMai, how- ever, that this type of the disease varies in frequency in different epi- demics. Variola jpurpurica is the gravest and most malignant form of the hemorrhagic type. The initial stage in such cases does not differ very greatly from that of ordinary variola. There is nothing peculiar about the rigor, fever, and headache ; the pain in the back, however, is intense and the prostration is generally excessive. Toward the end of the VARIKTII'.S OF SMALL/'OX. 535 initial staj^c a dilt'use cllloivscciicc npjtcars on various parts of" the trunk and extreniitios, while the face remains for a time exempt. The rash at first is scarlatinoid in apjiea ranee, and disa])])ears ])artially under pressure; later it heeonies more intense; peteehije, vihiees, and eeehy- moses ap])ear, esju'cially on the chest, the axilhe, the lower p(»rtion of the abdomen, the groins, the legs; and the dark red or purplish dis- coloration now present does not fade in the least by pressure. Th(> dis- coloration rapidly extends to the face, which also becomes swollen and puffy. The conjunctivae are injected ; the eyes become bloodshot aud surrounded by dark rings, owing to hemorrhage into the cellular tissue of the lids. Frc((ucntly the hemorrhage under the conjunctiva cover- ing the sclerotica is so great as to cause the conjunctiva to project beyond the lids, like a sac filled with blood, and prevent the eyes from closing, while the cornea remains luiatfccted and looks as if it were deeply sunk into the globe of the eye. This condition, together Avith the dark discoloration of the face and the tumefied features, g-ives to the patient a peculiarly hideous appearance. A close examination of the body often reveals in certain localities, particularly the axillae and groins, small and indistinct vesicles thickly set and filled with bloody serum. These vesicles never develop to any extent, but remain per- fectly flat, and are of a blackish or leaden gray hue. As the disease progresses the dark discoloration of the skin deepens on all parts of the body, until at last it is sometimes difficult to say, judging from the color alone, that the patient is not a native of Africa. Hence this form of the disease has long been known by the name of variolce nigra:. The eruptive process does not always afford unequivocal evidence of small- pox, and the disease is therefore sometimes mistaken for some other malignant affection, such as black measles and the like. In this, as in other severe types of variola, the pharynx and upper part of the air passage usually suffer. There is apt to be more or less cough, with bloody sputum. The tongue is large and red, and the breath often horribly fetid. Indeed, the odor from the body also is ex- tremely loathesome. There is persistent nausea and vomiting, and almost always severe pain or distress in the precordial region. The temperature is seldom very high, except in the invasive stage, but the pulse is rapid and feeble. Hemorrhages are quite certain to occur from the nose, bronchial mucous membrane, kidneys, rectum, and uterus. Women almost always suffer from metrorrhagia and, if preg- nancy exists, abortion. According to my experience, this type of small- pox occurs as commonly among young and robust persons as among those infirm or debilitated. Intemperate persons and drunkards, as well as lying-in women, seem peculiarly predisposed to this terrible form of the disease. One of the most extraordinary features about this fatal malady is that the mental condition of the patient often remains undisturbed until almost the last moment of life. There may be delirium or stupor, but usually the victim faces death with his mind clear and intellect unim- paired. I remember on one occasion, as I stood by the bedside of a most malignant case of purpuric variola, not thinking that the patient was conscious, of remarking to the resident physician that there Avas no ground for hope in this case. At once the patient sat up in bed and. 536 SMALLPOX AND VARIOLOID. with surprise, inquired, " Doctor, do you mean to say I can't get well ? " In less than twenty-four hours the patient was a corpse. The course of this type of sruallpox is very rapid. Death not in- frequently takes place in consequence of the greatly altered state of the blood before any clear and well pronounced symptoms of the disease appear. More commonly the eruption may be seen in confluent form on some parts of the body, but it never makes much progress. Death usually results from the fourth to the sixth day. I have never known a Avell marked case to recover. The hemorrhagic type of smallpox may assume still another form : I refer to the form which Curschmann designates variola hcemorrhagica pus- tidosa. In this variety, as soon as the vesicles appear, instead of filling with serum they fill with a sanguinolent fluid. In some cases the vesi- cles first appear, and immediately their contents become mixed with blood ; in still other cases this change does not occur until the eruption has reached the pustular stage. This hemorrhagic condition of the j^us- tules may be limited to certain localities or it may extend over the entire body. Petechige and purpuric spots, as already described, may be associated with this form of eruption.- The hemorrhagic pustules usually begin on the legs, although they may appear first elsewhere. An early examination in a case about to assume this condition shows that here and there a pustule jDresents a blue centre ; by degrees others take on the same appearance, and the color gradually deepens, until at last, in severe cases, the pustules on all parts of the body become distinctly hemorrhagic. At the same time, livid spots may be seen on the mucous membrane of the mouth and fauces. The gums are spongy and bleed readily. Hemorrhages occur from the nose and various internal organs, as in purpura variolosa. It is seldom, indeed, that hsematuria is absent or that metrorrhagia fails to occur in females. This form of heuiorrhagic smallpox is more protracted in its course than purpura variolosa, but almost as certain to end fatally. My own experience leads me to say that recovery from this type of the disease is extremely rare ; even the so-called milder cases, or those in which the symptoms are least pronounced, almost always terminate fatally. I have seen recovery in but few cases, and only among those in which the hemorrhagic condition of the pustules was not only limited to a com- paratively small number of these lesions, but appeared at a relatively late period of the disease, and in which the hemorrhage from the nose and internal organs was not excessive nor long continued. I have never known recovery to result in a case in which all or nearly all of the vesi- cles assumed the hemorrhagic character at an early stage, and in which there were well marked epistaxis, hematuria, conjunctival hemori'hage, and bloody stools, together with the usual concomitant symptoms, such as a rapid and feeble pulse and the peculiar livid, purplish, or indigo color of the skin. Varioloid. Varioloid is not a disease which simply resembles variola, as the name would imply, but is truly smallpox in a modified form. This is evident from the fact that the infection arising from this milder form of VARIOLOID. 537 the (liscMSc oivcs rise to variola vera in imjirotcctcMl persons. Since the introduction of" vaccination varioloid has Ix'coine ninch more fVecjnent than in t'ornier times. It is well known that the immunity conferred hy vaccination, althoni;h com[)lete at first, becomes thron<>;h lapse of time more (»r less im]xiire(l in the vast majority of individuals. The pro- tective intlu(>nce from this measure frequently diminishes very gradually for a varial>le lenuth of time, and eventually may disa])pear entirely. Hence persons previously vaccinated are liable to suffer from various grades of smallj)ox according" to the degree of j)r()tecti()n remaining. In every epidemic of the disease cases are seen not only so mild as to be scarcely recognizable, but also so severe that when they have finished their entire course the physician is in doubt as to whether the attack should be called variola or varioloid. It has been my rule to classify as variola all unvaeeinated cases, all malignant cases, and all vacci- nated cases in which the eruption pursues its regular course and is atteniled by secondary or suppurative fever, while I classify as vario- loid all vaccinated cases in which the eruption is markedly abridged in its course, and in which there is but little if any secondary rise of temperature. Of course it is well known that in some unprotected persons there is naturally but slight susceptibility to the infection, and that the disease among this class is mild and of short duration ; but such cases should be regarded simply as mild forms of variola vera. Besides vaccination, the only circumstance which determines the occur- rence of varioloid is a previous attack of variola. Varioloid cannot always be distinguished in the initial stage from variola vera, since the train of symptoms may be the same in each and equally severe. Occasionally, however, in varioloid the eruption ap- pears after an exceedingly mild initial stage ; this almost never occurs in unnKidified smallpox. The length of the initial stage is also varia- ble. While the duration of this stage in variola is quite uniformly three days, in varioloid it may be as short as twenty-four to forty- eight hours, or as long as four or five days. At the commencement of the invasive stage the temperature at once becomes more or less ele- vated : if it should rise very high, it usually drops suddenly at the outbreak of the eruption to the normal degree or even below, and does not again rise to any considerable extent unless complications occur. The initial exanthem, which has already been described as frequently appearing at this stage of smallpox, is, I believe, much oftener met with in varioloid than in variola vera. Indeed, this prodromous rash, not unlike measles in appearance, is so frequently followed by an exceedingly sparse variolous eruption that it might almost be regarded when pres- ent as the forerunner of varioloid. But if the rash should be petechial or purpuric in character, it is an indication that the attack will be severe. There is nothing peculiar about the eruption of varioloid except that it is milder in its course and of shorter duration than that of v^ariola. It almost always appears on the face, and rapidly spreads to other parts of the body, although at times it makes its appearance on the trunk and extremities quite as early as on the face. The lesions do not develop quite as regularly as in unmodified smallpox, it being not un- usual to find some pustules larger and farther advanced than others. 538 SMALLPOX AND VARIOLOID. The extent of the eruption and the duration of its course are also variable. It may be limited to a very few lesions on the face and hands, or it may assume a semiconfluent form on these parts, and also invade other parts of the body to a considerable extent. In the milder forms the lesions do not pass through all the stages, but become abor- tive at an early period ; in the severe forms the eruption passes through the various stages of papule, vesicle, and pustule, and is quite as pro- nounced as in unmodified smallpox. Between these two extremes the eruption may assume every possible phase. It may appear in the con- fluent or semiconfluent form, as just stated, but, instead of the inflam- matory action extending to the deeper layers of the skin, as in variola vera, it is limited to the upper layers ; hence the course of the eruption is shorter, desiccation occurs earlier, the scabs fall off more rapidly, and the scars are not so deep. This variety of smallpox was called by ear- lier authors " confluent superficial." More frequently the eruption of varioloid is less copious, but runs the same mild course. The papules very early assume the vesicular character and reach the pustular stage on the third or fourth day, completing their development from the fifth to the seventh day, when desiccation begins. The pustules dry up quickly, forming thin brownish crusts, which fall off much sooner than in the unmodified form of the disease, leaving either very super- ficial scars or slightly pigmented spots which entirely disappear in the course of a few months. When the modification of the eruption is still greater, it is not unusual to find that the lesions develop into large, solid, conical papulae, having at their apices a vesicular condition which rapidly desiccates and forms very thin crusts. After the crusts have fallen off the lesions remain tuberculated for some time, especially on the face, looking not unlike warty excrescences ; to this form of the eruption the name variola verrucosa has been given. Another somewhat common form of the erup- tion is that known as variola miliaris. In this the majority of the ves- icles are very small, not larger than millet seeds, and, without progress- ing any farther, turn yellow and rapidly disappear. Not rarely a few tolerably well developed pustules are found mixed with these smaller lesions. Still other varieties of the varioloid eruption have been de- scribed, and, according to the fancy of the author, designated by various terms, such as variola siliquosa, v. pemphigosa, v. globulosa, v. crijsfallina, etc. ; but as these varieties are of no practical importance, a description of them here is deemed unnecessary. The mucous membrane of the mouth and upper air passages is usually affected, although much less severely than in unmodified smallpox. Diseases of the eye, such as photophobia and corneal ulcer, may occur, and secondary phlegmonous processes, such as abscesses and furuncles, may follow, but these affections are also less apt to be severe. Complications and Sequels of Smallpox. — The skin is more frequently the seat of complications and sequelae than any other part of the body. Erysipelas occasionally appears w^hen desiccation is com- pleted and the crusts begin to fall. It more frequently attacks the face, but may appear on almost any part of the cutaneous integument. I have known it to assume a phlegmonous character on the neck and upper COM I'lAL'AT loss AM) S/U^I'hLyE OF SMALLPOX. 539 portion of the chest, renderinji: these |)ai"ts as dense and unyieldintr to the touch as if covered \vith a ])hister-(tf- Paris dressinjj;. During- desic- cation ;reatly improved, and some ilisa])pear entirely. Likewise, in searlet fever the temperature is high at the onset, and continues so after the rash has a]>peared. Not only in this respect does scarlatina differ from variola, but by the uniform ditfusion of the characteristic rash, the absence of papuhe, and the presence of angina. But between purpuric variola and malignant scarlet fever the diagnosis is often very difficult, as in both affections the rash may be diffused and intensely red or pur- plish, the fauces are usually inflamed, and the temperature, even in variola, does not fall when the eruption appears. In such cases I would advise that the entire cutaneous surface be carefully examined : very often small hemorrhagic maculo-papules or very flat and intensely })ur- ple vesicles may be found on some parts of the body, the presence of which Avould be sufficient to exclude scarlet fever. It should be remem- bered that in this form of variola the favorite seat of the eruption is the lower abdominal region, together with the inner surfaces of the thighs near the external genitalia. Next to this locality, the hemorrhagic ex- anthem shows a preference for the axillary regions. Attention given to these points will often aid very greatly in the differential diagnosis be- tween these malignant affections. When the eruption of variola first appears it is not infrequently con- founded with measles. The catarrhal symptoms, which are so promi- nent in measles and so rarely absent, constitute at this stage one of the most striking points of difference between these diseases. Equally im- portant also is the degree of fever. While the temperature in the initial stage of variola suddenly rises to 104° to 106° F., in measles it is rarelv hiirher than 102° to 104° F. In variola it falls soon after the eruption appears, while in measles it continues the same or may rise still higher. The eruption of measles frequently makes its appearance quite as early on the back as on the face, and the lesions are equally numerous on both of these localities ; while in variola the eruption begins on the face and extends gradually downward. If the eruption be carefully examined, it will be found to consist of innumerable maculse, and that the maculse of measles are larger than the papulae of variola ; that the maculse are set in clusters or groups,' while the papulae, even in confluent cases, are at first remarkably discrete ; that the maculte disappear or grow pale under pressure, while the color in the papulte is more persistent ; that the maculae are soft and velvety to the touch, while the papulae are hard and shotlike. The latter condition of the eruption in variola has always been regarded as a sym])tom of considerable diagnostic value — and justly so, too — yet the eruption of measles often assumes a distinctly papular character on some parts of the face, and especially on the wrists ; therefore care should be taken to examine the back of the patient before making a diagnosis. But it must be admitted that the eruption of these diseases is occasionally, for a very brief time, so similar in appearance as to defy the skill of excel- lent diagnosticians ; in such cases it is advisable to defer the diagnosis 542 SMALLPOX AXL) VARIOLOID. for twenty-four hours, by which time the eruption in either case will clearly reveal its individuality. On account of the swelling and the vesication in facial erysipelas that disease has been mistaken for variola ; but a careful physical ex- amination should be sufficient to avoid such an error. Glanders, in an early stage, is said to bear some resemblance to smallpox, not only as to the "febrile conditions, but also as to the cutaneous lesions, which con- sist of hard infiltrations in the skin, followed quickly by suppuration. But the lesions appear in successive crops and ulcerate rapidly ; more- over, the disease is very rare and occurs only among grooms and stablemen. Kashes produced by the ingestion of certain drugs, as well as various skin diseases of a vesicular or pustular character, have been mistaken for the eruption of smallpox ; but a thorough knowledge of the course and peculiar features of the variolous eruption is the physician's safe- guard against such errors. Vaccination with animal virus sometimes causes an ervthematous or rubeoloid rash, known as roseola vaccinosa, to appear froni the eighth to the twelfth day of the vaccine disease. I have quite frequently known this rash to have been mistaken for the eruption of variola, especially during epidemic visitations of the disease. The distinguishing features are that it accompanies vaccinia, that it is not preceded bv a very high temperature, and that it consists of maculse rather than papulae. If, after considering these points, the question of diagnosis cannot be clearly settled, the lapse of twenty-four hours will be sufficient to remove the uncertainty. A certain though comparatively rare form of secondary syphilis is occasionally met with in which the eruption closely simulates that of variola. This eruption passes through the stages of papule, vesicle, and pustule. It is preceded by elevation of temperature, although the rise is not as great as in variola. To differentiate between these diseases it is necessary to inquire into the history of the case and closely observe the course of the eruption. Those who are familiar with the lesions of smallpox will usually notice at once in the syphilitic patient something about the eruption which indicates that it is not variolous, yet the distinction cannot always be clearly defined until the case has made some progress. The pustules do not develop simultaneously, as in variola, but in successive crops, and are more protracted in their course. There is, perhaps, no disease more often confounded with smallpox than varicella. Of course this disease is very much milder in every particular than variola vera, and therefore liable to be mistaken only for the modified forms of the disease or varioloid. The differential diag- nosis between these diseases is postponed for consideration in the article on Varicella. Peognosis. — Since the introduction of vaccination the presence or absence of a typical vaccine scar on a patient is an important factor in the question of prognosis in smallpox. Formerly, smallpox was not only more common, but uniformly far more fatal, and therefore much more dreaded, than at present. During the last century but few diseases claimed a greater number of victims than variola, but at the present time, especially in countries where vaccination is carefully and systematically PROGXOSIS. 543 praotisc'il, the projxirtion of (U-aths tVoiu this inalady is not j^rcatei* than t\t P^'^' ^"^''it. of" the entire mortality, and where rexaeeination at the proper aiic is also entoreed this proportion is even nuieh less. In the prevaeeination pei'iod one tenth ot" all the children horn died fnmi smallpox ; now the mortality from that disease amonti' yonnt; children is almost //// where vaccination is compulsory. But after the lapse of several years the protection conferred by vaccination becomes, in most ])ersons, either partly or wholly exhausted, so that when the variolous contaiiium is introduced into a community the disease is seen in every possible urade of severity, and the death rate varies accordingly. Unmoditied smallpox is an exceedingly fatal disease, the death rate varying in different epidemics from 15 to 60 per cent. The epidemic which swept over this and other countries in the years 1870 to 1872 was everywhere characterized bv unusual malignancy, and the mortality among the unvaccinated cases was, in some places, as high as 64 per cent. In the absence of an epidemic influence, however, the disease is usually much less fatal. It is believed by some authors that the disease is more fatal at the beginning and during the maximum of an epidemic than when it is declining, but I am not sure that such is the case. Certain seasons of the year are also believed to exercise some influence over the mortality from the disease. It is probably true that a patient is less able to bear the depressing effects of confluent variola when the weather is excessively warm than when the temperature is cooler. In considering the prognosis in individual cases of variola vera there are various circumstances to be taken into account. First of all, the age of the patient is of great importance. It is comparatively rare for an infant under one year old to survive an attack of unmodified small- pox. So also at the other extreme of life the death rate is enormous. In children from one to five years of age the disease is also very fatal, but among those from five to fifteen years old the chances of recovery are rather better than in adult life. Sex has but little to do with the question of prognosis. Among women the mortality is somewhat increased on account of their liability to suffer from metrorrhagia or, when pregnant, from miscarriage or premature childbirth. The occurrence of either of these accidents or the presence of the parturient state strongly predisposes the patient to the hemorrhagic form of the disease. Among men intemperance adds very greatly to the danger. Drunkards or constant drinkers seem peculiarly prone to suffer from hemorrhagic smallpox. I have found almost every variety of the disease very fatal among bartenders. The powers of resistance against the exhausting influence of variola are often so diminished by chronic alcoholism that death results from a form of the disease from which a patient with a more healthy organism would recover. ]Mania a potu, of course, furnishes a very serious com- plication. Intemperate persons are apt to be badly nourished, and this condition is always unfavorable in smallpox. It need hardly be stated that the prognosis should be very guarded when variola occurs in a convalescent from some acute exhausting disease. AVith respect to the danger in individual cases, it is necessary to con- sider not only the type of the disease, but also the separate symptoms. During the initial stage there is no reliable symptom to indicate the 544 SMALLPOX AND VARIOLOID. gravity of the attack. Not infrequently the mildest eruption of vario- loid is preceded by a very severe febrile stage. If, however, the initial stage be very mild, it would be safe to prognosticate a moderate erup- tion. Severe lumbar pains may be present in both modified and unmodi- fied smallpox, yet if they be extremely severe there would be some reason to expect a hemorrhagic form of the disease. Having met with the initial exanthem [roseola variolosa) oftener in varioloid than in unmodified smallpox, I feel disposed to regard the presence of this rash as indicating that the true eruption will be of the modified form ; yet it must be remembered that this peculiar exanthem sometimes pre- cedes the eruption of variola vera. In estimating the danger in smallpox there is usually no better guide than the quantity and character of the eruption. As the eruption in varioloid is sparse or superficial and runs a course of short duration, this form of the disease rarely proves fatal. Discrete variola is also attended by no great danger, but confluence should always be regarded with apprehension. If the eruption be confluent on all parts of the body, the patient's condition should be looked upon as extremely perilous. In semiconfluent cases, especially when the eruption on the face is copious, the question of recovery becomes problematic. If the pustules acuminate well and are accompanied with considerable swelling, and if those on the extremities are surrounded with a crimson areola, and the patient takes nourishment freely, there is good ground for hope. If, on the other hand, the pustules on the face be flat, milky white in color, and pasty, with almost an entire absence of tumefaction, and if those on the extremities be surrounded with a dark red or livid areola, no reason- able hope of recovery can be entertained. It is also an ominous sign for evil in confluent variola to see here and there a vesicle on the face desiccating prematurely or to find some of the vesicles developing blue centres. The chief danger in confluent variola is from exhaustion. When the entire body is covered with pustules the quantity of purulent fluid gen- erated is enormous, and this amount of pus formation, together with the vast irritation and inflammation of the cutaneous integument, very seriously disturbs the vital powers of the patient. During the early period of maturation the patient's condition should be regarded as ex- tremely critical if the progress of the eruption be suddenly arrested and the swelling of the face and hands subside, leaving the skin in the spaces between the pustules pale ; if the pustules themselves shrink or collapse ; if the pulse be rapid, dicrotic, or feeble ; if the delirium and restlessness increase ; or if nourishment be refused or taken very reluc- tantly. When confluent variola runs its regular course, death seldom occurs before the end of the first week of the eruption : the greatest danger to life is found to be during the maturative stage or the second week of the eruption. The condition of the mucous membrane of the pharynx, larynx, and trachea should be regarded as only second in importance to the skin lesions in estimating the degree of danger in variola vera. If these parts become severely implicated by the variolous process, giving rise to such symptoms as a diphtheritic condition of the fauces, dysphagia, diffi- j'j:()rin/.AX/s. 545 culty of respiration, or a'dcina ol" the t;I(»ltis, the case should l)c \ icwed Avitli _i;rave apprcliciisioii. Kvcn hoarseness at an early j)erio(l ot" the niaturative stage should be looketl u})on with suspicion. Valuable information may often be gained by observing the nervous symptoms, especially at an advanced period of the disease. Great rest- lessness, insomnia, despondency, constant moaning, and grinding of the •teeth in children are unfavorable sym])toms. X^iolent and j)r()tractcd delirium, convulsions, or coma usually ])reclude all hope of I'ccovery. If, on the other hand, the state of the nervous system be traucpiil and the patient passes quiet nights, has a contented disposition, and enter- tains a confident hope of recovery, the probability of a favorable termination of the disease is greatly increased, even though the eruption be severely confluent. Even after a patient has passed safely through the perils of the regular stages of variola, his life may again be placed in jeopardy by certain complications. Fortunately, those which are most frequent — furuncles and abscesses — rarely lead to a fatal issue. The occurrence of pneumonia, pleuritis with effusion, erysipelas, or abortion should be viewed with deep concern. But the most fatal of the complications liable to arise are suppuration within the joints, septicaemia, pyaemia, empyema, and gangrene of the skin. When gangrene attacks the scrotum death, according to my experience, is inevitable. Recovery from the hemorrhagic or malignant form of variola is scarcely to be expected. Mildly hemorrhagic cases of varioloid may occasionally progress to a favorable termination. Purpuric variola invariably ends fatally, and the fatal issue is rarely delayed longer than four to five days from the earliest symptoms. Prophylaxis. — There is no prophylactic measure against smallpox of so great importance as vaccination. In .countries where this agent is carefully and systematically employed in infancy and repeated at the age of puberty epidemics of smallpox rarely if ever occur, and the deaths from that disease occupy a very low place in the mortuary tables. In view of the fact, therefore, that this very fatal and much dreaded disease may be prevented or modified and greatly limited in its spread by vaccination, it is highly important to a community that every individual should receive the benefits of this eminently protective agent. Gratuitous vaccination should be provided for the poor, and also for those who, through carelessness or indifference, would otherwise remain unprotected. Every nn vaccinated person should be looked upon as a constant menace to the health of a community, inasmuch as he is liable to contract smallpox and disseminate the contagium ; hence the accept- ance of vaccination should not be subject merely to the discretion of an individual whose judgment in regard to the matter may be warped by ignorance or prejudice, but should be made obligatory upon every citizen. But in the absence of any general statutory enactment very much can be done by local authorities to enforce vaccination by the adoption of certain restrictive measures. For example, no unvaccinated child should be permitted to attend school, public or private ; no child should be admitted into any institution for the care of children until vaccination has been performed ; no unvaccinated person should be enlisted in the army or navy or in the State militia ; and no unvac- VoL. I.— 35 646 SMALLPOX AND VARIOLOID. cinated immigrant should be permitted to land until vaccination has been properly performed. If vaccination were generally practised in infancy and repeated as circumstances required, there would be but little need of considering any other means of protection against smallpox ; but as it seems impos- sible to attain so desirable a result, it is necessary in the event of an outbreak of the disease to have recourse to other prophylactic measures. When a physician is called to a case of smallpox, his first duty is, of course, to vaccinate every member of the household in whom the opera- tion has not been recently performed ; next, he should, if possible, isolate the case. As isolation can only be accomplished with any degree of certainty by removing the patient to a special building or hospital, it follows that every city or town of considerable size should, at least in the event of an outbreak of smallpox, at once provide a well organized hospital, if none already exists, for the isolation and treatment of such cases. But if the patient must be treated at his home, every possible eifort should be made to separate him from the rest of the family : only those who are required to act as nurses should enter the infected apart- ment, and they should be protected by recent vaccination. In selecting an apartment for the patient preference should be given to the room which is most completely separated from all other parts of the house. It should be well ventilated, and, if possible, have an oj^en fireplace. All furniture which is not actually necessary for the comfort of the patients and attendants should be removed. While in attendance upon the sick the nurses should not come in contact with the other members of the family, and they should use every possible precaution in regard to cleanliness, disinfection of clothing, bedding, etc. A sheet wrung out in a strong solution of carbolic acid or, preferably, Labarraque's liquid, and suspended across the doorway, may aid in preventing the contagium from spreading to other parts of the house. During the illness of the patient the privileges of the well members of the house- hold should be restricted. They should be advised not to attend church nor public assemblages of any kind. The children, if there be any, should at once be required to leave school, and should not be readmitted until the family physician or some qualified sanitary officer certifies that the sickness has ended, that the period of incubation has passed, and that the house has been thoroughly cleansed and disinfected. Disinfection is highly important in preventing the dissemination of the variolous contagium. As the infecting principle clings to articles which have been used by the patient or which have been in the same apartment, all such articles as are worthless should at once be burned. All articles that can be laundried should be steeped for some time in some disinfecting solution, such as 2 fluidounces of chloride of zinc or 4 fluidounces of strong carbolic acid to a gallon of w^ater, and afterward boiled for half an hour. For the disinfection of woollen goods nothing is equal to superheated steam. All utensils used by the patient in eat- ing or drinking should each time be purified by boiling water. Even the secretions from the patient's mouth and nose or the excretions from his bowels should be disinfected by receiving them into a strong solu- tion of chloride of lime or some other equally powerful germ-destroying agent. riiopiiYLAXis. 547 Till' atti'iulaiits ii|)(»n the sick sIkjuIcI not bo more numerous than are actually reciuircd. Their elothiiii,^ should be made of such material as can be readily boiled and laundried. IJcibre associatinj^ with well per- sons they should take an antiseptic bath and i-hantre their entire cloth- ing. The physician also should exercise great care lest he himself might be the means of spreading the infection. He should not remain in the sick chamber longer than is necessary to make a careful examination of the ])atient ; his ])rescriptions should be written and the instructions given in another apartment. Before leaving the house he should take the precaution to wash his face and hands : the latter especially should be washed in some antiseptic solution. He should then delay visiting another patient until he has spent some time in the open air or, what is preferable, has changed his clothing. On entering the sick room he should not remove his overcoat nor even his hat ; the former should be kept buttoned up to the chin. It would, of course, be safer to use a long rubber coat or linen duster, which should be kept hanging in the open air during the intervals of his visits. The isolation of the patient should continue until all the scabs have fallen off and the skin has become quite smooth. Frequent bathing will aid in loosening the scabs, and the baths should be of an antiseptic character. Finally, the patient should not be permitted to associate with the public until his whole body has been washed w'ith some disinfecting solution, such as a 1 : 2000 solution of corrosive sublimate or a 3 per cent, solution of Labarraque's liquid. The safest way of using either of these solutions is simply to sponge the body, carefully wet the hair, and then have the patient take a bath in plain water, with the use of soap. If he then be provided with clean clothing, no one need hesitate to associate with him, although his skin may be red and his face deeply scarred. As the body of a patient who has died from smallpox is still capable of transmitting the contagium, certain precautions in regard to it are necessary. An effort should be made to disinfect the body by thor- oughly soaking it with some powerfuL disinfecting solution. There is, perhaps, nothing more reliable than chloride of lime. Six ounces of this drug to a gallon of water makes a very effective germicide. The body should be wrapped in a sheet or blanket saturated with this or some equally powerful solution before it is placed in the hermetically sealed casket, and the burial should ft»llow as speedily as possible, with- out, of course, a public funeral. From a sanitary point of view crema- tion of the corpse would be far preferable, but, unfortunately, this is for various reasons but seldom practicable. The sick chamber and every article which it contains should be thoroughly disinfected after the room has been vacated by the patient, either by his recovery or death. This may be accomplished by burning in the room 3 pounds of sulphur to every 1000 cubic feet of air space, the room having first been made as nearly air-tight as possible. The disinfecting power of the sulphur dioxide will be greatly increased by the presence of moisture. As already indicated, all muslin and linen goods should be subjected to the boiling temperature for half an hour, and then laundried. AYoollen clothing, pillows, mattresses, carpets, and all other articles which cannot be laundried should be so arranged in the 548 SMALLPOX AND VARIOLOID. room as to be thoroughly exposed to the influence of the sulphur diox- ide, or else they should be conveyed to a disinfecting plant and exposed for two hours to either dry heat or superheated steam at a temperature of 230° F. After the apartment has been disinfected and cleansed it is advisable that it should remain unoccupied for two or three weeks, when it can be regarded as perfectly safe for occupancy. Teeatment. — In considering the treatment of smallpox it should be stated, first of all, that there is as yet no drug or agent known that is capable of exerting the slightest influence over the course of the dis- ease after symptoms have once become manifested. But as scientific investigations are constantly adding to our knowledge important facts in regard to the causes of infective diseases, it is not improbable that before long we shall not only be able to recognize the specific cause of smallpox, but to antagonize its action. Until this new era arrives, how- ever, we must continue to treat the patient rather than the disease, by addressing our remedies to the symptoms as they arise throughout the various stages of the disease. During the incubation period of smallpox there are usually no symp- toms requiring treatment. The only question to be considered at this stage is. Can anything be done to prevent or modify the approaching malady? Certainly no result can be expected from the use of drugs. What can be expected from vaccination ? As the essential principles in the causation of variola and vaccinia are almost identical, it has been alleged that vaccination at this period of smallpox will hasten the vari- olous process, instead of modifying it. This view is extremely theoret- ical, and is certainly not based on experience. On the other hand, there are some who assert that hypodermic injections of vaccine lymph have produced good results. I would advise that this assertion be accepted cum grano sails. There are others, among whom may be mentioned Curschmann, who have never been able to see vaccination during the incubation stage exert any prophylactic influence whatever over the disease. My own experience is quite diflferent. I have often seen smallpox greatly modified by vaccination after infection had occurred^ and have not infrequently seen the disease prevented altogether. It is my belief that when vaccinia has advanced to the stage of the formation of the areola around the vesicle it begins to exert its prophy- lactic power against smallpox. In perfectly typical cases this stage is reached about the eighth clay. As the incubation period of variola is known to be from ten to twelve days, it is therefore quite possible for vaccinia to exert its protective influence in advance of the time when the earliest symptoms of smallpox should appear, provided that vaccination be not delayed too long after the infection has been received into the system. It may be said, in a general way, that the protection will be perfect or nearly so when the vaccine vesicle reaches the areolar stage in advance of any symptoms, and that in somewhat less advanced cases of vaccinia a modifying influence may be expected. As the modified form of vaccinia which results from revaccination is usually more rapid iu its development, protection against the approaching disease in such cases may be expected with a greater degree of certainty than in those under- going true vaccinia. In endeavoring to prevent or modify smallpox at this stage it is of TREATMENT. 549 vital iinportanco that the vacciiu- lyiiii)li ciinjloyed should he fresh and active, liovine lymph, as supplied to us on ivory points, is so often attended by failure, and, when it does succeed, its action is so slow, that dependence t'annot be placed on it in cases where vaccinia has to compete with variola. In such cases I would advise the use of humanized virus when it can be ])roi'ure(l, and es[)ecially that which has resulted from a long series of human transmissions. Tiiere is no virus nu)re reliable or more certain to give prompt results than that taken from a typical ves- icle on the eighth day. In using humanized virus it is important that several insertions should be made, as this will not only diminish the liability to failure, but, through the development of multiple vesicles, will bring the system more etfectually under the vaccine influence. During the initial stage nothing can be done to stay the progress of variola nor even to modify its course. The only thing that can be done is to endeavor to make the patient as comfortable as possible and to ameliorate special symptoms as they arise. The patient should be placed in a well ventilated bedroom in M'hich the temperature is from 68° to 70° F. A light diet and cooling drinks are most appropriate. As the fever is usually high, febrifuge mixtures, such as liquor potassii citratis or liquor ammonise acetatis, containing a little spiritiis setheris nitrosi or tinctura aconiti, may be given in suitable doses at frequent intervals. A good combination is as follows : 1^. Spiritus letheris nitrosi, Syrupi limonis, cici. fgiv ; Liquoris ammoniae acetatis, f 5v. — M. Sig. Give one to four fluidrachms, according to age, every two hours, in a little ice-water. Phenacetin also will often be found very serviceable in doses of from two to three grains, every two hours, until several doses have been taken or until there is a reduction of the temperature. When there is irrita- bility of the stomach the effervescing citrate of potassium is preferable to most other febrifuge mixtures. The swallowing of small pieces of ice is not only cooling in its effect, but is very useful when the stomach is irritable. AVhen this symptom is very distressing, as frequently hap- pens, such remedies as lime water, aromatic spirits of ammonia, subni- trate of bismuth, a little chloroform water, and the like may be used. I have found nothing more serviceable in moderating a high tempe- rature attended by a hot and dry skin than frequent sponging with cool water. At the same time, cold water, iced compresses, or the ice bag may be applied to the head. When this condition is present there need be no fear of suppressing the eruption by the use of cooling applications. At this stage the nervous symptoms frequently demand treatment. For the relief of cephalalgia and lumbar pains, which are often dis- tressing, large doses of some one of the bromide salts, caffeine, or phe- nacetin in doses of 5 or 10 grains, or, if preferred, some other analgesic of the coal tar series, may be employed. Convulsions, which are so common in children, may be relieved by warm baths or by giving in- ternally bromide of potassium or hydrate of chloral. The latter drug is especially serviceable in convulsions, but care should be taken to 550 SMALLPOX AND VARIOLOID. have it well diluted, as otherwise it will aggravate the throat symptoms. When it cannot be swallowed it should be given by the rectum. These drugs are also very useful for the relief of insomnia and restlessness, which so often demand attention. For these symptoms also Dover's powder, when the stomach is not irritable, will often act well, or hypo- dermic injections of morphine and atropine may be given with good re- sults. Care should be taken not to apply sinapisms to any part of the body for the relief of pain, as the irritation produced by them is very certain to greatly increase the eruption on that particular surface, with- out diminishing it elsewhere. After the eruption has fully appeared the remedies just described are no longer required, as the fever now remits and the nervous symp- toms usually disappear. At this stage various drugs and other agents have been recommended, and some of them from time to time highly vaunted, as useful in modifying the eruption, but all have proved un- availing. Efforts have been made to accomplish this desirable result by the internal and external use of the various antiseptic or antizymotic drugs, such as carbolic acid, sulphocarbolate of sodium, salicylic acid, salicylate of sodium, xylol, and some others ; but, while some writers strongly advocate their use, it must be said that none of these drugs have stood the test of experience. It has frequently been asserted that the exclusion of daylight from the bedroom is followed by good results. The same results, it is said, can be produced by excluding the ultra-violet rays, which have strong chemical action, by means of red window panes or by using red curtains tightly drawn around the bed. It is claimed by a recent writer that a patient thus treated will escape the stage of suppuration. I must, however, advise great skepticism in regard to this assertion. Those who are familiar with the history of smallpox will recall the fact that a similar treatment was introduced as far back as the time of Edward II. of England, whose son, it is said, was " treated for smallpox by being put into a bed surrounded with red blankets and a red counterpane, gargling his throat with mulberry wine, and sucking the red juice of pomegranates." It is perhaps unnecessary to make any further comment on this treatment than to repeat the very charitable criticism of Gregory, who said, " Let us, then, avoid the errors of our ancestors without reproaching them." When the eruption is slow in making its appearance, as sometimes happens in children with a feeble circulation and a depressed condition of system, heat should be applied and hot stimulating drinks given. A bath quite warm, followed by enveloping the patient in blankets, is often very satisfactory in its results. Convulsions in this condition are very common, and when they occur demand the free use of the remedies already mentioned. As the eruption progresses to the vesicular stage there is always considerable burning and itching of the skin. This may be relieved to some extent by oleaginous applications. When there is very much swelling, especially about the face, arms, and hands, and the burning pain is severe, there is nothing that gives so much relief as frequent applications of cold compresses or cloths wrung out in cold water and kept constantly applied. For the intense pain fre- quently experienced in the palms of the hands, tips of the fingers, and soles of the feet cold applications, even iced compresses, are also very TREATMENT. 551 serviceable, yet I liave seen rather Itcttci- results follow the use of (|iiit(' warm a|)])li('ati(>ns, such as warm hand and foot baths or hot {)()ulticcs. If these agents fail and the patient is unable to sleep, opiates may be resorted to. A little morphine or de(id(n'ized tincture of opium often acts like a charm. For the relief of the distressing symptoms resultinii- from inlhimma- tion and swelling of the mucous membrane (»f the mouth, fauces, and larynx, mouth-washes and gargles are recpiired, such, for example, as solutions of chlorate of potassium, boric acid, tincture of myrrh, glyce- role of tannin, and the like. The milder demulcent decoctions of flax- seed, gum arable, and slippery elm bark will often be found decidedly palliative. I frequently use with much advantage flaxseed tea sweet- ened with white sugar and slightly acidulated with lemon juice. Ice cold lemonade is generally relished by the patient. Great relief is some- times experienced by small pieces of ice being held in the mouth and allowed to dissolve slowly. Careful and frequent cleansing of the mouth usually affords considerable relief and enables the patient to swallow with greater ease. This may be accomplished In- the nurse covering her index finger with a soft linen rag, dipping it into acidulated water or boric acid solution, and thoroughly cleansing the entire buccal cavity. If this be followed by spraying the mouth and fauces with a weak solu- tion of cocaine, swallowing will sometimes be rendered easier in cases of dys])iiagia. The nervous symptoms are frecjuentlv so prominent during the eruptive stage as to demand treatment. Such symptoms as persistent insomnia and violent delirium are most common. Not infrequently this condition is attended by a flushed face and bounding pulse, in which case a saline purge and an ice bag to the head may be of service. Sulphate of morphine and tartar emetic, in doses of \ grain of each, repeated every two hours until a few doses have been taken, will frequently cjuiet the delirium and produce sleep. Of course some one of the bromides and hydrate of chloral are to be preferred in the larger proportion of cases. Care must be taken, however, not to use narcotics too freely, lest the patient lapse into coma or sink into collapse. When the delirium is violent or maniacal, it will be necessary to use some means of physical restraint to prevent the patient injuring himself or others, especially if he be large and muscular. Smallpox is by far most fatal during the stage of suppuration. The chief indications for treatment at this stage are to mitigate the suppura- tive fever, to disinfect the exudation from the pustules, and to oppose by every possible means the tendency to death from exhaustion. If the patient can be carried safely through this stage and the early part of the stage of desiccation, his recovery may be reasonably expected, unless some serious complication should arise. When the temperature is \evy high the ice bag should be kept on the head and sponging with cool or tepid water resumed. In warm weather the temperature of the patient may sometimes be reduced by covering him with a sheet wruno- out in cool Mater and renewing; it everv few minutes. Occasionall} cold apj^lications are not well borne, in which case tepid water may be tried. Cool immersion baths have not met with anything like the same results in variola as in typhoid fever. Some one 552 SMALLPOX AND VARIOLOID. of the antipyretics of the coal tar series will often be found useful, I have frequently used phenacetin, in doses of 2 or 3 grains every two hours until several doses have been given, with good results. When this drug, however, is discontinued the fever usually recurs, but during the short interval from intense fever the patient is often able to take a little more nourishment than he would otherwise do, and sometimes enjoys an hour or two of refreshing sleep. On account of the depressing eifect occasionally seen from the use of these drugs it is advisable to give stimulants at the same time. To allay the intolerable itching and to correct the offensive odor resulting from decomposition of the purulent material that exudes from the pustules certain local applications will be found of great service. Antiseptic Avashes may be used, such as a solution of boric acid (1 : 20), of carbolic acid (1 : 100), or of bichloride of mercury (1 : 2000). When the odor is highly offensive great benefit may be derived by keeping the patient's face, hands, and other parts of the body, if necessary, con- stantly mopped with a solution of hypochlorite of sodium. I frequently use with ad\'antage a 5 per cent, solution of Labarraque's liquid, direct- ing that not only the patient, but the bedding also, be sprayed every little while by means of an atomizer. A^arious antiseptic oleaginous preparations are also useful. There is nothing more convenient and, upon the Avhole, more serviceable than equal parts of olive oil and lime water containing a little carbolic acid or oil of eucalyj^tus. This should be applied freely three or four times a day with a large camel's hair brush. I have been using lately with considerable benefit an ointment composed of aristol 15 or 20 parts to 100 parts of vaseline. Two drachms of liquor sodse chloratse to an ounce of lard are also service- able. Likewise I have used with advantage antiseptic dusting powders, such as 15 parts of aristol to 100 parts of talc or powdered starch. It is, I think, scarcely necessary to speak at length of the various means which have been recommended from time to time for the preven- tion of pitting, for not even the highly vaunted methods when put to a critical test have been found worthy of the praise given them. To accomplish this purpose it is necessary that the pustular stage of the eruption should be either prevented or greatly modified, for the suppu- rative process is always attended by destruction of derm tissue, and any loss of this tissue is inevitably followed by scarring. After consider- able experience with many of the most highly lauded ectrotic measures, so called, I have come to the same conclusion as Gregory, that there is no peculiar method yet known for the prevention of pits and scars : "The masks and ointments formerly in use for that purpose, and so highly vaunted, are, in reality, more hurtful than beneficial." A little cold cream, vaseline, benzoated lard, or lanolin, containing some anti- septic, is all that can be recommended. As the vital powers of a patient suffering from confluent variola are severely taxed during the stage of suppuration, it is important that a supporting plan of treatment should be adopted. This is quite obvious when we consider how great the quantity of purulent material generated must be. Watson has estimated that it amounts to quarts. Besides this excessive strain upon the system, the vast irritation resulting from inflammation of almost the entire cutaneous integument is very exhaust- TREATMENT. 553 ing ill its effects, being comparable only t(j that w liidi results from an extensive burn. The first evidence of flagging of the vital forces is usually a sudden subsidence of the swelling and redness of the face and hands, causing the skin to become ])ale and the juistules to shrink or present a collapsed ai)pearaiK'e. If this condition continues, the ])ulse becomes rapid and feeble, the tongue i)ro\vn and dry, and subsultus tendinuni, general tremors, and delirium rapidly supervene. It is ad- visable to anticipate these symptoms by the early employment of sup- porting measures. AVheii maturation of the pustules begins the patient should receive a liberal amount of nutrients and stimulants. Milk, pei)toiiizcd if necessary, should be given at frequent intervals, I usu- ally insist that an adult })atient suticring from a severe form of variola shall receive during each twenty four hours from 2 to 3 quarts of un- skimmed milk, 2 to 3 raw eggs, and 6 to 12 ounces of good whiskey, the latter being given in the form of milk punch. The eggs may be well beaten and drank with the milk or they may be given in the form of eggnog. It is important that these supporting agents should lie faith- fully continued during the night as well as the day, for when prostra- tion is extreme the tendency to sink into collapse seems greatest be- tween midnight and morning. AVhen milk and whiskey cannot be taken in sufficient quantity, or when there is great repugnance to these articles, bouillon with eggs, a well prepared beef tea, nutritious broths, and a liberal amount of wine may be given instead. As a stimulant in cases of profound prostration Curschmann esteems very highly the Stokes cognac mixture, prepared as follows : E.. Cognac optimi, Aquse destillatse, da. f^xv ; Vitelli ovi, Xo. i., Syrupi, f^5vj. — M. Sig. Give a tablespoonful at frequent intervals. Usually but few drugs are required at this stage of the disease. The less the stomach is taxed with the ingestion of drugs, and the more com- pletely its labor is limited to the important function of sustaining the vital forces and the nutrition of the body, the greater ■s\-ill be the chances of recovery. If the bowels should be confined, rather than give purga- tives, enemas should be used. Sulphate of quinine is usually serviceable in tonic doses. "When the heart action is weak, sulphate of strychnine and digitalis will be found most useful. Carbonate of ammonium is also useful in eases of threatened cardiac failure. In case of great restless- ness and insomnia narcotics may be cautiously given hypodermically or by the rectmn. The occurrence of diarrhoea should receive prompt attention. In cases of varioloid usually very little treatment is required after the initial stage has passed, as this form of the disease rarely ends fatally. On the other hand, hemorrhagic variola almost always termi- nates fatally in spite of the best treatment. The drugs usually employed are the mineral acids, ergot or ergotin, sulphate of quinine, and tinc- ture of the chloride of iron, together with the external use of styptics and cold compresses ; but these agents are recommended, I regret to say, 554 SMALLPOX AND VARIOLOID. more in conformity with general usage than with any expectation of effecting a cure. Transfusion has also been tried, but the results have not been encouraging. The various complications liable to arise should be treated on general principles, according to their nature and the indications presented. Fu- runcles and abscesses should be opened as soon as they form, and the latter especially should receive antiseptic treatment. An effort should be made to prevent the occurrence of the serious forms of eye compli- cations by washing from the conjunctiva all purulent material as fast as it forms. This may be accomplished by carefully injecting under the lids a solution of boric acid (10 or 15 grains to an ounce of water), using a small syringe or dropper. The eyes should be carefully watched, and when a corneal ulcer appears it should at first be treated by the appli- cation of cold compresses. Besides thorough cleansing a solution of 10 to 15 grains of boric acid and 2 to 4 grains of atropine to an ounce of distilled water should be instilled into the eye once or twice daily. I have occasionally touched the ulcers very delicately with a stick of nitrate of silver brought to a fine point, as recommended by some authors, but with no decided benefit. Indeed, in spite of treatment, the ulcerative process too often continues until the ^^sion is entirely destroyed. Convalescence from smallpox may be hastened by tonics and a liberal diet. The compound tincture of cinchona is useful at times to increase the appetite, although, as a rule, convalescents eat heartily. In cases of great emaciation and exhaustion iron, cod liver oil, and the malt liquors are very useful. If there should be a constant occurrence of boils or a furuncular diathesis, some benefit may be derived from the administration of Fowler's solution or sulphide of calcium. The sepa- ration of the scabs may be hastened by the free use of glycerin or cos- moline and warm baths. If warty nodules remain on the face after the scabs have fallen off, their removal may be hastened by touching them once or twice daily with tincture of iodine. VACCINIA. By WILLIAM M. WELCH, M. D. Synonyms. — Latin, Vaccinia or Variolse vaccinae (Jenncr) ; English, Cowpox or Kinepox ; French, Vaccine ; German, Kuhpocken, Impf- pocken, or Schutzblattern ; Italian, Vaccina ; Spanish, Vacuna. Definition, — Vaccinia is a disease communicable only bv inocula- tion, and is characterized by one or more skin lesions, according to the number of insertions of the specific virus, running through the stages of papulation, vesiculation, and pustulation, ending in desiccation and falling of the crusts at the end of the third week. The process is attended by very little if any febrile reaction, and, when completed, confers immunity against smallpox. History. — Toward the middle of the eighteenth century an impres- sion arose among the common people employed in the dairies of England that a certain disease of cows known as cowpox would, when accidentally communicated to the milkers, afford them protection against smallpox. This belief gradually increased until, at length, in 1774, a Gloucester- shire farmer, named Benjamin Jesty, became so fully convinced of the prophylactic power of cowpox that he ventured to inoculate his wife and two sons with, presumably, some of the virus from the teats of a cow suf- fering from the disease. But the subject received no scientific considera- tion until it attracted the attention of Edward Jenner, a country physician of Berkeley, England, Avhere dairy farms were numerous. When he was yet a medical student, Jenner's interest was elicited in the matter by hearing a countrywoman remark that she could not take smallpox because she had been infected with cowpox. Later, when a practitioner of medicine, he took great pains to inquire into the facts upon which this tradition was founded, and he soon became convinced that there was a reality about it ; but, setting a good example to all investigators, he continued his researches for several years, and xilemonstrated most conclusively the value of his discovery before publishing hi^; observa- tions to the world. The first practical demonstration of the new inoculation, as it was called, was made by Jenner, May 14, 1796, in a peasant lad named James Phipps, aged eight years, whom he inoculated with virus taken from a vesicle on the hand of a dairymaid, who had been accidentally infected by milking a cow affected with cowpox. Wishing to test the protective efficacy of the vaccine disease, Jenner tried, on the first day of July following, to give this lad smallpox by inoculating him with variolous matter, but failed. He repeated the test several months later with the same negative result. After continuing his investigations for two years longer, and accumulating a mass of evidence that was simply 556 VACCINIA. incontrovertible, Jenner published, in London, June, 1798, his observa- tions in a paper entitled " An Inquiry into the Causes and Effects of the Variolse Vaccinae, etc." It must not be supposed that the great and important truth promul- gated in this paper was accepted without opposition. On the contrary, it was doubted by some and ridiculed by others. Some, indeed, carried their opposition so far as to attack the honesty and veracity of Jenner. Still others, even more bitter in their opposition, caricatured the effect of the inoculation by representing man transformed into a horrid monster presenting some of the characteristics of both man and the bovine animal. But the force of Jenner's facts was such that, in spite of this detraction, it was not long until his discovery was known and welcomed in every civilized country in the world, and the experience of a century affords a most complete confirmation of all that was claimed for it by its dis- coverer. The new inoculation was introduced into America by Benjamin Waterhouse, the first professor of the theory and practice of medicine in Harvard College. The first person subjected to its influence was his eldest son, aged five years. This occurred July 8, 1800. Observing that the vaccinia in this child passed through the regular course, as described by Jenner, he took virus from this case and with it inoculated the rest of his children. After the vaccine disease had run its course, he proceeded to test its efficacy against smallpox by taking his children into the smallpox hospital and exposing them freely to the contagium of that disease. Finding they resisted the contagium in the natural way, he had them inoculated with variolous matter. This also failed to pro- duce the disease. He then very truly remarked, " One fact, in such cases, is worth a thousand arguments." It is instructive to add that Waterhouse was greatly aided in his work of introducing the new inoculation in this country by Thomas Jefferson, then President of the United States. It was largely through his efforts that the virus of vaccinia was speedily disseminated throughout the Southern and some parts of the Middle States. As the result of Jenner's discovery the spread of smallpox has everywhere been greatly controlled and the mortality from that disease enormously diminished. In England and Wales, where the registration records are perhaps more complete than in most countries, it was found that before the introduction of vaccination the annual mortality from smallpox was at the rate of 3000 deaths in every million of the popu- lation. Since the adoption of this protective measure the ratio of deaths to the population from that disease has constantly diminished. Accord- ing to Moore,^ only 15 deaths Avere caused by smallpox in England during the year 1890. While this, undoubtedly, is an unusually small number, yet during the ten years from 1881 to 1890, inclusive, the average annual rate of mortality from that disease was only one seven- tieth part of what it was during the pre-vaccination period. Further- more, it has been found that where vaccination in infancy has been carefully and systematically practised, as in Germany, for example, the mortality from smallpox among children, instead of being enormous, as formerly, has become almost nil. ^ Text-Book of the Eruptive and Continued Fevers. ETIOLOGY. 557 Tlu' protection oonforrocl by vaccinia has not only greatly diniinishod the iiuinhcr of cases ot" sinall])ox, l)Ut has very consiiU'rahly reduced i\\v death rati" anionu' those attacked. Moore' oives statistics which show that in Shettiehl, thn-in*^- tlie outbreak of 1887-}S)S, of 4151 vacci- nated patients 200 died, a death rate of 4.8 per cent. ; while of 552 unvaccinated patients, 274 died, a death rate of 4f».(j per cent. A report bv Grinishaw of Dublin on the unusually widespread and malig- nant epidemic of smallpox which occurred in 1871-72 shows the com- parative death rate in sevi'ral hospitals aniono- the vaccinated and un- vaccinated patients to have been as follows : In Cork Street Her cent., three sears 1.75 per cent., four or more scars 0.75 per cent. Among those presenting uniformly typical scars the death rate was still less. The writer's experience on this point does not en- tirelv agree Avith that of Marson's, as mav be seen in the preceding table. According to the writer's experience, the qualitij of vaccine scars is a far more reliable indication of the degree of protection than the guan- titij. The table shows that when the scars are typical it makes no dif- ference whether they are single or multiple, the protection being practi- cally the same. There is no doubt that vaccinia characterized bv a single typical vesicle confers immiuiity against smallpox ; it is impossible for multiple vesicles to do more. However, as a safeguard against failure when the danger of variolous infection is imminent, it is advisable in vaccinating to make more than one insertion. The age at which it is proper to vaccinate a child is a matter of some importance. Unless some circumstance should arise requiring vaccina- tion t<;> be done earlier, it is advisable to defer the operation until the child is three months old. The most suitable age is from three to six months. It is not well to postpone the operation longer, else the systemic dis- turbances arising from teething may be added to the irritation from the vaccination, and thus increase the discomfort of the child. But where there is actual danger of exposure to the contagium of smallpox, denti- tion should not interfere with vaccination, nor should a newborn infant be considered too young to undergo the operation. Reyaccination. — Experience has demonstrated the fact that in a certain number of persons the protection from vaccinia in infancy is permanent, while in others it gradually diminishes, and after the lapse of a number of years frequently disappears entirely. This fact has been determined by noting the large number of persons in adolescent and adult life Avho are susceptible of revaccination ; also by observing that in all epidemics of smallpox a large proportion of the cases occur among persons who were vaccinated in infantile life. The statistics of smallpox hospitals in this country and in England show that from 41 to 78 per cent, of the admissions are post-vaccinal cases. It is very difficult to determine the proportion of persons vaccinated in infancy that fail of permanent protection, but it is believed to be not far from 75 per cent. Some years ago a very careful observation in a certain American city showed that of 2362 persons revaccinated with reliable virus (no child under twelve years old with a good scar being in- cluded in this number), 77.1 per cent, were susceptible to some form of vaccinia. AVe have no means of ascertaining the age or period of life at which the protection from vaccinia in infancy is liable to diminish or cease entirely, except by applying the test of revaccination or by noting at 566 VACCINIA. what age after primary vaccination any considerable nnraber of persons suifer from smallpox. Data tending to demonstrate the latter may be found in the following table : Under one year. One to seven years. Seven to four- teen years. Fourteen years and upward. Unvaccinated Vaccinated j Unvaccinated Vaccinated in infancy — good scars " " fair scars . " " poor scars Total number vaccinated . Unvaccinated Vaccinated in infancy — good scars " " fair scars . " " poor scars Total number vaccinated . Unvaccinated Vaccinated in infancy — good scars " " fair scars . ," ' " poor scars Total number vaccinated . Cases. Deaths. Percentage of deaths. 89 2 60 67.41 467 221 47.32 11 10 15 36 242 1 1 10. 6.66 2 5.55 72 29.75 55 23 59 2 2 9 3.63 8.69 15.25 137 1111 13 9.48 693 122 96 286 62.37 1406 664 1027 8.67 14.45 27.84 3097 504 16.27 Among the 5321 cases of smallpox admitted to the Municipal Hos- pital of Philadelphia since the institution has been under the writer's care, now exactly twenty five years, only two vaccinated patients under one year old were admitted. One of these was a child eleven months old who had been vaccinated two months previously and showed a good scar. The eruption consisted of only six small vesicles, and the child's health was scarcely disturbed. The other patient had the disease so indistinctly marked that it was almost impossible to feel certain of the diagnosis of varioloid. An exceedingly modified form of smallpox was occasionally seen among well vaccinated children between tlie ages of one and seven years, but no deaths occurred except when there was a serious complication. The child that died, whose case is classified under the head of "fair scars," was a foundling about a year old, badly nourished and very feeble, wdth a disordered digestion. The eruption consisted of only a very few small vesicles. Death really resulted from inanition. Very little need be said of the cases classified in this age-period under the head of " poor scars," as the vaccination in them had been in good part either imperfect or spurious. Between the ages of seven and fourteen years it is found that the post- vaccinal cases increased considerably, and occasionally death occurred, even when the infantile vaccination was quite thorough. At fourteen years of age, or the period of puberty, and thereafter, the protection is apt to diminish, and often disappears entirely. These facts lead to the con- clusion that when there is danger of exposure to smallpox all vaccinated children who have reached the age of seven years should be revaccinated : also that re vaccination should be practised systematically at the age of puberty whether smallpox be present or not. When the primary vac- cination is not done until the child is seven or eight years old, the pro- REVA C( 'fX. I TfON. 567 toction is more likely to he penuaneiit ; still, it is advisable to sui)je<'t sueh cliildreii to the test of revaceinatioii at tlu; period of life just mentioned. The writer believes that it may be laid down as a rule that if a ehild l)e successfidly vaccinated in infancy, and auain at the atic of puberty, the protection will be permanent. The exceptions to this rule, however, niav be sufficient to warrant a repetition of the vaccination whenever there is great danger of variolous infection. The question is often asked, What constitutes a successful revaccinij- tion ? This is a question about which there is some diversity of opinion. Many believe that unless the vesicle and areola observe the coui-se of true vaccinia the effect is merely local and devoid of prophylactic power. But it is evident on a little reflection that th(>re is no more reason why we should expect the vaccine disease produced by revaccina- tion to be typical than that we should expect smallpox after vaccina- tion to run the typical course of variola vera. If there be modified smallpox or varioloid after vaccination, so should there be modified vaccinia or vaccinoid. From these premises the conclusion may be deduced that as varioloid confers immunity against a recurrence of smallpox, so also does the modified form of vaccinia resulting from revaccination remove from the individual whatever suscei)tibility to the disease may be present. As to the value of revaccination there can be no question. Bousquet savs very truly that there never has been an epidemic of smallpox since the general employment of Jenner's discovery which has not proved the virtues both of vaccination and revaccination. He adds : " The success of revaccination is at the same time the effect and proof of the wants ■ of the system ; . . . . when it succeeds, it not only proves that the protective power of vaccination is diminished, but it supplies a remedy for this diminution." Among the earliest and most conclusive proofs of the value of revaccination are the statistics furnished by the AViirtem- berg, Bavarian, and especially the Prussian armies. Of 14,284 revac- cinated soldiers in AViirtemberg, only 1 case of smallpox occurred in five years; and only 3 among 26,964 revaccinated civilians. During three^ severe epidemics in Copenhagen not a single case of varioloid occurred among persons who had been revaccinated. Also, during a very malignant epidemic which a number of years ago nearly decimated Li^ge it is said that none of those who underwent revaccination suffered from the disease. Perhaps the mos! conclusive proof of all is that found in the statis- tics of smallpox hospitals. After an experience of thirty years in the hospital of London, Marson stated that but few patients were admitted during that time who had been revaccinated with effect, and that these suffered from varioloid in a very mild form. During this long service it was his custom to revaccinate all the nurses and sei'vants who had not had smallpox on their coming to live at the hospital, and not one of these contracted the disease. At a time, however, when a large number of w^orkmen were employed about the hospital most of them consented to be revaccinated, but there were a few that declined ; of the latter two took smallpox, while of the former all escaped. During the writer's experience of twenty-five years no resident physician, nurse, nor any other employe of the Municipal Hospital of Philadelphia who had 568 VAOCimA. been revaccinated before commencing duty has suffered from small- pox. Perhaps an exception should be made in the case of a female nurse who was revaccinated on the day of commencing work, and in whom the vaccine disease was almost typical. In the course of about two weeks one or two variolous vesicles appeared on her forehead near the edge of her hair. Preceding this symptom there had been very slight febrile reaction for a day or two, but she was at no time incapaci- tated from performing her usual duties. As the limits of this article will not permit of a more extended resume of the evidence in support of revaccination, the writer must conclude, believing that the testimony in its favor already adduced is too strong to admit of its neglect. In view of all the accumulated facts in favor of vaccinal protection, it does not seem entirely visionary to assume that if vaccination were efficiently performed in infancy and systematically repeated at the age of puberty, if not earlier, Jenner's so called dream — that vaccination is capable of extirpating smallpox from the earth — would verily become a realization. But whether this agent will ever be so universally and wisely employed as to confer on mankind its greatest possible benefit is doubtful. VARICELLA. Bv WILLIAM .M. WELCH, M. D. Synonyms. — English, Chickenpox, Waterpock, or Glasspock ; Ger- man. AVasserpoc'ken, Windblattern, or Schafpocken ; Frencli, La Yero- lette nr Verricelle ; Latin, Yarioki notha .-^eu spuria ; Italian, Rava- glione. Definition. — Varicella is a contagious eruptive disease, occurring chiefly in childhood, characterized by slight fever of short duration, and rapidly developing vesicles which begin to desiccate on the fourth or fifth day, leaving occasionally persistent scars. HiSTOKY. — Xo clear or exact description of varicella appears to have been given by writers previously to the seventeenth century, although the disease was evidently known before that time. Rhazes described a mild eruptive affection resembling smallpox, but which gave no protection against that disease. This affection was doubtless vari- cella. The first accurate description of the eruption of varicella was given by Riverius in 1646. Still later in the same century Morton also called attention to the disease, and stated that it was vulgarly called chickenpox in England. But these and other authors of that period, while recognizing something peculiar about this affection, regarded it as an exceedingly mild form of smallpox. The credit of first calling attention to the fact that variola and varicella are different diseases, each resulting from a distinct contagium, belongs to Heberden of Eng- land. His classic paper on this subject was published in 1767 in the first volume of the Transactions of the Koyal College of Physicians of London, and was long regarded as the standard work on varicella. Although Heberden believed in the specific nature of this malady, yet he called it varioke pusUke. The term varicella did not come into general use until after 1770, when universal attention was directed to the disease ; but, strange to say, it was not until the early part of the present century that the individuality of varicella was generally recog- nized. In 1820, however, Thomson of Edinburgh, and still later Hebra, the celebrated professor of dermatology in the Vienna L^niversity, re- vived the exploded doctrine of its identity with smallpox. But not- withstanding the great Meight of Hebra's authority- and the persistency with Mhich he advocated this doctrine, he has not succeeded in creat- ing doubt in the minds of any considerable number of clinicians and authors. Nothing, indeed, is easier than to prove that his teaching in regard to the relation of these diseases is erroneous. Etiology. — Varicella is a disease almost peculiar to early childhood. The vast majority of cases occur between the ages of one and ten years. L^nlike measles and scarlet fever, but quite similar to variola, chicken- 569 570 VARICELLA. pox not infrequently attacks infants at the breast under six months of age. Some authors believe that the susceptibility to the disease dimin- ishes after the tenth year and ceases entirely after puberty. Thomas of Leipzig thinks that this may be the correct explanation of the very infrequent occurrence of the disease among older children and adults. He says he never saw an adult suffer from varicella. There is no doubt, however, that the disease is by no means uncommon among persons in mature life. This fact is amply attested by the experience of those who are connected with hospitals for infectious diseases. Attacks in adult life would doubtless be far more frequent were it not that in the vast majority of persons the susceptibility is destroyed by the occurrence of the disease in early childhood. The aifection rarely if ever occurs more than once in the same individual. I believe I have never known a person to suffer from a second attack of varicella. Trousseau, however, says that second attacks are not uncommon. Like all acute exanthemata, varicella at times appears sporadically, and then again it prevails in epidemic form. It is hardly ever entirely absent in large cities. The seasons do not influence its prevalence, ex- cept that the opening of kindergartens and schools in the fall of the year often marks the beginning of moderate epidemics. The epidemics never assume the proportion or intensity of those of variola and scarlet fever, but are frequently so mild as scarcely to attract the attention of physicians. While smallpox is often absent in a community for several years at a time, at least where vaccination is carefully and systematically performed, varicella is met with annually, especially in thickly populated districts. Unlike smallpox, its spread is not limited by vaccination. The cause of varicella is a peculiar contagium. It must be admitted that nothing definite is known in regard to the nature of the specific virus, but there is no doubt that it owes its specificity to a micro-organ- ism. The infecting agent enters the system doubtless through the re- spiratory tract. From what is known of variola, one would suppose that the infecting principle of varicella should be present in the vesi- cles, yet it is questionable whether the disease has ever been communi- cated by inoculation. While a very few positive results have been reported by Hesse and Steiner, negative results have followed the very careful attempts at inoculation by such men as Heim, Vetter, Czakert, Fleischmann, Thomas, and Boyce of Europe, and J. Lewis Smith of this country. The period of incubation in varicella is perhaps more variable than in the other exanthemata. AVhile it is often difficult to fix exactly the time when the contagium enters the system in any given case, yet it has been found that when the disease breaks out in a private family or an institution for children the time that elapses between the appearance of the eruption in the first and second cases is usually from thirteen to seventeen days. This may therefore be regarded as about the usual period of incubation, although a much shorter period has been reported by some observers. It is evident from these considerations that there is a wide difference etiologically between varicella and variola — so wide, indeed, as to afford of itself conclusive proof that the diseases are essentially different. Most conclusive in favor of this opinion are the facts that varicella /'. I TlIOLOaiCAL A SA TOMY. 571 of't(Mi ])i'ovails ill ('oiuinuiiitics wlioiv variola is absent ; that the con- ta*iiiun of varicella never ^ives rise to variola in the nnproteeted, l)nt always to a disease presentinu; the same eharactcristics as the original atteotion ; that an attack of varicella confers no protection aofainst snialli)ox, nor vice vcrxCi ; that varicella occurs with identical synij)tonis and equal facility amoni>- the vaccinated and unvaccinated ; and that vac- cination, however recent and thorouuh, does not destrov the susce])ti- bilitv to varicella. Patiiologk'AL Anatomy. — The only pathological condition ])resent in varicella is that which results from the peculiar exanthem. The lesions a]^pear on almost every part of the body, and consist of vesicles varv- ino- ill si/e from that of a millet seed to a silver dime. They develop rapidly upon hyperjomic spots, which are but slightly if at all infil- trated. The deeper layers of the derm ai'c usually not involved, dilfer- ing in this respect from the lesions of variola. The vesicles begin to form in the centres of the hypersemic spots and grow by peripheral extension until their full size is attained. They are usually surrounded by an areola which is frequently quite broad. It is rare that the initial hyjiememia is present longer than a few hours before the vesicles liegin to form. Undoubtedly the lesions are exudative in character. As the exuda- tion of serum takes place in these morbid areas the superficial epi- dermic layer is raised from the deeper layers of the derm, and thus a distinct vesicle is formed. Varicella not being a fatal disease, opportu- nities for carefully investigating the anatomical structure of the vesicle, as displayed in sections, do not occur. There is reason to believe, ho^v- ever, that the vesicle is not originally a single cell, but contains delicate septa dividing it into compartments. These septa or partition walls not infrequently give way at an early stage of the exudative process, per- mitting the contents of the vesicle to run partly or wholly together. Owing, doubtless, to the superficial character of the vesicles and the rapidity and profuseness of the exudation, the umbilication so common in variola never occurs. The vesicles at first contain a serous fluid as clear as water. Later, owing to the slight admixture of pus cells, this fluid assumes an opales- cent or whey-like appearance. In those vesicles which run a more pro- tracted course the proportion of pus cells is greater, but not so great as in the pustules of variola. The contents are usually slightly alkaline in reaction. The duration of the vast majority of the vesicles is brief. Either from partial absorption of their contents or some mechanical cause, such as rubbing or scratching, the vesicles collapse, and desicca- tion begins when the process has not continued longer than two or three days. In the undisturbed vesicles desiccation usually commences in their centres, giving rise to a depression that is sometimes mistaken for umbilication. In the milder cases the scabs, which are small, fall off quickly, and are not followed by scars. But when the course of the vesicles is ])rolonged there is sometimes destruction of the lower layers of the derm, and permanent scars result. The number of scars from an attack of varicella, however, is never very large. The mucous membrane of the mouth and fauces suffers only very moderately from the eruptive process. 672 VARICELLA. Symptoms. — The stage of incubation of varicella is seldom attended by symptoms. In the majority of cases the first symptom noticed is the appearance of the vesicles. This is not only the testimony of care- ful and observing mothers, but has been confirmed by medical observa- tion iji institutions where opportunities have been afforded to witness outbreaks of the disease. Occasionally, however, there may be seen a short initial or precursory stage of not more than a few hours' dura- tion ; but even in such cases the febrile reaction is usually insignificant, as the temperature is not apt to rise higher than one or two degrees above the normal point. Exceptional cases sometimes occur among children in whom the onset of the disease is marked by slight rigors, considerable elevation of temperature, moderate headache, and vomit- ing. I have reason to believe from my experience that such a pre- cursory stage is not uncommon in adults. If a case of varicella be carefully examined at the very earliest stage of the eruption, the skin lesions will be found to consist of small roseo- lar spots. According to some writers, these spots appear first on the hairy scalp, face, and neck, but not infrequently they may be seen quite as early, or even earlier, on the trunk and extremities. A very favorite locality is the back. They are of the nature of maculae rather than papulae, and hence do not convey to the sense of touch the feeling of denseness or firmness, as do the papulae of variola. In the course of a very few hours distinct vesicles appear in the centres of these reddish puncta or rose-colored spots. These vesicles at first contain perfectly clear serum, and do not look unlike small blisters resulting from a moderate sprinkling of the skin with boiling water. Fig. 48. Varicella on the fifth day of eruption. AVhile the contents of the vesicles at first is perfectly clear or trans- parent, it very soon assumes a turbid or milky appearance from the admixture of pus cells ; but it never becomes so distinctly purulent as in variola. The vesicles vary very greatly in size. The average size IS that of a split pea, though some of them become as large as a silver dime, or even much larger, while others remain as small as lentil seed. They do not all appear at once, but come out in successive crops. That is to say, soon after the first vesicles have appeared there may be seen on the skin faint red points which rapidly develop into vesicles, and COMI'L U 'A TIOSS. 573 SO, a^'iiin, rt).sc'(.)la iiiul \cr-iclr.- appear hilwecu i\\vscd and are drying, and still others remain distended by sero-j)uridcnt Huid. The vesicles are either acuminate or ol(>])ular in form. They never assume that peculiar form of umbilication which is so characteristic of the eruption of variola. It is true when the vesicles are fully developed very many have a dc])ression in tlieir centres, but this depression is the result of commencing- desiccation, rather than that their epidermic cover- ing is held down by sweat glands or their follicles, as in variola. The vesicles, as already stated, usually run a very rapid C(jurse. Within a day or two after they are first seen many of the vesicles will be found to have grown flaccid, either from partial absorptif»n of their contents or rupture of their epidermic covering, and when in this con- dition they speedily dry up and disappear, sometimes without the for- mation of scabs. In those M'hich do not disappear in this way desicca- tion begins usually in their centres. Even Avhen desiccation has thus begun it is not unusual for several of the vesicles to continue to enlarge by peripheral extension until they attain the circumference of a silver dime, and, in some cases, that of a silver quarter dollar. Tliese larger vesicles usually reach their utmost limit of development M-ithiil a period of four or five days, then begin to fade, but the scabs which form are often so firmly attached that they do not fall oif spontaneously before the end of the second week. After the scabs have fallen there commonly remains upon the site of the vesicles slight pigmentation of the skin, but this, in most eases, gradually fades away without leaving permanent scars. It is only in those vesicles which run a protracted course and are accompanied by ulcerative action that scar formation results. There- fore, when scars result at all they are few and scattered ; never do they follow so large a proportion of the vesicles of varicella as they do pus- tules of variola. The mucous membrane is only very moderately attacked in varicella. Small and ill-defined vesicles may be seen on the soft and hai'd palate, the tongue, the mucous membrane of the buccal cavity and of the nares. When they occur in these parts they are always sparse, and rarely extend to the larynx and trachea. They sometimes appear on the mucous membrane of the external genitalia of girls or on the prepuce of boys, and make urination painful. I have never known the vesicles to appear on the conjunctiva; occasionally, however, they may be seen on the margin of the eyelids and slightly affect the con- junctiva at its continuity with the skin. Complications. — Complications rarely occur, and sequelse are quite unknown. A peculiar form of gangrene of the skin has been met with, especially in Ireland. Dr. Whitley Stokes of Dublin described this affection in 1807, and applied to it the name pemphigus gangrcpnosus. It has also been described by various other writers as dermatitis gcin- gnenosa. More recently (in 1881) Mr. Jonathan Hutchinson called attention to this dangerous, though fortunately rare, complication, and proposed for it the name varicella gangrenosa. It is not im- 574 VARICELLA. probable that this malady is met with only in children having a tendency to the development of so called spontaneous gangrene. It is said to occur more frequently among weakly and ill nourished children, though it is not confined to them. A very clear descrip- tion of the disease has been given by Dr. Eustace Smith. He says : ^ " In gangrenous varicella the vesicles, instead of drying up in the ordinary way, become black and get larger, so that a number of rounded black scabs, with a diameter of half an inch to an inch, are scattered over the surface of the body. If a scab be removed, it is seen to cover a deep ulcer. Around it the skin is of a dusky red color. All the vesicles do not take on the gangrenous action, so that we find many varicellous scabs' of ordinary appearance mixed up with the blackened crusts. The gangrenous process often penetrates deeply through the skin to the muscles, but under some of the scabs the ulceration is more shallow. These cases are very fatal. Mr. Warrington Haward has reported the case of a weakly baby twelve months old who weighed onlv six pounds and a half. The child was attacked with gangrenous varicella and died in a few days of pyaemia, with secondary abscesses in the lungs." Cases have also been reported in which gangrene attacked the scrotum, and proved almost as destructive to that tissue and as fatal to the patient as when the same complication occurs in variola. Diagnosis. — Eczema pustulosum and impetigo contagiosa have been thought l)y some to resemble varicella, but the points of resemblance are so slight as rarely to introduce into the question of diagnosis an element of confusion. The only disease with which varicella is liable to be confounded is smallpox in some of its varieties. There is usually no difficulty in diiferentiating between variola vera and varicella, but between the latter disease and certain forms of vario- loid the difficulty is often very great and mistakes are not uncommon. The teaching of most authors that varicella is a disease peculiar to childhood is, I think, responsible for many errors of diagnosis, inas- much as it tends' to create a belief that in adults eruptions resembling varicella always indicate smallpox. It should be borne in mind that the former disease is by no means infrequent in adolescence or in adult life. It ^vill often prove helpful to know whether or not the patient has ever been vaccinated. When a vesicular eruption suddenly appears in a child who has recently been successfully vaccinated, variola can be excluded from the question of diagnosis with a considerable degree of certainty. So also variola can be reasonably excluded when such an eruption appears in an unvaccinated child without having been preceded by severe constitutional symptoms, such as are peculiar to the initial stage of that disease. In children, however, older than ten years, and also in adults who have been vaccinated in infancy, the variolous erup- tion is often so greatly modified as to bear considerable resemblance to the lesions of varicella. It is this class of cases, in which the eruption shows no distinct characteristics, that not unfrequently taxes to the utmost the skill of the diagnostician. Although difficult, it is im- portant that a correct diagnosis should be made, since in the one case the contagium generated is usually innocent, while in the other it is fre- 1 Eustace Smith, Diseases of Children, 1884, p. 49. DT A GNOSIS. 575 qiientlv disnstrous in its results. Wlicii, howovcr, a history of exposure to either <>t' these eontagia can l)e obtained, the diagnosis becomes, of course, e(iiii])ai"atively easy. In dilVerentiatinu- between variohi and varieelhi it is very important to note the behavior of the fever. In the former the temperature suddenly rises, after a decided chill or repeated ri<;ors, to a considerable elevation. It not infrequently rises during the first twenty-four hours of the illness to 105° F., and continues high four or five days or until the eruj)tion has fully appeared. In varicella the temperature rarely or never rises so high, and no elevation is usually noticed at all until the vesicles have appeared. Even in modified smallpox or varioloid the temperature is apt to be high at first, and this symptom almost always precedes the eruption from two to four days. There is no secondary or suppurative fever in varicella, as in variola. It is true that in mild cases of varioloid, which variety of smallpox varicella more closely re- sembles, there is likewise no secondary rise of temperature ; hence other points of differentiation must be considered in such cases. It frequently happens in smallpox, especially in the modified forms of the disease, as well as in varicella, that no reliable history of initial fever can be obtained, so that in very many cases the diagnosis must be made from the appearance of the exanthem alone. It is therefore im- portant to bear in mind that the exanthem of varicella appears at first in the form of distinct vesicles containing clear serum ; that they are usually seen first in greatest number on portions of the body covered by clothing, especially on the back ; that they make their appearance in successive crops, and vary ver}' greatly in size ; that their epidermic covering is delicate, and can be easily broken by the finger nail ; that manv of them enlarge by peripheral extension, while desiccation is seen in their centres, causing a central depression ; that they run their course in two to four days, and form thin, brown scabs ; and that but few of them are follow^ed by permanent scars. On the other hand, the exanthem of smallpox first appears in the form of papulae, which are slowly trans- formed into vesicles, and then into pustules ; the papulae are dense and hard, and, to the sense of touch, seem like grains of sand buried in the cutis ; the eruption prefers the exposed surface of the body, such as the face, arms, and hands, being often only sparsely seen on the trunk ; the lesions usually begin on the face and are slow in spreading over the body, but they never come out in successive crops ; the vesicles are dense and firm, especially on the exposed surface of the skin, and can- not be readily obliterated by the finger nail ; they do not vary so greatly in size as in varicella ; they are umbilicated by their epider- mic covering being slightly drawn inward, rather than by desiccation commencing in their centres ; the exanthem requires from six to twelve days to pass through its various stages, and ends by the formation of comparatively thick, dark crusts ; and most of the lesions, especially those on the face and hands, are followed by permanent scars. AVhile the s%Tnptoms just enumerated are peculiar, respectively, to chickenpox and smallpox, and while there should be no difficulty in diagnosticating any case in which either series of symptoms is complete, yet it must be admitted that there are intermediate cases in which the symptoms are so at\q)ical that they cannot be readily assigned to either 576 VARICELLA. category. It may, however, be said, in a general way, that a mildly febrile exanthem appearing without prodromal symptoms, being dis- tinctly vesicular from the beginning, and commencing to desiccate on the second or third day, should be regarded as varicellous ; and, on the other hand, an acute exanthem preceded by an initial stage in which the tem- perature was high, beginning as papules and ending in vesicles or vesico- pustules, even though the period of evolution be short, should be re- garded as variolous. At any rate, it would be wise, for the safety of the public, to regard such a case as suspicious. If it should happen in a case in which the diagnosis cannot be clearly determined, that vac- cination had never been performed, it would be well to apply this test, for it is well known that variola renders an individual immune to vac- cinia, and that varicella does not. Prognosis. — The prognosis in varicella, even in infantile life, is uniformly favorable. The disease frequently runs so mild a course that the family physician is not summoned, or perhaps he may be called to decide as to the character of the eruption rather than to prescribe for the patient. A'^aricella, per se, never proves fatal. Some concurrent affection might arise to threaten the life of the patient, but no compli- cation is especially liable to occur. It is true, gangrene of certain parts of the cutaneous integument has been met with as a result of the vari- cellous process, but this is apt to occur only in children with some peculiar tendency to gangrene. The appearance of such a compli- cation would naturally be viewed with deep concern. Treatment. — As recovery invariably results from varicella, but very little is required in the way of treatment. The patient should be confined to the house, and even to the bed, for a few days, or until the fever subsides and the eruption has completed its course. The adop- tion of proper hygienic measures, such as regulating the temperature of the room, providing the patient with suitable diet, and giving atten- tion to bathing, is usually all that is required. A mild diaphoretic or febrifuge mixture may be given, and also bromide of potassium if the child be restless and sleepless. If there be much itching or irritation of the skin, cocoa butter or an antiseptic unguent may be applied locally. It is advisable to prevent rubbing or scratching of the vesi- cles, especially those on the face, as such injury increases the liability to pitting. The disease being quite innocent, it is usually unnecessary to adopt any special measures to prevent its spreading. When the patient has recovered it would be well to subject the bedchamber to the ordi- nary process of housecleaning. SCARLET fever; liv p. GERVAIS ROBINSON, M.D. Synonyms. — Scarlatina ; Scarlet rash ; Scharlach (German) ; Scar- latine (French). Definition. — Scarlet fever is an acnte, highly infectious disease, due, we may fairly believe, to the presence in the body of a specific organ- ism. Thougli the malady presents, in its clinical manifestations, more variations than any other exanthem, there are certain symptoms which are so frequently present as to be characteristic : there is a punctiform scarlet rash upon the skin which terminates in a lamellar desquamation ; an angina which is usually well marked ; a fever of varying degree ; and a noticeable immunity from future attacks. Etiology. — Scarlet fever, like other diseases of its class, has ever followed in the path of commerce. It seems to have been first intro- duced into this country in 1735. From the coast it crept inland until all the inhabited portions of the land were affected. It is curious to note that scarlatina when introduced into a virgin soil does not seem to possess the same virulence which is displayed by measles and smallpox under similar conditions. The writers who first described the disease in the United States regarded it as a mild affection. In this country, as in all other portions of the civilized world, scarlet fever has now become endemic in the large cities ; from these as foci from time to time epidemics arise. Periodicity. — Many facts have been adduced to sho^v that epidemics of scarlatina observe periodicity, but so many exceptions to such a law can be cited that it may be doubted if it in reality exists. Peculiarities of Epidemics. — No contagious disease varies so widely in the severity of the various epidemics as scarlet fever. Willan speaks of epidemics differing as much as " a fleabite and the plague." Syden- ham thought scarlatina so mild an affection that it hardly deserved the name of a disease. Two years later Morton found the same epi- demic exceedingly severe. In the epidemic of 1863 in London one fourteenth of the entire death rate was due to scarlet fever. In Stutt- gart in an epidemic which occurred in 1846 not one death was reported. Copland, writing in 1858, said : "There is no kind of fever which dis- plays a greater diversity in its nature and complications," and the expe- rience of all observers will bear out this statement. Season. — Although scarlet fever is present in large cities at all seasons of the year, it is generally most prevalent in the autumn and winter. ^ In the preparation of this article tlie writer begs to express his obligations to Dr. C. F. Hersman for valuable assistance. Vol. I. — 37 577 578 SCARLET FEVER. Below is presented a table showing the number of cases and deaths in the city of St. Louis for the past four years : For Municipal Year ending March 31, 1890. April . . May . . June . . July . . August . . September October November December January . February . March Cases. Deaths. Cases. Deaths. April May June July August 69 8 97 9 102 11 81 3 144 10 172 4 October November December January February March 258 21 253 15 237 18 171 10 141 3 157 8 September Total 1882 120 Total Year of 1891 : Year of 1892 : Year of 1893 : Year of 1894 : Cases. Deaths. Cases. Deaths. Cases. Deaths. Cases. Deaths. 103 142 115 82 114 114 99 119 135 125 99 89 12 6 4 8 6 5 7 16 4 1336 94 69 73 59 44 66 71 74 83 139 94 113 63 6 3 2 6 5 7 15 16 12 23 6 948 109 60 65 86 50 60 108 156 128 109 91 66 77 5 13 12 13 9 5 22 13 24 25 1056 153 84 75 41 19 45 61 65 64 75 87 57 56 731 55 A reference to this table shows that, though scarlet fever has been dis- tributed throughout the seasons of the year with more uniformity than has often been observed elsewhere, yet the preponderancy of cases in autumn and winter is preserved. Many writers have attempted to show that this seasonal prevalence is dependent on the temperature, moisture, electrical conditions, amount of ozone present, etc., but the proofs of such relations at present rest on the vaguest grounds. It may be that when the cause of scarlatina is better known something in its life his- tory will explain this fact. In the mean time, certain factors may be ■cited as partial explanation. In the autumn and winter, in our climate, the surface of the body is exposed to frequent chillings, among the poor often for long periods, and with them sufficient food is more difficult to obtain at these seasons than at other times of the year. Fodor has found that some bacteria introduced into animals reduced by hunger and cold are more apt to thrive than when inoculated upon the same animals in good condition. Furthermore, in the autumn and winter lesions of the respiratory mucous membrane are especially frequent, and it is probable that the poison of scarlatina usually enters the body by inhalation Then at this time of the year there are more oj)portunities for personal contact among children, especially by confinement in schools with large numbers of other children. Hershey^ states that 70 per cent, of scarlet fever cases come from infection at school. As might be expected, scarlet fever generally shows the highest mortality in those years when the most widespread epidemics are 1 Medical News, April 22, 1894. ETIOLOUY. 579 pri'st'iit, and at those seasons of the year when cases are most nunier- ons. Bnt here, a; an extensive epidemic tlie rela- tive mortality is less than in ordinary years, and, as Hehra has shown, it will often happen that the malady is as intense at one season as at another. This may be illnstrated from the table of the mortality of scarlet fever in St. Lonis, ji:iven above. In 1890 there was the greatest nnmber of eases, with a mortality of G.'> ])er cent., while in 1894 there M'as a small number of eases, with a mortality of 7.5 per cent. Age. — Scarlet fever is essentially a disease of childhood. Though no age is exempt, the majority of cases occur in the first ten years of life. After this the liability to contract the disease decreases rapidly with each succeeding decade. The liability to attack is at its height in the fifth year. The report^ of the Registrar General of England for 1886 contains so much of value in this connection that it is here reproduced. The report is based upon nearly half a million deaths from scarlatina occurring in England and Wales from 1859 to 1885 ; on 17,795 cases admitted during 1874-85 into the London Fever Hospital and the ^Metropolitan Asylum hospitals at Stockwell and Hammerton ; on 5000 in Christiania from 1870-82 ; and on the returns of all known cases of scarlet fever for some large towns in England where notification of in- fectious diseases has been for some time compulsory. The conclusions drawn from a study of this yast material are — (1) The mortality is at its maximum in the third year of life, and after this diminishes with age — at first slowly, afterward rapidly. (2) This diminution is due to three contributory causes : («) the increased proportion in the population at each successive age-period of persons protected by a previous attack ; (b) the diminution of liability to infection in successive age-j^eriods of those who are as yet unpro- tected ; (e) the diminishing risk in each successive age-period of an attack, should it occur, proving fatal. (3) The liability of the unprotected to infection is small in the first year of life, increases to a maximum in the fifth year or soon after, and then becomes rapidly smaller with advance of years. (4) The chance that an attack will terminate fatally is highest in infancy, and diminishes rapidly with years to the end of the twenty- fifth year, after which an attack is again somewhat more dangerous. (5) The female sex throughout life, the first year possibly excepted, is more liable to scarlatina than is the male sex. (6) The attacks in males, though fewer, are more likely to terminate 'fatally. (7) Hence the longer an attack is deferred the less likely is it to occur at all and the less likely is it to end fatally. It is no doubt true that the exemption of the first year of life from attack is more apparent than real : the child at the breast is more pro- tected from exposure than those old enough to run about and mingle with other children. The author has observed in his own family a severe case in a child nine months of age, followed by general dropsy. That advance in years does really bring immunity Murchison tries to prove by stating that if the mortality in England and Wales is calculated ^ A Contribution to the Xatural History of Scarlet Fever, Gresswell, p. 172. 580 SCARLET FEVER. at 6 per cent., then the number of cases of scarlet fever in these countries is less than one half the births, so that a large number reach adult life who have not been protected by an attack in childhood. Congenital Scarlatina. — Several cases have been reported of congenital scarlet fever. On the other hand, Murchison has observed two healthy children born from mothers suffering with scarlet fever. Although it must always be difficult to determine the presence of the rash of scarlet fever in newborn babies, whose skins are already red and often des- quamate soon after birth, still, as many authenticated cases are on record in which similar diseases have been present at birth, we may believe that it is possible for children to be born with scarlatina. Nor are the observations of authors that sometimes children unaffected are born of affected mothers, while at times the disease is transmitted to the foetus, insusceptible of reconciliation. Normally, the placenta acts as a filter, keeping back from the foetus formed elements from the maternal circulation. Bacteria are thus generally not allowed to pass into the foetal circulation, but under some circumstances, as has recently been shown, through a pathological condition in the placenta disease germs may pass to the foetus. It has been observed that a babe while suckled by a mother affected with scarlet fever has escaped the disease. It is possible that this phenomenon has relation to certain recent obser- vations which go to show that the milk of animals attacked by certain infectious diseases may acquire an antitoxic j^roperty. Sex. — The statistics gathered by the Registrar General of England, quoted above, show that the female sex is more liable to scarlatina than the male, but such figures are often misleading. Indeed, most authori- ties are agreed that sex in itself exerts no influence on predisposition. Richardson ^ has expressed his opinion thus : " Male and female are alike susceptible if they are alike exposed." Race. — It is not possible, on account of the confusion which exists in nomenclature and the inadequate returns from many countries in regard to scarlet fever, to determine what effect race has upon jjredis- position and upon the severity of the disease. According to D'Alves,^ scarlet fever attacked the Brazilian Indians with great intensity. Murchison states that scarlet fever makes no distinction among the different races living in New Zealand. It has been stated that scarla- tina does not occur among the Japanese. Ashmead "^ has reported a case occurring in a Japanese living in Brooklyn. The writer is of the opinion, judging from his own experience, that scarlatina is less common among negroes than among whites, but it is difficult to decide this point on account of the uncertainty of the diagnosis in negroes, and because they are not under such thorough medical control as are the whites. Social Position. — Though social position exerts no influence on sus- ceptibility to scarlet fever, it influences decidedly the severity of the affection, the mortality being less among the rich than among the poor. This can be explained on the ground of better attention, food, and hygiene in the case of the well to do. LoGolity. — It has never been proven that residence in cities or in ^ Natural History of Scarlatina, Gresswell, p. 175. '^ Cyclopedia of the Practice of Medicine, \'^on Ziemssen', vol. ii. p. 185. ^ jSfew York Medical Journal, Jan. 10, 1894. ETIOLOd Y. 581 the i-ouiitry, the iiatuiv of the soil, or the altitude have any iiitluenee upon predisposition. IntfuciK'c of Previous Hcdlth. — The previous state of health is of douhti'ul influence upon predisposition to searlet fever, though it would seem but reasonable that those whose physiolo»i;ieal resistanee has been diminished should fall a more ready prey. Loesehner and Koestlin state that scarlatina very often follows in the wake of measles. It is probable that a weakened condition of the (>;eneral health from other diseases predisposes to scarlet fever. Thus, Ehler ' states that in Ice- land in 1779 the majority of the lepers perished during a scarlet fever oi)idemii'. Occupation. — Occupation has no eifect u])on ])redisposition. Certain callings are attended by more abundant opportunities for infection than others. Murchison states that almost one third of all the patients received into the London Fever Hospital are nurses and servants from families Avhere scarlatina is prevailing. ISusccptihilifi/ in General. — The susceptibility to scarlet fever is much less universal than to measles or smallpox. It not uncommonly hap- pens that only one child of a family will develop the disease, though all have been equally exposed. It has been noticed that where one of two toAvns between which there is constant intercourse has been attacked the other has escaped for a long time. A person may live immune in an aifeeted neighborhood, and on removing to a distant place may develop susceptibility luider no more favorable circumstances for infection than those by which he was previously surrounded. Unlike measles, scarlet fever on entering a community for a long time exempt does not attack all those not already protected ; the same vagaries of susceptibility are noted here as under other circumstances. It has been observed that the longer an epidemic lasts the more likely are those who at first escaped to yield to the attacks of the disease. The variations in the intensity of scarlatina are as unaccountable as are the irregularities in suscepti- bility. Two children in the same family may contract the disease from presumably the same source ; one may have scarlatina in its mildest form, while the other perishes under a malignant attack. It is a fact worthy of notice that in some families a special susceptibility to scarlet fever is manifested. Instead of one or two children being attacked, the whole family is rapidly affected. Under such circumstances the disease may assume so severe a form that many of the cases terminate fatally. The writer is acquainted with a family in which out of 12 cases occur- ring in a week 7 died. Pree/nanci/, Puerperal State, Wounds. — Many authors hold that preg- nancy increases the liability of women to scarlet fever. On the other hand, observers of wide experience (Trousseau) have seen no pregnant woman attacked during extensive epidemics. The belief has long been held that women in the puerperal state are especially liable to scarlatina. It is but fair to conclude that in their exhausted condition such women would be more readily attacked by any infectious disease ; but it must not be forgotten that the statistics brought forward to prove this increased susceptibility to scarlatina are largely from hospitals, where, especially in former days, the virus of scarlet fever always existed, so that it w^as 1 Tfie Medical Week, Nov. 30, 1894. 582 SCARLET FEVER. often more a question of exposing a large number of lying-in women to infection than of susceptibility being increased by childbed. Another source of error lies in the great similarity of certain septicsemic rashes which may attend the puerperium to scarlet fever. It used to be quite common, after surgical operations, to see a scar- latiniform rash develop. In some of the English hospitals this has occurred with such frequency as to necessitate the closure of the wards for a time. When we consider how tenacious of life is the virus of scarlet fever, and how inadequate in former years was the disinfection of instruments and dressings, we can readily believe that some of these cases were real scarlet fever. No doubt most such cases have been rashes accompanying septic infection. Hutchinson ^ reports a case of a woman who on the fifth day after an amputation died of what seemed to be real scarlet fever. No case of scarlatina had occurred recently in the hospital^ but on inquiry it was found that the disease had been in the woman's family several months before. Hutchinson thinks that in this case the germs of the malady were present in the woman when admitted, and were aroused to activity by the disturbance following the operation. The Contagium. — Today no one doubts the infectious nature of scarlet fever, though not many years ago there were those who argued against this idea. The virus is of so volatile a nature that merely coming for a moment into the presence of one aifected with the disease suffices to reproduce it in a susceptible person. Not only is the malady immedi- ately infectious, but the contagium may be conveyed by fomites. These fomites may consist of the human or other animal body, of food, of letters or papers or books, of merchandise — in fine, of almost any article that may pass from person to person in the exigencies of daily life. Palante notes the case of a woman who, after remaining only a moment in the room of a scarlatinous patient, returned home, a distance of six miles^ and gave the disease to her children. Several cases are on record in which a domestic animal occupying the room of a patient has conveyed the disease. Hamilton^ mentions that during an outbreak of scarlet fever in Dublin two children who were ill were isolated in the top of a house and every precaution taken to prevent the spread of the malady to healthy members of the family. After a fortnight other children, who had been kept in the basement, took the disease, and it was found that a cat, which had been in the habit of spending the day with the sick children and the night with the well, had conveyed the contagium. A letter written in the room of a scarlet fever patient has often con- veyed sickness and death to distant homes. Books in libraries for cir- culation among the poor are frec^uently used to relieve the tedium of recovery from scarlatina and become ready carriers of the disease. Time and again milk stored in the chamber of a person ill of scarlet fever has initiated an epidemic of the disease. The tenacity of the virus is great, and it has often happened that it has been revived after lying dormant for long periods. Von Hildenbrand's classical coat retained its contagiousness for a year and a half. Duffin ^ records an instance where the paper had been left on the walls after a case of scarlet fever had occurred in a room. New paper was put on several ^ Archives of Surgery, April, 1893. ^ JBritish Medical Journal, June 3, 1894. ^ The Clinical Journal, April 5, 1894. ETIOLOGY. 583 times without rcniovino- the oUl. Finally, a new family came and took down all these layers of paper, liberating the scarlet fever })oison and causing an outbreak in the family. An almost indefinite number of instances illustrating the longevity of this poison might be collected from the literature w^ere it important or necessary to produce further examples. Mode of Communk'ai'wn. — It is usually considered that the virus enters the body through the respiratory mucous membranes. The fact that the stress so often falls upon the pharynx early in the disease might be looked upon as pointing in this direction. Kaposi states that children with chronic tonsillitis are more prone to the malady, and this gives additional support to the idea that the respiratory tract generally affords the site of entrance. Some have supposed that the virus enters with the food or drink. That it may at times gain entrance in other ways is proved by inoculation experiments. The disease has been produced by inoculation with blood, epidermic scales, serum from vesicles, and nasal and pharyngeal secretions. Miquel ^ claimed to be able to produce a local reaction comparable to vaccination by the inoculation of serum from vesicles, the subjects of this treatment being then found to be refractory to scarlet fever. But, as a rule, the disease when produced by inoculation has been more severe than that arising spontaneously, so that it has not to the present time been possible to use this method to procure immunity. Tinmunity. — As in other exanthems, so in scarlet fever, one attack confers immunity from future attacks. Whatever the scientific explana- tion of this immunity may ultimately prove to be, it certainly involves some profound change in the system, for it usually persists throughout life. There are exceptions to this rule : a few wtU authenticated in- stances of repeated attacks are on record. In the popular estimation repeated attacks are more numerous than they can be shown to be in fact — this largely on account of errors in diagnosis. Thus, a child has German measles or some erythema and the attending physician pro- nounces it scarlet fever : when the child really develops scarlatina it is regarded as a second attack. jSIany writers of wide experience have never seen an undoubted instance of a second attack. It has often been noticed that during an epidemic of scarlet fever many persons, both those who have had the disease and those not so protected, suffer from angina, wdiich has frequently been regarded as scarlatinous. Because this sore throat occurs at the same time as scarlatina does not show that it is the result of the germ of that disease. Indeed, it has been shown that the severe forms of throat trouble which often manifest themselves in scarlatinous patients are the result of secondary infection. These anginas are undoubtedly contagious, and thus a great number of the sore throats seen during an epidemic of scarlet fever may be entirely in- dependent of that disease. Such instances, then, cannot be admitted as constituting second attacks of scarlatina. In some cases which are characterized by an unusually prolonged febrile stage, in the second or third week an erythema again appears upon the body : to such cases Thomas gives the name " pseudo-relapses." In other instances after convalescence is begun a rash accompanied by other morbid symptoms ' Maladies de la Peaii, Kaposi, p. 267. 584 SCARLET FEVER. appears ; to this condition Thomas apjilies the term " relapse." Some observers have thought that repeated attacks of scarlet fever constituted a family peculiarity-. Troganowsky ^ found that in two of his cases of second attacks both parents had experienced the disease twice. Mur- chison has observed relapses in two sisters. It is said that relapses and second attacks are generally mild in character. Time of Greatest Infectiousness and Length of the Period of Infec- tion. — At which period of its evolution scarlet fever is most contagious is a question which has never been definitely decided. It would seem probable that the virus was being liberated in greatest quantity when the disease was at its height. This is not so important a question, how- ever, as is the inquiry, Is scarlet fever contagious at all periods of the disease, and if so how long does the contagiousness last ? The answer to the first part of this question is rendered more difiicult by the vary- ing suscej)tibility to the disease and by the great tenacity of the virus. If a child in the period of incubation is brought into contact with another child, and the second child fails to contract the disease, this will not show that scarlet fever is not contagious in the period of incubation, since the exposed individual may have been one of those not decidedly susceptible. Again, if the disease occurs in one child in a family who is at once isolated and kept so till all signs of sickness have disappeared, and if when this child joins the others another case appears, this does not prove that the original case was liberating the poison at the time of his restoration to the family circle, for we know how readily objects about a patient at the height of the disease may be infected and how difficult it is to remove from them the contagium. Reasoning from what has been shown to be true in smallpox and measles, it seems likely that in the period of incubation, before any active signs of illness are present, scarlatina is infectious. How long the possibility of infection endures has not been exactly determined. It is indeed probable that this period may vary in different cases. We would certainly not overstep the line were we to say that as long as any morbid phenomena attribut- able to the attack of scarlatina exist there is a possibility of infection. In fact, it is likely that such a statement does not cover the whole truth, for in some cases of diphtheria ^ it has been shown that Loffler's bacillus can be demonstrated long after all clinical evidence of disease has ceased, and what is true for this malady may very well hold for other infectious diseases, scarlet fever among the rest. Incubation. — The incubation period of scarlatina, as usually stated, varies within wider limits than are assigned to the same stage in the other exanthems. Formerly the incubation was estimated at from one to eight Committee of the Clinical Soc, 1892 Bristowe, 1887 Guinon, 1892 Striimpell, 1887 Usual time. 2 or 3 days. 6 to 8 days. 4 or 5 days. Minimum time. Maximum time. 1 day. Often less. Less than ") 4 days, j 7 days. Occasionally longer. 7 days. ^ f'udopedia of the Practice of Medicine, Von Ziemssen, vol. ii. p. 189. '' Medical News, Nov. 10, 1894. ETIOLOGY. 585 days. Kt'ct'iit observations, however, seem to show that the period (»f' incubation is marked by narrower limits. William.s' in a report for the Clinieal Soeiety of London tabuhites the foregoing opinions as to the lengtli of the stage of ineiibation in scarlatina. (See table, page 584.) Hamilton - from an experience of a severe epidemic among troops claims that the period of incubation of scarlet fever is three or four days. In some inoculation experiments the time of incubation has been seven days. Gerhardt is authority for the statement that, an abscess having been opened with a knife that had been used on a scarlatinous patient, scarlatina was developed four days later. Bokai'* reports two cases of tracheotomy in which scarlet fever developed sixteen hours after exposure. Soerensen * states that in 10 cases operated upon by Paget in Avhich scarlet fever developed the period of incubation was one day in 2 cases, two days in 3, and three days in 3 cases. The same author remarks that in 9 out of 12 cases of puerperal scarlet fever the period of inculiatiou was three days. It would seem probable from these figures that where infection occurs through a wound the time of incubation is shortened. On the other hand, it may happen that the incubation period is prolonged. Kaposi states that in rhaehitis and other conditions of ill health a prolonged incubation not uncommonly occnrs. Instances have been reported in which the time of incubation was several weeks. In some of these instances, where a case occurs in a family and a second case does not develop for weeks after the first, it is not necessary to assume that the incubation is thus lengthened, but rather that the poison did not, for some reason, affect the person at the first exposure. Besides, it is often difficult or impossible to exclude opportunities for infection other than the one from which the long incubation has been -counted. Still, since there is a possibility that these long periods of incubation do occur, a physician would be wise not to pronounce a child entirely out of danger till several weeks have passed since exposure. Occurrence icith Other Exanthems. — It is quite well established that other acute exanthems may occur at the same time as scarlet fever. Hirschprung narrates 2 cases, in each of which scarlatina and varicella were both present. Wolberg reports the case of a boy who was first attacked by scarlet fever ; a few days later the temperature rose and a ■crop of variola vesicles appeared. Hardaway has seen scarlet fever develop in the period of crusting in a case of variola. Brand has noticed the concurrence of scarlatina and typhoid fever. Taylor has seen 2 cases in which measles, scarlet fever, and diphtheria occurred simultaneously. Many other such instances might be gathered, but these will serve to illustrate this relation of scarlatina. Micro-organisms in Scarlatina. — Though many claims have been made to the discovery of the micro-organism which is the active factor in the production of scarlatina, no one of these has as yet received sufficient confirmation to merit its acceptance. In 1882, Ecklund described certain colorless corpuscles which he had found in the urine of scarlet fever patients. Similar bodies were found in the soil and ^ Practitioner, July, 1894. - British Medical Journal, June 3, 1S94. ^ Pester medicinisch-chirurgische Presse, v. p. 990. ^ Internationaler Idinische Rundschau, Jsos. 6 and 7, 1889. 586 SCARLET FEVER. surface water of regions in which epidemics of scarlatina were prevail- ing. Others have verified this observation as far as the appearance of the bodies in the urine is concerned, but their relation to scarlet fever has not been determined. Klein has obtained from the blood and tis- sues of scarlatinous patients a streptococcus which when injected into calves and guinea-pigs brings about symptoms resembling those of scarlet fever. He has found a similar organism in vesicles on the teats of cows to which an epidemic of scarlatina has been traced. Edington and Jamieson have isolated a bacillus which is described as 1.2 to 1.4 micromillimetres long and .4 micromillimetre in width. The bacilli are found in the blood of scarlet fever patients during the first two days only, and in the desquamating epidermis after the twenty-first day. Inoculation upon rabbits caused fever, erythema, and a subsequent desquamation. Shakespeare in this country has confirmed these obser- vations. His account of certain experiments is interesting: "A calf was inoculated and at the same time given some of the culture in milk. The calf was in good health at the time and had a temperature of 99.5° F. Six hours from the inoculation the calf developed great sickness, and the temperature, taken in the axilla, registered 103° F. The calf was left for the night, but in the morning was found dead. Small portions of the spleen and kidneys were placed in Koch's jelly and developed the characteristic bacilli. With this a second calf was inoculated when one day old. The inoculation was done w^ith scrupulous care, and a previous examination showed no bacilli in the calf's blood. His tem- p'erature in the rectum was 99.6° F. The inoculation was done at 6.30 p. M. The following morning the temperature was 104° F. There were sickness, great prostration, diarrhoea, and soreness of the throat. In the afternoon the skin of the thorax, upper abdomen, and inner sides of the fore legs presented a general redness which increased toM'ard evening. By the next day the animal was better and continued to im- prove. On the sixth day desquamation set in." The growth of the bacillus used in these experiments is, in cultures, very rapid, and this is of interest in view of the short incubation period in scarlatina. Doehle^ has observed in the blood of 5 scarlet fever patients twa distinct parasites : (1) Small, flat, spherical corpuscles, measuring 1 micromillimetre, provided generally with a whiplike appendage of about the same length, which has a bulbous extremity ; (2) corpuscles made up of two nuclei surrounded by a clear zone two or three times as large in area as the nuclei. This zone is finely granular and contains pigment granules. Movement in these cells occurs by contraction of the protoplasm. They may be outside or inside the red corpuscles. The author claims to have observed these parasites in the blood of measles and smallpox. These illustrations aiford an idea of the diversity of the bodies described as the germ of scarlet fever. Before we can accept any one of them as expressing the truth many control experiments must be brought forward in substantiation. Scarlatina in the Lower Animals. — For a long time it has been a ques- tion whether there is a disease of lower animals corresponding to scarlet fever in man. The knowledge of the unity of smallpox and vac- ^ Revue mensuelle des Malades de I' Enfance, July, 1894. I'A'rHULOUJCAL AXATOMV. 587 cinia has p;iv(Mi additional ii)torost to this quostion. SoaHatina is said to liavo bt'cii observed in doi^s, oats, swine, horses, and cows. Ileini ' states that a doo' whieh had hun in the same bed witli a child who had searlatina had a fever with a searlatiniibrni rasli which terniinat<'d in desquamation. The t::reatest interest of" this question is as to whether scarlet fever exists in cows, for if it does wo can readily see how the milk from infected animals may spread the disease to man. An epidemic of scarlet fever occurred in T^ondon in 1885 which has become historical as the " Hendon outbreak." The source of this epi- demic was traced to a herd of cows which was affected with a contaj^ious disease that oould be inoculated upon healthy cows and man. From ulcers upon the udders Klein isolated an organism which he thinks identical with one he had obtained from human beings affected with scarlet fever. Others who have investigated the Hendon disease have failed to agree that the malady from wdiich the cattle suffered was scar- latina. Hill- reports an outbreak of scarlatina at Sutton Coldfield, where all the homes invaded had the same milk supply. At the dairy from which the milk was obtained no case of human scarlet fever oould be found. One cow which had recently calved and had been in the herd only a short time was in poor ooiKlition, and indications of recent ulcerations were found on her teats. The authorities declined to inter- fere. Soon a number of fresh oases of scarlatina appeared, and on a second visit to the dairy the cow was found to be desquamating in ex- tensive patches. There was an ulcer on one teat and an eruption on the udder. A second cow presented indications of the same condition. The dairyman voluntarily ceased selling the milk and no further cases arose. In August, 1892, an epidemic in Glasgow^ ^ was traced to the milk supplied from a certain farm. At this farm a child Avas found suffering from scarlet fever, but the date of sickening made it probable that the child was one of the victims, and not the source from which the milk was poisoned. The cows were found to be suffering from a teat erup- tion. Lymph and crusts were sent to Klein, who found a streptococcus resembling one Avhich he had isolated from the Hendon outbreak. Lymph from these cows inoculated on calves produced two different eruptions, one of which was vaccinia, and the other of specific charac- ter, but entirely distinct from vaccinia. These instances serve to illus- trate what seems to be the belief of the day, that there is a disease of cow^s the virus of which is capable of causing scarlet fever when intro- duced into the human being. It must be said that by no means all authorities are agreed on this subject. The practical point for the phy- sician is that in all epidemics the origin of which is obscure the milk supply should be carefully scrutinized. Pathological Axato:my. — The most characteristic anatomical changes of scarlet fever are found in the skin and mucous membranes. Though a great number of pathological conditions are found in the course of scarlet fever, they have no essential relation with this malady, but are often present in other infectious diseases. An exception may be made in the case of nephritis, which occurs with such frequency as to ^ Cyclopedia of the Practice of Medicine, Yon Zierassen, vol. ii. p. 166. ■■* British Medical Journal, July 18, 1892. ^ Ibid., January 7, 1893. 588 SCARLET FEVER. deserve a position as one of the most important of the anatomical changes found with scarlatina. If seen in the commencement, the rash of scarlet fever is found to begin as small, pale red spots. In the course of a few hours these become confluent. The affected integu- ment then presents a uniform scarlet background dotted thickly over with minute points of a darker hue. The skin has a swollen, ceclema- tous appearance. On pressure the red color may be made to disappear, but when the rash is at its height there usually remains behind a faint yellowish staining of the surface. Sometimes it happens that there are points of a more purplish color which pressure will not dissipate, due to small hemorrhages into the skin, and in rare instances quite large areas are involved in the hemorrhages. The small red dots which are seen on the scarlatinous skin may become so much elevated as to constitute small papules, or in rare instances minute vesicles appear upon the skin. Microscopically the efflorescence is found to be due to a dilatation of the capillaries of the skin caused by paralysis of the vascular walls. In looking at a section one is struck by the fact that the epidermis and papillary body are folded, while the cutis is stretched and relatively- shortened. Unna^ explains this by stating that while the cutis was engorged the epidermis was gradually stretched, and that when by the section the cutis was allowed to recontract, it could not readily follow. The fact that the cutis is able to contract, he thinks, shows that there was not a true oedema of the skin. There are no indications of an inflammation in the strict sense of the word. When the eruption is at its height parakeratosis can be noted in the epidermis. Unna does not regard this as depending on the paralysis of the bloodvessels, but rather as a result of disturbance of the vasomotor centres, for the same para- keratosis is to be seen in scarlatina sine exanthemate. The darkened points mentioned above are due to an unusual dilatation of the sub- epithelial capillaries. These may represent small emboli due to the localization of the scarlatinal poison. Unna believes that it is from these points that the hemorrhages arise. Sometimes an interstitial oedema occurs in the neighborhood of the follicles, which in life causes the form of scarlatina known as scarlatina papulata. The exfoliations and other alterations in the epidermis are, according to Unna, the direct results of the action of the poison of scarlet fever, and are not to be regarded as arising from a true inflammation of the skin. The alterations which arise in the throat are even more constant in scarlet fever than the skin eruption. Some^ have gone so far as to assert that the essential point in diagnosis is the tonsillitis, as cases are extremely rare where it does not exist. In its mildest form the angina presents itself as a uniform redness of the soft palate, uvula, anterior palatine arches, and tonsils. If the process is of more severity, the red color is of a deeper hue ; there are oedema and swelling of the affected parts and a muco-purulent discharge ; the mucous follicles are swollen and may rupture, leaving shallow ulcers. The lymphatic ganglia lying over the tonsils at the angles of the jaws are enlarged and often tender to pressure. In more severe cases the ^ Lehrbuch der Spedellen pathologischen Anatomie, von Dr. J. Orth, Achte Lieferung. Erganzungsband, ii. Tlieil. " British Medical Journal, Jan. 9, 1893. rATllO LOGICAL ANATOMY. 589 redness and injection of (lie niiieous inenil)nine extend into the mouth and nose. The nioi-l)id ])roeess in the tonsils may result in an interstitial infiam- niation with great enlargem(!nt, and even the formation of abscesses. In ordinary cases there is little if any involvement of the larynx, but in severe oases the laryngeal mucous membrane nuiy be affected to such a degree as to cause stenosis or abscesses.' When the inflam- mation falls with peculiar intensity upon the tonsils, there may result gangrene of a part or a whole of these organs. In cases of the greatest severity the inflammation extends from the fauces to the cellular planes of the neck. This is accompanied by great infiltra- tion, swelling, and brawniness of the tissues. In most of these cases the cellulitis results in larger or smaller collections of ])us. The infil- tration may cause such interference with nutrition that large masses of tissue slough. On the separation of such gangrenous masses the muscles, vessels, and deeper structures of the neck may be exposed. If a large vessel be involved in the slough, rapidly fatal hemorrhage may occur. A false membrane is not an infrequent accomj^animent of scar- latinal angina. It is sometimes confined to the tonsils, but may involve the whole pharynx as well as the larynx and nose. It has long been a (juestion whether such membranes represent simultaneous attacks of scarlatina and diphtheria. The discovery of a specific bacillus in association Avith diphtheria has done much toAvard the solution of this question. Recent investigations have shown that in a large number of the membranous throat affections accompanying scarlet fever the bacillus of Luffler cannot be found, Williams^ in 35 cases in which a mem- l)rane was in the throats of scarlatinous patients found Loflfler's bacil- lus in 12. In cases of pseudo-membrane which are not diphtheritic various micro-organisms have been found. Booker^ has reported ex- aminations of the membrane from the throats of scarlet fever patients. In none was Loffler's bacillus present. In all he found a streptococcus which differed from the streptococcus of erysipelas principally in that it did not live so long in culture media. Examinations made by Jack- son^ and others by Councilman^ also showed streptococci. Bourges^ found in 17 cases of pseudo-membrane with scarlet fever in some a streptococcus, in others the daphylococcufi pyogenes aureus, the bacterium coli commune, and the staphylococcus jjyogenes albus. As Weigert has shown, the essentials for the existence of a false membrane are a sufficient necrosis of the epithelium and a fibrin-con- taining exudate. Reasoning from this fact and the observations men- tioned above, we arrive at the conclusion that the false membrane which occurs with scarlet fever does not necessarily imply that diph- theria is present as a complication : such a condition forms no neces- sary part of the morbid process of scarlet fever, but is often due to the action of bacteria which have been secondarily engrafted on the already inflamed throat. In a very large majority of all scarlatina cases nephritis of one ^ La Semaine medicale, May 7, 1893. ^ American Journal of the Medical Sciences^, Nov., 1893. ^ Johns Hopkins Hospital Bulletin, Oct. and Nov., 1892. * Boston Medical and Surgical Journal, Aug. 17, 1894. * Ibid. ^ " Les Origines de la Scarlatine," These inaugurale, Paris, 1891. 590 SCARLET FEVER. grade or another occurs. This nephritis is of the type known as glomerulo-nephritis. In many cases the involvement of the kidney is only of slight degree, while in some cases it progresses till a marked type of parenchymatous nephritis results. Klebs was the first to draw attention to the frequency with wdiich scarlatinal nephritis was a glom- erular affection. He found the only noticeable condition to be the accu- mulation of small angular nuclei and a finely granular matter in Bow- man's capsules. More recent observers have found the glomerular affection, but it is not necessarily the only change. Klein finds the changes to consist in increase of the nuclei covering the glomeruli, hyaline degeneration of the tunica intima, and multiplication of the nuclei of the tunica media of the minute arteries, leucocytal infiltration along the course of the vessels, and parenchymatous changes the inten- sity of which depends on the degree of the infiltration of the leucocytes. Many observers describe also a marked increase in the interstitial tissue, and ascribe to it a part in the production of the other changes. In this connection it is interesting to note that Fenwick ^ has extracted from the spleens of rapidly fatal cases of scarlet fever a substance which introduced into the circulation of animals tends to produce an acute parenchymatous nephritis. Symptoms. — It is a very difficult matter to give a comprehensive yet succinct account of the symptoms of a disease which presents so variable a course as scarlatina. It will perhaps be best for purposes of description to divide the affection into those cases which have an ordinary or typical course, those which are malignant, and those in which variations from the normal course of the malady are to be noted. The Ordinary Form. — As a rule, in the period of incubation there are no symptoms or they are so slight as to pass unnoticed. Some- times, however, slight malaise is complained of if the patient be old enough to give expression to his sensations, and if the temperature be • taken a slight evening rise may be detected. The stage of invasion is ushered in abruptly, so that commonly the exact time of the beginning of illness can be stated. In a large proportion of cases chilly sensations are experienced in the commencement of an attack, and in some a decided rigor. In young children it may happen that a convulsion is the first symptom of illness. The temperature rises rapidly, and in a few hours attains a considerable degree. It may reach 102°, 103°, 104° F., or even higher. The increased temperature is accompanied by those symptoms which usually mark fever from any cause, such as headache, loss of appetite, flushing of the face, sparkling eyes, and thirst. Coin- cident with the elevation of the temperature there is an increase in the rapidity of the pulse, and it is a thing to be noted that the pulse rate in scarlet fever is out of proportion to the height of the fever. Vomiting is one of the most important of the early symptoms of scarlet fever. It may occur but once, but it is apt to be repeated during the first day. Smith has found vomiting present in 162 out of 214 cases of scarlet fever. Thomas states that it occurs more frequently as an initial symptom of scarlet fever than with any other disease of child- hood except smallpox and pneumonia. Vomiting in the early period of ^ British Medical Journal, Aug. 19, 1894. SYMPTOMS. 591 st'iirk't lever ha.s been variously interpreted. It is generally regarded as a nervous phenomenon, but by some it is thought to indicate a catarriud eondition of the stomach. In rare instanees vomiting may continue through the course of the disease, constituting one of the most embar- rassing symptoms, as it may seriously interfere with the administratiun of food and medicine. In a certain })roportion of cases there is a mild diarriuva, which usually ceases after a day or two. In a small number of the more severe cases this symptom assumes alarming proportions. At this period of the disease the tongue is usually coated with a thick whitish fur, through which the swollen hvjienemic papilhe may be seen protruding. From the very onset of the malady there is sore throat. In adults and older children this is evinced by difficulty and pain on deglutition. The different characters presented by the throat have been sufficiently dealt with under the heading of Pathological Anatomy (page 588). In the ordinary cases it is only the less severe forms of throat trouble which are found. The lymphatic ganglia over the tonsils at the angle of the jaws are enlarged and tender on pressure. There is little evidence at this period of any catarrhal involvement of other raucous membranes. The symptoms presented in the stage of invasion on the part of the nervous system vary considerably in different cases. As already men- tioned, it is not uncommon to have one or more convulsions, and it is worthy of note that, occurring at this time, they are not of such grave significance as when seen at a later date. Nearly always from the first there is marked prostration. Often the patient lies in a dull, apathetic state. In other cases restlessness with twitching of the limbs occurs. The Bash. — Generally before the end of twenty-four hours from the initial symptoms the rash makes its appearance. Sometimes it is not developed till the second day, and in very rare cases not till a later , period. The rash appears first on the neck, chest, shoulders, or lateral parts of the face in rather ill defined patches. The patches rapidly coalesce, till in the course of a few hours, nearly always less than half a day, the whole body is covered. The lips and alte nasi generally escape the rash, and when the cheeks are brightly tinged the contrast between the scarlet and white portions of the face gives a peculiar and striking appearance. The characters of the rash have already been mentioned. It begins as small points of a red color, but in a very short time becomes a diffuse scarlet erythema, wdth innumerable points of a deeper hue scattered over the surface. The rash as usually seen very closely resem- bles the appearance caused by the application of a mustard plaster. In some cases where the rash is rather mild the original red points may remain discrete. This is said to be most prone to happen on the abdo- men. The rash generally is best developed on dependent parts and regions kept warm, as on the back and at the flexures of the joints. Although the involved surface may appear smooth to the eye, yet if the hand be passed gently over it a fine roughness can be detected. The scarlet color can be made to disappear by pressure, but returns as soon as the finger is raised. If sufficient irritation of the capillary walls be produced, as by stroking the skin roughly with a pencil, a white line persists for some moments. At one time this phenomenon was supposed 592 SCARLET FEVER. to be characteristic of scarlet fever, but we now know that it is common to many erythemas. The surface involved is hypersesthetic, and a sen- sation of itching and burning is often experienced. The time required for the full development of the rash varies. In mild cases it may reach its height on the first day. In other cases the full bloom of the efflorescence is not attained till the second, third, or even fourth day, and in rare cases at a later date. When the eruption is at its height the skin is tense and swollen and has an oedematous look, especially about the eyelids. While the rash is reaching its full development the other symptoms are increasing in severity. The temperature in ordinary cases may reach its maximum as the rash comes out, a height of 105° F. being not uncommon. It may remain at this point till the rash has attained its acme and then gradually decline. At other times there is a steady increase in fever pari passu with the progress of the eruption toward full bloom. In rather mild cases, when the rash is not fully developed till the second day, it often happens that in the morning of that day there is a decided remission in the febrile movement. The tongue by the fourth day has usually lost its coating and has become of a bright red, often glazed, color. It is studded over with swollen papillse (strawberry tongue). The throat symptoms increase in severity. Besides the redness and oedema already noted, the tonsils become covered with a layer of yellow- ish pus. The inflammation not infrequently extends forward into the buccal caA'ity and upward into the nose, from which there is a muco- purulent discharge. Usually by the time the disease has reached its height the vomiting and diarrhoea which may have been present at first have ceased, and constipation exists. The nervous symptoms also increase, and there may be delirium with restlessness or sometimes profound somnolence. The pulse remains rapid. The urine at the height of the malady is high colored, loaded with urates, and diminished in quantity. In the majority of cases at this time at least a trace of albumin can be found, and often it is consider- able in amount. Some authors (as Bartels and Thomas) ascribe the albuminuria of this period to the pyrexia, while others (Steiner and Eisenschitz) think that it indicates an organic lesion of the kidney. It is the latter view which is now accepted. Indeed, this is the only log- ical opinion, for it often happens that there are in the urine evidences of renal mischief other than albumin. Red and white blood cells and hyaline and blood casts can frequently be detected. In many similar diseases it has been shown that nephritis can exist early in the illness, and Klein has found glomerulitis in scarlet fever as early as the second day. Obermiiller first called attention to the presence in the urine of scarlatinous patients of peptone. Arslan,^ after extended observations, thinks this is a symptom of the greatest importance. His conclusions are as follows : (1) No peptone is found in mild cases ; (2) the urine contains peptone in grave cases associated with complications, the occur- rence of the latter being preceded by peptonuria ; (3) the presence of considerable quantities of peptone is an unfavorable sign ; (4) the pres- ' Gazette medicale de Paris, Feb. 25, 1894. SYMPTOMS. 593 eiice of peptone is not inlluenccd by ;ill)iMnin or by the condition nfthe pulse or tempcraturo. The eruption stays out in lull bloom from a few hours to one day. It fades from the body in the order of its appearance, often lin<»;ering long'cst on the backs of the iiands and feet. Generally by tlie end of the third day from the be<;iiininii' of decline the rash will have entirely vanished. The whole duration of the ei-u])tiou is from three to seven davs. Oeterloney/ by counting- from the commencement of fever to its subsidence, found the average duration in 40 cases to be six and a half days. ^^'ith the fading- of the rash all the other symptoms grow better. The fever falls by lysis, the throat heals, the appetite returns, the nervous symptoms disappear, and the urine grows more abundant and of lighter color, while anv albumin which it mav have contained usually disappears. Dcsqiiaiudfioit, may begin as early as the third day, though most often not till about the time of the fading- of the rash. In rare cases it has first appeared at a considerable period after the termination of the eruption. The character and amount of the desquamation depend in large degree upon the severity of the preceding eruption. Where the rash has been slight the desquamation may be furfuraceous. In typical eases, however, it occurs in large lamellae, and in severe cases, in regions where the epidermis is thick, as on the hands, perfect casts of the member may be exfoliated. Desquamation usually continues for a week or ten days, though it may be prolonged, and in some cases a second or even third desquamation has occurred.^ By the time desquamation is completed convalescence is well estab- lished and all morbid symptoms have passed away, save that the pulse is apt to continue rapid, sometimes until convalescence is far advanced. Even with the beginning of convalescence the disease cannot be treated as though it were a thing- of the past, for, as we shall see, although an attack may have been mild, the patient is more or less liable to serious sequelae. Such unfortunate accidents are especially liable to result if recovery has been too readily assumed and the safeguards which should have been thrown around the convalescent have been too soon relaxed. Between the ordinary form of scarlet fever which has been outlined and the grave form to be described there are all grades of severity. An eifort has been made in the description to indicate this and to keep con- stantly before the mind of the reader the marked variations in the course of the malady. 3Ialignant Forms of Scarlatina. — In almost every epidemic of scarlet fever there occur a certain number of cases which may properly be called malignant on account of their great tendency to a fatal issue. In some epidemics the number of these cases is especially striking, so that we are led to believe that at such times the poison of scarlet fever is of unusual virulence. In one form of malignant scarlatina the intoxication is so severe that death may result on the first day of the period of invasion, the patient ^ System of Medicine, Pepper, vol. ii. p. 506. ^ Cyclopedia of the Diseases of Children, Keating, p. 567. Vol. I.— 38 594 SCARLET FEVER. being overwhelmed before the eruption has manifested itself. Where the fatal termination is not so immediate, the symptoms from the first indicate the gravity of the case. The manifestations on the part of the nervous system are severe. There are intense headache, extreme restless- ness, delirium, convulsions, and not uncommonly the patient rapidly falls into a state of coma. The fever reaches an untoward height, a tempera- ture of 107° F. and even higher having been observed. The pulse attains such a degree of rapidity that it may be impossible to count it. Great irritability of the stomach is a frequent symptom, and the dangerous condition may be rendered even more unfavorable by constant vomiting. In those who survive the rash is slow in coming out, and is frequently of a more dusky hue than is observed in the ordinary cases. In the small proportion of cases which recover the whole course of the illness is apt to be lingering and tedious. Another form of scarlatina of marked malignancy is the hemorrhagic type of the disease. The symptoms are severe from the onset ; hemor- rhages from the various outlets of the body occur. There may be epis- taxis, bleeding from the gums, and hEematuria. When the eruption appears it assumes a hemorrhagic form. At first petecliise are seen in the skin, but these rapidly grow larger, and the entire surface may be involved in large hemorrhagic areas. Death often takes place on the second or third day. Post-mortem parenchymatous hemorrhages are found to have occurred in the various organs. Scarlatina anginosa should be classed among the malignant varieties of the disease. The stress of the attack seems to fall upon the throat. The mucous membrane of the throat presents from the beginning much swelling, and is apt to show a cyanotic or livid hue. A membranous exudation forms, which may extend into the larynx, mouth, or nose. The lymphatics of the neck rapidly enlarge. Xecrosis or gangrene of the affected structure results, and the breath has an extremely fetid odor. The patient lies semicomatose, the picture of one suffering from profound septicaemia. If death does not terminate the scene too early, there may be an extension of the inflammation to the cellular planes of the neck. The tissties may become swollen to such a degree that the neck is even with the chin. There is much infiltration and brawniness, so that the mouth can no longer be opened to inspect the throat. Diffi- culty in breathing may result from the swollen condition of the tonsils and the pressure of the infiltrated tissues of the neck, or from an exten- sion of the trouble into the larynx. The cellulitis may lead to the formation of abscesses of the neck or gangrene of large portions of tissue may result, the separation of which may lead to fatal hemorrhage. Variations from the Ordinary Course of Scarlatina. — It has been indicated above that scarlet fever presents a great number of variations from Avhat we may term the normal course of the disease. Although it would be an endless task to catalogue all, it is necessary to consider some of the more important of these abnormal forms. Though no case of scarlet fever can be regarded as entirely free from danger, there are many cases which are extremely mild. In these cases the febrile symptoms are slight, the temperature not rising much above 100° F. ; the nervous symptoms are absent ; the involvement of the throat is limited to a slight catarrh, with some injection and redness SYMPTOMS. 595 of" the tonsils and faiicos. The rash is never very distinct, and is not of that briti'ht scarlet color which is so characteristic of the eruption in its typical I'orni, but has more of a ])ink hue and fades in a day or two after its appearance. The patient does not feel ill enough to jjo to l^ed. Under pro})er treatment these cases run a course as favorable as the sym|»tonis are mild, but, unfortunately, it is this class of cases which is often dia^iuosed "scarlet rash," and to which the name scarlatina is applied by ignorant persons under the im|)ression that this term implies an eruption entirely distinct from scarlet fever and not tlangerous. These mild cases sometimes are followed by the sequelae of scarlet fever, and demand as much care as the more severe types of the disease. Cases of scarlatina have been reported in which thntughout the ill- ness there was no rise in the temperature. It is very likely that many such instances have i)cen cases of scarlatinoid erythemas. It is not im- possible, however, that scarlatina may ruu its course without fever, since the same apyretic course has been seen in typhoid fever. Fies- singer' in a paper on this subject draws these conclusions : (1) There is a form of scarlet fever in which the fever is entirely absent. (2) This form may be observed in the same epidemic and alongside the grave and pyretic forms ; it is contagious, and may give rise to the ordinals- form of the disease, complicated with Bright's disease or with pseudo- membranous angina. (3) There is no local symptom to differentiate the apyretic from the pyretic form. (4) The pulse is not always accel- erated in the apyretic form. (5) The ap^Tetic form is characterized by the absence of general phenomena. The diagnosis of this form of scarlatina from other erythemas must be very difficult, and could be made only in the presence of an epidemic or when some of the well known sequelae of scarlet fever follow. Most authors are agreed that scarlet fever without the rash may occur. During the epidemic cases of sore throat of greater or less severity are observed, after which desquamation or nephritis follows. The writer knows of a young medical man who had never had scarlet fever, and who, while attending some severe cases of scarlatina, was seized by a chill followed by an intensely sore throat. On the second day the urine became bloody and a hemorrhagic nephritis was found to be pres- ent. In this case no desquamation was observed. In speaking of this subject under the heading Immunity, page 583, attention was called to the fact that the true scarlatinal nature of such attacks, however prob- able it may seem, is generally open to question. Cases in which the rash is present M-ithout the sore throat have been reported, l^ut their occurrence is doubted by many authorities, and it seems to the author justly so, for we know that there are a number of erythemas which very closely simulate scarlatina, the chief differential point being the absence of sore throat. In some cases of scarlatina the fever is peculiarly prolonged, and the patient falls into a low condition to which the term typhoid is applied. In such cases the local lesions are not sufficiently severe to account for the long continuance of the fever. The temperature is high, and may continue in a more or less remittent form for several weeks. The nerv- ous symptoms are marked and peculiar. A low form of mental hebe- ^ Gazette medicale de Paris, March 4, 1894. 596 SCARLET FEVER. tude develops, and the patient lies partially unconscious with a dull, apathetic expression, his hands aimlessly fumbling Avith the bedcover- ing. The tongue and lips are dry and cracked and sordes accumulates on the teeth. The likeness to typhoid fever is still further carried out by the fact that there is marked enlargement of the spleen and there may be diarrhoea. It is stated that after death in some of these cases Peyer's patches and the mesenteric glands have been found enlarged.^ Thomas and Gumprecht^ have recorded cases in which the fever persisted for from eight to fifteen days beyond the usual period, but without serious symptoms. In these cases defervescence occurred more or less abruptly, and at no time was there hyperpyrexia. The cause of this long continued fever seemed to be streptococcus infection which had occurred through the tonsils. Bouveret ^ has noted in some cases a secondary hyperpyrexia which occurred on the ninth or tenth day and after the rash had disappeared. The temperature rose rapidly to 105° or 106° and was accompanied by grave nervous symptoms. Talamon * refers to cases in which there was hyperpyrexia even from the first day, Avhich persisted for a period of eighteen or twenty days. The fever was not dependent upon any local lesion, but was the essen- tial element and constituted the entire danger. Talamon found that cold affusions as ordinarily practised are worthless, in such cases the OJily efficient treatment being full cold baths at frequent intervals. In this connection the writer would mention certain cases that he has seen w^hich were marked from the first by a hyperpyrexia which could not be controlled even by cold baths, the patients rapidly dying from the effects of the high degree of fever. Relapses. — Reference has been made to relapses of scarlatina under the heading Immunity, page 583. Here it is only necessary to mention that the form to which Thomas has given the name pseudo-relapse varies in its course considerably from the ordinary form of the disease. The rash may appear only on limited regions of the body ; when it affects the face the region about the mouth and nose is not exempt. The eruption does not reach its full development on all the affected portions at nearly the same time, but progresses in an irregular manner. The behavior of the temperature during the pseudo-relapse is irregular, and the maximum of the rash and the highest fever do not coinoide. Variations in Type. — In general it may be said that marked varia- tions in the course of scarlet fever are caused by the complications which may arise. This part of the subject will be more particularly referred to in speaking of Complications, page 597. The most important variations which occur in the local symptoms of scarlet fever are the different forms which may be presented by the eruption. It may happen that the rash develops first ujdou some unusual site, as the abdomen, back, or limbs. Again, it may appear on the whole surface at the same time. The rash may occupy only certain regions, as one half of the body or the upper portion, while the rest is free. It has been noted occurring on very limited areas, as upon a small part ^ Cyclopedia of the Practice of Medicine, Von Ziemssen, vol. ii. p. 269. ^ Deutsche medicinische Wochenschrift, July, 1 888. ^ Revue de Medecine, April, 1893. * La Medecine moderne, Sept. 15, 1893. ' COMI'LICATloys jyjf SEQUELyK 597 of the belly, on tlie neck, or in the flexnre.s of tlie joints. Some anthors state that scarlatina is prone to avoid paralyzed liinl)s. The niinnte characters of the erui)tion may also vary. It may not be of the nsnal scarlet color, bnt a liuhter red, and in cases where for any reason there is marked slnuuishness of the circnlation a very dusky hue may be noticed. The rash instead of becoming confluent may occur as small red macules. Reference has already been made to the fact that in most oases on passing the hand over the surface a roughness can be felt. In some cases there are more decided elevations of the skin, which can be detected by the eye as numerous minute, acuminate papules ; to this form the term papular scarlatina has been apj)lied. There may occur over the surface, especially in regions kept warm, a crop of miliary vesicles constituting vesicular scarlatina. Should the contents of the vesicles become purulent, we have the form of the disease which is <'alled pustular scarlatina. Those grave forms of scarlatina in wliich extensive hemorrhages occur in the skin have been already described. In other cases small petechife may be observed at various points upon the surface, and this feature in itself does not indicate malignancy of the attack. Such is a description of the most commonly observed departures from the usual course of scarlatina. We must now consider the coiu- plications which may attend and the sequelfe which may follow attacks of the malady. CoMPLiCATioxs AXD Sequel.e. — It may be said that in scarlatina the complications are commonly the results of unusually intense morbid action on the part of organs which are affected in the normal course of the disease. The line between complications and sequelae is not sharply drawn, and that which began as a complication may by long duration become a sequel. There is no stage of scarlet fever which is free from liability to complications. AVhile they are most frequent in severe epi- demic and grave cases, still, even in the mildest case serious complica- tions may arise. It may here be mentioned that just before a com- plication of some important organ is discovered the rash, which has been out in full bloom, will suddenly fade. This phenomenon is pop- ularly known as " striking in," and among the laity, and formerly even in the profession, the complication which existed was regarded as the direct attack of the rash upon the affected organ. Hebra first showed that " striking in " was to be regarded as the result and not the cause of the complication. Among the most important as well as the most frequent complications of scarlatina the affections of the nervous system deserve a place. Those malignant cases in which the patient falls almost at once into coma have been considered, as well as the delirium which may arise from hyper- thermia. Convulsions occur chiefly at the beginning and toward the close of an attack of scarlet fever. In the first instance they are usually due to the action of the scarlatinal poison upon the nervous centres, while in the second they are often an accompaniment of the condition known as uraemia. Convulsions may also indicate the onset of a grave complication, and may thus occur at any period of the disease. All the symptoms of an acute meningitis may be present, and it is often a matter of much difficulty to decide whether that rare complication really exists, 598 SCARLET FEVEB. for in cases presenting such a train of symptoms a post-mortem exami- nation has not infrequently shown an absence of the anatomical features of meningitis. A case ^ has recently been reported in which persistent hiccough set in on the third day. The paroxysms came on every two or three minutes, and were so severe that eating, drinking, and sleeping were interfered with. The attack lasted seven days, and terminated in recovery. The severe forms of angina which occur with scarlet fever have been described. In addition to what has been said, it may here be mentioned that necrosis of the tissues may result in perforation of the soft palate ^ or an external opening into the pharynx, so that food cannot be swal- lowed." In cases of severe cellulitis of the neck the inflammation may extend down into the mediastinum. A very frequent complication of scarlatina is membranous deposit in the throat. The discussion of the significance of this symptom will be found under the heading Diagnosis (page 604). The fact that the Eustachian tubes open into the pharynx makes inflammation of the middle ear a common complication. The inflam- mation from the fauces creeps up into the tympanic cavity, and, as the Eustachian tube is very often occluded, the products of inflammation have no means of escape. By the accumulation in the middle ear are caused pain, increase in fever, and bulging of the membrana tympani. When the Eustachian tube is completely occluded the pent-up secretions can escape only by a perforation of the drumhead. After this has occurred in favorable cases a purulent discharge exists for a shorter or longer time, and then the opening in the membrane heals with very little permanent injury to the ear. Unfortunately, in a great many cases this happy result is not obtained. If pus be for long pent up in the tympanum, permanent injury may be wrought to the delicate structures there contained, necrosis of the small bones may result, or the inflammation may extend to the mastoid cells. The mucous mem- brane which lines the bony walls of the tympanum largely contributes to their nourishment, and when this function is disturbed by the inflam- mation necrosis of the bone may result. This is a serious condition, as the anatomical situation of the tympanum renders it easily possible for other important structures to be involved with it. Septic thrombosis may occur in the adjacent sinuses or veins ; meningitis or abscess of the brain may result. Even if no such serious accident follows, total destruction of the drumhead with loss of the ossicles and a chronic purulent discharge may be the final outcome. Where a gangrenous condition of the fauces has existed, gangrene has been observed to extend up the Eustachian tube and so involve the ear. When the ear is affected during an attack of scarlet fever in children who are old enough to speak, pain will be complained of; in younger children it will be evinced by putting the hand to the ear or by pressing the ear against the pillow. Such actions on the part of children should always ensure an examination of the ears. It has been mentioned that in cases of any severity there is often more or less involvement of the Schneiderian membrane. Under ordi- ^ Lyon medical, Sept. 11, 1893. ^ The Medical Weel; Nov. 9, 1894. '' System of Medicine, Pepper, vol. i., p. 512. - COMPLICATIONS AND SEQUELjE. 599 narv cirt-umstant'cs tlic ni()rl)iil j)ntt;('ss ^ivcs rise to a piinik'iit diri- oliai'tro, and resolves without any permanent damage to tlie mucous membrane. At times, however, ulceration occui-s and alarminu' licmoi-- rhaiic may result. Infiannnatiiin of the larynx is most common where scarlet lever is eom[)licatcd l)y diphtheria. Stenosis of the laiynx may ensue from the amount of pseudo-membrane formed or from coincident oedema. Some- times ulceration of the larynx results. l^ronchitis is one of the rarer complications of scarlet fever. Both erou])ous and catarrhal })neumonitis may occur durinu' the course of scarlatina, and are more likely to prove fatal when appearing during a nephritis than when manifested earlier in the disease. Gan- grene of the lung has been observed. CEdema of the lung is a serious accident that may arise at any period of the disease. It is usually accompanied by sudden foilure of the heart's action. A more important complication is pleuritis, which may develop as secondarv to some lung troul)le, but more often occurs independently, coming on during desqua- mation. Pleurisy may attain considerable proportions Avithout causing symptoms which would attract attention to its existence, but its presence is usually manifested by cough, difficult breathing, and pain on the atFected side. The pleuritis of scarlet fever, just as the other serous membrane inflammations which complicate the disease, shows a tendency to become purulent. Such empyemas run the same tedious course seen in those which arise under other circumstances. The involvement of the buccal mucous membrane which is observed in scarlatina amounts usually only to a catarrh, but there may occur quite severe ulcerations of the cheeks and gums, and in rare cases the gangrenous condition called noma. The symptoms on the part of the gastro-intestinal mucous mem])rane may be severe. Attention has already been called to the fact that in some cases vomiting is persistent and becomes a serious complication. Diarrhoea may also be a grave symptom. In rare cases the gastro- intestinal disturbance may be so intense early in the disease as to cause death. In such cases it is possible that a large dose of scarlatinal poison has been taken in with the food or drink, and has come in the first in- stance into contact with the gastric or intestinal mucous membrane. In the latter part of an attack of scarlet fever dysenteric symptoms may arise — tenesmus, pain on pressure over the colon, and bloody stools. The circulatory apparatus is liable to attack. The heart action is usually very rapid and it may become weak and irregular. Post- mortem examination shows that the cause for this is often found in a fatty degeneration of the muscular fibres of the organ. In life such a condition, by the weakness of the walls of the heart which it occasions, may lead to acute dilatation. Fibrinous coagula sometimes form within the cavities of the heart, and pieces of these, washing away in the blood stream, may give rise to embolism of the peripheral arteries. It not infrequently happens that during scarlet fever murmurs are heard over the cardiac region. These murmurs present different characters and depend on various causes. Some are hsemic murmurs. Some of them are no doubt caused by a relative insufficiency of the valves due to the weakened and dilated condition of the walls of the heart. Such abuor- 600 SCARLET FEVER. mal souuds disappear as convalescence advances. In other cases the murmur persists and other signs of organic valvular lesion develop. Thrombosis of veins has been reported as occurring as a complica- tion of scarlatina. When this takes place in the veins of the cerebrum a varied train of nervous symptoms follows, the character of which will depend on the vein aifected. Inflammation of arteries may arise during the course of scarlatina. Siredey ^ has reported such an occurrence in the aorta. Inflammation of the pericardium, though not a common complication, is one which has been frequently observed. It manifests the same symptoms and signs as when found under other circumstances. Kot infrequently the accumulation in the pericardial sac is purulent. Peritonitis, with accumulation of pus and adhesions between the intestinal coils, is sometimes found with scarlet fever. The writer well remembers a case in which all the symptoms of peritonitis — distention of the belly with gas, constipation, vomiting, and marked sensitiveness to pressure — came on toward the close of an attack of scarlatina. The urine was scanty with a trace of albumin and an occasional cast. So certain were those who had the case in charge that a septic peritonitis was present that it was proposed to open the belly for drainage. It was decided that the condition of the child was too bad to justify such a procedure. At post-mortem examination no trace of peritonitis was present, but there was a nephritis of such intensity that it seemed strange that the capsules of the kidney had not been ruptured by the enormous swelling of the organs. The affection known as scarlatinal rheumatism is a synovitis coming on usually during the latter part of the period of eruption or the first of desquamation. It attacks most often the phalangeal, ankle, and wrist joints, but may involve any articulation. As a general thing, there is little swelling, but the joint is painful and tender. Some be- lieve that this affection is really rheumatism complicating scarlet fever, but the writer does not believe that this assumption is necessary to explain the symptoms presented, and prefers to regard scarlatinal rheu- matism as a synovitis clue to the action of the poison of scarlet fever. It is thought by some authors that the presence of scarlatinal rheuma- tism increases the liability to valvular disease of the heart. Generally the inflammation of the joints subsides in a few days, but in rare in- .stances a suppurative synovitis develops, with destruction of the joint. AYhen large articulations are thus affected a fatal pyaemia is the frequent result. Periostitis may complicate scarlet fever, and when severe may lead to necrosis of bone. Separation of the epiphyses of bones ^ is one of the rarer accidents which may occur during scarlet fever. Myositis is an unusual complication. It may be manifested as a cer- tain amount of infiltration into the muscle, with pain and difficulty of motion, or the process may go on to the formation of abscesses. During the height of the eruption there sometimes occurs a conjunc- tivitis, though this is not a common complication. A keratitis may develop which may lead to the formation of an abscess or an ulcer of the cornea. Occasionally the whole cornea sloughs and the eye is destroyed by a panophthalmitis. A purulent panophthalmitis can also ^ The Medical Week, iSTovember 9, 1894. ^ Canadian Practitioner, January, 1894. - coMrucATioys axd sequels. 601 occur from a septic embolus lodjriuji; in tlie eye. When there is a diph- theritit' complicatiou in the throat the membranous intlamination some- times attat-ks the eve and may lead to its destruction.' That other infections diseases may complicate scarlatina has been mentioned on a previous pai!:e. All the exanthemata have been observed in conjunction with it. Of course the gravity of tlie affection is added to by such complications. Certain skin lesions may arise durino; the course of scarlatina. The most important are erysipelas, urticaria, herpes simplex, furunculus, and ganurene of more or less extensive areas. Scarlatinal Xcphritia. — Perhaps the most important complication of scarlatina is nephritis. By many nephritis is classed as a sequel, but if, as is o;enerally believed, the nephritis really finds its origin in the slight affection of the kidney Avhich occurs at the height of the erup- tive stage, it is certainly more appropriate to consider it as a (.'omplica- tion. As has been mentioned, if a careful urinary examination is made when scarlatina is at its height, it can usually be shown that there is present a more or less severe inflammation of the kidney. In the majority of cases this subsides Avith the decline of the malady, and if the case be properly cared for recovers without having caused any note- worthy objective symptoms. In a certain proportion of cases, on the other hand, the inflammation of the kidney progresses, and in the course of time gives evidence of its presence by severe symptoms. Although nephritis is more prone to occur in some epidemics than in others, there is no case of scarlatina so mild that it may not develop. Indeed, the very mildness of a case of scarlet fever may render the occurrence of nephritis more likely, because in such cases the necessary precautions are apt to be neglected. The writer has seen cases in which a diagnosis of " scarlet rash " had been made by an ignorant person, and the children allowed to be out of doors during the whole course of the disease, as they did not seem ill, in wliich a severe nephritis with general anasarca developed. The first noticeable symptoms of nephritis commonly manifest themselves in the declining period of scarlatina, during desquamation or immediately after it, though cases are reported in which nephritis is supposed to have first developed a number of Aveeks after an attack of scarlet fever. Catching cold has always been regarded as the chief determining factor in scarlatinal nephritis. It not infrequently happens that as soon as the severe symptoms attending the rash are past the patient is allowed to be up, and is thus exposed to injurious influences, among which exposure of the surface to varying degrees of temperature is certainly one. Probably a more important factor is posture and the increased work which the exertion of being up and around throws on the kidneys. In 179 cases which GresswelP examined albuminuria returned in 130 after getting up, at times vary- ing from twenty-four to thirty-one days after the beginning of illness. In some cases the onset of symptoms attributable to nephritis is abrupt. The fever, which has declined to near the normal, will rise again, there will be headache, perhaps vomiting, restlessness, and a very .small amount of highly albuminous and even bloody urine. In the ^ Atlanta Medical and Surgical Journal, Marcli, 1891. ^ A Contribution to the Natural Histoi'y of Scarlatina, Gresswell. 602 SCARLET FEVER. majority of cases, however, the iuaiiguration of the nephritis is more gradual. Perhaps the fever does not decline so rapidly as it should, or, having reached a point almost normal, it may continue there, this small degree of fever being for the time the only indication that things are not progressing favorably, or it may be the fact that the urine is grow- ing gradually scantier that first attracts the attention to the presence of nephritis. Unless a careful examination of the urine has been made at frequent intervals, it may happen that oedema will be the first evi- dence of renal mischief. Dropsy is very commonly first perceived in the eyelids or in the hands and feet ; in those who have been constantly in bed it may appear first upon the back. In a severe case the oedema extends all over the body, the skin is much swollen and pits on pres- sure, and often where the swelling is greatest there will be tenderness. The oedema may affect other organs. Pulmonary oedema or oedema of the glottis may reach such proportions as to render breathing impossi- ble. Accumulations of fluids in the serous cavities of the body may be so large as seriously to interfere with the function of important organs, as the heart or lungs. It occasionally happens that one of these internal dropsies is first to develop, and the anasarca appears only at a later date, or it has been noted that oedema of an internal organ — the lungs, for instance — has been the only manifestation of dropsy. Oedema after having persisted for a time subsides as the nephritis grows better, but where the the kidney lesion passes into a chronic form the oedema may also become chronic. The excrementitious products which should be eliminated in the urine accumulate in the blood during the nephritis, and often in such cpiantities as to give rise to alarming symptoms. The term uraemia is applied to this condition, and although it is a misnomer it is retained, because by long use it has acquired a definite significance. The symp- toms of ureemia vary much in intensity. They may be manifested only as more or less severe headache, vomiting, restlessness, twitching of the muscles, or sudden dilatations and contractions of the pupils. In more severe cases convulsions occur, and these may be succeeded Ijy coma. There is usually a definite relation between the ureemic symptoms and the C|uantity of the urine, the former ])ecoming more severe as the latter grows less. It is worthy of note that children often bear uraemia better than adults, recoveries having been observed under the most unpromis- ing circumstances. The condition of the urine in scarlatinal nephritis varies greatly in different cases. In the milder cases it is slightly diminished in cpian- tity, while in severe cases it may be as little as 50 c.c. in twenty-four hours, or anuria may exist for cjuite long periods. The specific gravity is higher than normal. The color is of a reddish yellow, or may be red or a smoky greenish hue from the blood which the urine contains. The amount of albumin varies from a mere trace to such a quantity that the urine solidifies on boiling. On standing there falls from the urine a more or less copious sediment made up of urates and uric acid and formed elements from the kidney in varying amounts. Renal epithe- lium may be found in differing states of preservation, some of the cells much swollen, others showing fatty degeneration. In most cases red blood corpuscles and leucocytes can be seen. The most significant signs COMPLICATIOXS AaD SEQUELM OOo of renal iiiHainmatioii are the easts, of wliich several different f »-nis may I)e found. Hyaline easts are nearly always j)resent, and at times tlu'V are vcrv lonn', Hat, and eonvohited, with the ends unev(-n, the so- called cylindroids. Epithelial easts also can jrenerally be deni(jnstrated, and when blood is present in the urine blood casts are formed. Althonjtjh the results of a urinary examination usually afford the most certain evidence of nephritis, it sometimes happens tliat marked renal changes exist without the appearance of albumin or easts, or these may occur at one time and be absent at another examinaticju. The writer recalls a case in which post-mortem there was found a very severe nephritis apparently involving the whole of both kidneys, in which in life the only changes in the urine were a slight diminution in quantity, a small amount of albumin, and an occasional hyaline cast. The course of scarlatinal nephritis presents many variations. In ordinary cases in the course of a week or ten days the oedema and other symptoms have disappeared and convalescence is begun. Careful urinary examinations will often show traces of albumin and casts for long periods even in these favorable cases. In rare cases a small amount of oedema persists, the patient does not recover health, but l^eeomes anaemic; the urine constantly contains albumin and casts; the heart becomes somewhat hypertrophied ; and a chronic form of Bright's dis- ease is established. When death occurs during an acute scarlatinal nephritis it is generally due to oedema of some important organ or to urtemic poisoning. Death may also occur from some acute intercurrent inflammatory trouble, as a pneumonia or pericarditis. As has been mentioned, no sharp dividing line between the compli- cations and the sequels of scarlet fever can be drawn. It is customary to apply the term sequelae to those morbid manifestations which appear after the activity of the scarlatinal poison has presumably exhausted itself, as well as to those complications which persist after other evidences of the malady have passed away. Only the most common and import- ant of the sequelfe can be here considered. The inflammation of the throat may leave in its wake a chriiuic h^^iertrophy of the tonsils. A perforation of the soft palate or of the septum of the nose may result from local gangrene. It has been mentioned that, owing to the inflammatory changes occurring in the ear as complications, a long continued purulent dis- charge may be a sequel. When necrosis of the bony structures of the tympanum has occurred, it may happen that serious intracranial mis- chief, such as abscess of the brain, develops even long after the original damage was sustained. In the eyes total blindness may result from the severity' of the affec- tions caused by the scarlatinal poison. Chronic interstitial keratitis, iritis, and neuro-retiuitis are among the important sequels in these organs. Tubercular infection of the lung, larynx, bones, and lymphatic ganglia may follow^ in the wake of scarlatina, just as we see it develop- ing after other acute affections. Paralysis of various muscles or groups of muscles not infrequently remains after an attack of scarlet fever. This paralysis is of similar nature to that which comes on after diphtheria and other infectious dis- 604 SCARLET FEVER. eases. Chorea in a number of instances has first manifested itself after scarlet fever. When scarlatinal rheumatism has taken the form of a suppurative synovitis, permanent ankylosis of one or more joints may result. Chronic valvular heart troubles are not infrequent sequelae of the acute attacks of endocarditis which complicate scarlet fever. Owing to the weakening of the heart walls, it may happen that when the patient who has recently experienced scarlatina has been up and around for a while an acute dilatation of the heart develops with a relative insuf- liciency of the mitral valve. The writer thinks it probable that some of the reported cases of oedema coming on in the period of convalescence without any kidney trouble are of this nature. Basedow's disease has been observed to occur suddenly after scarlet fever. ^ In the skin and its appendages sequelae may follow. Erythemas more or less diifuse have often been noted after desquamation has com- menced. Kaposi believes that relapses are generally to be thus explained, the rash representing a secondary erythema and not a scarlatinal recru- descence. Erythema nodosum, urticaria, herpes zoster, and localized gangrenous conditions of the skin sometimes develop after scarlet fever. An alopecia more or less complete may follow, just as we find it after other infectious maladies, and in a few cases permanent canities has been reported. After an attack of scarlatina there is often left a profound ansemia which may last for a long time without any discoverable lesion of an important viscus to account for it. Diagnosis. — It may be said that before the rash has appeared it is impossible to make a positive diagnosis of scarlet fever, since at this time there are no characteristic symptoms, such as occur in measles. During an epidemic if a child is seen who has been vomiting and has a high temperature with catarrh of the pharynx, it may be strongly conjectured that the patient is suffering from scarlet fever, but the physician will be wise not to commit himself positively to such an opinion. As a rule, since the period of invasion is so short, the physician will not see the case till the eruption has appeared. Generally when the rash has become fully developed the diagnosis offers little difficulty. The height of the fever, the evident illness of the patient, the character of the rash and the positions which it first occupies upon the body, the sore throat, the enlargement of the ganglia at the angles of the jaws, and the pres- ence in the urine of a trace of albumin will declare the nature of the disease. In the malignant cases where death occurs before the eruption comes out the diagnosis can be made only by considering the height of the fever, the nervous phenomena, and the fact of the existence of an epidemic or history of exposure, with the possibility of excluding other causes for the same train of symptoms. The chief difficulties in diagnosis will often arise in connection with those cases which present irregularities in their course. In all such cases a point of the very highest diagnostic value will be to establish the probability of infection. In those rare cases which run their course Avithout fever, to which reference has been made, one will have the greatest difficulty in arriving at a diagnosis of scarlet fever, for a rise in temperature is so essentially connected with ^ Wiener medicinische JSldtter, B. 15, H. 28. DIACSU^IS. G05 onr ideas of scarlet fever that its absence will always throw dotiUt on the (lia_i>-n()sis. If in addition to a eharaeteristie rash there were sore throat and alhuniin in the urine, the |)resuni])tion woidd l)e in favor of scarlatina, and this wouhl be nineh strenj;'thened should lanicUar des- quamation or nephritis dcveloj) at the usual time ; and esj)ecially would the supposition be confirmed should an ordinary case of scarlet fever occur after exposure to infection from the anomalous case. In view of the likelihood that scarlatina may occur without any eru[)tion, it seems to tlu' Avriter that during- an epidemic all cases of sore throat, especially where albumin is ])resent in the urine, should be regarded with suspicion, and if possible treated as though they were cases of scarlatina. This will no doubt be a difficult and often a thank- less task, but in our ])resent state of knowledge a due regard for the public safety dictates such a course, more especially as the sore throats which occur during an epidemic of scarlatina are infections whether they be scarlatinal or not. The cases of scarlatina in which the nervous symptoms are such as to cause a resemblance to cerebro-spinal meningitis can usually l)e dis- tinguished from the latter aifection by the facts that in scarlet fever there is an inflammation of the throat, while in meningitis the rash most often presents itself in the form of petechise. When seen after the first stages of the illness have passed away the typhoid form of scarlatina might be mistaken for typhoid fever, but the history of the onset, and perhaps the presence of desquamation, w'ould help to distinguish the two maladies. Those cases in which the rash comes out first in some unusual site need not create confusion, as in a short time, under ordinary circum- stances, the eruption extends all over the body, when the usual jiicture of scarlatina is presented. More difficulty is experienced in coming to a conclusion wdiere the rash occupies only limited portions of the sur- face, for the disease is apt to be mistaken for an erythema. In scarla- tina there are fever, sore throat, strawberry tongue, albumin in the urine, and ^vhen desquamation occurs it affects not only the portions of the skin which have been involved in the eruption, but also those parts wdiich were free from the rash. This combination of phenomena could hardly occur with an erythema. Especially in cases where the rash of scarlet fever remains discrete the disease may be confounded with measles or rotheln. In measles the incubation period is much longer than in scarlatina : the invasion period of measles occupies four days wath well marked catarrhal symp- toms, but lacks the sore throat, the high fever, the vomiting, and the nervous phenomena of scarlet fever, while albumin is absent from the urine. The eruption of measles is maculo-papular and of a duskier hue than the rash of scarlatina ; the borders of the lesions of measles are crenated, and they are often collected into crescentic groups, while the Avhole face is affected by the eruption, the region about the mouth not being avoided, as is the case in scarlatina ; the rash of measles stays out on the body in full bloom a shorter time than the eruption of scarlet fever. The desquamation of measles occurs as furfuraceous scales, while in scarlatina large lamellre are usually thrown off. Finally, the com- plications and sequelae of the two diseases are entirely different. 606 SCARLET FEVER. In rotheln the period of incubation is much longer than in scarlet fever. Eotheln often has no invasion stage, the first evidence of the disease being the rash, and if there are premonitory symptoms they are not so severe as those seen in the invasion of scarlatina. The rash of rotheln occurs as round rose-red spots, with well defined borders ; it most resembles scarlatina when it becomes confluent, but this generally occurs only in patches, and these lack the color and punctate appearance usually presented by the eruption of scarlatina ; and, furthermore, rotheln affects' the region about the mouth. In rotheln there is sore throat, but it is generally not so intense as the angina of scarlet fever. In rotheln there is slight fever, and the patient is often not at all ill, but the opposite is true for scarlatina. The tongue of scarlet fever is characteristic, that of rotheln is only coated. The urine of rotheln is at most febrile urine, while in scarlatina the urine contains albumin and casts. In rotheln the glands along the course of the sterno-mastoid are involved ; in scar- let fever those at the angles of the jaws, and, moreover, the degree of enlargement of the glands has a more constant relation to the condition of the throat in scarlet fever than is noticed in rotheln. After rotheln desquamation is rare, and the disease has no special complications or sequelfe. There is no likelihood of confounding scarlatina with smallpox after the true eruption of the latter disease has appeared, but there are certain pre-eruptive erythemas with smallpox which might lead to confusion. Smallpox, when the eruptions referred to are apt to appear, is charac- terized by severe lumbar pains and intense headache, while there is no sore throat nor the peculiar tongue of scarlatina. The erythematous rashes of smallpox usually occur in certain regions, especially the tri- angle of Simon and the pectoral triangle, and are very prone to exhibit a petechial character. Accompanying epidemics of influenza rashes have been observed which might cause the affection to be mistaken for scarlet fever. In influenza there is usually severe aching pain in the back and limbs ; the throat is sore, but generally the angina is not so intense as that seen with scarlatina ; in influenza there is commonly a bronchitis or other involvement of the lung. The rash of influenza partakes more of the character of measles than of scarlet fever, usually occurring as small, discrete red macules,^ The rash of influenza is more evanescent and irregular than that of scarlatina, often going and returning several times during the course of the malady. Erysipelas could hardly be mistaken for scarlet fever. The rash of erysipelas is limited to a region of the body, often develops around a wound, and does not present the punctate redness seen in scarlatina. There is also more hypersesthesia of the affected area and more oedema of the subcutaneous tissue than is observed with scarlet fever, while desquamation in erysipelas is confined to the region which has been involved by the eruption. There are a large number of drugs which ingested cause an eruption resembling that of scarlatina. The more important are here mentioned : benzoic acid, boracic acid, salicylic acid, antipyrine, arsenic, belladonna, chloral, chloralamide, chloroform (inhaled), digitalis, mercury, hyoscya- 1 Hardaway, oral communications. DLiGNOSIS. 607 um>, iodine compouiuls, opium j)rep;iriiti()iis, plK'iiacctin, tar, ([iiiniiie, rhul)arl), strainoniiim, strvchniiu', sul|»lioiial, tii])t'rciiliii. Tlic above list iiicliuk's only a sniall iiunihcr of the (Iruos which at one tiino or another have been observed to be followed by a rash more or less re- seml)linii- scarlatina. It is to be noted that many substances when applied to the skin are capable of causing a scarlatiniform erythema, as mustard for instance. Specially are certain substances used in modern antiseptic surgery capable of causing such an eruption. Among these may be mentioned carbolic acid, iodoform, and bi(;hloride of mercury. l)('»l ill with a piece of flannel, and then the surface washed with warm water. In the case of the palms and soles the soap siioid'l he used several times a day. Ivieh use ol' this soap npon the l)ody should be followed with inunction of the ointment rec(»nunended above. The length of time which must be .spent in the sick room is a ques- tion concernini!: which there is a variety of ojiinion. The only safe rule is that the patient must remain isolated till desquamation is entirely completed. In the opinion (»f the writer it is the wisest plan to con- fine the jnitient strictly to bed till des([uamation is finished. Reference has already been made to the injurious effects of exposure of the sur- face to varvinty degrees of temperature, and of the erect posture. Both of these evil influences are best avoided by a sufficientlv long stay in bed. The diet of the person suffering from scarlet fever should be light, but nutritious. ^lilk forjus the ideal food in a large proportion of the cases. Where it is not readily taken in its simple form, s«jme one of its preparations may be substituted, as, for instance, koumyss, kefyr, or peptonized milk. Often the addition of lime water renders the milk more digestil)le. In older patients the diet may occasionally be varied by allowing a soft-boiled i^g^, or oysters raw or stewed with crackers or toast. The patient ought to be fed at frequent intervals, and only small amounts given at a time, as very often the digestive processes are so impaired as to render the proper preparation and assimilation of any but small quantities of food impossible. Under such circumstances systematic stufBng of the patient can be only injurious, as a large amount of material is introduced which will not be taken up by the tissues, but must be removed from the body partly by the kidneys, which are already incapable of their normal amount of work. In some cases the stomach is so irritable that it cannot be made to retain food ; when this is the case rectal alimentation must be used, though this form of feeding is not so well borne by children as by adults. Water both in its ordi- nary form and carbonated alkaline waters should be allowed as freely as the patient desires. Therapeutics. — From time to time many remedies have been vaunted as specifics in the treatment of scarlatina. It is hardly necessary to refer to belladonna, which has enjoyed a reputation with some, appar- ently for no better reason than the fallacious one that because it can produce a rash like scarlet fever it can also prevent or cure the disease. Illingworth claims that biniodide of mercury is a specific, and Duke says it arrests fever and prevents desquamation. Shakhovsky lauds salicylic acid as being capable of preventing all complications and of arresting them when present. A wide experience with any or all of these remedies will probably convince the practitioner that their appar- ent specific action depends more on the mildness of the epidemic than the curative nature of the drug. The milder forms of the disease demand little in the way of internal medication. The diet and hygiene should be arranged in accordance with the principles already set forth. The author has for many years made it a rule to administer to nearly all cases of scarlatina iodide of potassium and bichloride of mercury. It has seemed to him that these drugs at least modify the severity of the symptoms and complications. 614 SCARLET FEVER. For a child three years of age the iodide of potassium may be given in the following prescription : ]^ . Potassii iodidi, gr. xlviii ; Syrupi limonis, 5j ; Aquam, ad giij. — M. Sig. A teaspoonful three times a day in water. The bichloride is most elegantly administered in the form of Van Swieten's liquid. To a child of three a third of a teaspoonful should be given in water three times a day. It has been the custom for a long time to administer in scarlet fever tincture of the chloride of iron. For this drug it is claimed that it is of use in counteracting the acute ansemia which often exists, that the chlorine it contains has a valuable antiseptic action, and that the local eifect upon the throat as the medicine is swallowed is beneficial. The iron is often combined with chlorate of potash, as in this prescription : I^. Potassii chloratis, 3j ; Tincturse ferri chloridi, Siss ; Syrupi, q. s. ad §ij. — M. Sig. Half teaspoonful every three hours for a child three years old. Wilson of Philadelphia has recommended the administration of chloral throughout the whole course of the disease. He claims that by this means the nervous symptoms are controlled and the condition of the patient is rendered more comfortable. The drug is to be given in small doses at repeated intervals, and any deep narcotism is to be avoided, but the patient is to be kept in such a condition that though easily aroused he soon falls asleep again. Wilson recommends the fol- lowing manner of administration : ]^. Chloralis, gr. xxx ; Syrupi lactucarii (Aubergier), Aquse, da. gj. — M. Sig. Teaspoonful as often as necessary for a child of three. The condition of the bowels should receive attention. When consti- pation exists a mild aperient or an enema should be given. The im- portance of preventing constipation would assume much importance could we accept Mahomed's opinion as to the frequent causal relation of this condition to nephritis. No part of the treatment of scarlatina is more important than the local treatment of the throat and nose. By proper care of these regions not only may the severe throat complications often be prevented, but ear trouble can usually be averted.^ An ice bag applied over the neck tends to subdue the faucial inflammation and at the same time often lowers the temperature. Swallowing of small bits of ice at frequent intervals exerts a beneficial influence, as is often evinced by the lessened pain on deglutition. Some antiseptic wash should be used in the nose ' Spencer, oral communication. TRKATMEXr. (jlo ;iii(l tliroat as oIUmi as possible It not iiiiVc(|ii('iitlv happens that then; is siicli turiicsc'oiu'c aiul suclliiiji; of the iiiirrior (iirhiiiatcd Ixxly as to hinder the free access of the antise})tic to the })osterior narcs. This can usually be overcome bv applying- to the turl)inate(l body with a (-(jtton swab a 4 per cent, solution of cocaine. In older children ami adults the antiseptic solution iiiay be a[)plie(l by a spray apparatus or nasal douche, but in young- children it is often necessary to use a dro})ping tube for this purpose. A great number of antiseptic fluids have been suggested, but perhaps none is better than a 2 or 3 per cent, solution of boric acid. Six to ten drachms of this, warmed to the temperature of the body, should be used in the nasal cavities two or three times a day. \Mien a s])ray apparatus can be used the throat should also l)e sprayed with the same solution. If the throat symptoms are mild, this alone suffices, but when the inflammation is intense great good is derived from the thorough application with the cotton holder of a 10 per cent, alcoholic solution of salicylic acid. This should be used once or tAvice a day. After the use of all these applications it is well t(j api)ly Ijoth to the nose and throat an antiseptic oil. This can be used in a spray, or a few drops may be introduced into the nose, whence they will run back int(j the throat. A good formula for such an oil is — ^. Camphora?, Menthol, aa. gr. iij ; Albolene, 5J. — M. In the case of individuals who can gargle it is of advantage to use an antiseptic solution for this purpose at frequent intervals. According to Yeo, one of the best preparations to be thus used is chlorine water made in the following way : Into a sixteen-ounce flask put eight grains of chlorate of potash. Upon this pour one drachm of hydrochloric acid. AYhen the green vapor has filled the bottle pour in water little by little, corking and shaking after each addition, till the bottle is fiill. This not only makes an excellent local application, but by many is prized as an internal remedy, a teaspoonful or two being swallowed every two hours. Another jirescription AA'hich is frequently used by the writer as a gargle and also as a spray is — Ki. Acidi carbolici, 3ss ; Glycerini, 3v ; Sol. pot. chloratis sat., q. s. ad Iv. — M. Sig. Dilute at time of use -with equal parts of warm water. The treatment outlined above is sufficient for the ordinary cases of scarlet fever. Since any additional treatment will depend on the sever- ity of the particular symptoms presented by each case, it will facilitate matters to discuss the treatment of some of the more important symp- toms which are likely to arise. One of the chief symptoms which the physician is called u]3on to combat is fever. As long as the temperature remains below 103° F., it does not constitute a dangerous condition unless it be unduly pro- longed. gr. XX ; 3SS } gr. ad s}y .— M gr. viij ; gr. XX ; 3iij ad §iv .— M 616 SCARLET FEVER. For the reduction of temperature the use of drugs is not, as a rule, to be so highly recommended as the abstraction of heat by means of the application to the body of cold. Quinine is a drug which has some antipyretic action, and used in reasonable doses it also acts as a tonic. One half to three grains, according to age, given every two hours, may be considered as expressing the limits of the usual dose for children. Quinine, according to Yeo, if given dissolved in the chlorine water men- tioned above, will have a more decided eifect in lowering temperature than if given in powder or capsules. It seems also to exert a more decided action when given in an effervescing mixture. The formula for the alkaline portion of the mixture is — Vy. Sodii bicarbonatis, Potassii bicarbonatis, Potassii chloratis, Aquam, The formula for the acid part is as follows II . Quininse sulphatis, Acidi citrici, Syrupi limonis, Aquam, From a dessertspoonful to a tablespoonful of each portion of this pres- cription is mixed together at the time of administration. The drugs which have the greatest potency in reducing temperature are the coal-tar derivatives. The best known of these are antipyrine, phenacetin, and acetanilid. It may be said that all of these prepara- tions are dangerous on account of their depressing effect, and if given should be used with caution, especially in a disease like scarlet fever, where the vital powers are already below par. Phenacetin is the safest of these drugs, and it has the advantage that its sedative effects are quite marked. If administered, it is best given in small doses at fre- quent intervals, for the effect desired can be thus more exactly obtained than if large doses are exhibited. By far the best and safest manner of controlling the temperature is by direct abstraction of heat from the body. There are a number of methods by which this can be accomplished. A simple means is to apply bags of ice to portions of the body where a considerable volume of blood is flowing close beneath the surface, as over the neck and wrists. In this way a marked reduction of temperature can often be effected. A more prompt effect is produced by sponging the whole body with cool water or equal parts of water and alcohol. To be of avail the sponging must be repeated at frequent intervals. The cold pack is an efticient method of reducing fever, but one that it is often impossible to use on account of the prejudices of the parents or friends of the patient. In practice the cold pack is thus applied : A blanket is spread upon a cot ; over this a sheet wrung out of water at a temperature of 70° F. is placed. The patient is envelojjed, with the exception of his head, in the sheet, and the blanket is wrapped over all. When a suf- TIIKATMKST. 017 ficieiit rediic'tioii of tempcratiirc has hcen secured, the patient is re- moved tV(»m the pack and wrajjped in a drv, warm l>lanket. The most powerful as well as the most certain method of rapidly lowerino; the temperature is the lull cool bath. A l)athtuh hnye enough to admit <»f the patient's lyinir at len Acidi carbolici, TTLv ; Aquse laurocerasi, 3v ; Aquam, ad gij. — M. Sig. Teaspoonful every hour. For diarrhoea quite often the application of cold compresses over the belly will suffice. Internally such a powder as the following may be administered : ^. Bismuthi subcarbonatis, 3ss ; Pulveris ipecacuanhse compositi, gr. v. — M. Fiant pulvereSj^JSTo. x. Sig. One every two hours for a child three years old. To treat appropriately the complications and sequelse of scarlet fever will often demand all the skill of even the most accomplished physi- cian. Here only the treatment of the more important and most common of these conditions can be considered. The treatment of the throat iniiammation as it is seen in the ordi- nary cases of scarlatina has been sufficiently dealt Avith, and it only remains to make some suggestions as to the treatment of the severer forms of angina. In cases where there is a false membrane or slough the throat should be first cleansed by means of a spray of peroxide of hydrogen, and then one of the antiseptic solutions recommended above should be used. There are many Avho make use of a 1 : 500 or 1 : 1000 solution of bichloride of mercury applied to the throat on a cotton swab after the pharynx has been cleansed with the peroxide. When there is TREATMENT. (519 cellulitis of the neck an ice haf>: should he constantly applied. As soon as it can be determined that pus has tonned an opening must be made under antiseptic precautions, and thorough drainarnil and I^abes, have described micro-organisms found in the lungs of patients dead of pneumonia after measles, but it til)le animals, pseudo-membranes were })ro- duced, and frequently death followed. If a certain amount of a bouillon culture was injected subcutaneously into guinea-pigs, death was caused with characteri.stic lesions. Loffler's failure to find the bacilli in every case examined is now ex])lained by the fact that certain varieties of pseudo-membranous inflammation not due to the diphtheria bacillus, 648 DIPHTHERIA. such as occur especially in scarlet fever, were then wrongly considered to be true diphtheria. In 1887 further studies by Loffler added to the proof of the depend- ence of diphtheria on the diphtheria bacilli. In 1888, D'Espine found the bacilli in 14 cases of characteristic diphtheria, and proved them to be absent in 24 cases of mild sore throats which, clinically, were believed not to be cases of diphtheria. In the same year the first portion of the results of the very important investigations of Roux and Yersin was published, and the dependence of the disease on the diphtheria bacilli may be considered to have been established. Roux and Yersin found the diphtheria bacilli were present in all characteristic cases, and that these bacilli possessed the cultural and pathogenic qualities of those described by L5ffler. They found, too, when the bacilli were inoculated upon the healthy mucous membrane of the trachea of the rabbit, no inflammation followed ; but if the inoculation was made on the abraded membrane, phenomena occurred which strikingly resembled those present in membranous laryngitis in man — i. e. congestion of the mucous mem- brane, followed by the formation of a pseudo-membrane, oedematous swelling of the tissues and of the glands of the neck, dyspnoea, stridulous breathing, and asphyxia. Injection of cultures beneath the skin of rabbits and guinea-pigs in sufficient quantity caused their death in from thirty-six hours to five days, the period varying in ratio to the suscepti- bility of the animal and the number and virulence of the bacteria intro- duced. The same result followed the injections of filtered cultures, showing that the products formed by the growth of the bacilli were, by themselves, capable of causing the general lesions. Roux and Yersin were also able to produce in animals characteristic diphtheria paralysis. They produced this in many cases where the in- oculated animals did not succumb to a too rapid intoxication. Paralysis commenced in a pigeon three weeks after the inoculation of the pharynx and after all membrane had disappeared and the animal seemed to have completely recovered. In rabbits the paralysis usually commenced in the posterior extremities, and then gradually extended to the whole body, causing death by paralysis of the heart or respiration. In rare instances the muscles of the neck or of the larynx were first paralyzed, and thus characteristic symptoms were caused. The authors conclude: "The occurrence of these paralyses, following the introduction of the bacilli of Klebs and L5ffler, completes the resemblance of the ex])erimental disease to the natural malady, and establishes with certainty the specific rule of this bacillus." Finally, the microscopic changes in the internal organs of animals dying of experimental diphtheria produced by the bacilli have been shown by Welch and Flexner, and by Babes and others, to be essentially the same as those produced by diphtheria in man, and thus a still further proof is afforded of the specific role of this bacillus. The results of the various observations detailed above have since been confirmed by a great number of combined clinical and bacteriological investigations, so that all who have studied the bacteriology of diphtheria would now agree with the following statement made by Welch' in an address on diphtheria : "All the conditions have been fulfilled for dipli- 1 Welch, Medical News, May 16, 1891. PLATE X. 6. Colonies of pseudo-diphtheria bacilli, X 160 c. Coloaies of diphtheria bacilli, x '2.-UJ. Ml! I V L.^mi: '^^ Z^ theria bacilli, X 1000. /. Pseudo-diphtl e. Diphtheria bacilli, X 1000. /. Pseudo-diphtheria bacilli. ,' 1000. g. Streptococci, v 1000. I 4 /t. Streptococci, X 1000. I. Streptococci, X 1000. Diphtheria Bacilli and Streptococci, THE Diruriir.iiiA iiacillcs. 649 theria wliioli aiv lu't'cssarv to tlic most riiiid jn-oof oi' tlio ilependeiice of an intc'ctivc disease upon a given iniero-oriranism — \i/.. the eonstant preseni-e <»t" this oriianism in the lesions of the disease, the isolation of the oro-anisni in pnre enlture, tiie reprodnetion of the disease hy inoeula- tions of pure cultures, and similar distribution of the ortranism in the experimental and in the natural disease. In view of these facts we must agree with Prudden that we are now justified in saying that the name dij)htheria, or at least primary diphtheria, should he applied, and exclu- sivelv applied, to that acute infectious disease usually associated with pseudo-memhranous alfection of the mucous membrane which is primarily caused by the bacillus called the bacillus diphtherite of Lofiler." Characteristics of the Loffler Bacillus. — Groirth on Blood ^cruiii. — If we examine the growth of the diphtheria bacillus in pure culture on blood serum, we will lind at the end of ten to twelve hours little colonies of bacilli which appear as pearl-gray or whitish-gray slii»-htlv raised points. The colonies when separated from each other mav increase in forty-eight hours, so that the diameter may be one fourth of an inch. The borders are usually somewhat uneven. Those colonies, lying together, fuse into one mass, especially if the serum is rather moist. Durmg the first twelve hours the colonies of the diphtheria bacilli al)0ut equal in size those of the streptococci ; but after this time the diphtheria colonies become larger than those of the streptococci, nearly equalling those of the staphylococci. The diphtheria bacilli in their growth never liquefy the blood serum. When cover-glass preparations made from the blood serum tubes are examined, the diphtheria bacilli are found to possess the following cha- racteristics (Plate X., f/, e) : The diameter of the bacilli varies from 0.3 to 0.8 u, and the length from 1.5 to 6.5 tjt. They occur singly and in pairs, and very infre- quently in chains of three or four. The rods are straight or slightly curved, and usually are not uniformly cylindrical throughout their entire length, but are swollen at the ends or pointed at the ends and swollen in the middle portion. Even from the same culture different bacilli differ greatly in their size and shape. The two bacilli of a pair may lie with their long diameter in the same axis or at an obtuse or an acute angle. The bacilli possess no spores, but have in them highly refractile bodies. They stain readily with the ordinary aniline dyes and retain their color after staining bv Gram's method. AVith an alkaline solution of methyl blue, the bacilli, from blood serum especially, and from other media less constantly, stain in an irregular and extremely characteristic way. The bacilli do not stain uniformly. Certain oval bodies situated in the ends or in the central portions stain much more intensely than the rest of the bacillus. Sometimes these highly stained bodies are thicker than the rest of the bacillus ; again, they are thinner and surrounded by a more slightly stained portion. The bacilli seem to stain in this pecu- liar way at a certain period in their gro^^'th, so that only a portion of the organisms taken from a culture at any one time will show the characteristic staining. In old cultures it is often difficult to stain the bacilli, and the staining, when it does occur, is frequently not at all characteristic. Groirth on 1 per cent. Alkaline Glycerin Agar, and Method of Ob- taining Pure Cultures. — It is frequently desired to obtain the diphtheria 650 DIPHTHERIA. bacillus in pure culture. This is most readily accomplished by removing with a platinum needle a portion of the mixed growth of bacteria in a serum tube, and lightly streaking it over the surface of the nutrient agar contained in a Petri dish. Though the growth of the diphtheria bacilli upon agar is less certain and luxuriant than upon serum, the appearance of the colonies when ex- amined under the microscope is more characteristic. If the diphtheria colonies develop deep in the substance of the agar, they are usually round or oval, and, as a rule, present no extensions, but if near the surface from one or both sides they spread out an apron-like extension which exceeds in surface area the rest of the colony. When the colonies develop entirely on the surface, they are more or less coarsely granular, are nearly translucent, and usually have a darker centre. The edges are sometimes very jagged, and frequently shade off into a delicate lace-like fringe ; at other times the margins are more even and the colonies are nearly circular. With a high power lens the edges show sprouting bacilli (Plate X., c). The colonies are gray or grayish white by reflected light, and pure gray with olive tint by transmitted light. The growth of the diphtheria bacillus upon agar presents certain peculiarities which are of the utmost practical importance. While the bacilli from the majority of cases grow rather feebly, some grow luxuri- antly. If a large number of the bacilli from a recent culture are im- planted upon a properly prepared agar plate, a certain and fairly vigorous growth will always take place. If, however, the agar is inoculated with the exudate of a throat which contaius but few Loflfler bacilli, or from a serum tube containing also a growth of other bacteria, no growth what- ever of the bacilli may occur, while the tubes of coagulated blood serum inoculated with the same material contain them abundantly. Again, agar prepared from broth made from different specimens of beef, or to which different peptones have been added, varies somewhat as to its suitability for the growth of the bacilli. Because of the uncertainty of obtaining a growth by the inoculation of agar with a few bacilli or with bacilli of diminished vigor, agar is a far less reliable medium than blood serum for use in cultures made for diagnostic purposes, and is, therefore, not to be recommended. All agar should be tested by means of a pure culture of the diphtheria bacillus before being used experimentally. The agar is prepared by adding 1 per cent, of agar to the required quantity of broth. The broth is prepared in the same way as that used in the blood serum mixture, except that it contains no glucose. The agar must be thoroughly dissolved in the broth, and to accomplish this in an ordinary Arnold sterilizer it is necessary to boil the mixture for from three to six hours. Sufficient alkali must be added to make the agar slightly but distinctly alkaline. Many advise that before final sterilization 5 per cent, glycerin be added. The bouillon agar sterilized on three successive days may be kept for many months in litre flasks. Growth in Broth. — All the varieties of the Loffler bacillus experi- mented with have grown in slightly alkaline broth with or without the addition of 1 per cent, glucose. The characteristic growth is one showing fine grains. These deposit along the sides and bottom of the tube, leaving the broth nearly clear. In some cultures for twenty-four Tin-: BLOOD SEllVM MIXTIUIES; CULTURES. 051 or forty-oight hours there is a more or less dilfiise (;l<»ii(liiiess, and, exeej)- tionally, a lihn forms over the surface of tlic broth. On shakinjr the tube this film breaks up and slowly sinks to the bottom. As a rule, the baeilli eause the alkaline broth to beeome aeid, or at least distinctly less alkaline, within forty-eight hours. As a rule, within a week the acid reaction changes again to the alkaline. This may occur in forty-eight hours or, exceptionally, not at all. These differences are due largely to the cluiraeter of the meat from which the broth is made, especially upon the amount of glucose contained. AiiiiiKil Iiwcn/dfioii.s as (t Test of Mrtilcucc. — Animal ex[)eriments form the only reliable method of determining with certainty the viru- lence of .the diphtheria bacillus. For tliis purjjose alkaline broth cultures of forty-eight hours' growth should be used for the subcutaneous inoculation of guinea-pigs. The amount injected may vary from ^ to i- per cent, of the body weight of the animal inoculated. In the great majority of cases, when the bacilli are virulent, this amount causes death within seventy-two hours. Some bacilli are so virulent that y-J-jj of of this amount causes death. In the autopsy the characteristic lesions described by Loffler are found — namely, at the seat of inoculation there is a grayish focus surrounded by an area of congestion ; the subcutaneous tissues for an extensive area around are congested, and at times very oedematous ; the adjacent lymph nodes are swollen, and the serous cavities — especially the pleura — frequently contain an excess of fluid, usually clear, but at times turbid ; the lungs are usually congested. If the organs are subjected to microscopical examination, the lesions described by Welch and Flexner, Babes, and others are found. There are numerous smaller and larger masses of necrotic cells, which are permeated by leucocytes. The heart and the voluntary muscular fibres usually show degenerative changes. The number of leucocytes in the blood is increased. From the area surrounding the point of injection virulent bacilli may be obtained, but in distant areas and organs they are only occasionally found. Bacilli which in cultures and in animal experiments have shown themselves to be characteristic may be regarded as certainly true diph- theria bacilli, and as capable of producing diphtheria in man under favor- able conditions. The Preparation of Lopfler's Blood Serum Mixtures ; the Media Used for Making Cultures for Diagnostic Pur- poses. Collection of the Blood Serum and /fe Preparation for Z^ffi>jiTifEiii.i hacilij. 055 In cases in which the disease is confined to the hirvnx or hntnchi, and where, therefore, there is no visible exndate against wliich the swab can be rnl)l)cd, snr|)risini«;ly accnrate resnlts can be obtained from the exam- ination ot" cnltnres, but in a certain [)roj)ortion of cases no diphtheria bacilli will be fotuul in the first culture, and yet will be abundantlv jjresent in later ones, the bacilli having probably l)een coughed up more freely as the disease progressed. I believe, therefore, that absolute reli- ance for a diagnosis cannot l)e placed on a negative result in cultures from the ])harynx in purely laryngeal cases. In nasd diphthci'ia a negative result may be obtained from a culture made from the throat, and yet the i)acilli be found in cultures from the nose. In making a diagnosis from a culture it is essential to know the dura- tion of the disease in the case from which it was made, becanse, although bacilli may remain present and alive in some throats for manv weeks, it is, nevertheless, important to remember they may vanish early and sud- denly, and that, therefore, the cultures cannot I)e certainly relied im after the meml)rane begins to disappear. The use of antiseptics shortly before making the inoculation of a cul- ture tube may render the culture useless for diagnosis. It has been found in a few instances that a culture made from a case of diphtheria shortlv after a thorough irrigation with a 1 : 4000 solution of bichloride of mer- cury gave no diphtlieria bacilli, though one made just before and one made some time later gave them al)undantly. It is a curious fact that under such circumstances a vigorous growth of other organisms may take place. The above conclusions are true only when the inoculations have been properly made, and, in judging cultures received from physicians in general, the greatest care must be taken. Some cultures are made care- lessly, and some evidently without taking the pains to even read the instructions, which should always accompany the outfit, or to glance at the condition of the coagulated serum in the tube. If, therefore, when nr) diphtheria bacilli are found the bacterial gro\\'th is scanty, the media dry or contaminated, or the inoculation in any way faulty, the case nnist be referred back for another culture. The second culture in these cases not infrequently contains the bacilli when the first did not. The absence of bacilli in a culture proves the case to be one of false diphtheria only when it has been possible to make it under the proper conditions. A most important practical question is the following : If, in cultures, bacilli are found wliich possess the shape, size, and staining character- istics of the diphtheria bacillus, can they, without further cultural or animal experiments, be considered as virulent diphtheria bacilli ? Since it is the custom of many, following the example of the Xew York City Health Department, to make a bacteriological diagnosis in suspected cases of diphtheria from the examination of the growth on the original blood serum tul)e without waiting for further cultural or animal experiments, it is of the greatest practical im])ortance to ascertain to what extent Ijacilli appearing upon the serum in every way characteristic of the diphtheria bacilli can be assumed to be virulent. To test the virulence of bacilli, four days at least are required, for before inoculating it is necessary to obtain them in pure culture, for otherwise it would be impossible to determine whether the changes pro- 656 DIPHTHERIA. duced in the inoculated animal were due to the supposed diphtheria bacilli or to other micro-organisms injected with them. It is further necessary to grow the bacilli in proper media, and to inoculate suscep- tible animals at a period when the growth of the bacilli in the media has reached its maximum. It is only when these precautions have been fol- lowed that accurate results will be obtained. The present almost uniform practice is to inoculate half-grown guinea-pigs with from 0.25 to 0.5 per cent, of their body weight of a twenty-four or forty-eight hours' cul- ture of the bacilli grown at 37° C. in simple nutrient or glucose alkaline broth. It is important to remember that it is not safe to decide, because the growth derived from one bacillus is not virulent, that all the bacilli from that thi'oat are not virulent. The cultures from several bacilli must be tried. The majority of those who have inoculated bacilli de- rived from pseudo-membranes and possessing the characteristics of the Loffler bacilli have found, as Loffler did, that they were always virulent. The researches of Hofmann, Beck, and others, however, showing that in a certain number of healthy throats there were bacilli which closely re- sembled the L5ffler bacillus, and yet were not virulent, stimulated others to subject the bacilli from large numbers of cases of suspected diphtheria to the test of animal inoculation. In 1890, Eoux and Yersin published the results of some examina- tions as to the virulence of the bacilli obtained from 100 cases of diph- theria : 55 of these were fatal cases, and in all of them virulent bacilli were found, although in a few, together with many virulent bacilli, there were a few non-virulent ones. Among the 45 cases which recovered many were very mild, and in 10 of them they found no bacilli of suf- ficient virulence to cause the death of guinea-pigs when injected in mod- erate amount. From all of them, however, they obtained bacilli capable of causing inflammation in the guinea-pig at the point of injection. This varied from slight, transient oedema to extensive necrosis. From further experiments they proved similar bacilli were capable under proper condi- tions of regaining their virulence. They further showed that, in these milder cases, among many non-virulent or slightly virulent bacilli there were usually a few virulent ones ; therefore they believed that in most of these 10 cases fully virulent bacilli may have been present in the throat with the slightly virulent ones which by chance were used for the inoculations. Virulence of the Bacilli found in Ten Cases of Throat Inflammation of such a Character as to Arouse a Suspicion of Diphtheria. Severity. Weight Amount of of guinea- culture pig, injected, gms. CO. 390 1.33 210 0.5 220 0..5 620 3.33 ■niiratinn nf Persistence of iSfter Loffler bacillus inoculatfon ^^^er recovery inocuiauon. ^^ patient. 1. Milfi case . 2. Mild case ; adult ; never in bed 3. Removed to Diphtheria Hospital ; severe case 4. Rather mild ease 5. Very mild case 479 6. Fatal case ; croup .... - I 675 7. Fairly severe case, followed by measles .... 443 8. Moderately severe case 435 9. Very mild case 500 10. Contracted from a mild case ; no membrane present 250 1.5 1.33 1.33 1.66 40 hours . . 50 hours . . 40 hours. 25 hours . . No reaction. 40 hours. 40 hours . . 4 days . 40 hours. 40 hours. 38-41 days. 44 days. 42 davs. 20-24 days. 15-23 days. 15-19 days. VULTURES; DIPHTHERIA RACILLI. G57 In order to cleterniiiie tlio vinilciu'c ni" the Wacilli ()l)taiii('(l in the or- dinary rontine examinations from snspected eases of" diplitlieria hlood serum eultures from 40 eases were selected in wliieli haeilli were found having; the characteristic appearance of the virulent diphtheria bacilli. The cultures tested were selected before any information was possessed of the severity of the cases from which they were obtained, and were used for experiments on animals. The table given on the preeeding page presents average exam[)les of the cases. We found that the bacilli obtained from 40 cases of suspected diph- theria, two thirds of which were mild, proved in every case except 1 to be virulent, and in all but 3 fully so. If these results are con- sidered in connection with those obtained by other American and by European observers, we must conclude that for diagnostic purposes all bacilli found in throat inflammations of cases suspected to be (li])htheria, which possess the morpliological and cultural characteristics of the Loffler bacilli, must be regarded as virulent, unless animal inoculations prove otherwise. Further, it should be remembered (as shown by Roux and Yersin, and as confirmed by others and by ourselves) that the ab- sence of virulence in a culture derived from one bacillus is not sufficient to prove that cultures fi'om other bacilli from the same case would not be virulent. This may have been true in the only case out of the 40 in which virulent bacilli were not found. In 3 of the above cases the cultures from the first colony selected were not virulent, while from others they were fully so. If a piece of membrane be removed from the throat during the period of invasion of diphtheria and examined microscopically or by cultures, the presence of abundant diphtheria bacilli will be noted. If, a few days later, when the membrane has begun to loosen, another bit be examined, the diphtheria bacilli will be found to be partly or at times wholly replaced by other micro-organisms, mostly cocci. If, several days later, after the complete disappearance of the membrane, cultures be made from the mucus of the throat, it will be found the bacilli of diphtheria in many of the cases will have disappeared from the throat. This rule is not, however, without many exceptions, for it will be frequently found, days after the complete disappearance of the membrane and after the return of the throat to a healthy condition, that fully virulent bacilli linger in the throat. In order to test the virulence of the bacilli in the throats of con- valescent cases, they were obtained in pure culture from a large number of healthy throats in convalescent diphtheria cases and used for the inoculation of the guinea-pigs. The table of selected cases (see next page) gives the average results of these experiments. In each case, in testing the virulence of the bacilli derived from it, we employed the last culture or the next to the last culture made from it in which the bacilli were found to be present. The results in these cases tested, as well as in those before recorded by others, prove con- clusively that the bacilli, which in a certain proportion of cases persist in the throat after an attack of diphtheria, are always virulent for some time. In the exceptional cases in which the bacilli persist for a very long time it is found they occasionally lose their virulence a few days before their final disappearance, while in other cases they retain their Vol. I.— 42 658 DIPHTHERIA. virulence to the end. That the cases themselves are not so liable to spread diphtheria is probably because of the relatively small number of bacilli present in convalescent throats as compared with the number found in those showing the lesions of diphtheria. Case No. Severity of the diphtherial!! the case. The bacilli tested had persisted after recov- ery for— Virulence. Weight guinea- pig, gms. Amount injected, c.c. Life of guinea-pig after injection. 1 2 3 4 6 6 7 Mild case Very mild case Mild case Severe case Very mild case Fairly severe case .... Mild case 10 days . . . 12 " ... 33 " ... 18 " ... 25 "... 26 " ... 50 " ... 250 440 226 229 505 347 410 0.5 1.5 1.00 1 1.00 1.66 1.33 3.00 8 days. 40 hours. Extensive necrosis with final recovery. 9 days. 40 hours. 5 days. 2 " The Pseudo- and Non-virulent Diphtheria Bacillus. — Since the general adoption of bacteriological examinations for purposes of diagnosis in diphtheria the characteristics of the non-virulent bacilli and the fre- quency with which they occur have had added to their scientific a very practical interest. In 1888, Hofmann published the results of the bacteriological examinations of a number of diseased and healthy throats, which for a time threw doubt on the specific character of the Loffler diphtheria bacillus. Further research has largely dispelled the confusion which his discoveries seemed to make. Hofmann's results were similar to those of Loffler, in that he found the virulent bacillus in all of 8 cases of true diphtheria, but in further search he was surprised to find in the throats of 26 out of 45 persons, none of whom was suffering from diphtheria, a bacillus which very closely resembled the Loffler bacillus. The bacilli from a number of these healthy throats were obtained in pure culture and inoculated into animals. The majority had no virulence whatever. The bacilli from the different cases varied somewhat in their characteristics. Some in appearance, manner of staining, and growth on media seemed identical with the Loffler bacillus, while others presented slight but constant dif- ferences. Between the extremes were many gradations. Those bacilli which did not possess all the characteristics of the virulent bacillus differed in the following respects : They were shorter, thicker, and more uniform in size. On agar they grew in whiter and thicker colonies, whose circumference was more circular and less notched. They also grew at a lower temperature than the virulent bacilli (20° to 22° C). Hofmann was undecided whether all of these bacilli were really Loffler diphtheria bacilli which had lost their virulence, or whether they were a different species of bacteria and of a saprophytic nature. He was also undecided whether, even among these non-virulent bacilli, there might not be included different species. Roux and Yersin found in a hospital for children in Paris, wdiere cases of diphtheria occurred from time to time, that 15 out of 45 children contained in their healthy throats non-virulent bacilli resembling the rSKL'DU-DlI'lJTIIJJJllA BACILLI. GoO L()tHei' l)acilliis. In a Freiit'li villa<;e where no diphtheria liad been present tor a h)ni>: time they made eultnres from tiie healthy throats of 55) ehildreii liviiii;' in a school. In 2() of tiiese non-virulent bacilli were found. In an examination of the throats of 10 attendants in a (hphtheria iK)S})ital non-\irnlent haeilli were fonnd once. Thus in 114 liealthy throats the non-virnlent bacilli were found 42 times. In all of these throats the bacilli were present in very small numbers. The bacilli found, when studied in ])nre culture, ditfi^'red somewliat from each other. The majority were identii-al in all their characteristics with the Lofiler bacillus, except as to their lack of virulence. The minority resembled those described by Hofmann. Roux and Yersin regarded the occasional slight diii'erences in growth, shape, and staining as too slight and inconstant to distinguish the virulent from the non- virulent bacilli. Animal experiments alone sutficcd to determine the (piestion of virulence, and they regarded as arbitrary a division founded on the reaction of the guinea-pig to inoculation, since they found that ba- ■cilli from cases of diphtheria may possess every degree of virulence, from those which cause death within twenty-four hours to those which caused only a temporary (pdema. With such variations it is a difficult matter to determine what should be the proper line of division between the virulent and the non-virulent bacilli. To fully prove that these bacilli belong to the same species they believe it is necessary to derive non-virulent bacilli from the virulent ones, and to give virulence to those entirely lacking it. They found it was possible to produce an attenuation of the viru- lence of the bacilli in a number of ways. They also found it possible to greatly increase the virulence of bacilli by injecting them together with 2i virulent culture of the streptococcus of erysipelas ; but were unable, on the other hand, to give back virulence to those bacilli which had been completely robbed of their virulence by the above methods, or to those w*hich had no virulence when obtained from the throat. If we now turn to the work of Escherich, we find results which tend to show that the virulent and some of the non-virulent bacilli are differ- ent species of bacteria. He found the bacilli from every case of diph- theria examined to be fully virulent, and in a few cases, where he ob- tained characteristic bacilli from the healthy throats of persons exposed to diphtheria, he found them also to be virulent. Escherich did indeed find in a moderate number of throats of per- sons not suifering from diphtheria bacilli similar to those described by Hofmann. Thus in Munich he found this non-virulent bacillus in 2 throats out of 70, and in Grez in 11 out of 250, or 13 times in 320 •cases. These bacilli, however, all possessed certain cultural and mor- phological characteristics which were sufficient to separate them from the virulent bacilli. They were, as in some described l)y Hofmann, plumper and shorter than the Lofffer bacilli and more uniform in size. He noticed two new points of difference which seemed to him important. The non-virulent or pseudo-diphtheria bacilli, when spread on a cover- glass, lie in parallel row'S, while the virulent diphtheria bacilli lie at every angle and the most varied positions. The second diff'erence was still more marked. He found, as had all others wdio had noticed this point, that the virulent l^acilli in their growth in neutral or slightly 660 DIPHTHERIA. alkaline bouillon changed the reaction of the bouillon to acid in the course of forty-eight hours. The amount of acid formed differed in different cultures and liad no relation to the degree of virulence. He then noticed that the substance produced during the growth of the pseudo-diphtheria bacilli always made the bouillon more alkaline instead of acid. Therefore, if at the end of forty-eight hours litmus was added to the different bouillon cultures, it turned red in the virulent ones and blue in the pseudo-diphtheritic non-virulent ones. It should be noticed that this difference in reaction was not found by Roux and Yersin in the cultures of the non-virulent bacilli tested by them. Escherich, in conclusion, states his position as follows : " Since we have found constant cultural differences between the true and the pseudo-diphtheria bacilli, we can give the pseudo-diphtheria bacilli no diagnostic value." If we review the remaining literature of this subject, we find some investigators have been led by their results to adopt views similar to those of Roux and Yersin, others to those of Escherich, and still others have been forced to content themselves with the position of Hofmann — viz. that we are not in a position to affirm whether all these bacilli are of one or of different species of bacteria. The relationship between these bacilli is not only a matter of great interest, but has also been one of great practical importance in bacterio- logical examination carried on for purposes of diagnosis. In order to study these various bacilli, especially the non-virulent forms, and to clear up, if possible, some of the questions connected with their classification, cultures were made upon blood serum from 330 healthy throats. When any of the varieties of bacilli described above were discovered in the cultures, they were isolated, and in the great majority of cases tested as to their virulence on guinea-pigs. In these examinations I had the help of Mr. Alfred Beebe. The results are given in the tables below. Results of Cultures made from the Throats of Healthy Persons lohere there had been no History obtained of Direct Contact ivith Diphtheria. From where. Total cases. Virulent cha- racteristic diphtheria bacilli. Non-virulent Non-virulent characteristic pseudo- diphtheria 1 diphtheria bacilli. 1 bacilli! New York Dispensary, by Dr. J. H. Huddleston Northern Dispensary Nos. 1 to 151 152 to 16.3 164 to 189 } •■■ 5 12 21 Throughout the city of New York College of Physicians and Surgeons— Students New York Foundling Hospital Dispensary . Orthopsedic Hospital (through kindness" of Dr. Chappell). Female ward 190 to 193 194 to 242 243 to 257 258 to 267 268 to 275 276 to 330 330 4 2 3 1 Male ward .... New York Foundling Hospital, by Dr. Adams Totals 3 1 i S ■ 24 27 The bacilli found may be divided into three groups : (1) Bacilli identical with the Loffler diphtheria bacillus in growth, producing acid in bouillon, but having no virulence. I)[l'llTUi:niA BACILLI L\ HEALTHY THROATS. GGl (2) Bacilli not luivini: all the cliaractoristics of the Loffler bacillus in growth, ])r(>(liiciii appar- ently healthy, but infected, children, as well as the sick one, were at once quarantined, but already 1 of the family to which the baby had been sent had contracted diphtheria from it. The practical value of bacteriological examinations of the throats of liealthy children in families where isolation has not been carried out in the first days is further shown by the fact that those children in whom the bacilli are found are extremely apt to develop diphtheria in the course of a few days, when no cleansing treatment is adopted, while they seem much less liable to do so if kept under treatment or immunized with antitoxins. The detection of the virulent bacilli in throats prevents the dissem- ination of diphtheria by allowing us to isolate those infected. A very striking instance of this was the following : In a family of 4 children 1 was sick with diphtheria. The Department inspector found 3 other children in the same bed with the sick child, who was constantly spitting upon and soiling the bedclothes. He made cultures from these 3 children, whose throats appeared healthy, as Avell as from the sick one ; all contained abundant characteristic L5ffler bacilli (these were later shown to be virulent by the inoculation of guinea-pigs). When the inspector visited the same family three days later he found 2 of the previously healthy children had meanwhile sickened and died, and that the third was severely ill. This child finally recovered. From the observation detailed above we cannot escape the conclusion that all members of an infected household should be regarded as under suspicion, and in those cases where isolation is not enforced the healthy as well as the sick should be prevented from mingling with others until cultures from the throat have shown the absence of bacilli or a sufficient lapse of time gives the presumption that they are not carriers of the con- tagium. Summarij and Conclusions on Diphtheria Bacilli in HealfJii/ Throats. — It has been shown that children, and to a less extent adults, who are brought in direct contact with true cases of diphtheria very often receive the diphtheria bacilli into their throats, and that these bacilli may persist and develop in these throats for days or weeks. In some cases Ave have found that true diphtheria followed the appearance of the bacilli in the res])iratory passages, M'hile in others no disease developed, though they might be the source of diphtheria in others. The examination of the throats of 330 healthy persons dwelling in Xew York tenements in whom no contact with diphtheria was known revealed the presence of 664 DIPHTHERIA. virulent bacilli in but 8 persons, 2 of whom later developed diph- theria. We must conclude, then, that virulent diphtheria bacilli are to be found in the throats of a small proportion of healthy persons throughout localities where diphtheria prevails, and that they have been derived either directly from diphtheria cases or from those who have been in contact with them. The examinations of the throats of the 330 healthy persons showed that in 24 bacilli existed in every way identical with the Loffler bacillus, except that they were not virulent in animals. As some of the bacilli in cases of true diphtheria are known to gradually lose their virulence, and as this loss can be caused artificially, it seems that these bacilli, characteristic except as to virulence, should be regarded as true diphtheria bacilli which have lost it. They are probably incapable of causing diphtheria. The examination of the same throats showed that in 27 there were bacilli present which were so uniform in their peculiarities, as to staining, size, shape, and the production of an alkali instead of an acid, that there seems to us to be even more reason to separate them from the diphtheria bacillus than there is, for example, to separate the colon bacillus from that of typhoid. We have never found bacilli possessing these peculiarities to be viru- lent, nor have they appeared to have any connection with diphtheria. It seems to us that to these bacilli alone the name pseudo-diphtheria bacillus should be given. The Persistence of Bacilli in the Throats of Convalescent Cases. — The length of time elapsing between the inception of the disease and the date on which a culture showed the absence of the Klebs-Loflfler bacillus from the throat of the patient was tabulated for 1736 cases. In many of the cases cultures were made at infrequent intervals, and the bacilli may therefore have disappeared at an earlier period than that recorded. In cases where cultures show the disappearance of the bacilli on the fourteenth day or over, the average interval between these cultures and the last culture showing the presence of the bacilli is prob- ably about eight days. The tabulation is as follows : Time from inception of dis- 1 ^^^^ ^ ^g^l^ ^ 42d day. 35th day. ease bacilli disappeared, j .> j •/ j Number of cases 1721 1706 1676 1622 Per cent, of total cases (1736) . . 99.13 98.27 96.54 93.43 Time from inception of dis- \ _ 28th day. 21st day. 14th day. 7th day. ease bacilli disappeared, j ^ ■ .z •- Number of cases 1468 1131 558 57 Per cent, of total cases 84.57 65.09 31.91 3.28 Time from inception of dis- j g^j^^.^^. ^^^ ^ 4th day. 3d day. ease bacilli disappeared, j . .' .^ ^ Number of cases 34 24 14 4 Per cent, of total cases 1.96 1.38 0.81 0.23 In the remaining 15 cases, or 0.87 per cent, of the total, the bacilli were found to have disappeared as follows : On the 57th day, 1 ; 59th day, 2 ; 60th day, 1 ; 62d day, 1 ; 64th day, 1 ; 65th day, 2 ; 68th, 72d, 73d, 74th, 75th, 77th, and 93d days, 1 each. DIl'IITHKRIA BACILLI. 665 TliL'^o tiirurc's cornjhorato the oonclu.sion drawn from observation of cases dnring the previous year — viz. tliat in a large proportion of all cases (about four-hftiis) the lvlei:)s-Lot!ler InieiUus disappears by the end of the fjurth week from the beginninn; of the disease; that in about two-thirds of all eases it disa[)})ears hy the end of the third week ; and in one-third of all eases by the end of the second week ; while in a small proportion of eases (about 3 per cent.) disappearance occurs within one week from the inception of the disease. The length of time elapsing between the inception of the disease and the date of the last culture showing the presence of the Klebs-Lofiler bacillus in the throat of each patient was tabulated for the above 1736 cases, and tor 414 atlditional cases, making a total of 2150 cases. This increased number is due to the fact that for various reasons (death of the ]>atient, etc.) no final culture showing the disappearance of the bacilli was made in the additional cases. As stated for the previous tabulation, the average interval between the last culture showing the presence of the bacilli and that showing their disappearance is probably about eight days, the additional cases in which no final culture was taken, of course, excepted. The bacilli may, therefore, have persisted in many cases for a longer period than that recorded. Of the 2150 cases tabulated, in 864 the last cultures showing ba- cilli to be present were made within six days or less from the incep- tion of the disease, and may be considered in the main as made for diagnosis. The remaining 1286 cases are tabulated as follows : Time from inception of dis- I -^r, i -, i i.i i j , .,,. ^ ^ r ■ ■ ' th dav and over. 14th da v and over. ease, bacilli present, J Number of cases 1286 7-11 Per cent, of total cases (2150) . . 59.81 34.46 Time from inception of dis- \ / 21st day 28th day 35th day 42d day ease, bacilli present, J ' ' I and over. and over. and over, and over. Number of cases 328 155 68 31 Per cent, of total cases 15.25 7.21 3.16 1.44 Time from inception of dis-1 .ri»i i j 'a^\ ^ ^ ^ ease, bacilli present, f " " ^^'^ ^^^ ^°^ '^^^^^ ^^'^ *^^-^' ^^^ °^^^- Number of cases 16 9 Per cent, of total cases 0.79 0.42 In the 9 cases in which cultures showed the presence of the bacilli for 56 days and over from the inception of the disease these cultures were made as follows : One each on the 57th, 58th, 60th, 61st, 62d, 63d, 64th, 88th, 90th, and 91st days, respectively. The above tabulation is chiefly ri:i in wliicli the (lini^^nosis had been sottlod by bacteriological examination. After several months the niaj) presented a very strikin*^ appearance. Wherever the densely crowded tenements were located, there the marks were very numerons, wiiile in the districts occujiied by private residences very few cases were indicated as having occurred. It was also aj)})arent that cases were far less ahundant, as a rule, where the tenements were in small groups than in tlie regions of the city Avhere they covered large sections. At the end of six months tiiere were square miles in which nearly every block occupied by tenement-houses contained marks indicating the occurrence of 1 or more cases of diph- theria ; and in some blocks many cases (15 to 25) had occurred. As the platting' went on from time to time the map showed the infec- tion of a new area of the city, and often the subsequent-ap])earance of a local epidemic. It was interesting to note two varieties of these local epidemics : in one the subsequent cases evidently were from neighbor- hood infection, while in the second variety the infection was as evidently derived from schools, since a whole school district would suddenly become the seat of scattered cases. At times, in a certain area of the city from whicli several schools drew their scholars, all the cases of diphtheria would occur (as investigation showed) in families Avhose children attended one school, the children of the other schools being for the time exempt. Another fact noted, perhaps as important as the foregoing, was that Avith the most careful inquiry it was impossible to find any connection with preceding cases of diphtheria in about one half of the first cases of diphtheria occurring in diiferent houses. The two following histories are instructive as showing that special conditions, which are largely unknown to us, determine in every indi- vidual the occurrence or escape from diphtheria under exposure : Two children in a family were taken sick with diphtheria and removed to the hospital. The servant (who was and remained apparently healthy) went to another family, where the youngest child developed diphtheria a week later. In the mean time a case developed in the family living in the next apartments. There were in this latter family three otlier children who were not isolated at all from the sick child, yet none of these developed diphtheria. The child of a man who kept a candy store developed diphtheria ; there were four other children in the family, and these were in no way isolated from the sick, yet none of them acquired the disease ; but children who bought cand}' at the store and other children coming in contact with these in school developed it. The secondary cases ceased to develop as soon as the candy store had been closed. Many similar histories could be given to illustrate the fact that the majority of persons, and even, perhaps, the majority of children, are not ordinarily very susceptible to diphtheria, and that in addition to receiving the germs of the disease into the respiratory passages they must be in a condition favorable to the development of the disease. It seems to be generally true that the more malignant a case of diph- theria is the more likely it is to cause diphtheria in others. This may be due to the high grade of virulence possessed by the bacilli, or to the peculiar association of other micro-organisms in the membrane, or to 668 DIPHTHERIA. the wider dissemination of the infectious matter through the dis- charges. It is also well known that young children are much more susceptible to diphtheria than older persons. It is comparatively rare for the parents of children sick with diphtheria to contract the disease, although in nearly every case they must at some time receive the germs into their throats. The blood of many adults has been shown to have antitoxic proper- ties to the diphtheria poison. At times, however, parents and nurses become infected, as in the following cases : (^A) Two months before a child living on the floor below the present case had diphtheria. Until a few days before the sickness of the patient the two families had kept apart. For the last few days they had visited each other, and the first patient, the mother, carried the child who had recovered from diphtheria. When the mother became ill she was still allowed to nurse and carry her children. Three days later her two children were discovered to have contracted the disease. The mother, too sick longer to nurse her children, confided their care to the father, who himself became infected. Antiseptic cleansing of the nostrils and throat was neither used in treatment nor prophylaxis in these cases before their admission to the hospital. (jB) In another case, five weeks before, there existed diphtheria in the flat below. The first new patient taken sick was a child, aged two and a half years, three days later another, aged four, and then the mother herself became ill. The children died ; the mother went to the hospital and finally recovered. When she left home her seven months' baby went to a friend's, where, three days later, two of the children developed diph- theria, and then finally the baby itself. The baby came to the hospital and died, and one of the other children died. From the throat the bacilli may be deposited upon the hands, other parts of the person, on handkerchiefs, bed linen, clothes, toys, and eating utensils. Under favorable conditions they may live from one to eight weeks on these infected substances, and under exceptional circumstances, as when the light is excluded and sufl&cient moisture is present, for eight or nine months. As the infected persons and things are scattered, the bacilli may be carried to healthy persons long distances away from the original disease. As time passes the number of living bacilli diminish, and where they are dry enough to float as dust they soon die. Conditions Favoring the Groioth of the Bacillus and its Length of Life Outside of the Body. — Diphtheria bacilli probably do not increase in water, on walls, carpets, etc., but they may possibly in milk, meat, and soups ; but even here the saprophytic bacteria are apt to crowd them out. Low temperature, moist air, and darkness protect the life of the bacilli. In warm weather either the germs quickly dry and die, or if moisture is present other germs grow and displace them. The prolonged light of summer also aids in killing them. Artificial heat in wdnter may do the same. Sea air is more favorable to the life of the germs than the drier, clearer climates. Thus in dark, damp cellars and basements we would expect most favorable conditions for the increase of disease. The habit of quickly cleansing dirty clothing prevents the spread of diphtheria, while putting j>ii'nTii/:n/A jiac/lij. (j(j9 iiitri'tcd clothiiiii' away in dark closets li<'l|ts to spread tlie iideetiou later. Ill many teiieiiu'iit-lioiises an epidemic of diplitheria lasts IVom two to three months. First one case occurs, then in several weeks another in the same family, and then hiter in other families; sometimes after six or sev'on months another case develoi>s, hut this perhaps is another infection from outside. Seldom area nuinher of families at once attacked. In li(t\' houses with ej)idemics only three were a,<;ain atta(;ked with mnnei'ous cases. Nowhere is it shown that a special locality, the gi'ound, or the air has any marked influen(!e upon diphtheria, but the people themselves, their communication with each other, and their habits of life o-ive rise to a slighter or greater outbreak of diphtheria. The history of an e])idemic of di])htheria which started on h'isher's Island, New York, in the sunnner of 18U1 is so instructive in showing- how unrecognized and convalescent cases started the disease that J will give its details, for many of Avhicli I am indebted to my friend Dr. li. i\I. l^iinter. From a number of the later cases I made cultures, so that besides the clear clinical evidence the nature of the cases was confirmed by bacteriological examinations. Fisher's Island lies between the eastern end of Long Island and Con- necticut, and is a summer resort. At the time of the epidemic ])erhaps one thousand people w^ere on the island. On Wednesday, in the last week of August, 1891, a seven-year-old boy, and, a day later, his mother, who were living in an isolated cottage, were taken ill with ^\•hat seemed to be a simple, well marked tonsillitis. A day later a young man living in one of a cluster of cottages, the inmates of which ate at a common table, developed a severe croupous tonsillitis, which would be suspected to be diphtheria if that disease were prevalent. There w^as now an intermission for three days, when suddenly in one day 15 cases of w'ell marked tonsillitis and half a dozen slighter sore throats appeared. The day before a severe storm had swept the island. In another day some of these cases began to resemble true dijihtheria, and the patients were quarantined; some of the children died. After this day's outbreak only 6 further cases developed on the island. These 25 cases of undoubted diphtheria and half a dozen of a more doubtful character occurred in eight separated cottages or groups of cottages. More instructive still than the outbreak on the island are the epi- demics started in other places by the scattering summer residents. The following cases emphasize the danger of sending away or receiving persons from diphtheria households. Among the group of cottages where the chief outbreak of diphtheria occurred was a family in M'hich one child w^as attacked with the disease, who afterward died. As soon as the case was considered to be diphtheria the nurse and another child M'ere sent home to a town in New Jersey. On the way home the nurse complained of a slight sore throat, but no attention was paid to it. Several days later the young child had diph- theria, and from these cases 24 others developed in the town. The town authorities had the sanitary conditions thoroughly investi- gated by a sanitary engineer, but, although in some of the houses the sanitation was faulty, in others there w^as nothing to complain of. 670 DIPHTHERIA. From one of the isolated island cottages a mother, a nurse, and two children left the island for their home on the mainland at the time of the outbreak, but before its nature was suspected. The nurse com- plained of a sore throat, and when at home developed diphtheria. Being in a physician's family, the nurse was carefully isolated. After recovery everything which had been in contact with her was burned or disin- fected. Ten days after she returned to the care of the children, and three days later the eldest child contracted diphtheria and died. Here a person who was supposed to have entirely recovered still carried infection. From another cottage on the island, after diphtheria had broken out, a grandmother with one of the children returned home to New Haven, developed diphtheria, and died. This was the origin of other cases in that city, A young man who was mentioned as coming to the cottages ill on the day of the first cases returned home three days later and died of diphtheria. It may be stated that although the drainage and sanitary conditions on the island were not at that time first class, yet they were no worse than in many other resorts, and to them could not be attributed the out- break. In the year following but two cases occurred on Fisher's Island. The Bacteriology op Pseudo-diphtheria. The pseudo-membranous inflammations which frequently complicate scarlatina (page 594), and to a less extent other infectious diseases, are, as a rule, not diphtheritic in character, and bacteriological examinations will show the diphtheria bacilli to be absent. The same is true for the ordinary acute cases of tonsillitis and pharyngitis and for some of the cases of acute pseudo-membranous laryngitis. Thus in the exudate in 40 cases of this character which I carefully examined bacteriologically, the cultures from all contained streptococci, and on most of the plates the streptococci far outnumbered all other micro-organisms. As in normal throats, so here, the streptococci taken from different ■cases, or even from different colonies of the same case, differed greatly in their growth and appearance. In most of the plates the long chained streptococci resembling the streptococcus pyogenes were the most numer- ous, but in quite a number the short chained cocci were in the majority. Staphylococci were often present in large numbers, and other bacteria were frequently added. Communicabilify. — Persuaded by my clinical experience and by the results of examinations of normal throats, that streptococci were prob- ably harmless while the mucous membranes were intact, I tried the following experiment : Inoculation of Human Throats with Streptococci. — A very thick cul- ture was made on agar plates from a severe follicular tonsillitis in a young child, so that there was obtained a luxuriant growth of strepto- cocci growing both in long and short chains, and also of other micrococci. A large amount of these mingled bacteria were, with the permission of a patient, plastered on a swab and then rubbed gently on his right tonsil and into its crypts. He felt a peculiar sensation in the tonsil for some TlIK'llAcrKinolJKIY OF J'SEUDO-DIPIITHERIA. 071 twelve hours ; this then jKisscd away, and was jn'cjl^ahly simply the result of the nieehanieal irritation. The next inorninii" the tonsil aj)])eare(l healthy exeept for a small [)ateh in a erypt ; from this and from the throat eultures were made. The j)lates _i»;ave very numerous eolonies of streptocoeei, while etdtures made from the same regions the day previous t(j the experiment gave \ery few streptocoeei. A second trial was made in a similar way from a culture of strepto- coccus pyogenes, eighteen hours old, from a case of extensive pseudle that the pyogenic cocci are not sufficient, as a rule, to excite an inflammation in the throat. A change appears neces- sary in the mucous membranes, either from the influence of some infec- tious disease or of some exposure, before the bacteria find the throat a proper soil for rapid increase and the mucous membrane vulnerable to their action. The following clinical cases confirm these views, and are cases in which the communication of the disease seems at first glance certain : (1) A family of eight — mother aged forty-five, six children whose ages ranged from twenty-five to ten, and a grandchild, aged two — slept in two rooms of a tenement just under the roof. Two days previously a heavy snow had fallen, and the day before the roof leaked, thus caus- ing the rooms to be very damp. The next morning four of the chil- dren had more or less marked tonsillitis, with follicular deposits or croupous patches, and on the following day the baby had an attack of croup. (2) In a school for young girls, on a day early in the winter, five were taken with follicular tonsillitis, and on the next day three more were attacked. (3) A nurse attends a patient with croupous tonsillitis, and has to pass frequently from the warm room to a much cooler hallway. On the third day the nurse is attacked with an inflammation much like that of his patient. The physician in charge ascribes it to a direct infection from the patient to the nurse. In many other similar cases the same exposure to cold, wet^ or other 672 DIPHTHERIA. deleterious influences which caused the first cases is the probable cause of the later cases, and not a direct infection. Of very many cases of pseudo-diphtheria examined, only a minority have been in known contact with others having similar inflamma- tions. Another important consideration tending to show that exposure rather than direct infection is usually the exciting cause is the fact that these inflammations are very prevalent in the cold and wet months. About the first of December they begin to multiply in dispensary and private practice, and increase till April ; then slowly diminish until June, to remain very infrequent until winter approaches. This rapid increase in the late winter and early spring is not found to be true to the same degree in diphtheria. The histories of many of these cases would indicate that the bacteria already present in the throat had been excited to a new growth by some exposure, rather than that a new infec- tion had been received. Some of these croupous inflammations may indeed be due to a recent direct infection, for one would expect that the bacteria from a fresh inflammation would be somewhat more virulent than those which had long lain dormant in the throat. The proof of this is, however, diffi- cult, for it is impossible to tell from cultures and the histories often give no assistance. Where attendants on the sick or persons in scliools and hotels are attacked after other cases have developed, it is difficult to determine whether they have derived the disease directly from the pre- vious patients or have developed it simply because they were subjected to the same sanitary influences as the first. The important fact is that if persons keep themselves from exposure to cold and other deleterious influences they are in little danger of contracting this variety of acute throat inflammation. In order to test to what degree, if any, pseudo-diphtheria is commu- nicated from one person to another, 450 cases, as nearly consecutive as possible, were investigated, all sources of infection were sought for, and the cases were followed up for two weeks after complete convalescence. In none of these was isolation or disinfection enforced by the Health Department. This is such an important question that the results of the investigation of the first 100 consecutive cases is summarized below in tabular form. As a comparison, a summary is given of 50 consecutive cases of true diphtheria which were taken from the same district and at the same time of the year as the first 50 cases of pseudo-diphtheria : Summary of Tabulated Cases. Total number of eases History of contact with other cases No history of contact Families in which more than one ease developed Recovered Died Cases complicated with scarlet fever Table 1 Table 2 Table 3 (50 families). (50 families). (50 families). Pseudo- Pseudo- True diphtheria. diphtheria. diphtheria. 56 57 60 7 7 33 49 50 27 5 4^ 13 56 53 46 42 17 4 63 1 Two had scarlet fever. ^ Three had scarlet fever._ 3 Six others had been in contact with scarlet fever, but never showed any characteristic rash. I'ATllULOUU'AL AyAKJMY Of DJl'llTlIKIilA. ()73 We find, therefore, in 113 cases of false or pseudo-diphtheria oe- enrrin>»; in 100 families, that 14 oeciirred at tlie same time with or shorth' after some otlier ease, and that it is j)ossihle to assdnu; tlie dis- ease liad been direetly eommunieated to them. In 9 of tlie 100 families more than 1 case devel<)ped. In these, as in the other 350 cases of })seudo-diphtheria investigated, it did not seem that secondary cases were any less liable to occur when the primary case was isolated than when it was not. In this connection one should remember that mild throat inflammations are very freciuent, especially in the early spring months, and that it is quite possible, where two cases occurred in a family together or within a short time of each other, that they may have both been due to exposure to some common conditions rather than to direct transmission. The presence of streptococci in nearly all healthy throats in New York City renders this assumption almost a probaliility. The presence of the same germs in healthy throats as well as in those of patients suffering from pseudo-diphtheria prevents us from deciding the point by bacteriological examinations. All of the 14 cases, except the 3 who had scarlet fever, were mild, and, indeed, leaving out of consideration the cases which occurred as complications of scarlet fever, there was only 1 death in 113 cases of pseudo-diphtheria, and in this case there was no history of infection or contact with other cases. Pathological Anatomy of Diphtheria. — The most charac- teristic feature of diphtheria is the formation of an exudate or pseudo- membrane. This usually appears on the mucous membrane of the tonsils, uvula, soft palate, pharynx, and nose. It frequently, however^ attacks the larynx and bronchi, either primarily or as an extension from the pharynx. Upon the mucous membrane of the tonsils and adjacent organs the lesions usually first appear as white thin patches of exudate or pseudo-membrane. Later in severe cases the membrane becomes thick, covering a large portion of the mucous membrane, and mav have a dirtv grav or vellowish tinoe. The tissues underlying and surrounding the pseudo-membrane are more or less intensely hypersemic and swollen. When the membrane is thick and adherent, it leaves on being torn off a bleeding surface which is quickly covered anew by false membrane. In some of the milder cases the exudate may easily be rubbed off and no bleeding occurs. The membrane may be made of visible layers, and they may be peeled off one from another. This is especially true of that covering' the uvula and soft palate, both of which may be oedematous and enor- mously swollen. The membrane in the larynx and trachea is of less thickness, and usually is less tough, than that of the pharynx and soft palate. Although, as a rule, the exudate in the larynx is thin and friable^ yet at other times it is thick and fibrous, so that a complete cast of the larynx and trachea may be coughed up or torn off. The swelling of the submucous connective tissue in the region of the ventricles of Morgagni, the false cords, and the aryepiglottic folds may give rise to marked obstruction to the breathing space. The formation of the ]>seudo-niembrane is due partially to the necrosed epithelium, and partly to the deposition of a coagulable serous Vol. I.— 43 674 DIPHTHERIA. exudate upon it. This is thrown out gradually, and thus may be formed in several layers. The connective tissue of the mucous membrane is hypera?mic and infiltrated. Sooner or later the epithelium under the pseudo-membrane is partly or completely lost, and the underlying tissue is covered instead with a network of fibrin which contains more or less partly or com- pletely degenerated epithelial cells and leucocytes. This network of fibrin frequently extends down into the submucous tissues. The fibrinous mass may be composed of a very fine reticulum of fibrin or of a narrow meshed network of tolerably thick bands. It may either contain many leucocytes in the spaces of the network or be mostly devoid of cellular elements. The superficial layer of the false membrane is frequently found early in the disease already broken down into granular detritus and permeated by masses of cocci and diphtheria bacilli. The degenerated epithelium usually disappears entirely by solu- tion or desquamation, but isolated vestiges may still be met with beneath the membrane when the epithelium has not become necrotic in its whole thickness, and also when the exudation has spread over adjoining portions of mucous membrane where the epithelium has not degenerated. The tissues beneath the pseudo-membrane are always more or less the seat of small-celled infiltration, and frequently also of fibrinous exudate or hemorrhage. The bloodvessels are congested, the lymph channels dilated and filled with fluid rich in fibrin. If the necrosis in diphtheria restricts itself to the epithelium, healing Avill take place without the formation of a scar. The necrosis may, however, extend to the connective tissue, in which case the tissue of the latter, including the vessels, may be entirely de- stroyed. There may be also in the tonsils and adenoid tissues areas of necrosis. In these cases a depression is left which fills up with gran- ulation or cicatricial tissue. Heart. — The pathological changes in the heart are among the most important lesions in severe diphtheria. Marked parenchymatous degen- eration of the heart fibres up to almost complete fatty metamorphosis may occur. The muscle fibres are degenerated, the nuclei are broken down or have disajjpeared, and the fibres themselves cease to be continu- ous. The endothelium of the vessels is swollen and the leucocytes are increased, and hemorrhages may be present between the muscle fibres. These alterations are only marked in the late cases ; in those quickest fatal only slight parenchymatous (changes are apparent. The valves of the heart may be the seat of fibrinous deposits. In the pericardium there may be collections of serous or more rarely purulent fluid. Kidneys. — In most severe cases the kidneys are in a state of more or less acute nephritis. The kidneys are usually hypersemic and enlarged, more rarely anaemic. The capsule is commonly non-adherent; the sur- face of the kidney is smooth, and is frequently the seat of small hemor- rhages. Upon the cut surface the markings are indistinct and shoAV degenerative parenchymatous changes. The cortex is thickened and reddish gray or yellowish gray in color. Microscopically, the signs of marked parenchymatous changes are evident up to complete necrosis of the epithelium lining the tubules. In these tubules evidences of hemor- rhages and casts are found. The epithelium of the glomerular capsules .vr.i//'7v>.i/.s' (H- i'u.\nYS(;i:.\L i>ii'iiriii:i:i.[. <;7.'> is swollen and pml iterated, and the vessels of" tlie tufts an; e()m])ressed by hcmorriiajies and exudates into tiie eapsule. The endothelium in the walls of the ki(hiey vessels is found proliferated or nnderj^oing degenera- tion. Frequent and small hemorriiages oeeur through the walls of tlie vessels. In severe eases tlic urine contains ahundant alhumin, degen- erated kidney epithelium, leucocytes, and hyaline easts, and in the most severe coarse and fine granular casts. Blo(^d cells are infrequent. The adenoid tissue of the spleen, intestines, and lymphatic glands shows the same areas of increased leucocytes and the same necrosis and hyaline degeneration of the tissue cells as are found in the kidneys and other organs. The submaxillary lymph glands are enlarged, often hemorrhagic, and may even be the seat of su})])uration. The lungs in cases dying of laryngeal diphtheria are frequently the seat of areas of broncho-pneu- monia or of general bronchitis. Subpleural ecchymosis is frequent, and the lungs exhibit areas of atelectasis or emphysema. Nervous St/stem. — Paralyses of the muscles of the palate, pharynx, heart, and voluntary muscles are due to degeneration of the peripheral nerves. The degeneration extends the whole length of the affected nerves, including the anterior and posterior roots. This is also true of the phrenic and cranial nerves. Minute hemorrhages are frequently pres- ent in the nerves. The spinal cord and brain show no marked lesion. Symptoms of Pharyngeal Diphtheria. — 3Iild Cases. — Those in which the local lesions are moderate in degree and in which the constitu- tional symptoms are not serious. These may be divided into two classes. In the first the onset is sudden ; the temperature rises to 103° F. in the first twelve hours, and then rapidly falls, so as to reach the normal one to two days later. With the rise of temperature the throat symptoms develop. The mucous membranes appear hyperseraic and congested, and after a few hours more or less extensive patches appear on the swollen tonsils, soft palate, pharynx or uvula. The loc^al symptoms increase for twenty-four hours, and then remain stationary. With the rise in temperature and the local signs of inflammation there are rapid pulse, loss of appetite, and some prostration. At the end of forty-eight hours the constitutional symptoms abate. The temperature is rarely above 101° F. The pulse may still be rather rapid, but is regular and of good force. The local inflammation subsides in from three to seven days, and the patient is fairly well except for a slight anaemia. In the second class the throat inflammation develops slowly. There is a little pain on swallowing. The glands at the angle of the jaw are usually a little swollen and the throat feels sore. Inspection will show slightly swollen tonsils, with follicular deposits of exudate or small patches of pseudo-membrane. The temperature is not elevated more than one or two degrees or it may be normal. Except for slight loss of appetite, restless sleep, and slight prostration the symptoms are mainly those of a subacute throat inflammation. The exudate may be strongly adherent, so that it can only be removed by force, or it may be loosely attached. The diphtheritic deposit remains from two to seven days, and then recovery is established. A moderate amount of ansemia persists for some weeks. Some cases in either of these two types may, instead of recovering, suddenly begin to extend and develop into the 676 DIPHTHERIA, most severe type. Even in these mild cases slight paralysis may occur up to three weeks after apparent recovery. Severe Cases. — Here, again, two extreme types of invasion are noted. The local and constitutional symptoms may slowly develop, or they may become fully developed within the first twenty-four to forty-eight hours, either with or without high temperature. In exceptional cases a chill is the first symptom noticed. The mind is usually clear, although in the worst cases mild delir- ium or stupor may develop. The mucous membrane of the pharynx and tonsils is reddened and swollen. The uvula may be oedematous, elongated, and greatly swollen. Portions or all of the mucous mem- brane of the tonsils, the pharynx, and the soft palate are covered with more or less thick and fibrinous pseudo-membrane of a grayish color. The glands of the neck and their adjacent tissues may be slightly or markedly swollen. If the nasal cavities are involved, the breathing and voice are affected. From the nose flows a discharge which may be of an intensely irritant character. The nasal obstruction may be partial, in which case the irrigating fluid passes easily, or it may be total, so that it is only possible to force fluid through the nose under high pressure. After forty-eight to seventy-two hours the fever, if present, com- monly subsides. In favorable cases the pulse becomes less frequent, and remains of fair force and regularity. The appetite improves and the intellect remains clear. After forty-eight hours the local symp- toms remain stationary from the third to the fifth day, and then the swelling subsides ; the membrane begins to loosen at the edges, and soon peels off, leaving a superficially ulcerated surface, or it may more grad- ually melt away. The glands of the neck decrease in size, and the jjatient is convalescent and certain to recover unless dangerous par- alysis develops. In other cases the course of the disease is unfavorable. The temper- ature may fall nearly to the normal, but the pulse becomes more rapid, feeble, and irregular, or it may in certain toxic cases suddenly for a time become very sIom^, 40 to 50 to the minute. Before death the heart's ac- tion usually becomes more irregular and rapid. Other patients grow apathetic. The urine is apt to be scanty and contain albumin and casts. These cases may suddenly develop ursemic convulsions and die, or may gradually waste away. Some develop a persistent nausea and vomit all food. Others suffer from paralysis of deglutition and of the muscles of respiration. Still others seem to be recovering from the diphtheria when the symptoms and physical signs of pneumonia develop. The temperature then rises to 103° or 104° or even 106° F. In other cases the false membrane does not limit itself to the pharynx, but spreads to the larynx. These patients then have added the special symptoms due to obstruction to the breathing. Finally, there are a group of cases that seem to die as if from gradual systemic poisoning by toxin. They lose weight, become pale and anaemic, have no appetite, the tongue is dry and coated, and they gradually sink away. Malignant Cases. — There are certain cases of diphtheria which run an especially malignant course both in children and adults. Within twenty- four hours the tonsils, palate, and lateral portions of the pharynx are covered with thick membrane and are enormously swollen, the breath is SYMPTOMS OF LMiyyOICAL DlVUTllKlllA. 077 sweetish, the saliva dribbles from the mouth, the uUmds of the neck and their siirroiiiidinu' (issues are g-reatly swollen. The tt'uiperatiire is fre- (|ueutlv but slightly elevated or it may be subuoi-mal. The heart's acti(jii is rapid :uul feeble or it may be very slow aud irregular. 'I'he intellect, at first clear, becomes cloudy. Within three to live days the most robust die. Another class of malignant cases are the so-called septic cases. The amount of local swelliuii: and exudate on the tonsils and palate may not be very extensive, but it is of a dirty, oauu-renous appearance. If the nostrils are invaded, there is a bad-smell int;-, thin discharge. The temperature runs a hi.uh, irregular course from 103° to 106° F. The tongue is dry and coated and the appetite is poor. The glands of the neck are moderately or greatly swollen. The extremities are cool, the pulse is rapid and feeble. Pneumonia or su])puration of the middle ear frequently develops. With an irregular high temperature the chil- dren become more and more apathetic until death usually supervenes. Symptoms of Laryngeal Diphtheria. — The symptoms in laryn- geal diphtheria differ somewhat according as to whether the process is a primarv one or is an extension of a pharyngeal diphtheria to the larynx. In the first case laryngeal symptoms are added to those already present. In larvngeal diphtheria the symptoms are those due both to the absorption of the poison of diphtheria and to the mechanical obstruc- tion of the larynx. The obstruction occurs more quickly in children than in adults. The symptoms may develop slowly ; the child complains of a sore throat, of a little hoarseness, has loss of appetite and slight fever. There may be a dry, hard cough. In some within twelve to twenty-four hours the hoarseness becomes marked, the breathing is somewhat obstructed, the temperature reaches 100° to 103° F., and the child is restless. Soon, un- less relief is given or the process subsides, the symptoms of laryngeal obstruction are fully developed. The respiration is noisy ; inspiration and expiration are labored and prolonged. Cyanosis is developed, and there is marked recession of the soft parts of the chest in the epigastric and jugular regions. The accessory muscles of respiration are called into action and the chest is held expanded. In spite of every exertion inspiration and expiration are insufficient. At short intervals the child will sink back as if exhausted, the breathing is feebler, and for a moment or two the child dozes, only to awaken again to struggle for air. It throws itself about the bed — lies first on one side, then on the other. Until cyanosis is marked the intel- lect may be clear. Frequent desire to urinate is manifested, which adds to the distress of the child. As the obstruction increases attacks of almost complete suffocation take place ; the child struggles violently for air, sitting up and using all its powers. After a time respiration may become freer, and the child sinks back only to have renewed spasms later. Sooner or later it becomes exhausted ; the breathing becomes more and more feeble ; the extremities are cold and the skin is of cadaveric hue. Death follows from an attack of suffocation or slowly by asthenia. The duration of life in fatal cases is usually from two to seven days when operative relief is not given. In purely laryngeal cases, when operative relief is not given and death results early, the temperature frequently remains but little ele- 678 IHPIITIIKRTA. vated, although in a few it may reach 103°-104° F. If, on the other hand, the kings are involved, the temperature is, as a rule, elevated to 102° or 104°, or exceptionally 106°, F. After intubation or tracheotomy the temperature frequently rises, in the more severe cases, within twelve hours to 102°-104° F. When operative relief is attained the breathing becomes natural, mucus and shreds of membrane are coughed out, and the child sinks back to sleep. In a portion of the cases the relief is permanent, and the patient progresses uninterruptedly to recovery. In others the symptoms of obstruction again appear, while in still others a secondary pneumonia develops to delay convalescence or cause death. Symptoms of Diphtheria in Detail. — General Condition. — There are a moderate number of cases having very limited patches of pseudo-membrane in which no appreciable symptoms of constitu- tional poisoning show themselves. They are mostly discovered be- cause of their association with more marked cases. Even mild cases show loss of appetite and of the desire for work or play. They become more or less pale and anaemic. The more grave cases soon exhibit severe constitutional effects. They soon have marked prostration, are restless or apathetic, or both by turns. If they live long enough, they become emaciated. The sleep is uneasy. In septic cases mild delirium or stupor may develop. These cases give the impression of being very dangerously ill. Temperature. — The cases differ greatly. Many, both mild and severe, begin with a temperature of 102° to 104° F. In the great majority the fever subsides, and even in the most severe uncomplicated cases the temperature is apt to range from 98° to 101° after the first forty-eight hours. Some, severe from the start, have a normal or even subnormal temperature. A certain proportion of septic cases, and all having a complicating pneumonia, develop a high temperature. Other complications, such as otitis or the development of an abscess, will cause elevation of temperature. A rise of temperature to 103°-104° F. in a case of laryngeal diph- theria indicates usually a beginning bronchitis or pneumonia. Nervous System. — In the mild cases, except for a certain amount of apathy, no symptoms are present ; in the more severe, there may be also observed the general symptoms of mild delirium, restlessness, and rarely convulsions ; also, apathy and stupor in the severest cases. Cireulatory Apparatus. — In mild cases the pulse is frequent, and perhaps slightly irregular. In bad cases it may be very frequent^ 120-160, and weak. The force of the heart apex beat is diminished and the sounds indistinct. After the third or fourth day the rapid pulse may suddenly become markedly slowed. From 120 it may fall as low as 45 or 50. It is irregular and varies in force. This is an extremely grave symptom. After twenty-four to forty-eight hours, if the patient lives, the pulse is apt to again become rapid and feeble, and so remain until death. Digestive System. — In the mildest cases there is little digestive dis- turbance, but in those of any severity loss of appetite is noted. In the worst toxic cases no food at all may be retained. The bowels are not, as a rule, affected. COMPLICATIONS OF DIl'lITIir.mA. 079 Tlw Urine. — In the mildest cases, usually no all)iimin is found in the urine, but exceptionally, after the third or fourth day, it may aj)pear. in the more severe cases casts, kidney detritus, and large quantities <)f albumin are usually present. In the worst cases partial or total suj)- pression of urine is apt to occur. These may later develop uraemic symptoms. Lymph (rlands. — The lymphatic glands in the neck are usually somewhat enlarged. In the more septic cases they may become enor- mously swollen. Suppuration is rather infrequent. Skin. — A small percentage of cases develop a general erythema, which niav resemble scarlet fever or measles. An urticaria may also appear. In severe and septic cases hemorrhages occur in the skin as well as in the mucous membranes. Joints. — The joints, except in septic cases, are very seldom affected in diphtheria. CoMPLiCATroxs OF DIPHTHERIA. — Pneumonia. — The most feared complication of laryngeal diphtheria is broncho-pneumonia. In pharyn- geal diphtheria it occurs but seldom. It may develop within twenty- four hours or it may not occur till convalescence is established. In these a little fever remains, and the lungs give the signs of a mode- rate bronchitis. The temperature then slowly or quickly rises and the respirations become more rapid. Physical examination shows be- ginning broncho-pneumonia, perhaps in one or both lower lobes be- hind, or, again, in disseminated areas throughout both lungs. In these cases the pneumonia is apt to run a subacute but progressive course. After one to three weeks the child succumbs to exhaustion. Heart Failure. — From the beginning of the separation of the mem- brane until well into the fifth week all severe cases are in danger of heart failure. When this symptom is threatening the patient is pale and the pulse is small and irregular. It is usually rapid and weak or verv slow and irregular, 40—50. The extremities are cold. The mind remains clear and anxious. The attack may pass off or the pulse may be lost : the patient loses consciousness and death comes gradually. Others, apparently well, suddenly become unconscious, and die almost instantaneously of heart failure. Paralysis. — This is one of the most characteristic symptoms of diph- theria. Frequently with the final separation of the membrane, but also often after weeks, paralysis develops in the muscles of the soft palate, less frequently in those of deglutition, of the eye, of the respiratory organs, or finally of groups of muscles throughout the body. AVhen the palate is affected speech is nasal and fluids regurgitate into the nostrils. When the muscles of accommodation are affected, the child cannot read and the pupils do not react. When the voluntary muscles in general are af- fected the patient may be completely helpless. As a rule, complete recov- ery takes place within from three to eight weeks, but in the worst cases marked atrophy occurs and months elapse before recovery takes place. Relapses. — In a small number of cases, after partial or complete disappearance of the membrane, a slight recurrence results. With the exudate's appearance the temperature may rise and the glands of the neck become swollen. As a rule, the lesions clear up in a few days. The lymphatic glands may remain slightly enlarged for weeks or months. 680 DIPHTHERIA. The only cases in which a relapse is serious are the laryngeal ones. A relapse may occur as late as the fourth week. Diagnosis of Diphtheria. — In deciding whether a doubtful case is one of diphtheria or not it is necessary to take into account whether the patient has been exposed to diphtheria, to scarlet fever, or to other infectious diseases. If in any case exposure to diphtheria is known to have occurred, even a slightly suspicious sore throat must be regarded as probably a mild diphtheria. If, on the other hand, no cases of diphtheria have been known to exist in the neighborhood, even cases of a very suspicious nature would probably not be diphtheria. In judging from the appearance and symptoms of a case one must first acknowledge that there are certain mild exudative inflammations of the throat ])elonging both to diphtheria and pseudo-diphtheria which appear exactly alike, have similar symptoms, and similar duration. It is even possible to examine two cases, knowing that one is surely diph- theria and the other surely is not, and yet be unable to determine which is true diphtheria and which is pseudo-diphtheria. It is not meant to imply that a case is one of true diphtheria simply because the diphtheria bacilli are present, but rather that the doubtful cases not only have the diphtheria bacilli in the exudate, but are capable of giving true charac- teristic diphtheria to others, or later developing it themselves ; and that those in whose throats no diphtheria bacilli exist can under no conditions give true characteristic diphtheria to others or develop it themselves. It is indeed true, as a rule, that cases presenting the appearance of ordi- nary follicular tonsillitis in adults are not diphtheria. It is also true that now and then a case having this appearance is one of diphtheria, and almost every physician has seen such cases from time to time in households infected with diphtheria. On the other hand, in small chil- dren mild diphtheria very frequently occurs with the semblance of ordi- nary follicular tonsillitis, and in large cities where diphtheria is prevalent all such cases must be- regarded as more or less suspicious. Appearances Characteristic of Dijjhtheria. — The presence of irregular shaped patches of adherent grayish or yellowish gray pseudo-membrane, especially if they are on some other ]3ortions than the tonsils, is, as a rule, diagnostic of diphtheria. Occasionally in scarlatinal angina or in any severe phlegmonous sore throats patches of exudate may appear on the uvula or borders of the faucial pillars, and still the case may not be one of true diphtheria ; these are, however, exceptional. Thick grayish pseudo-membranes which (;\()sis or i>ii'irriii:i:iA. 081 fiiucial j)illars, arc rarely diplitliurilic. As a rule, pst'iidd-incnibrancMtus inHaiMiuatitms (■(miplicatinn: scarli-t IV-vci- and otlicr intcc-tiou.s diseases are not diphtheria. But from time to time such cases, if they have been exposed to diphtheria, may he (;omplieated by it. Tin' K.viuUifc III hijihtlicrKi contrI I'llTII IlIUA. 083 mild clciiiisin^ solution, siidi :is Dohdl's, oi- a weak disinfectant, siidi a.s 1 : 10,000 atiiU'oiis solution of hicliloridc of nuTcnrv. ,Vn imnHiiii/- inj; dose of antitoxin, tojxotiier with the fre(|nent cleansint.'' of the thnnit, will practically ensure an iinmunity from diphtheria. Local Treatment. — If one could destroy the diphtheria bacilli at a time when they are localized to one spot of mucous membrane, the dis- ease miirht be at once aborted and its extension to distant ]»arts mi^iht be prevented. Many clinicians of great experience in the treatment of diphtheria have advised various methods to accomjdish this desired residt, but Fig. 49. Position of child during irrigation. personally I believe that their success must always be limited, and for the followino; reasons : The diphtheria bacilli are not limited to the £,exact spot where the pseudo-membrane has developed. They are pres- ent in the throat secretion, bathing all parts of the pharynx and tonsils 684 DIPHTHERIA. before even tlie local lesions are manifest. Lying thus in the crypts • and recesses of the parts, they are not all killed by such antiseptic fluids as are attempted to be applied to them. Further, at those places where local lesions are apparent the bacilli are already present lieneath the superficial layers of membrane, and cannot be directly influenced by antiseptic fluids. If the bacteria were upon a dead surface, we could kill them, but to destroy tliem without injuring the living epithelium is a very different undertaking. Just a year ago a series of experiments were carried out by the resident physicians of the jN'ew York Hospital for Contagious Diseases (Drs. White and Somerset) to test the comparative value of irrigating the nose and throat with simple cleansing solutions and with disinfectants (1 : 4000 bichloride of mercury and 5 to 10 volume solu- tions of peroxide of hydrogen). After a pretty thorough trial it was very difficult to see more than a trifling advantage in the antiseptic solutions. If we attempt to kill the bacilli by caustics or actual cautery, we are apt to injure the tissues without killing all of the bacteria, so doing prob- ably more harm than good. I believe, therefore, that we should not use any treatment which will irritate or lacerate the mucous membrane. I believe that no swab should be used to make applications to the mucous membrane unless it is done by the physician or by a trained nurse, and only then with the greatest care. Personally I prefer to trust to irriga- tion. For the nostrils I prefer a simple tepid salt solution. This is best applied through the fountain syringe. If the nostrils are so firmly plugged that great pressure is needed, then an ordinary hard-rubber syringe can be used. To its point is attached a short rubber tube, end- ing in a bulb to fit the nostrils. The force needed may be very great, but the shock is of less harm than the continued total occlusion of the nostrils with the probable production of sepsis. When the local lesions of diphtheria are limited to the tonsils, irri- gation of the nostrils is unnecessary, but when the posterior nares are involved, the nostrils should be irrigated three to six times a day. Even weak solutions of peroxide of hydrogen are often very irritating to the nasal mucous membrane. Great care should be taken if it is thought desirable to use this substance in the nostrils. For the irriga- tion of the mouth and pharynx either a normal salt solution or a 1 : 4000 bichloride of mercury or a five-volume peroxide of hydrogen solution may be employed. If antiseptic solutions are used small blunt- pointed glass or rubber syringes are employed. In older children and adults the cleansing and soothing effects of irri- gation are often marked. In these cases I prefer to use irrigation with warm salt solution every hour or two, and then every three to six hours to irrigate with some antiseptic solution, especially a 1 : 1000 bichloride solution. The irrigation of the throat is, as in the case of the nostrils, best carried out by the fountain syringe. In young children the irriga- tion of the nose and throat, either with simple salt solution or with an- tiseptics, every few hours, is of great service unless they struggle against it. Such cases to be handled properly need the greatest amount of good judgment. When the strength is good and the nostrils and pharynx are full of TREATMEXT OF J.ARYSfn-.AL DTPJTTTTKnrA. 085 discharge and niemUrano, it is well to insist on flcansin: internally of the tincture of the chloride of iron or of the bichloride of mercury in small fre(|uent doses lias considerable local effect upon tlu> niucoiis membranes of the throat and pharynx. In hospital cases the irrigation of the nostrils witli salt water, 1 per cent, boric acid solution or 1 : 4000 bichloride solution, has not appeared to cause ear trouble. Indeed, suppuration of the middle ear has been rather less frequent when this method was employed. General Trcatmcni. — The air in the patient's room should be as pure as possible and kept at a temperature of 70°— 72° F. The treatment of diphtheria by antitoxin will be considered later (page 692). The drugs suggested for the treatment of diphtheria have been num- berless, but few of them have proved themselves as of use generally. At the New York Hospital for Contagious Diseases mild cases are given an abundance of light diet, milk, broth, eggs, etc., and a dose of 1000 units of antitoxin. This and the local treatment is all they receive. ]More severe cases are given brandy from half an ounce to twelve ounces in the twenty-four hours, according to the severity of the disease and the amount of prostration and the weakness of the heart action. In these severe cases and in any where paralysis threatens, strychnine is given three times a day in doses of -^-q to yto grain. As the patients begin to convalesce they are given the carbonate or albu- minate of iron as a tonic if they show much anaemia. A complicating pneumonia is treated as it is when present in other conditions. The antipyretics are to be avoided, because of their depressant effect, and also because the temperature is, as a rule, not seriously high in diphtheria. The tincture of the chloride of iron in moderate doses may be of benefit, both locally and for its tonic effect, though if it causes nausea or vomiting it should be stopped. Large doses do not appear to have any more beneficial effect than small, and are more apt to cause irrita- tion of the stomach. The internal administration of bichloride of mer- cury has not seemed to me to be of any great value. Good observers advocate small doses of quinine. I myself have had but little experi- ence with its use. AVhenever paralysis of the muscles of deglutition has become suf- ficiently marked to prevent the swallowing of food, it is necessary to feed through a soft-rubber tube passed through the nose to the pharynx and cEsophagus. Teeatmext of Laryngeal Diphtheria. — For the relief of obstruction in laryngeal diphtheria there is the inhalation of the fumes of suljliming calomel, the inhalation of warm steam with or without lime or other additions, the application of warmth or cold over the larynx, and the use of medicines internally, especially those causing nausea or vomiting. The first two are the most important means of combating the begin- ning laryngeal obstruction. DIPHTHERIA. Calomel Fumigation. — This was first advocated by Corbin in 1881, and has since been extensively used. The inhalation of subliming calomel does not, as some claim, destroy the diphtheria bacilli, but it does apparently, in some cases, greatly relieve the obstruction with its accompanying symptoms. This so often follows each employment of it that there seems no doubt of its action. It does not, however, afford relief in all cases, even when used very early. The method of employing calomel fumigation varies with the appa- ratus at hand. The child should be put in an im])rovised tent so as to confine the fumes sufficiently to fill the tent with a rather dense white smoke. Ten to twenty grains can be thrown on a few live coals placed on a shovel and held under the tent while it sublimes, or a lump of live coal may be put in an iron or earthenware vessel and over it a strip of iron or an iron spoon upon which the calomel is placed. In the larger cities a suitable apparatus can be bought ready for use, M^hich is, of course, more convenient. Steam. — The inhalation of warm steam is certainly at times of great benefit. To the water may be added equal parts of lime water, or to each pint one or two teaspoonfuls of compound tincture of benzoin. The warm damp vapor is the chief thing. The steam should be inhaled as warm as possible, and the patient is protected from the damj^ness by a covering of oil, muslin, or a thin blanket. If in a strong child the laryngeal symptoms increase so that it seems as if intubation will soon become necessary, it is well to try the effect of vomiting. For this purpose a dose of ^ to 1 fluidounce of syrup of ipecac should be given every ten minutes until effective. Instead of ipecac, tartar emetic or the yellow subsulphate of mercury, ij-v gr. to a child of two years, and repeated, may be given. If an attack of vomiting does not give appreciable relief, it is not well to repeat it, as it exhausts the child and offers but slight hope of benefit. If a child is much prostrated, it is unwise to resort to emetics at all. Intubation and Tracheotomy. — If in spite of treatment the laryn- geal stenosis advances so far that actual obstruction to breathing is marked and increasing, we must resort to intubation or tracheotomy. By one or the other of these means we overcome the obstruction to the entrance of air through the larynx, and thus prevent suffocation, unless the membrane is too extensive below the end of the tube. We also aid the expulsion of mucus and portions of membrane through the opening formed by the tube. The insertion of the tube does not, of course, limit the extension of the disease or prevent complications. The apparent improvement due to the removal of the obstacle to respira- tion will therefore only be permanent when the disease itself is not too severe. The time at which intubation should be performed is a question of the greatest importance. The insertion of a tube into the larynx is not wholly a matter of in- difference even in trained hands. More or less abrasion of the swollen and inflamed laryngeal mucous membrane may be caused by its inser- tion, and its presence for several days is very likely to cause a superficial ulceration, either where its lower end impinges on the trachea or where its sides cause pressure. 'n;/: \r.]/i:.\T or lahysciwi. nirirriih'h'/A. r,87 On the other IkukI, so soon as the hirvn<^eal stenosis becomes so marked that tlie person strn(i,<>;les ibr air, and in spite of" tlie struggle suftieioiit aeration of" the blood does not take place, that condition is a great detriment t(^ tlie condition of" the chihl loiii;- before anv a(;tnal suf- focation is impending. In spite, then, of tiie j)ossibh' injury to the larynx of the insertion and retention of the tube, we should not wait too long and thus allow a greater injury to occur. If, therefore, the stenosis steadily increases and the retraction of the epigastric and jugular regions becomes decided, and cyanosis is evident, it is better not to wait longer. If it is expected to intubate, one would operate at a somewhat earlier Fk;. 5U. O'Dwyer's intubation instruments. period than if it is intended to do tracheotomy, since the latter is a some- what more serious procedure. Intuhiition Iii.sfriDnenta. — The outfit used is that devised by O'Dwver. 688 DIPHTHERIA. It consists of a series of six tubes of varying sizes, both as to the cali- bre and length. They are arranged to fit the larynx at diiFerent ages ; the tubes usually supplied are those suitable for children, but especially prepared tubes for adults can also be procured. Besides the set of tubes there is an introducer, an extractor, and a mouth gag. The tube as seen in the photograph is enlarged at its upper end posteriorly ; there is also a moderate swelling in the middle portion, which fits into the ventricles of the larynx. Through the lip of the upper end of the tube there is a perforation for the passage of a strong thread. The introducer consists of a straight wooden handle ending in a steel rod, which at its last inch is curved downward at an angle of 90°. It ends in a small screw tip on to which the small rod which holds the tube screws. Over the rod of the instrument a flexible outer tube is attached ; this may be shoved down over the rod, thus pushing the tube from the holder after it has been placed in the larynx. The extractor is shaped like a pair of laryngeal forceps ; the lower arm ends in a wooden handle. Through the juncture of the steel and wooden parts there passes a screw which is so placed that it can be made Fig. 51. Position of child during operation of intubation. to project a greater or lesser distance from the handle, and thus prevent the full approximation of the two arms of the extractor. This regulates the extent to which the tips can be separated. If by any means, there- fore, the tips of the extractor have not entered the tube, they are thus TEEATMENT OE LARYXGEAL DIPHTHERIA. 689 prevented from sj)rcadinir too widely apart and injuring the tissues of the hirynx. Intubdiion hi Ldrifiigeal Diphihcria. — Position for Iniubation. — The child f^hould be wrapped in a sheet or in a blanket, so as to confine the extremities, but leave the neck exposed. Pin the sheet behind. The child should i)e held in the lap of one nurse, sitting in upright position with the la-ad against the left shoulder. The mouth gag is inserted in the left side of the mouth, and held in place by a second nurse who stands behind and who at the same time steadies the child's head. The head should be kept erect. If necessary the child can be intubated lying down, and some, indeed, prefer this position. Insertion of the Tube. — The index finger of the left hand is passed along the dorsum of the tongue until it feels the epiglottis. It is then passed behind the epiglottis until it touches the arytenoids. In a small child the epiglottis is often difficult to feel, and in any case where there is much swelling it may be impossible to make out its exact location. To insert the tube, which has been selected of the proper size and placed on the introducer, it is passed along the iuuer side of the index finger down to the tip of the finger ; the handle bars are tlien raised and the tube is passed downward and forward into the larynx. In doing this the finger is pushed slightly aside by the tube. The beginner is very apt not to pass the tip of the tube sufficiently forward, and may thus pass it into the cesophagus. The tube having passed into the larynx, place the tip of the index finger of the left hand on its upper end, push the tube off with the obturator, and withdraw it. In the insertion of the tube and in the extraction of the holder one should be sure to keep the tube in the median line. It is also very essential to have the child's head kept perfectly still. A thread which has been passed through the eye of the head of the tube is left until one is perfectly satisfied that the tube is not clogged with membrane and that it is giving proper relief to the child. It is also necessary to be sure that the tube has not passed into the pharynx and cesophagus. After the insertion of the tube it is well to give the child a little water and whiskey, in order to cause it to cough by the slight irritation ; it is also valuable as a stimulant to the child after the exertion occasioned by the passage of the tube. After the insertion of the tube the operator is usually able to ascer- tain whether it has relieved the stenosis within a few minutes, but in exceptional cases, where the child is very weak, it may be impossible to determine this for half an hour. In very young children it is possible to intubate without using the gag, but in older children one runs the risk of being severely bitten without it. Treatment of the Patient ichile Intubated. — It is frequently the cus- tom to raise slightly the foot of the bed on A\hich the child lies, and it is always well to keep the child prostrate if possible. A matter of vital importance is the feeding of the child. This is first attempted with the child lying down, with the head depressed be- low the rest of the body. If the child does not take fluid nourishment Vol. I.— 44 690 DIPHTHERIA. in this way, it is allowed to drink in the natural manner. If it is im- possible to feed the child by either of these means, it must be fed by a stomach tube passed through the nose into the stomach. For a child of one to two years the tube should be the size of a No. 6 catheter ; for a child of three to four years, a No. 8 catheter. Some physicians pre- fer, instead of a fluid diet, food which is of greater consistency or even Fig. 52. ^v reeding child wearing intubation tube. entirely solid At the Willard Parker Hospital for Contagious Dis- eases, however, fluid diet is, as a rule, preferred. Extraction of the Tube. — At any time after the insertion of the tube it may be coughed up, or it may become obstructed by membrane either blocking the tube or filling up the trachea below. Whenever the tube becomes obstructed it must be instantly removed. In those cases in which, however, the tube is neither coughed up nor obstructed it is found best to leave it in for such a period that seven days have elapsed from the time of the beginning stenosis. If the tube is re- moved earlier, it will usually have to be replaced, with the danger always of creating slight abrasions or injuries of the larynx. Method of Eaytracting the Tube. — The child is held in exactly the same position as for intubation. As in intubation the index iinger of the left hand is passed along the dorsum of the tongue, then behind the epiglottis, and downward until it feels the end of the tube and makes out its lumen. The finger should detect Avhether the tube is lying in the proper position — that is, with the long diameter of the opening lying from before downward. The extractor is then passed along the finger. TUKATMKST OF LAUYMIKM, DJJ'JJTlIh'lUA. 091 as the tube was in iiituhation, until one brings the ti]) of the extractor a<»aiiist till' side ot" the tip of the finger and the opening into the head of tlie tube. A beginner must be eai'eful that he does not mistake tiie shouhU'r of tile extraetor for tlie tube. Tlic handle of tiie extractor shouUl be raised to a horizontal jiosition, as otlierwise only the tip will enter into the tube and the danger of slij)ping will be very great. 'I"'he extraction is accomplished by lifting the extraetor witli its tube until it touclu's the hanl palate, and then the handle is lowered through an arc of 90° and the tube removed. In young chihb'en, as in intubation, a gag is not necessary. The extractor, as stated in the descrij)tion of the instrument on page 688, is provided with a safeguard in the shape of a screw which passes through the lower arm of the handle so as to come in contact with the upper arm. This, by ])ro])er adjustment, serves a double purpose. First, it })revents the opening of tiie jaws of the ex- tractor to such a degree as to injure the soft parts if by chance it should not have entered the lumen of the tube ; and, second, it gives informa- tion as to wliether the tip of the extractor is witliin the lumen of the tube. For with the screw properly set it will be impossible to obtain the click of one arm of the extraetor against the screw if the tips are within the lumen of the tube. When, for any reason, a person is un- skilled in the extraction of the tube — and for the beginner the extrac- tion is rather more difficult than the insertion — it is possible in an emergency, in the majority of cases, to easily expel the tube by placing the child face downward with the body slightly elevated, and pressing gently against the trachea along its anterior surface, just below the end of the intubation tube. This method should not be used when one is skilled in removing the tube with the extractor, because there is always danger of causing abrasions of the mucous membranes by too forcible pressure. The tube is removed from the mouth by the finger. Another form of extractor has been used, that devised by Dillon Brown. This is employed like the previous method when one is not skilled in handling the extractor invented by O'Dwyer. In order to use the Brown extractor a special set of intubation tubes is necessary. These have, at the anterior edge of the head, a small loop. This allows an extraetor to be used which is attached to the finger and which ends in a little hook. The finger is passed, with the hook attached, over the dorsum of the tongue until it touches the tube, when the hook is passed into the loop and the tube thus removed. In cases where a great deal of swelling is present the swollen tissues are apt to cover up the little loop on the end of the tube and make it very difficult to remove the tube by this extractor. At the hospital, immediately after the extraction of the tube, the child is given A^ grain of morphine hypodermically, and an ice bag is applied to the larynx. It is sought in this way to lessen the irrita- tion and swelling in the larynx. The child is still kept in a recumbent position for one or two days. ^yhen the tube does not give relief, one of two things is possible : either a tube with a much larger lumen, but which is lighter and shorter, may be inserted, or tracheotomy must be performed. In but few cases will one of these large calibre tubes succeed where the ordinary tube has failed. Tracheotomv will more often o-ive relief, but in these cases the 692 DIPHTHERIA. membrane is so extensive that in spite of the temporary improvement tlie majority of the cases finally succumb. Although at the autopsy frequently a moderate degree of ulceration is found, yet it is probable that this takes place chieHy in those cases where the resistance of the tissues has been greatly lessened by the severe toxic infection. There are a few cases where, on account of paralysis or the growth of granulations, the child is unable to breathe without the tube. Here a secondary tracheotomy may be tried, and the granulations may be re- moved by operation. The tube probably predisposes somewhat to pneu- monia, and in some cases it seriously interferes with the feeding of the child. In those cases where the ordinary tube does not afford sufficient space for the expectoration of the mucus and loosening membrane, the wider tube devised by O'Dwyer may be substituted. These are usually bad cases. The Advantages and Disadvantages of Intubation and Tracheotomy Compared. — Intubation has the following advantages : It requires no cutting operation and causes no danger of hemorrhage or of external wound infection. The consent of the parents is more easily obtained. It is generally easily performed by one accustomed to the procedure. It requires but one, or preferably two, assistants. The time of leaving the tube in the throat averages less. The nursing is simpler. The objections are : the danger of the ulceration of the tissues from pressure, the difficulty of administering nutriment, and the more frequent insufficiency of the relief afforded. In about 2 per cent, of the cases it will be found that the child cannot breathe without the tube for weeks after the disappearance of all other symptoms. If this is due to paralysis, recovery usually takes place after weeks or months. If the obstruction is due to a growth of granulations, it may be necessary to remove them by operation, and to do this a preliminary tracheotomy will generally be necessary. Commonly in America intubation is first performed in all cases, and tracheotomy only in those in ^vhich the relief is not satisfactory, either at the time of the insertion of the tube or later. Here tracheotomy may give free breathing, but in a majority of these cases the membrane, still extending, will again produce obstruction, and thus the fatal termination is only somewhat delayed. Diphtheria Antitoxin in the Treatment of Diphtheria and as an Immunizing- Agent. — The foundation for the treatment of diphtheria, and to a less extent of certain other diseases, with antitoxin rests upon the fact — and it is well to keep in view that it is a fact — that the blood and serum of animals immunized against certain diseases c(mtain sub- stances, called antitoxins, which, when injected into healthy animals, will give them immunity to the same diseases. Further, not only will the serum confer immunity to later infection, but will, if not given too late, prevent the otherwise fatal outcome of the disease in animals already ill. The result is much the same whether the antitoxin is given to an animal before or at the same time as the dose of toxin or virulent bac- teria, but varies greatly for each hour's delay in giving the antitoxin after the infection has taken place. The longer this period is the greater the amount of antitoxin needed and the more doubtful the recovery. ANTITOXIS L\ THE TREATMENT OF DIPHTHERIA. 693 TIk' Hrst jiiildicatiiiii (Icinoiistratinir the antitoxic power of the serum of atiiniuls iiuimuii/etl auainst (lij)litheria in tlie treatment of experimental diphtheria was maile by von liehring- in Deeemher, 1890. The first trial of antitoxin serum in human diphtheria was made in the autumn of 1.S91 in the city (»f Berlin. Mtidr of Action of ^intitoxiii. — It seems probalde that antitoxin does not aet directly in any way upon the toxin, but rather upon the tissue elements in such a way as to make them insusceptible to the poisonous action of the toxin. After the cells have been to a certain extent affected bv the toxin, the protective power of the antitoxin can no longer be exerted 'and the lesions progress in spite of it. Derivation of Antitoxin. — From the fact that the antitoxin devel- oped in the blood of an animal is only antitoxic for the special toxin with which it was injected — that is, tetanus antitoxin only immunizes against tetanus poison, diphtheria antitoxin against diphtheria poison, etc. — it would ajipear that the antitoxin must be derived from the toxin. A substance which seems to be the same as diphtheria antitoxin has indeed been obtained from diphtheria toxin by electrolvsis. There are certain facts, however, which teach us that the living tissue elements probably are actively associated in the transformation. Thus in animals freshly immunized small doses of toxin will produce far larger amounts of antitoxin than these same doses will produce when the animals have been long under treatment. The amount of antitoxin produced seems to depend more on the extent of the reaction of the an- imal to the injections than on the amounts of toxin introduced. The diphtheria antitoxin is obtained for medicinal purposes almost entirely from horses. These animals receive repeated doses of diphtheria poison in constantly increasing amounts until, after from two to four months, their blood serum contains sufficient amounts of antitoxin to be service- able for treatment in human diphtheria. The power of the diphtheria antitoxin to neutralize the poisonous effects of the diphtheria toxin in animals is, as before said, an absolute fact which has been shown to be uniformly true in thousands of experi- ments. AVe have every reason to expect that, since the toxin in human diphtheria is, so far as we can determine, exactly the same toxin as that in diphtheria in animals, this power of the antitoxin to make harmless the toxin will manifest itself in man under similar conditions. AVe have every reason, therefore, to expect it to almost certainlv pre- vent, for a time at least, an attack of diphtheria, but as to its exact value at different stages in the development of the disease onlv clinical experience can determine. " If," as AA^elch ^ so well states it, " the curative effects of the serum are brought about through the agency of the living cells of the bodv, we can understand why these effects ^vill not follow the injection of the serum with the certainty and precision of a chemical reaction. The cells must be in a condition to respond in a proper way to the introduction of the antitoxic serum. For one reason or another this responsive power may be in abeyance; we know that it may be weakened or destroyed by the intense or prolonged action of diphtheria poisons, or ' "Welch, Bulletin of the Johns Hophins Hospital, July, 1895. 694 DIPHTHERIA. by other previous and coexistent diseases, or by inherent weakness, or there may even be some individual idiosyncrasy which hinders the cus- tomary response of the cells to the antitoxin. " Clinical experience shows that cases of diphtheria inherently refractory to antitoxic serum are exceptional, although they do certainly from time to time occur." The antitoxic serum exerts no bactericidal effect upon the diphtheria bacillus, although when administered in proper quantities sufficiently early in the disease it arrests the spread of the local inflammation which is caused by the bacillus. Virulent bacilli, so far as the results in New York gb, seem to persist in the throat for about as long a period as in the cases formerly not treated with antitoxin. One of the most important characters of antitoxin is that it requires a definite quantity to neutralize the effects of a definite quantity of toxin. In animals the curative dose of antitoxin stands in a definite quantitative relation to the size and susceptibility of the individual and to the amount and intensity of the poison in the system. If an animal does not receive a sufficient amount of antitoxin, it fre- quently dies almost as quickly as one having received no antitoxin at all. We have no method of deternaining how much and how viru- lent the poison may be in a given case of human diphtheria, nor how susceptible to toxin the patient may be. The dose of antitoxin, there- fore, in human diphtheria is empirical, the main factors to determine it being the age of the patient, the estimated duration of the disease up to the time of the administration of the remedy, and, most important of all, the severity and extent of the disease. As the serum is capable of inducing unpleasant symptoms, it is desirable not to give an excessive quantity. It is, however, necessary not to err on the opposite side and give too little, for it is far more important to give sufficient to overcome the dangers than to endeavor to avoid by too small a dose the after possible unpleasant effects. It is very important to bear in mind that the diphtheria antitoxin only immunizes against the poison of the diphtheria bacilli, and that, in so far as the lesions in any case of diphtheria are due to the action of the poisons produced by other bacteria, these lesions will be in no way influenced. The lesions of diphtheria are, as a rule, at the beginning mainly due to the action of the toxin of the diphtheria bacillus, but later inflam- mation may take place, due to other bacteria, so that septiceemia or pneumonia may develop, which, being due not so much to the diph- theria bacilli as to streptococci or pneumococci, will of course advance without regard to the use of the diphtheria antitoxin. These facts impress us still further with the importance of using the antitoxin early, for we are not only thus enabled to immunize the cells against diphtheria toxin, but by preventing the advance of the disease we ward off these later infections. We have no way of gauging accurately at any given period of the disease the extent of the damage already inflicted upon the cells of the body. If the nerve cells have already been so damaged that paralysis must follow, or the cardiac nerve cells or muscular fibres have been similarly injured, or the renal epithelium so affected that degeneration ANTITOXIN IN THE TREATMENT OF DIPHTHERIA. 095 ami iiej)hritis ensue, the admiiiistralion of antitoxin cannot restore those cells wliicli arc already on the way to deti-cneration and death. The eft'ects wiiich follow the injection oi' the antitoxic serum in individual cases are not new and strannn will ell trcnunent was begun, i Cases. ^^I}!lu}^l 1 Cases. 57 131 131 88 199 Mortality, percentage. First flav . . 11:; 8 85 i 19.29 35.11 32.82 37.50 37 69 Sei-ontl (iav 1 IC. 24.32 ' Third dav l;!2 24.27 Fotirth diiv i 102 30.39 Fifth dav and over ' 221 34.36 Total 1 714 28.39 606 34.32 Careful investig-ation at the homes of many of the ]Mtients showed that they had been siek, as a rule, longer than stated in the hosj)itals records. This table is nevertheless of great value. It shows, in the first place, so far as figures can show, that the epidemics of 1895 and 1894 were of about the same severity, the cases admitted after the beginning of the fifth day having about the same mortality in both years. The cases ad- mitted, however, on the first two days show a very different mortalitv. This is true also, but to a less marked extent, for the cases in which treatment was begun on the third day. Too much emphasis cannot be placed upon the importance of giving antitoxin early in diphtheria. There is no doubt in my mind that most cases wdiich die in spite of the early administration of the usual treatment would be saved if antitoxin were given within the first thirty-six hours of visible disease. Let us now turn attention to the .statistics reported bv Baginskv. They certainly give a very favorable showing for antitoxin. Baginsky ^ reports the following as the results of the treatment of diphtheria before and after the use of antitoxin : Cases receiving no antitoxin, 1890-1894. Cases receiving antitoxin, 1894-1895. Year. Cases. Deaths. Percentage. Cases. Deaths. Percentage. 0-2 243 2-1 333 4-6 274 6-8 197 8-10 124 10-12 73 12-14 ...... 43 154 176 104 54 24 11 6 63..36 .52.85 37.98 27.41 19.;% 15.07 13.95 87 146 116 79 58 20 15 22 25 20 3^ 2 2 25.28 17.12 17.24 11.39 5.17 10.00 13.30 Laryngeal Diphtheria under Antitoxin Treatment (Baginsky). Cases. Deaths. | Percentage mortality. Intubated Tracheotoraized . 25 11 5 20 8 72 Not intubated 36 11 13 303^ Total laryngeal cases 47 13 23 ' Loc. eit. 698 ■ DIPHTHERIA. A most convincing demonstration of the power of antitoxin is furnished by the experience of Baginsky during an involuntary pause in the serum treatment caused by failure in the supply of serum. Between March 15, 1894, and March 15, 1895, there were treated in Baginsky's service by antitoxin 525 children, with a fatality of 15.6 per cent. During the period of forced interruption of the serum treat- ment, this period being chiefly the months of August and September, 126 children were treated without antitoxin, with a fatality of 48.4 per cent. There was absolutely no selection of cases in either group. In his comments upon this experience Baginsky says : " It is all the more remarkable as the ratio of mortality of those treated with the serum both before and after the period of interruption varied within very small percentage figures. " If one will permit figures to speak at all, there has scarcely been made on human beings a more demonstrative test of the curative power of a therapeutic agent. It was an experiment ibrced upon us, but it proved to us how terrible was the form of disease which we were treat- ing, and how numerous would have been the victims without the use of the healing serum." Another proof that the cause of the lower death rate is not due to the cases being milder is seen in the universal lowering of the death rate in laryngeal diphtheria. I quote again a paragraph from Welch's summary: "No one can claim that laryngeal diphtheria requiring in- tubation or tracheotomy is anything but a severe disease. " If the benefits of antitoxin are unmistakably manifested in these operated cases of croup, then the test is an experimentum crucis, and puts an end to the objection of those 's^ho assert that the apparently favorable results of serum therapy in diphtheria are attributable mainly to the large proportion of mild cases treated. " Before the introduction of the serum treatment a collective investi- gation was set on foot by the German Gesellschaft f iir Kinderheilkunde to determine the average fatality following intubation. "In 1893 von Ranke reported to the society that 1445 cases of diphtheria with laryngeal stenosis treated by intubation gave a fatality of 62.5 per cent. This result was interpreted in favor of intubation as opposed to tracheotomy. There is a difference of 33.6 per cent, between this percentage and that obtained from our 342 intubation cases treated with antitoxin. This difference is so great that, after making all pos- sible allowance for diflPerences in the series of cases entering into the two groups of statistics, it seems impossible to explain it otherwise than as a powerful additional support of the arguments already presented in favor of the claims of antitoxin. Here certainly the objection that the cases treated by antitoxin were light ones cannot be made. " During the enforced two months' (August and September) interrup- tion of the serum treatment in Baginsky's service there were 116 cases of laryngo-stenosis, with a fatality of 62.2 per cent., as opposed to a fatality of 37.8 per cent, in the serum periods which preceded and fol- lowed the pause. The percentage of operations rose to 55.2 as opposed to 18.1 per cent, during the periods of serum treatment, and this without any change in the general character of the cases admitted. " During the serum periods there were more intubations than trache- ANTITOXIS IN THE TREATMILXT OF DII'IITIIERIA. 699 otoniii's, whorcns (lining ilic j):iii.-c' tlici'c were 40 traclieotomics and 19 intubations, V.\ ol' the latter i'c'(|uirini:: secondary traelieotoiny." Tlie following- statistics, showino- the results of treatment with anti- toxin in 24,768 cases, as contrasted with those not receiving antitoxin, liave been furnislicd nie by Dr. Girade. They have been compiled without the least attempt to favor antitoxin. They comjirise all the cases given in the journals l)y observers reporting over 10 cases: Table I. Mortality in iJijjIitJieria treated icith Antitoxin and Previous Mortality icithout Antitoxin. Cases. Deaths. ifortality, Previous mortality, per cent. per cent. Hospital cases .... 15,o60 3009 19.0 Private ctises 9,208 995 10.1 Total 24,768 4004 16.0 30 to 40 (Cases moribund at the time or dying mthin twenty-four hours after are included in these statistics.) Table II. Mortality of Diphtheria treated With and Without Antitoxin at the Same Time or during the Same Period. cases. Deaths. ^pl-taUty. Hospital with antitoxin 7986 1754 21.0 " ^vithout antitoxin 9039 3309 36.4 Private with antitoxin 3161 412 13.0 " without antitoxin 4255 1717 40.0 Total with antitoxin 11,147 2161 19.1 " without antitoxin 13,294 5026 37.8 (The antitoxin cases were often severe cases taken as tests.) Table III. Mortality of Operative and Nonoperative Cases of Diph- theria treated with Antitoxin, and Previous Mortality of Operative Cases ivithout Antitoxin. Cases. Deaths. Mortality, Previous mor- per cent, tahty, per cent. Nonoperative cases .... 12,066 1491 13.5 Operative cases 3,082 1135 .36.7 65 Total 15,148 2626 16.6 Tracheotomy 1355 569 42.0 70 Intubation " 1173 361 30.8 51.5 Intubation and second tra- cheotORiv 52 37 71.0 Intubation or tracheotomy. 502 168 .33.2 Table IV. Mortality of Diphtheria rvith Antitoxin, arranged according to Age. cases. Deaths. ^p^-tality. 0-2vears 1494 469 31.4 2-5 vears 3678 762 20.7 5-10 years 3184 473 14.8 Over 10 years 1444 99 6.9 Total 9800 1803 1^4 (chiefly hospital). 700 DIPHTHERIA. Table V. Mortality of Diphtheria with Antitoxin, arranged according to Day of Disease on which Treatment was Commenced. cases. Deaths. Mortality, First and second day 4,232 267 6.3 Third and fourth day 3,870 656 17.2 After fourth day . ." 1,984 605 34.6 Day unknown " 339 44 13.0 " Total 10,425 1672 16.0 (Cases moribund or dying within twenty-four hours inchided.) Leaving statistics, let us look more closely at the results noticed in individual cases. Beneficial Results of Antitoxin. — Upon the Local Process. — In the cases in w^hich I have made or seen an injection made within the first twenty-four hours of the disease the results have been so remarkable that I have attributed them to the antitoxin. Following are the histories of two typical cases : Case I. A boy eleven years old had had for twelve hours malaise, with pain on swallowing. Inspection showed the tonsils and portions of the palate to be covered with a soft, slightly adherent exudate. The boy was injected with 1000 units, and twelve hours later his throat was clear and temperature normal. I do not believe this Avould have been a severe case without antitoxin, but the effect seemed magical. Case II. The second case was a baby one year old, with a slight croupy cough for twenty-four hours, and stenosis just beginning. Tem- perature 102 ; patient restless and without desire for food. Injected 600 units, and found the baby on the following morning practically well. When the disease has progressed several days — and these cases are the ones seen in the hospital — the benefit is not so apparent. I believe, however, that a marked effect is still produced. There have been very few cases, indeed, of pharyngeal or tonsillar diphtheria in w^hich the membrane has increased after admission. I believe that the same result has taken place in laryngeal diphtheria. Even in well developed cases the pseudo-membrane itself has seemed to me to separate somewhat more quickly than formerly, there being usually seen after thirty-six to forty- eight hours a line of demarkation separating the membrane and making it look like a slough ready to be cast off. The swelling of the throat tissues and of the glands of the neck also appears to me to begin to abate earlier. The ulcerated surface left in some cases after the separation of the membrane is covered with a soft exudate until healing occurs some days later. In laryngeal diphtheria, if the intubation could be put off for eighteen hours, it was, with very few exceptions, avoided altogether. The time during which the cases remained intubated seemed to me to be shorter than before the use of antitoxin. Many children coughed up their tubes in from twenty-four to forty-eight hours, and quite a number were able to do without them afterward. Others required the tube from three to eight days. Exceptional cases occurred, as previous to the use of antitoxin, when the tube had to be worn for weeks. The general condition of patients was beneficially influenced. The loss of appetite and the apathetic condition are less apt to occur, and when present seem ANTITOXiy IS Till-: TIIKATMENT OF J)IPHTHERIA. 701 more quickly rclicvcil. In cases iu wliicli treutiiicnt wus begun very late, us a rule no good effects were noted. /// Kff'ccfs of Aitfifo.vin Scrum. — A small jierccntagc of the cases have a slight rise of" temperature inunediately after an injection. In a very few cases abscesses develop at the seat of the injection. This is a pre- ventable accident. Mcushes. — These are peculiar to the serum injections. They are iiii- doubtedlv partly due to the horse serum, not altogether to the antitoxin. Thev occur in from 5 to 20 per cent, of the cases according to the cha- racteristics of the serum. The eruption may be limited to the point of injection, or may more or less com])letely cover the whole body. It most often appears as an urticaria, but may very closely resemljle scarlet fever or more rarely measles. It usually develops between the tenth and fif- teenth days. In some cases all the forms may be united in one person. Following the eruption, desquamation may occur. In al)OUt one fifth of the cases there is a rise in temperature of 2°-4° F. This lasts from one to three days. In a small percentage of cases there is accompanying the rash great tenderness over the joints of the extremities. These i)ains last, as a rule, one to four days. In one case in the hospital the joint affection was more serious. The child, aged fifteen months, was admitted on April 25th with severe stenosis. The temperature was 101° F. The child was intubated and did well. It received two injections of 1200 units each. On the 27th there was a macular eruption over the body ; twenty- four hours later the joints of the hands and feet became intensely painful. The child dreaded the least handling. The knees and the two joints of the left thumb became more swollen, and appeared like acute articular rheumatism. Before the eruption developed the child's condition was rendered more serious by the appearance of a broncho-pneumonia, which continued gradually to increase until death, two weeks later. There have been, in New York, four cases reported in which the joint lesions per- sisted for several weeks. These all finally recovered. The urticaria and erythema which at times accompany the rise in temperature are in certain cases very distressing, and in a person already prostrated might not be wholly without danger to the patient. I iiave seen in watching over 1500 cases no serious effects upon the heart, kidney, or nervous system which I attribute to antitoxin, with the possible exception of two cases of scarlatina complicated with diphtheria. In these two there was an almost complete suppression of the urine. This was probably due to the scarlet fever and diphtheria, and not to the antitoxin. Since it has been suggested by some that injections of antitoxin with the accompanying horse serum have a disintegrating effect upon the red cells of the blood, we investigated the matter very carefully in the laboratory of the New York Health Department. J. S. Billings, Jr., one of the assistant bacteriologists of the depart- ment, examined very carefidly the blood in 15 babies after they had received doses of antitoxin for immunization. The children received from 200 to 400 units each. No alteration was discovered in charac- ter of the red or white blood cells. The number of the Avhite cells practically remained unchanged. The number of the red cells showed, however, in half of the cases, a very interesting change : in 7 of 702 DIPHTHERIA. the 15 a gradual diminution in their number took place from day to day until by the sixth day there was a loss of from 200,000 to 600,000 in each 5,000,000 of their cells. After this date the number rapidly increased, imtil upon the fourteenth day the numbers had returned to the normal. In adults receiving 1200 units the same result took place. From 6,000,000 the count dropped to 5,400,000, and then re- turned to the normal at the end of ten days. None of these persons showed any evidences of anaemia except in the examination of the blood. The cells contained their normal amount of haemoglobin. The blood of a series of cases of diphtheria treated with antitoxin was compared with that in a number in which no antitoxin was used. The diminution in the number of the red blood cells was greater in those not receiving the antitoxin. No marked effect was noticed upon the number of the white cells. Limitations of Antitoxin. — Diphtheria antitoxin, so far as is known, has no action upon the cells in causing them to resist any poisons other than those produced by the diphtheria bacilli. Here we see at once a limitation in the cure of the complex disease called diphtheria, for it is as correct to class some of the cases met with as pneumonia complicated with diphtheria as to call them diphtheria complicated with pneumonia. Upon the pneumonia, so far as it is not due to the diphtheria bacillus, one cannot hope that the antitoxin will have any curative effect. Another limitation is suggested by the results of experiments upon animals. It is known that after the infection has proceeded to a moderate degree it cannot be arrested by antitoxin. Experience shows that in human beings also the cells no longer react to antitoxin after a certain degree of poisoning has taken place, and this point in some cases seems to occur very early. I doubt if we are justified in saying that in these the actual lesions have progressed so far that without any further poisoning life has become impossible. I believe it may be possible that even after the administration of antitoxin the poison goes on producing further lesions, the cells already affected by the toxin not responding to the antitoxin. There are exceptional cases in which even when the antitoxin is given early it apparently fails to fortify the cells against the diphtheria poison. In the hospital the effects of antitoxin upon laryngeal diphtheria, though in one way striking, are in another disappointing. More children live than formerly, but it seems as though still more should live. Many survive the acute infection only to die later of the complicating broncho- pneumonia. It has occurred in cases of diphtheria treated with antitoxin, just as in cases not so treated, that a relapse may take place four or five weeks after recovery from the disease. Pneumonia is much less frequent in private practice, and seems to be less frequent under hospital treatment abroad. Special hospital conditions were probably accountable for it. The following case illustrates a class which end fatally, and yet, although the disease is thoroughly established and the patients are under the influence of the toxin, one cannot help feeling disappointment when, although they respond to the antitoxin partially, they finally die. Case III. Alice M , aged sixteen years, a girl strong and well nourished, was admitted to the hospital on the third day of her illness ; the glands of her neck, both tonsils, and the peritonsillar tissues were greatly USE OF AyriTOXIX IX I'llEVENTING DIPHTHERIA. 703 swollen. rho whole area extending hack into the pharynx was covered by a thielv dirty white adherent membrane; her nostrils were partially obstructed ; temperature 99° F. ; pulse 108. Her intellect was clear. 1000 units of antitoxin were injected; same amount was injected twenty-four hours later. Thirty hours after her admission the swelling and infiltration were much less; the membrane had lessened and was of more benign character. Pier heart was irregular, but she felt better ; the temperature was 99° F. and the pulse 110. Four days after her admission her heart action became much more irregular, and her pulse was but (36, falling the next day to 34. The patient had repeated attacks of heart failure ; all nourisiiment was vomited, so that stimulants had to be given by rectum. The patient died on the fifth day of her stay in the hospital. Autopsy showed extreme fatty degeneration of the heart and extensive degeneration of the other organs. Use of Diphtheria Antitoxin in Preventing- by Immunization the Development of Diphtheria. — The results obtained under my observation in a number of children's asylums and hospitals and in the crowded tenements of New York have been so very favorable that they encourage the hope that a general use of antitoxin for immuniza- tion will to a large extent limit the spread of diphtheria. At the Mt. Vernon branch of the New York Infant Asylum a case of diphtheria developed on February 18, 1894. Cases continued to develop from time to time, so that in September alone 14 cases occurred. From that time until January 14th there was hardly a day in which a case did not develop. On January 16th and 17th, 221 children were each injected with from 100 to 200 units of von Behring's serum. No bad effects were seen, and during the next month but 1 case of diphtheria developed ; this was on the fourteenth day. From February 22d to 27th, 5 cases appeared, and the children were again immunized. This time they each received from 125 to 225 units of von Behring's standard of a serum prepared under the direction of the New York City Health Department. No cases appeared after the second immunization for a period of five weeks. Cultures made from the throats of those in the neighborhood of this case showed diphtheria bacilli in the throats of 6 of the children. These 6 were given 200 units each on March 30th. One of these chil- dren developed a small patch two weeks later, but had no constitutional symptoms. A case developed on May 3d, and one on May 27th, in the children immunized on February 27th. The hospital has remained since then free of diphtheria, so that no third general immunization has been thought necessary. At the Nursery and Child's Hospital in New York in the three weeks preceding April 18, 1895, there were 15 cases of diphtheria. Upon that day 136 children, varying in age from three weeks to four years, were immunized by receiving from 50 to 200 units each. The children showed no bad effects from the injections. A temporarv rise in temperature occurred in one fourth of them, which lasted for six to twelve honrs. From the day of the injections to the present time no diphtheria has developed in the hospital, with two very interesting exceptions — a physician and a nurse who had not been immunized. Since then the hospital has been free from diphtheria. 704 DIPHTHERIA. At the House of Reception of the New York Catholic Protectory 2 cases of diphtheria developed on July 7, and 3 cases on July 8th and 9th, 1895. On July 9th and 10th the remaining 67 children were injected with 150 to 600 units each. (The children's ages varied be- tween two and a half and fifteen years.) No diphtheria developed after the injections in any of these children. In August a new set of chil- dren were received, and August 5th a case of diphtheria developed among these, and on August 10th a second. On this day the 37 children who comprised the new lot were injected with from 200 to 600 units of the Health Department's serum. No more diphtheria developed. The dosage was graded as follows : 2 years 1 case 200 units. 3 " 1 " 250 " 6 " 1 " 350 " 7 to 12 years . . • ... 20 cases 400 to 500 units. 13 to 20 " 14 " 500 to 600 " The injection having been made in the forenoon, most of the children showed temperatures of from 99° to 99.5° F. the same evening, two or three reaching 100°, and one 100.6° F. During the two days on which observations were made most of the temperatures subsided to normal, a few remaining at 99° F. No cases except those mentioned later showed any constitutional symptoms after the injections. In only 2 cases was there any local irritation. In 1 of these the symptoms promptly sub- sided without treatment ; the other, unfoi'tunately, developed an abscess. In the last group of cases, 37 in number, specimens of urine were obtained before the injections to compare with those taken after the administration of the serum. The results of the examinations are as follows : Before immunization, August 9tli. After immunization, Aug. lltli. Aug. 13th. Sp. gr. Albumin. Sp. gr. Albumin. Albumin. Case 1 " 2 " 3 " 4 '• 5 " 6 10.22 10.24 Trace. Negative. 30 per cent, in vol. Negative. 10.30 Negative. Trace. 60 per cent. 16 per cent. Negative. One child showed 30 per cent, in volume of albumin (the urine, after boiling and the addition of nitric acid, was allowed to stand for twenty- four hours, and the deposit was then estimated) in the urine before treat- ment, and after the injection there was about 60 per cent, in volume. The urine from the sister of this child showed no albumin before the injection, and gave not the slightest evidence of illness other than the albuminuria at any time, and neither showed any temperature reaction. In both of these cases, as in all the others, the albumin had entirely disappeared two days later. Nine days after the injections 1 case developed an urticaria which lasted for twenty-four hours. No other cases showing the skin rashes were observed. At the Reception House of the Juvenile Asylum in USE OF AXTITOXIX IS ritEVENTIXG DIPHTHERIA. 705 New York 4 cases of diplitlieria developed during the week ending April 1 1, l^i05. On tlie Titli the children (to the number of about 70) were injected with from 200 to 400 units. No cjises occurred afterward, except that the boys' attendant and an engineer who handle(l tlio clothes from the diphtheria cliildren, and who hail received immunizing injections, develoj)ed diphtheria. To nu' these results seem conehisive as to the immunizing power of injections of from 100 units of antitoxin upward. Although in these institutions it was impossible to say that any special child would develop diphtheria, still it was an absolute certainty that in each of these institutions more cases would have developed unless in some wav the children could l)e immunized. About one sixth of the children had slight albuminuria, and a much smaller jiercentage developed it to a greater extent. In none, however. Mere there any other symptoms pointing to any deleterious action on the kidneys, and in none was the albuminuria more than transitory. In the blood there was noticed, as before stated, a slight temporary diminution in the number of the red blood colls ; no other changes were observed. Iiiiiiiunizatloii by Xcw YorJ: Health Department In.spedors In Infected Familiefi. — For some months past in families in which diphtheria has occurred, and in which there were other children exposed to infection, the Health Department inspectors, a<:'ting on their own judgment as to the necessity, have immunized some of these exposed persons. Most of these cases have been among the tenement-house population. A few cases taken at random from the reports of the inspectors illustrate the method : Fainilji 1. — Five children in family ; 2 cases of diphtheria ; the other o children, aged nine, eleven, and thirteen years, were immunized ; no further cases occurred. Fa mill/ 2. — Three children in family; 1 case of diphtheria ; 2 other children, aged eight and sixteen years, immunized ; 1 child had diph- theria bacilli in the throat at the time. Xo further cases of diphtheria Family S. — Three children in family ; 1 case of diphtheria, 1 of the remaining 2 children immunized ; second child, aged sixteen, not im- munized. This child developed diphtheria three weeks later, and was successfully treated with the antitoxin. Cases like the foregoing might be repeated almost indefinitely. 232 persons had been immunized in this way up to October 1, 1895, and of these at least 93 (many of the others were not examined bacteriologically before being immunized) had diphtheria bacilli present in their throats when treated. The cases were kept under observation until the premises had been disinfected, and this was done until the throats of all were free from bacilli. Among the 232 persons immunized by the inspectors 3 developed' mem- branous croup within twenty-four hours of the time when they were treated, who in fact had diphtheria before l)eing injected, but all recov- ered. Three others had mild pharyngeal diphtheria — developing 1 on the nineteenth, 1 on the thirtieth, and 1 on the thirty-first day after injection, and 1 developed a fatal diphtheria on the fifty-fifth day. The cases detailed number altogether 1043; 224 of these were im- YoL. I. — 45 706 DIPHTHERIA. munized once with von Behring's sernm, and the second time with the New York Health Department serum. In a large percentage of the whole number diphtheria bacilli were present in the throat when the serum was administered, and all had been exposed to diphtheria under conditions more or less favorable for the transmission of the disease. Among those immunized 3 cases of diphtheria occurred between one and thirty days after the treatment ; i. e. 1 on the twelfth, 1 on the seventeenth, and 1 on the nineteenth day, respectively. Twelve cases developed diphtheria later as follows : On the thirtieth day, 2 ; thirty-first day, 1 ; thirty-third day, 1 ; thirty-seventh day, 1 ; thirty-ninth day, 1 ; fortieth day, 2 ; forty-second day, 1 ; fifty-second day, 1 ; fifty-fifth day, 1 ; sixty-sixth day, 1 ; ninetieth day, 1 . The 4 cases that developed croup within twenty-four hours of the injection undoubtedly had the disease at the time of injection. Table showing the Number of Cases Immunized in New York City, and the Results. c =e COr- •gSi li ' fi^ ■o 'S ■gj 3 j: 2 £o ' £.ai '3 S bcS s c ^S-i^ p.^ !§• c ~ = 'S s c3 '■3% o 'm QD U i, b'''?, ^ « so to r -M i^S. o p g ce ^"a =^.25§ o ® ^ c — ^ o oS O > 5 of; 'o ri S c o o^ 6^.§i V o d -a ; ~ X •= IZi !2i ;zi •^ ;z; a New York Infant Asylum (1st im- munization). New York Infant Asylum (2d im- 224 100 to 200 1 mild on the 19th day. 1 mild on the 6 107 cases in 108 days. 245 125 to 225 4 6 cases in 12 davs. munization). ] 12th day. Nursery and Child's Hospital . . 136 j 50 to 200 46 cases in 90 days ; 15 cases in 15 days. New York Juvenile Asylum . . . 81 150 to 250 12 cases ; 3 cases in 2 days. New York Catholic Protectory . . 114, 150 to 600 1 5 cases in 3 days. Bellevue Hospital 11' 175 to 225 2 cases in 10 days. (1 : 30 One or more cases in 3-^ 1 : 31: more than 90 fam- U : 55' ilies. Health Department Inspectors . . 232 150 to 250 1 mild on the 19th day. 3 4 Total 1043 . . 3 18 i Altogether, therefore, excluding these, 16 cases of diphtheria occurred among 1014 persons — 3 in from one to thirty days, and 13 in from thirty to one hundred and ten days after immunization. These cases were all mild, excepting 2, 1 of which proved fatal from diphtheria, and in the other death seemed to be due to broncho-pneumonia complicated by a mild diphtheria. During ninety days preceding immunization, under practically the same conditions, it may be said that more than 225 cases of diphtheria occurred. By the use of antitoxin it has been possible to stamp out completely diphtheria in four great institutions for the care of children in which it was prevailing in more or less epidemic form. In no instance have there been, so far as can be determined, any serious results from the administration of the remedy for this purpose. The duration of immunity in many cases is apparently not more than thirty days, but it may be for a much longer time. The doses required to confer immunity are probably between 50 and 300 antitoxin units,, according to the age of the individual treated. PSEUDn-nirnriiJUHA. 707 A siiiiiinary ol" I'liscs ivpurlcd in the joiiriKils is as lollctws: Iimiuinlzdfion />;/ Aiifito.vin. Total I'ast's iiiimiini/A'il li),o7(). Antitoxin units iiijivti'd ")0 to 1000 fusnally 150- 200). Attai'kod witliin ;{("l (lays 129 niild, all ri'covi'ivd. Attac-ked after 30 days 20 mild, all recovered. (No serious after-effects observed wliicli could be ascribed to the antitoxin injected.) Conclusion on Diphtheria Antitoxin. — Diphtlicria antitoxin lias a marked curative effect in diphtlieria. The results are very strik- ing when the injections are used early in the disease, and when the diphtheria is nn(!oniplicated with pneumonia or sepsis. In Avell devel- oped cases and in those having complications its benefit is less marked. In cases already profoundly under the influence of the diphtheria toxin and in a dying condition it is useless. The total amount required in the treatment of a case varies from 1000 to 0000 units of von Behring's standard, and is determined b}^ the severity and duration of the disease and the weight of the patient. An injection of 100 to 300 units of antitoxin in a person will give an almost certain immunity from diphtheria for four weeks. If security is desired for a longer period, the injection must be repeated. Diphtheria antitoxin will not cure all cases of diphtheria in which the element of mixed infection is marked, even if given early in the disease. It does not destroy the diphtheria bacilli. It is desirable with the antitoxin to use other treatment, both local and constitu- tional. The injection of diphtheria antitoxin Math its accompanviug horse serum is attended in a moderate percentage of the cases with disagreeable results, but in very few if any with serious ones. Xo cases have been observed in which the kidneys showed any evidence of being seriously affected. It does not appear to have any deleterious effects on the blood, other than to cause a moderate temporary diminu- tion in the number of red blood cells, and even this is more than coun- terbalanced by its lessening the action of the diphtheria poison. Large injections in persons not having diphtheria are more apt to cause unpleasant and even somewhat serious after-effects, than in those affected by the disease. It is well, therefore, to be fairly sure of the diagnosis in adults, in whom, as a rule, but little danger exists, before giving a full injection. PSEUDO-DIPHTHERIA, INCLUDING NON-DIPHTHERITIC MEMBRANOUS LARYNGITIS, OR CROUP. Pseudo-diphtheria is not a distinct disease like diphtheria. The name is used to cover all inflammations of the upper air pasisao-es not due to the diphtheria bacilli which simulate the less characteristic cases of di])htheria. The bacteriology of pseudo-diphtheria has been already considered in the earlier part of this article. (See page 670.) Manv oif the varieties of pseudo-diphtheria are considered imder other headings, such as tonsillitis, the throat lesions complicating scarlet fever, acute 708 DIPHTHERIA. laryngitis, etc. These will be, however, grouped together here, and briefly considered in connection with a few illustrative cases. Clinical Divisions. — 1. Extensive pseudo-membranes, mostly con- fined to tonsils, soft palate, and pharynx : a, uncomplicated ; b, compli- cating infectious diseases. 2. Pseudo-membranes involving the larynx. 3. Pseudo-membranes and exudates confined to the tonsils. 1. Illustrative Cases. — Extensive Fseudo-membranes, confined Chiefiy to the Tonsils, Soft Palate, and Pharynx. — Case I. Feb. 5th. Female aged eight. Clinical history : Tonsils covered by large, irregular, ad- herent, whitish patches. Fauces and tonsils swollen and livid in color. Temperature, 104° F. ; pulse, 40 ; respiration, 20. February 6th. Tonsils, sides and tip of uvula, and faucial pillars cov- ered by a thin, friable, grayish pseudo-membrane, which leaves a bleeding surface on removal. The appearance is as if on a mucous membrane denuded of its superficial epithelium a thick paint had been applied. February 7th. Tonsils and faucial pillars clear of membrane; superficial ulceration on pillars, and adherent membrane to uvula. Temperature remains between 102° and 104° F. ; pulse, 118 to 130; respiration, 24 to 30. February 16th. Ulceration on uvula nearly healed. Temperature normal. No albumin in urine at any time. No great prostration. Case II. February 27th. Female, aged nineteen. Clinical history : Both tonsils and adjacent surfaces of uvula covered by a thin gray mem- brane. Tonsils much swollen and painful. Great hypersemia of pharynx. Temperature, 99.6° F. ; pulse, 100. No albumin in urine. February 29th. All symptoms abated. Membrane disappeared. No swelling of glands. Case III. February 3d. Female, aged sixteen months. Clinical history : Thin, adherent, semi-translucent membrane on tonsils and ad- jacent surfaces of uvula. Nostrils occluded, but no membrane visible. Croupy voice and breathing. Slight swelling of glands of neck. Tem- perature, 100.2° F. ; pulse, 136; respiration, 34. February 4th. Membrane nearly disappeared. Child nearly well. February 6th. Throat perfectly clean. Child is well. Evening temperature, 100° F. ; pulse, 118 ; respiration, 28. Case TV. February 3d. Jennie K , aged eighteen. Clinical his- tory : Thin adherent pseudo-membrane on sides and tip of uvula. Some hyperemia of pharynx. Temperature, 101.4° F. ; pulse, 100. Mem- brane remained four days. After the first day temperature and pulse sank to the normal, and patient did not appear sick. No albumin in urine. Discharged on the sixth day. In these cases there is first a redness and swelling of the mucous membrane of the pharynx, tonsils, and fauces, with later a thin purulent discharge. Cultures at this time reveal very abundant colonies of strep- tococci. The epithelium of the inflamed mucous membrane, where the irritation is intensified by the contact and friction of adjacent surfaces, becomes necrotic, and the denuded surface becomes covered by a thin pseudo-membrane, composed mostly of streptococci held together by a small amount of fibrin. The streptococci may also penetrate into the denuded mucous membrane. If one looks at a well marked case, having the patient open the mouth rsKri)<)-i>ii'iiriii:i:i.\. VOf> sligljtly, :uk1 ik'pivsst's tlic li>nt2,iu' Jiist a lilllc, (Ik- iiillaincd uvula is seen lying botweon and against the swollen tonsils. On the portions of the uvula thus irritated by contact, on the f'aueial pillars lying against the tonsils, and, in extreme cases, on the lateral walls of the ]>harynx and on the soft palate spreading up from the sides of the uvula, one finds the pseudo-membrane, which is always light grayish in color, thin, an()-i)fi'iiTi{i':iiLi. 71 1 Pseiulo-incmhraiic on upper portion of led toii-il and adjacent surface of anterior and jiosterior i)illars. Well on tliird day. No fever. Cash III. March 5, 189:2. Female, a^ed twenty-one. Clinical liistorv : Both tonsils are nearly covered hy irrefi;nlar, senii-adlierent pseiulo-menibranons patches. (Considerable swellinii; and liypenemia. No swelling of glands. Not nuicli })ain ; slight constitutional symptoms. Temiierature, 101° F. >Iareh 7tli. Tonsils nearly clean. Feels well. March Stii. Perfectly well. In adults thick croupous patches, adherent or non-adherent, if con- fined to the tonsils after twenty-four hours, very rarely have anything to do with true diphtheria. The same bacteria (the streptococci) which under certain influences cause an inflamed throat or a follicular tonsil- litis, under others seem to produce a croupous tonsillitis. Two n)eml)ers of a family may be affected, one with the former, the other with the latter disease. In a few cases a very complete history of direct trans- mission of the contagium is obtained. The croupous deposit or pseudo- membrane lasts from two to seven days. All cases recover without complications. The intimate connection of some cases of croupous tonsillitis with scarlet fever is brought out in the following example : Female, aged twenty-one, was admitted to the hospital with marked croupous tonsillitis, with constitutional and local symptoms, on May 20th. The three previous days she had taken care of a child sick with scarlet fever, and on the last day also of the mother, who was attacked with croupous tonsillitis. Both she and the mother had come in frequent direct contact with the child. Two physicians attended a gentleman sick with malignant scarlet fever and croupous tonsillitis. Both were attacked with croupous tonsil- litis, and one w'ith scarlet fever also. Proc4Xosis. — With the exception of cases in which the larynx is involved uncomplicated cases of psendo-diphtheria are not dangerous to life. Although non-diphtheritic croupous laryngitis is less dangerous than diphtheritic, still the danger of suffocation without operative relief and of complicationg pnemnonia is ever present, and the mor- tality is considerable. Pseudo-diphtheria complicating infectious diseases during their early stages adds somewhat to the danger of the disease, and is usually an indication of a severe infection. Teeatmext. — The treatment of pseudo-diphtheria is similar to that of equally severe cases of diphtheria, with the exception of the anti- toxin. In cases not involving the larynx the temperature, general pains, and local soreness can be somewhat alleviated by giving internally salol gr. V every three to six hours or phenacetiu gr. v every six to eight hours in adults, gr, iii in children. Antipyrine, antifebrin, and salicylate of soda are also employed with good effect in the tonsillar cases. PERTUSSIS. By J. P. CROZER GRIFFITH, M. D. Synonyms. — Whooping cough ; Tussis convulsiva. Definition. — An infectious disease, occurring principally in chil- dren, and characterized by a cough of a peculiar paroxysmal nature and by more or less bronchial, laryngeal, and nasal catarrh. Etiology. — Age. — Among the most powerful predisposing causes of whooping cough age would seem to hold a prominent place. The great majority of cases occur before the sixth year, and over half of these before the fourth year, according to the estimates of West. Be- fore the age of six months the disease is not so common, although less unusual at that period of life than are scarlet fever, measles, and some of the other infectious diseases of childhood. In a few reported cases it seems to have developed before birth. It does not often occur after the age of ten years, although adults sometimes are attacked by it. The chief cause for this immunity of adults doubtless is that the majority of them suffered from the disease during childhood. There is, however, probably a lessened susceptibility to it with advancing years. Sex does not appear to exert any decided etiological influence. It has often been stated that pertussis is more common in girls than in boys, but the truth of this does not seem to be entirely confirmed by statistics, which are not at one upon this point. The extensive statistics of Vladimiroff favor the greater frequency in girls. The state of the previous health is important. It is the general opinion that weakly, delicate, or sickly children acquire whooping cough more easily than do those who are well. An attack of measles is often followed by one of pertussis. This association is especially well illus- trated in epidemics of the two disorders. Indeed, the statement is often made that an epidemic of measles predisposes to the development of one of whooping cough. It does not seem clear, hoAvever, whether the asso- ciation is only accidental or whether it is actually etiological. Whatever causal relation other diseases may have to whooping cough, it appears certain that its development is not at all hindered by their existence. Climate, season, and geographical jjosition do not seem to exert any real, influence. The disease, it is true, is more prevalent in the civilized parts of the world, but this depends merely on the foct that it has not yet been carried to other regions or has not yet become firmly established there. There are contradictory statistics regarding the frequencv of the disease at any one period of the year, which show that season cer- tainly has but little bearing. The station in life is likewise without much influence. The poor are 713 714 PERTUSSIS. perhaps more subject to it, on account of the greater ease of its diffu- sion which their unhygienic method of living occasions. The exciting cause of whooping cough is infection. Consequently, the disease occurs in epidemics, although in the larger cities it is practi- cally endemic. The epidemics seem to have a disposition to appear at intervals of about two years. The virulence of the infectious principle is so great that nearly all children exposed to it will contract the dis- ease. -The infection is transmitted by the breath and by the secretions from the respiratory tract. Comparatively close contact is required, although this need be of but very short duration. Probably the poison enters "by way of the respiratory tract, but it is not certain that this is in- variablv the case. It is possible for the disease to be carried by a third person from the sick to the well by means of handkerchiefs, clothing, and the like ; but this is certainly of very rare occurrence. The infec- tiousness of whooping cough is present during the whole of the attack, but especially in the paroxysmal stage. Pathology. — The nature of the infection, as indeed the nature of the disease itself, is not definitely understood. It is not even ad- mitted by all writers that the disease is of an infectious nature. De Mussy claimed that it is due to the irritating pressure of enlarged bronchial glands upon the terminal filaments of the pneumogastric nerve. Other writers have advanced the theory that it is of the nature of a pure neurosis, the result of some functional disturbance of the pneumogastric, recurrent laryngeal, phrenic, or sympathetic nerves, or of the medulla. Still others have thought it to be a simple bronchial catarrh associated with a neurotic condition. The whole analogy of the affection to diseases of the infectious class indicates, almost beyond ques- tion, that it too belongs to this class. Various organisms have been supposed to be the cause. The larva of insects were assigned as the active agents by Linnseus. Bacteria were described by Poulet and by Letzerich, and a protozoon was found in the sputum by Deichler. The observations which have been the most promising are those of Afanassiew, who isolated a short bacillus from the sputum of pertussis patients which he named the bacillus tussis convulsivw. He was able to obtain pure cultures of this which, inoculated upon the respiratory mu- cous membrane of animals, produced some of the symptoms of whoop- ing cough, with a catarrhal state of the respiratory tract and a tendency to broncho-pneumonia. Moncorvo has also described a bacillus found in the sputum, and more recently Ritter has found a small coccus which he believes to be the germ. It is evident that further research is greatly needed in this direction. The manner in which the germs of the disease, whatever they may be, produce the symptoms is also by no means clear. It is possible, on the one hand, that they act primarily upon the respiratory tract, occa- sioning a catarrhal inflammation, or, on the other hand, that the nervous system is primarily affected. There is no question that a catarrhal con- dition of the respiratory tract is present in ^^hooping cough. Some writers have claimed that this is most marked in the nose, others hold that it is predominant in the bronchi. It would seem from the obser- vations of Meyer-Huni and of Von Herff that the mucous membrane of the nose, larynx, and trachea down to the bifurcation is the region of the SYMPTO.VS. 715 res})iratoi'v tract most att'ccteil. Of" this tlu' part whicli is prc-eniiiu'iitly involved is the " cough region " — /. e. the posterior wall of the larynx in the intorarytenoid space. If we accept the view that the infection is <>hieflv local, with a secondary involvement of the nervous system, it would seem likely that a small (|uantity of mucus, rising from l)elow, lands upon the cough region and sets up a jiowerful irritation of the hvpersensitive filaments of the superior laryngeal nerve. This occasions, through reHex action, a series of repeated expiratory efforts which con- tinue until the mucus is expelled. A long-drawn, crowing inspiration follows, due to a spasm of the glottis, itself de])endent upon an irritation of the convulsive centres in the medulla. It seems very much mcjre probable, however, that whooping cough is actually an infectious dis- ease of the nervous system, Avith a secondary localization of the process upon the respiratory mucous membrane, exactly similar to the relation between measles and its respiratory symptoms. According to this view, some poison in the i^lood, produced by the infectious germs, occasions a great excitability of the superior laryngeal nerve oi* its centres in the medulla, and of other portions of the central and periph- eral nervous apparatus which control respiration and cough. There are various grounds for this hypothesis. In the first place, the even occasional occurrence of pertussis shortly after birth as a result of foetal infection indicates that the microbes must be in the general circu- lation. Then, too, paroxysms are brought on quite independently of the presence of mucus on the cough region. Thus excitement of any sort, drinking, crying, or sudden change of air will occasion them, all acting rather through the nervous system than in other ways. The greater frequency of paroxysms at night probably indicates the diminished degree of resistance of the respiratory centre in the medulla at this time, as a result of which convulsive respiratory efforts become more frequent. Of course, with this central excitability of the respiratory nervous system dependent on the infection, any local excitation, such as mucous -or other irritant to the respiratory mucous membrane, will produce cough. The presence of pathogenic microbes on the respiratory mucous membrane might only indicate that this was the seat of entrance and chief seat of growth, and the disease would be in this respect exactly analogous to typhoid fever. There are no characteristic post-mortem lesions. Emphysema is quite commonly found in bad cases, alone or combined with other pul- monary complications, especially broncho-pneumonia. Enlargement of the bronchial glands has been noted, but is not characteristic. Atelec- tasis is a common condition. Symptoms. — The attack is ordinarily divided into four periods : (1) incubation ; (2) invasion, or the catarrhal or premonitory stage ; (3) the paroxysmal or whooping stage ; and (4) the terminal stage or stage of decline. There is no very sharp division between these, since they pass gradually into each other. (1) Incubation. — During this period no symptoms of the disease pre- sent themselves. Statistics are at variance res^arding its lenp:th, and the fact that the invasion takes place so insidiously makes the determination of the exact duration of the incubation difficult in most cases. It probably lasts from two to seven days, with an average of three to four days. 716 PERTUSSIS. (2) Catarrhal Stage. — At the beginning of this period there are pres- ent the evidences of a severe cold, such as slight hoarseness, obstruction to breathing through the nose, sneezing, tickling in the throat, a dry cough, and malaise. Although there is often some slight fever, especially in the evening, it is disputed whether this is merely the result of the catarrhal condition or whether it should be considered as the direct result of the action of the infectious poison on the nerve centres. Treatment may produce temporary amelioration in some cases, yet the tendency is for the symptoms to grow gradually worse in spite of it. This is especially true of the cough, which becomes more frequent, occurs in longer paroxysms, and is decidedly worse at night. Examina- tion of the chest at this period shows either an entire absence of r^les, or a. number of them too insignificant to account for the severity of the cough. In a smaller number of cases there is a decided bronchitis dur- ing the premonitory stage, with numerous rales and considerable fever, but this is to be regarded rather as a complication. The premonitory stage lasts during a time w^hich varies with different cases and whose exact length is difficult to determine, owing both to the insidiousness of its onset and the fact of its merging into the next stage. In some cases it continues but two or three days, while in others the whoop- ing stage never comes on. The younger the child, the less in many cases is the length of the invasion. It may be said to average about two weeks. (3) The Paroxysmal Stage. — The typical and fully developed paroxys- mal cough of pertussis is marked by the occurrence of the " whoop," and it is customary to date the beginning of the paroxysmal stage from the time when this symptom first appears. A typical paroxysm of whoop- ing cough, or a " kink," is very characteristic. Often it comes on very suddenly without any w^arning. In other cases some sensation just before the paroxysm warns the child that one is about to begin. This sensation varies with different children. It may be a tickling in the nose or larynx, or a strong inclination to cough, or a pain in the region of the sternum. If the child has been lying down, it sits up quickly and perhaps grasps at the side of the bed. If it has been playing about the room, it drops its toys and runs to its nurse or seizes upon any object near it for support. The cough then begins, and consists of a series of rapidily repeated, short, explosive expiratory efforts, follow^ed by a long- drawn crowing inspiration. The short coughs are, as stated, little more than efforts at expiration, for auscultation reveals almost no sound of breatliing, and only a series of impulses against the ear can be perceived. The expiratory efforts, wdthout inspiration between them, continue for a few seconds, during which time the face becomes swollen and cyanotic,, the eyes are prominent, congested, and watering, the tongue is protruded and driven against the teeth, saliva flows from the mouth, and the pulse grows rapid. The whoop which follows is the result of a spasm of the glottis. The ear against the chest wall at this moment hears at most a very feeble inspiration or none at all. Immediately after the whoop another series of expiratory efforts usually begins, and this alternation of expirations and whoop may be repeated several times. The whole attack lasts, as a rule, from a few seconds up to one or two minutes, but exceptionally it may continue for from ten to thirty or even more SYMPTOAfS. 7 1 7 iiiimitL'>. In such a case, and often in tlie slinrter attacks, momentary periods oi' rest occur, and then the coughing returns. In the hitter ])art of a paroxysm ro]w mucus may flow in abundance from the moutli, and vomiting is very a])t to follow. In bad cases the paroxysms may be attended by hemorrhage from the nose or mouth or beneath the conjuneti\'a\, or even in the brain or elsewhere. The urine and fteccs may be expelled by the violence of the coughing, yometimes a whoop immediately precedes the lirst of a series of expiratory efforts. .Vfter an attack is over the child may be left pale and exhausted for a short time, but soon resumes its play if it is strong. Some degree of swelling of the face, cyanosis, puffiness of the eyes, and blueness of the tongue persists betw(,'en the paroxysms and gives the child a very character- istic ap})earance. The paroxysms are nearly always most numerous in the night. The number of paroxysms which occur in twenty-four hours varies greatly in different children. In the mildest cases there may be only six or eight, and these may occur almost entirely at night, leaving the child but little disturbed during the day. In severe cases, however, they may number forty or eighty, or even more, in twenty-four hours. A paroxysm is brought on by excitement of any kind, crying, singing, swallowing, exercise, the use of a tongue-depressor, a sudden change in the temperature of the air inhaled, the breathing of air vitiated by car- bon dioxide, and so on. Examination of the chest during the paroxysmal stage shows freedom from bronchitis, except perhaps of the slightest grade. Fever is absent or only occasionally present. If constantly present, some complication must be suspected. In mild cases the general condition of the child is unaffected, but in severe ones the nutrition and strength may suffer greatly from the frequent vomiting of the food taken and from the loss of sleep. The continuance of the paroxysmal stage is characterized by the occurrence of the paroxysms with unabated severity. Its actual duration is difficult to determine, and is very variable. It averages from three to six weeks, but may greatly exceed this. (4) The Stage of Decline. — This is reckoned from the time when a dis- tinct diminution in the severity of the disease can be observed. The preceding stage merges so gradually into it tliat its exact commencement can scarcely be determined. The paroxysms grow steadily less frequent and less severe. The cough has a much looser quality, and finally, although slowly, loses its paroxysmal character almost entirely, while the whoop becomes more and more infrequent. There is a muco-puru- lent bronchial secretion, and moist rales are heard in greater numbers in the chest. Hemorrhage and vomiting no longer occur. Finally, all whooping ceases and the disease changes into a simple bronchitis or the cough stops entirely. The duration of this stage is even more variable than that of the two preceding ones. It ranges from ten days to several months. Should the winter season be approaching, occasional paroxysms with whooping may continue until spring, sometimes after all persistent cough has ceased. It not seldom happens that all cough disappears for some time, but returns again, even with whooping. Such a return cannot with reason be called a continuation of the third staee. It is 718 PERTUSSIS. often found that cough with whoop occurs at intervals for months or even during a year after the original attack began, being brought on even by slight bronchitis. The terminal stage may safely be said to have ceased when once cough has disappeared if only for a brief period, for whooping occurring after this is rather a habit than anything else, and is to be considered a pure neurosis without any infectious element. Complications and Sequels. — Complications connected Avith the respiratory apparatus are the most frequent. Bronchitis is very com- mon, and when it develops early it may at first greatly obscure the diag- nosis of the case. One of the most dangerous complications is broncho- pneumonia. This is most apt to occur in feeble or rickety children or in those who have been subjected to exposure to cold or to improper hygiene of any sort. It is very prone to develop where measles has immediately preceded the attack of pertussis, but its most frequent cause is the occurrence of atelectasis. Atelectasis alone is a frequent complication in young children, especially in those who are weakly or rhachitic. It may be widespread or may be localized in a small area. Its onset is indicated by the ordinary symptoms of this disease, com- bined with a diminution or disappearance of the paroxysmal nature of the cough. Emphysema is a common complication, but is usually only temporary, although this is not always the case. Empyema, croupous pneumonia, and pleural effusion are of less frequent occurrence. (Ede- ma of the glottis is not common. Hemorrhage from the nose is ob- served almost too often to be regarded as a complication. The same is true of hemorrhage from the mouth, but true hgematemesis, in which the blood comes originally from the stomach and is not first swallowed and then vomited, is unusual. Hemorrhage under the conjunctivae is frequent, but that from the ear or lungs or under the skin is rare. Meningeal hemorrhage is not at all uncommon, and is the cause of many instances of convulsions and cerebral palsy. A superficial ulceration on and at each side of the froenulum linguce is so common that it can almost be called a symptom. It is probably pro- duced by the forcible driving of the tongue against the lower incisor teeth during coughing. It cannot be said to be diagnostic of whooping cough, for it may be seen in cases of severe cough from other causes. Loss of appetite, diarrhoea, and indigestion are frequent complications. The looseness of the bowels tends to be somewhat chronic, and the pas- sages contain considerable mucus. Prolapse of the rectum, hernia, or involuntary evacuation of fseces may be produced by the violence of the cough. Convulsions constitute a not infrequent and a dangerous complication, often, as stated, the result of cerebral hemorrhage. General oedema of the skin and subcutaneous emphysema are very unusual oc- currences. Hemiplegia, paralysis of other forms, persistent spasm of the glottis, aphasia, and sudden blindness are occasional complications. Albuminuria is quite frequent, and acute nephritis has repeatedly been observed. Sugar is sometimes found in the urine. Other distinct diseases may accompany whooping cough oi" develop as sequelse. Thus diphtheria, varicella, or other infectious disease may occur with it, but measles is especially likely to do so or still oftener to pre- cede it. Rhachitis, ansemia, or other constitutional disease may be either a sequel or a complication. Tuberculosis is one of the sequelse most apt RECUR llKSrE A.\l> lti:LAPSK—I)IA(;S()SlS. 719 to (lovoloj) and most to be dreaded. It is liable to come on ehielly in cliildrcn \\\\o iia\'e had pertussis very badly or whose general nutrition is much below normal from other canses. Its favorite seats, from whieh a more or less general alleetion may extend, are the bronchial and intes- tinal glands and patches of broncho-pneumonia. Various paralyses, blindness, deafness from rupture of the membrana tympani, epilepsy, aphasia, and disseminated sclerosis are among the numerous sequelae whieh have occasionally been reported. Uecukrence and Relapse. — Pertussis has a remarkable tendency to what appear to be relapses, yet which are not to be considered as such in reality. As has been pointed out, the return of whooping after the disease has apparently ceased is rather a neurosis than an evidence of a return of the disorder, since it is no longer infectious at this stage. Recurrence of pertussis is extremely rare. Le Gendre was able to collect only 8 cases in addition to 1 seen by himself. Diagnosis. — In the early stages the diagnosis of whooping cough is difficult or impossible. The existence of a cough which becomes more and more paroxysmal as time passes, in spite of treatment directed to a possible bronchitis, renders the existence of pertussis very suspi- cious, especially, too, if physical examination does not reveal a bronchitis which is at all commensurate in severity with the intensity of the cough. Vomiting occurring after the paroxysms of coughing and the greater frequency of the attacks at night are also diagnostic points. Of course the prevalence of an epidemic of the disease or the existence of other cases in the family are additional confirmatory signs. The development of the whoop will settle the matter finally, except in those cases where the disease never passes the catarrhal stage. In these cases the occur- rence of vomiting, the congestion of the eyes, and the character of the cough are often sufficient to render a diagnosis possible ; but it is especi- ally in such cases that the prevalence of the disease as an epidemic or its existence in other members of the family renders the most valuable service in determining the nature of the attack. Sometimes a severe acute bronchitis with an unusually spasmodic cough greatly resembles pertussis, but the existence of decided fever, shortness of breath, and numerous rales in the chest generally serves to distinguish it. The difficulty is especially great at the close of an attack of measles. Here we have, on the one hand, the existence of a severe bronchitis which may appear to account for the severity of the cough, and, on the other hand, the tendency w^hich pertussis has to appear after an attack of rubeola. Broncho-pneumonia is most liable to develop in the later stages of pertussis. When it occurs during the catarrhal stage it may alter the character of the cough and even prevent entirely the development of the whoop, making the diagnosis difficult. A pro- longed terminal stage of pertussis may simulate tuberculosis of the lungs. Only continued observation of the case will render it possible to deter- mine whether this disease is actually developing. Tuberculosis of the bronchial glands may occasionally be the cause of a paroxysmal cough Avhich greatly resembles that of pertussis. The long continuance of the affection, the absence of distinct stages, of vomiting, and of very cha- racteristic whooping, and the history of previous wasting and of fever, serve to distinguish it. 720 PEBTUSSIS. Prognosis. — The danger of whooping cough is far greater than is com- monly supposed. Statistics show that a very large number of children die of it. For instance, J. Lewis Smith states that 4840 deaths from it occurred in New York City during a period of fifty years, this equalling 1 out of every 79 deaths from all causes. W. W. Johnston says that an estimate based on the census of 1880 shows that over 100,000 chil- dren died of whooping cough in the United States during ten years : 120,000 persons fell victims to it in England and Wales between 1858 and 1867, and 85,000 in Prussia between 1875 and 1880. Not only is the actual number of deaths large, but the proportion of fatal cases to the whole number of cases is very considerable. Statistics ^vould indi- cate that the relative mortality is from 3 to 15 per cent., and occasionally higher. The mild cases of course recover, and it is upon the complica- tions that the mortality largely depends, although in severe uncompli- cated cases death may be caused by the great exhaustion produced or by other ways. The younger the child the greater is the danger to life. After the age of five years few succumb, while under that of two or three years the death rate is at its highest. Rather more females die than males, probably the result of a less degree of strength of constitu- tion and of resistance possessed by them. Badly nourished children raised amongst unfavorable hygienic surroundings naturally sufPer the most. Any constitutional disease, such as rickets, increases the danger. The previous occurrence of measles just before the development of pertussis renders the prognosis much graver. Both the summer and the winter seasons bring their dangers with them. In the first the occur- rence of intestinal complications and the debilitating influence of hot Aveather add to the danger, -while in the latter the liability to the development of respiratory disorders distinctly increases the risk. Broncho-pneumonia complicating pertussis makes the prognosis most grave and is a common cause of death. Convulsions, too, constitute a common fatal ending. Tuberculosis occurring as a sequel adds greatly to the death rate. Treatment. — Prophylaxis. — In the light of the danger and the great infectiousness of pertussis every effort should be made to guard children from the disease. The custom so prevalent of allowing children suffering with it to play freely W'ith others in the streets or parks cannot be too strongly condemned. Children should be strictly kept from the slighest contact with those who are even suspected of having whoop- ing cough, since it is infectious in the catarrhal stage as well as later. Unfortunately, the difficulty of recognizing the malady at this period renders the task almost herculean. AVhere an epidemic is prevailing it is better to remove unaifected children entirely from the locality. This is especially true in the case of weakly or very young subjects. It is impossible to determine exactly how long infectiousness con- tinues. It grows less during the last stage, and it may ordinarily be assumed to have ceased entirely by the end of two months after the onset of the disease. Quarantine may be discontinued after the child has ceased to cough for a few days, even though coughing return, with or without the whoop, afterward. As has previously been remarked, this later coughing is rather a neurosis or of a purely catarrhal nature than in any Avay partaking of the original infectious character. Both in the TREATMENT. 721 eases in which the (Xiuo:h roturns :it intervals for months and in tiiose in which one or two paroxysms daily persist for an indefinite time it wouhl be as clearly entirely impraetieable to continue quarantine as it would be unnecessiiry. In such cases isolation may cease two or at most three months after the onset. Since there is a possibility, althouirh a remote one, of ti'ansmittinjj: the infection by the bed- or body-linen, disin- fection of this should be carried out, as well as of the room, after the disease is over. , Treatment of the Attack. — In the treatment of pertussis the physician often encounters a problem which taxes his resources and ingenuity to the utmost. The mildest cases require only careful supervision or are easily relieved to a very satisfactory extent by medication. In the severe cases, on the other hand, the condition is far different. Here we must be ready to employ one plan of treatment after another until some- thing of benefit is found, for there is no disease of which it is truer than of pertussis that the treatment which has acted like a charm in one case or series of cases may fail utterly in another series or individual. Even in one family one child may be greatly relieved by one drug and another only by another. Then, too, we must not fail to employ our remedies in sufiticiently large dose before decrying them as useless. So also it is only early in or at the height of the disease that we can come to any conclusion regarding the virtue of any plan of treatment, for almost anything will seem to benefit when the attack is about to undergo its natural decline. Treatment maybe conveniently divided into — (1) hygienic; (2) lo- cal ; (3) general. 1. Hygienic treatment is of great importance. Children who are not suffering from any respiratory complication should be kept in the fresh air as much as possible. There is no doubt that air vitiated by carbon dioxide increases the number and intensity of the paroxysms. On the other hand, they must not be recklessly exposed, since the tendenev to respiratory complications is so great. Damp and windy weather must be avoided and the children confined in airy rooms. It is an excellent plan to have two large rooms — one for the day and the other for the night — and to air each thoroughly before it is used. The num- ber of paroxysms at night is often considerably diminished in this ^\■ay. Clothing must be sufficiently warm, and food should be nutritious and easily digestible, and given frequently in small quantities in eases where the tendency to vomiting is troublesome. Nutrient enemata may be required in some of these cases. Change of climate often works wonders, especially in the stage of decline. It should, however, never be employed at the expense of unaffected children. 2. Local treatment has been largely employed. It may be di\"ided into (a) insufflation of powders into the nose or larynx ; (6) applications of solutions by the spray or brush or by irrigation; (e) inhalation of volatile substances and of gases. (a) Quinine by insufflation has been one of the most popular methods of local treatment. The formula first recommended by Letzerieh con- sisted of a mixture of this drug, bicarbonate of soda, and powdered acacia. With this insufflations were made into the larynx three times a day. Very excellent results with quinine have been obtained by a numV)er of Vol. I.— 46 722 PERTUSSIS. physicians. Laryngeal insufflations are not easy to employ in the case of young children, and it is quite certain that in the hands of any one not especiallv skilled in the manipulation the greater number of them never reach the larvnx at all. On this account nasal insufflations of quinine are to be preferred. Among the other powders which have been recom- mended for insufflation into the nose or larvnx are resorcin, boric acid, benzoin, iodoform, salicylic acid, borate of soda, antipyrine, and tannin. Of these benzoin appears to hold the most prominent place and to have most authority in its favor. Boric acid is also serviceable in many cases. I have found it useful by nasal insufflation, but the results were not so good as those obtained by internal medication. Eesorcin is also highlv praised. Guttmann recommends sodium sozoiodol for nasal insufflations. Various combinations of powdered drugs for insufflation have been recommended by different writers. Thus, boric acid and powdered coffee are praised liy Guerder, and benzoin, salicylate of bis- muth, and quinine by Moizard. (6) One of the earliest methods of local treatment for pertussis was the application of a weak solution of nitrate of silver to the larynx, recommended by Watson in 1849. Some later observers have obtained good results with it. A solution of cocaine of a strength of from 2 to 15 per cent, has been used as an application to the pharynx by the brush or sprav. It can undoubtedly do good, but the effect is liable to be only transitory and the remedy is not devoid of danger. Alarming svmptoms produced by the application have been reported. Among tiie other drugs in solution which have been used locally as a spray or on the brush are peroxide of hydrogen, morphine, resorcin, bromide of potassium, chloride of ammonium, alum, tannic acid, and salicylic acid. Resorcin is one of the best of these. It has been especially recommended by Moncorvo, who applies it in 2 per cent, solution with a brush to the larynx once daily. Irrigation of the nares is advocated by numerous writers. For this purpose we may use peroxide of hydro- gen, a saturated solution of boric acid, sulphate of iron in the strength of 1 grain to the ounce of water, bichloride of mercury, 1 : 6000, and salicvlic acid, 1 : 1000. The procedure is very unpleasant to the child, is not devoid of danger to the Eustachian tubes, and is not in any way superior to insufflation or atomization. (c) Desmartes in 1859 first recommended the inhalation of the air from the purifying rooms of gas-works, and since then the value of the treatment has often been urged. Later studies have not sustained the claims which have been made. Among the numerous other sub- stances recommended for inhalation are carbolic acid, creasote, eucalyp- tus, turpentine, terebene, tar, petroleum, thymol, pumilene, benzine, camphor, ozone, naphtluilin, nitrite of amyl, and compressed air. Of these the one which would seem to be most generally esteemed is car- bolic acid. This may be vaporized from a saturated solution in a croup- kettle or steam atomizer or from sponges or cloths wet with it and hung about the room, or it may be inhaled from a respirator placed over the mouth and nose. It may also be volatilized by placing a few crystals upon hot iron. The fumigation of the room with burning sulphur was strongly advocated by ^Slohn, and his experience has been confirmed by others. ' The sulphur should be burned after the child has been re- TREATMEyT. 723 moved in the morning and dressed in clean elotlies. After five liours the room should he well aired, and then slept in that ni<:;ht. Inhalation of ehloroform or ether has been advise cases oocnrrini*- sporadically in tlicii- hospital j)raetice. The j)n)dromal svmptoms last a few honrs to perhaps two days. In excep- tional cases they may continne four to eight days. Stage of Swelling. — Generally by the second or third day after the beirinnino- of symptoms evidences of involvement of the parotid ^land apj)ear — if, indeed, as stated, they are not the first signs of the disease. A dnll, aching', continnons pain beg'ins in the region of the ear and cheek on one side. It is made worse l)y pressnre and by every move- ment of the jaw for eating or speaking. It hinders to a considerable extent the opening of the mouth, and often renders it impossible. Pain in the ear is not uncommon. Swallowing and the movement of the head are often painful. The degree of pain, slight at first, increases gradually during several days, coincidently with the increase of swell- ing. Its intensity varies with the case. Sometimes it is but slight, and may even be almost wanting, except upon movement of the jaws, while in other cases it is constantly severe. Rilliet and Barthez have described three especially painfnl points as being very frequently pres- ent — viz. on the mastoid process, on the temporo-maxillary articulation, and over the submaxillary gland. Swelling commences a few hours after the first development of pain and increases rapidly, reaching its height by the second to the fourth day, or sometimes not until the sixth day. It begins in the region of the parotid gland, between the descend- ing portion of the lower jaw and the mastoid process. Although it may remain confined to this area, it often spreads backward, forward, and downward owing to the involvement of the submaxillary and sub- lingual glands, the connective tissue of the face and neck, and the cervi- cal lymphatic glands. The ear seems lifted up and pressed outward, and, in cases of extensive swelling the outline of the lower jaw dis- appears and the whole side of the face and neck seems much swollen. The skin over the swelling usually is pale and shining. Only seldom is it reddened. Pressure with the finger generally meets with an elastic resistance, but when there is much cedematous infiltration of the skin pressure is very painful and leaves an indentation. In cases of very extensive swelling the oedema may extend even to the upper part of the chest. After the swelling has reached its height the diminution in size begins. The rapidity with which this occurs is very variable. Generally no trace of it remains by the seventh or eighth day after its first appearance, although it occasionally persists a longer time. In the majority of cases both parotids are attacked, but it is only^ exceptionally that the swelling in them comes on simultaneously. Ac- cording to some writers, the gland of the left side is usually the one first swollen. The second parotid is involved one or tw^o days after the first begins to enlarge. Sometimes the interval is longer, and it may ha])pen that the disease has nearly disappeared from the first side before it shows itself on the second. Almost always the second swelling is less pro- nounced than the first. 728 EPIDEMIC PAROTIDITIS. Fever of varying degree, mentioned among the prodromal symptoms, continues during the stage of swelling, its height depending largely upon the severity of the attack. As a rule, it is slight, with morning remissions and evening exacerbations, and it gradually rises until it reaches its height, generally not much more tlian 102° F., Avith the maxi- mum of the swelling. Then it falls rapidly to normal. Occasionally, especially in severe cases, the temperature rises higher than this, and may continue in the neighborhood of 104° F. for several days. The pulse and respiration maintain their normal ratio to the temperature. Some degree of malaise and prostration may be present. Redness of the fauces and lining of the cheeks and severe tonsillitis are some- times observed. Ringing in the ears and some deafness are not uncom- mon during the height of the disease. The secretion of saliva is sometimes increased, but is oftener diminished. Gerhardt found by introducing a cannula into the duct of Steno that the saliva from the affected gland came more slowly than normal, but exhibited no material changes in character. The pressure of the swollen glands narrows the fauces and increases the difficulty in swallowing, makes the voice nasal, and may cause dyspnoea by pressure on the larynx, CEdema of the larynx is sometimes produced. Vomiting, diarrhoea, and epistaxis are occasionally seen. In the form of the disease sometimes called the tv- phoid type there is a prominence of threatening nervous symptoms, such as delirium, restlessness, adynamic state, and involuntary evacua- tions. Enlargement of the spleen often accompanies the severe cases. One of the most interesting of the symptoms of mumps — too inte- gral a part of it to be called a complication — is the involvement of the genital apparatus, especially the testicle. This was once considered to be the result of metastasis, the transmission to the testicle of some poisonous substance produced in the parotid gland. The fact that occa- sionally the testicle is the first to be affected or, as in the cases reported by Kovacs and others, is alone involved, proves that this theory is in- correct and that orchitis is simply a localization of the specific poison upon the testicle. The severity of the parotiditis seems to have no influence on the tendency to orchitis. The involvement of the testicle is very rare in children. It is oftenest seen in youths and young adults, but here, too, its frequency varies greatly with different epidemics. Laveran reports it as occurring in 1 out of every 3 cases among patients in the army, while the observations of some others place its frequency at much less than this : 699 cases of mumps occurring in 14 different epi- demics, collected by Comby, gave 211 cases of orchitis, a percentage of 30. As a rule, orchitis begins six to eight days after the appearance of the parotid swelling. In the majority of instances only one testicle is attacked. In the cases where both suffer the inflammation begins in the second from two to four days after the first is affected. The process is a true orchitis, and the epididymis is only occasionally involved, and then generally to a less degree. The symptoms of the testicular involvement consists in a renewal of the fever, which had grown less or disappeared, but which now reaches 101° F. or more. Not infrequently severe or even threatening symptoms attend or precede the process, such as vomiting, severe diar- rhoea, rapid, feeble pulse, profound depression of strength, delirium, ( 'OMPUCA TIONS AND SEQ UELyE-I)I. I CNOSIS. 729 aiul tyj»lit>i(l syinptdiiis. There is dull oi' .severe pain in the testicle M'ith swelling and tenderness. The skin of the scrotum is red and tender and sonietinies (edematous. The inflammation reaches its heigiit by the third or ioiirth day, continues severe from two to three days, and then rapidly g-rows less. The severe li'eiieral symptoms usually diminish i'a[)idly by the time the testi<'ular s\vellin I. GENERAL ETIOLOGY AND MORBID ANATOMY. Definition. — An infectious disease due to the bacillus tuherculosis, characterized by the presence of nodular bodies called tubercles (or diifuse infiltrations) which may undergo caseation or sclerosis, and which may finally ulcerate or in some situations become calcified. I. General Etiology and Morbid Anatomy. — (1) Tuberculosis in Animal'<. — In reptiles the disease is rare, though occasionally, as Sibley has shown, it is found in them in a state of confinement. In birds the disease is common in the domestic fowls, but there are differences which warrant the separation of avian from other forms of tuberculosis. In Domestic Animals. — One of the most important etiological facts in connection with the disease is its widespread occurrence in animals from which man derives a considerable share of his food. Bovines are chiefly affected. Recent studies and the improved methods of inspec- tion have demonstrated the very widespread existence of the disease. In the United States no compulsory systematic inspection is made at the abattoirs, but a good deal of information has been collected of late years. Of 5297 cattle slaughtered in Maryland, 159 were tuberculous (A. W. Clement), and of 15,506 animals slaughtered at the Brighton abattoir, near Boston, 29 were tuberculous (Burr). Careful inspection of herds has been made in some of the States, and the tuberculin test employed to determine the presence of the disease. The New York State Commission examined 947 animals and condemned 66. On the continent of Europe much more accurate statistics are avail- able. Thus for the four years (1890-93, inclusive) the percentage of tuberculous animals among 132,294 oxen and cows slaughtered in Copenhagen was 17.7. At the Berlin abattoir in the year 1892-93, 21,603 animals out of 142,874 showed evidences of tuberculosis. In the same year 125 calves out of 108,348 showed signs of the disease. In Great Britain there are no satisfactory records to show the incidence of the disease in cattle. In sheep the disease is very much less common. The percentage at Berlin is about 1.5. Horses are rarely attacked. Dogs and cats are not very liable to the disease. Cadiat has recently investigated carefully the subject of tuberculosis in the dog. At Alfort there were 40 cases ^ I beg to acknowledge the valuable assistance I have received in the preparation of this article from my assistants, Dr. George Bluraer and Dr. T. B. Futcher. 731 732 TUBERCULOSIS. of the disease among 9000 post-mortems. The disease, he states, orig- inates usually in the intestines, and the virus is probably transmit- ted through bones which have been previously picked by tuberculous patients or the dogs have licked up what has been left on their plates. When one considers the very close contact of the dog as a domestic pet, it is somewhat remarkable that the disease is so rarely seen in it. In other animals kept as pets, such as the rabbit and guinea-pig, the disease, under natural conditions, is very rare. Both of these animals, however, are very susceptible to the disease when inoculated. Among apes and monkeys kept in confinement tuberculosis is the most formid- able disease with which these animals have to contend. (2) General Statistics of the Disease in Man. — Tuberculosis is the most universal scourge of the human race. It prevails more particularly in the large cities and wherever the population is massed together. It is estimated that in civilized countries one-seventh of the deaths are due to this disease. In the United States Census Report for 1890, 102,188. deaths were reported to be due to consumption. It is difficult to get accurate statistics as to the number of deaths due to other forms of the disease, but at a low estimate one can say that at least 150,000 persons die annually in the United States of all forms of tuberculosis. An estimation based on the Census Report gives the total number of per- sons in this country infected with tuberculosis as 1,050,000, or 1 in every 60 of the population (Vaughan). The death rate from tuberculosis in the cities is very much higher than the average ; thus Hirsch states that while the general death rate is 3 per thousand, that of Vienna is 7.7, and of Munich and Glasgow 4 per thousand. Geographical jjosition has very little influence. The disease is per- haps more prevalent in the temperate regions than in the tropics, but altitude is a more potent factor than latitude ; in the high regions of the Alps and Andes and in the central plateau of Mexico the death rate from tuberculosis is very low. The influence of race, which has been much studied, is probably less owing to any inherent differences than to the conditions under which the individuals live. The Indians of this continent are very prone to the disease. Matthews states that the death rate in the older reservations in the East was three times as great as that of the Indians still living in the Northwest. In this country the Irish and the negroes appear specially prone to the disease ; on the other hand, the Hebrews possess a relative immunity. For the six years ending May 31, 1890, the average annual death rate from consumption in New York City, per 100,000 of population was — for the Irish, 645.73 ; for the colored, 531.35; for the Germans, 328.80; for the American whites, 205.14; and for the Russian-Polish Jews, 76.72 (J. S. Billings). The interesting question arises as to w^hether tuberculosis is on the increase or on the decrease. E. F. Wells, who has tabulated an im- mense body of statistics on this subject, states that the evidence is in favor of a very positive decline in the prevalence of the disease. While the last decennial census of the United States does not show any decrease, yet in many of the larger cities there has been a striking diminution. The question has been considered very carefully by James B. Russell GENERAL KTIOLOGY AND MORIUI) ANATOMY. 1?>:\ of Glasgow in his Sanitary Ili.stoi-i/ ul)to(lly tho long, narrow, Hat chest witli depressed sternum is eoninionly cnonoli seen iu tnbereulous patients, but tliere are only too many individuals with perfectly well-shaped chests who fall victims anmially to the dis- ease. The tuberculous or scrofulous diathesis, ujion which formerly so much stress was laid, is now regarded simply as an indication of a , type of conformation in which the tissues are more vulnerable and less capable of resisting infection. Bencke's investigations on the viscera of phthisical patients indicate that the heart is relatively small, the arteries projwrtionately narrow, and the pulmonary artery relatively wider than the aorta. He suggests that this may lead to increase in the intrapulmonary blood pressure, and so favor catarrhal processes. The lung volume he found relatively greater in those affected wdth tubercu- losis. A study of the composite portraiture of pulmonary tuberculosis has been made by Galton and ISIahomed. In 442 patients they sepa- rated two types of face — one ovoid and narrow, the other broad and coarse featured. This corresponds in an interesting way to the diathetic states formerly recognized — namely, the tuberculous, with thin skin, bright eyes, oval face, and long, thin bones ; and the scrofulous, with thick lips and nose, opaque skui, large, thick bones, and heavy figure. These conditions, on which so such stress was formerly laid, indicate, as Fagge states, nothing more than delicacy of constitution, incomplete growth, and imperfect development. (e) IitfJuence of Age. — No age is exempt. The disease is met with in the suckling and in the octogenarian. Pulmonary tuberculosis occurs most frequently, as stated by Hippocrates, from the eighteenth to the thirty-fifth yeaV. From the fifth to the tenth year individuals are less prone to the disease. At different ages different organs are more prone to be involved. During the first decade the bones, meninges, and lymph glands are more frequently affected than at subsequent periods. {d) Sex. — The influence of sex is very slight. Women are perhaps somewhat more frequently attacked than men, due, possibly, to the fact that in a more sedentary, in-door life they are more liable to infection. Pregnancy and lactation also are two conditions which are apt to lower, perhaps, the resistance of the organism. (e) Race. — The negro, wdio it is stated is not specially prone to the •disease in Africa, is in America and in the West Indies very subject to tuberculosis. The relative immunity of the Jews has been mentioned (page 730). (,/') Occupation is an important predisposing factor. The inhalation of impure air in occupations associated with a very dusty atmosphere renders the lungs less capable of resisting infection. The incidence of pulmonary tuberculosis among the workers in mills and factories is very high, and in certain occupations, such as glass-workers, stone- cutters, and coal-miners, and the whole group of trades which lead to pneumonokoniosis, favors the development of tuberculosis. {[/) Certain local conditiom influence infection, among which the fol- lowing are the most important : Catarrhal Bronchitis. The influence of catarrh of the respiratory passages in pulmonary tuberculosis is well recognized. How' often is a neglected cold blamed as the starting point of the disease ! It seems to 746 TUBERCULOSIS. act by lowering the resistance and favoring the conditions which enable the bacilli either to enter the system or, when once in it, to develop. The liability of lymphatic tuberculosis in children is probably asso- ciated with the common catarrhal processes in the tonsils, throat, and bronchi. Certain of the specific fevers predispose to tuberculosis, among which measles and whooping cough stand pre-eminent. They are often associ- ated with a bronchial catarrh. In some of the cases it is probably not a fresh infection which follows, but the blazing of a smouldering fire. Typhoid fever is thought by some to predispose to tuberculosis, but my experience is opposed to this view. Of other affections, influenza, vari- ola, and syphilis are all believed to favor the development of the dis- ease. Diabetes, as is well known, very often, terminates in pulmonary tuberculosis, particularly in young persons. Chronic heart disease, arterio-sclerosis, aneurysm of the aorta, forms of chronic nephritis, cirrhosis of the liver, and the various forms of cerebro-spinal sclerosis, all are conditions which favor infection. It is remarkable in how many of the subjects of these disorders in general hospital practice the fatal event is a terminal acute tuberculosis, most frequently of the serous membranes. Subjects of congenital or acquired contraction of the orifice of the pulmonary artery usually die of tuber- culosis. On the other hand, mitral valve disease, particularly stenosis, is stated to antagonize the disease (J. E. Graham). In children catar- rhal entero-colitis probably favors the development of tabes mesenterica. The influence of hsemoptysis and pleurisy will be referred to later. Trauma. Surgeons have laid great stress upon this as an etiological factor in tuberculous processes. Experiments indicate that tissues wdiich have been bruised, and which would in health have readily and rapidly destroyed organisms, promote their growth under the altered conditions. Probably in the case of tuberculosis following trauma the injured part is for a time a locus minoris resistentioe, and if bacilli are present they may by it receive a stimulus to growth or under the altered conditions be capable of multiplying. Not only in arthritis, but in pulmonary tuber- culosis, traumatism may play a part. The question has been thoroughly studied by Mendelssohn, who reports nine cases in which, without frac- ture of the rib or laceration of the lung, tuberculosis developed shortly after contusion of the chest. Operation upon tuberculous lesions may be followed by a general infection. Resection of a strumous joint is occasionally followed by acute tuberculosis. Of 837 resections, 225 ended fatally, 26 with acute tuberculosis (Wartmann).^ The General, Morbid Anatomy and Histology op Tubercle. (1) The Distribution of Tubercles in the Body. — The distribution of tubercles in the organs and tissues of the body varies greatly according to the primary seat of the disease and according to certain peculiari- ties of individual organs and tissues ; the bacilli may find their Avay into the circulation either by the blood or lymph channels, and lead to the formation of scattered foci of tubercles which are found in the internal ^ A recent study of the question is to be found in vol. ii. of Bevue de la Tuberculoses by Depage and Gallet. GENERAL ETIOLOGY AND MORBID ANATOMY. 747 orii'ans. In ciiscs oC licncral t iilxTciildsis, wlici'c the hacilli arc carried into llic hlood in lar^c nnnihcrs, the tuhcrck! nodules are evenly dis- tributed throu<;hout the organs, thou<;h to inacroscopieal investij^ation they seem to be nuieh more numerous in one organ than in another. Miliary tubercles in the liver are often very difficult to distinguish mae- roseopieally, whilst, on the other hand, those in the sj)leen and kidney are usually easily made out. On microscopical examination, however, the liver, which to the naked eye has seemed to contain l)ut few tuber- cles, is often found studded with them. The great difficulty in making out tubercles in certain organs, particularly in the pancreas and thyroid gland, has led to the belief that these organs are relatively immune to the attacks of the bacillus. This belief, as Chiari pointed out, is false, microscopical examination showing in most cases of miliary tubercu- losis numbers of tubercles in both the organs mentioned. Certain of the organs and tissues of the body, however, do seem to be almost immune against tuberculosis, particularly the oesophagus, the inner lining of the larger arteries, and the voluntary muscles. The fact that the latter are resistant is often strikingly illustrated in cases in which both layers of the pleura are infiltrated by the tuberculous process, which, however, stops sharply at the subjacent intercostal muscles. The one organ which is almost always affected in tuberculosis, as seen at the autopsy table, is the lung, and this is true both of children and adults. Here may be mentioned the very frequent occurrence of healed lung tuberculosis in all classes of cases, the healed area generally appearing in the form ©ither of an area of dense fibrous material or of an encapsulated caseous or calcareous nodule. Apart from the lung, the organs are affected with tubercle with varying frequency at varying periods of life ; in children the lymph glands, bones, and joints are attacked most fre- quently. (2) Changes Produced by the Tubercle Bacilli. — The Nodular Tuber- cle. — The most distinctive lesion produced by the bacillus tuberculosis is the nodular tubercle, accurate descriptions of the histology of which we owe particularly to the painstaking researches of Baumgarten. The fact must never be lost sight of that in their early stages tubercles do not present any peculiarity in their histological components or arrange- ment. Similar aggregations of cells mav be caused bv foreien bodies, certain animal parasites, and the dead products of the tubercle bacilli, and in certain stages the so-called lymphomata of the liver, occurring in typhoid fever, are strikingly like young tubercles. The evolution of the tubercle following the introduction of the tubercle bacillus into the tis- sues may be traced as follows : («) The MuUiplication of the Tubercle Bacilli. — This begins almost immediately after the introduction of the organism. The growth is quite rapid, and is accompanied by its dissemination into the surrounding tis- sues, partly by direct growth, and partly by mechanical dissemination in the lymph stream. The action of phagocytes in connection with the dissemination of the bacilli has not been accepted by most pathologists, and probably does not occur. From an early date many of the bacilli are found in the fixed tissue cells of the affected tissue. (6) The Ilultiplication of the Fixed Cells. — From the fifth day after the introduction of the tubercle bacillus into the tissue changes can be 748 TUBERCULOSIS. made out indicative of multiplication of the fixed cells by the indirect method of subdivision, as evidenced by the abundance of karyokinetic figures to be found in the affected region. This cellular subdivision aifects not only the fixed connective tissue cells of the part, and the endothelial cells, and the lining of the smaller bloodvessels, but the cells of the parenchyma of the affected tissue can also be seen to be in a state of active subdivision. As a result we have the production of rounded or irregularly cuboidal cells with vesicular nuclei, which re- semble epithelial cells, and are hence called epithelioid cells. Almost from the first appearance of these cells tubercle bacilli can be demon- strated in tlie interior of a certain number of them. In some only a single bacillus can be made out ; in others the cell is closely packed with a mass of bacilli, often having the appearance of a typical " leprosy cell." (c) The Invasion by Leucocytes. — Following the formation of the epi- thelioid cells other cells are soon to be made out in the tubercle which are evidently of vascular origin, as they show no signs of multiplication, the only changes they undergo being of a regressive character. These emigrant cells are of two varieties — the polynuclear leucocyte, and the small mononuclear element of the blood, the so-called lymphocyte. The polynuclear leucocytes appear much more susceptible to injury than the mononuclear variety, ancl undergo regressive changes with great rapidity. The mononuclear variety, on the other hand, are much more slowly destroyed, and as the tubercle increases in size the leucocytes represented are in large part these small round elements which are situated particu- larly at the periphery of the nodule. (d) The formation of a Reticulum. — About the tenth or eleventh day a fine network is to be seen between the cells composing the tubercle — a network first pointed out by Wagner, and which is best demonstrated in specimens hardened in osmic acid. This reticulum is composed, accord- ing to some pathologists, of the pre-existing connective tissue elements which have undergone a rarefaction from the pressure of the growing tubercle cells. It exists particularly at the periphery of the tubercle, and the fibres composing it can at times be made out to be directly continu- ous with the fibres of the surrounding connective tissue. The recent researches of Falk would tend to show that there is also present in the tubercle nodule from an early stage — that is to say, before the existence of degenerative changes — definite fibrillary fibrin, also most abundant at the periphery of the tubercle, and undergoing destruction in the subse- quent degenerative processes through which the tubercle passes. (e) The Formation of Giant Cells. — In the large majority of tubercles there are present, besides the varieties of cells above mentioned, large cells containing from four or five to twenty-five or thirty nuclei — so called giant cells. These are formed either from the fusion of individual cells or much more probably from the indefinite multiplication of the nuclei in a single cell, the protoplasm failing to divide with the nuclei. The character of the nuclei in these cells is the same as that of the epi- thelioid cells composing the tubercle, and the great mass of evidence goes to show that the giant cells are epithelioid cells whose nuclei have subdivided indefinitely, whilst their protoplasm has lost its power of subdivision, probably on account of the injurious influence exerted upon it by certain products of the tubercle bacillus. The giant cell is gen- GENERAL ETIOLOdY AND MORBID ANATOMY. 749 CM'ally in('i;iil:ii'ly round or o\al in shape. It varies in diaiueter from two to tliree niiki-ons, and often sliows at various points on its periphery distinct branching j)roh)ngations. The giant cell is not by any means characteristic of tuberculosis, but the type of giant cell associated with this disease — Tjanghans' giant cell — is so characteristic and so seldom found in other conditions that it has been called by certain (Jcrman writers the lingcr-])ost of tuberculosis. The chief characteristic of the tuberculous giant cell which distinguishes it from most other forms is the peculiar arrangement of its nuclei, either around the periphery of the cell or at one or both of the poles. This is due to the fact that the centre of the giant cell, like the centre of the tubercle, in the mid-por- tion of which it generally lies, is particularly prone to undergo degener- ative changes, so that whilst at an early stage in its development nuclei exist throughout the protoplasm of the giant cell, those in the centre of the cell are soon destroyed, the remaining one having a mural or polar arrangement according as the cell is round or oval. (3) Tlie Degeneration of Tubercle. — The ultimate fate of all tubercles is degeneration. This is not due, as was formerly supposed, to lack of nutrition, for much larger areas than those represented by a tubercle may be nourished without a direct blood supply. The agents which lead to the degeneration of the tubercle are the tubercle bacilli themselves and their products. In order to produce this degeneration the living bacilli themselves are not necessary, the researches of Prudden, and later of Kostenitsch, having shown that the dead bacilli and the bac- terial products are capable of setting up exactly similar changes. The forms of degeneration which the tubercle may undergo are two — caseous and fibrous. (a) Caseous Degeneratioii (Caseation). — This form of degeneration, which is the most common, may occur at any stage in the process of tu- bercle formation. It is often seen in the very earliest stages, and in its most characteristic form is seen in tuberculous glandular masses and in certain forms of lung tuberculosis. Weigert pointed out that the process was one of coagulation necrosis. The cells in the centre of the tubercle die slowly, and are transformed into coagulated homogeneous or finely granular masses, showing absence of nuclear staining or at most but fine nuclear fragments taking the stain. These masses subsequently undergo fatty infiltration and take on a white, opaque appearance re- sembling cheese ; hence the name caseation. In the miliary tubercle these caseous masses are seen as the opaque yellow centre of the nodule, the gray, translucent periphery representing the non-degenerated por- tion of the tubercle. The aggregation of many caseous tubercles leads to the formation of the much larger masses so commonly seen in the more chronic forms of the disease. At the beginning of the process the tubercle bacilli can still be demonstrated Avith good staining reactions in the degenerated mass. At a later date many or even all the bacilli may lose their staining power, though this a])parently harmless material is still capable of setting up the disease when inoculated into susceptible animals. In some instances, as in certain forms of lung tuberculosis, the caseous material everywhere contains large numbers of tubercle bacilli. The cheesy masses may undergo secondary changes, some of which are favorable, others unfavorable, to the progress of the disease. In 750 TUBERCULOSIS. some instances they soften and break down into a rather thick, grumous fluid, forming the so-called tuberculous abscess. The contents of such abscesses do not, however, consist of true pus, but mainly of broken- down cellular products, often showing an extreme grade of fatty change. Another form of softening with true pus formation is seen where the caseous focus becomes secondarily infected with pus organisms. Here, besides the detritus above mentioned, we have all the constituents of true pus. A more conservative process may often take place in the caseous material, leading to the production of a dense fibrous capsule about the mass — so-called encapsulation. In these instances the fluid element of the caseous material may be almost entirely absorbed, leaving the encapsulated substance as a dry and friable, but still somewhat cheesy-looking, material. In some other instances a deposit of lime salts takes place in the caseous area, Avhich here, again, may become sur- rounded by a fibrous capsule and remain innocuous in the tissues for years. (6) Sclerosis. — In many cases, particularly in individuals who possess good powers of resistance, a more conservative process occurs in the tubercle — the so-called sclerosis or fibroid change. This is seen most frequently in the lungs and in the peritoneal cavity, and is the method by which the spontaneous cure of tuberculous lesions takes place. The process consists in the formation, sometimes with, sometimes without, caseation, of fibrous tissue, with the disappearance of the tubercle as such, the final result being its transformation into a small nodule of dense fibrous tissue. In the case of the already cheesy tubercle the fibroid process takes place from the cellular part of the nodule surround- ing the caseous centre, the new cells originating from the pre-existing tubercle cells. Where the process tends to be fibroid from the beginning the whole tubercle may lose its cellular structure at an early period and become transformed into a small fibrous tumor mass. (4) The Diffused Infiltration Tubercle. — In many parts of the body, more particularly in the lungs, the tuberculous process, except in very acute cases, does not manifest itself as discrete nodules, but as a more or less extensive diifuse process, which results from the fusion of many small tuberculous areas. As a matter of fact the small nodule which we are accustomed to regard as the ultimate tubercle — the miliary tuber- cle — is, as has been pointed out by Virchow, in many instances not single, but a mass of very small tubercles, the true ultimate tubercle ibeing submiliary in size and on the limit of visibility so far as the naked eye is concerned. As seen in the lung the areas of infiltrated tubercle present to the naked eye a grayish, translucent appearance, and often particularly in the later stages, a caseous centre. These areas vary greatly in extent, some occupying only a few lobules, and again a Avhole lobe, or even a whole lung, being affected. In many instances the course of the smaller bronchi is beautifully mapped out by the pro- cess, which occurs as a series of peribronchial tuberculous masses. At times a whole lobe is consolidated, giving rise, after caseation has taken place, to the appearance designated as caseous pneumonia — a condition previously regarded as being due to the superaddition of the tuberculous infection upon a preceding croupous pneumonia, but which we now know to be entirely due to the action of the tubercle bacillus. The ACUTE TUBERCULOSIS. 751 whole ju'dccss, tVoin the t"i)riii;iti(iii ol" the miliary tubercle to tlie com- plete consolidation of a lari;c lol)e of the lun«^, can he followed out step by step with suitable pre})arations. (5) !SiroHi(lity of an extremity. Diagnosis. — The (Ha;ue and uncertain features of the j)r()dn»iual stao;e may sometimes awaken one's sus])ieions, ])artieularly in a family in Avhich tuberculosis has prevailed. The symptoms of onset — head- ache, fever, and vomiting — are common enoujj-h in many disorders of childhood, ])articularly in the initial stage of the fevers. A day or two usually suffices to clear u]) the diagnosis. There arc three conditions, however, which demand s])eeial notice : First, the symptoms associated with otitis media in children. On sev- eral occasions I have seen cases in which headache, vomiting, and fever were most suggestive of oncoming meningitis, and iji which the whole trouble was due to middle-ear disease. In an instance which I saw recently the child had made little or no complaint of the pain in the ear, and it was not till the third or fourth day, after presenting symptoms of great severity, that a discharge took place from the right ear, with prompt relief. Second, the cerebral symptoms which are associated with gastro- enteritis in children. There may be convulsions, coma, squint, and con- tracted pu]iils, with irregularity of the pulse and Cheyne-Stokes respi- rations. The condition has been called false hydrocephalus, or, as Marshall Hall termed it, the " hydrencephaloid" state. The child is in a semicomatose condition, with the eyes open and the fontanelles depressed. A third important condition is associated wdth pneumonia, more fre- quently in children than in adults. The cerebral symptoms maybe the more marked from the onset, and not a single feature of the early stages of meningitis may be lacking — the vomiting, constipation, intense headache, photophobia, and even the cry. The local pulmonary symp- toms may be completely obscured or overlooked. Very often, too, in these cases the pneumonia is of the apex, and there may be little or no expectoration. I have known cases in which there w^as not a suspicion entertained of the existence of pneumonia ; but the autopsy showed the meninges to be perfectly free from exudate and a localized consolidation of the apex or of a lower lobe. In a few instances, too, children who are teething or who have a transient dyspepsia present for a day or \\\o cerebral symptoms which mav sugg&st meningitis. Typhoid fever may simulate closely tuberculous meningitis. On several occasions I have performed autopsies on supposed meningitis and found the meninges free from all inflammation, while the intestines showed the lesions of typhoid fever. It is w'ell to remember Stokes' dictum, that in the fevers " there is no single nervous symptom which may not and does not occur independently of any appreciable lesion of the brain, nerves, or spinal cord." The differential diagnosis between the tuberculous and the simple forms of meningitis is not always possible. The history of a previous tuberculous lesion or the presence of some focus of disease or caseous glands, the recent recovery from one of the fevers, the more insid- ious onset, the protracted course, and the symptoms pointing specially 760 TUBERCULOSIS. to involvement of the base are all points which favor the diagnosis of tuberculous meningitis. Peog-nosis. — Tuberculous meningitis is almost invariably fatal In- stances of recovery are on record, but there is always in these a doubt as to the diagnosis. I have not seen an instance of recovery in a case which I regarded as tuberculous. The possibility, however, cannot be denied. Wallis Ord and Waterhouse have reported a case of recovery in a child of five years after trephining and drainage. A recovery has followed Quincke's lumbar puncture. III. TUBERCULOSIS OF THE LYMPHATIC SYSTEM. I. Tuberculosis op the Lymph Glands (Scrofula). The very word scrofula has almost disappeared from our vocabularies. In a recently issued voluminous work on Pediatrics the name does not occur in the index. This remarkable change has followed the demon- stration of the tuberculous nature of scrofulous lesions. Formerly special attention was given to different types of scrofula, of which two important forms were recognized — the sanguine, in which the child was slightly built, tall, with small limbs, a fine clear skin, soft silky hair, and was mentally very bright and intelligent ; and the phlegmatic type, in which the child was short and thick-set, with coarse features, muddy complexion, and a dull, heavy aspect. Tuberculous adenitis occurs at all ages, and, though more common in children than in adults, it is not at all infrequent in the middle periods of life, and may be met with in extreme old age. So far as I know, there is no instance on record of congenital tuberculous adenitis. Practically, in all cases the disease follows infection from without, and it is specially prevalent in the three great groups of glands which stand at the gateways of the lymphatic system — namely, the cervical, the tracheo-bronchial, and the mesenteric. While it is doubtless possible for tubercle bacilli to pass through a normal mucous membrane, yet re- curring catarrhal inflammation, by rendering the passage more easy and by exciting slight adenitis of the neighboring glands, is probably a special predisposing factor. In a child with a constantly recurring naso- pharyngeal catarrh the bacilli find the gateways less strictly guarded, and are taken up by the lymphatics and passed to the nearest glands. The importance of the tonsils as an infection atrium will be referred to later, as local disease of these glands seems not uncommon. In condi- tions of health the local resistance — or, as some would put it, the phagocytes — would be active enough to deal with the invaders, but the irritation of a chronic catarrh weakens the resistance, and the bacilli are enabled to develop and gradually to change a simple into a tuberculous adenitis. The frequent association of tuberculous adenitis of the bronchial glands with whooping cough and with measles, and the de- velopment of tubercle in the mesenteric glands in children with intesti- nal catarrh, find in this way a rational explanation. After all, as Vir- chow pointed out, an increased vulnerability of the tissue, however brought about, is the most important factor of the disease. TUBERCULOSIS OF TlIK LYMrHATK^ SYSTEM. 7(51 Certiiin ucncnil icaturcs ol" (iibcrciiloiis adenitis iiia\' Ix- first I'dciTcd to: The local cliaractci' ol" the diseaso. In a iii'cat inajorily ol" all cases tlic cervical iN'inph j^lands are alone involved, [)crlia])s on only one side. The bronchial lymph "lands are very often f'onnd affected withont any evidence of other tuhercnlous lesions in the hody, and one oi- two of tiie mesenteric t>lands may he fonnd cheesy. Tuhercnlous adenitis tends to heal spontaneously in a very consid- erable ])roportion of all cases. Nowhere are healed tuben-ulous lesions more common than in the bronchial and mesenteric lymph glands. The cheesy masses in tuberculous adenitis frequently break down into puslike liquid, which is nsnally sterile. This softening; — or su])- puration, as it is often called (though true pus may not be present) — is often the result of a mixed infe(;tion. The existence of an unhealed focus of tuberculous adenitis is a con- stant menace. One can safely say that in more than three fourths of all cases of acute tuberculosis the infection has been derived from cheesy lymph glands. It has been urged by Marfan that scrofula in childhood affords a sort of protection against tuberculosis in adult life, but the evidence of this is by no means satisfactory. Clinical Forms. — (1) Generalized Tuberculous Lymphadenitk. — There are cases in which the lymphatic system is alone affected, and the glands, internal and external, with or without the serous surfaces, pre- sent advanced tuberculosis without much involvement of the viscera. This is a more common type of the disease than is usually supposed, and occurs both in children and in adults. In the former there are cases in which the lymph glands are progressively involved, usually be- ginning in the groin and then attacking those of the axilla, and lastly the cervical and internal groups. Lesage and Paschal, who have de- scribed a nu?nber of cases, believe that the affection is due in some to cutaneous tuberculosis, but in others they think it may be congenital. The symptoms are those of a progressive cachexia without much fever and without signs of disease of the lungs or of the abdominal organs. In children such cases must be carefully distinguished from the general slight enlargement of the glands in syphilis, and from the moderate enlargement of the superficial lymph glands which may follow the infec- tious fevers. In adults a tuberculous polyadenitis is not so common, but there are cases in which the bronchial, retroperitoneal, and mesen- teric glands are greatly enlarged and caseous, usually with involvement of the cervical groups ; there may be high and irregular fever, and the patient may die without involvement of any of the viscera. In the acute form some of these cases resemble very closely Hodgkin's disease, as in a patient in the Montreal General Hospital in whom this disease was diagnosed, and whose enormously enlarged cervical and axillary glands were found post-mortem to be tuberculous, (2) Loccd Tuberculous Adenitis. — («) Cervical Group. — The drainage area of the lymph glands of the neck includes the superficial and deep structures of the head and neck. The most important groups are the superficial cervical beneath the platysma, which drains the side of the head and neck and face and external ear, and the deep cervical group along the carotid sheath, which drains the mouth, the tonsils, the palate, 762 . TUBERCULOSIS. pharynx^ and larynx. The submaxillary and suprahyoid groups drain the lower gums, the front of the mouth and tongue, the chin, and lower lip. Tuberculous adenitis of the glands of the neck is by far the most common form. Fortunately, it often remains local, and formerly was regarded as the most typical and characteristic manifestation of scrofula. It is very prevalent among the children of the poor and in those who live in the crowded, unhealthy dwellings in large cities. Children in foundling hospitals and asylums are also specially subject to it. In this country it is very prevalent among the children of the negro race. In the widespread prevalence of tubercle bacilli in the dust of cities and in institutions any of us may inhale or swallow the germs. The habits of children render them very much more liable than others to become infected. As already mentioned, the bacilli can probably pass through healthy mucosa. The slight catarrhal troubles of the naso- pharynx which are so common in children probably open the portals and allow the bacilli to reach the lymph glands. Preliminary irritation and enlargement of the glands in connection with eczema of the scalp or ear or with conjunctivitis or keratitis weaken, no doubt, the powers of resistance. The glands may enlarge rapidly at first, and become soft and painful. The swelling may, however, be gradual and painless from the outset. The enlarged " kernels," as they are popu- larly called, are usually more prominent on one side than on the other. As they increase the individual tumors can be felt, separate, smooth, and firm. Often a chain of glands can be felt from the angle of the jaw to the clavicle. As they enlarge they form knotted masses in which the outlines of the individual tumors can be just felt. The skin is, as a rule, freely movable, but as areas of softening occur it becomes adherent and reddened, and finally ulcerates, discharging a cheesy matter and a thin, watery pus. The opening thus formed has very little tendency to heal, and the skin about it is livid and under- mined. Many of the glands may suppurate in this way, and when healing ultimately takes place the sides of the neck are disfigured by irregular, unsightly scars. When the glands are large and growing actively there is fever, and the patients are usually anaemic. Death rarely follows, and a considerable proportion of all cases get quite well. In other instances the axillary glands are involved, and there is a con- tinuous chain extending beneath the clavicle and the pectoral muscles. In many of these cases the tracheal and bronchial glands are also attacked, and there is a special liability to involvement of the pleura ; and in young adults tuberculosis of the cervical lymph glands is not infrequently followed by involvement of the apex of one lung. (6) Tracheo-hronchial Group. — The lymph glands within the thorax are of the greatest importance in connection with tuberculosis. The sternal are placed along the course of the internal mammary vessels ; the intercostal, along the heads of the ribs and sometimes extending out- ward ; the anterior mediastinal group, between the lower part of the sternum and the pericardium ; the cardiac group, in the interpleural space about the arch of the aorta ; and, lastly, the tracheal glands, on either side of the windpipe, and the bronchial proper, continuous with them, which surround the main bronchi and pass deeply in the roots of TUBERCULOSIS OF T1U-: LYMPHATIC SYSTEM. 7(}3 the lungs. Tlu'rc arc also elands in the |»(>stcrior nicdiastiniini aloiiu- the thoracic aorta and (os()j)hatins. Tnl)crculosis ot" these {ii-taiit is the loriiiatioii (tf tunun'-like bodies. These iiuiy he — {(t) Oiiu'ittd/, duv to })iiekeriii^' and i-<)iliiin ,,|' thj., incmhraiie until it forms an elonuated linn mass attached to the ti'ans\'erse colon and lyinj;- athwart the ii])j)i'r ])art of tiu; abdomen. Tliis cordlikc .structure is tbuntl also with cancerous peritonitis, but is much more common in tuberculosis. (Jairdner has called .s])eeial attention to this form of tumor, and in children has seen it undergo (gradual resolution. A reso- nant |)ercussion note may sometimes be elicited above the mass. Thou<^h usually situated in the umbilical region, the omental mass may form a })roniiiient tumor in the right iliac region. (6) S((ccu/((ted exudation, in which the effusion is limited and con- fined by adhesions between the coils, the parietal ])eritoncum, the mesen- tery, and the abdominal or pelvic organs. This encysted exudate is mo.st connnon in the middle zone, and has frequently been mistaken for ovarian tumor. It may occupy the entire anterior portion of the peri- toneum, or there may be a more limited saccular exudate on one side or the other. It may lie completely within the pelvis proper, a.ssociated with tuberculous disease of the Fallopian tubes. (c) lit rare cases the tumor formation may be due to great retraction or thickening of the intestinal coils. The small intestine is found .short- ened, the walls enormously thickened, and the entire coil may form a firm knot close against the spine, giving on examination the idea of a solid mass. Not the small intestine only, but the entire bowel from the duodenum to the rectum, has been found forming such a hard nod- idar tumor. (d) Mesenteric glands, which occasionally form very large, tumor-like masses, more commonly found in children than in adults. This condi- tion may be confined to the abdominal glands. Ascites mav coexist. The condition must be distinguished from that in children, in which, with ascites or tympanites — sometimes both — there can be felt irregular nodular masses, due to large caseous formations between the intestinal coils. Xo doubt in a considerable number of cases of the so-called tabes mesenterica, particularly in those with enlargement and hardness of the abdomen — the condition which the French call carreau — there is involve- ment also of the peritoneum. Another important event in tuberculous peritonitis is the occurrence of occlusion of the bowel, which may be due either to contraction of fibroid bands or to a kink in the bowel caused by adhesions. In other cases there has been chronic ulcerative disease of the mucous membrane, with secondary involvement of the peritoneum and cicatricial contrac- tion of some of the ulcers. It is possible, too, that the great retraction and thickening of the intestinal coils may lead to symptoms of obstruc- tion, while in other instances the acute tuberculous peritonitis mav cause such infiltration of the muscular coats as to induce a paralytic distention. The diagnosis of tuberculous peritonitis is often very easy. In other cases it is extremely complicated. The only general disease with which it is apt to be confounded is tyjjhoid fever. The slow onset, the slight abdominal .symptoms, the local tenderness, and the gastric features often suggest enteric fever. The gradual development of the ascites or the presence of nodular masses may be the first .symptom to suggest a 774 TUBERCULOSIS. local peritonitis. In the ascitic form the diagnosis may rest between an acute miliary cancer, cirrhosis of the liver, and a chronic simple peri- tonitis — conditions which usually offer no special difficulties in difFer- entiation. A most important point is the simultaneous presence of a pleurisy. The diagnosis of the peritoneal tumors in this affection is sometimes very difficult. The omental tumor is a less frequent source of error than any other, but a similar condition may occur in cancer. The diagnosis of the saccular exudate from ovarian tumor is now made much more frequently than a few years ago. The most suggestive j)oints for consideration are the history of the patient and the evidence of old tuberculous lesions. The physical condition is not of much moment, as in many instances the patients have been robust and well nourished. Irregular febrile attacks, gastro-intestinal disturb- ance, and pains are more common in tuberculous disease. Unless in- flamed, there is usually not much fever with ovarian cysts. The local signs are very deceptive, and in certain cases have conformed in every particular to those of cystic disease. The outlines in saccular exudation are rarely so well defined. The position and form may be variable^ owing to alterations in the size of the coils of which in parts the walls are composed. Nodular cheesy masses may sometimes be felt at the periphery. Depression of the vaginal wall is mentioned as occurring in encysted peritonitis, but it is also found in ovarian tumor. Lastly, the condition of the Fallopian tubes, of the lungs, and of the pleurae should be thoroughly examined. The association of salpingitis or epi- didymitis with an ill defined anomalous mass in the abdomen should arouse suspicion, as should also involvement of the pleura or the apex of one lung. (4) General Serous Membrane Tuberculosis. — There is a group of cases of tuberculosis in which the serous membranes are chiefly involved, either simultaneously or more commonly one after another, forming a clinical type fairly distinctive and readily recognized. There have been several interesting studies of this condition, notably the Paris Theses of Moran and Boulland in 1884 and 1885 and the careful study of Vierordt.^ The pleuro-peritoneal membranes may be alone involved or the pleuro-peritoneal and pericardial surfaces. There are, as noted by Boulland, three groups of cases : First, an acute tuberculosis, with rapid evolution of the disease in pleurae and peritoneum, generally con- secutive to local disease of the tubes in women, or of the mediastinal or bronchial lymph glands. Second, cases in which the disease is more chronic in its nature, with exudation in both peritoneum and pleurae, the formation of cheesy masses, and the occurrence of ulcerative and suppurative processes. In this group the pleural involvement is much more commonly secondary to the peritoneal, or both may be a sequence of pulmonary tuberculosis. And, third, there are instances in which the pleuro-peritoneal affec- tion is still more chronic, the tubercles hard and fibroid, both the mem- branes showing much thickening, often with very little exudation. A knowledge of the existence of this combined infection is some- what important, as the cases are often of great obscurity. More com- monly the affection begins in the peritoneum and may be extremely '^ Zeitschrift fur kliniiiche Medicin, Bd. xi. ACUTE PNEUMONIC I'lITHLSIS. 775 chronic, ami tlicn <;r;uliially invades tlic |)lcnra. In other instances there is a snbaeute plenrisy and snl)se((nent invasion of tlie peritonenni. The eases often liave a very protraeti'd course; there are periods of great iin[)rovenient and there may he little or no fever. IV. TUBERCULOSIS OF THE LUNGS (PHTHISIS ; CONSUMPTION). I. Acute Pneumonic Phthisis. Synonyms. — Tuberculous infiltration (Laennec); Caseous pneumonia ; Scrofulous pneumonia (Virchow). Two main types are recognized — the pneumonic and the broncho- pneumonic. The former is more common in adults, the latter in chil- dren. The disease is apt to attack persons who have been debilitated by previous illness or weakened by exposure and dissipation. Either form may, however, occur in persons in apparently good health. Pathology and Morbid Anatomy. — This acute form of pul- monary disease, also known as pAf/ws?*.? florida and galloping con- sumption, is essentially an aspiration tuberculosis. In nearly all instances the disease is secondary to a pre-existing tuberculous focus, most frequently in the lung itself, either an apical cavity, often of very small size and usually communicating freely with a bronchus, or a softened gland has ruptured into a neighboring bronchus. In the pneumonic type a whole lobe, or even a whole lung, is in- volved, while in the broncho-pneumonic only lobules or collections of lobules are affected. According to the observations of Prudden, this varying distribution of the lesions would seem to depend partly upon mechanical causes and partly upon the number of tubercle bacilli dis- tributed from the infecting area, as he was able bv resulatino- the dosap-e and the method of distribution to produce experimentally either the lobar or lobular form. When in his experiments relatively small quantities of the bacilli were introduced into the lung, and care was taken to distribute them equally throughout the organ, small discrete areas of consolidation resulted. When larger quantities of bacilli, in larger amounts of fluid, were introduced, and no great effort was made to bring about an equal distribution of the suspension, large areas of consolidation, resembling the areas of pneumonic tuberculosis in man, resulted. According to Frankel and Troje, the morphological differ- ences between the so-called cheesy pneumonia, which is a tubercu- lous broncho-pneumonia, and the organized tissue structures known as tubercles is primarily due to the fact that while the tubercles are devel- oped in the interalveolar structures of the lungs, to which the bacilli are brought by the blood or lymph vessels, largely free from intermingled poisonous substances, the infection by aspiration is intra-alveolar, and the bacilli are accompanied by greater or less quantities of diffusible poisonous material developed at their original seat. Thus, while in the vicinity of metastatic tubercles, miliary or otherwise, the metabolic prod- ucts of the growth of the tubercle bacillus gradually produced may incite exudation and cell proliferation beyond the limits of the focus of 776 TUBERCULOSIS. productive inflammation, this is not, and cannot be, so extensive and quickly developed as under conditions which involve the sudden acces- sion to the air spaces of the lungs not only of tubercle bacilli, but of greater or less quantities of already elaborated poison, as is the case in the tuberculous broncho-pneumonia of acute phthisis incited by aspiration. Notwithstanding this community of causation, the types of the dis- ease present certain differences, both clinically and pathologically, that deserve separate description. (o) The Pneumonic Form. — On removal of the lung the portion affected does not collapse, but is solid and airless. The overlying pleura is usually covered by a layer of exudate, either fibrinous or case- ous, of varying thickness. The appearances on section vary consider- ably according as the exudative or the tubercle element predominates. AVhen the former only is present, with but slight formation of actual tubercle nodules, the gross appearances can, in the earlier stages, almost exactly resemble those seen in croupous pneumonia, though a close search will almost invariably reveal the presence of miliary tubercles in the consolidated area. In other cases, when the formation of actual tubercles is on a par with or exceeds the exudative process, the appear- ance on section is somewhat different. The cut surface does in a man- ner resemble that seen in lobar pneumonia in that it is studded with granulations, which, however, are larger and smoother than those seen in the disease mentioned. On close inspection these granules are seen to be miliary tubercles, and the surrounding lung may present the ap- pearances of an ordinary pneumonia, or, more commonly, those associ- ated with desquamative pneumonia — viz. a reddish gray, very translucent appearance. These appearances of desquamative pneumonia or of ordi- nary croupous pneumonia may often be combined in the same lung, cer- tain areas showing one variety, whilst the other variety is seen in ad- jacent or distant areas. In the later stages of the disease the picture is much more characteristic ; but the origin of the process in the nodular or exudative form cannot be made out with the naked eye, the subse- quent caseation having masked the original lesion. The appearance of the cut surface at this time has been described as resembling Rochfort cheese — a whitish yellow background streaked with blackish lines, the background representing the caseous material, the streakings the pig- mented bands of connective tissue. Occasionally cavities are seen with ragged, necrotic walls. These are probably, for the most part, due to secondary infection of the tuberculous tissue with pus-producers. Various intermediate steps can be seen between the early and caseous stages as above described ; the process is not, as a rule, uniform, so that the lungs are frequently seen presenting a mixture of the above appear- ances, in parts caseous, in parts gelatinous, and in parts showing tuber- cle nodules. The bronchi in all these cases, particularly the smaller ones, usually show evidences of active inflammation in a congested and thickened mucous membrane and purulent or muco-purulent contents. The tubercle nodules as seen in these lungs differ in no respect from those seen elsewdiere and previously described. The exudative phenom- ena vary within very wide limits, but the essential elements of the ACUTK I'SEUMONIC rimifsis. 717 exiuhitt' arc in all casrs the saiiu — red and white (polyniiclear aMe ijiiantities of tibrin, and in fact any of the various combinations of the above described essential elements may occur. The most typical form of j)neinnonia, however, is that first accnrately described by Laen- iiec as ii'elatinons pneumonia — a form in which the exndate consists of an albuminous fluid deri\'ed from the blood and i^reater or smaller lunn- bers of cells of an e})itlielioid ty])e originatin*^ from the descpiamation and proliferation of the epithelial lining of the alveoli. The appear- ances under the microscope in the last stage are those of large areas of caseation surrounded by larger or smaller areas, either of one of the tvpes of pneumonia above mentioned or of tubercle formation. (b) The Broiic/to-pncionoiilr Tiqh'. — Little need be said of this type, which occurs more freipiently in children than in adults. As has been stated above, the difference between this and the preceding form is merelv one of degree. Here, as in the pneumonic, we have the differ- ences in appearance according to the stage of the disease and according as the exudative or nodular elements predominate. The sole difference lies in the distribution of the lesions, which in this class of cases are confined to limited areas of lung substance, generally in the neighbor- hood of small bronchi. In connection with both these forms of tuberculosis it is necessary to discuss the question of associated or secondary infections in acute lung tuberculosis. Can all the above described changes be due to the action of the tubercle bacillus itself or are they due to mixed infections ? The careful observations of Frankel and Troje would seem to support the view of the specificity of the tubercle bacillus, whilst the equally care- ful studies of Ortner appear to negative these results. The recent re- searches of Prudden would seem to put the matter beyond all ques- tion of doubt. This observer was able to show in the clearest manner that the tubercle bacillus could produce not only distinct tubercle nodules, but also the various kinds of exudative phenomena, the exu- dates varying in appearance in different cases, which phenomena occurred absolutely without association with other organisms. The fact that these latter had not subsequently crept in was shown by cultures at the autopsy on the affected animal. Symptoms. — (a) Pneumonic Form. — In many cases the disease sets in abruptly wdth a chill, which may follow an exposure to cold or come on in the course of a drinking bout (Frankel and Troje) ; in others the disease sets in more insidiously. The temperature rises quickly, and there are all the initial sym])toms of ordinary pneumonia — pain in the side, cough, and shortness of breath. Usually by the time a physician sees the case hepatization is well marked, and he discovers an area of consolidation in a low^er lobe or in an upper lobe, with pos- sibly a friction murmur and loud tubular breathing. The expectoration is usually blood-tinged and typically pneumonic. The local disease progresses, and an entire lobe may be involved or the upper and middle lobe on the right side. Occasionally an entire lung is invaded with greqt rapidity. Xo doubt at this time may be in the mind of the physician 778 T UBER C UL OSIS. as to the nature of the case, which is regarded as one of simple hjbar pneumonia. In some instances the previous history of the patient affords warrant for a suspicion which is unheeded in the presence of such a characteristic onset. The fever is at first high and persistent^ with but slight daily variations, but it becomes more irregular as the disease progresses. The pulse is rapid, from 120 to 140 beats per minute. The respirations are much accelerated at first, but with exten- sive consolidation and high fever there may be neither urgent dyspnoea nor cyanosis. Instead of the expected crisis on the ninth or tenth day, the fever persists and becomes more irregular. The expectoration changes, is less rusty, and becomes muco-purulent or purulent and of a greenish color. There may be no expectoration throughout. In a case under my care a few years ago, in which the consolidation was uniform from apex to base, there was no expectoration and very little coughs Even in the second or third week the physician comforts himself with the thought that perhaps it is a case of unresolved pneumonia, and it is not until signs of cavity-formation develop or until tubercle bacilli or elastic tissue is detected in the sputa that he becomes convinced of the existence of an acute pneumonic phthisis. A diagnosis may never be reached intra vitam, and the case may be sent to the post-mortem room without the slightest suspicion that it is anything but an instance of protracted pneumonia. A violent haemoptysis may occur at any time in the course of the disease. Among other points which may be men- tioned are — enlargement of the spleen, a diazo reaction in the urine, and occasional oedema of the lower extremities. There may be active de- lirium or only an apathy and dulness proportional to the extent of the fever. The diagnosis of acute pneumonic phthisis offers many difficulties. The mode of onset may be in every respect identical with that of croupous pneumonia. A healthy, robust-looking young Irishman, a cab-driver, who had been kept waiting for hours on a cold, blustering night, was seized the next afternoon with a violent chill, and the fol- lowing day was admitted to my wards at the University Hospital, Philadelphia. He was made the subject of a clinical lecture on the fifth day, when there was absent no single feature in history, symptoms, or physical signs of acute lobar pneumonia of the right upper lobe. It was not until ten days later, when bacilli were found in his expectora- tion, that we were made aware of the true nature of the case. I know of no criterion by which cases of this kind can be distinguished in the early stage. The presence of the greenish, often grass-green sputa, upon which Traube laid much stress, is a point of a good deal of importance. By far the most valuable information is obtained by a systematic study of the expectoration. The tubercle bacilli, as a rule, are not present at first, and may not be found for a week or ten days or even later. They may be present early, and Friinkel and Troje found them in one case in which the sputa were still pneumonic. The examination for elastic tissue is very important, as in a majority of the cases the caseous areas begin to break early. Traube called attention to the absence of breath sounds in the consolidated region, a point which Herard and Cornil also speak of as important, but suppression or enfeeblement of the breath sounds is by no means uncommon in other types of pneumonia. ACUTE PNEUMONIC PHTHISIS. 779 The course of flic (liscosc is very varial)lc. In :i majority of the cases death occurs within six weeks. Death may l)e caused as early as the eighth or tenth (l:iy. Tiiere are cases in wliich with very severe onset and rapid consolidation of a lobe the symptoms subside within three or four weeks, and the condition passes into one of chronic phthisis, which does not prove fatal for hve or six months or even longer. (/>) P>ronc}io-pneuiiionk- Fonn. — In adults the picture is that of a rapidlv progressing y>//^A/.s/N /for/r/o. Persons in good health are rarely attacked, but most frequently those who are debilitated from any cause or convalescent from the acute diseases. Some of the most rapid cases follow luemoptysis. There may be at the outset repeated chills, with sweats and intermittent pyrexia, which may lead to the diagnosis of malarial intermittent fever. The temperature is high, the pulse rapid, and the cough distressing. The general symptoms may be out of pro- portion to the amount of local disease. The apices are most commonly involved, and there is at first only slightly impaired resonance, with harsh breathing and numerous fine rales. Subsequently, as the areas coalesce, the resonance becomes still more defective and the breathing may be tubular. In very acute cases the fever may be high. There is early delirium and the patient sinks into the so-called typhoid state. With the progress of the local disease there is rapid loss in weight and strength, irregular fever, sweating, and the sputa show numerous tu- bercle bacilli and much elastic tissue. The disease may prove fatal within from six to ten or twelve weeks, and a majority of the cases of galloping consumption belong to this type. There are cases in which for five or six weeks the symptoms are of the greatest severity, and the immediate prognosis looks hopeless, but the fever subsides, the consti- tutional symptoms mitigate, and a case which may have looked des- perate drags on and eventually becomes chronic. The acute tuberculous broncho-pneumonia is a very common form in children, and may come ou spontaneously or follow one of the in- fectious diseases. Clinically, it is very difficult to distinguish from the simple form. The onset may be acute in a previously healthy child or the disease follows measles, diphtheria, or whooping cough. The tem- perature rises rapidly, the cough is severe, and there may be signs of consolidation with fine crepitant and subcrepitant rales at one or both apices. There are no physical signs which enable us to differentiate a simple form of tuberculous broncho-pneumonia. The localization is not of much value, since we find, commonly enough, in children the tuber- culous process beginning at the base or in the central portions of the lung. In the course of the disease indications of value develop. The oscillations in temperature are greater in the tuberculous cases ; sweats are more common. The child emaciates rapidly, and there may be local features indicating breaking down of the lung tissue. As young children rarely expectorate, there is great difficulty in getting the sputa for examination. Occasionally they can be obtained in the vomitus, and as the sputum is swallowed the tubercle bacilli can occasionally be determined in the stools. The duration of the very acute cases is from three to five weeks. In other instances the severity of the symptoms mitigates within two or three weeks, but the irregular fever persists ; 780 TUBERCULOSIS. there is loss of flesh, cough, hectic fever, and sweats. The physical signs indicate softening, and there is gradually developed a clinical picture of chronic pulmonary tuberculosis. n. Chronic Ulcerative Tuberculosis of the Lungs. Synonyms. — Phthisis pulmonum ; Consumption ; Chronic phthisis ; Chronic ulcerative phthisis. In this form, which embraces by far the largest number of cases of pulmonary tuberculosis, the lesions proceed to caseation and ulceration, and there is produced at last the only too common picture of pulmonary consmnption, characterized by cough, irregular fever, emaciation, night- sweats, etc. Though at first a tuberculous process, in a majority of cases the lungs become the seat of mixed infection, and many of the prominent symptoms are due to the absorption of the toxins of various organisms in purulent foci and cavities. Pathological Anatomy. — (1) The Distribution of the Lesions. — The primary lesion is, as a rule, in one of the upper lobes, usually at a point a short distance below the apices. The question as to which apex is involved the most frequently has been studied by various authors. The statistics on the subject vary, some claiming that the right, others that the left, side is most often aifected, while in other cases the two sides have been equally involved. Of 427 successive cases at the Johns Hopkins Hospital, the right apex was involved in 172, the left in 130, and both in 111. Various hypotheses have been advanced to explain the cause of this peculiarity of distribution of the lesions, but none are entirely satis- factory. The distribution cannot be explained on mechanical grounds alone, and in our present knowdedge of the subject we feel obliged to call in a local weakness of the part or a predisposition, a weakness con- sisting perhaps in some preceding catarrhal condition. From its original seat near the apex the tuberculous process travels downward with greater or less rapidity toward the base. This process of spreading is in the great majority of cases the result of the aspiration of infected material from already affected regions in the upper part of the lung into the lower bronchi. Associated with this process there is also a gradual dissemination of new tubercles from the old centres. The colonization, radial in character, is due to the carriage of tubercle by the lymph streams. Much more rarely local extension may occur through the blood current. The tubercles of aspiration origin have their most frequent seat at the point where the bronchioles narrow down just at the entrance to the. vestibule of the air sac ; they are also found in the walls of the smaller and larger bronchi. Tubercles of blood origin are generally evenly scattered throughout the lung, those of lymph origin occurring near old foci. The mode of extension has been carefully described by Kingston Fowler, who finds that in its onward progress through the lungs the disease follows, in a majority of the cases, distinct routes. In the upper lobe the primary lesion is not, as a rule, at the extreme apex, but from an inch to an inch and a half below the summit of the lung; and nearer ClinOXIC ULCERATIVE TUBERCULOSIS OF THE LUNGS. 781 to the })()sl('ri()r and cxtciiial borders. 'I'lic lesion here tends to spread downward, i)rol)al)lv iVoni inhalation of the; virus, and this accounts for the frequent circumstance that examination behind, in the supraspinous fossa, will give indications of disease before any evidences exist at the apex in front. Anteriorly, this initial focus corresponds to a spot just below the centre of the clavicle, and the direction of extension in front is along the anterior aspect of the upper lobe, along a line running about an inch and a half from the inner ends of the iirst, second, and third interspaces. A second less common site of the primary lesion in the apex " corresponds on the chest wall with the tirst and second inter- spaces below the outer third of the clavicle." The extension is down- ward, so that the outer part of the upper lobe is chiefly involved. In the middle lobe of the right lung the affection usually follows the upper lobe on the same side. In the involvement of the lower lobe the first secondary infiltration is about an inch to an inch and a half below the posterior extremity of its apex, and corresponds on the chest wall to a spot opposite the fifth dorsal spine. This involvement is of the greatest importance clinically, as "in the great majority of cases, when the physical signs of the disease at the apex are sufficiently definite to allow of the diagnosis of phthisis being made, the lower lobe is already affected." Examination, therefore, should be made carefully of this posterior apex in all suspicious cases. In this situation the lesion spreads downward and laterally along the line of the interlobular septa — a line which is marked by the vertebral border of the scapula when the hand is placed on the opposite scapula and the elbow raised above the level of the shoulder. Once present in an apex, the disease usually extends in time to the opposite upper lobe, but not, as a rule, until the apex of the lower lobe of the lung first affected has been attacked. Lesions of the base may be primary, though this is rare. Percy Kidd makes the proportion of basic to apical phthisis one to five hun- dred, a smaller number than existed in my series. In very chronic cases there may be arrested lesions at the apex and more recent lesions at the base. (2) The Lesions in Chronic Ulcerative Phthisis. — («) Tubercles. — The miliary tubercle is the essential element in the early stages of chronic ulcerative phthisis, the nodules at this time being usually situated at the apex in connection with the air cells and smaller bronchi. As the pro- cess proceeds the nodules coalesce and form conglomerate tubercles, the breaking down of which, with the subsequent further destruction of tissue, leads to cavity formation. When the disease has reached its chronic form the miliary tubercles present in the lung are found, in the great majority of instances, to have one of two distributions : (1) A dissemination due to aspiration of tuberculous material, the tubercles being situated in the air cells or the walls of the smaller bronchi ; (2) the distribution due to dissemination of tubercle bacilli by the lymph current, the tubercles being scattered about the old foci in a radial manner. ]Much more rarely there is a scattered dissemination from infection here and there of the smaller vessels, the tubercles then being situated in the vessel walls. (6) Pneumonia. — In all cases of chronic phthisis patches of pneu- monia are found distributed throuo;h the lung. One form is a true 782 TUBERCULOSIS. broncho-pneumonia, having its origin in the smaller bronchi. The exudate in these cases fills up the bronchus and the surrounding air cells, and may present varying appearances. In the beginning it is in some cases the ordinary muco-purulent exudate, in some fibrinous or fibrino-purulent, in others gelatinous. Subsequently, when the exudate undergoes (;aseation, a cross section of the aiFected area then gives the typical appearance of caseous broncho-pneumonia — viz. the bronchus in the centre of the cheesy material, surrounded by an area of lung consolidation, also caseous. The longitudinal section has a somewhat dendritic or foliaceous appearance. As these areas soften cavities are formed ; the breaking down is due in most instances to a secondary infection with pus organisms, though the tubercle bacillus itself is capable of causing it. In other instances, particularly in very chronic cases, a chronic interstitial pneumonia is set up in the region surrounding the caseous mass, with the result that it may be completely surrounded by a dense fibrous capsule. Under these circumstances the fluid elements of the cheesy mass may be absorbed, and it remains as a firm, dry, friable nodule, or it becomes the seat of a deposition of lime salts, and a hard, calcareous mass results. The second type of pneumonia is not connected with the bronchi, but with the tubercle nodules. This pneumonia may occur at any stage of the tuberculous process, and is often seen surrounding the very youngest tubercles. The exudate is sharply confined to the alveoli in the immediate neighborhood of the tubercles, and where these are closely packed almost the v/hole of the lung substance between them may be consolidated. Here, as in the acute pneumonic tuberculosis, the exudate may be of varying types, the essential elements being the serum, leucocytes, and red corpuscles of the blood, together with fibrin and the desquamated and proliferated alveolar epithelium. The proportion of these elements varies greatly, but, though the type of exudate may simulate any form of pneumonic exudate, by far the most common variety in these cases is the gelatinous (described by Laennec), an exu- date containing often but few cellular elements, and these mostly epi- thelial in character. The number of tubercle bacilli found in such an exudate is very small indeed, and from the arrangement of the pneu- monic patches about tubercles and their sharp localization it seems probable that the exudate is due to the products of the tubercle bacillus, and not to the organism itself. The exudate in this form of pneumonia may undergo caseation or fatty degeneration, the former much more frequently. The caseous material presents the same appearance here as elsewhere ; the fatty degenerated alveolar contents have a whitish or yellowish white opaque appearance. (c) Cavities. — Two kinds of cavities are found in the lung in chronic phthisis — the bronchiectatic and the ulcerative. Though not necessarily of tuberculous origin, bronchiectatic cavities are frequently met with, most commonly at the apices of the lungs, for the reason that the tuberculous process is most common there. The cavities are found particularly in connection with the medium sized and small bronchi, and vary in size from a pea to a hen's egg ; pure bron- ochiectatic cavities, however, rarely reach the latter size. The shape CHRONIC ULCERATIVK TUBERCULOSIS OF Till: LUNGS 783 varies eonsideraWly : in soiiu' iiistaiiccs a loiiji; stretch of hi'oiiclms is ditl'usolv dilated, eaiisinti" a I'lisiibriii ea\ity ; in other instances only u part ot" the bronchial wall tiives way, eausinti' a saceidated cavity. In another elass ot" cases shar|)ly delined dilatations occur, takinji' in the whole bronchial circumference and causing a localized globular cavity. In all the wall of the cavity is, as the name implies, of bronchial origin, usuallv sharply defined and smooth on its inner surface, though the granulation tissue which lines it may be the seat of more or less exten- sive ulceration. In the larger cavities the ulcerative process genendly extends bevond the bronchial wall and involves the lung substance, and we have a combination of the bronchietatic and ulcerative forms of cavities. The ulcerative cavity may occur in one of two ways — either as the result of an extension of the ulcerative process from a bronchiectatic cavitv into the lung, or from the breaking down of tuberculous masses in the lung irrespective of connection with bronchi. In both of these cases it is probable that the destructive process results in most instances from an invasion of a tuberculous lung by the pus organisms, particu- larly the streptococcus, though, as the work of Prudden has shown, the bacillus of tuberculosis is capable itself of causing ulcerative processes of limited extent. The ulcerative cavities, like the bronchiectatic, are most frequently found at the apices, though in late stages of the disease they may be scattered through the lungs. They vary in size from cav- ities the size of a marble to those involving a whole lobe or even a whole lung, in some instances only a thin shell of a lung remaining outside of the cavitv. A majority of these cavities communicate with bronchi by openings of various sizes and having varying positions. The appearance of the ulcerative cavity differs in the acute and chronic stages. The acute form, which is seen in acute phthisis, and in chronic phthisis in those parts of the lung in which the disease is pro- gressing, is distinguished from the chronic by its lack of a definite wall, and is Ijounded only by broken-down caseous material and necrotic lung tissue. In the caseous tissue of the fresh lung cavity tubercle bacilli are often present in enormous numbers. As the process of formation of these cavities is acute, they are the form especially liable to rupture into the pleura and cause pneumothorax. The chronic form differs from the acute in having a definite wall, composed in the main part of dense fibrous tissue, the result of a chronic interstitial pneumonia in the surrounding lung. Inside this framework is a layer of granulation tissue, which shades gradually into the fibrous layer, and may contain tubercles or show caseation of its most internal portion. At times no definite tubercles can be made out, but the tissue may present the microscopical appearances spoken of as tuberculous granulation tissue, the process consisting in a diffuse infiltration with epithelioid cells and occasionally giant cells. The walls of such cavities are generally extremely irregular, being crossed by bands representing resistant areas of dense fibrous tissue or the remains of bronchi or bloodvessels. The cavities are often crossed from side to side by tra- beculae in which, as in those of the walls, are bloodvessels, many of which are obliterated, either as a result of an endarteritis or by an atro- phy, following the destruction of the tissues which they supply. In 784 TUBERCULOSIS. many instances, however, obliterative process does not take place, and the bloodvessels, being more resistant to the ulcerative process than the surrounding tissue, remain exposed, either in the wall of the cavity or in one of the bands crossing it. In these exposed vessels, devoid of their normal support, aneurysms are particularly liable to form, varying in size from a pea to a walnut, and their rupture in the later stages of the disease is the most common cause of profuse haemoptysis. The extension of the cavities takes place by the gradual ulceration of their inner walls, which occurs in a patchy manner, some portions of the wall being resistant, whilst others, especially those containing caseous tubercles, are easily broken down. The contents of the cavities consist of broken-down tissue (caseous material or destroyed lung tissue) and pus secreted from the lining wall ; more or less blood may be present from the rupture of small vessels. In the most chronic forms of tuberculosis, where the reparative tends to exceed the destructive processes, cavities become surrounded by an exceedingly dense fibrous Avail and a cessation of the ulcerative process may occur. Such cavities, termed quiescent, have smooth, almost fibrous walls, which secrete practically nothing. They may undergo contrac- tion by the shrinking of the outlying fibi'ous tissue, but, except in very small ones, complete obliteration does not occur. (c?) Involvement of the Pleura. — The pleura is involved to a greater or less extent in all cases of tuberculosis, either in an acute or chronic process. In the acute form the various types of exudate may occur, the sero-fibrinous being the most common. A large number of the pleural exudates, which are bacteriologically sterile, are of a tuber- culous origin. Purulent and hemorrhagic exudates are less often found ; in the case of the former the polynuclear leucocytes may con- tain large numbers of tubercle bacilli. Definite tubercles are not neces- sarily associated with any of these processes, though in the great major- ity of instances they will be found if carefully looked for. Here, as in other forms of pleurisy, complete return of the pleura to normal does not take place. In many instances partial or entire obliteration of the pleural sac occurs from the adhesions and subsequent organization of the exudate : in other cases, particularly in connection with the more acute forms of phthisis, the exudate undergoes extensive caseous changes. The pleurisy is quite commonly secondary to a pneumothorax. The chronic forms of pleurisy are, as a rule, more sharply localized than the acute, though they often spread, coincident Avith the spread of lung involvement. They almost invariably result in adhesions between the tAvo layers of exudate, which subsequently undergo organization and may become extremely dense and firm. (e) Changes in the Bronchi. — The larger bronchi are generally the seat of inflammation, acute or chronic in character and due to organisms other than the tubercle bacillus. Besides these non-specific lesions, tuberculous lesions occur, either in the form of tubercles in the mucous membrane or of ulcerations varying from small superficial losses of substance to large serpiginous ulcerations, invohnng at times all the coats and leading to dilatation of the bronchus. The medium-sized bronchi are also subject to both nodular and ulceratiA'c processes. As has been previously mentioned, the smaller bronchi are the starting point CHROyiC VLCERATIVK rrilERCULOSIS OF THE Luxas. 7o|)|»y or millet seed in size, but with ra«i<;-ed edges and angular shapi', wliirli are necrotizing fragments of pulmonary tissue sej)arated during the process of excavation. I have found these identical in structure in one case with the small masses often loosely attached to the interior of cavities, consisting of i-apidiv degenerating cells and nuclei, and having precisely the same apj)earances as are found in caseous tubercle." Andral states that this form of sputa was noted by Hippocrates, who compared them with grains of hail. Occasionally in cases of very rapidly softening tuberculosis quite coarse fragments of the necrotic lung tissue may be expectorated. Fil)riuous casts of the bronchial tubes are occasionally expectorated in pulmonary tuberculosis. Jficroscopieal Examination. — The chief jwrtion of the muco-puru- lent sputum of pubnonary tuberculosis is made up of pus cells. E})ithe- lial cells from the mouth and pharynx and trachea and bronchi are also present in vai'ying numbers. Alveolar epithelial cells are present in numbers in the early stages of the disease, and their siguiiicance has been much discussed. The lumps of gelatinous-looking sputa which Bayle compared to boiled rice are composed almost entirely of these swollen, rounded cells, containing myelin, often carbon grains and fragments of dust. They were thought by Buhl to be distinctive of desquamative pneumonia, but they may occur in large numbers in simple bronchitis, and are quite common even in the morning expectoration of perfectly healthy individuals. I do not think their presence is of any significance whatever in tuberculosis. E/axfic Tissue. — The presence of elastic fibres in the sputum is an indication of destruction of tissue in the air passages or lungs. It is found in gangrene, abscess, and in all cases of tuberculosis with soften- ing. For the purpose of examination it is unnecessary to resort to the tedious method of boiling the sputum with caustic potash. I have used for many years the following plan, which was shown to me at the Lon- don Hospital by Sir Andrew Clark. The method depends upon the fact that if the sputum be spread in a sufficiently thin layer fragments of the elastic tissue can be readily seen with the naked eye. The thicker, puru- lent portions are placed upon a glass plate 15 by 15 cm., and flattened by a second glass plate 10 by 10 cm. In this compressed grayish layer of sputum any fragment of elastic tissue shows at once as a grayish yel- low spot, and can be examined at once under a low power, or the upper- most glass is slid along until the fragment is exposed, when it is picked out and placed upon the ordinary microscopic slide. Fragments of bread, collections of milk globules, portions of epithelium of the tongue infiltrated Avith micrococci, also show opaquely against a black back- ground, but with a little practice they can readily be distinguished. Every portion of elastic tissue in the sputum, even \vhen quite small, can be readily picked out in this Avay. The elastic tissue from the lungs is very characteristic. The arrangement of the fibres is such that they show the outlines of the air cells. Elastic tissue from the bronchial wall forms an elongated network or two or three long narrow fibres may be seen close together. From the bloodvessels a somewhat similar arrangement of elastic tissue may be seen, or occasionally a fenestrated membrane which looks as if it had come from the intima of a o^ood-sized 790 TUBERCULOSIS. artery. Elastic tissue is present in every instance of pulmonary tuber- culosis with destruction. It may be found, too, very early in the disease, before the local signs of softening are at all marked. Tubercle Bacilli. — The presence of the bacillus tuberculosis in the sputum has enabled us to make the diagnosis of the disease at a much earlier period than formerly, and with an absolute certainty, even before the physical signs are in any way distinctive. While the bacilli may be present in sputum which looks entirely glairy and mucoid, they are more likely to be found in the grayish yellow streaks of purulent sputum, which should be picked out for the purpose of examination. They may be found sometimes in the expectoration in a case of fresh haemoptysis in a person who has had no suspicion whatever of tuberculous disease. The method has already been given for demonstrating the bacilli in sputa (p. 734). The number of bacilli varies in different cases. Usually when soft- ening is progressing rapidly they are very abundant, and they occur in large numbers also in the nummular sputa of old cavities. On the other hand, there are patients who present all the local and general features of pulmonary tuberculosis, yet in whose sputa bacilli cannot be demonstrated for weeks or even for months. In other cases, again, with quite pronounced lesions for long periods, the bacilli in the sputa are very scanty. Indeed, there are cases on record in which the bacillary nature of the lung lesion has only been determined post- mortem. Other forms of micro-organisms are frequently present in the sputum in pulmonary tuberculosis — the staphylococci, streptococci, the pneumo- coccus, the bacillus pyocyaneus, and the proteus. In long standing cases with cavity there may be aspergilli, sarcinse, the leptothrix, and the oidium albicans. Calcareous fragments may be coughed up in chronic pulmonary tuber- culosis. Formerly a good deal of stress was laid upon their presence, and Morton described a phthisis, a calcidis in pulmonibus generatis. Bayle also described a separate form of j^hthisie calculeuse. The size of the fragments varies from a small pea to a large cherry. As a rule, a single one is coughed up ; sometimes large numbers are coughed up in the course of the disease. Usually they are not associated with any special symptoms, though there are cases in w^hich hsemoptysis has occurred. They are formed in the lung by the calcification of caseous masses, and it is said also occasionally in obstructed bronchi. They may come from the bronchial glands by ulceration into the bronchi, and there is a case on record of suifocation in a child from this cause. Hcemoptysis. — One of the most famous of the Hippocratic axioms says, " From a spitting of blood there is a spitting of pus." A large majority of the older writers on the subject thought that the phthisis was directly due to the inflammatory or putrefactive changes caused by the hemorrhage into the lung. Morton in his interesting section, Phthisis ah Hcmnoptoe, rather doubted this sequence. Laennec and Louis, and later in the century Traube, regarded the haemoptysis as an evidence of existing disease of the lung. Desault, indeed, as far back as 1783 had said that instead of the term. phthisis ab hcemoptoe the state- ment should be haemoptysis from phthisis (Wilson Fox). From the CHRONIC UlJ'F.nATIVE TrilElU'ULOSIS OF THE LUXOS. 791 :U'('iii-;itr xicws of" Laciiiicc niid Louis the |)ro(rssioii wms led ;i\\;iv Wv Graves, and partii'ularly Wy Xicincyer, wiio held tliat tlio Ijlood in tlie air tvlls set up an iullaininatory process, a eoinnion termination of wliich was easeation. Since Koeh's discovery "vve liave learned that many eases in which tlie ])hysieal examination is negative show, either during the period of hemorrhage or immediately after it, tubercle bacilli in the sputa, so that o])inion has veered to the older view, and we now regard the appearance of luemoj)tysis as an indication of existing disease. In young, apparently healthy persons cases of haemoptysis may be di- vided into three groups. In the first the bleeding has come on with- out premonition, without overexertion or injury, and there is no familv history of tuberculosis. The physical examination is negative, and the examination of the expectoration at the time of the hemorrhage and subsequently shows no tubercle bacilli. Such instances are not uncom- mon, and, though one may suspect strongly the presence of some focus of tuberculosis, yet the individuals may retain good health for many years and have no further trouble. Of the 386 cases of haemoptysis noted by Ware iu private practice, 62 recovered and pulmonary disease did not subsequently develop. In a second group individuals in apparently perfect health are suddenly attacked, perhaps after a slight exertion or during some ath- letic exercises. The physical examination is also negative, but tubercle bacilli are found sometimes in the bloody sputa, more frequently a few days later. In a third set of cases the individuals have been in failing health for a month or two, but the symptoms have not been urgent and perhaps not noticed by the patients. The physical examination shows the pres- ence of well marked tuberculous disease, and there are both tubercle bacilli and elastic tissue in the sputa. A very interesting systematic study of the subject of haemoptysis, particularly in its relation to the question of tuberculosis, has just been completed in the Prussian army, and has been issued by Franz Strieker.^ During the five years 1890-95 there were 900 cases admitted to the hospitals, which is a percentage of 0.045 of the strength (1,728,505). These, of course, were selected men at the healthiest periods of life. Of the cases, in 480 the hemorrhage came on without recognizable cause. Of these 417 cases, 86 per cent, were certainly or probably tuberculous. In only 221, however, was the evidence conclusive. In a second group of 213 cases the hemorrhage came on during the military exercise, and of these 75 patients were shown to be tuberculous. In 118 cases the hemorrhage followed certain special exercises, as in the gymnasium or in riding or in consecjuence of swimming. In 24 cases it developed during the exercise of the voice in singing or in giv- ino; command or in the use of wind instruments. A verv interesting- group is reported of 24 cases in wliich the hemorrhage followed trauma, either a fall or a blow upon the thorax. In 7 of these tuberculosis was positively present, and in 6 other cases there was a strong probability of its existence. Among the conclusions which Strieker draws the folhjwing are the ^ Festschrift zur 100 jdhrixjen Stiftungsjeier des medizinisch-chirurgischen Fried rich- Wil- hdms-Jnstiiuts, Berlin, 1895. 792 TUBERCULOSIS. most important : namely, that soldiers attacked with haemoptysis with- out special cause are in at least 86.8 per cent, tuberculous. In the cases in which the hseraoptysis follows the special exercises, etc. of military service, at least 74.4 per cent, are tuberculous. In the cases which come on during swimming or as a consequence of direct injury to the thorax about one half are not associated with tuberculosis. Haemoptysis occurs in from 60 to 80 per cent, of all cases of pul- monary tuberculosis. It is more frequent in males than in females. While it may occur at all ages, and even in quite young children, yet it is most common in young adults. In a majority of all cases the bleeding recurs. There are cases in which it is a special feature throughout the disease, so that a hemorrhagic or hgemoptysical form has been recognized. The amount of blood brought up varies from a couple of drachms to a pint or more. In 69 per cent, of 4125 cases of haemoptysis at the Brompton Hospital the amount brought up was under half an ounce. A distinction may be drawn between the haemoptysis early in the disease and that wdiich occurs in the later periods. In the former the bleeding is usually slight, is apt to recur, and fotal hemorrhage is very rare. In these instances the bleeding is usually from small areas of softening or from early erosions in the bronchial mucosa. In the later periods, after cavities have formed, the bleeding is, as a rule, more pro- fuse and is more apt to be fatal. Single large hemorrhages, proving quickly fatal, are very rare, except in the advanced stages of the disease. In these cases the bleeding comes either from an erosion of a good-sized vessel in the wall of a cavity or from the rupture of an aneurysm of the pulmonary artery. The bleeding, as a rule, sets in suddenly. Without any warning the patient may notice a warm salt taste and the mouth fills with blood. It may come up with a slight cough. The total amount may not be more than a few drachms, and for a day or two the patient may spit up small quantities. When a large vessel is eroded or an aneurysm bursts, the amount of blood brought up is large, and in the course of a short time a pint or two may be expectorated. Fatal hemorrhage may occur into a very large cavity without any blood being coughed up. The character of the blood is, as a rule, distinctive. It is frothy, mixed with mucus, generally bright red in color, except when large amounts are expectorated, and then it may be dark. The sputa may remain blood-tinged for some days or there are brownish black streaks in the sputa, or " friable nodules consisting entirely of blood corpuscles " may be coughed up. Blood moulds of the smaller bronchi are sometimes expectorated. The microscopical examination of the sputum in tuberculous cases is most important. If carefully spread out, there may be noted, even in an apparently pure hemorrhagic mass, little portions of mucus from which bacilli or elastic tissue may be obtained. Dyspnoea. — In the early stages the respirations may be a little hur- ried, and in a few instances the dyspnoea is quite marked. When the disease is advanced, so long as the patient remains at rest there is no shortness of breath, but on attempting exercise or making any special effort the respirations are much hurried. It is remarkable how much CHROXrC ULCERATIVE TUBERCULOSIS OE THE LUNGS. 793 Iiinii" tissue nuiy \)v (lestn>yt'(l without any sense of resjiiratorv distress so long as the patient remains (juiet. Occasionally, even early in the disease, there are attacks of dyspntea at nitrht almost asthmatic in cha- racter. Emotion or sudden exertion may at any time cause hurried hreathinii-. Marked dyspntea is usually due to some intercurrent trouble, the development of a lobar pneumonia or of miliary tuberculosis, a rapidly advancino* broncho-])neum()nia or the development of pneu- mothorax. Cifatiosis is also not a common sym])tom in chronic pulmonary tuber- culosis. It is seen most commonly under conditions whicli cause dyspncea. In advanced cases with much fibroid change the dyspnoea may be cardiac, and the advancing cyanosis may also residt from tlie gradual dilatation of the right chamber of the heart. P((ii) in the chest is a very variable symptom. In some eases it is present from the outset, and the patient at the examination will place his hand accurately over the portion of the lung affected. In other instances it is absent throughout. When present it is most comraonlv due to pleurisy, and is situated below the clavicle, along the sternal margin, or in the scapular regions. In cases of apical tuberculosis with early involvement of the pleura the pain may be a very distressing feature. In other cases the lower thoracic zone is the seat of the chief pain, particularly on drawing a deep lireath. In many instances it is only a dull, aching sensation. When such shrinkage and contraction occur, Avith great thickening of the pleura, the intercostal nerves may be involved, and the pains persist long after the active symptoms of the disease have disappeared. The sensitiveness to percussion may be very much increased, and the patient may wince even on light percussion over the affected area. General Symptoms. — Fever. — Aretaeus seems to have been the first to recognize phthisis as a febrile disease. His description is most characteristic : " It is accompanied by febrile heat of a continued cha- racter, but latent, ceasing indeed at no time, but concealed during the day by the sweating and coldness of the body ; for the characteristics of phthisis are that a febrile heat is lighted up which breaks out at night, but during the day lies concealed in the viscera, as is manifested by the uneasiness, loss of strength, and colliquative wasting. For had the febrile heat left the body during the day, how should not the patient have acquired flesh, strength, and comfortable feeling ? " ^ Morton, so far as I know, was the first to recognize two types of fever in pulmonary tuberculosis — the inflammatory and the putrid inter- mittent or hectic.^ To get a proper idea of the daily range of fever in any case it is necessary to take the temperature every two or three hours. The usual 8 A. M. and 8 p. m. record may be very deceptive, giving neither the maximum nor the minimum temperature of the day. It may be said at the outset that a continuous type of fever is not often seen in pul- monary tuberculosis. Except in certain instances of acute pneumonic phthisis, a twenty-four hour record, with a variation of only a degree, such as is seen not infrequently in the early stage of lobar pneumonia or of typhoid fever, is most exceptional. Much more commonly the fever 'Sydenham Society's ed., p. 310. - Phthisiolorfia, p. lUci. 794 TUBERCULOSIS. is remittent in character, with an afternoon exacerbation. An inter- mittent type of pyrexia, also quite common, is met with sometimes in the very early stages of the disease, but is most frequent in the stage of cavity. In the initial period of pulmonary tuberculosis fever is one of the most important sym})toms. Usually toward the afternoon the patient feels a little flushed, and the thermometer records a temperature of two or two and a half degrees above the normal. The morning temperature at this time may be subnormal. In other instances, par- ticularly when there is rapid invasion and consolidation of the lung tissue, there is pyrexia throughout the tweuty-four hours wdth a marked afternoon exacerbation. The fever of onset in pulmonary tuberculosis may be accompanied with chills and sweats, simulating very closely a malarial intermittent fever. In this latitude to confound early tuber- culosis with malarial fever is an extremely common error. The sweat- ing which sometimes accompanies the fever of the early stages, and which may come on in the early hours of the night, rarely has the pro- fuse and soaking character of the sweats of the later stages. This fever of onset is often associated with two other important symptoms — a chloro-anseraia and dyspepsia. Both of these are very variable. The aneemia may be most marked. Generally speaking, the presence of fever is a good differential criterion between early tuberculosis and chlorosis, but the instances of the latter disease in which fever is a marked feature may for a time be quite j)uzzling. The dyspeptic symptoms are common accompaniments of the fever, but in some instances with a daily afternoon pyrexia the tongue may be clean and the appetite and digestion good. In the period of softening — the second stage, as it is sometimes called — the fever is more pronounced, and, when the disease is progress- ing, remittent in character, not reaching the normal, but with a daily exacerbation in the late afternoon or evening. At this period a temper- ature of 103° or 103.5° F. is common. Temperatures above 104° are rare. The daily remissions are from two to three degrees. Often in this stage the remissions may be more marked, and the temperature may fall through the morning hours to normal, or even below this point. In a few instances one sees the so-called inverse type, in Avhich the tem- perature is higher in the morning hours than in the evening. In the stage of cavity the hectic tyjDC of temperature may be strongly pro- nounced. To get a proper idea of the diurnal range a two-hourly record is necessary, A morning and evening observation may give an entirely incorrect idea of the range. When the hectic is fully established, during a very considerable part of the twenty-four hours the patient is not only afebrile, but has a subnormal temperature. The afternoon ex- acerbation may reach from 103° to 105° F., and the maximum is usually reached some time between six and ten in the evening. After midnight the temperature begins to fall, and by eight o'clock is usually nor- mal, reaching from 96.5° to 97.5° F. The fall in the morning is usually accompanied by a profuse sweat. A slow rise then takes place through the late morning and early afternoon hours. The extreme daily range may be remarkable, from eight to ten degrees being not uncommon, and there are instances on record of a diurnal range of 12 and 14.5° F. This wide variation is most commonly seen in the very late stages of the disease. CHRONIC ULCERATIVE TUBERCULOSIS OF THE LUNGS. 7J)o Fever is ilic most important j)r()ti;n()sti(' syiiiptoiii in imlmoiiarv tiihci- t'nK)sis. With a tciniR-ratiirc ranjiv from 101'^ to lO.'}"^ or 104° F. tlie disease is surely progressing-. It is most exceptional to find a[)yrexia associated either with the active development of tnborclcs (n* of caseation or with rapid softening-. There are rare instances on record in which with a temperature at or below 99° the local signs and general symp- toms indicate a i)r()gressive lesion. TIk' PiiJ.sc. — The heart's action is quickened in early stages in [)ro- portion to the height of the fever, in later stages Ijcaring a closer rela- tion to the degree of weakness. In young, excitable persons the pulse in the early stages may be very ra])id, from 112 to 120, and there is great irritability of the heart, palpitation on slight exertion, and short- ness of breath. There are instances in which pal])itation and cardiac irritability are the most distressing symptoms of the early stage. In the high fever of rapid extension the pulse may be dicrotic. As the emaciation proceeds the superficial veins, particularly of the arms and hands, may be very prominent. In many cases of chronic phthisis the pulse is soft and full and the veins of the hands prominent. It is by no means infrequent to see pulsation in the peripheral veins, particu- larly those of the hands, and the capillary pulse in the nails may at times be readily seen. Sweats. — At any stage of the disease profuse sweating may occur. In the fever of onset this may be associated with the chills, and the group- ing of the rigor, fever, and perspiration may lead to the diagnosis of malarial fever. The sweats occur more frequently in the stages of soft- ening and cavity formation. The most characteristic are the sweats Avhicli occur with the falling temperature of the early morning hours, and which may be of a drenching character and very exhausting to the patient. They may occur with great persistency and resist all treat- ment. As a rule, they are general over the surface, but in some in- stances they may be localized to the trunk. While the most profuse and distressing sweats are nocturnal, in many cases they occur at any time during the day if the patient happens to fall asleep, or they may follow the taking of food or any sudden emotional disturbance. In con- sequence of the profuse sweating the skin of the trunk is often covered with sudaniina or a red miliary eruption. Sweats in the early stages are sometimes followed by a sense of comfort, and the patient congratu- lates himself that the fever is " breaking." Morton speaks of this as a fraudidenta pax. In a much larger proportion of cases the sweats are exhausting and excessively disagreeable. Emaciation. — Loss of weight, one of the most obvious of the general symptoms of tuberculosis, and one from Avhich the two most common names, phthisis and consumption, have been derived, is an early and constant feature of the disease. Next to the thermometer, the scales give us the best index to the progress of the disease.^ In a few rare ' The wasting of a consumptive has never been described more graphically than by Sir Thomas Browne in his well known Letter to a Friend: " In this consumptive condi- tion and remarkable extenuation he came to be almost half himself, and left a great part behind him which he carried not to the grave. And though that story of Duke .John Ernestus Mansfield be not so easily swallowed that at his death his heart was not found to be so big as a nut, yet if the bones of a good skeleton weigh little more than twenty pounds, his inwards and flesh remaining could make no bouffage, but a light bit for the 796 TUBERCULOSIS. instances the disease may make rapid progress without causing great loss of weight, but, as a rule, the emaciation is in a measure proportional to the extent of the local disease and its progress. It bears an important relation also to the fever, and the higher and the more persistent this is the greater is the loss in weight. AVith moderate temperature one may see occasionally a gain in weight, but rarely with a pyrexia reaching above 101° F. Other agencies besides the fever may influence the loss in weight, more particularly the dyspepsia which is so common, and the diarrhoea. Physical Signs. — («) Inspection. — The patient should be in the sittiug posture, before a good light, and in the case of a male stripped, in a female at least the upper portions of the chest exposed. Attention should be first given to the shape of the chest, which is often in tuber- culous subjects long and narrow. Both Hippocrates and Galen laid great stress upon defective conformation of the chest in phthisis, the former describing particularly the so-called winged scapulae. In a large proportion of cases the thorax is long and narrow, with wide intercostal spaces, the ribs more vertical in direction than normal, and the costal angle very narrow. Frequently the chest is flattened in an antero-pos- terior direction,, or the costal cartilages of one or both sides may be prominent, while the sternum is depressed. Occasionally the lower sternum presents a deep cavity, the so-called funnel breast (Trichter- brust). The two sides of the chest may be un symmetrical. In the earlv stages no difference may be noticed in the clavicular regions, but in apical disease w^hich has lasted for any time there are changes which at once attract attention : the clavicle on the affected side is more prominent ; the supra- and infraclavicular spaces are more distinct ; and there may be well marked flattening corresponding to the first, second, and third ribs of this side. In very long standing cases the intercostal spaces may be much narrower and the affected side con- siderably shrunken. The condition of the prsecordia should be carefully noted, as a wide area of impulse, particularly in the second, third, and fourth interspaces, is often associated with chronic tuberculosis of the left apex. SjDCcial attention should then be given to estimating the mobility of the two sides, noting particularly whether the apices expand equally or whether the movement on one side is retarded. Defective expansion of one apex is an early and valuable sign, particu- larly in women. While marked deviations from the normal are common enough in the thoraces of persons affected with pulmonary tuberculosis, it is well to bear in mind that there are many cases in which the patients show perfectly well formed chests. (6) Palpation. — With the hands placed beneath the clavicles one can estimate well the degree of expansion or any deficiency on either side. Standing behind the patient with the thumbs in the suprascapular and the fingers in the infraclavicular spaces, one can often judge very grave. I never more lively beheld the starved characters of Dante in any living face ; an aruspex might have read a lecture upon him without exenteration, his flesh being so consumed that he might in a manner have discerned his bowels without opening of him : so that to be carried, sextd cervice, to the grave, was but a civil unnecessity ; and the com- plements of the cofRn might outweigh the subject of it." CHRONIC ULCERATIVE TUIiEUCVLOSIS OF THE LUNGS. 797 accuratoly the relative iii()l)ility oi' ilic two sides. The condition of" ilie intercostal spaces, the exact jiosition of the aj)ex heat, the j)resence or absence of" })aiM in any region, are als<» pt)ints to he estimated by paljtation. On asking the patient to count while palpation is made at the different parts, one estimates the vocal vibrations, which are normally more forcible at the right than at the left apex, and which are much increased in all stages of tuberculous disease at the apices and over any part of the lung where consolidation has taken place. On the other hand, if a pleural exudate complicates the disease, the fremitus is greatly diinin- ished or absent. (c) Pereussio)!. — In the early stages of pulmonary tuberculosis this method of examination gives us less valuable information than inspec- tion or auscultation. With well marked deficient expansion at an apex there may be scarcely any change in the percussion note Ijeneath the clavicle. In other instances the resonance is only slightly defective. In a few cases one meets with a hyperresonant note or a distinct Skodaic resonance. One of the earliest and most valuable signs is defective resonance above, upon, or below one clavicle. In a considerable jjro- portion of all cases of phthisis the change in the note is first found in these regions. A comparison between the two sides should be made also when the breath is held after a full inspiration, as the defective resonance may then be more clearly marked. In the early stages the percussion note is usually higher in pitch, and may require an experi- enced ear to detect the difference. In recent consolidation from caser»us pneumonia the percussion note often has a tubular or tympanitic quality. A wooden dulness is rarely heard except in old cases with extensive fibroid change at the apex or base. Over large thin-walled cavities at the apex the so-called cracked-pot sound may be obtained. In thin subjects the percussion should be carefully practised in the supraspinous fossae and the interscapular spaces, as they correspond to very important areas early involved in the disease. In cases with numerous separated cavities at the apex, without much fibroid tissue or thickening of the pleura, the percussion note may show little change, and the contrast between the signs obtained on auscultation and percussion is most marked. In the direct percussion of the chest, particularly in thin patients over the pectorals, one frequently sees the phenomenon known as myoidemrt, a local contraction of the muscle causing bulging, which persists for a variable period and gradually subsides. It has been thought by some to be more frequently met with in pulmonary* tuber- culosis than in other diseases. It has, I think, no special significance. (d) Auscultation. — Corresponding areas on the two sides should be examined, at first during quiet respiration, then during deep breathing, and finallv durino- the act of couofhins;. In verv earlv disease of one apex the inspiration on quiet breathing may be scarcely audible ; expira- tion is, as a rule, prolonged. On the other hand, the earliest noticeable change may be a harsh, rude inspiratory murmur. On deep breathing it is well to remember that the normal pitch is somewhat higher and the expiration somewhat more prolonged at the right than at the left side, particularly at the apex. The inspiration may be jerking or wavy, the so called cog-wheel rhythm, which is best heard when the patient draws 798 TUBERCULOSIS. a deep breath slowly. It is by no means limited to or characteristic of tuberculosis. With pneumonic consolidation and caseation there may be during both inspiration and expiration the most typical tubular breath sounds. Rales early accompany these changes in the respiratory murmur. They are due to the associated bronchitis. They may be only heard on deep inspiration or on coughing, and very early in the disease are crack- ling in character — the so-called dry crackling or subcrepitant rales. Ou coughing they may disappear, or they may become louder and moister in quality. With this there may be sometimes at the end of inspiration a piping bronchial rale. As the disease progresses the adventitious sounds become louder, and what is known as the mucous or moist rale is heard, which is louder, moister, and more bubbling in character. Sometimes at the very end of inspiration these moist rales have a very clicking quality. In each instance it is important to note the quality of the rales on quiet and deep breathing and on coughing, and to observe whether they occur with both inspiration and expiration, and whether the character of the respiratory murmur is obscured or not. When cavities form the rales are louder, more gurgling, and resonant in quality. Over an area of consolidation the breath sounds are tubu- lar, and in the large excavations loud and cavernous or have an amphoric quality. In the unaffected portions of the lobe and in the opposite lung the breath sounds may be harsh and even puerile. The vocal resonance is usually increased in all stages of the process, and bronchophony and pectoriloquy are met with in the regions of consolidation and over cav- ities. Pleuritic friction may be present at any stage, and, as mentioned before, occurs very early. There are cases in which it is a marked fea- ture throughout. When the lappet of lung over the heart is involved there may be a pleuro-pericardial friction, and when this area is consol- idated there may be curious clicking rales synchronous with the heart beat, due to the compression by the heart of, and the expulsion of air from, this portion. An interesting auscultatory sign, met most commonly in phthisis, is the so-called cardio-respiratory murmur, a whiflBng sys- tolic bruit due to the propulsion of air out of the tubes by the impulse of the heart. It is best heard during inspiration and in the antero-lateral regions of the chest. A systolic murmur is very often heard in the subclavian artery of one or other side. It has been thought to be due to compression of the artery by the apex of the lung or to pressure by a thickened pleura. It is heard best, as a rule, during expiration. It is of no moment, and occurs in thin-chested persons apart altogether from any disease of the apices. Sig'i'is of Cavity. — In long standing cases, if the cavity is at the apex, signs of retraction in the infraclavicular region become intensified. Very pronounced unilateral retraction in this region with immobility is a sign of great value. Usually the muscles have undergone atrophy and the chest walls are thin. In very rare instances in a thin-walled cavity there is slight bulging in the first and second interspaces. The vocal fremitus is much increased, a point of great moment in the diiferentiation of very large cavities from pneumothorax. The per- cussion sound over a cavity may be very variable. In a few instances, CHRONIC ULCERATIVE TUBERCULOSIS OF THE LUNGS. 799 wlu'ii there is not niiicli thickeiiiiii;' oi" the pleura oi' iii(hirati(»ii oi" the surromnliiiu' hiiiii' tissue, the note nuiy bo lull and clear. Mure coni- nionlv theii' is a hiii'h-pitehed wooden note, whieh may luivc a tympa- nitic or even an amphoric (|uality, and which may undcru-o many altera- tions. The tympanitic quality may disappear when the cavity is lull of liquid. The note may change distinctly in pitch when the mouth is opened or closctl (W'intrich's sign), or alters during deej) inspiration or deep e.\j)iration or with the change in the position of the patient. The cracked-pot sound — bruit dc pot file — is lieai'd over large cavities with thin walls. To elicit it the patient should draw at first two or three deep breaths, and then breathe quietly with the open mouth. The per- cussion stroke shoidd be quick and forcible. The cracked-pot sound is not distinctive of cavity. It is heard sometimes over the normal chest in childhood, over the upper portion of a lung compressed by fluid, in the earlv stages of pneumonia, and over the apices in some instances of acute tuberculosis, and in pneumothorax. On auscultation over a cavity the breath sounds are heard very much altered in various grades — tubular, cavernous, or amphoric. It is im- portant to bear in mind that the inspiratory murmur heard over cavities of medium size may be typically tubular or blowing. In larger excava- tions the quality of botli inspiration and expiration may be what is termed cavernous, a variety of the bronchial breathing which possesses in a high degree a hollow quality very difficult to define, but readily appreciated by the ear. In very large cav'ities both inspiration and expiration may be typically amphoric. There may be a sharjj, hissing sound, as if the air was passing from a narrow opening into a wide space. Over the entire area of a large cavity there may be dead silence (Walshe), which may be due either to complete filling with secretion or to tempo- rary blocking of the tubes. Cavernous rales are coarse, bubbling in quality, resonant, and on coughing they may be very loud and gurgling. They are usually increased by deep inspiration or by coughing ; they are not always present, and in some large cavities the breath sounds may be perfectly dry. In very large, thin-walled cavities the rales may have an amphoric echo, almost resembling that of pneumothorax. Metallic tinkling is rarely heard. In large excavations of the left apex the heart impulse may cause gurgling sounds or clicks synchronous with the sys- tole. They may even be loud enough to be heard at a little distance from the chest wall. A large cavity with smooth walls and thin fluid contents may give the succussion sound when the trunk is abruptly shaken (Walshe), and even the coin sound may be obtained. The vocal fremitus is greatly increased over a cavity. The whisper- ing pectoriloquy is heard better than under any other circumstances, though it is not, as was supposed, pathognomonic of a cavity. In large apical cavities the heart sounds may be heard with great intensity, and there may be a loud systolic murmur, which is probably always trans- mitted to, and not produced in, the cavity. Complications of Pulmoxary Tuberculosis. — 1. IntheBespi- ratory System. — The larynx is rarely spared in chronic pulmonary tuber- culosis. As already stated, the first symptom may be huskiness of the voice. Involvement of these parts is indicated by alterations in the character of the voice, pain, particularly in swallowing, and a cough 800 TUBERCULOSIS. which is often wheezing, and in the hitter stages very ineffectual. Aphonia and dysphagia are the two most distressing symptoms of the laryngeal involvement. When the epiglottis is seriously diseased and the ulceration extends to the lateral Avail of the pharynx, the pain in swallowing may be very intense, or, owing to the imperfect closure of the glottis, there may be coughing spells and regurgitation of food through the nostrils. Bronchitis and tracheitis are almost invariable accompaniments of chronic pulmonary tuberculosis. When the former extends beyond the area involved in the local disease it may increase the dyspncea, and in the smaller tubes may lead to patchy areas of broncho-pneumonia. Extensive ulcerative tracheitis may exist with- out any symptoms. Pneumonia is a not infrequent terminal complication of chronic phthisis. It may run a perfectly normal course, while in other in- stances resolution may be delayed, and one is in doubt, in spite of the abruptness of the onset, as to the presence of a simple or a tuber- culous pneumonia. Emphysema of the uninvolved portions of the lung is a common fea- ture, rarely producing any special symptoms. There are, however, cases of chronic tuberculosis in which emphysema dominates the pic- ture, and in which the condition develops slowly during a period of many years. (General subcutaneous emphysema, which has been met with in a few rare cases, is due either to perforation of the trachea or to the rupture of a cavity closely adherent to the chest wall.) Gangrene of the lung is an occasional event in chronic pulmonary tuberculosis, due in almost all instances to sphacelus in the walls of the cavity, rarely in the lung tissue itself. Complications in the Pleura. — As already mentioned, a dry pleurisy is a very common accompaniment of the early stages of tuberculosis. It is most frequently met with at the apices, and results from the direct involvement of the pleura over the affected portions of the lung. It is always a conservative, useful process. In some cases it is very exten- sive, and friction murmurs may be heard over the sides and back. The cases with dry pleurisy and adhesions are of course much less liable to the dangers of pneumothorax. Pleurisy with effusion more commonly precedes than develops in the course of pulmonary tubercu- losis. Still, it is common enough to meet with cases in which a sero- fibrinous effusion develops in the course of the chronic disease. There are cases in Avhich it is a special feature, and it often, I think, favors chronicity. A patient may during a period of four or five years have signs of local disease at one apex with recurring effusion in the same side. Owing to adhesions in different parts of the pleura the effusion may be encapsulated. Hemorrhagic effusions, which are not uncommon in connection with tuberculous pleurisy, are comparatively rare in chronic phthisis. Chyliform or milky exudates are sometimes found. Purulent effusions are not frequent apart from pneumothorax. An empyema, however, may develop in the course of the disease or as a sequence of a sero-fibrinous exudate. Pneumothorax is an extremely common complication of chronic pulmonary tuberculosis. It may oc- cur early in the disease, but more frequently is late. It may prove fatal in twenty-four hours. In other instances a pyo-pneumothorax develops CHROMC ULCERATIVE Tl'liERCULOSIS OF TllE IJ'SHS. 801 and till' |t;ui('nt liiiircrs for weeks or months. In a third ltoiij) of eases it seems to have a beneheial etfl'ct on the (-(Xirse of the (hsease. Dahmd reported a etise from my wards in Piiihidelj)hia in whicii a patient with ehronie |)hthisis and pneumothorax was luxlcr observation for nearly four years. 2. Symptoms referable to Other Organs. — («) Cardio-vascular System. — The retraetion of the left upper lobe exposes a larfje area of the heart. In thin-ehested subjects there may be pulsation in the second, tiiird, and fourth interspaces close to the sternum. Sometimes with much retrac- tion of tiie left upper lobe the heart is drawn up. A systolic murmur in the second left intercostal space, near the sternimi, is common in all stages of phthisis. Apical murmurs are also not infrequent, and may be extremely rough and harsh without necessarily indicating that endo- carditis is present. The association of heart disease with ])hthisis is not, however, very uncommon. I met with 12 instances of endocar- ditis in 216 autopsies. The symptoms are indefinite, and a diagnosis could rarely be made unless embolic features were present. The arterial tension is usually low in phthisis, and the capillary resistance lessened, so that the pidse is often full and soft even in the later stages of the disease. The capillary pulse is not infrequently met with, and pulsation of the veins in the back of the hand is occasionally to be seen. (6) Blood Glandular System. — An early chloro-ansemia is a striking symptom in many cases. In the later stages the blood count rarely sinks below 2,000,000 per c.mm. The blood plates are, as a rule, enormously increased, and are seen in the withdrawn blood as the so- called Schultze's granule masses. Thev are of interest chieflv from the fact that every year or two some one announces their discovery as a new diagnostic sign in phthisis. The leucocytes are greatly increased, particularly in the later stages. (c) Gastro-intestinal System. — The tongue is usually furred, but may be clean and red. Small aphthous ulcers are sometimes distressing. A red line on the gums, a symptom to which at one time much attention was paid as a special feature of phthisis, occurs in other cachectic states. Extensive tuberculous disease of the pharynx, associated with similar affection of the larynx, may interfere seriously with deglutition and prove a very distressing and intractable symptom. Of late special attention has been paid to the gastric symptoms of this affection. Tuberculous disease of the stomach is rare. Ulceration mav occur as an accidental complication, and multiple catarrhal ulcers are not uncommon. Interstitial and parenchymatous changes in the mucosa are common (possibly associated with the venous stasis) and lead to atrophy, but these cannot always be connoted with the symp- toms, and they may be found when not expected. On the other hand, when the gastric symptoms have been most persistent the luucosa may show very little change. It is impossible always to refer the anorexia, nausea, and vomiting of consumption to local conditions. The hectic fever and the neurotic influences, upon which Iramermann lays much stress, must be taken into account, as they play an important role. The stomach is often dilated, and to muscular insufficiency alone may be due some of the cases of dyspepsia. The condition of gastric secretion Vol.. T.— 51 802 TUBERCULOSIS. is not constant and the reports are discordant. In the early stages there may be hyperacidity ; later, a deficiency of acid. Anoi-exia is often a marked sympton at the onset ; there may be positive loathing of food, and even small quantities cause nausea. Sometimes without any nausea or distress after eating the feeding of the patient is a daily battle. Nausea and vomiting, though occasionallv troublesome at an early period, are more marked in the later stages. The latter may be caused by the severe attacks of coughing. S. H. Habershon refers to four different causes of the vomiting in phthisis : (1) central, as from tuberculous meningitis ; (2) pressvire on the vagi by caseous glands ; (3) stimulation from the peripheral branches of the vagus, either pulmonary, pharyngeal, or gastric ; and (4) mechanical causes. Of the intestinal symptoms diarrhoea is the most serious. It may come on early, but is usually a symptom of the later stages, and is associated with ulceration, particularly of the large bowel. Extensive ulceration of the ileum may exist without any diarrhoea. The associated catarrhal condition may account in part for it ; in some instances it is due to amyloid degeneration of the mucous membrane. {d) Nervou)i System. — (1) Focal symptoms may be due to the devel- opment of coarse tubercles and areas of tuberculous meningo-encepha- litis. Aphasia, for instance, may result from the growth of meningeal tubercles in the fissure of Sylvius, or even hemiplegia may develop. The solitary tubercles are more common in the chronic phthisis of chil- dren. (2) Basilar meningitis is an occasional complication. It may be confined to the brain, though more commonly it is a (3) cerebrospinal meningitis, which may come on in persons without well developed local signs in the chest. Twice have I known strong, robust men brought into hospital with signs of cerebro-spinal meningitis in whom the exist- ence of pulmonary disease was not discovered until the post-mortem. (4) Peripheral neuritis, which is not common, may cause an extensor paralysis of the arm or leg, more commonly the latter, causing foot- drop. It is usually a late manifestation. (5) Mental Symptoms. It was noted, even by the older writers, that consumptives had a peculiarly hopeful temperament, and the spes phthisica forms a curious charac- teristic of the disease. Patients with extensive cavities, high fever, and too weak to move will often make plans for the future and con- fidently expect to recover. Apart from tuberculosis of the brain, there is sometimes in chronic phthisis a form of insanity not imlike that which develops in the con- valescence from acute affections. The question of the mutual relations of insanity and phthisis is dwelt upon at length in Mickle's Goulstonian Lectures.^ (e) A remarkable hypertrophy of the mammary gland may occur in pulmonary tuberculosis, commonly in males. It may only be on the affected side. It is referred to in another place. (/) Genito-urinary System.. — The urine presents no special peculiari- ties in amount or constituents. Fever, however, has a marked influence upon it. Albumin is met with frequently, and may be associated with the fever or is the result of definite changes in the kidneys. In the latter case it is more abundant and more curdlike. Amyloid disease of 1 Lancet. 1888, i. cnnosic rLcHHATiVF. rri'.EncrLosis nr rni: j.r\<;s. 803 tlie kiiliioys is not uiicdininoii. It> |)r('sci)cc is sliowii Wy ;ill)iiiiiiii ami tube oasts in the urine, and sometimes l»ya a.reat inci-casc in tlie amount of the urini'. In other instanees there is dropsy, and tlie ])atients liave all the characteristic features of ehrouie liriolit's disease. P^.s /// the urine may be due to disease of tlie bladder or of the pelves of the kidneys. In some instances the entire urinary tract is involved. In jnilmonarv phthisis, iiowever, extensive tubt'reulous disease is rarely foiuul in the urinary or< vcr>erculosis may be the direct result of the tuberele l)aeillus or its toxins, or it may follow secondary infection with other germs, particularly the strej>tococcus pyogenes, the micrococcus lanceolatus, and the staphylococcus pyogenes. The fre- quency of this secondary infection and the relative significance of these germs are not yet fully decided. The introduction of the tubercle bacilli into the lungs of a rabbit through the trachea induces the various phases of pulmonary tuberculosis, but cavity formation is rare. If, on the other hand, into the lungs of a rabbit which are the seat of extensive consolidation the streptococcus pyogenes is introduced, then cavities form rapidly, and the anatomical picture is very similar to that of chronic ulcerative tuberculosis in man. It is very probable that in man, too, the effect of contamination with these pus organisms is a very important one in hastening necrosis and softening, and also in the chronic cases they doubtless produce in large amounts the toxins which are responsible for many of the symptoms of the disease. Diseases Associated with Pulmoxary Tuberculosis. — Lobar pneumonia, as already mentioned, is a not uncommon complication which carries off a certain number of cases. It may be difficult to distinguish from an acute tuberculous pneumonia. In chronic ulcerative tubercu- losis, however, this form is not so common, and rapid consolidation of the lower lobe, with rusty expectoration and high fever, is much more likely to be a simple croupous pneumonia. With tuberculosis, either in the acute or chronic form, typhoid fever may coexist. In 4 cases of 80 autopsies in typhoid fever tuberculous lesions were present. There are cases on record also of acute miliary tuberculosis and typhoid fever present in the same subject. There is a widespread opinion that typhoid fever predisposes to tuberculosis, and "Wilson Fox in his treatise on diseases of the lungs gives references to a number of cases. In my experience it has been very rare. I have no recollection of an instance in which tuberculosis has developed either during convalescence, or immediately after recovery, from typhoid fever. Erysipelas sometimes attacks the subjects of chronic phthisis, who are not, however, specially liable to the disease. There are a number of cases on record in which an attack of erysipelas has been beneficial, and after recovery the severity of the pulmonary symptoms has miti- gated, and there are cases in which cure has been reported. On the other hand, I have known cases in which the attack has proved rapidly fatal in persons far advanced in the disease. TUBERCULOSIS. The eruptive fevers rarely develop in the course of pulmonary tu- berculosis. Malaria was formerly thought to antagonize tuberculosis, a view for which there is no special warrant. The early chills and fever of developing pulmonary tuberculosis are very apt to lead to error in diagnosis, and cases are often treated for weeks or months as malarial intermittent fever. Heart Diseases. — Endocarditis is not verv^ infrequent in pulmonary tuberculosis. It was present, as already mentioned, in 12 of my post- mortems and in 27 of Percy Kidd's 500 autopsies. The subject has been considered in a monograph by Teissier (Paris, 1894). The endo- cardial lesions are, as a rule, vegetative, rarely caseous, and due com- monly to the associated micro-organisms, but in a few instances the tubercle bacillus has been present alone. Ulcerative lesions are rare. Both Louis and Rokitansky held that there was a certain antagonism between valvular disease and pulmonary tuberculosis — a view which has not been borne out by subsequent studies. Certainly stenosis of the pulmonary artery and aneurysm of the aorta predispose to tubercu- losis pulmonum. A terminal acute tuberculosis is a common event in all forms of cardio-vascular disease. The relation of mitral stenosis to pulmonary tuberculosis is still a matter of debate. In 9 of 54 cases of stenosis Potain found pulmonary tuberculosis present. Teissier con- cludes that it is antagonistic to the progress of the disease. In long standing cases of the disease arterio-sclerosis is very common. Phlebo- sclerosis is also not infrequently met with. The frequency of the renal changes may possibly be correlated with this arterio-sclerosis. Ormerod noted 30 cases of chronic renal disease in 100 autopsies. The association of gout and rheumatism with pulmonary tuberculosis has often been referred to, particularly by the older writers, among M'hom Morton described a species — phthisis de arthritide. In institu- tion life, particularly in the almshouses, the subjects of chronic joint troubles are very often attacked by tuberculosis, and it is probably a matter entirely of greater liability to infection. Peculiarities of Pulmonary Tuberculosis at the Ex- tremes OF Life. — (a) Infancy. — Tuberculosis is a widespread aflPec- tion in the early periods of life. AVhile extremely rare in the newborn, and not at all prevalent in the first three months of life, the cases increase rapidly throughout the latter half of the first year and during the second year. In the statistics of the late Professor Parrot, of 219 cases in children under three years there were from one day to three months 23 cases ; from three to six months, 35 cases ; from six to twelve months, 53 cases — a total of 111 cases under one year. Pulmonary cavities were present in 57 of the cases, and in 50 the lung disease was the only manifestation. Of 125 cases at the Xew York Foundling Hospital, reported b}' Xorthrup, in 34 cases the disease was extensive and the seat of the primary infection was not clear, but the bronchial glands were large and cheesy. In 42 cases of general tuberculosis the only caseous masses were in the bronchial glands. In 9 cases the tubercles were limited to these glands and to the lungs, the latter containing only miliary tubercles, while the bron- chial glands were in a state of advanced caseation. In 13 cases there was tuberculosis of the bronchial glands only. These extremely sug- Finn'fin I'lnnisfs. 809 gestivc figures slmw the lii^cat prcN nlciicf dl" iiircctioii tlinmuh tlic bronchial ])ass:iu'('s. On the othci' hand, of 127 I'atal eases ot" tiihereii- losis in ehildren nol<'(l hy Wdodhead, the niesenterie glands were tuheretdoiis in 100. \\'alter C'arr in the examination of" the bodies of 120 tuberculous children concludes that the disease starts much more frequently in the thoracic than in the mesenteric glands. Of 500 auto|)sies in children at the Mmiich Pathological Institute, in loO tul)ereulosis was present, and in over 92 per cent, of these the lungs were involved. [/)) Old Age. — The prevalence of tuberculosis in the aged, i)articu- larly in institutions, has been long known. The physicians to the large hospitals for old people, as at the Chelsea, the Bicetre, and the 8alpetriere, have long recognized the great frequency of tuberculosis as a cause of death. In the post-mortem room of the Philadelphia Hospital, to which the bodies of aged persons were sent from the iilmshouse department, it was extremely common to find old or re- cent tuberculosis. An important study of the subject has been made recently by Barie.^ In the year 1891 there were in Paris 10,649 :ed and caseated in both instances. From syphilitic ulceration the condition would be recoi>;ni/ed by the historvof the ease and the absence of any impntvement under treatment with iodide of potassium. In doubtful eases inoculation tests should be made or a portion excised for inicrosco})i(;al examination. (c) Palate. — Tuberculosis of the hard and soft palate nearly alwavs results from an extension of the disease from nei<2jhborin<>' parts. Barker records a case in a <>'irl of fifteen years in whom there had })een such an extensive destruction of the hard and soft palate and the alveolar process that many of the teeth iiad become loosened and several had fallen out. The disease had extended into the nasal cavity. {d) The saUcarij glands belong to that small group of organs of the body which seem to possess an immunity against tuberculous infection — an immunity, however, which in their case is relative, not absolute. The literature contains only a very few accounts of such a condition. Von Stubenrauch,' in reporting a case of tuberculosis of the parotid gland had been unable to find records of a previous case after a careful search of the literature. Frerichs, however, had previously recorded an instance in which both parotid glands contained four or five caseous foci, each about the size of a lentil. The submaxillary and sublingual glands were normal, although the patient presented advanced tuberculous lesions in various organs of the body. Leguen and Marien have recently re- ported a case resembling that of Stubenrauch, in both of which the gland presented a distinct localized swelling, the skin remaining normal in appearance and freely movable over it. The tubercles develop in the interacinous connective tissue, and the writers agree in considering that infection occurs by way of Steno's duct. Dmochowski claims to have found the sublingual gland tuberculous in 6 instances out of 15 autopsies on patients with pulmonary tuberculosis. (e) The tonsil has in recent years been shown to be much more com- monly the seat of tuberculosis than was formerly supposed. The appar- ent infrequency no doubt was due to the fact that in many instances the disease simulates very closely the ordinary hypertro])hied tonsil, for which it is often mistaken. Cohnheim in 1878 advanced the theory that the majority of the cases of tuberculosis of the lips, buccal mucous mem- brane, and pharynx were surface infections due to the ingestion of food, particularly milk, containing tubercle bacilli. In 1884, Strassmann, working under Cohnheim and Weigert, found the tonsils involved in 13 instances out of 21 autopsies. Dmochowski found them tuberculous in all of his 15 cases, and demonstrated tubercle bacilli in the lymphatics between the tonsils and the cervical lymph glands. The latter observa- tion is interesting in connection with the views of Schlenker,- who claims that the majority of the cases of tuberculous cervical glands result from ^ Archiv fixr Chirurgie, 1894. '^ Virchoiv's Archiv, 1893, Bd. cxxxiv. 812 TUBERCULOSrS. infection with tubercle bacilli which gain admission by way of the tonsil. A large number of his cases of tuberculous cervical adenitis Avere defi- nitely of a descending variety and associated with tuberculosis of these glands. The majority also had pulmonary tuberculosis, and he regards surface infection of the tonsil by tuberculous food and sputum far more common than infection by way of the circulation. The disease may occur as a superficial ulceration. More commonly there is an infiltra- tion of the tonsil with miliary tubercles, which produces a greater or less hypertrophy which it is practically impossible to distinguish from an ordinary enlarged tonsil without a microscopical examination. Case- ous foci occasionally develop. (/) Pharynx. — In extensive laryngeal tuberculosis an eruption of miliary tubercles on the posterior pharyngeal wall is not uncommon. In chronic phthisis an ulcerative pharyngitis, due to the extension of the disease from the epiglottis and larynx, is one of the most distressing of complications and renders deglutition extremely painful and difficult. Adenoids of the nasopharynx may be tuberculous, as shown by Lermoyez. Macroscopically, they do not differ from the ordinary vegetations found in this situation. He records a case in which pulmonary tuberculosis set in soon after the removal of adenoid vegetations which were shown to be tuberculous, and thinks that in such instances the tuberculous focus in the adenoids may be the point of departure of general infec- tion. Verneuil points out the risk of infection which is run in curette- ment of ordinary pharyngeal vegetations, especially since Straus has demonstrated the frequency of tuberculosis in the nasal cavities of men. {g) The Oesophagus. — Tuberculosis of the oesophagus is a compara- tively rare occurrence. It is only since the appearance of Weichsel- baum's and Beck's articles in 1884 that this affection of the oesophagus has attracted attention. In 1893, Flexner, in reporting a case which occurred in my wards, was able to find in the literature records of only 19 well authenticated cases. Frerichs examined 30 cases of acute and 250 cases of chronic tuberculosis. Of the acute cases, 8 had tubercu- losis of the pharynx, tonsils, or tongue without any involvement of the oesophagus. Of the chronic cases, only 1 case of oesophageal tubercu- losis occurred. The cases may be classed under three headings : The first includes those which result from direct extension of the tuberculous process from some of the neighboring structures, and constitutes the largest percentage of the cases. A group of caseous bronchial glands may become united by adhesions to the oesophagus, and finally ulcerate through into the latter. Penzolt has reported 3 cases of oesophageal tuberculosis resulting from the rupture into it of abscesses due to caries of the vertebrse. Slight ulceration of the upper part of the oesophagus following pharyngeal tuberculosis occasionally occurs. The second class of cases embraces those instances in which there is a history of a previ- ous lesion of the oesophageal mucous membrane, and which must be con- sidered as a predisposing factor to tuberculous infection. Breus records a case in which tuberculosis of the oesophagus followed a stricture due to the swallowing of a caustic alkali, and Eppinger an instance in which it followed a stricture which he attributed to the oi'dium albicans. Finally, in the third class must be placed those cases which occur in the TUBERCULOSIS OF THE ALIMENTARY CANAL. «13 course of an aciilc (lisscmiiiatcd niiliai'v tul)ci'('iil()>is, and lliosc instances in which there has appai'ently heen an infection of the iniicons menihi-ane with tiil)en'nh)us s[)utuni, without the jiresenee of any previous })re(ns- posing lesion. The case which occurred in my wards behjuged to this class. On tiie anterior wall of the cesopiiagus there were two tuV)er- culous ulcers, measuring 4 and 7.5 mm. respectively, one of which had perforated into the left pleural cavity, causing a purulent |)1( n- risy. The disease is not associated with any very definite symptoms. The occurrence of pain, difficulty in swallowing, and evidence of stricture in the course of chronic lung and lymph tuberculosis or caries of the vertebroe should lead one to suspect involvement of the (jesophagus. (/() Stoiiach. — Miliary tubercles in the wall of the stomach are not uncommon; tuberculous ulcers of the organ are very rare. Many of the reported cases are doubtful. Marfan^ in 1887 in reviewing the subject was able to collect only 14 authentic cases. Letorey^ quite recently reported a case and gave an analysis of 21 cases. Nearly all writers are agreed that the disease is secondary. It is commonest in the middle period of life, although occasionally children are aifected. The condition is found more frequently in males than in females. Of 19 cases collected by Letorey in which the sex was mentioned, it occurred 16 times in males and 3 times in females. In the great majority of in- stances the ulcers are single, although occasionally they may be multi- ple. In a recent case in one of my wards there were numerous ulcers of various sizes. As a rule, the ulcers are associated Avith tuberculous ulceration of the intestines. Litten, however, has reported 1 case and Frerichs has noted 2 instances in which the stomach was the only part of the alimentary tract which showed ulceration. The pyloric extremity and the greater curvature are usually involved. The ulcers vary in size from a pin's head to 3 or 5 cm. in diameter. In the case reported by Musser, how^ever, there was a large tuberculous ulcer three by one and a half inches in extent. Cheesy tubercles as large as a pea, both ulcer- ated and non-ulcerated, have been found in the stomach, but they are very rare. In Oppolzer's case an ulcer of the colon perforated the organ. Perforation of the stomach is not an infrequent occurrence. It occurred six times in Marfan's cases, three times by a tuberculous gland. As a rule, the condition is latent; in 8 of Letorey's cases the ulceration was suspected during life and was verified at autopsy. Occasionally severe ha3matemesis follows erosion of a bloodvessel by the ulcerative process. It has been the immediate cause of death in at least 2 in- stances. Death sometimes results from a peritonitis occasioned by the perforation, as in Paulicky's case, although it generally occurs as a re- sult of advanced tuljcrculosis in other organs. (i) Infesfincs. — Tuberculosis is by far the most common cause of intestinal ulceration. No part of the intestinal tract enjoys an immunity against tuberculous infection. The disease may be (1) primary in the mucous membrane, or more commonly (2) secondary to disease of the lungs, or in rare cases the aifection may (3) extend from the peritoneum. (1) Primary intestinal tuberculosis occurs most frequently in children in association with enlargement and caseation of the mesenteric glands 1 Paris Thesis, 1887. ^ Ibid., 1895. ht angles to the long axis of the intestine, so that nlcers are finally formed which entirely encircle the bowel, the so- called girdle ulcer. This direction of spreading is due to the fresh tubercles developing along the lines of the bloodvessels and Ivmphatics, which run transversely to the long axis of the intestine. Such ulcers mav be simulated by embolic ulcers due to the plugging of a vessel supplying a portion of the mucous membrane with nourishment, but would be distinguished by the presence of tubercles about the edges and on the base of the ulcer. By the coalescence of adjoining ulcers the greater part of the mucous membrane of the large and small intestine may become destroyed. The process is not confined to the mucosa and submucosa alone, but invades the muscular layers, and very frequently extends to the serous coat, which often presents numerous miliary tubercles over an area corresponding to the situation of the ulcer. From these there may sometimes be seen rows of tubercles extending along the lymphatics which lead from the diseased area to the mesenteric glands, which are usually caseous and considerably enlarged. The tuberculous ulcer then has the following characteristics : (a) It is irregular, rarely ovoid or in the long axis, more frequently girdling the bowel ; (6) the edges and base are infiltrated, thickened, and often caseous ; (e) the submucosa and muscularis are usually involved ; and (w ipiite advanced changes before the mucous menil)rane of the pelvis is involved to any extent. The disease may be confined to one kidney or progress more extensively in one than in the other. The less seriously aifected kidney may only show a pyelitis or a superficial necro- sis of one of the pyramids. On the other hand, one kidney, although not showing a tuberculous process, may be the seat of a serious nephri- tis, prol)ably an advanced amyloid degeneration. The ureters are usu- ally thickened and the mucous membrane ulcerated and caseous. In- volvement of the bladder, vesicular seminales, and testes is not uncom- mon in males. The symptoms of renal tuberculosis are variable, but they are prac- tically those of pyelitis. The condition is for many years compatible with fair health. The urine may be purulent for a long period, and yet the patient may have little or no distress. With our present know- ledge it is impossible to distinguish accurately cases in which the erup- tion of tubercles first occurs in the vicinity of the pelvis from those in which the cortex is first attacked. Fenwick, however, claims that in the pelvic form blood and pus appear in the urine in small amounts, either coincidentally with renal pain or soon after its appearance ; that renal colic appears relatively earlier than in the cortical form ; that the stages of the disease are passed through more rapidly ; and that the bladder is earlier involved. When, however, the tuberculosis primarily attacks the cortex, it must first break into the pelvis before very charac- teristic symptoms are prodticed. Polyuria, resulting from the irritating effect of the minute tubercles, would probal)ly be the first svmpt(^m complained of, even before any aching in the kidney is experienced. The urine would be of low specific gravity, and would contain more albumin than could be accounted for by the presence of the trace of pus. Hemor- rhage from the two situations also varies. In the early stage of the pelvic form the bleeding is usually slight and intermittent, whereas when a cortical deposit sloughs out suddenly into the pelvis there mav be profuse but transient hematuria. In renal tuberculosis, when the bladder becomes involved, or even earlier, micturition is frequent, and many cases are mistaken for cystitis. The possibility of nature afiect- ing a cure is shown by the accidental discovery of the so-called scrofu- lous kidney, in which the organ has become converted into a series of cysts filled with a putty-like substance. When the disease becomes ad- vanced and both organs are affected constitutional symjitoms are more marked. There is irregular fever, -with rigors and loss of weight and strength. Recurrent chills are common. General tuberculosis is fre- quent. In only one of my cases were the limgs uninvolved. Occa- sionally a cyst may perforate and cause general peritonitis. The pain suffered varies greatly : it may be of a dull, aching character, situated over the region of the affected kidney, or, as occasionally happens, 824 TUBERCULOSIS. severe and colicky, owing to the plugging of the ureter by some of the caseous material. Physical examination may detect special tenderness on one side, or the kidney may be palpable in front on deep pressure ; but tuberculous pyelo-nephritis seldom causes a large tumor. Occasionally the pelvis becomes enormously distended, but this is rare in comparison with cal- culous pyelitis. The urine presents changes similar to those of ordinary calculous pyelitis — pus cells, blood, epithelium, and occasionally definite caseous masses, and even moulds of the pelvis. Albumin is present in considerable quantity, but tube casts are not commonly seen. Care- ful and persistent examination of the urinary sediment for tubercle bacilli will usually demonstrate their presence. The very close resemblance between calculous pyelitis and renal tuberculosis, both in the gross pathological changes and in the symptoms produced, renders it in many instances extremely difficult to distinguish between the two affections. Hsematuria occurs in both, but in tuber- culous disease it occurs less frequently, is not so profuse, and is less influenced by exercise than is the hsematuria of calculous pyelitis. Renal colic is not so frequent as in the latter affection. The presence of tuberculosis elsewhere in the body, particularly in a testis or the pros- tate, and the discovery of tubercle bacilli in the urine, should leave little doubt as to the true nature of the disease. Tuberculosis of the Ureters, Bladder, and Urethra. It is doubtful whether primary tuberculosis of a ureter ever occurs. It is almost invariably involved secondarily to some other part of the genito-urinary system, particularly the pelvis of the kidney. The dis- ease usually occurs as a result of a direct extension of the tuberculous 23rocess from the kidney, or in rarer instances from the bladder by ex- tension upward. Surface inoculation by bacilli contained in the urine from a tuberculous kidney no doubt often occurs. In advanced cases the whole of the mucous membrane of the ureter may be extensively ulcerated and the walls thickened and caseous. In such a case it is quite possible on deep palpation to feel the ureter as a thickened, more or less irregular cord. Tuberculosis of the bladder is quite common. It may be primary, but is generally secondary to tuberculosis elsewhere in the uro-genital tract. Extension of the disease from the kidney may occur in various ways : First, by surface inocculation. The urine coming from a tubercu- lous kidney is laden with irritating products, which finally cause swell- ing and congestion of the vesical mucous membrane, particularly over the trigone. This leads to frequency of micturition, owing to irritation of the vesical neck. Later excoriation of the surface occurs or an abrasion of the mucous membrane is produced by needless instrumenta- tion. The soil having been thus favorably prepared and a means of en- trance for the bacilli produced, infection readily takes place. In such cases, therefore, if the mucous membrane remains intact, the chances of infection are much diminished, so that every possible means of ascertain- ing the true cause of the bladder trouble should be adopted before sounding for stone is performed. TUBERCULOSIS OF TIIK rilETERS, BLADDER, AND URETHRA. 825 Secondly, the l)l;i(M(i- may he involved as a ivsnlt of direct exten- sion of the disease alonii; the line of the ureter. The mucous mem- brane about the oritiee of the urethra becomes swollen and congested, and this is followed by ulceration, whicii gradually extends along the corres))()ndinii' trigonal limi). 'riiinllv, in a yrcat many more instances than is generally supposed th(> bladder is involved secondarily to renal tuberculosis as a result of infeetit)n through the bloodvessels. Cystoscopic examination of the bladder in suspected cases quite frequently shows the presence of tuber- cles beneath the mucous membrane without there being any superficial ulceration — a point strongly suggesting a blood infection. The disease sometimes extends from the prostate, the infection creeping rather uniformly up from the anterior angle of the trigonum. The spread of the disease probably takes place along the lymphatics of the submucous coat. Occasionally the bladder is invaded from an infected seminal vesicle. Not infrequently there is a direct extension of the disease from the recto-vesical fold of peritoneum in cases of tuberculous peritonitis. Tuberculous ulcerations of the intestine may lead to adhesions to the bladder with secondary involvement of the latter. In the female, invasion may be from a tuberculous uterus or vagina. The extent to Avhich the tuberculous process may have advanced varies considerably. In primary vesical tuberculosis the middle coat alone may be found involved if the disease has not become too far advanced. Other cases may show only a slight localized ulceration, or the whole of the vesical mucous membrane may present irregular, deep ulcerations, the bases of which are covered wdth a caseous exudate. The bladder is usually contracted and the walls very much thickened. The urine is purulent and contains particles of caseous material. In primary tuberculosis of the bladder the symptoms produced may not appear until some considerable time after involvement. When they do present themselves, however, the resemblance to those caused by •calculus may be quite marked, especially when the tuberculosis begins in the posterior wall. Frequency of micturition and pain in the glans or mid-penis, particularly in the latter situation, are usually the first symptoms which attract the patient's attention. Fenwick found these to be the earliest symptoms in 76 per cent, of his cases, whilst in many of the remainder hemorrhage was the first symptom. The frequency of micturition is at first most marked during the day, but later the night is also disturbed by repeated calls to empty the bladder — a point which would be strongly against the probability of the symptoms being due to a calculus. These symptoms are followed in from a few days to a few months, according to the acuteness of the disease, by the appearance of blood in the urine. This varies in amount, and may consist of a few drops at the end of micturition. The hemorrhages are usually transi- tory, and are not specially influenced by rest, as are those of vesical calculus. Pus is usually present in the urine from the beginning, at first in small amounts, but increasing in quantity as the disease advances. During the act of micturition the stream is often suddenly arrested, the patient checking it voluntarily, owing to the severe pain and spasm. This differs from the stoppage of the stream by a calculus engaged in 826 TUBERCULOSIS. the mouth of the urethra, which is beyond the patient's control and which usually increases the pain. The frequency of micturition, which was at first due to the vesical irritability and exaggerated " distention reflex," is later partially produced by the diminished capacity of the bladder, o^dng to the gradual contraction. In advanced stages of vesical tuberculosis the symptoms are much the same whether the infection is primary or secondary. Protracted cvstitis, which has come on without apparent cause, is always suggestive of tuberculosis. The renal regions, the testes, and the prostate should be examined with care. The judicious and careful use of the cystoscope is of infinite value in arriving at the true nature of the disease if repeated examinations of the urinary sediment have given negative results. Tuberculosis of the urethra, as a primary infection, is extremely rare. Secondary tuberculosis, which is more common, may result from direct invasion from the prostate by continuity or by surface inoculation or bv blood infection from a focus higher up. ^Miliary tubercles in the urethra are not uncommon in patients who die of general miliary tuber- culosis. The chief symptoms of urethral tuberculosis are excessive pain on urination or instrumentation and a marked tendency to bleeding on slight manipulation. When definite ulceration occurs the first ounce or two of urine passed nearly always contains tuberculous detritus. Primary tuberculosis of the urethra may strongly simulate stricture, but the extraordinary amount of pain caused by the most delicate instrumentation, even after the use of a strong solution of cocaine, should lead one to suspect tuberculosis. Tuberculosis of the Prostate and Vesicul-^ Seminales. The prostate is frequently involved in tuberculosis of the uro-genital tract, some writers claiming" that it never escapes. In Krzyincki's cases it was affected in 14 out of 15 males. In 37 males Orth found the prostate involved in 17 cases. The disease may occur as a primar}' infection, but more commonly results from extension from some adjacent or distant organ. Many cases of primarv tuberculosis of the prostate follow chronic folhcular inflammation of the gland. The lowered resistance produced by such an inflammation seems to be an important determining factor. In certain instances prostatic tuberculosis appears to date from an attack of gonorrhoea. The involvement of the posterior urethra in the gonor- rhceal inflammation excites into acti\'ity any slumbering tubercular focus which mav be already existent in the prostate. Secondary infec- tion generallv follows tuberculous involvement of the testes, bladder, or kidney. That following testicular disease is commonest of all. More marked changes occur in primary tuberculosis of the prostate and in cases in which the disease is secondary to involvement of adjacent parts than in those in which it is secondary to pulmonary tuberculosis, for in the latter case death is likely to occur "before the prostatic disease becomes far advanced. In primary tuberculosis of the organ the tubercles generally first appear about "the acini of the glands, although occasionally the sub- mucous tissue of the prostatic urethra may be invaded. In the latter TUBERCULOSIS OF PROSTATE AND VESICULJE SEMINALES. 827 instance tlu' deposit uiulcrgoi's caseation, aiul lc:i reproductive organs of the female have for a long time been known to be occasionally the seat of tuberculosis, but it is only within the last few years that tuberculous att'ections of these parts have been recognized as comparatively frecjuent occurrences. Laparotomy in tuber- culous peritonitis has revealed the fact that in very man\^ instances in women the Fallopian tubes are also involved. This discovery has ex- cited interest in the subject, owing to the strong probability that the tubes may be in many instances the source of origin of the peritoneal disease. The careful and systematic microscopic examination of specimens from the operating room and autopsy table has shown that primary tuberculosis of the tubes is not at all uncommon, and that many cases, which macroscopically would appear to be of a simple inflammatory character, are really tuberculous (J. Whitridge Williams). Genital tuberculosis in the female, as has already been stated, is much less frequent than in the male, the proportion being 1 to 3. The disease is most common between the ages of twenty and forty years — that is, during the period of greatest sexual activity. Cases have occurred as early as ten weeks and as late as eighty-three years of age. Although statistics vary considerably, the frequency of genital tuber- culosis may be judged from the fact that various pathologists have found it present in from 1 to 8.5 per cent, of all autopsies on phthisical women. Kelly had found tuberculosis present in 1 out of every 12 operations for the removal of tubes and ovaries which were the seat of past or present inflammatory disease. Certain portions of the genital tract are attacked much more frequently than others, the order of fre- quency being as follow^s : tubes, uterus, ovaries, vagina, cervix, and vulva. Vulva. — Tuberculosis of the vulva is a rare occurrence, only 3 authenticated cases, in which tubercle bacilli w^ere found or in which inoculation experiments gave positive results, having been reported up to 1893 (Williams). The vagina is practically always involved. The lesion produced exhibits all the characters of an ordinary tubercular ulcer. The presence of tubercle bacilli in the secretions or of tubercles in the scrapings from the ulcer would differentiate the disease from car- cinoma or syphilis, for which it might be mistaken. Vagina. — The vagina is usually involved secondarily to a tubercu- losis of some portion of the genital tract higher up, particularly the uterus. It may, however, be the only seat of tuberculosis in the geni- talia, and Friedliinder claims that it may be the primary focus of the disease in the body. Occasionally it becomes involved secondarily to disease of the bladder or rectum by direct extension, in which case vesico-vaginal or recto-vaginal fistula not infrequently result. The upper third of the posterior wall of the vagina is usually involved, as 830 TUBERCULOSIS. this is the area with which the exudate from tuberculous foci higher up usually comes in contact. The disease may occur either as an erup- tion of miliary tubercles or as an ulcerating surface. Tuberculosis of the vagina might be mistaken for granular vaginitis, hard or soft chancre, carcinoma, or papular and ulcerative syphilides. Here, again, the microscope is of invaluable service in clearing up the diagnosis. Uterus. — Tuberculosis of the body of the uterus is very rare and is nearly always secondary. It is generally associated with tuberculosis of the tubes, from which the process extends. The uterus, however, may be the only seat of tuberculous disease in the body. Rarely does the process extend beyond the internal os to involve the cervix. It may occur as a miliary tuberculosis, with or without the formation of ulcerations. In nearly all cases there is at first an eruption of miliary tubercles in the endometrium, a form of the disease met with par- ticularly at autopsies on women who have died of some other disease, the condition never having been suspected during life. A few minute ulcerations may be present. The endometrium between the tubercles may be reddened or may appear normal. The form of uterine tuber- culosis generally met with, however, is the chronic diffuse tuberculosis (caseous endometritis). Here the entire uterine cavity is filled with caseous material ; the surface of the endometrium is covered with exu- date, and presents irregular and jagged ulcers, the floors of which are studded with tubercles in various stages of development. Later the muscular wall of the uterus becomes infiltrated with tubercles and undergoes hypertrophy. The cervical canal may become obstructed by caseous exudate, and the latter, accumulating in the uterine cavity, produce a pyometra. The cervix of the uterus is much less frequently involved than the body. It is seldom associated with disease of the latter, but not com- monly occurs along with vaginal tuberculosis. Friedlander reported a case in which it was the only seat of tuberculosis in the body. The disease generally presents itself in the form of an eruption of miliary tubercles or as an ulcerating surface. In advanced cases the condition might be mistaken for carcinoma of the cervix, but the examination of sections of a minute portion of the diseased area would reveal the true nature of the disease. Fallopian Tubes. — The Fallopian tubes are by far the most frequent seat of genital tuberculosis. In a large percentage of cases the disease is associated with tuberculosis of the uterus or ovaries or both. The special attention which has been paid to local affections of these parts by gynecologists during the last decade has taught us that primary tuberculosis of the tubes is not at all uncommon. The disease may produce a most characteristic form of salpingitis, in which the tubes are enlarged, the walls thickened and infiltrated, and the contents cheesy. The fimbriated extremity is usually closed, and the fimbrise are frequently bound down to the ovary. When both ends of the tube become occluded a very large pus sac may result. Between this and the mildest cases, in which only a few visible tubercles are studded over the mucosa, all grades exist. The condition is usually bilateral. It may occur in quite young children. Although, as a rule, the disease is evident on macroscopic examina- tubP.rculosis of the brain and cord. 831 tion, yet there are specimens wliit-li to the iiakt-d eye appear to be ordinary cases of salpingitis, but which on microscopic examination show tlie mucosa to be studded Avith numerous miliary tubercles (Welch antl \\'illiams). These cases of " unsuspected tuberculosis" constitute 75 per cent, of all the cases of tuberculosis of the Fallopian tubes which have l)een operated on in the :ical department of the Johns Hopkins Hospital. Tuberculous salpiui^itis may cause serious local disease with abscess formation, and it may be the starting point of peritonitis. It is practically impossible to make an absolute diagnosis of tuber- culosis of the tubes. The association of a thickened tube with an ill delined mass in the abdominal cavity should arouse one's suspicions. Ovarii. — Although comparatively rare, tuberculosis of the ovary is more common than was formerly supposed. It may be the only seat of tuberculosis in the genital tract, as is sometimes the case when found associated with tuberculous peritonitis. Primary tuberculosis of the ovary probably never occurs. The disease may manifest itself as an eruption of tubercles over the surface of the ovary, or there may be more extensive involvement with the production of an ovarian abscess. YII. TUBERCULOSIS OF THE BRAIN AXD CORD. In connection vdx\\ acute miliarv tuberculosis a few scattered g'ran- iiles may be met with on the meninges. One of the special forms of acute tuberculosis affects the meninges, and has already been described. (See Acute Tuberculous Meningitis, page 754.) The disease occurs in two forms in the brain — namely, a localized chronic meningo-eucephalitis, in which there is thickening of the mem- branes and small nodular tubercles ; and the larger tuberculous tumor, which may attain the size of a walnut or larger, and which is often solitary. These forms develop slowly, are essentially chronic, and have the clinical characters of a tumor. The tuberculous brain tumor is met with most commonly in children. Of 148 cases collected by Bribram, 118 were under fifteen years of age. Tubercles are usually found in other organs as well, particularly the lungs and the bronchial glands. In a few rare cases the brain alone is involved. They are frequently mnltiple — in 100 out of 183 cases, according to Gowers ; in 20 per cent., according to Starr. The growths range in size from a pea to a walnut ; occasionally larger, somewhat diffuse masses are found. They are almost always attached to the me- ninges ; rarely are deep in the brain substance. The masses may really look imbedded in the white matter of the cerebrum, but on section are found to be attached to the pia mater at the bottom of a sulcus. They occur most frequently in the cerebellum, next in the cerebrum, and then in the pons. The tuberculous tumor is, as mentioned, usually attached to the meninges, is grayish yelloAV in color, firm, hard on section, cheesy, yellow, and is often surroimded by a translucent connective tissue. The centre of the growth may be semi-diffluent. In other cases lime salts are deposited. The tuberculous growth may produce symptoms by causing destruction of, or pressure upon, the contiguous brain sub- 832 TUBERCULOSIS. stance, or, growing about the arteries of the meninges, maA^ block the blood current and cause areas of softening. Growing about the longi- tudinal fissure, it may compress the sinus and lead to thrombus forma- tion ; and, lastly, it not infrequently excites a tuberculous meningitis. The symptoms of tuberculous growths in the brain are those of tumor. The occurrence in children, the coexistence of tuberculous lesions elsewhere, or the presence of a healed gland or joint disease are among the features which would suggest the tuberculous character of the growth. Tuberculosis of the spinal cord occurs in the same forms as in the brain. Acute tuberculous meningitis is very rarely confined to the cord ; it is almost always cerebro-spinal. A tuberculous tumor in the cord is rare. Of 130 tumors of the cord collected by Lloyd, 15 were tubercle. Herter has reported 3 cases, and collected 24 instances from the literature, in all of which save 1 the condition was secondary. VIII. TUBERCULOSIS OF THE MAMMARY GLA^'D. Excellent descriptions of tuberculosis of the breast were given by Astley Cooper in 1829, by Nelaton in 1839, and by Velpeau in 1854. For nearly three decades following the latter date very few cases were recorded, and it was not until the appearance of Dubar's monograph in 1881 that mammary tuberculosis became generally recognized. With the exception of histological details, Velpeau's account has never been surpassed. Tuberculosis of the breast is much more common than has hitherto been generally supposed. Mandy^ has collected 40 cases, only 1 of which occurred in the male. Other cases of mammary tuberculo- sis in the male have been reported by Horteloup and Poirier. The disease is commonest between the fortieth and sixtieth years. It is said never to occur in children, but Payne observed a case in an infant which was also the subject of general tuberculosis. Traumata and con- ditions associated with the puerperal state seem to favor its development. The majority of cases occur in women who have borne children. Of 35 cases collected by Powers,^ 22 were in married women, and of these 21 had borne children. The right breast appears to be oftener affected than the left. In only 1 of Powers' cases were both glands diseased. Velpeau recognized that the disease may be either primary or sec- ondary, and subsequent investigations have borne out his views. In primary cases it seems likely that infection takes place through the milk ducts, although the bacilli may enter from infected fissures by way of the lymphatics. The great majority of cases are secondary to some other focus in the body, usually the lungs. Mammary tuberculosis occasionally occurs in the form of scattered nodules throughout the gland, resembling often, in the early stages, alveolar hypertrophy. Both the parenchyma and the stroma of the gland are involved, and the nodules may undergo caseation. A second variety of the disease occurs in the form of rather large caseous tumors, which on section closely resemble tuberculous lymph glands. These soften and break down, and frequently involve the skin. Fistulse ' Brima' Beitrdge, viii. " Annals of Surgery, 1894. TUBERCULOSIS OF Till': ARTERIES. 833 which discharge ;i thin caseous matter rrc(jtiently (leveh)i). These, together with the idcers, present a characteristic tuhereuh)us aspect. The nipple is quite often retracted in the aho\'e forms. Mammary tuberculosis not infrequently takes the form of a cold abscess. The axillary glands are involved in about two thirds of the cases. The dangers to which children are exposed by sucking Momen who are the subject of tuberculosis of the breast is shown in a ease i'e])orted bv Niepce/ in which a nurse whose milk contained tubercle bacilli su(dcle"d a child born of healthy parents, with the result that the child soon afterward died of tuberc;ulous meningitis. The disease runs a chronic course, lasting months or vears. The diagnosis can be made by the general appearance of the fistuke and ulcers and by the iinding of tubercle bacilli. Simple opening of the abscesses, with scraping of the cells, is not sufficient. With a radical operation, in which the breast and axillary glands are thoroughly removed, the chances against secondary local recurrence are good. The skin of the breast is occasionally the seat of lupus, which mav affect either the areolar region or the skin elsewhere. In 1836, Bodor described an interesting condition of the l^reast in subjects who suffered from pulmonary tuberculosis, in which the gland became temporarily enlarged, without there being any local tuberculous lesions. The condition has been quite frequently observed since that date. The enlargement is only temporary, disappearing in a few weeks. It is commonest in men, and usually only one gland is affected. The condition is usually found on the same side as the most advanced pul- monary changes. The breast is firm to the touch, and is often quite sensitive to pressure. Thomas^ has collected several cases, and reports 1 himself in which the histological examination showed the enlargement to be due to the development of fibrous tissue about the acini, which were considerably atrophied. IX. TUBERCULOSIS OF THE ARTERIES. In chronic tuberculous disease of the lungs and other organs the arteries are often involved in an acute infiltration ; tubercles mav develop in the walls and proceed to caseation and softening, which mav be fol- lowed by the formation of a thrombus, or hemorrhage mav occur. The recent observations of Hektoen, referred to under Tuberculous Men- ingitis (page 756), show that there may be the production of tubercles of the intima, and a diffuse subendothelial proliferation due to the implan- tation of bacilli direct from the blood. By direct extension into vessels the bacilli are widely distributed. Tuberculosis of the smaller arteries plays a very important role in meningitis, in which from the adventitia the tuberculous disease may invade the media and intima and lead to occlusion or thrombus formation. Primary tuberculosis of the larger bloodvessels is almost unknown. Occasionally the aorta is invaded from a cheesy mass in a lymph gland outside the vessel. In a case reported by Flexner a patient with chronic tuberculosis presented a nodular mass in the aorta 2.5 cm. 1 Paris Thesis, 1886. - Ibid., 1893. Vol. I.— 53 834 TUBERCULOSIS. below the origin of the left subclavian artery. It was pale, translucent, apparently made up of several smaller masses. It was found to be a tubercle seated directly upon the intima, and consisted of several masses with caseous centres. The most interesting feature was that both media and adventitia were perfectly normal. There were no caseous glands in the vicinity of the aorta. Prognosis in Tuberculosis. At one time or another tubercle bacilli effect a lodgement in a con- siderable proportion of all individuals, justifying the old German axiom : " Jedermami hat am Ende ein bischen TubereuloseJ' Infection with the bacilli does not necessarily mean the establishment of a pro- gressive and fatal disease. The subject is a wide one, and there are several aspects in which it may be considered : (a) The Natural or Spontaneous Cure of Tuberculosis. — The spon- taneous healing of local tuberculosis is an every-day aifair. Disease of the bones, of the joints, and adenitis may heal without the aid of the knife or of medicines. The percentage of persons with evidence of tuberculous lesions, active or obsolete, is remarkably high. It is stated that in the autopsies at the Paris Morgue, made, as a rule, upon the bodies of persons who have committed suicide or who have been killed accidentally, nearly 75 per cent, show tuberculous foci — either calcareous or cheesy nodules in the mesenteric or bronchial glands, or puckering Avith caseous or calcareous nodules at the apices. The per- centage in observations which have been made of late years on this point in hospitals has been very striking, as showing the widespread prevalence of the disease. In 1000 autopsies at the Montreal General Hospital, excluding the 216 cases dead of pulmonary tuberculosis, there were 59 cases which presented tuberculous lesions in the lungs. This estimate is low, as I excluded (which I really should not have done) the solitary cheesy nodule unless there were colonies of tubercles in the vicinity. These 59 cases died of various diseases and at various ages, a majority of them between forty and sixty years. My experience tallies closely with the larger figures of Heitler, taken from the Vienna post-mortem records, in which, of 16,562 cases in which the death was not directly due to pulmonary tuberculosis, there were 780 instances of obsolete tubercle. The more recent observations have shown a much higher percentage : thus, Bollinger found traces at autopsy of former tuberculosis in 27 per cent. ; Massini in 39 per cent. • and Harris in 38.8 per cent. The spontaneous arrest of pulmonary tuberculosis is, after all, a very common affair. Clinically it is shown by the complete recovery of patients in whose sputa elastic tissue and bacilli have been found, and anatomically by the presence of lesions in all stages of repair. A clear distinction should be drawn between arrest and heal- ing. The latter term may be applied when in the granulation products and associated pneumonia a scar tissue develops and the caseous areas become cretaceous. When the fibroid change encapsulates, but in- volves the entire tuberculous area, the tubercle may be called involuted or quiescent, but it is not harmless, as may be shown by the fact that usually about such apparently quiescent areas there are small colonies rjioayo^i'S l\ tuherculosis. 835 of iniliarv tubercles. Cavities of any size rarely heal, in the proper sense of the term. They may become ^-reatly reduced in size, and an U])[)er lobe of a luui;" with numerous cavities may be so contracted by sclerosis and shrinkage that it lias not one third of its natui-al dimen- sions. Ijaennec described with _ii:reat accuracy the natural process of cure in tuberculosis, and suo;<2;ested that as tubercles in the g-lands heal, the same could take place in the lesions of the lungs. At the apices of the lungs the following common conditions arc held to signify healed and obsolete tub(>rcuh)us processes : (1) The thickening of the ])]eura, usually at the posterior surface of the apex, Avith subjacent induration for a dis- tance of a few millimetres. This has, perhaps, no greater significance than the milky patch on the pericardium. (2) Puckered cicatrices at the apex — cicatrices compIMes of Laennec — depressing the pleura and on section showing a large pigmented fibrous scar. The bronchioles in the neighborhood may be dilated, but there are neither tubercles nor cheesy masses. This may sometimes, bnt not always, indicate a healed tuber- culous lesion. (3) Puckered cicatrices with cheesy or cretaceous nodules, and with scattered tubercles in the vicinity. (4) The cicatrices fistuleuses of Laennec, in which the fibroid puckering has reduced the size of one or more cavities which communicate directly with the bronchi. (6) The FcK-tors of Prognosis in Established Pulmonary Tuberculosis. — Many years ago Flint called attention to the self-limitation and intrinsic tendency to recover in well marked pulmonary tuberculosis. Of 670 cases, 44 recovered, and in 31 the disease was arrested. The factors upon which one may lay stress in estimating the prognosis in a case with well marked symptoms, say at one apex, are as fol- lows : Previous good health and a sound ftimily history are perhaps the most important. A strong digestion is a third most important favoring factor. A fourth, and perhaps most essential of all, is the possibility of living in a favorable environment. A slow, gradual onset \vithout high fever and without rapid consolidation and caseation is also a good omen. Cases beginning with pleurisy appear to run a more pro- tracted and favorable course. Of the special symptoms fever is perhaps the most valuable element. With apyrexia the local disease rarely makes much progress. The higher, the more irregular, and the more persistent the fever, cseteris paribus, the more grave is the prognosis. The facility with which the fever is reduced by the open-air treatment is another important point, as are also the frequency and severity of the recur- rences of the pyrexia which are so common in the chronic forms of the disease. Recurring attacks of haemoptysis are unfavorable, more par- ticularly when they are followed by spells of high fever. Not very much stress is to be laid upon the number of bacilli in the sputa, since they may be extraordinarily abundant from a very small focus of local disease. On the other hand, persistence for a long period in very large numbers is usually an unfavorable element in prognosis, while a gradual diminution is a hopeful feature. In pulmonary tuberculosis the primal vice control the situation, and the better the digestion and the more able the patient is to take a varied and nourishing diet the better are his prospects. There are no more unfavorable cases than those in which, early in the disease, w'itli pronounced gastric symptoms, there is a marked chloro-anfemia. 836 TUBERCULOSIS. (c) The Duration of Pulmonary Tuberculosis. — Laennec placed the average duration at two years. As mentioned, a case of acute pneu- monic phthisis may prove fatal within ten days, whereas in the chronic form the disease may persist for twenty or more years. The probable duration in each individual case must be estimated according to the factors already mentioned. The large statistics of different authors vary very much ; thus in Pollock's tabulation of over 3500 cases the mean duration of the disease was a little over two years and a half. " Williams's returns for 1000 patients in the better classes give only 198 deaths, and the mean duration of life in the latter after the com- mencement of the disease was seven years and eight months, while only 36 per cent, of these patients lived less than nine years. Of the survi- vors, the average duration of whose life was eight years and two months, as many as 68 patients, or 8 per cent, of the whole number, had lived more than twenty years from the commencement of the disease " (Wilson Fox). (d) Tuherculosis and Marriage. — Under the subject of prognosis comes the question of the marriage of persons who have had tuberculo- sis or in whose family the disease prevails. The folloAving brief state- ments may be made with reference to it : (1) Subjects with healed lymphatic or bone tuberculosis marry with personal impunity and may beget healthy children. It is undeniable,, however, that in such families scrofula, caries of the bone, arthritis, cerebral and pulmonary tuberculosis are more common. Which is it, " heredite de graine ou heredity de terrain," as the French have it — the seed or the soil, or both ? AVe cannot yet say. The risks, however^ are such as may properly be taken. (2) The question of marriage of a person who has arrested or cured lung tuberculosis is more difficult to decide. If a male, the personal risk is not so great ; and when the health and strength are good, the external environment favorable, and the family history not extremely bad, the experiment — for it is such — is often successful, and many healthy and happy families are begotten under these circumstances. In women the question is complicated with that of childbearing, which increases the risks enormously. With a localized lesion, absence of hereditary taint, good physique, and favorable environment marriage might be permitted. When tuberculosis has existed, however, in a girl whose family history is bad, whose chest expansion is slight, and whose physique is below the standard, the j^hysician should, if possible, place his veto upon marriage. (3) With existing disease, fever, bacilli, etc. marriage should be abso- lutely prohibited. Pregnancy and parturition hasten the process in almost every case. There is much truth, indeed, in the remark of Dubois : " If a woman threatened with phthisis marries, she may bear the first accouchment well ; a second, with difficulty ; a third, never." (On this subject the monograph of Reibmayr, Die Ehe Tubercidoser, may be consulted with advantage.) Prophylaxis in Tuberculosis. The measures directed to the prevention of tuberculosis may be con- sidered under — first, those which are concerned with the destruction of 'niOPlIYLAXIS IS TI'BERCULOSIS. 8:37 the witloprcad livrin ; aiul sccoikI, iiieasiires diroctetl to maintain tiic nutrition of the individual at its niaxiniuni. General Mcdsurcx. — ((/) Disinfection of the sputum. The most com- mon method of dissemination of the disease is with the ex])ectoration of tubercuh)us patients. In a dried form it is spread l)roadeast witii the dust, and every patient in the stage of eavity is a focus of danger. W'lien one considers that such a patient may, as shown by Xuttall, expectorate, at a very moderate estimate, from two to four billions of bacilli in the twenty-four hours, the danger is by no means imaginary. The patient .should be directed always to use a spit-cup or the handkerchief, and never to spit (»n the floor or on the ground. The sputum may be disin- fected bv tliorouii:h boilino- or a solution of carbolic acid of the strena-th of 1 : 20 may be put into the spit-cup. The handkerchiefs used by the patients should be thoroughly boiled. It should be explained frankly to the patient that the risk practically is from this source alone, and the friends should be given to understand that with due precautions the danger of nursing and caring for a consumptive is very s/igJit indeed. The patient should occupy a single bed in a well-ventilated, airy room. In the advanced stages, when the diarrhoea is present, the stools should be carefully disinfected. The disgusting habit of expectorating in public, which is so common in this country, should be tabooed, and in public conveyances, such as street-cars, should be strictly forbidden. It is no hardship to ask a con- sumptive to carry some convenient form of spit-cup. As already mentioned, the public has already been pretty widely instructed as to the importance of care in dealing with tuberculosis. Hospital authorities and health boards could issue with advantage a leaflet such as that which Cornet has prepared, which reads as follows : " Protection from Consumption. " The most destructive disease of the human race is consumption (tuberculosis ). It carries off a seventh of the population. In Germanv alone there die yearly of consumption wellnigh 150,000 people. " It has now been discovered that this disease is caused by the inhala- tion of a germ, a so-called bacillus. It is infectious — that is, it can be given by any person to another. But neither the breath nor the per- spiration of the patient is at all dangerous, as used to be supposed. Infection generally takes place through the spit, and, according to the latest inquiries, especially when the spit is discharged by the consump- tive upon the floor or in a handkerchief, where it dries and becomes dust, and some of the swarm of germs contained therein are inhaled by healthy people. " Many other diseases, such as diphtheria, pneumonia, and various forms of catarrh, may be communicated in a similar wav. " Consumptives endanger not only those about them, but themselves, through the drying of their spit, because they again inhale the dis- charged and dried bacilli, and thus infect hitherto sound parts of their lung's. " Such infection may be avoided if consumptives — and, indeed, all who have a chronic cough with expectoration — keep this expectoration 838 TUBERCULOSIS. always moist ; if they give up spitting on the floor or into a hand- kerchief, and always use a spittoon which is emptied down the water- closet. " Spittoons must be placed wherever necessary, in every enclosed space frequented by men. They ought not to be filled with sand or sawdust, but either left entirely empty or supplied with a very lit- tle water. They ought to be at hand in sufficient numbers in every apartment of houses, in workshops and factories, in counting-houses, schools, offices, public places, in corridors and on stairs, so as to give every one a convenient opportunity of observing these injunctions. " In this way healthy people who have to remain within the same room as consumptives will be almost entirely protected from infection. " Posters ought to be put up in factories, workplaces, etc. forbidding most strictly spitting upon the floor or into a handkerchief. " On the street, where spitting can scarcely be prevented, certain other circumstances diminish the risk of infection. " Let every man, even though suffering from an ordinary cough, dis- charge his spit, not on the ground, not in a pocket-handkerchief, but always in a spittoon. " Milk ought, as far as possible, to be used only after boiling, espe- cially by children, invalids, and convalescents. " By the strict observance of these injunctions consumptives are made almost harmless to those about them ; and all the more that the bacilli can live outside the body only for about six months, it may be hoped that, if these rules are followed out by the sick, consumption in general will diminish." (6) In large cities the health boards should be empowered to carry out certain regulations. The measures which have been adopted by the Board of Health at New York are not only extremely reasonable, but may be recommended to other cities as models to follow : "1. The department will hereafter register the name, address, sex, and age of every person suffering from tuberculosis in this city, so far as such information can be obtained, and respectfully requests that here- after all physicians forward such information on the postal cards ordi- narily employed for reporting cases of contagious disease. This informa- tion will be solely for the use of the department, and in no case will visits be made to such persons by the inspectors of the department, nor will the department assume any sanitary surveillantie of such patients, unless the person resides in a tenement-house, boarding-house, or hotel, or unless the attending physician requests that an inspection of the premises be made ; and in no case where the person resides in a tene- ment-house, boarding-house, or hotel Avill any action be taken if the physician requests that no visits be made by inspectors, and is willing himself to deliver circulars of information or furnish such equivalent information as is required to prevent the communication of the disease to others. " 2. Where the department obtains knowledge of the existence of patients with pulmonary consumption residing in tenement-houses, boarding-houses, or hotels (unless the case has been reported by a physician and he requests that no visits be made) inspectors will visit the premises and family, will leave circulars of information, will instruct PllUVllYLAXlS AV TlBKlirUUhSlS. 839 till' ptrsoii siitl\'vin<2: from ('onsiini])ti()ii luul the family as to tlie measures which should be takeu to <2;uar(l a<;:iiust the spread of the disease, and, if it is considered neeessarv, will make sueh rec^onimendatioiis for tlu; cleansing or renovation of the a[)artment as may he re(|uired to render it free from infections matter. "3. In all cases where it comes to the knowledge of the tlepartment that premises which have been occupied by a consumptive have been vacated by death or removal, an inspector will visit the ])remises and direct the removal of infected articles, sueh as carpets, rugs, l)edding, etc., for disinfection, and will make such written reconnnendations to the board as to the cleansing and renovation of the apartment as may be required. An order embodying these recommendations will then be issued to the owner of the premises, and compliance Avith this order will be enforced. No other persons than those there residing at the time will be allowed to occupy such apartments until the order of the board has been complied with. Infected articles, sueh as carpets, rugs, etc., will be removed by the department, disinfected, and returned, without charge to the owner. " 4. For the prevention and treatment of pulmonary tuberculosis it becomes of vital importance that a positive diagnosis shall be made at the earliest possible moment, and, that the value of bacteriological examinations of the sputa for this purpose may be at the service of physicians in all cases not under treatment in hospitals, the department is prepared to make such bacteriological examinations for diagnosis, if samples of the sputa, freshly discharged, are furnished in clean, Avide- necked, stoppered bottles, accompanied by the name, age, sex, and address of the patient, the duration of the disease, and the name and address of the attending physician. Bottles for collecting such sputa, with blank forms to be filled in, can be obtained at any of the drug stores now used as stations for the distribution and collection of serum tubes for diphtheria cultures. After the sputum has been obtained, if the bottle, with the accompanying slip filled out, is left at any one of these stations, it will be collected by the department and examined microscopically, and a report of the examination forwarded to the attend- ing physician free of charge. " 5. The authorities of all public institutions, such as hospitals, dispensaries, asylums, prisons, homes, etc., will be required to furnish to the department the name, sex, age, occupation, and last address of every consumptive coming under observation within seven days of such time." (e) Inspection of Dairies. — A certain proportion of cases of tubercu- losis, particularly in children, are caused by the drinking of milk of tuberculous cows. Every dairy supplying milk to the city should be systematically inspected, and full power should be given to confiscate and kill suspected animals. Where this systematic inspection is not carried out the milk should be boiled. {d) Skilled veterinary inspection should be made at the abattoirs of the carcasses of all animals. There is much less danger of infection through meat than through milk. The widespread diffusion among the public of knowledge on the sub- ject of tuberculosis will undoubtedly be very beneficial. Such societies 840 TUBERCULOSIS. as have been organized in Philadelphia for the prevention of the disease will do great good by teaching proper measures of protection against the disease and by influencing public opinion in the right direction. Many persons, even among physicians, regard it as a great hardship that a consumptive should be under the surveillance of the health board, but the measures required to be carried out in the interest of public safety are neither exacting nor irksome. Sanitarians, however, must not be content with such measures as are directed against the seed alone. In the larger cities, particularly those with narrow streets and high tene- ment-houses, these measures must be combined with others directed to improvement of the conditions under which many of the people live, particularly to obtaining clean, dustless streets and affording a maximum amount of fresh air and sunshine. Individucd Prophylaxis. — A mother with pulmonary tuberculosis should not be allowed to suckle her child. An infant born into a family in which tuberculosis has prevailed or born of tuberculous parents should be watched with special care, and guarded particularly against catarrhal affections of all kinds. The convalescence from the fevers of childhood, more particularly measles and whooping cough, should be watched with special attention. A frequent cause of impaired vitality in young children is the condition of the tonsils. On the first indication of mouth-breathing a thorough examination should be made for adenoid vegetations, which if present should be removed. If a child has also recurring attacks of tonsillitis and the organs are at all enlarged, it is best to have them cut out. The child should be clothed in flannel and live in the open air as much as possible. The sleeping room at night should be well ventilated. It is a good practice for the mother to bathe the throat and chest of the child every morning with cold water. The meals should be at regular hours, the food plain and substantial, and the child should be encour- aged to drink milk. Many children have when young an aversion to fats of all kinds, but they should be encouraged to take cream and but- ter and milk. If the child becomes anaemic or its health seems failing, cod-liver oil, the syrup of the iodide of iron, and arsenic are the best tonics. If the thorax is naturally long, narrow, and contracted, something may be done to improve the condition by systematic pulmonary gymnastics and regulated exercises. In the choice of an occupation preference should be given to an out-door life. Families with a marked pre- disposition to the disease should, when jjossible, reside in an equable climate. Treatment op Tuberculosis. (a) Dietetic Treatment. — As the healing of a tuberculous process is largely dependent upon the state of general nutrition, the question of diet becomes of the very first importance. Persistent failure properly to digest food is an unfavorable feature in any case. The variations in this respect are remarkable. There are patients in whom the appetite and digestion are not disturbed in the slightest degree, and while, as a rule, these are the most hopeful subjects, even in such, in spite of active powers of digestion and assimilation, tuberculosis may make rapid prog- ress. So soon as the disease is recognized the practitioner should Ti:i:.\TMi:y'r of 'niiKiirrLOsrs. 841 empluisizt' to the jKitieiit and to tlic friends the necessity of the most carefnl attention to diet, and his instrnetions shouhl be speeiiie, not genera h 111 the initial stages, with irregnhir f(!ver and ii-ritative cougli, there is loss of appetite, at times nansea or even a jiositive aversion to food. Care should he taken that this eondition is not aggravated hy eongh mixtnres, ereasote, cod-liver oil, and hypopiiosphites with which tiie patient is too often at this period drenched. In the prononnced gastric irritability of the early stages it is best to confine the ])atient to a liquid diet, consisting of one of the milk preparations, with or withont egg albumen and meat juices. The milk may be taken either raw, diluted with Apollinaris or seltzer water, or half an ounce of lime water is added to each glass, or it may be peptonized, though, as a rule, the dis- agreeable taste is very objectionable to tuberculous patients. Butter- milk, koumyss, or kefir sometimes agrees much better than the simple milk. When there is an insuperable objection to milk, the meat juices and scraped meat and meat cakes may be used, and these articles made from the fresh meat are to be much preferred to the beef peptonoids and other similar preparations on the market. Eggs form a most important article of dietary in early tuberculosis. Patients are not always shle to eat the yolk, but when the proper amount of milk is not borne the egg-white is a useful addition, and is usually easily digested. When there is much gastric irritability, a glass of hot w^ater early in the morning, or in extreme cases lavage, will be found useful. It is rarely necessary to resort to Debove's method of forced feeding, in which, after lavage of the stomach, a mixture is given through the tube, containing a litre of milk, an egg, and one hundred grammes of very finely minced meat. A patient will sometimes take this three times a day without special disturbance. It is not often that one has to resort to rectal alimentation in the early stages of tuberculosis. When solid food can be taken a varied diet may be given, in which the albu- minous elements largely prevail, and to which are added the more easily digested forms of vegetables. Usually four or even five light meals are better borne than three large ones. On a mixed diet the patient does not need so much milk, and if plenty of cream and good butter is taken it is well not to insist upon its use. These measures may prove of no avail whatever in the treatment of a case unless the patient's surround- ings are favorable, and improvement in the digestion may not occur until he removes from home or begins an open-air life. As already mentioned, very special care should be taken not to aggravate the dys- pepsia by medicines. As a rule, the bitter tonics, with acids, and the preparations of malt are well borne and are very useful. In the later stages of tuberculosis the dyspeptic symptoms may again be the most troublesome symptoms to combat, and the patient usually does best upon the albuminous diet referred to above. Alcohol should not be given as a routine matter to tuberculous patients. It is often beneficial in cases with feeble digestion and high fever and in the later stages of the disease, when the heart's action be- comes rapid and weak. There are cases in which three or four ounces of whiskey, taken as milk punches or given with the egg albumen, seem to promote the appetite and improve the general nutrition. Routine 842 TUBERCULOSIS. administration is not advisable, and there is no evidence to uphold the old idea that the persistent use of alcohol promotes fibroid changes in the tuberculous areas. (6) Pulmonary Gymnastics. — In incipient cases much benefit results from systematically carried out forced inspiratory movements, which increase the chest capacity and favor particularly expansion of the apices. The patient should be directed to draw slowly the fullest possi- ble inspiration, raising at the same time the arms above the head. At the end of the act the breath may be held for a few moments. These efforts may be repeated slowly for from ten to fifteen minutes, morning and evening. The practice should be carried out systematically, and intercurrent hsemoptysis or high fever should be alone regarded as con- traindications. Sometimes pains in the side are produced at first, prob- ably from stretching of pleural adhesions, but they usually disappear with persistence in the effort. (c) Climatic Treatment. — The essence of the treatment of tuber- culosis by climate is a life in the fresh air. A majority of the un- fortunate victims of tuberculosis live in small rooms in small houses, and even the outside air can scarcely be called pure ; yet even in our larger cities it is at any rate fresh in comparison with the quality of the air breathed in rooms heated above 70° and with all possible ave- nues of ventilation closed. As a large proportion of all patients are unable to seek any change, the first duty of the physician is to see what can be done in the way of fresh-air treatment at home. The patient and friends must first be convinced of the necessity for fresh air and their minds disabused of the dread of catching cold. Even in small houses the sunshine reaches some rooms for a certain period of the day^ and the patient should be covered warmly in the bed, the bed wheeled in the sunshine, and the windows opened ^\^dely. In other instances the patient may rest for hours on a couch on the veranda. Even in the winter months no degree of cold contraindicates this open-air life. With plenty of rugs and clothing this practice may be carried out even with the most delicate patients, who, as a rule, quickly learn to- appreciate the benefit. The sleeping room should have a southern exposure, and if possible an open fireplace. The patient should sleep with the window partially open, and it is an easy matter even in small rooms to prevent any draught from blowing directly upon the bed. In the comparatively limited number of persons who are able to- leave their homes the doctor is called upon first to decide Avhether the patient is in a condition to travel, and second to choose the locality to- which to send him. Patients with disease localized at one apex and without high fever or much constitutional disturbance can be sent away with advantage. Cases "svith rapid tuberculous consolidation, high and irregular fever, and rapid loss in weight are better at home until some lull takes place, or, at any rate, until there is some positive indication that the case is not one of phthisis florida. With well marked cavities, hectic fever, night sweats, and progres- sive emaciation the physician should, when possible, resist the importu- nities of the patient and friends (which are often under these circum- stances most urgent) and keep the subject at home. In deciding upon a suitable climate there are many questions to be Tin: ATM EST OF Tl'IIERCULOSIS. 843 considered besides those relatiiii:' directly to the disease, ])articularly tiie patient's ciivinnstances, constitution, etc. The climatic treatment of tuberculosis is, after all, only the open-aii- plan under more favorable auspices. There arc three requirements in a suital)le climate : pure atmosphere, an equable temperature not subject to rapid variations, and a maximum amount of sunshine. Livinlic institutions in snitaldc localities not far distant, to which cases of cai'ly pulnionaiy tiihci'cnlosis can be sent for systematic treatment. The civic health board will in future provide for two classes of pulmonary tuberculosis — the early curable cases, which will be sent to sanitaria, and the chronic, incurable cases, which will be cared for in Avell conducted hospitals in the immediate vicinity of the city. ((') GKNKiiAii Mkdicai. TREATMENT. — So far as wc know, there are no agents wdiicli have a s})ecial and pecidiar action on the tuberculous processes. The chief remedies employed against the disease influence the general nutrition, increase the normal physiological resistance, and perhaps render the tissues less liable to invasion. The following are among the most important remedies which act usefully in this w'av : Creasofe and its Dcvivdtivoi. — Under the use of these preparations many tuberculous patients increase in weight and present a general amelioration of the local symptoms. The best beechwood creasote should be used, given either in pill form or in capsules, alone or, as Soramerbrodt recommends, with cod-liver oil. If the pills and capsules disagree, it may be given in a solution with tincture of gentian, alcohol, and sherry wine. Sometimes the carbonate of creasote is better borne by the stomach ; as it contains over 90 per cent, of creasote, the dose is the same. The good effects of creasote depend very much upon the amount the patient is able to take. One rarely sees such good effects from the small doses, though it is well to begin with a couple of minims twice a day. Patients who are tolerant of large doses do better, and ten, or fifteen, or twenty minims, or even half a drachm, three times a day may be taken. If, as is only too frequently the case, the drug dis- turbs the stomach, it may be given by the rectum as an emulsion with oil and e^or. Other methods are by inhalation and subcutaneously. Of derivatives of creasote, guaiacol is the one which has been most frequently used. It may be administered in pearls of one or tW'O min- ims three times a day, or it may be given hypodermically in doses of one minim in olive oil, and is very often for this purpose combined with iodoform. The carbonate of guaiacol may be substituted in doses of from three to five grains. Creasote has no direct action on the tubercle bacilli, but under its use in some cases the cough lessens, the expectoration diminishes, the sweats disappear, and the general nutrition improves. It constitutes the least unsatisfactory drug in the treatment of the disease. Arsenic influences very favorably the nutrition, and may be used in doses of from three to five minims of Fowler's solution three times a day, increasing if it is well borne. In pill form, in doses of from Jg to gljy, increasing up to ^l^" of ^ grain, it is less apt to disturb the stomach. Patients who can take large doses for a considerable period of time are sometimes much benefited. The hi/pophosphites, of \Yhich various ])reparations are on the market, are useful as general tonics. They have no specific influence upon the tuberculous processes. The hypophosphite of lime and the syrup of the iodide of iron are sometimes found useful in c()ml)i nation. Cod-liver oil is useful in many forms of tuberculosis. It acts better 846 TUBERCULOSIS. in children than in adults. It may be given in teaspoonful doses three or four times a day. When well borne and assimilated its use is often followed by a marked im2:>rovement in the general condition. In an emulsion with hypophosphites it is sometimes better borne. In the glandular tuberculosis of young children it seems particularly bene- ficial. Iron is useful in the anaemia of tuberculosis under certain conditions. When much fever is present or when digestion is greatly disturbed it is useless, but in the chloro-ansemia of the early stages there is no remedy more valuable. Great care must be taken not to disturb the stomach, particularly with the stronger preparations of iron. Children usually take the syrup of the iodide of iron readily. (/) Treatment of Special Symptoms in Pulmonary Tuber- culosis. — (1) Fever. — No single condition in tuberculosis is more diffi- cult to combat than the pyrexia. Wlien high and j)ersistent the patient should be at rest, and when practicable in the fresh air and sunshine for a considerable part of each day. Sponging with tepid water will be found beneficial. Drugs are most unsatisfactory. Quinine, digitalis, and the salicylates may be tried, and the combination of the two former drugs is sometimes followed by good results. Antipyrine and phena- cetin, if used at all, should be employed with caution, as in full doses both these drugs are apt to cause much depression. The external appli- cation of guaiacol, fifteen to twenty-five minims, rubbed on the skin, is often followed by a prompt but transient reduction in the fever. (2) Simating. — This is frequently associated with the fever, particu- larly in the later stages of the disease. It may occur independently as a result of exhaustion. The sweating is usually most distressing at night and in the early morning hours. Sponging at half-past nine or ten in the evening with tej)id or cold water will sometimes reduce the temperature and prevent the sweating. Of the few trustworthy rem- edies for this symptom, atroj)ia heads the list. It may be given in doses of from yl^ to gl^ of a grain. It often has an unpleasant effect in drying the mouth. Aromatic sulphuric acid, alone or in combina- tion with gallic acid, is sometimes beneficial. When the sweat seems to be induced by the cough, opiates are indicated. Of the scores of other remedies suggested for night-sweats few are efficacious. (3) Cough. — The patient should be instructed to restrain the cough as much as possible. The irritative cough of the early stages of the disease is best treated Avith codeine in doses of from one sixth to one third of a grain. When more severe morphine may be necessary. Sometimes the combination with dilute hydrocyanic acid is very beneficial. When the cough is associated with much expectoration, particularly in the morning, it is best treated by warm alkaline drinks, taken immediately on waking, warm milk and Apollinaris water, to which has been added a pinch of salt and bicarbonate of soda. Inhalations of creasote, terebene, or the oil of eucalyptus are very serviceable in reducing the amount of catarrh. Some of the most distressing forms of cough rise from the laryngeal irritation, and for such local treatment is indicated. (4) For the diarrhoea of chronic phthisis and of intestinal tubercu- losis large doses of bismuth are useful, combined with Dover's powder. Enemata of starch and laudanum may be tried or the acetate of lead ' Tlll'.A'l'MENT OF TrUKRCrLnSlS. 847 -aud opium [)ill. In other instanci's tlic ucitl dianlKjL'a luixturo, contain- ing iu each dose ten to twelve minims of the dihite acetic acid, one eighth of a grain of acetate of morphia, and a grain of the acetate of lead, may he tried. It is usually impossible ttituti' the hiiho ot" syphilis. With the ap|)oarancc' oi" the chancre heuins the ><» called second period of incidMifioii. This period is ill delined and iudeliuite in its extent. It is made to include the development oi' the chancre, the enlaruement of neiohhoriuo- lyni])h ii'lands, and that series of ehantjjes which takes place within tlic system hefore the ai)pearanee of eruptions on the skin. During' this time the patient may retain the full vijror and appearance of health, or there may be jjrodromal symptoms, such as mahiise, inappetence, headache, slight muscular j^ains, and occasion- ally a low or hio'h temperatiu'c, showing that the system is slowly being brought untler the influence of the poison. Then follows the first exan- theni, and with its appearance the establishment of syphilis within the system is comjilete. Up to this time the course of syphilis is reasonably certain and un- varying in different individuals. There are abont the same changes and they occnr in abont the same succession, differing only in the length of time occupied in their evolution and development. After the appear- ance of lesions upon the skin and the thorough invasion of the body no such orderly succession of symptoms can be predicted. The trouble may end at once ; it may become quiescent for a time and then break out with added intensity and vigor ; it may go through a series of changes increasing in energy and variety of expression until it expends its force and then subsides ; or it may enter at once upon a malignant and destructive course in which the integrity of various organs may be involved or life itself threatened. Syphilis is a constitutional disease always. The involvement of the system may be severe, or it may be so light as to give rise to scarcely appreciable symptoms. Limitation of all symptoms to the chancre means that the systemic manifestations have been mild and the skin affections overlooked, or that the nature of the local lesion presented was misunderstood. Syphilis is a chronic disease, persisting usually for a long period of time and seldom presenting symptoms that can be classed as acute. Under favorable and early treatment most cases recover in from two to four years. Some cases are so mild that all symptoms vanish after the expiration of a few months, and never reappear. This happens at times with no treatment at all or that only of the most in- different nature. In other cases the symptoms are severe from the be- ginning. Bone and brain lesions appear with or precede the skin erup- tions. The skin may be quickly filled with ulcerating gummata instead of the more frequent macules and papules. The integrity of every organ in the body may be threatened and a fatal ending may ensue. This malignant form of the disease is called by the French '^ galloping" or "lightning" syphilis, and the terms are apt and appropriate. It is fortunate that such cases are rare. Stages in Sr/philis. — Ricord divided the course of syphilis into three periods, designating them, respectively, the primary, secondary, and tertiary stages. The primary stage beo;an Avith the appearance of the initial lesion and continued until the development of generalized skin eruptions. The skin eruptions ushered in the secondary stage. This was more indefinite in course and extent, but was made to include the 852 SYPHILIS. exanthemata occurring in the course of the disease, loss of hair, affec- tions of the nails, sore throat, and mucous patches within the mouth cavity and elsewhere upon the mucous surfaces. The tertiary stage followed the secondary, and was still more indefinite in its course. It was supposed to begin at about the end of the first year and to continue until the termination of the disease. This classification, while of great service in the past, is not now regarded with the favor once accorded it. Its errors are becoming more apparent every day, and the time is not far distant when it will be entirely discarded. Its chief fallacy lies in the fact that it endeavors to make syphilis conform to a time schedule and a regular, unvarying succession of changes. Such a course syphilis does not pursue, and any attempt to make it appear that it does is mis- leading in the extreme. The tertiary stage in many cases never makes its appearance, all symj)toms of the disease ending with the termiuation of the skin eruptions. Again, the secondary stage, as far as any of its chief manifestations are concerned, may be wanting entirely, and so called tertiary symptoms follow close upon the appearance of the chancre. The primary stage is the only one described by Ricord in which the symptoms are possessed of sufficient constancy and definite- ness to warrant their being grouped as belonging to one 'period of the disease. Syphilis must be recognized as a disease not following any one defi- nite course and manifesting itself in a series of symptoms appearing at a certain time after the development of the chancre, these running their course within specified and exact limits, then to disappear and be suc- ceeded by another set of symptoms equally clear and concise ; but as a disease that, starting from a fixed point, pursues many different lines of evolution and expresses itself in a great variety of symptoms. Only in such manner can an intelligent conception of the malady be obtained. Etiology. — The belief is wellnigh universal among scientific and medical men that syphilis is caused by a living germ. So many of the clinical facts and manifestations of the disease can be given a ready and satisfactory explanation by the assumption of such an hypothesis that the evidence is overwhelmingly in its favor. ^Moreover, reasoning from analogy, we are able to reach the same conclusions. Syphilis un- doubtedly belongs to the infectious granulomata. Its infectiousness, the course it pursues, the development, structural anatomy, clinical ap- pearances, and ultimate termination of its various lesions are all in accord with diseases of this class. In this group of affections are in- cluded leprosy, tuberculosis, glanders, lupus vulgaris, mycosis fungoides, and actinomycosis. All of these diseases are known to be inoculable ; bacteria are found constantly in their lesions ; and in some, as in tu- berculosis, glanders, and actinomycosis, certain of these organisms are positively known to be the causative agent in their production. These facts furnish good evidence for our belief that syphilis originates in the same manner. While the existence of a bacterium that produces and perpetuates syphilis is highly probable, its detection, isolation, and thorough demon- stration have not yet been accomplished. In 1884, Lustgarten described a bacillus which he had found in syphilitic tissues and which he believed to be the microbic element of the disease. The bacillus was from three SVMrTUMS. 853 to sovcMi niicroinilliiiu'trcs in Iciiiitli, or aljoiit tlic size of" the tulxTclc bacillus, had a sliiilitly cui'vcd or S-sliapctl a|)|)('araiu'f, and had Uiioh- like cnlariiciiu'iits at its ends. Since niakin- ftund alone or in tirouj)s of two to eight within cells somewhat resembling, but larger than, white blood corpuscles. They occur most frecpiently near the advancing border of the lesion, rarely deep within its substance. The staining method employed in their demonstration is briefly as follows : Thin sections of the part to be examined are made througli the border of the lesion, including, if possible, sound as well as syphi- litic tissue. These sections are placed in a solution consisting of 100 parts of aniline water, and 11 parts of a concentrated alcoholic solution of gentian violet. In this they are allowed to remain for twenty-four hours. Then the temperature of the solution is raised to 40° C and the immersion is continued for two hours longer, after which the sections are removed and placed in absolute alcohol for five min- utes. On removal from this they are dipped for ten seconds in a 1|- per cent, solution of permanganate of potassium, and are then decol- orized in sulphurous acid largely diluted with distilled water. If after a thorough attempt it is seen that decolorization of the specimen can- not be completely effected, the process of washing in alcohol, perman- ganate solution, and a stronger solution of sulphurous acid must be repeated. The section when ready for mounting must be colorless to the naked eye. When decolorization is complete the section is washed in distilled water, cleared in the usual way with oil of cloves, mounted in glycerin or Canada balsam, and examined with a yV inch oil immer- sion lens. The bacillus thus described may be the active causative agent of syph- ilis, but enough has not been done as yet to prove it such. Lustgarten did not carry his work to completion, nor has any other investigator done so since. It is not enough to find certain forms of bacteria present in the syphilitic tissues. They must be found constantly in all at least of the earlier lesions. They must be removed from such lesions, isolated from all other species of bacteria, and pure cultures must then be made upon suitable media. From these cultures inoculation experiments upon individuals free from any taint of the disease must be made, with the result of producing in them demonstrable syphilis. In the lesions of syphilis thus produced the same germs must be found. These are essen- tially Koch's la\vs, and in the round that they require can complete proof alone be obtained. Only when this shall have been accomplished wdll the bacillus of syphilis be completely demonstrated. One great difficulty in the way of demonstrating the germ of syphilis is the fact that animals are immune to the disease. Inoculation experiments have been tried repeatedly upon them, but only in rare instances with in- different success. The help afforded in the study of tuberculosis by animals is here denied. Symptoms. — Syphilis is a disease that expresses itself in a great 854 SYPHILIS. variety of ways and with a multitude of symptoms. Frequently it expends its entire energy in an attack on one organ or one set of organs. Thus the symptoms may be confined entirely or in large part to the skin, to the bones, to the nervous system, or to any one of the various organs or systems of organs of which the body is composed ; or a number of organs may be attacked simultaneously or in succession. Again, in its encroachment upon a given organ it is not by any means uniform in the lesions that it produces or the effects to which it gives rise. There is no lesion of the skin known to the physician that syphilis may not reproduce, and in its involvement of deeper structures it fur- nishes nearly as extensive a list of jjathological phenomena. Hence the study of symptoms presented by syphilis must be a study of its dif- ferent lesions and their varying expression in different organs. The First Period of Incubation. — After the syphilitic virus has gained entrance to the system an interval occurs in which there is no appreciable evidence of infection. This interval occupies a period of time varying from ten to thirty days. At the expiration of this incu- bative period the hard chancre or initial sclerosis makes its appearance at the point where infection took place. The length of this incubative period varies within quite wide limits. Ten days appears to be the shortest time on record in which the date of infection was indisputable, while periods as long as sixty and seventy days have been noted by careful observers. Very long or very short periods are exceptional, however, and always open to suspicion. The great majority of chancres occur at about the end of the third week. The point at which the chancre is situated is always the point where contamination with the syphilitic virus has taken place. Infection never occurs at a distance from this point. Two or more points may, how- ever, be infected at the same time, and if this occurs there will be an equal number of chancres resulting. Thus it may happen that a man may get a chancre of the lip at the same time with a chancre of the penis, the one acquired by kissing, the other by coitus with the same woman. But this is unusual. During this incubation period it is highly probable that the virus does not remain localized and latent, but that it undergoes distribution with developmental changes too delicate for our coarse methods of ap- preciation. Certain it is that infection of the system occurs within a relatively short period of time after contamination has taken place. This is shown by the fact that if an abraded surface or open wound through which the poison is supposed to have passed be thoroughly cau- terized or dee^jly extirpated within a few hours after inoculation has taken j)lace, it does not in any wise affect the appearance of the chancre or the course of the subsequent syphilis. Chancre. — A chancre is that changed condition of the normal or un- sound skin or mucous membrane produced by infection with the virus of syphilis, and occurring at the point where such infection has taken place. It is characterized by a varying degree of induration and an accompanying enlargement of the neighboring lymphatic glands. Better and less confusing terms for its designation are the " initial sclerosis " and the " initial lesion " of syphilis. The initial sclerosis does not occur in hereditary syphilis, and is SYMl'TOMS. 855 iioviM* wantinu; in the iU'(|iiir('(l ionii. It may he so sli<>;ht in its in;miics- tations as n()t to attract the j)ati('ii('s attciitioii, or it may \)v liiddcti (looplv beyond the external o[)enin<4s of the body, siK-h as in the iiKuitli cavity or vagina, and thus escape detection, but its existence' is none the less certain. Cases of sy[)hilis in which il is declared to have been absent are simply cases in which it was overlooked or misunderstood. It is one of the few symptoms in syphilis that is constant and uuvaryinj^ in its a[)])earance. The initial lesion is the first symptom of sy|)hilis to declare itself after infection, and it is also the first conclusive proof that infection has taken place. The site of its appearance is always definite. It occurs at the point or points of infection, and in no other localities. It is usually single, but if there has been coincident infection at two or more })()ints, there will be a corresponding- number of initial lesions. This frequently happens on the glans or foreskin when the rupture of a number of her- petic vesicles has opened different passageways for the entrance of the specific virus. Here as many as a dozen or more distinct- and individual lesions may occur, each presenting the typical characteristics of a hard chancre. The chancre of syphilis is not auto-inoculable. Its virus can be deposited npon the broken skin or mucous membranes of the individual upon which it occurs, and no chancre will result. In this it differs from the chancroid, which can be freely inoculated at different sites upon its bearer. When the chancre appears upon a surface that is brought con- stantly in contact with an opposing surface, it is apt to produce a lesion that looks as if auto-inoculation had taken place. This happens fre- quently upon the inner surface of the foreskin and the glans penis or between the lips of the vulva. If such secondary lesion be examined carefully, it will be found to be superficial, not at all indurated, and perhaps slightly ulcerated. It is caused by the irritation produced by the chancre, and not by any specific action of the syphilitic virus. No mistake need occur if careful examination of all lesions presenting them- selves be made. Sites. — As syphilis is acquired most frequently in the contacts of sex- ual intercourse the initial lesion is found oftenest upon the genital organs. In the male it occurs upon the glans penis, in the sulcus coronarius near the frsenum, upon the inner or outer surface of the foreskin, on the skin of the penis or scrotum, and at the meatus urinarius or deep within the urethra. In the female the parts oftenest attacked are the labia majora and minora, the fourehette, the preputial covering of the clitoris, the entrance to the vagina, the os uteri, the perineum, and the inner surface of the thigh. Other parts of the body where chancres may be met with are the lips, tip of the tongue, the tonsils and walls of the pharynx, the nipples and breasts in nursing women, the base of the nail and finger tips in sur- geons, physicians, and accoucheurs, the lobe of the ear, the parts about the eye, and the umbilicus. In short, any part of the body where a break in the overlying structures may occur, and to which the virus of syphilis can be carried, may become the seat of chancre. Chancres 856 SYPHILIS. occurring upon the genitals of either sex are spoken of as genital chan- cres, while those occurring elsewhere upon the body are known as extra- genital. All chancres have at least three determining features in common. These are — the period of incubation already described, a peculiar thick- ening and hardening in and about the lesion known as induration, and a characteristic enlargement of the lymphatic glands in the near neigh- borhood. These features are constant and diagnostic. Induration. — Induration, in its degree and extent, diifers very much in diiferent chancres according to their anatomical location and the amount of external irritation to which they are subjected. The thick- ening may involve only the base of the lesion, seeming to the touch like a bit of parchment set within the tissues, or it may produce a mass the size of a marble and varying in density from that of cartilage to bone. The induration frequently can be detected at the outset, or, if inappreciable then, will usually make itself apparent within a few days. It continues to increase for a period varying from ten to fifteen or more days. At times the occurrence of induration is deferred some- what longer, but it never fails to show itself. If the thickening be slight, it may disappear entirely before the chancre heals, but if extreme it usually disappears slowly. Some trace of it can often be discovered at the time of the first macular exanthem unless this be much delayed. Occasionally it persists for longer periods, as for six and eight months. Bubo. — The accompanying glandular enlargement is known as syph- ilitic bubo. When the chancre is situated upon the penis, the bubo ex- ists in both groins. It is said at times to be one-sided, when the chancre is not situated near the median line. This statement, however, needs confirmation. Enlargement upon one side only is of doubtful charac- ter. The glands are but slightly or not at all painful, and freely movable beneath the skin. They usually form in a series decreasing in size from the one nearest the chancre. In size they vary from that of a billiard ball to that of a hazelnut. The skin is not inflamed as in chancroid, and they rarely suppurate. Double inguinal adenopathy, with a characteristically indurated chancre appearing at the end of an incubative period of not less than three weeks, is sufficient to establish a diagnosis of syphilis. Treatment has a marked influence upon the duration and character of the bubo. Form. — Chancres assume a variety of forms. They are frequently developed upon the site of pre-existing lesions, such as herpetic vesi- cles, smokers' patches, fissures, and excoriations, and take on certain of the features presented by such lesions. Anatomical location, pres- sure effects, friction, and treatment all tend to modify the chancre and in various ways determine the form that it shall take. No one lesion can be taken as the type of all chancres. Each must be studied by itself. Only the commonest forms can here be described. Erosion. — This is the simplest type and the one most frequently met with. It appears as if a limited area of the epidermis or mucous mem- brane had been rubbed or scraped away. This form is frequently spoken of as the chancrous erosion. It is the primary form of the initial lesion, but with its simplicity it is the form that presents the greatest difficulties in the Avay of diagnosis. At the outset it is not SY Ml '/'(>. ]fs. 857 much larii'iT tluin the siiriacc of a piuhcad, is roiiii(lc(l oi- dval in out- line, and a])j)c'ars as il' the epithelium had been removed hy friction with the (dotliino- or o|)posiii scale or be the seat of a tiny vesicle. Jnvolvement of the hair follicK' fre(juently occurs, and the papule is then pierced l>v the hair fihunent. Limitation of the miliary |)apules to exposc^d sur- faces, such as the face and the hands, s(jmetimes takes place, while the parts of the body protected by the clothing are the seat of much larger varieties. In cachectic and anaemic patients the appearance of a crop of miliary pajniles is often the precursor of. an extensive pustular syphiloderni soon to follow. Lenticular papules are the most frequently met with of any of the early syi)liilodermata. They are liable to occur at any time during the first two years after infection, and may appear at a still later period. They vary in size from a large pinhead to a coffee bean, have a flat- tened or rounded surface, are seldom much elevated, and are frequently surrounded by a fringe of scales known as the corona veneris. The base of the papule is usually quite firmly indurated. The summit is smooth and glistening or capped with a thin firmly adherent scale. Often the papules are so slightly elevated as to be distinguishable from macular lesions only by the sense of touch. Such lesions are known as maculo-papules, or the summit may be converted into a pustule without the base undergoing any change, the lesion then being called a papulo- pustule. In syphilis scaling papules are frequently met with that are difficult for any but the expert to distinguish from the lesions of j)Soriasis. The scales here lack the lustrous appearance presented in psoriasis and are not so freely shed. On the contrary, they are frequently so firmly attached to the surface as to require some force on removal, and when the scale is lifted away there are no minute bleeding points found beneath as in the psoriatic lesion. Other lesions can usually be found in the near neighborhood or elsewhere upon the surface of the body that are unmistakably syphilitic. Papules frequently appear in the palms and on the soles, and in such localities present features somewhat different from any shown in other parts. This is owing to the density of the epidermal coverings in the regions named. Instead of involving the epidermal layers thronghout, as is usually the case, they here appear to be buried beneath the epi- dermis or confined at least to its lower strata. Later they make their way to the surface and become true scaling paj^ules, not at all or only slightly elevated. • The epidermis covering the centre of the lesion is first cast off, thus giving to its summit a pitlike depression. The edge of this depression is surrounded, by a fringe of torn and dirty looking epithelium. The centres of the palms and soles are the parts usually first to be affected. Later the papules by peripheral extension and coalescence may form scaling patches covering surfaces as large as, or larger than, a silver dollar, or they may remain as distinct and discrete papules, wdiile thickly studding the surface. Extension to the digits may take place. They are not often productive of any sensation. 862 SYPHILIS. Frequently they appear with the first exaiithem, and persist during a part or the Avhole of the course of the disease, or they may appear after all other symptoms of the malady have vanished, and continue for a number of years in spite of vigorous and energetic treatment. The eruption is usually symmetrical, but the right hand is the one most apt to be severely affected. Moist Papules. — Papules presenting a moist and secreting surface are found upon the skin in situations favoring such development. Warmth and moisture are necessary conditions, and such factors are found in the axillae, between the nates, in the perineal region, between the scrotum and thigh, within the lips of the vulva, and underneath the overhanging breasts of fleshy women. Here the papules begin as in the dry form, but are quickly converted into lesions little or not at all elevated, and having a circumscribed eroded surface secreting a sticky, mucilaginous fluid. Sometimes they are covered by a grayish pellicle looking much like diphtheritic membrane. The lesions when plentiful and fully develoj^ed give forth an almost unbearable odor. This form of moist papule differs in no wise from mucous patches seen within the mouth cavity. Its structure, development, and complete evolution are the same as the mucous patch, and it is frequently called by the same name. About the mucous outlets of the body a different kind of moist papule is apt to form. This variety is characterized by hyperplasia of the cell elements, with consequent elevation of the resulting lesion. Papules of this kind are known as condylomata and occur in either a flat or pointed form. Flat condylomata appear as eminences varying in size from a ten- cent piece to a silver dollar, and having a whitish or grayish white, macerated surface bathed in a tenacious, mucoid fluid or covered with an adherent grayish pellicle. The secretion is extremely offensive in odor and in the highest degree infectious. Often the irritating effects of the secretion beget a similar lesion upon the apposed surface when the condyloma is between the buttocks, so that two lesions of like nature are brought face to face. This form of condylomata may be single or multiple. Frequently the lesions form a complete collarette about the anal or vulvar openings. They are often the seat of intense itching and burning sensations, and productive of the greatest discomfort. Flat condylomata are absolutely diagnostic of syphilis. Pointed condylomata, or venereal warts, seen so often in syphilitic subjects, differ from the preceding form, not only in their character and appearance, but in the fact that they are not strictly syphilitic lesions. They are produced at any time when the parts are subjected to undue and long continued irritation, such as happens when pathological dis- charges like those of gonorrhoea and leucorrhcea flow over the vulva, over the perineum, and over the anus, or, in the male, are imprisoned beneath the foreskin. Secretions from certain syphilitic lesions, such as moist papules and flat condylomata, give rise to them as well. Hence it happens that they are found accompanying true lesions of syphilis as an accident only of the process. It is important, therefore, that too much significance should not be attached to this form of condylomata in determining the presence or absence of syphilis. sYpnrfjs OF THE Sk'fx. 863 One or inniiv of these pointed |>;ii)iiles may he jireseiil. They are filitbrni or eonieal in shaj)t', with a hroad or narrow hase and a tufted apex. When nudtiph' they frecpiently form mas.scs as hirge as a jjood- sizod hen's egg-. Inspeetion t)f sueh mass always shows it to be made nj) of a great niunher of distinct and individnal wartlike strnetures. The lesions may be dry, but are usnally covered with moisture. This mav be a true secretion on the part of the wart or be sweat arising from the warmth of the part. The lesions are a[)t to bleed readily and freely upon the slightest irritation or surgical interference. The sidcus coro- narius in the male and the inner surface of the labia majora and minora in the female are often the sites of their occurrence. Absolute cleanliness and the use of disinfecting solutions, such as l)oric acid, corrosive sublimate, and permanganate of potassium, are the essentials in treatment. If persistent, the lesions may be snipped oif with a pair of scissors or removed with a curette, and the base then be touched with a pencil of silver nitrate or a drop of carbolic acid. Pustules. — Pustules are frequently met Avith in syphilis. They occur oftenest in the ill fed, unclean, debilitated subjects seen in public prac- tice. Well cared-for patients seldom exhibit them. This fact strongly suggests their being an accident rather than a definite symptom of syphilis, and such belief is gaining ground among syphilographers. Pustules are usually developed from papules. They seldom appear as elementary lesions. The summit of the papule is first converted into a minute vesicle. As this enlarges its contents become turbid, and then pustular. The pustule may be confined to the apex of the papule, occupying only that space first showu in the vesicle, or the entire papule may become involved in the process. Pustules mav appear on any part of the body. In the early stages of the disease they are apt to be symmetrical and extensive in their distribution. Later they appear in groups having a circinate arrangement. The pustules vary in size from a pinhead to a pea. Early in the course of the disease they are small, and more abundantly developed than when occurring at later periods. When first appearing they are discrete, but later may become confluent and give rise to superficial or deep ulcers. The lesions may be clustered in circinate groups or be distributed freely without definite arrangement. Frequently they in- volve the hair follicle, especially on the face and scUlp. A dull ham- red areola is often distinguishable at the base of the pustule or of the papule on which the pustule rests. When ulceration does not follow, the pustules disappear and exfoliation of the epidermal coverings takes place. If the pustules have been large and deep, well marked cicatrices are left as relics of the troulole. Pigmentation frequently occurs, the stain having a dark coppery hue. Ulcers arise by coalescence of a number of pustules or by enlarge- ment of individual lesions. They are apt to occur late in the disease and in cachectic and anaemic subjects. Only the superficial layers of the epidermis may be involved in the process, or the ulcer may burrow deeply into the skin and subcutaneous tissue. Superficial ulcers are usually small, not often increasing much beyond a ten-cent piece in size. The base is indurated and the ulcer is covered by a light, friable, greenish yellow or dirty looking crust. 864 SYPHILIS. ■ In the later stages of syphilis, or early when the disease is pursuing a severe course, large pustules occurring in groups of half a dozen or more may appear at different sites upon the body. These pustules unite and form what is known as the pustulo-ulcerative syphiloderm. This ulcer is deeply seated, frequently painful, and secretes pus in abundance. It is capped by a large dark green or brownish crust, underneath which a well of blood and pus can always be discovered. The pus dries readily, and the resulting crust is more or less firmly adherent to the edge of the ulcer. When the crust is removed and the lesion cleaned of its contents, the ulcer shows a punched-out appearance. The sides are j)recipitous and the base is uneven and granular. Such ulcers leave a deforming cicatrix unmistakable to the eye of the trained observer. Bupia is a term employed to designate ulcers occurring in syphilis in which the crusts assume a conical or oyster-shell shape. The crust is made up of a number of layers, the one at the bottom covering the greatest extent, and each succeeding layer becoming smaller as the summit is approached. The crusts may reach an inch or more in height and cover an area as large as a silver half dollar. They are produced by successive additions to the crust from beneath, while the ulcer enlarges peripherally. The layer at the top represents the first one formed. The ulcer may be superficial or deep. Rupia occurs only in uncleanly, uncared-for subjects, and generally indicates a severe and persistent type of the disease. Tubercles. — Tubercles are of frequent occurrence in syphilis. They may appear at any time in the course of the disease after the expiration of the first three months, but are seen more frequently in late rather than in early stages of the malady. They occur oftenest in those cases in which early treatment has been improperly conducted or entirely neglected. Tubercles differ but little in their characteristics from gummata. They are apt, however, to occur at a somewhat earlier stage and to run a milder and more tractable course. They also appear in greater number and involve the skin less deeply. But in the clinical features that they present it is often a matter of considerable difficulty to distinguish them from the gummy tumors (Plate XL). Tubercles may appear upon any part of the body surface, but are found most frequently upon the face and the extremities. The tip of the chin, the alse of the nose, and the integument covering the knee and elbow joints are favorite sites for their occurrence. They may occur singly, but usually develop in groups of half a dozen or more. They appear as small pea- to bean-sized nodules, set well within the tissues of the skin, and present externally a globoid surface. They are firm to the touch, and in the earlier course of their development are usually painless. In color they vary from a dark red to a coppery hue. Their color varies with any change in the blood supply of the part, such as is apt to ensue after violent exertion. There is then a decided deepening of the previous stain. The circular form of grouping distinctive of syphi- litic lesions is here frequently met with. Often extension of the process is by the formation of new rings about or in conjunction with similarly formed groups. In this way figure-of-8 and other odd looking arrange- ments are formed. PLATE XI. Tubercular Syphiloderin, Resolutive and Serpiginous. (Hyde. From a photograph of a hospital patient. SYPirilJS OF THK SKIN. 805 'riil)('rol(>s (litt'cr niuch in thf ooiirst' that they pursue and in the manner in whk-h resohition takes })hi('e. Fre([uently the h-sion under- goes degeneration, .and absorption of its products takes phice witliout destruction of the overlying integument. This happens frequently upon the face. In such cases there is the formation of a true scar without breaking down and removal of the epidermal layers. The scar is de- pressed and oftentimes pigmented. The pigment usually disai)])ears in the course of time. Sometimes resolution occurs in this manner in one part of the group while the lesions in another part are still in full pro- cess of development. Degenei'ation and destruction of the tubercle by ulceration is a fre- quent method of its removal. Softening of the summit occurs, the roof wall breaks down, and the degenerated products of the lesion are discharged. The ulceration goes on to complete removal of the tuber- cle, and may extend much more deeply into the tissues. In this latter case the deep extension of the ulcerative process is undoubtedly due to gummatous infiltration of the tissues about and below the tubercle proper. After destruction of the tubercle is complete, repair ensues by the formation of a cicatrix. Frequently, where the process is unrecognized and unchecked, the lesions continue to develop in circles or parts of circles about the sites of existing tubercles, each new crop gradually enlarging the area affected. In this way patches may be formed covering the greater extent of the forearm, the thigh, or one or both buttocks. At the border of the area is the line of advancing tubercles, many of them in a state of ulceration, while within, the process is represented only by the lesion relics of the disease in the form of scar tissue. The process is extremely indolent, and in many cases may continue for a number of years. Gummata. — Gummata usually occur in the skin late in the course of the disease. In malignant cases or where the progress of the malady is rapid and destructive they may appear \vithin the first six months after infection. They present the appearance of firm nodules deeply set within the skin or subcutaneous tissue. At first they are freely mov- able over the deeper structures and within the skin itself, but later they become attached to the underlying periosteum, bones, cartilage, or muscles. The skin becomes reddened and inflamed, finally breaking down and permitting the discharge of the gummy mass. Gummata vary in size from a pea to an orange. They are spherical or globoid in shape, or may be flattened and irregular in outline. In their earlier stages they are sensitive in a slight degree only, but later they become extremely tender and painful. They are usually single or but few in number. Rarely they occur in great numbers, as hundreds in one subject. Any part of the body surface may be the seat of gummata, but they are seen with greatest frequency upon the lower limbs and the integument of the forehead and scalp. The effect of gravity acting upon the blood no doubt influences their frequent development upon the limbs. The tendency of gummata wherever occurring is toward ulceration and destruction of the part. This may occur in the skin with startling rapidity, a few days only sufficing for complete softening and removal of the tissues affected ; or the lesion may persist for weeks and months, Vol. I. — 55 866 SYPHILIS. with no evidence of change occurring in its substance save that of gradual enlargement. Frequently the gumma extends deeply into the tissues, involving muscle, bone, and cartilage in its destructive course. When this occurs upon the face frightful deformities are likely to result. Thus the cartilages and bones of the nose may be attacked and entirely destroyed, or the lobe of the ear be in part or wholly removed. The severitA^ of the process can only be likened to the ravages made in the same region by malignant disease. The importance of early recognition of the condition is apparent. Ulcers resulting from the destruction of gummata are apt to be sluggish and indolent in their deportment. Their size is determined by the lesion from which they arise. They are circular, oval, or irregular in outline. The edges may be thickened or undermined, the sides precipitous, and the floor uneven, foul, and dirty with Ijrown or greenish colored pus. In cachectic and poorly nourished patients such ulcers may become the seat of gangrene. "When the necrotic mass is entirely eliminated the ulcerative process ends and repair begins. Healthy granulations cover the floor and sides of the ulcer, the thick- ened edge is smoothed out, and the process is completed by the forma- tion of a cicatrix. This cicatrix is circular in outline, smooth, white in the centre and pigmented at the border. The scar is deep and firm, usually being attached to the parts beneath. Its recognition is fre- quently ©f great value in establishing a diagnosis of preceding syphilis. At times a diffuse gummatous infiltration of the skin or subcutaneous tissue takes place. This is apt to occur over the back or upon the lower extremities, as the parts of the leg between the knee and ankle. The skin becomes reddened, swollen, tumefied, and sodden. Xodules ai)pear at various points, break down quickly, and discharge their typical gummy exudate. The process if unrecognized may go on for long periods of time, resulting in great thickening of the integument and the production of abundant scar tissue, or the entire gummatous area may break down, forming a single gigantic ulcer. Upon the abdomen gum- matous infiltration is apt to result in a serpiginous ulcer. Gummata are, however, rare in this location. In the genital region such infiltration results in contraction and deformity of the penile organ or in narrow- ing of the entrance to the vagina. Affections of the Hair due to Syphilis. — The hair is frequently affected in the course of syphilis. The nutrition of the filaments may be impaired in so slight a degree as to give rise only to a certain amount of dryness and lack of lustre, or the process may be so severe as to bring about an extreme and deforming alopecia. These syphilitic alopecias are important from a diagnostic standpoint because of the help they furnish in arriving at exact conclusions regarding the existence of the disease. They appear as the result of one of two processes : either the hair falls as the result of defective nutrition, with no structural change occurring in the part from which it arises, or there is a preceding organic change in such part. The alopecia in the first form may be said to be due to a primary process, while in the other it is secondary. In the primars^ form the hair may come out slowly or very abruptly. There may be a gradual thinning of the hair of the scalp and of other parts of the body, a few filaments only coming away each day, mitil the SY riff US OF THE NATLS. 867 complote loss bceomcs decidedly apparent, or the process may be cha- racterized l)v the development of numerous bald patches no larj^er in size than a ten-cent piece. A\ hen these patches occur upon the scalp they affect the back and sides of" the head more than other parts. In these regions the bald areas are set so thickly as to alm,- ciciiti'lt'C's. lipon the .siirlac-c' <»1" tlio tongue they usually present themselves as loni^- linear eraeks extendino- (lee[)ly into its substance. Often they appear as if the tissues hacl been dei'tiy divided by a sharj) knife. Their walls are then in close contact, and their separation is needed to reveal the extent of the fissure. Fissures usually follow mucous patches or areas of small-celled intiltration. Tubercles occurring upon the tongue and mucous membrane of the mouth resemble enlarged or hyperplastic moist papules. They are rounded or tiattened nodules involving the tissues somewhat deeply, and occurring at points where there is but little pressure, as on the under surface of the tongue. Gummata do not develop in the mouth until a late stage of the dis- ease has been reached. They may occur in any part, but most fre- quently attack the tongue. They begin in either the deep or superficial tissues, and are ai)t to run a much more rapid course than when occur- ring elsewhere upon the body. The supei'ficial variety is first noted as a small, round, reddened nodule appearing in the mucous membrane. The nodule is slightly elevated and is moderately firm to the touch. The lesion may increase in size slowly, but its most frequent course is to enlarge with startling rapidity. The centre becomes necrotic, case- ous degeneration follows, and the roof wall, which at first is tense, is broken down and a gaping ulcer results. There may be but one or there may be several of these lesions scattered over the tongue, the hard palate, and the cheeks. The gummata are seldom painful, and often are not discovered until softening and ulceration have occurred. Gummata originating in the deeper structures, such as the muscular tissues of the tongue and the bones of the hard palate, are apt to be much more formidable and severe in the course they pursue. The neo- plasm usually occurs singly. Its onset is insidious and without pain. It is a circumscribed, indurated, firm tumor, varying in size from a hazelnut to an olive. Degeneration and ulceration occur at times with great rapidity. Perforation of the palate may take place within a week from the first appearance of the nodule. If not promptly checked, the process may go on to more or less complete destruction of the roof wall. Ulcers in which a marble may be hidden destroy with the same rapidity the tissues of the cheek and tongue. The ulcers are round, oval, linear, or irregular in shape. Their edges are elevated and roughened or some- times undermined. Even wdth the most marked ulceration the pain is not often severe. The prognosis is good. Repair of the soft tissues occurs with the production of cicatrices that are markedly deforming. Destruction of the hard palate can be remedied by the use of an obtura- tor. Treatment must be energetic and chiefly by the use of the iodides, pushed in increasing drop doses of the saturated solution until the ulcer yields. Locally, antiseptic w^ashes and stimulating applications of car- bolic acid, iodine, or silver nitrate are of decided value. Tonics such as iron, strychnine, and quinine are usually needed. Syphilis of the Dig-estive Tract. — Syphilis seldom attacks the oesophagus. Gummatous infiltration of its walls, resulting in cicatricial stenosis and narrowing of the lumen, has been described. Little is known definitely regarding syphilitic affections of the stomach. Gum- mata have been discovered in post-mortem examination of syphilitic 872 SYPHILIS. subjects in whom no appreciable gastric symj)toms were present during life. Gummatous infiltration of limited or extended areas of the mucous and submucous tissues may result in considerable fibrous thickening of the walls of the organ. In the intestinal tract the rectum suffers with greatest frequency and needs separate description. Elsewhere the walls of the intestine may become the seat of gummata. These are super- ficial and seldom give rise to serious symptoms. Syphilis of the Heart and Bloodvessels. — Syphilis appears to find in the vascular system conditions favoring its first expression. In the chancre, before marked invasion of the body by the syphilitic virus has taken place, constant and characteristic changes are noted in the vessels entering and leaving the part, and throughout the course of the disease the bloodvessels are apt to suffer in a marked degree. This is doubt- less due to the abundant development of connective tissue entering into the formation of the arteries and veins. The Heart. — The heart suffers less frequently than do the vessels, but when affected the intensity of the trouble is greater and more serious mischief is apt to result. Not infrequently a fatal termination ensues. Manifestations of syphilis in the heart usually appear late in the disease. When attacked the heart may become the seat of gum- mata or a specific fibrous myocarditis may develop. Gummata may occur in any part of the heart, but appear most fre- quently in the endocardium, along the edges of the valves, and in the in- terventricular septum. The neoplasms vary in size from a pinhead to a hazelnut, and appear as circumscribed, spherical, non-vascular, yellow- ish or whitish bodies set somewhat deeply in the tissues aifected. They show on section a necrotic, cheesy centre surrounded by a connective tissue capsule. From this capsule strands of fibrous tissu. can be seen radiating into the surrounding parts. No trace of musci lar elements remains at the site of the nodule. They apj)ear to have undergone fatty degeneration with complete absorption. Small gummata have been found in the chordse tendinese. When this occurs, shortening, thicken- ing, and weakening of these structures take place. Death produced by their rupture has been known to follow. In stillborn infants affected with hereditary syphilis the heart has been found thickly studded with minute gummata. Fibrous myocarditis of the heart due to syphilis occurs as the result of an arterio-sclerosis or obliterating endarteritis of the coronary arteries.' The part of the heart supplied with blood by the branches of the par- ticular artery aifected becomes impoverished, undergoes degeneration, and its structures are replaced by fibrous tissue. Any part of the heart may be affected. Frequent sites of its occurrence are the papillary muscles and the septum. These parts are thickened, become dense and firm, and are found on section to be composed almost entirely of fibrous connective tissue with only a meagre vascular supply. Occa- sionally spindle cells are found mingled with the fibrous elements. Gummata frequently exist in intimate association with this form of affection. The endocardium in some cases undergoes a like fibrous change. It is then greatly thickened, becomes gray or grayish-white in color, and takes on somewhat the consistency of cartilage. The rigidity produced often interferes greatly with the action of the heart. syrirrrrs of the iiemit axi> bloodvessels. 873 Aitcitri/siii of the lu'art walls Ixdiiidiiit;- the vciitiMclts may occur. This liappons as the result of sof'toiiinj:: and excavation in a ^uninia o|)eniui»- into the ventricular cavity, or it is due to the dilatation of an area of tibrous myocarditis. The walls of such aneurysms are com- posed of dense til)rous tissue, and their cavities arc fre(juently Idled -with thrombi. The symjitoms produced by syphilitic disease of the heart arc not distinctive. The history of each case as re<>;ards skin lesions and other characteristic symptoms must usually be relied U])on to estaljlish the diag-nosis. By some it is thought that the dyspncea occurrinii- in dis- eases of the heart is apt, when the trouble is due to sy])hilis, to come on more frequently at night when the patient is resting quietly in bed. This fact, however, is not well established, and to(j much reliance should not be placed upon its diagnostic importance. Many persons suffering with syphilis with marked involvement of the heart go through life without manifesting any signs of trouble in the organ, the condition •only being disclosed at the autopsy. With obliterating endarteritis of the coronary arteries and its resulting heart lesions death may ensue j:?uddenly and without marked prodromal symptoms. The Bloodvessels. — Syphilis affects the bloodvessels both early and late in the course of the disease. The greater part of its energy is expended upon the arteries, while the veins very largely escape. Little is known regarding the effects of the disease on the capillaries. Fatty degeneration and gummatous changes in their walls have been ob- served. The most frequent lesions met with in the walls of the arteries are gummata, aneurysm, arterio-sclerosis, and obliterating endarteritis. Obliterath g Endarteritis. — This is by far the most frequent and serious trouble occurring in the arteries that is due to syphilis. The smaller arteries are principally affected. There is partial or complete closure of the lumen of the vessel due to proliferation of the endothe- lial elements in the intmia. The specific virus of the disease or the product of such virus circulating in the blood excites the ]3rolife ration by means of its irritative action. Thickening of the intima takes place, layer after layer of the endothelial cells forming one within the other until the vessel is nearly or entirely closed. The adventitia is attacked, and gradually all the coats of the vessel become affected. A true inflammation may be excited, with subsequent production of gran- ulation tissue. This latter is converted into fibrous connective tissue having a marked tendency to contract. If the lumen of the vessel is still partly patent, the contractility of this newly formed tissue is usually sufficient to close it. The nutrient vessels are made to share in the process and are completely obliterated. The process is usually confined to limited and localized areas. The arteries at the base of the brain and the coronary arteries suffer most frequently. Arteries in any part of the body, however, may be affected. Gummata. — Gummatous changes occur in the larger arteries. They are localized or diffuse. The adventitia suffers more often in the cir- cumscribed form than do the other coats. The lumen of the vessel is partly closed by pressure of the mass inward. The narrowing is still further accomplished by thickening of the intima. Thrombi frequently 874 SYPHILIS. form at the narrowed point. The gumma undergoes its peculiar changes, softens, discharges its contents into tlie circulating blood, and then be- comes the seat of an aneurysm. In the diffuse form the gummatous infiltration occurs between certain of the vessel's coats, such as the intima and adventitia. The entire circumference of the vessel wall may be involved or only a part be affected, while the process may extend along the artery for some distance. Fatty or cheesy degenera- tion of the gummy infiltrate takes place, and later calcification, leading to the production of atheroma. The carotids and arteries of the brain appear to suffer most frequently. The weakened walls of vessels affected in the brain are liable to rupture suddenly when subjected to strain and give rise to apoplectic seizures. Arteriosclerosis. — Syphilis is one of the many causes capable of pro- ducing arterio-sclerosis of the bloodvessels. This condition when due to syphilis is seen most frequently in robust individuals between thirty and fifty years of age who have suffered from the disease in early life. The affection is apt to be generalized. The lumen of the vessels is enlarged, instead of being narrowed as in endarteritis. The intima is thickened and often becomes the site of atheromatous change. The walls throughout are hardened and inelastic. To the touch they feel like whipcords placed beneath the skin. The condition is in no wise distinguishable from the same disease when it is caused by alcoholic or lead poisoning or gout, nor does it appear more amenable to treatment. Iodide of potassium in full doses is indicated and may be tried in in- terrupted courses, pushing it each time to the patient's limit of toler- ance. A well regulated, quiet life must be insisted upon. Syphilis of the Genito -urinary Organs. — In men the penis is fre- quently the seat of the initial sclerosis. This has been described (page 854). CEdema and diffuse swelling of the organ are complications liable to occur in connection with chancre, especially if the lesions be large and subject in any manner to irritation. Phimosis and paraphi- mosis are produced as complications. The organ then is swollen, hot, and tender. The lymphatics become inflamed and painful, and seem to the touch like whipcords running along the dorsum of the penis and encircling its root. These conditions, while productive of some dis- comfort and much alarm on the part of the patient, seldom occasion serious mischief. Rest, elevation of the organ, frequent immersion in warm boric acid solution, and the administration of a laxative inter- nally usually suffice for their removal. The glans penis, owing to interference with the return circulation by the chancre, sometimes assumes a bluish color, suggestive of gan- grene. This is apt to occur with large, deeply indurated chancres situ- ated in the sulcus coronarius. The discoloration vanishes with resolu- tion of the chancre. Balanitis and posthitis may result from irritating discharges from the primary sore. Consecutive lesions occur in the varying forms seen elsewhere upon the surface of the body. Scaling papules may be found at times upon the glans penis when no other lesions indicative of syphilis can be dis- covered. A slight catarrhal discharge from the urethra is sometimes noted as occurring in early syphilis. This is probably due to the pres- ence of mucous patches within the walls of the passage. Gummata sirJiiLis uF THE (!KMT(j-rnisAnY onaAMs. 875 aj)pcai'ini; as Hnn, splu'rical nodules occur within the corpora caver- nosa. 'riu'V (Icvi'lop slowly and without pain, the patient first notin*:- that the penis is "crooked" when erect, and later discovering- a "Iuni[)" deep within the tissues o{" the or^an. The tendency of" such neoplasms is toward deiicneration, with al)S()rption of the j)roducts and ^the suhsequent development of circiunscrihed areas of fibrous connec- \tive tissue. Permanent deformity of the organ then results, (jiummata arc not apt to occur in the corj)Us s|)on<>iosum. When doin<»; so they give rise to exceediuiily rebellious strictures of the urethra. A pecidiar condition resembling a circular band j)lace(l alxjut the penis results occasionally from a fibnms development taking place within the cavernous bodies. This band may encircle the penis com- pletely or only in ]Kirt, and usually interferes greatly with perfect erec- tion of the organ. Syphilitic affections of the testicles and their appendages are common, but, owing to the slight distress occasioned, are often overlooked. It should be the invariable rule of the ])ractitioner to examine these organs at the time of the patient's first presentation when the body is searched for specific lesions, and throughout the course of the disease the testicles should be ^vatched with care. Trouble occurring here may show it- self early or late. The epididymis usually betrays some slight degree of irritation at the time of the first eruption. It becomes somewhat swollen and is painful to the touch. Later in the course of the dis- ease a circumscribed area may become the seat of inflammation. This is a true specific epididymitis, and is to be distinguished from that due to gonorrhoea by its slow, insidious, painless onset, and by the fact that the globus major instead of the globus minor is the part most often affected. One or both organs may be attacked. Circumscribed gum- mata or diffuse areas of gummatous infiltration occur late in the disease. They are painless and slow in growth. The gummatous infiltration may involve the entire epididymis or be confined to a portion of the organ only. The discovery of a lump in his testicle is often the first indication given the patient of existing trouble. Extension of the pro- cess to the testicle proper and to the cord often takes place. When dis- covered early treatment is usually successful in removing the deposit and saving the organ. If neglected, irreparable damage maybe done and a useless organ may result. Trouble in the testicle usually begins late in the disease, and is due to the formation of gummata. These may appear first in the substance of the testicle, or they may begin in the tunica vaginalis investing the organ, and from this extend to the deeper structures. In the tunic they can be felt as small, round, firm, freely movable nodules. If deep in the testicle, they cannot be detected by touch until they have enlarged to a considerable extent. There is no pain. They may be single or multiple. The testicle may be invaded throughout its entire substance by the gummatous deposit or the process be limited to a portion only of the organ. The gummata enlarge slowly. Their substance is dense, often as hard as ivory. The testicle increases in size, sometimes becom- ing as large as a child's head. Its weight drags u])on the cord, ])rodu- cing uncomfortable sensations in the groin and abdomen. Aside from this there is no pain. Pressure, unless excessive, elicits little or no 876 SYPHILIS. response. The surface is smooth. In this it differs from tuberculosis, in which the organ is uneven and rough. Occasionally there is effusion of fluid into the tunica vaginalis with the formation of hydrocele. One or both testicles may be aif'ected. The course of the malady is exceed- ingly slow, years often being occupied in the process. The trouble ends in absorption of the gummy exudate and the development of fibrous tissue, leaving a shrunken, withered organ, or softening of the gumma may result in complete destruction of the testicle. This, how- ever, is unusual. Fungous growths sometimes arise. During the prog- ress of the affection there is oftentimes no marked change in the sexual appetite. Syphilitic orchitis responds readily to specific treatment begun early in the attack and pushed with sufficient vigor. The iodides are indicated in full doses. Locally, inunctions of the oleate of mercury in 5 per cent, strength are of value. The tendency of the disease is to destroy the seminiferous tubules, and when such destruction has taken place repair cannot ensue. In women chancres occur as frequently upon the genitals as they do in men, but, owing to their being hidden from sight, are not as readily recognized. The os uteri and vulvar portal are favorite sites. Chancres are seldom seen upon the vaginal walls. They may occur in the urethra. The early lesions of systemic syphilis may develop upon the vulva and within the vaginal canal, most frequently as condylomata or mucous patches. Condylomata present the features described elsewhere (page 862). Mucous patches occurring upon the vaginal walls differ but little from those ajDpearing in the mouth cavity. These patches give rise to but little distress unless irritated by leucorrhoeal discharges. In such cases the lesions are greatly aggravated and frequently very painful. Mucous patches of the vagina and os uteri, whether occurring early or late in the course of the disease, are undoubtedly the most fruitful source of infection. The posterior wall of the vagina may be involved in the syphilitic affections occurring in the rectum. The remainder of the tract is not often the site of gummata. Little is known regarding early syphilitic affections of the uterus and ovaries. In both, gummata may develop in later stages. In the ovary the changes taking place resemble those occurring in the testicle. The gummatous deposit may be diffuse or cir- cumscribed and lead to wasting and shrinkage of the organ. The bladder is rarely attacked by syphilis. It is believed to be affected slightly in the early stages of the disease, but little is known regarding the condition. At the most, it is probal^ly but a transient hypersemia. Gummata, papillomata, and hypertrophic growths due to syphilis occur in later stages. Fistulous tracts may be formed by ex- tension of ulcers occurring in neighboring organs. The kidney may be affected at any time in the course of the disease after the development of systemic syphilis. Early manifestations of trouble differ very much from those occurring at later periods. They are sudden in their onset, not often being announced by any prodromal symptoms. Oedema occurring in and beneath the lower eyelids is usu- ally the first evidence furnished showing that the kidney is affected. This is more noticeable in the morning after the patient rises from rest SYPiiiTjs OF THE ai'.Mro-rinsMiY run; ass. Sll than latiT in the conrsc of the day. Tlit' (I'dcinatous condition later appears in the extremities and in other parts of tlie body. Examination of tiie urine sliows albumin in small or larg;e quantities, jjranular easts, blood, j)us, and kidney epithelium. The amount ])asscd in twi'utv-i'our hours is somewhat lessened or even ; and old syphilitic w(nnen long' after syniptonis of the disease have ceased. Syphilis of the Bones. — Syj)hilis is liable to affect the bones or their })eriosteal coverinj2;s at any period early or late in the course of the disease. As a rule, the attack is late, several years elapsing between the appearance of the chancre and the time when definite lesions of the bones first show themselves. The earliest effects of syphilis manifested in the osseous system are what are known as osteocopic pains. These pains occur at or about the time of the first exanthem or even before it. They are not always present : in some cases they are light and transient, while in others tliey are extremely severe and produce the most intense suffering. The pains are grinding, boring, or splitting in character, and are usually referred to the joints with deep extension into the bones forming such parts. The knee, elbow, and shoulder joints are most frequently affected. The pains are not stationary, but shift from one part to another with considerable rapidity. They are worse at night, often occurrinp- at a oiven hour and making rest for the remainder of the night impossible. During the day complete freedom from pain is often experienced. Patients, if they be aware that mercury is being given them, often attribute these pains to its use. This idea is entirely erroneous, and there is no indication for cessation of the drug if the pains come on after its use has begun. Its dosage should rather be increased than diminished if ptyalism be not imminent. Nodose swellings may occur upon the tibia, scapula, sterniuii, and bones of the skull shortly after the appearance of the first exanthem. The lesions are tender and at times extremely painful to the touch. Usually they disappear within a few weeks. Such nodes must not be confounded with those occurrino^ later in the disease, in which there is gummatous deposit in the part. The earlier lesions are circumscribed areas of hypersemia with slight exudation into the periosteum, but no new cell formation. Late lesions of bone occurring in syphilis have been classed by Lancereaux as follows : («) Inflammatory osteo-periostitis ; (6) Gummata ; ((•) Dry caries. Such lesions may occur at any time after the sixth month and as late as the twentieth year. Any bone in the body may suffer, Tlie tibia, ulna, sternum, scapula, clavicle, and the bones of the cranium, of the nose, and of the face, suffer most frequently. One bone only may be affected at a given time or a number may suffer simultaneously or in succession. Inflammatorii Osfeo-periostltis. — The lesions occurring in this form of bone syphilis are true nodes. Any of the bones may be affected, the superficial ones, such as the tibia and bones of the skull, most fre- quently. The periosteum and superficial layers of tlie bone are the parts attacked. The j)rocess begins in the connective tissue of the part and consists of inflammatory swelling, with the production of Vol. I.— 56 882 SYPHILIS. numerous embryonic cells. The bloodvessels of the Haversian canals are involved in the process, and the canals are enlarged and filled with a plastic exudate resembling bone-marrow. There is consider- able determination of blood to the part. Thickening of the tissues occurs with the formation of a distinct tumor involving the periosteum and the parts of the bone immediately beneath. In size the tumor varies from a pea to a walnut, and is soft and doughy to the touch. The overlying skin is freely movable and is not reddened in the earlier stages of the lesion. The swelling is exceedingly tender upon pressure, and is usually the seat of a dull, continuous, grinding sensation, very liable to be intensified at night when subjected to the warmth of the bed. If the node occur upon the inner table of the skull, it is apt to produce continuous and severe headache or nervous symptoms of con- siderable gravity. The nodes, unless subjected to appropriate treatment, enlarge rapidly, the skin becomes red and adherent, the tumor softens, breaks down, and finally discharges upon the surface, with the production of a deep carious ulcer. Dead bone comes away at frequent intervals. The ulcer runs a sluggish, indolent course, after which the cavity closes with the forma- tion of a depressed cicatrix surrounded by a hard bony ridge. At times the nodes do not undergo ulceration, but are converted into new bone extremely dense and hard in its organization. These growths are persistent and are known as exostoses. Such exostoses may be found in the periosteum, and they are freely movable upon the bone beneath. Later they may become attached to it. Grummata. — Gummata are found in and underneath the periosteum, within the bone substance, and in the medullary canal. The long bones, bones of the skull and face, the ribs, and the bones of the fingers and toes, are most frequently affected. Gummata occurring early in the course of the disease are far more apt to be numerous than when developing late. They form rapidly and are extremely painful, the pain being nocturnal in character. When involving the periosteum, gummata can be felt as moderately firm tumors varying in size from a pea to a walnut. The neoplasms may soften, break down, and discharge outward with the production of typical degenerate syphilitic ulcers, or they may un- dergo resolution and absorption without the production of such lesions. In the long bones gummata are found most frequently w^ithin the medullary canal. The bone enlarges either locally or throughout the greater part of its extent. The Haversian canals entering the cavity become distended with the degenerated, cheesy products of the gum- matous lesion. The pain is intense, continuing with unabated fury both day and night. The process ends by absorption of the gummy material or the production of carious bone. Calcification may take place. In the flat bones of the skull the process is somewhat different, owing to their peculiar anatomical structure. The diploe is the part that is here most frequently attacked. The gummy deposit may be so extensive as to separate the tables, one or both of which may become carious. iS^ecrosis of the inner table gives rise to serious brain symp- toms. In the outer table sequestra are frequently formed and removed by ulceration. Destruction of scalp tissue occurs and a deforming cica- trix results. SYPHILIS OF THE SERVOUS SYSTE^r. 883 Dry Caries. — This atfoction is declarod by Vircliow t<} be fluo to syphilis alone, and is fbnnd most l"r('(|iicntly attackiiii; the frontal and parietal bones. The proeess begins as a ture and liem()rrhag:e into the surrouiidinn' tissnes result. The size of the lesion is here in no wise projjortioned to the gravity of" the symptoms re- sulting', occlusion of the smallest artery in the internal capsule giving rise to the most serious and disastrous consequences. Aneurysmal dilatations or pouches of the arterial walls may be })roduced by the disease. Paralysis coming on as the result of thrombosis is slow in its onset, while that caused l)y rupture of an aneurysm is sudden. When slow in its approach, numbness is first noted in the foot, hand, or cheek, or it may be that some slight difficulty in speech is first expe- rienced. These symptoms increase slowly in intensity and extent until a part or the whole of one side is paralyzed. Several days may be occu- pied in the process. Or, when rapid, the patient, without premonition of coming trouble, suddenly finds himself unable to speak or to use hand or foot. Consciousness is not completely lost. This feature is almost typical of syphilis. The senses are deadened and mental activity is decidedly in abeyance, but the patient can still be aroused sufficiently to show by signs that he is conscious of his surroundings. Convulsions are not often present. The reflexes of the affected side are exaggerated. Recovery may be rapid, slow, or delayed indefinitely. Atrophy of the parts paralyzed is unusual, but contractures may occur. No grouping of symptoms referable to syphilis of the brain is pos- sible. The best established feature of such symptoms is their varia- bility. Headache is always present. It usually begins insidiously, increases gradually, is nocturnal in character, and is usually described as grinding, boring, or hammering in nature. Gummata of the brain, if large, may give rise to all the symptoms produced by the different forms of brain tumor. In these symptoms may be included convul- sions, vomiting, and optic neuritis. Occasionally syphilitic disease of the brain may be manifested in emotional or psychical disturbances, such as mental hebetude, hysteria, hypochondriasis, stupor, somnolence, dementia, or mania. Syphilis of the Cord. — The cord is not as frequently attacked as is the brain. The trouble may begin in the bones, in the coverings of the cord, or in the cord itself. Gummata and a diffuse proliferation of the connective tissue elements are the forms of syphilitic affi?ction most likely to occur. Symptoms arising from such involvement are mani- fested in exaggeration of the reflexes, loss of control of the sphincters, spastic paralysis of the lower limbs, anaesthesia or partesthesia, lanci- nating pains in the back and down the thigh, and contractures. The relation of syphilis to tabes dorsalis appears to be definitely settled. Erb, in a series of 369 cases of the latter disease, established the fact that 89 per cent, of the patients had previously suffered with syphilis. Such a preponderance cannot be regarded in any light but that of cause and effect. The Peripheral Nerves. — Specific involvement of the peripheral nerves may occur, and is characterized by mild or severe neuralgias, by vague, indefinite sensations, by burning ])ains in the toes or fingers, and by para?sthesia of limited or extended areas of the skin. The sensations produced are sometimes distressing in the extreme, and are a])t to increase as the disease progresses. The symptoms are often rebellious 886 SYPHILIS. to treatment, requiring the largest doses of the iodide to subdue them. Syphilis of the Eye. — All of the tissues of the eye, the soft parts about it, and the bones forming the orbit may be the seat of syphilitic affections. Owing to the delicacy and sensitiveness of the structures involved such afFections are apt to be grave. The Orbital Bones. — Gummata may form in the periosteum or in the orbital bones, and by their pressure effects give rise to severe pain in the eye, disturbances in vision, or displacement of the globe. Nodes are not rare. The bones may be affected by periostitis, osteitis, carious degeneration, and necrosis. The inflammation excited by such processes may extend to the eyeball and give rise to a deep seated or superficial cellulitis. Abscess may follow with discharge through fistulous tracts in the eyelids. Such sinuses are frequently rebellious to treatment, and may require surgical interference before they can be closed. Pain is often intense, and constitutional disturbances due to depression are some- times great. The adjacent cerebral structures may become involved. In gummata of the orbit treatment should be prompt and energetic. Reliance must be placed upon the iodides, and they must be given often in the largest doses. Their administration should be accompanied by mercurial inunctions of the feet each night. Supportive measures are needed. The bitter tonics, iron, quinine, strychnine, cod-liver oil, and the malt extracts are often necessary to improve the general condi- tion. Locally, fomentations of boric acid solution, as hot as they can be borne, are often grateful, or, if they are not productive of comfort, cold may be tried. Operative measures to remove dead bone or evacuate abscesses are sometimes necessary. The Lachrymal Apparatus. — The lachrymal gland and ducts may be the seat of a chronic catarrhal process. This is usually associated with some thickening of the Schneiderian membrane or disease of the nasal passages. Stricture of the lachrymo-nasal duct is apt to follow. Atten- tion to the patient's history with reference to a luetic taint or unmis- takable symptoms of syphilis in other parts are needed in establishing the diagnosis. Treatment is by antisyphilitic measures, and in case of stricture by clivulsion of the duct with large-sized probes. The Eyelids. — The initial sclerosis may occur either upon the inner or outer surface of the eyelid. The lesion is here characterized by the same signs as when appearing elsewhere. Usually considerable oedema of the parts ensues. Enlargement of the pre-auricular, parotid, and submaxillary glands on the side affected constitutes the bubo. Chan- cres occurring on the mucous surface of the eyelid may interfere seri- ously with sight. The early consecutive lesions may appear on both surfaces of the lids, but are not frequent. Upon the mucous surface they are produced only after the part has been irritated in some manner. Mucous patches appearing upon the conjunctiva usually follow a mild course and respond readily to treatment. Local measures consist in protecting the eye w^ith a shade and stimulating the lesions slightly by the application each day of a mild solution of silver nitrate. One to three grains of the salt to a fluidounce of distilled water is sufficient. Gummata may appear upon the eyelid, usually late in the course of SVl'IIILIS OF THE FAi:. 887 the tlisoasc. Tlicir site of pn-fiTciu't' is aloii^- tlu' free Ixji'dcr. \n size they vary from a pinhcad to a pea. Care iiiiist he cxtTciscd in distiii- guishin<»' thciii iVoin cystic or tihroid tumors, which they arc a|)t to resemble. (Jiimmata usually involve all of the tissues of the lid, while either of the forms of tumor noted are frequently confined to a single layer, as to the integument or conjunctiva. The ( hiijunctird. — Injection and inflammation of the ocular con- junctiva are common in syphilis and are usually accompanied by an iritis of the same eye. Two cases of chancre oi' the part have been reported. Consecutive lesions may occur in connection with the first skin erujjtion. The lesions appear as circumscribed macular spots or small ])aj)ular elevations, coppery in hue and without injection. They are seldom numerous. Gummata are rare. They are found oftenest in the pal[)cbral conjunctiva, but may develop in the ocular portion at the border of the cornea. The neoplasms vary in size from a i)iuhead to a pea, and are usually spherical in shape. The inner surface is often reddened, while the outer is whitened or yellowish. They are liable to terminate in ulceration. If numerous, the nodules may interfere with the nutrition of the cornea in sufficient degree, by pressure upon the lymphatics, to bring about destruction of the part and complete loss of vision. IVie Cornea. — The cornea is far more frequently affected in inherited than in acquired syphilis. A diffuse interstitial keratitis sometimes appears, giving to the part a cloudy, muddy appearance. The process begins at the centre and spreads gradually to the border of the cornea, or it may follow the reverse direction, beginning at the periphery and advancing toward the centre. The affection is always chronic, lasting often for years. A true punctate keratitis may arise. In this form the lesions are pinhead sized, grayish looking deposits. They are never vascularized and never ulcerate. Gummata have been observed. The Sclerotic. — Syphilitic affections develop here in the form of epi- scleritis, parenchymatous scleritis, or gummatous deposit. Episcleritis occurs as a superficial congestion of the sclerotic. It is never extensive, though several patches may be discovered at once upon the visible portion of the membrane. The conjunctiva is usually injected at the same time, and in a measure obscures recognition of the process in the sclerotic. There is but little distress accompanying the condition. Parenchymatous scleritis is deeper and far more severe. Exudation is marked. The conjunctiva is swollen and elevated. An iritis usually accompanies it. The pain may be light or severe. The process is always chronic. Atrophy and thinning of the tissues may follow, but ulceration never takes place. Gummata developing in the sclerotic appear first as small reddened, interstitial deposits. If unchecked in their course, they enlarge, extend into other coats of the eye, and may go on to complete destruction and removal by ulceration of the eyeball. The Iris. — Inflammation of the iris due to syphilis is an exceedingly common affection. It appears early in the course of the disease, usually shortly after the subsidence of the exanthemata, but it is by no means rare at later periods. One eye only may be involved or both may suffer in succession or simultaneously. liecurrences may happen. The patient first notices uneasy sensations or decided pain in the eye ; 888 SYPHILIS. light is distressing to the organ ; there is inability to see clearly, and epiphora results. Inspection shows the pupil small and sluggish in its reaction to light, and of a dull hazy color ; the iris is discolored and slightly swollen ; the conjunctiva is lightly or deeply injected ; the lids are cedematous, and there is more or less lachrymation. As the result of posterior synechia the iris may become attached to the crystalline lens. Serous iritis may give rise to exudation into the anterior chamber of the eye. The aqueous humor then becomes muddy and semigelatinous in consistency. The iris and lens are pushed back by the exudate, and sight is seriously interfered with. Nodular lesions may occur in the iris or on its surface, due to organization of the plastic material fur- nished by the inflammatory process. The membrane may be thickly covered with these bodies, and by their means become firmly attached to the capsule of the crystalline body. In such cases the iris exhibits the convexity of the lens. The prognosis is good if treatment be begun before adhesions have formed. Rest, exclusion of light by means of a shade or colored glasses, and freedom from worry are essential measures in treatment. Antisyphilitic medication must be continued, but it is not often of value to push it much beyond the average dose. Local measures are of the greatest importance. Complete mydriasis must be produced and continued until the process is at an end. Two to five drops of the fol- loAving solution should be instilled into the eye three times each day until the pupil is widely dilated : ^. Atropinse sulphatis, gr. j ; Aquse destillatse, 3iv. — M. Sig. Two to five drops in the eye three times a day. Pain may be lessened by the addition of an eighth of a grain of morphia to the above solution or by the use of warm fomentations. The Ciliary Body. — Syphilitic cyclitis or inflammation of the ciliary body is a somewhat rare but exceedingly grave affection. Owing to the anatomical location of the structure, the signs displayed in its affections cannot be observed by the naked eye nor by the aid of the ophthalmo- scope, and reliance must be placed upon the subjective symptoms alone in determining the diagnosis. The affection may be serous, plastic, or gummatous. Its development and course are marked by severe pain, visual disturbances, ciliary injection, more or less diminution of tension, and serous exudation into the vitreous humor, obscuring or completely destroying vision. Usually the iris and choroid are implicated in the process, and the affection is then designated an irido-choroiditis. When the iris is not involved it is often retracted toward the part of the ciliary body affected. Such retraction frequently results in considerable deepening of the anterior chamber. Particles are visible floating in the vitreous humor. Minute deposits on the membrane of Descemet can be detected. The aqueous humor may become dark and turbid. Glaucoma is a frequent result of posterior synechia. Gummata may extend into the ciliary body from the iris or develop in it primarily. Atrophy of the body usually results after gummatous infiltration. SYPHILIS OF THE IJAIi. 889 The Choroid. — Choroiditis is next in i"r('(|U('ncy to iritis as a syphilitic affection oi" tiic eye, and is often associated with it. Two forms have been noted, ditVcrinji,- in the htcation of the trouhh- ratiier than in the j)ceu- liarity or severity of the syni[)tonis numifestech The iirst form is confined to the anterior portion of the choroid and is always acconij)anicd by an iritis. The second affects the ])()sterior portion of tlie membrane only. In eitiier ease there is exndation into the [)(»sterior chamber with resnlt- inir clondiness of the vitreons humor. FK)ccnli floatin<>; free in tiic humor in the anterior part of the chand)er are visible. Reticulated bauds, ajipcaring like cobwebs, may be formed by the plastic exudate. Small yellow specks can be seen with the o})hthalmoscope upon the fundus or upon the wall of the posterior chamber. Atro})hy of the cell elements at the place where these bodies are situated is apt to follow. The retina is frequently affected in conjunction with the choroid. The optic nerve usually shows a hypenemic condition. True gunimata are not known to appear in the choroid. Choroiditis occurs late in the course of the disease and usually in patients past middle life. The Refhia. — Syphilitic retinitis occurring without previous impli- cation of the choroid is rare. One or both eyes may be affected. Subjective sensations consist of slight pain, dimness of vision, photo- phobia, flashes of light, slight lachrymation, and night-blindness. The retina appears as if obscured by a veil, the retinal vessels are hypersemic, the fundus is indistinct, and the disk engorged. Loss of vision is slight or marked in degree. The affection may be confined to the fundus and the parts in the near neighborhood, or the peripheral portion of the retina may alone be affected. Syphilitic retinitis may be acute, sub- acute, or chronic. Vision is usually spared, though it may be greatly diminished. A peculiarity of syphilitic retinitis is that it is apt to occur wdien there are no other symptoms of the disease manifested else- where in the body. Reliance must be placed upon the history in such cases. Early recognition is essential to its successful treatment. Mixed treatment is indicated, either by combination of the iodide and the mer- curial in solution, or, better, by the administration of the iodide inter- nally and the use of the mercury by inunction. The ojitic nerve may be affected either within the orbit or within the cerebral tissue. The inflammation develops usually in connection with retinitis. The symptoms presented are those of choked disk. There is engorgement of the vessels ; the nerve is greatly swollen and infiltrated ; its color is red or reddish gray, and its retinal border is wdiolly obliter- ated. Usually but one nerve is affected. Partial loss of sight often results. Only rarely does complete blindness follow. Syphilis of the Ear. — The ear is not often the seat of syphilitic invasion, but when attacked, especially in its deeper structures, it is apt to suffer severely. Chancres due to kissing or biting are met with occa- sionally upon the external ear, and one case of chancre in the meatus has been noted. In the early stages of the disease the integument of the auricle may display any of the consecutive lesions incident to that period. At a later stage the substance of the lobe may become the seat of gummata. Such deposits may occur within the lobule or upon either surface of the cartilage, and the affection is apt to pursue a rapid and de- 890 SYPHILIS. structive course. Eemoval of a large part of the lobe may be effected. Superficial ulcerations result from gummatous nodules in the skin. Early consecutive lesions occur within the canal. They may be moist or dry and at times give rise to a tormenting pruritus. A dry form of seborrhoea developing in the part is sometimes seen in early syphilis. The accumulations of sebaceous material may be sufficient to effectually plug the passage. Intractable ulcers may appear within the walls of the canal. The ulcers are usually painful and productive of free discharge. Exostoses occur at the meatus, but some doubt exists as to their being due to syphilis. The bony growths are not distin- guishable from similar lesions occurring in individuals free from the disease. Condylomata are by far the most frequent form of syphilitic lesion found in the meatus. The affection occurs with greatest fre- quency in the early stages of the disease, and severe ulceration is apt to follow. The lesions begin as dry papules the size of a millet seed and enlarge to that of a pea. The papule becomes moist, the ej)ithe- lium is macerated and removed, and a typical secreting vegetation remains. Considerable pain attends the development of the lesions. Annular contraction of the meatus due to cellular infiltration in the true skin may result in partial deafness. Macules and papules may develop on the membrana tympani. If ulceration of the lesions takes place, perforation of the membrane is apt to result. Small gummata have been described as occurring in this structure. Affections of the tympanum are not well understood. Its intimate relationship with the naso-pharynx by means of the Eusta- chian tube makes it liable to participate in the troubles arising in that region. This usually happens in the form of a diffuse catarrhal inflam- mation of the lining membrane of the cavity, with closure of the tube and the production of partial or complete deafness. This form of serous inflammation is frequently seen in children suffering with hereditary syphilis. A true suppurative inflammation due to syphilis may arise. It is distinguishable in no wise from suppuration of the middle ear due to other causes, save that local treatment has little or no effect upon it, while it responds readily to antisyphilitic measures. A small-celled in- filtration of the parts may occur as an independent affection or follow- ing one of the above described forms of inflammation. It gives rise to considerable thickening of the walls, and may produce ankylosis of the ossicles. Symptoms of trouble taking place within the middle ear are declared in diminution or complete loss of hearing, earache, suppura- tion, and discharge. Little is known regarding syphilitic affections of the labyrinth. Thickening of the lining membrane owing to a hyperplastic inflam- mation of the parts may occur. Gummata have also been found. A sensation of ringing in the ears, vertigo, and deafness are the chief symptoms. Pathological Anatomy. The pathological anatomy of syphilitic lesions is, with very few exceptions, not distinctive. Microscopical study of the lesions shows, in the same manner as does the clinical study of the disease, the imita- tive faculty of syphilis. The structural features of syphilitic neoplasms PATIfOLOaiCAL AXATOMY. 891 in all essential respects are like tlujse seen in a nniltitnde of lesions (luo to other niorUid [)roeesses. Yet here, as in their <;rossi'i' f'eatnres, those ehan>ies present some eharaeteristie a])pearanees that reveal to the eye of the trained [)athologist their true natnre. The ini|)rint of -yj)hilis is npon them. The most eharaeteristie lesion of syphilis is the jjjnmmy tumor. It is not eoniined to any sta*ie of the disease, bnt occurs either early or late in its conrse. ^lieroseopical examination of such a tumor in the earlier period of its development reveals a circumscribed or diffuse mass of embryonic cells enveloped in a gelatinous basement substance and surrounded by a hypememic area. Epithelioid and giant cells sometimes ap])ear. The cells are of a low order of organization and exceedingly fragile. Within the hyperaMiiic zone first formed a free development of connective tissue takes ])lace, forming an apparent envelope for the embryonic mass within. From this envelope connective tissue pro- cesses invade the tumor substance and radiate into the surrounding tissues. Infiltration of the newly formed connective tissue with sphe- roidal and epithelictid cells takes place. Xew formed bloodvessels ramify freely in the mass, and there is a considerably increased flow of blood to the part. Enlargement of the neoplasm may be rapid or slow and by peripheral extension. It will be seen from the description thus far given that the lesion is not essentially a tumor in which there is a new growth occurring, but a neoplasm arising from a hyperplastic inflammation and belonging distinctively to the granulation type. A gumma may disappear at any stage of its early development by resolution, absorption of its products taking place, or it may and does most frequently undergo cheesy degeneration. When this happens one or more necrotic points first appear within the substance of the nodule. These enlarge, become fused, and in time occupy the greater part of the tumor. The mass now appears as if composed of finely grated cheese pressed closely into a compact body. A wall of granulation tissue forms about the cheesy mass. This product of coagulation necrosis may be removed by absorption, or ulceration with destruction and sloughing of the nodule may follow. A cicatrix then results. A second feature of syphilitic inflammation that is more or less typical in its nature is the frequency with which the process invades the vascular structures. The arteries show the specific inflammation in its completest development. As the result of the process infiltration of the walls of the vessel with small round or polyhedral cells takes place, producing an appearance that has been likened to the arrangement of the coat-sleeve about the arm. This infiltration occurs chiefly within the perivascular lymph spaces and between the coats of the artery. Considerable thickening and rigidity of the walls results. The pro- cess may be localized or extended throughout considerable areas. The product may be absorbed, but more often results in the formation of fibrous connective tissue, with the production of a limited arterio- sclerosis. The vessels in the near neighborhood of the chancre are affected early. The initial sclerosis in view of its mcII defined clinical aspects ought to present definite structural features. This, however, is not the case. Its minute anatomy is not definitely characteristic. The changes por- 892 SYPHILIS. trayed are those liable to occur in any low grade of inflammation. There is an abundant development of small round cells within a more or less dense connective tissue stroma. The parts are freely invaded by leucocytes. Giant and epithelioid cells sometimes occur. Proliferation of connective tissue elements takes place. The small bloodvessels en- tering the part display the above described coat-sleeve infiltration of their tunics. This latter feature is continued along the vessels to parts at some distance from the initial lesion. The newly formed con- nective tissue shows a tendency to persist unchanged for some length of time, but is finally absorbed. The induration of the chancre is caused by dense infiltration of the connective tissue spaces with cells and by oedema of the corium and epidermal layers at the borders of the lesion. It is also probable that the syphilitic poison exerts a specific influence upon the lymph of the part affected, and that this action of the virus is partly responsible for the induration that takes place. The cells de- veloping in the part vary but little in size at first, but later many of them become much enlarged and oftentimes multinuclear. The earlier lesions of the skin, such as macules and papules, present no structural features that distinguish them from like lesions produced by low grades of inflammation not syphilitic. There is congestion of the corium with exudation into its parts, and a resulting hyperplasia of the epidermis. Pustular lesions present a torn condition of the epider- mal structures, with partial or complete destruction of the corium and a mingling of the products of necrosis with blood and leucocytes. They are in no wise distinguishable from the pustules occurring in other dis- eases. Lesions of the mucous membranes have the same features as those presented in like lesions appearing upon the surface of the skin. In the lymph glands infiltration of the vascular channels with sphe- roidal and epithelioid cells appears to be the chief pathological process. The free production of new connective tissue is a characteristic feature of the syphilitic process. This occurs in connection with the develop- ment of many of the different lesions or as , the result of their disinte- gration and resolution. This tendency is particularly well defined in the nervous system, and especially late in the course of the disease. It is undoubtedly the element that makes syphilis an etiological factor in the production of tabes dorsalis. Diagnosis. Early recognition of the chancre is chief in its importance in the diagnosis of syphilis. Such recognition depends upon several factors, no one of which can be omitted with safety. First and of greatest im- portance is the history with reference to the time of suspected infection. Sores appearing within ten days after exposure to a possible source of infection are probably not syphilitic in nature. Those occurring later than ten days, and especially at about the end of the third week, are to be regarded with suspicion. Peference must be had, in determining the length of time that has elapsed between contamination and the appear- ance of the sore, to records not only of the last, but of previous indul- gences in sexual intercourse. A sore may be found upon the genital organs shortly after coitus that in reality had its origin some weeks Dr.\(;x()Sfs. ,si»;i previously in a similar exposure. The production and examination i)i' the person suspected tt) be the sourei' ol" the troul)le is alwavs a desir- able, but often an unpleasant and imj)ossibk', means ol' verilyin^- the dia_-e that the hroiiiinc and iodine compounds have been ingested is usually suitieient to establish a dis- tinction in the case of bromic or iodic acne. The pustules of syphilis show a well defined areola, while ulcerative lesions are nearly always present. The tliatiiiosis of late manifestations of the disease must dej)end uj)on the history, upon the typical grouping-, upon the usually sluggish action, and upon the destructive course of the lesions. Treatment of Syphilis. The proper treatment of syphilis takes into consideration the im- provement of the patient's general health by hygienic measures, as Avell as the medicinal attack to be made upon the disease. Neither can be neglected with safety, and only as they are made to supplement and assist each other can the best results of treatment be hoped for. Atten- tion must be directed early to the patient's habits and methods of life, and if these be found faulty or vicious they must be corrected. Pre- vious periods of ill health should be made the subject of inquiry, and provision be made for their recurrence or resulting sequels. If the patient be surrounded by unhygienic conditions or engaged in business calculated to produce ill health, a change of location or of employment should be urgently recommended. Hopefulness and cheerfulness on the part of the person aifected must be secured if possible. Despond- ency, often seen in patients of this class, frequently nullijSes the physi- cian's eiforts. Upon the untiring watchfulness with which the practi- tioner guards these factors depends in a large part the favorable or unfavorable outcome of the therapeutical measures he institutes. Hygienic Measures. — Everything looking toward the maintenance of the patient's health on the highest plane possible is of utmost value in the treatment of syphilis. As in the treatment of disease in general, so in syphilis it may be affirmed with truth that the patient presenting and maintaining a sound body is in the best condition to resist the encroachments of the malady. To the end of securing such a con- dition proper nutrition of the body is chief in importance. Any conditions or disturbances interfering with digestion or assimilation must be removed as early as possible. The diet should be ordered in such manner that there will be no return of the trouble, while ample nourishment is secured. In arranging the diet reference must be had to peculiarities of the patient's case, such as extreme plethora or aneemia. In general it may be said that a person suifering with syphilis needs a generous diet of nutritious and easily digestible articles of food which have been well and simply cooked. Meals should be had at regular intervals, and should be eaten slowly and with care in thoroughly masticating the food. Very hot or very cold drinks or dishes, as well as highly seasoned foods or an undue amount of sweets, should be inter- dicted. Fresh fruit, fresh vegetables, and fresh meats if well cooked may be permitted in abundance. Tea and coffee, if drunk sparingly and after the meal, do no harm. Lemonade mav be taken if agreeable. 896 SYPHILIS. It is well always to prohibit the use of alcoholic beverages, not because the moderate use of the milder stimulants is harmful, but to avoid danger of their abuse on the part of the patient. A majority of individuals suffering with syphilis are persons who have indulged their appetites with reference to alcohol freely, and limitation of its use is to them of decided advantage. When permitted, drinking should be allowed only with the meals, and then in small quantities of the lighter wines or liquors, such as claret or Rhine wine, and beer, ale, or porter. Drinking at a bar should never be tolerated. In weak and cachectic subjects alcoholic stimulants are frequently indicated, and the practi- tioner need not then hesitate to use them. A moderate amount of daily exercise in the open air is essential. The regulation of this must be determined by the patient's habits and occupation. For persons engaged in sedentary pursuits at least one hour should be devoted each day, when the weather will permit, to walking, rowing, or riding. Outdoor sports that do not call for too great exertion, such as tennis and golf, are of decided value both in the exercise they furnish and the diverting influence they exert upon the mind. Fatigue of both body and mind should be strictly guarded against. Proper bathing of the body needs careful attention. Hot baths, not- withstanding their vaunted specific proj^erties at certain springs and resorts for the cure of the disease, are in the early stages of the malady productive of a great deal of harm. The popular Turkish and Russian baths, as well as hot tub baths, should be strictly prohibited. In their place sponging of the entire surface each day with cool or, in the case of weak and anaemic patients with tepid, water should be ordered. If a small quantity of salt be added, as a handful to two or three gallons of water, the result will be found decidedly exhilarating and refreshing. Friction of the surface after the bath with a flesh brush or coarse toM^el should not be omitted. The bath is best taken in the morning imme- diately after rising. If such a course be pursued, many of the severer syphilodermata will never make their appearance. Bathing of the body in the case of women should be stopped at the time of the monthly period. Tobacco in all forms is decidedly injurious, and frequently produces lesions that give rise to great discomfort. When its use is persisted in, it is apt to excite severe ulcers, mucous patches, and fissures of the lips and parts within the mouth cavity. Tobacco also exerts a vicious influ- ence upon the system, interfering in a decided manner Avith the best results to be obtained from therapeutical measures. Its use, either by chewing or smoking, should be abandoned promptly and completely at the outset of the disease. Especial attention should be given to the care of the mouth and to the protection of the throat. Thorough cleaning of the teeth by means of the toothbrush and tepid water should be attended to after each meal. The brush used should be sufficiently firm to remove all particles of food clinging to the teeth, but not harsh enough to wound the sensitive mucous membrane covering the gums. Other sources of irritation, such as holding a pipe or cigar between the teeth, chewing a toothpick, gum, or other substance, should be prohibited. Decayed teeth should TJti-:A'nn:xT of syi-iulis. 897 be oxtnu'tod or have their oavitics filh'd ; sharj) iirojcctioiis must Ijc romuh'd oil' ami atHMimiihitions of so-caUccl tartar he thoroiiulily sc'ra[)t'(l away by a t'ai)abU» ck'iitist early in the courrie of the disease. The tliroat must be kept warm by the use of ample coverings in cold weather, and the wearing' of a beard by men should be encouraged, both for the pro- tection it alViii'ds and to guard against the ill effects produced Ijy close shaving. The scalp needs proper attention as well, in order that loss of hair may be avcrtetl. Indiscriminate washing of the head with each ablu- tion of the face is harmful. In its stead thorough cleansing of the part with warm water and a good toilet soap, such as the Kieger or Sarg fluid soap, should be secured once in ten days or two weeks. After each washing the hair should be well dried, and a few drops of oil of olives or sweet almonds should be thoroughly applied. Polishing of the scalp with a moderately stilf brush should be practised each morning. In men clipping of the hair is not needed if the individual does not prefer to wear it in that manner. Singeing is decidedly harmful and should never be permitted. The crown of the hat should be perforated to permit as free ventilation of the scalp as possible. In women the hair may be worn in any form suited to the individual, provided that there be no tension exerted upon the filaments. The use of the curling iron should be prohibited. Treatment of the Chancre. — The belief that syphilis can be aborted by excision of the initial lesion is entertained now by only a limited number of syphilographers. Admitting that the poison is confined at an early stage to the chancre, its accompanying glandular enlargements and the intervening lymphatics, removal of all the foci established there- in, even with great loss of tissue and severe mutilation, can hardly hope to be effected. Excision of the chancre can only be justified when its exposure on the fiice or other external part by betrayal of the patient's condition seriouslv interferes with social or business engagements. Its removal then must not be with any hope of staying the subsequent course of the disease. That course of treatment is best for the chancre which seeks to remove all sources of irritation from the lesion and to keep it in a thoroughly aseptic condition. The simpler such treatment the better are the results obtained. The chancre should be thoroughly cleansed at frequent intervals with soap and warm water, after which the sore should be dried and bathed with a saturated solution of boric acid as hot as can be comfortably borne by the patient. This should be done at least twice a day at times best suited to the patient's convenience. After bathing with the boric acid soluti(^n the part should be dried and dusted freely with some unirritating antiseptic poM'dcr, such as boric acid in combination with talc or starch in the proportion of one to four, aristol, iodol, europhen, calomel, or iodoform if its odor be not offensive to the patient. Other solutions of value when boric acid is not at hand are permanganate of potassium in the strength of one grain to the fluid- ounce of water, bichloride solution 1 : 20,000, or a ^ to 1 per cent, solu- tion of carbolic acid. These should always be used warm. Chancres of the penis or finger may be conveniently immersed in such solutions contained in a cup or tumbler and allowed to remain for ten or more Vol. I. — 57 898 SYPHILIS. minutes at a time. If the lesion be productive of much pain, as hap- pens sometimes in the case of mixed chancre, such immersion may be continued for hours with great advantage and comfort to the patient. Chancres of the finger may be protected by a light bandage neatly applied, but in general no dressing is needed for the lesion in other parts. A bandage should never be wrapped about the penis. Here a square of muslin or unbleached sheeting may be fastened in the form of an apron to the under side of the shirt, and the parts then be gath- ered loosely about the penis. In this way the underclothing need not become soiled with the secretions from the chancre. All dressings used about the lesion or becoming soiled in any way with its virus should be destroyed by burning. Chancres of the tongue, tonsil, and mouth cavity should be painted lightly once each day with a solution of silver nitrate in the strength of ten grains of the salt to an ounce of distilled water. If chancre of the lip or external part shows signs of suppuration, it should be touched with an applicator, made of a toothpick and a bit of cotton, dipped in the following solution : ^. Hydrargyri chloridi corrosivi, gr. j ; Tincturse benzoini, .^j. — M. Sig. External use. This solution is decidedly stimulating and should not be too freely used. Chancres of the os uteri and vaginal cavity are best treated by the use of boric acid douches as hot as can be borne. The permanganate of potassium and bichloride solutions can be used here as well. The douching should be practised at least once in the day. Frequent appli- cations of the nitrate solution, used as in the case of mouth lesions, help to promote healing and resolution of the sore. Tampons are not often needed. OEdema of the penis calls for its prolonged immersion in a hot borated lotion, and subsequent elevation of the organ along the groin. This can be accomplished easily by putting a broad band of muslin firmly about the abdomen and then passing another between the limbs and fastening it before and behind with safety pins. To those who can secure it a jock-strap furnishes a support that can be more easily and quickly applied. If the lymphatics become swollen and tender, the application of the following ointment after sponging the parts affected with hot water will usually give prompt relief: 1^. Tincturse belladonnse, TTLx ; Extract! opii (aqueous), gr. ij ; Vaselini, Iss. — M. Sig. External use. Care should be exercised in the use of the above ointment, as the mydriatic effect of the belladonna may be readily produced. Systemic Treatment of Syphilis. — When to begin the systemic treat- ment of syphilis is a question concerning which a great diversity of opinion exists among syphilographers. This, however, is not the place to give in detail the different views entertained nor to promote by a pro- TRKATMF.M nf SYI'IIIIJS. 899 loniif'd discussion :uiv one |):irticiil;ir course ol" jtroccdiirc. Success does not do[)end so much uj)on tlii' time that :intisy])hilitic measures are hc^i'ini as upon their intolliiicnt direction after once ht-ing- instituted. It is believed that what is said in the loUowini:- patfcs will a|)|)ly as well to treatment first employed alter the erM])tion of tlie syphih)(lermata as when the course is ordered at an earlier sta*>-e. Treatment should he <'()mmenc(Ml as soon as a ))ositive (hauiiosis of syphilis can be made, and it shouhl not under any circmnstances be instituted before such time is reached. If the ])ractiti()ner is in doubt, he siiould wait. If he is to guide his patient through the disease to its successful termination, his own mind must not be clouded by a doubt as to the nature of the malady he is combating. It will be an act of wisdom on his part to err on the side of too great caution, rather than to begin mercurial medication upon insufficient grounds. Treat- ment once begun is apt to modify the nature of the symptoms mani- fested and to prevent a typical expression of the disease, so that if the practitioner be not sure of his position at the start, he has no means of verifvino' his diagnosis later. The result will alwavs be a weak and ineifeetual course of medication at a time when energetic treatment is productive of the greatest benefit. The question thus turns on the diagnosis of syphilis. Most practi- tioners prefer to wait until the disease manifests itself in unmistakable constitutional symptoms, such as a generalized exanthem, glandular en- largeiuent, and sore throat. If treatment be begun promptly at such time and pushed vigorously, the great majority of patients will respond readily and will make complete and good recoveries. But it is not always necessary to wait for all of the above described symptoms in order to make a diagnosis, and in so doing valuable time is often lost. As has been said elsewhere, a sore appearing at the end of a ^^■ell defined incubative period, presenting the characteristic slugijishness and indu- ration of chancre, and accompanied by typical enlargement in both groins, is sufficient to establish a diagnosis of syphilis and to warrant the commencement of systemic treatment. Experience justifies the assertion that measures thus early begun, if properly directed, result in the production of a milder and far more tractal)le form of the disease than is otherwise the case. Mercury. — There is no drug comparable with mercury in the treat- ment of syphilis. Centuries of use have attested the efficiency of its action in checking and curing the disease. The employment of the drug, hoAvever, needs skilful direction. To the abuse, and not to the [)roper administration, of mercury can be traced all of the ill results with which it has been so often charged, while the charlatan has not hesitated to attribute to the action of the drug many specific expressions of the disease. There are two methods of employing mercury — one by the way of the stomach, the other by the skin. The first is knoAvn as the internal method of administration, the second as the external. Both are valuable means, and both ai^e equally effective in the results they produce. Their individual or combined employment throughout the course of the disease must be determined by the necessities and emergencies arising in the case. 900 SYPHILIS. In the internal administration of mercury the protiodide, biniodide, bichloride, blue pill, gray powder, and mild chloride are the prepara- tions of the metal commonly employed. Of these, the protiodide is by far the most reliable and effective in the results it produces. There are few patients who cannot tolerate its action, even in very large doses, and its use can be continued for longer periods of time without appar- ent diminution in the good to be obtained from it. In the early stages of syphilis it is often necessary to increase the dose very largely to meet various conditions of the disease that may arise. Under such circum- stances it is' well to give the drug in pill form uncombined with other medicinal agents, as follows : ^. Hyclrargyri iodidi viridi, gr. xij ; Confectionis rosse, q. s. Misce et fiant pilulse No. Ix. Sig. One pill after each meal. Or use may be made of the Garnier and Lamoureux pill. This pill contains one centigram of the protiodide, and, owing to the manner of its preparation, can often be tolerated by the stomach when the drug in its pure state would prove irritating. In beginning medication one of the above pills should be given after each meal. If urgency in the treatment of the disease is demanded, as when a well developed exanthem accompanied by mucous patches and sore throat is first presented, the number of pills taken may be gradually increased until subsidence of the symptoms becomes manifest or constitutional effects of the drug begin to appear. In sucih increase it is well to order the patient to take one pill after each meal for the first three days. Then an additional pill is to be taken after the noon meal for the next three days, making four pills taken during each day. During the succeeding three days two pills are taken after the morning and evening meals, and but one at noon. In this way the number can be pushed gradually up- ward until as many as twenty or more pills may be taken during each day without the production of toxic symptoms. These large doses, however, are rarely needed and seldom reached. In general, it will be found that from six to nine pills a day are sufficient to bring the disease under subjection or to produce gastric disturbances necessitating the stoppage of further increase. During this time the patient should be under strict observation by his physician. Daily inspection of the individual should be had, and as soon as evidences of toxic action on the part of the drug are manifested the increase should be stopped and the number of pills being taken reduced one half. Toxic effects are first shown in the protiodide by increased peristaltic action in the intes- tinal tract. No attention need be paid to the symptoms if the number of loose stools does not exceed two or three in the day, but when they become more numerous and are accompanied by severe griping pains, it is time to stop pushing the drug. Sometimes the first effects of the protiodide appear in the usual evidences of hydrargyrism, such as soft- ening of the gums with the formation of a red line at their border, fetor of the breath, and a metallic taste in the mouth. If improvement in the specific symptoms has not been noted before 'rj!i:ATM]:.\T of svrjiiLis. ' ooi tlio l)t'i]^iimino: of toxic oflt'cts, tlic protiodidc slidiild not he coiitimicd loiigor in the hope that it may ])rove iK'Hclicial, l)iit it iiiiist he discon- tinued and some other ju'eparation he siihslitnted. Jt is usually of decided advantai;e to comhine a liuht course ol" mer- curial inunction with the intei'ual administration ol" the jirotiodide. A scruple of the oilicinal blue ointment should be thoroui^hly rubbed into the sole of one foot each night before the patient retires to rest. The foot should be bathed first in warm water, and afterward be thoroughly dried before applying the ointment. A light sock may be drawn on to protect the sheets from being soiled. On the following night the <»ther foot may be treated in like manner. Between ten and twenty oi' these rubbings may be given as seems best to the physician. Such inunctions should be discontinued promptly if constitutional effects of the drug intervene. Iron in some form is indicated if the patient be in any wise anaemic or cachectic. It is well always to begin its administration in small doses at the time that mercurial treatment is instituted, in order to prevent the appearance of the above-named conditions and to check in a measure the peristaltic action produced by the protiodide. The follow- ing will be found valuable : I^. Ferri et quininae citratis, oj~iy j Syrupi limonis, f Sij ; Aquse destillattie, q. s. ad fovj. — M. Sig. A teasjjoonful in water before two meals. Attention should be directed early to the enlarged glands both of the bubo and those appearing later in different parts of the body. It should be remembered that these glands are foci for distribution of the virus and the products of syphilis, and that a direct attack on the seat of the disease can here be made. The integument over each gland should be sponged at night with warm w^ater, and after drying, the following ointment should be gently and lightly rubbed in : I^. Unguenti hydrargyri, 3ij ; Lanolini, 5ss. — M. Sig. External use. If the ointment be warmed slightly before applying it to the skin, better penetration w^ill be secured. Care should be exercised not to produce a dermatitis by its too frequent application. With subsidence of the symptoms decrease in the amount of the protiodide taken should be ordered, until a dose is reached that will hold the disease well under control and suppress all symptoms of it. This dose should be continued steadily, with such increase or decrease in quantity as varying conditions of the disease may seem to indicate, for a period varying from one and a half to two years. The iron and the protiodide may conveniently be combined as follows : ^. Hydrargyri iodidi viridi, gr. xvj ; Ferri et quinine citratis, 9iv. Misce et fiant capsulie Xo. Ixxx. Sig. One after each meal. 902 SYPHILIS. Or, ^. Hydrargyri iodidi viridi, gr. xvj ; Massse ferri carbonatis, 9iv. Misce et fiant capsulse Xo. Ixxx. Sig. One after each meal. The above prescriptions can often be used interchangeably with con- siderable value, the different forms of the iron apparently agreeing well with the stomach. If at any time symptoms of the disease make their appearance, the amount of the mercury can be increased by the taking of one or more protiodide pills with each dose. In order to relieve the stomach of the burden placed upon it, internal treatment may be suspended at intervals of three months and a course of inunctions substituted. In general such course should not last for a longer period than two weeks, and should be followed by a return to the protiodide. If it should be found after a thorough trial of the protiodide that success cannot be obtained with its use, or if it disagrees in any manner with the patient, its further administration should be stopped and some other preparation of mercury tried in its place. The bichloride is of decided value and can be given as follows : ]^. Hydrargyri chloricli corrosivi, g^'- j~y 5 Tincturge ferri chloridi, Acidi hydrochlorici diluti, da. f .^ij ; Syrupi limonis, f 5ij ; Aquee destillatse, q, s. ad f 5vj. — M. Sig. Teaspoonful in water after each meal. Or the above can be given after the first and last meals of the day, and a pill containing one fifth grain of the protiodide after the middle meal and at night when retiring. The biniodide may be tried in pill form in the dose of one fiftieth to one twenty-fifth of a grain, or it may be combined in capsule with the forms of iron given in connection with the protiodide. Calomel in doses of one tenth of a grain can be employed every hour in the day until the cathartic action of the drug is made manifest, when it should be administered less frequently. The gray powder in pill form is sometimes serviceable when the others fail : ly. Hydrargyri cum cretse, .9iv. Fiant pilulse No. Ixxx. Sig. One pill after each meal. If all these methods fail, resort must be had to some one of the external methods. The method by inunction is to be preferred. Ilercury hy Inunction. — This is always a valuable method of admin- istering the drug, because it relieves the stomach of an enormous burden otherwise placed upon it, and leaves it free to perform its natural func- tions. The great drawbacks to the more frequent employment of mer- TREATMEST OF SY I'll I LIS. 903 ciiry by imiiiction arc its sc'einin<;- dii'tincss and the disliUc that patients luive to the labor iiivolvi'd in the aj)|)liration. W lien, for any reason, the st4^^)nuu'h cannot be made to tolerate the varions mercurial prepara- tions, or when the })atient does not improve under such treatment, in- unctions should be employed. The hour before retiring is the time best suited for their application. The body may be divided into as many regions for the purpose as suits the j)ractitioner's wishes or the patient's convenience, the essential factor being to rub the ointment in well. Six- divisions are usually suHicient, and instructions may be given as follows. The patient is ordered on the first night to bathe well with soap and warm water the arms above the elbows, the shoulders, and the chest region above the nipple line ; then to dry the parts and to rub thorough- ly into them from one half to two drachms of mercurial ointment. The officinal ointment of the PharmacopaMa of 50 per cent, strengtli has stood the test of time and may be used with good results, but the mercurial ointment prepared by many druggists, in which the metal in the same strength is incorporated with lanoline as a basis, furnishes a preparation oifering decided advantages in the ease with Avhich it can be applied. On the following night that part of the anterior surface of the body between the nipple line and the crural angles is treated in like manner, and then on succeeding ni2:hts the followinp; res-ions in the order named : the posterior surfaces of the body that can be easily reached and the buttocks ; the lower limbs as far as the knees ; the limbs below the knees ; and lastly, the soles of the feet. After each inunction the patient clothes the part subjected to the process with some suitable gar- ment and retires to rest. Upon the upper segment of the body the night shirt protects the sheets in sufficient manner. When the lower half is undergoing treatment a pair of drawers may be drawn on. If at any time before complete inunction of the body is accomplished the parts where the ointment has been applied show signs of irritation, such regions may be washed clean with soap and warm w'ater and dusted Avith starch or finely powdered talc. If no signs of trouble appear, bathing should be postponed until the seventh night, when the entire body should be cleansed of all traces of the ointment by means of a Avarm bath. If needed, the entire process may be repeated, beginning on the following night, or the inunctions may be continued on the soles of the feet, shifting at regular intervals from one foot to the other. The mouth must be Avatched carefully while the inunctions are in progress, and, if the gums show signs of coming trouble, the process must be stopped and a bath ordered. Merciinj by Fumigation. — This plan of using mercury is of decided value when extreme urgency in the symptoms calls for immediate action on the part of the drug. Fumigation is especially useful in those cases of extensive syphilodermata in which the lesions cannot be made to submit to ordinary forms of treatment, or when their rapid removal from the face and exposed parts is necessitated by the patient's desire for secresy. In the large cities many of the bathing establishments furnish admirable facilities for giving mercurial fumigations, and when con- veniently situated it is well for the physician to make use of the ad- vantages offered. In the country or whore the patient cannot be induced to attend one of the institutions named the practitioner can 904 SYPHILIS. carry out the treatment at the patient's own home in the following manner : The individual is stripped naked and seated upon a cane- bottomed chair. A heavy woollen blanket is fastened closely about the neck, the folds being allowed to fall to the floor in the form of a tent completely investing the person. Underneath the chair a pan of boiling hot water is placed over a good-sized spirit lamp. Care must be taken not to let the blanket come in contact with the flame. This can be prevented by placing weights upon the edges resting on the floor and pinning the opening in the rear. The steam from the boiling water induces free perspiration of the body. As soon as the skin has become well moistened the mercurial chosen for sublima- tion is placed above an alcohol flame underneath the blanket. The receptacle in which the mercurial is contained may be made of a bit of tin rolled up at the edges and supported upon suitable rests. Calomel and cinnabar are the two preparations of mercury best suited for use in fumigation. They may be used singly or with better results in combination. When used alone, from a scruple to a drachm of either preparation may be employed. If in combination, it is well to use about three parts of cinnabar to two of calomel. Thus a half drachm of cinnabar and a scruple of calomel may be taken. The fumigation should continue for from ten to thirty minutes if no untoward symp- toms present themselves. If the patient becomes faint or experiences unpleasant sensations, the process must be stopped at once, the body wiped dry, and a stimulant administered. It is a good plan in the case of weak and debilitated patients to give a small quantity of brandy or sherry wine before beginning the operation. After the fumigation the patient should retire to rest. Care must be exercised in not per- mitting the body to become chilled during or after the operation. Such fumigations should not be given oftener than every second day, and ought not to exceed four in number. Supportive and tonic treatment must be continued while they are being employed. Fumigation of the mouth cavity and nasal passages is frequently needed in the case of obstinate syphilitic lesions appearing in these regions. An Ermold's calomel sublimer furnishes an elegant and easy method of supplying the fumes for such purpose. In its place a hot flatiron or fire shovel may be used. Five to ten grains of calomel can be placed on one or the other, and as the fumes rise they can be drawn slowly into the mouth and nose by inhalation. Irritation of the bronchi must be guarded against by not prolonging the process nor repeating it at too frequent intervals. Treatment of Syphilis by the Hypodermic 3IethocL — The value of this method in the treatment of syphilis is not definitely decided. There are some syphilographers wlio give it their hearty support, but they are few. The pain associated with the operation and the occasional disas- trous results that have followed its use interfere with its extensive em- ployment. The claim that great rapidity and certainty of cure can be effected by the method still demands verification. Only the briefest outline can be given here. Either the soluble or insoluble salts of mercury may be used. Cor- rosive sublimate, as indicated in the following formulse, is most fre- quently employed : Till-: ATM r.yr nr syriiiLis. 905 ^. Ilydraruvri clildi-idi ('((iTo.-ixi, ^r. \ ; Sodii cliloridi, i;t. 'i' ; A(iua' (lcstillat:i\ f.-^j.— M. Sig-. Jnjcct IVoiu one luill" to oiu' drachm every tliird day. 1]/. llydrartivri ehloridi corrosivi, gr. x ; Acidi tartariei, 3.ss ; A(iu;e destillatie, f 5J. — M. Sig. Inject ten nnnims twice a week. ^. Hydrargyri chloridi eorrosivi, gr. j ; Glycerin i, AqutB destillatffi, da. f 3j. — M. Sig. Inject ten minims daily. Other solnble salts of mercnry that may be tried are asparagiu-mer- <3ury in 1 or 2 per cent, of mcrcnrial strength ; the oxycyanide, gr. xv of 1.25 per cent, of mercnry ; the carbolate of mercnry, gr. ^ to |^; and the benzoate, mercuric albuminate, and peptonate. Among insoluble preparations, calomel, gray oil, yellow oxide, black oxide, salicylate, protiodide, biniodide, cinnabar, sulphate, and metallic mercury are a partial list of the different forms used. The use of the insoluble salts is less satisfactory than is that of the soluble varieties. The manner in whi(;h calomel is used can be taken as the type for most of the compounds given. The salt should be first thoroughly sterilized by subjecting it for at least one hour on two successive days to the action of steam, and then employing it as in the following : I^. Hydrargyri chloridi mitis, gr. ss ; Glycerini, T||x ; Aquse destillatse, TTLx. — M. Sig. Inject every four days. The amount may be increased so that two grains a week can be given. Instead of the above formula the following is sometimes used : I^. Hydrargyri chloridi mitis, gi'- j ; Mucilaginis acacise, Tllxx. — M. Sig. Inject every four days. In performing the operation asepsis is of the greatest importance. The site of operation must receive as thorough preparation as for any sur- gical operation, the hands of the operator must be alisolutely clean, and the instrument and preparations used be sterilized. The injection should be made deeply into the tissues, the buttocks furnishing a favorite site. The patient should lie flat upon the belly while the operation is beino- performed. The needle used should be about one half longer than that ordinarily employed in hypodermic medication. Care must be exer- cised not to make the injection into a bloodvessel. Hydrargyrkm—ThQ toxic effects of mercury may follow quickly upon its first administration or appear only after the druo- has been 906 SYPHILIS. given for a long period of time and in very large doses. The first symptoms are usnally manifested in soreness and sponginess of the gums. A distinet red line is formed at their border, and the mucous membrane bleeds readily. The teeth feel long, and unpleasant sensa- tions are experienced when the jaws are brought forcibly together. There is an increased flow of saliva, the tongue is heavily coated and swollen, and the breath is decidedly offensive. These symptoms may come on slowly or rapidly. If the drug be continued, all of the above manifestations become intensified. The saliva flows in a stream from the mouth, the swollen tongue fills the mouth cavity and projects be- tween the lips, necrosis of the jawbones takes place, the teeth fall from their sockets, there is high fever, the bones and joints ache, and pain and distress are felt in every part of the body. Prophylaxis consists in keeping the mouth perfectly clean and removing from it every means of irritation. At the first signs of ptyalism the mercury should be promptly suspended and iron tonics 1)6 given. If severe symptoms come on, the patient must be made to remain quiet, the emunctories of the body be kept open, the diet should be nutritious and of easily digested foods, and the mouth treated with soothing lotions of myrrh and honey. The gums should be gently wiped several times a day with a bit of soft clotli moistened in the following : ^. Tincturse myrrhse, Tincturse cinchonse, da. f 5ss. — M. Sig. External use on gums. Lotions of oatmeal water and honey are frequently grateful, as are mild solutions of potassium chlorate. All liquids, either beverages or washes, should be gently warmed before using. If the case be care- fully managed, a good recovery will usually be made. Often slight salivation is of decided benefit in the treatment of the disease. The Compounds of Iodine. — The compounds of iodine are indispen- sable in the treatment of syphilis. They cannot, however, take the place of the mercurials in the general measures instituted for the relief of the disease. The field in which the iodides are found useful is limited, and their employment should be restricted within such limit- ations. No treatment of syphilis can be more unwise than the indis- criminate giving of the iodine salts, as is often done early in the course of the disease. There is more of truth than error in the statement that mercury cures syphilis, while the iodides but check its progress. De- pendence must be placed upon the salts of mercury to eradicate the disease from the system, while the iodides are useful in bringing under subjection late symptoms that are to be regarded as sequelae rather than actual manifestations of syphilis. The iodides are indicated in the fol- lowing conditions : First, when gummata make their appearance, during any stage of the disease, in the skin or in deeper and more vital organs ; second, in those cases where the patient cannot be made to tolerate mer- cury in any form ; third, where mercury has been administered for a long period of time it is frequently of value to interrupt the course and in the mean time to give the iodides ; fourth, when syphilitic lesions cannot be made to respond to vigorous mercurial treatment. TJilUTMhWT OF SY I'll I LIS. 907 When the iodides ;uv <>iv('n accordiiio- to tlio nhovc indications tlicir intelli,e of usefnhiess, and is the most effec- tive in obtainint>- desired results. The iodide of sodium comes next in point of effieienev. The iodide of potassium may be o-iven in solution in teaspoonfid doses containiuii: five, ten, or twenty trains of the salt three times a day, but it is better ])raetiee to p:ive it in droj) doses of a saturated solu- tion, as follows : I^. Potassii iodidi, .^j ; Aquse destillatse, q. s. ad f sj. — M. Sio'. Drop doses as directed. One drop of the saturated solution represents nearly one grain of the salt. In giving" the drug in this manner its dosage can be varied to suit the conditions and necessities of the cavse. It is well to begin its administration in live drop doses after each meal and at bedtime, increas- ing the dose one drop each time or one drop in the day as the urgency of the case may demand. The increase should be pushed steadily until relief is obtained from the symptoms or until signs of iodism make their appearance. Often doses running up each to a hundred or more grains are demanded, and are well borne by the patient. The drug- should be given in milk or pure water, and always after the taking of food. Oftentimes the iodide can be tolerated better when combined with essence of pepsin, as follows : ^. Potassii iodidi, ,^j ; Essencise pepsini, 5ij. — M. Sig. Drop doses as directed. This represents the drug in about one third the strength of the saturated solution, and its dose must be correspondingly increased. When a fixed dose of the iodide is to be given for an extended period of time, it may be used as in the following formula : I^. Potassii iodidi, 5 ss-iiss ; Syrupi aurantii corticis, f.^iij ; Aquse destillatse, q. s. ad f.^viij. — M. Sig. Teaspoonful in water after each meal. The iodide sometimes causes considerable distress in the stomach and interferes greatlv with digestion M'hen taken imraediatelv after eatino-. In such cases it is well to give the following as soon as the meal is finished, and the iodide an hour afterward : !^. Tincturse nucis vomicre, foss; Essenciffi pepsini, ad fsvj. — M. Sig. Teaspoonful in water after each meal. 908 SYPHILTS. The iodide of potassium should always be stopped if marked consti- pation occurs during its administration or if disturbances in the kidney arise. Measures for the relief of such conditions should be instituted, and the use of the iodide should not be resumed until the normal func- tions of the parts have been restored. lodism. — The toxic effects of the iodides are more readily shown than is the case with mercury. Such results of the drug's action may be expressed in a great variety of lesions appearing upon the skin or in the production of salivation — a metallic taste in the mouth, coryza, con- stipation, fever, and all of the symptoms of peritonitis ; or it may occa- sion attacks of vomiting which increase in frequency and severity, weakness, anaemia, and loss of sexual appetite. The commonest symp- tom of iodism is iodic acne. The lesions appear upon the face, neck, chest, and back with greatest frequency, and are difficult to distinguish from the like symptoms of acne vulgaris. Frequently the smallest dose of potassium iodide will cause the eruption to appear, while if the drug be pushed properly the lesions will vanish. Urticaria of severe type is liable to be produced. In case of dangerous symptoms arising the iodide should ahvays be stopped and a tonic be given. Usually all manifestations of trouble disappear readily when such a course is pursued. Mixed Treatment. — By this term is meant the use of the iodide and the mercurial in combination. It is evident that the combined action of the drug can be secured in various ways. The iodide can be given internally and the mercurial externally by inunction, fumigation, or injection ; the iodide can be given at one time of day and the mer- curial at another, or the two can be given internally in the same dose. To the last method the term " mixed " is usually applied. This method of medication is useful in early stages of the disease, when the develop- ment of tubercles, gummata, or bone and brain lesions calls for the administration of the iodides. If the symptoms are urgent, treatment should be begun by giving the iodide internally and the mercurial externally. In this way either drug can be increased or diminished as indications demand. When the disease has been brought well under control, the two salts may be com- bined as in the following : ]^. Hydrargyri ioclidi rubri, gr. i-ij ; Potassii iodidi, .5ss-ij ; Syrupi glycyrrhizse, f §ij ; Aquam destillatam, ad foviij. — M. Sig. A teaspoonful in water after each meal. Or, ^i. Hydrargyri iodidi rubri, gr. i-ij ; Sodii iodidi, .oss-ij ; Syrupi zingiberis, giij ; Aquam destillatam, ad sviij. — M. Sig. Teaspoonful in water after each meal. The bichloride may be given in the same manner : Tin: ATM EST OF SY I'll I LIS. 909 ]^. H\xlrai'nyi-i cliloridi corrosivi, gr. i-iij ; Potnssii iotlidi, .>^'^-'j ; Synipi f syriiiijs. 911 i-acli cavity iiiiiy l)c filled with boric acid, ciiroplicii, oi- indotorni, and covered with a lii;ht dressing-, such as a hit of siirireon's plaster. This can be removed readily and the dressing i-c|)eated as often as needed. Usually once in twenty-four houi-s is suilicient. In the case of g:umniata and tubercles, spon*>^in^ with warm water and the apjdi- cation of mercurial ointment in fidl streu- with the disease tiiey may at times [)ro(lnce children that never dis- play any symptoms of syphilis. A syphilitic woman may ])roducc a number of syi)hilitic foetuses, then bring a healthy child into the world, iind follow it in successive pregnancies with a number of children that iire unmistakably suffering with the disease. If the mother be infected during the course of her pregnanc^y before the termination of the seventh month, the chances are that her child will inherit the disease. After the seventh month the child usually escapes unless it be infected at birth by syphilitic lesions in the maternal passages. Such infection constitutes the acquired, and not the inherited, form of the disease, and is classed as infantile syphilid. Abortion. — Few women suffering from active constitutional syphilis at the time of their conception carry its product to full term. Abortion is the rule, though exceptions to it may occur. In early stages of the mother's disease the foetus is carried for a short time only. Usually the first product of conception after the development of constitutional syphilis is cast off before the expiration of the second or third month. Successive pregnancies are carried for longer and longer periods, until a viable child that may live for a few hours is brought into the world. Later the result is the production of a living child that may exhibit symptoms of syphilis before the expiration of the fourth month or re- main entirely free from the disease throughout life. It is questionable if syphilis can remain latent throughout childhood and show itself for the first time at the puberal epoch. The probability is that in the cases apparently presenting such a condition the early symptoms of the disease were overlooked or misinterpreted. In the great majority of cases it can be asserted with safety that if the child inherits syphilis, unmis- takable evidence of the disease will become apparent before the end of the first year. Symptoms of Inherited Syphilis. — A living child the subject of inherited syphilis may show no symptoms of the disease at the time of its birth. Usually, however, its features are drawn and pinched and the skin is wrinkled, giving to the infant's face the appearance of a ^* little old man or woman." The child does not grow^, but remains puny and impoverished. The weazened look deepens and the skin assumes a sickly sallow hue. Characteristic lesions of syphilis may not appear for weeks or perhaps for months. When they are first announced they usually show themselves about the mucous outlets of the body, as the mouth and anus. Here they are displayed in the form of moist papules, mucous patches, and condylomata. Fissures show themselves within the mucous membrane at the angles of the mouth, while the skin bordering the part becomes the seat of similar lesions or of scaly reddened areas. Mucous patches develop in the mouth and throat, the tongue and inner border of the lips showing them often in 916 SYPHILIS. varying numbers. The borders of the anus show moist papules, fissures, excoriations, and condylomata. The umbilicus may be aifected in like manner. Coryza develops. Chief among the symptoms are snuffles. These are diagnostic of inherited syphilis. The discharge, at first thin and serous in nature, later grows profuse and becomes thick and muci- laginous. Swelling of the nasal membranes closes the passages. The process interferes greatly with nursing, and may wholly prevent it. The child experiences great difficulty in breathing. Extension of the inflammation from the nasal passages into the pharynx and larynx occurs, giving rise to a peculiar husky cry. Destruction of the bones of the nose may take place, with complete removal of that organ. Dry, scaling patches appear on the body, chiefly in the neighborhood of the buttocks. These dry patches are readily converted into moist lesions, owing to the warmth of the parts and the tenderness of the infant's skin. The condition changes from bad to worse. Nutrition is but feebly carried on, marasmus intervenes, and death closes the scene. The above is the picture often seen in inherited syphilis. But in the inherited form of the disease, as in the acquired form, syphilis varies greatly in the manner and severity of its expression. Especially is this true if treatment be instituted early and carried on with vigor and under intelligent direction. The worst forms of the malady may be changed for the better and a great degree of improvement produced. It should be remembered that mercury is not contraindicated in a pregnant w^oman who is suffering with syphilis, and that in the admin- istration of the drug exists the only measure that in any wise affords her a guarantee of producing a living child and of giving that child a chance to reach maturity. If the malady is not to pursue the severe course outlined above, the symptoms of the disease are apt to be delayed. The child is well nour- ished at birth, increases in weight, and is plump and apparently healthy. Symptoms of syphilis usually become apparent before the end of the fourth month, but may not show themselves until somewhat later. They arise first, as in the severe form, about the mucous orifices, and are declared in the different varieties of moist lesions. Characteristic snuffles soon appear. An erythematous eruption of a part or the whole of the body surface may ensue. This rapidly becomes coppery in hue, and papules may develop. If unchecked, the skin lesions may take on any of the forms seen in acquired syphilis, and their subsequent be- havior is in accord with the course that is there pursued. Dry papules arise upon the hands, feet, and face. Moist papules and condylomata appear about the anus and in all moist localities. Nodes, exostoses, and gummata develop within the bones, often resulting in great deformity of these structures. The brain, heart, lung, liver, eye, and testicle may become the seat of gummatous infiltration. Treatment of Ixheeited Syphilis. — Treatment of a child liable to be the subject of inherited syphilis should begin while it is still in the womb of its mother. This is done by subjecting the mother to vig- orous antisyphilitic measures. The sooner such a course is instituted after conception has taken place, and the more energetically it is pushed, the better will be the child's chances of coming into the world free from symptoms of the disease and remaining healthy afterward. IIEIIKDITARY SYPHILIS. 917 The plan of treatment best suited for mother and eliild undcM- sueli conditions is that of mercurial inunetion. This should be j)ush('d at varying- intervals to the point of produeinn' distinct constitutional symp- toms, care being taken noi to cause actual salivation. With the first sign of systemic effects, such as the formation of a red line at the border of the gums, factor of the breath, or a marked metallic taste in the mouth, the inunction should be stopped and mixed treatment by the combined use of potassium iodide and l)iniodide of mercurv be substi- tuted. This latter course may be continued for from two weeks to one month as seems best to the judgment of the j)hysician, when the inunc- tion should again be resorted to. During this time hygienic and other measures calculated to improve the mother's health should not be neg- lected. The mercurial preparations found useful in the internal treatment of syphilis can be employed, but not with the advantage to be obtained from the inunction. When used care must be exercised not to push their action sufficiently to bring on intestinal irritation and diarrhoea, as by such a course abortion may be brought about. If the mother be suffering from late forms of the disease, such as gummata of bone, brain, or skin, potassium iodide should be given interna 11 V in full doses, while the inunction is being continued exter- nally. Lesions in the vagina, such as mucous patches and ulcers, need care- ful attention. The parts should be subjected each day to warm douches of boric acid or permanganate of potassiiun solution, extreme caution being used in not throwing the stream too forciblv against the uterine neck, as by such procedure premature labor may be excited. Frequent application by the physician of a solution of silver nitrate to the lesions is of decided value in promoting their resolution. When the child is born with unmistakable symptoms of s^-philis or develops such symptoms shortly after birth, its treatment must be begun at once. Great care, however, must be exercised by the physician in determining that the infant is actually suffering from syphilis. The offence is unpardonable on the part of the practitioner to pronounce every ailment of early childhood due to syphilis because the parents are suffering from the malady. Many children of parents who are the sub- jects of syphilis never show the slightest taint of the disease, and this is particularly apt to be the case when the mother has been given care- ful and energetic treatment. Treatment of the child may be by the internal or external method as seems to the physician best suited to the case. External treatment should be by inunction, and is to be chosen in preference to the internal administration of mercurials when the tender skin of the infant can be made to tolerate the applications. This can be accomplished in most cases by exercising thorough care in the cleanliness of the child and by shifting, at frequent intervals, the places to which the ointment is being applied. Mercurial ointment may be used in the form of the offici- nal preparation or it may be combined with equal parts of pure vase- line or lanoline. Brodie's method furnishes decidedly the best means of applying the unguent. This is done by spreading the ointment freely upon the child's bellyband and keeping this in close contact with 918 SYPHILIS. the skin. The part must be watched carefully, in order that a derma- titis may not be excited. At the first appearance of redness the oint- ment must be applied to some other portion of the body. This can be easily done by putting a band about one of the infant's limbs and spread- ing this with the ointment, as in the case of the bellyband. In this manner the inunction can be continued for quite long jieriods of time. It is often of great service to suspend the external treatment as occa- sion demands and resort to internal measures during the interval. Where inunction is contraindicated or impossible, internal medication may be instituted. Any of the mercurials used in the treatment of syphilis may be employed, but some, as calomel and the gray powder,, seem productive of better results than others. Calomel is to be pre- ferred in beginning the course, and, if it is found effectual in its action,, should be continued. It may be given in doses varying from one twen- tieth to one half of a grain three times a day. The calomel may be combined in powder form with sugar of milk, or one of the tablet trit- urates supplied by all drug houses may be rubbed up fine and given in a little milk. It should always be administered after the child has been fed either at the breast or from the bottle. The gray powder may be given in the same manner as the calomel and in doses varying from one tenth to one grain. The bichloride can be tried when the above do not answer the purpose. It can be given in solution in doses of one two hundredths to one fiftieth of a grain. A teaspoonful of this can be administered in milk three or four times a day. The protiodide, binio- dide, and black oxide may be tried in doses suited to the child's age, but are not often well tolerated by the infant's stomach. The mercurial given internally must be promptly stopped upon the appearance of diarrhoea. Tonics and cod-liver oil are frequently needed in the treatment of the infant. Iron may be given in the form of the citrate of iron and quinine, as follows : I^. Ferri et quininse citratis, 3j ; Syrupi aurantii florium, Aquae destillatse, da. f 5J. — M. Sig. Three to five drops in milk twice a day. Cod-liver oil is indicated when the child does not increase in weight,, but remains puny and poorly nourished. The pure oil should be given. None of the much vaunted emulsions can be trusted not to disturb the stomach. The dose of oil should begin with ten drops, given best in milk, twice a day. This amount should be increased slowly as the little patient becomes tolerant of its action, until as much as a teaspoonful is being given two or three times a day. When brain, bone, or visceral lesions arise, potassium iodide is indicated, and should be given three times a day in doses varying from one half to four grains each. The drug is extremely apt in these little sufferers to produce its peculiar acne and other forms of iodic rashes. Often the iodide can be given better combined with the biniodide of mercury, as indicated in the formula for mixed treatment (page 908) From three to ten drops of the mixture can be given in milk three times a day after the infant has taken food. SYPHILIS AND MARRIAGE. 019 Local treatinc'iit of sy})liili(ic lesions is indicated as in the adult, and the means described as iiseliil in .such cases can be employed here if modified to suit the tender conditioji of the infant's tissues. Mucous patches in and about the mouth should recreive special care. The mouth should be kej)t thorouiihly clean, and be treated freely each day with a mixture of honey and boric acnd aj)plied on a raj^ wrapped about tlu> end of the finger. Snuffles should be treated by thoroughly cleansing the nose with warm boric acid solution, drying, and then painting the nasal ])assages lightly with a weak solution of silver nitrate. After- ward the parts may be sprayed with liquid albolene. A drop or two of Bellamy's iodized phenol in an ounce of albolene can be used with advantage in spraying the throat. The anal and umbilical regions should be kept scrupulously clean. If condylomata make their appearance in such places, they should be cleansed with warm water or boric acid solution, and then dusted thickly with calomel and talc in the propor- tion of 1 : 4. The treatment of the mother should be continued in the form suited to her case. If possible, this should be by means of the mercurials, as potassium iodide is capable of suppressing the flow of milk. Such an accident is of serious import in the treatment of the child. The child should always be nursed at its mother's breast, never at the breast of another Avoman. If for any reason the mother cannot supply the nourishment needed, the child may be fed on pasteurized cow's or goat's milk. Syphilis and Marriage. The length of time that must elapse between the date of infection and the time when marriage can be safely permitted depends entirely upon the course pursued by the disease. In some severe cases marriage ought never to be contracted. The number of such cases, however, is limited. In the majority of individuals infected in early life a time comes when it is safe for the patient, whether man or woman, to marry. For the individual who is sound and healthy at the time of infection, and who enters upon a thorough and effective course of treatment at once, following it faithfully for a period of two and a half or three years, marriage can be safely entered into between the third and fourth years. This, however, should not be done unless the disease has shown no manifestations during a period of at least six months, in which all medi- cation has been suspended. In no case, no matter how slight may be the earlier symptoms, should the physician give his consent to marriage before two years from the time of infection, and this only when vigorous antisyphilitic measures have been followed during the greater part of that period. The vouno: man eng-ao-ed to marrv at the time of contracting the dis- ease should be urged to make a frank statement of his condition to the woman in question, and to ofier her a release from the agreement. She should be told fully the danger of her contracting the disease, even if she chooses to condone the fault and to continue the engagement, and the restrictions that will have to be placed upon her actions with refer- ence to caresses and like approaches. Complete separation of the parties interested is advisable under such circumstances. 920 SYPHILIS. In the case of husband and wife the same frankness on the part of either should be required. Here, where the husband is so often at fault, a free, honest confession of his sin to his partner nearly always results in forgiveness and the continuance of the marriage bond. Sepa- ration by living at a distance from each other for a period of two or more years is the most desirable plan to be followed in such cases. If such a course cannot be pursued, cohabitation should be strictly forbid- den and the occupying of separate beds be insisted upon. LEPROSY. By ISADORE DYER, M. D. Synonyms. — Lepra ; Elephantiasis Graecorum, Hebrseorum ; Leon- tia.sis ; Satyriasis ; Ophiasis ; Tzaraath (Hebr.) ; Kushta (Ind.) ; Juzam Dalfil (Arab.); Fa-Fung and Ta-ma-fung (Chin.); Boasi (So. Am.); Lebbra (Ital.); Radesyge, Spekalshed (Xorweg. ). Definition. — Leprosy is an endemic, infectious, constitutional dis- ease, due to a special bacillus, ^vhich in its development gives rise to structural changes of the skin and mucous membranes, nerves, bone, and other tissues, attended with general symptoms, anaesthesia, loss of tissue, and final deformity or death. History and Distribution. — At the time of Christ leprosy was prevalent in the East. Before this era the history of leprosy is quite obscure. Indefinite references are made in the Bible in the books of Exodus ( iv. 6 ) ; Leviticus (xiii. 24, 25, 43, 52) ; Numbers (i. and xii.), and Deuteronomy (xii.). It existed, probably confined in the early his- tory of the world to Egypt and the Orient. In India the disease was recognized as early as fifteen hundred years before Christ. Six hundred years before Christ the Persians instituted measures to rid the country of the disease (Leloir). Celsus describes the condition in detail as early as the year 25 a. d. At this time Greece and Italy had been invaded. Giilen in the second century chronicles the further spread of leprosy into Spain, France, and Germany. As early as 636 a. d. lazarettos were established in Italy. In the tenth century England and Scotland were afflicted. In the eleventh and twelfth centuries, during the Crusades, the disease spread all over Europe, reaching then the acme of its force and determining the subsequent measures for its control. At this time (at the death of Louis VIII., 1229) it was estimated that there were nineteen thousand leprosaries in Europe and two thousand in France alone.' Yielding to this enforced control, the disease gi-adually disappeared from the fifteenth to the seventeenth century, surviving only in a few isolated districts. AVitli the disappearance of the disease in Europe it began in the col- onies of the Americas and the islands of the Pacific and Indian oceans. Xo country or climate has been spared in the gradual distribution of the disease. It has spread wherever it has been introduced. Its appearance in a new country has always been directly traceable to importation from an affected countr}'. It is endemic in Xorthern and Eastern Africa, Madagascar, Arabia, Persia, India, China and Japan, Russia, Norway and Sweden, Italy, ' Leloir, Traite de la Lepre, Paris, 1885. 921 922 LEPROSY. Greece, France, Spain, in the islands of the Indian and Pacific oceans. It is prevalent in Central and South America, Mexico, in the West Indies, the Hawaiian Islands, Australia, and New Zealand. It is found also in New Brunswick, Canada. In the United States the majority of cases occur in Louisiana and California, while from many other States cases are occasionally reported, notably from New York, Ohio, Penn- sylvania, Minnesota, Missouri, the Carolinas, and Texas. In Louisiana leprosy has been gaining foothold since 1758, when it was introduced by the Acadians. Varieties. — The varieties of leprosy usually described are three : 1. The tubercular ; 2. The ansesthetic ; 3. The mixed. In the development of the bacilli of leprosy in the economy there are evolved neoplastic growths to which Leloir has given the name of "^ lepromes" These may occur at any part of the body and are respon- sible for the lesions of the disease. As they occur in the skin, in the mucous membranes, or in the nerves, muscles, bones, etc., so the affection is determined. For purely clinical reasons the disease attacking the skin and mucous membranes is given the name tubercular or cutaneous leprosy, while that attacking the nerves is called nerve leprosy, or the anaesthetic leprosy, or tropho-neurotic leprosy. The mixed is the "complete" type sharing the physical charac- teristics of both of the above. Another variety is sometimes separated,, the " macular." This may as well be called a type, as each is but a stage in the development of the entire disease, and it is indeed difficult to draw the fine lines necessary to the separation of the mixed from the merging ansesthetic and tubercular types. It is rare, moreover, to observe a case in which the pure tropho-neurotic or the pure tubercular type is maintained to the conclusion of the case. Etiology. — The direct cause of leprosy is the bacillus lejwoe ; the in- direct, contagion. This position needs some discussion, as the question of the contagiousness of leprosy is still an open one. The contagiousness of leprosy is difficult of demonstration, because it is impossible to determine the period of incubation, and as yet no- primary lesion has been discovered. Of all bacillary diseases, it alone is discriminated against by the anti-contagionists, and that with no posi- tive argument. It is accepted as a bacillary disease and as infectious by many wdio will not admit contagion for lack of actual evidence. It resembles bacillary infectious diseases, especially tuberculosis and syphi- lis, in its methods of development. Further than this, there are evi- dences of contagion which cannot be combated — namely : 1. The undoubted spread of the disease. This is particularly nota- ble in the Sandwich Islands and in Louisiana. 2. Its recrudescence after years of quiescence, even after apparent eradication, as in Brittany in France, 3. The history of individual cases of the disease in persons foreign to the region or climate who had contracted the disease when exposed,, as Father Damien, Father Boglioli (Professor Jones's case in New Orleans), and numerous instances of nurses and attendants. 4. The accidental contagion, as in the medical student (reported by ETIOLOGY. 923 Van Dyke Carter from Dr. Ilatcli's notes) in India who was aoci- dentally cnt while makinj:; a post-mortem on a le})er. 5. Several members of the same family affected and successively with no history of ancestral leprosy. The author has 4 instances of this in point:' 1, granddaujrhter and grandmother (Germans), the former affected two years before the latter ; 2, two brothers (native Creoles), one affected several years before the other; .'], mother and daughter (negro Creoles), daughter affected seven years before the mother; 4, father and daughter (Irishj, daughter affected seven years before the father. Xo history of exposure or of family tendencies in any of these cases. 6. The origin of the disease in single members of a family living in a leprous community. 7. The effect of isolation or segregation on the spread of the disease. ( Vide Sandwich Islands in 1885, 4500 cases ; Norway and Sweden in 1895, approximated 2500 cases ; etc.J 8. The fact that neither age nor sex nor race is spared, while poverty and overcrowding and conditions of inferior hygiene seem to determine the selection of the lower social strata, as with many other infectious diseases. 9. Inoculation has been successful in one case (Arning), even if there may have been family predisposition. 10. Experiments with animals reproduce the disease in loco, if not systematically. 11. The bacillus is capable of culture on suitable soil (Byron et ah). 12. Leloir tabulates cases of direct infection between husband and vn.{e in 17 cases, also tabulates cases of suggested infection from clothes and from the occupancy of houses formerly used by lepers (op. cit.). 13. The disease can be traced from one country to another. 14. The bacillus is found in leprous tissue and nowhere else. There are, besides, certain predisposing or general factors in the production of leprosy which must be considered. Chief among these is heredity. The fact that the disease occurs in successive generations and collaterally argues some force in heredity as a factor. Leprosy has never been proved hereditary or congenital, most cases occurring at ages precluding such an hypothesis. The Report of the British Leprosy Commission in India, after the examination of 2000 cases (1893), concludes " thcit leprosy in India cannot he considered an hereditary disease, and they ivould even venture to say that the evidence ivhich exists is hardly sufficient to establish an inherited predisposition to the disease by the offspring of leprous patients to an appreciable degreed If the child is removed, leprosy is only rarely developed, and then it cannot be proven that there was no exposure to a possible infection (ibid.). In many so-called hereditary'' cases the child was affected first. A child often becomes leprous without family history and with no subsequent development in parents. The author has recorded 2 such cases: 1. A girl child of twelve with the disease two years ; 2. A boy of six with the disease one year and a half. It is rare to see leprosy under the fifth or sixth year. Indi\ddual predisposition is to be regarded among this class of gen- eral causes, as it must explain the exemption of one person while another 924 LEPROSY. is attacked. Among the contributing causes are the constitutional con- ditions, among which are syphilis, malaria, tuberculosis, scurvy, alcohol- ism, and sexual immorality. Bad nutrition, bad hygiene, fish diet, espe- cially in districts where half-raw fish is eaten, pork diet, changes of temperature, a moist climate, and vaccination (?) are further probable elements in the production and propagation of this disease. The majority of those affected are males, while the age ranges indefi- nitely from six to seventy-five, but cases are more numerous between the ages of thirty and fifty (Leloir and British Leprosy Commission). Pathology. — The bacillus of leprosy in its development gives rise to certain exudative changes, which begin ordinarily in the corium and are associated with changes in the lymph vessels or the bloodvessels themselves. The nerve lesions show a proliferation in the interstitial connective tissue. All these neoplasms (says Neisser) show a corre- sponding structure — a cell mass separated by sparse fibrillary interme- diate tissue. The cellular elements, like lymph corpuscles, gradually grow in size until they are four or five times the original volume. The cells are spheroidal, spindle-shaped, or rounded. The tumors in leprosy are granulation tissue, made up of cells which grow and form the " giant " cell of the disease, finally breaking down and disappearing, leaving behind masses of connective tissue, fibrillary in character, most marked in the regions where the nerve is affected. These cells are grouped as well around the bloodvessels, causing them to hypertrophy and become varicose and much thickened. Ultimately the leprous tissue is absorbed or eliminated, or it may be destroyed by some ulceration brought about by external factors. The bacillus leprce was discovered in 1868 by Hansen, but the descrip- tion of it was not published until 1880,^ and confirmed by Neisser in 1879.^ Others to describe the bacillus were Cornil, Thoma, Hillairet, John Hillis, Kobner, Atkinson, Koch, Unna, and Thin. The bacillus leprce is described as a small rod bacillus, from one half to three quarters of the diameter of a red corpuscle in length, and in breadth about one fifth that length. It is straight or slightly curved, with pointed or rounded extremities. It occurs in short chains or beads resembling the tubercle bacilli (Byron), and may have its extremities clubshaped (Fig. 53, p. 925). The bacillus is readily stained with the anilines and by Gram's method.^ The bacilli are seen either contained within the "giant" cell or dis- tributed in irregular groups in the granulation tissue. The bacilli occur in all leprous tissues of the body. They are found in the secretions, with the exception of the urine. Kobner alone claims to have found them in the blood. Arning claims to have found the bacilli in the earth from a leper's grave (quoted in British Leprosy Commission). Various specimens of earth were examined by the Brit- ish Leprosy Commission in India, and in several instances the germ was found. Various fish have been examined for the bacillus, but with negative results. ^ Quart. Journ. Microscop. Science, Loudon, 1880, N. S. xx. 92-102; Virchow's Arch., 1880, Bd. 79, p. 31. ^ Breslauer Artzl. Zeitschrifl, 179, Nos. 20, 21 ; Virchow's Archiv, Bd. 84, p. 514. ^ Sternberg, 3fan. of Bacteriology, 1892, New York. symptoms: 925 Among' otliors, livruii nuidc :i |)iirc culture ol" the biu-illus in agar- agar. This he has descriluMl in (h'tail.' In 1884, Arning inocuhited Kcaiiii, a Hawaiian, with leprosy, which was foUowcd in six inontiis by a w<'ll marked h'prons tnbereh' at tlie site of the iii<)cul:itii)ii. 'Hiree years later ICeaiui had well marked le|)rosy. Fig. o3. Bacillus lepras (Byron). Discredit, however, is cast upon this experiment because the nephew, son, and maternal first cousin of Keanu Avere lepers. In animals Damsch, Campana, and Vossius have succeeded in repro- ducing the disease in loco, but not elsewhere. Melchior and Ortmann^ succeeded in distributing the disease to the visceral organs, etc., follow- ing the introduction of a freshly extirpated leprous tubercle into the anterior chamber of a rabbit's eye. Symptoms. — All cases begin with the same preliminary manifesta- tions, and it is only a small differentiation which determines the several stages. The incubation of leprosy is not definite. It is variously esti- mated at from a few weeks to twenty or even forty years, and the time is often wrongly reckoned from the possible exposure at a remote period, when it may have occurred far more recently. There are, however, cer- tain prodromal manifestations wdiich may determine the period of inva- sion. The one most constant symptom is the occurrence of fever, inter- mittent or irregular in periods and in type. Among the other notable symptoms are malaise, anorexia, dyspepsia, epistaxis, dryness of the nasal passages and respiratory tract, vertigo, headaches and neuralgias, rheumatic pains, articular pains, and exaggerated functions of the cutaneous fat and sweat glands. The latter especially is a notable symptom in developing lejjrosy, the sw^eating being almost periodical and associated rather with nervous than with febrile disturbances. There is in all instances a sense of anxiety, of anticipated calamity. 1 Research. Loomis Lab., 1892, ii. 87-90. ■^Berlin. Hin. Wochen., 1885, No. 13; 1886, No. 9. 926 LEPROSY. There may be pruritus or hyperesthesia of the skin, with neuralgic pains in all locations. These are the premonitory evidences of leprosy, often associated with indefinite eruptions of erythematous patches at various and irregularly selected parts of the body. Eed at first, these spots become brownish, the borders white and occasionally thickened. These fade, and reappear in the same or other parts of the body, some fading, while others are making their appearance. Some persist for days, weeks, or months, finally fading, often quite rapidly. This is the macular stage of leprosy, really only a group of symp- toms of the premonitory stage. Xow there may appear bullae on the extremities, at the knees and elbows, wrists and ankles, but most often over the articulations of the phalanges of the fingers and toes. These may come in groups of bullee, none larger than a spHt pea, or in single lesions the size of half a pigeon's egg, which appear as clear blisters filled with a yellowish white, semi-translucent fluid. Quickly, however, they become cloudy and pustular if they do not break through their thin walls. They heal quite rapidly, leaving behind a faint pigmenta- tion or a superficial scar. Successive eruptions may recur for months or years before the determinate symptoms of confirmed leprosy appear. These may be characteristic at the start. The tubercles may appear at once, and they vary in phvsical charac- teristics. They may be described as spherical or rounded nodosities, varying from the size of a pin's head to that of a hazelnut, hard and ■elastic to the touch, pale or red brown in color, at times copper colored, smooth, and telangiectatic. In the negro these tumors are shiny and dusky brown, with a marked tue of red, the surrounding skin being much darker in color, especially immediately proximate to the periphery of the lesion. The lesions are •discrete and form distinct individual nodosities, or they mav become •confluent, forming irregular oblong or gyrate bunched masses. Often the eruption begins quite differently. The macules of the pre- monitory eruption may remain or other patches form, which vary in size, averaging the size of the palm. Usually simply hyperaemic or wine colored, they may be violaceous, livid, brown, yellow, or almost black. The centre is sometimes darker than the margin, sometimes depressed, free from color, an annulated lesion forming the patch. 1. The Tubercular Type. — In these patches the tubercles now form. There is a sudden rise of temperature, persisting irregularly. The patches thicken and grow elevated, become nodulated and bunched, forming irregular nodosities which gradually assume shape. They may remain under the skin, but more often grow until they are much enlarged and cause deformity by their prodigiousness. This constitutes the tubercular form of leprosy. The most frequent seats of the lesions are the face, the hands, the feet, the forearms, and the lower extremities. The face oifers the favorite location for the eruption, and it is selective of the forehead, the eyelids, the nose, lips, chin, cheeks, and ears. The nose is flattened, infiltrated, hypertrophied, lobulated. The cheeks are likewise thickened, bunched, and nodulated. The ears become leathery, thickened, many times enlarged, and the lobules hang pendulous, often a mass of highly developed tubercles. The tubercles tend to confluence. They also tend to grow, and may become immensely hypertrophied. SVMI'TfJMS. 927 * exfoliate, or become compliciited with (imIlmiki. Spontaneous retrogres- sion may obtain. Then tlu' lesions soften, sink into the skin, shrivel, and finally disappear, leaving a })igniented spot to mark the site. More often, however, the process is different. They become inflamed, sup- purate, and slough in part or entirely. They may ulcerate in a sujK'r- ficial way, gnidiially destroying the suljjacent tissues, attacking in turn the tendons, ligaments, and l)ones. (Jn the mucous membranes the tubercK's ulcerate readily, producing at tirst disturl)ances, then destruc- tion of the affected region. Within the nasal cavity the septum gives way to the process, and early in the disease disfigurement results, with a consequent interference with speech and smell. Leprous deposits likewise form in the conjunctiva, gradually extend into the cornea, and affect the vision, finally causing ulceration and blindness. The glands are much enlarged in all regions, but particularly in the submaxillary and cervical. The mental faculties are not much affected, excepting that there is a constant anxiety on the patient's part, anticipating some unknown and inapprehensible misfortune. The testicles gradually atrophy, and, if the disease begins before puberty, the physical development is greatly retarded.^ Tubercular leprosy develops rapidly, and is liable to attack any region of the body. The destructive process attendant upon the ulcer- ating lesions, especially of the extremities, is more than likely to result in mutilation and deformity, in which this does not differ from the type presently to be described. 2. The Ancesthefic Type. — The anaesthetic or tropho-neurotic form of leprosy, or, as Leloir calls it, the " systematic nervous leprosy," differs in no respect from the tubercular in its period of invasion. The bullous eruption, however, usually appears as the single lesion, incessantlv re-forming, until finally there is only an ulcer left, which becomes obsti- nate and persists with constant destruction of tissue. From this periph- eral lesion anaesthetic or nerve leprosy may start. Beginning on one finger, the balance of the digits of the affected hand will one by one be attacked, followed by those of the hand on the other side. The feet may follow or present lesions at the same time. This is often the his- tory. The ulcer becomes a trophic one, with a localization in the fleshy part of the heel, great toe, or the ball of the foot. It is painless and persistent. It is characterized by the sharply cut edges, the sur- rounding infiltrated and thickened skin, and the typical nauseous discharge. The anaesthesia starting from these lesions extends up the hand and arm, associated with loss of sense of heat and cold, pain, and even touch at times. Then, or before, the macules of anaesthetic leprosy appear. The characteristic and most important lesion of this type is the macular patch, with a well defined pigmented, usually brown, periphery around an atropine centre, free of color or of a parchment yellow hue. The edges are often thickened and elevated. The patches are often serpigi- nous or gyrate as a result of confluence. These patches are always markedly amesthetic, the discolored parts being most anaesthetic and proportionate to the degree of color. ' Neisser, in v. Ziemssen's Cyclopcedia. 928 LEPROSY. *■ These are the lesions of the eruptive stage of the ansesthetic type, or Leloir's " period of invasion." The patches themselves may anoma- lously become hypersesthetic, or points of hypersesthesia develop at other parts of the body. Likewise, anaesthesia may occur without any deter- mining lesions. Neuralgic pains are common, and marked thickening of certain nerves occurs, notably the ulnar. Just here an almost constant symptom is evident. This is the anaesthesia of the little finger, which is present even before any lesions have appeared on the hand. Following the eruptive stage is the permanent stage or the stage of degeneration. It is marked clinically by trophic disturbances, atrophies, paralyses, etc. Motor paralyses of the face, hands, and feet are soon evident. Insensibly the patient loses the power of grasping objects, the sense of touch, as well as loss of muscle control, being gone. There follows muscle atrophy of the face, distorting it, and of the hand, causing contractures. Ectropion of the lower lids results, so that the eyes cannot be closed. The lips become flabby and the lower one drops. The extensor and flexor muscles of the forearm contract, and the " claw- hand " results. The muscles of the lower extremities are aflected in the same way. A shuffling gait, due to inability to raise the feet, and final incapacity of motion, result. Then come atrophy of the skin, shrinking of the skin, and a general appearance of senility. There are numerous trophic disturbances, such as falling of the hair, loss of pigment of the liair, loss of teeth, shedding of the nails, ulceration of the gums and of the nasal passages. The ulcers over the articulations of the phalanges extend to the articulation, cause the phalanges to fall, or, occurring in the middle phalanges, cause shortening or contraction. Dry gangrene, or necrosis, occurs ; absorption of the bone and deformity result. The mutilating process may progress to the loss of the entire hand or foot. 3. The Mixed Tfpe. — The " mixed " type of leprosy is, as its name suggests, a combination of the two varieties just described. It is the complete development of these two stages, with the symptoms and cha- racteristics of each. It may begin with the ansesthetic macule and the prominent tubercle, both well defined and occurring simultaneously. More often one variety, usually the tubercular, assumes the type of the other. In this form of the disease the lesions are perhaps more promi- nent and the symptoms are more profound. Oedema of the extremi- ties is quite common ; the fingers lose their shape, become tense and shining, looking as if the skin would burst. The course and the result of mixed leprosy are the same as with the other stages. Diagnosis. — The diagnosis of leprosy can be made readily when the disease is well developed. Tubercular and ansesthetic leprosy can scarcely be differentiated until the lesions have matured. In the former the early bullous eruption is more often in groups ; in the latter, in a single recurring lesion. The folloAving list contains the determining points in the diagnosis of all stages and types : 1. Habitat, whether community or family domicile ; 2. History of contact with, or exposure to, the disease ; 3. Anaesthesia ; 4. Trophic disturbances ; PROGNOSIS— TREA TMKNT. 929 5. Eruptions of biillie in successive crops or of a single one recurring ; 6. Porforutin. One case ri('ger and b^riiukel have obtainetl a to.valhiunin through j)reeij)ita- tion with aleoliol, wiiich they found much more active than the basic bodies discovered by the former. Even this toxalbumin is much less poisonous than the Ultrate itself. Further experiments in this direction have not as yet led to any definite knowledge as to the composition of this remarkable [)oison. It probably is not an albuminous l)ody, as it develops readily in matter free from albumin. Tetanus occurs at all periods of life. It is met with in newly-born children (tetanus neonatorum) and in advanced life. It is more frequent in males, on account, no doubt, of their greater exposure to the exciting causes. It is considered to be more frequent in the dark-skinned than white people, even in the same country. It has long been recognized that it is much more frequent in hot than in cold countries. In the East Indies, Central America, and the West Indies it is much more common than in Europe or North America. The development of the tetanus bacillus is favored by its being introduced in company with other bacilli, especially those having pyo- genetic properties (streptococci, staphylococci, etc.). It was formerly taught that cold was an exciting cause of the so-called idiopathic form, but in the light of recent researches this idea must be given up. The not infrequent appearance of tetanus in soldiers wounded in battles can be more readily explained by the contamination of the wounds with earth than by supposing that cold is an active agent. In all probability mental anxiety, alcoholism, and other debilitating causes have a more or less predisposing influence, as they lessen the resisting power of the tissues in general. Puerperal tetanus, a not uncommon variety in hot countries, but extremely rare in temperate climates, is one of the most serious forms in which the disease is met with. It occurs after abortion, and also after labor at or near the full time. It generally occurs where there has been some complication, either during or after the expulsion, hemorrhage, conditions requiring the use of the forceps, adhesion of the placenta being the most frequent. It is not necessary to assume that in puerperal tetanus there is any special cause or factor at work other than the bacillus. Tetanus neonatorum, like the puerperal variety, is a disease essen- tially of tropical countries. There is, however, one striking exception to this rule : in the island of Heimacy, near Iceland, the population at one time was kept up only by immigration, almost all the children dying from tetanus.^ The infection in tetanus neonatorum occurs through the umbilical wound. Tetanus occurs also after the operation of circumcision in hot countries. Pathological Anatomy. — In a few cases of tetanus slight changes have been found in the central nervous system. It is, however, ex- tremely doubtful whether they have any significance, being probably the result of the fever and convulsions directly, rather than the effects ^ Gowers' Z^iseases of Nervous System, vol. ii. p. G79. 938 TETANUS. of the poison. Dilatation of the bloodvessels with slight capillary- extravasations are the most frequent changes described. In several cases examined within the past few years, and according to modern methods, no lesions have been detected. No constant changes have been found in the peripheral nerves. In a few cases the nerves at the seat of infection and for some distance have been inflamed. The changes found in the heart and lungs depend on the immediate cause of death, and have no connection with the action of the poison. The muscles in some cases are torn as the result of the violent contraction ; frequently they are also the seat of small hemorrhages. The wound which is the seat of infection may be found cicatrized or in a state of suppuration. Usually the tetanus bacillus can be discovered after death in the wound. Symptoms. — The period of incubation varies between one and twenty-two days. In a case of accidental inoculation with a filtrate of the tetanus bacillus in the left hand the first symptoms were expe- rienced on the fifth day. In the great majority of cases the period varies between five and ten days. As a rule, the onset is slow, the first symptom usually complained of being a sense of stiffness in the movements of the neck or jaw. Some hours or a day or two may supervene before any special difficulty is experienced in opening the jaws. In a few cases the first tetanic symptoms set in in the part nearest the seat of infection. In the case just quoted of accidental inoculation in the left hand the first tetanic spasms began in the same extremity. The rule, however, is, at least in the human subject, for the first tetanic symptoms to appear in the masseters or in the muscles of the neck. It is rare for difficulty of swallowing (tetanic spasms of the oesophagus) to be the first symptom complained of. The rigidity of the muscles gradually increases, and soon involves those of the face, producing the condition known as the risus sardonicus. The angles of the mouth are drawn outward and downward, the upper lip being firmly pressed against the teeth, giving rise to the peculiar appearance. The rigidity of the muscles of mastication prevents the patient from being able to open the mouth, hence the terms "trismus" and " lockjaw." The rigidity of the muscles of the neck causes retraction of the head, and, as the spasm gradually involves the muscles of the back and lower extremities, causing an arching forward of the trunk, when the rigidity of the muscles of the trunk and lower extremities is pronounced, as it nearly always is in severe cases, the patient lies with only the back of the head and heels touching the bed (opisthotonos). It is extremely rare for the body to be arched forward (emprosthotonos) or to one side (pleurothotonos). The chest is more or less fixed in a state of expira- tion, and the abdomen is retracted. The abdominal rectus can be felt in thin persons contracted into hard tumorlike masses. Not infrequently, from rupture of vessels in the muscle masses, sanguineous tumors are formed. The lower limbs are usually rigid in the form of extensor spasm. The muscles of the upper limbs are seldom rigid. Symptoms pointing to rigidity of the diaphragm are not unusual, as severe, cramplike pain in the epigastrum and feeble voice or total aphonia. innuornouic tetanus. 939 The rio:iclity <>t" the (lillcrcnt iniisclcs is an almost constant condition (hirin<2: the j)ro^i'Css of the disease, vtrryin^, however, from hour to hour. It often ceases (hiriny' sleep, whether hron^ht about spontaneously or artificially (chloral, oj)iuni, ehlorolurm). The muscles, however, at once assume their rii^id state when the j)atient awakes. In addition to the constant rigidity, in nearly all severe cases are sudden exacerbations, coming on with great suddenness and lasting from a few seconds to two or three minutes. The jnx'vioiis muscular distor- tions are greatly intensified. The (;ontractions of the filatures are fright- ful to behold. The face and extremities become livid. The tongue may be caught between the teeth. These intermittent })aroxysms may arise spontaneously or from some outside irritation, such as a draught of cold air, the least touch, or a voluntary effort. The suffering of the patient is agonizing in the extreme. During all this suffering the mind remains clear. The temperature varies much in different cases. Frequently it has been fonnd normal throughout the entire course of the disease. As a rule, there is a moderate pyrexia, from 101° to 102° F. In fatal cases the temperature, if not elevated in the earlier stages, generally rises to 103° or 104° F. before death. In those cases where pyrexia is present throughout it is usually found that there is no morning fall or evening rise. Sometimes a slight rise during the period of exacerbation has been noticed. Again, very sudden and very irregular changes occur in the course of the pyrexia. Hyperpyrexia is not infrequent in the fatal cases, the temperature rising for some time after death. Temperatures of 110°, 111°, 112°, 113°, and even 114° F., have been recorded. The cause of the pyrexia is not fully established. No doubt the excessive muscular work is an important factor. The writer has met with hyperpyrexia in a fatal case of strychnine-poisoning. One hour before death the temperature was found to be 108°, and in half an hour it had reached 109° F. The same cause being at work in tetanus — muscular overaction — will account for some cases. It, however, must be remembered that in pontine and cervical cord lesions hyperpyrexia is a fairly common symptom. The pulse is slightly quickened, especially during the acme of the paroxysms. It is often small (vasomotor spasm). In fatal cases it becomes very weak and rapid, 160 to 200 in the minute. In severe cases the skin is bathed with perspiration. The urine is usually scanty and high colored. The amount of nitrogen excreted is said not to be increased, even when pyrexia is present. The patient may be unable to pass urine, owing to the spasms of the abdominal muscles. Obstinate constipation from this cause is the rule. Cephalic Tetanus or Hydrophobic Tetanus. — Under this heading it is necessary to describe a rare variety of tetanus which was first observed by Rose. It results from wounds in the region innervated by the cranial nerves, especially the fifth. The special feature of this variety is that the trismus is associated with paralysis of the face on the same side as the injury. Usually there is also marked spasm of the pharynx and oesophagus, hence the term hydrophobic tetanus. In addition to the ])aralysis of the seventh nerve, paralysis of the third and fourth nerves has been met with. 940 TETANUS. The paralysis of the facial has the distribution of a peripheral palsy, but it is not attended with any changes in the electrical reactions. In the few cases examined after death no inflammatory or degenerative changes have been found in the nerve. These facts, together with the observa- tion that in some cases the paralysis has disappeared after a few days, while the tetanus symptoms have steadily progressed to a fatal ending, lend strong support to the view that it is brought about in a reflex manner, and is not due to any coarse lesions in the nerve trunk. Cephalic tetanus runs, as a rule, a feverless course. Course of Tetanus. — The duration of the disease is very variable. In very rare cases a slight but temporary rigidity of the muscles of the neck and jaw is the only manifestation of the poison. Cases presenting such a course have been called abortive forms. It is more than doubt- ful whether it can be fully established that such cases are really tetanus. In very severe cases death may take place within two or three days or even in a shorter period. The duration in a fatal case is, however, usually from eight to twelve days. In the cases that recover the dis- ease ends very gradually, the intermittent spasms disappearing, and then more slowly the persistent rigidity ceases. Recovery is usually complete in from three to six weeks. In the case already alluded to of accidental inoculation with a tetanus filtrate the symptoms had all disappeared on the fort}"-first day in the same order in which they appeared. True relapses are unknown in tetanus. Death may be brought about in various Avays. In the acutest cases it is usually produced through spasm of the respiratory muscles, death being due to asphyxia through the arrest of respiration. Sudden death may also arise from cardiac failure during a paroxysm. Death may be slow, due to gradual exhaustion. Cases are reported where the patient succumbed from exhaustion even after all spasm had ceased. Diagnosis. — During the first few days there may be uncertainty as to the nature of the disease. The stiflhess of the neck may be mistaken for rheumatism, but it is soon followed by the trismus, which clearly points to tetanus. In trismus from dental irritation, tonsillitis, or in- flammation of the temporo-maxillary joint there can be no difficulty in making a differential diagnosis. The characters of the developed disease may be simulated by strych- nine-poisoning, hydrophobia, hysteria, and tetany. In strychnine-poi- soning the onset is sudden, the spasm being general. In tetanus the onset is slow and progressive, the spasms beginning in the jaws and neck and involving the trunk muscles after some hours or even days. In strychnine-poisoning the muscles of the extremities are more affected than those of the trunk ; the contrary is the case in tetanus, the upper extremities being very rarely the seat of spasm. The reflex excitability in strychnine-poisoning occurs early, while it is a late event in tetanus. In the former death or recovery takes place in a few hours, while in the latter it is usually a question of many days. The differences are so striking that ordinary care in examination should prevent a mistake. In hydrophobia the first symptoms are attacks of difficult}' of breath- ing from attempts to swallow. There is no rigidity of any of the mus- cles in the early stages of the disease. In the later stages the tetanoid r/iO(;.\()s[s^ Tin:, i tmf.st. 941 attacks do not n'senihlc those <•!' tclamis. Tlic diU'crciu'c in the iiien- bation period and the previous liistory afford in themselves sufficient evidence, in the jj^reat majority of eases, to eh'arly (hlTcreiitiate hetween the two diseases. Trismus histineneral tonie sj)asm, it alternates with ticneral convulsions. Its onset is sudden, as is also its disappearance. Further, there will be a history of similar previous attacks, together with the stigmata of hysteria. The positions of the hands antl arms in tetany are sufficiently charac- teristic to prevent any mistake being made in diagnosis. Prognosis. — In all the different types of tetanus tiie mortality is very high. It is greatest in the puerperal type, extremely few cases recovering. It is said that recovery is almost unknown in tetanus after abortion. In the otlier varieties it ranges between 45 and 90 per cent., as a rule being nearer the latter than the former figure. The severer the injury the graver the j^rognosis. Tetanus following lacerated wounds or compound comminuted fractures is more serious than that following slight wounds. In suppurating wounds the danger is greater than in those that heal by first intention. The sooner the symptoms supervene after the infliction of the wound (infection), the greater the danger. Probably not more than 3 or 4 per cent, of cases recover where the symptoms arise before the end of the tenth day. If the incubation period is from two to three weeks or more in duration, then the chances of recovery are much greater (25 to 50 per cent.). Exposure to cold at the time of infection lessens the chances of recovery. Unfavorable symptoms are early general muscular rigidity, difficulty in swallowing, and considerable pyrexia. In tetanus neona- torum the prognosis is the better the longer the interval after birth. Treatment. — Preventive. — In all cases of wounds contaminated with earth, manure, etc. it should be a rule to make a thorough bac- teriological examination for tetanus bacilli. Splinters of M'ood, etc. removed from wounds should also be examined with the same end in \'iew. If such procedures were common practice, there can be no doubt that in some cases tetanus might be prevented. If some of the suspected material is injected under the skin of a mouse, and if the animal dies in two or three days with the symptoms of tetanus, it should be suffi- cient warning to make a most thorough disinfection of the wound and place the patient on the special serum treatment which will be presently fully referred to. It is here unnecessary' to dwell on the importance of thorough cleans- ing of wounds, no matter how simple they may appear at the time. In deep-seated wounds this precaution is especially necessary, as it is in this class of injuries that the tetanus bacillus finds the appropriate conditions for its development. If it has been demonstrated that the secretions of a wound contain the tetanus bacillus, then it may be a justifiable prac- tice to excise the infiltrated parts, or even to amputate if the wound is situated on an extremity. If the symptoms of the disease have set i)i, experience shows that nothing is gained by either cauterization, excision, or amputation. In the uncommon cases -where the symptoms first 942 TETANUS. develop in the immediate neighborhood of the wound it would be sound practice to remove a portion of the peripheral nerve leading to the wound area. Several cases are on record where this procedure has been successful in preventing the further development of the disease. Treatment. — The treatment of the developed disease will be con- sidered under the following heads : 1. By antitoxin serum ; 2. Ordinary medicinal agents ; 3. General management. The Antitoxin Serum Treatment. — It has been clearly shown by Kitasato, Behring, Roux, and Vaillard that the blood serum of animals rendered immune to the tetanus poison has marked therapeutic powers. Kitasato and Behring first showed that it was possible to confer com- plete immunity against the tetanus poison, even in animals the most susceptible to it. Mice, rabbits, and horses are very^ susceptible to tetanus. Behring's method of conferring immunity in these animals consists in injecting a bouillon culture weakened with trichloride of iodine at intervals of three to eight days. On the first day the bouillon culture is diluted with 0.25 per cent, of the trichloride ; on the second day, with 0.20 per cent. ; on the third day, with 0.15 per cent. ; and on the fourth day, with the undiluted culture. The injections are continued at intervals in gradually increasing doses until complete immunity is obtained. The blood serum of an animal rendered immune after the above method is capable when injected into another animal of conferring im- munity to the action of the tetanus poison. It has been proved by Behring that mice when injected with a certainly fatal dose of tetanus poison can be saved by the use of the immunizing serum, provided this has been effected within five hours of the first appearance of the symptoms of tetanus. If twelve hours have elapsed before the serum has been injected, then it has been found to have no controlling influ- ence. He also demonstrated that the injection of the immune serum a quarter of an hour after the injection of the tetanus poison had much less effect than when used immediately before. He found that it required a serum a hundred times more potent to have the same eifect when injected a quarter of an hour after as when used before the introduction of the poison. As to the results of the antitoxic serum in the tetanus of man, expe- rience up to the present has not been sufficiently extensive to fully demonstrate its usefulness. A number of cases have been recorded where it apparently proved eifective in saving life, but as a certain num- ber of cases recover under all forms of treatment, it would be prema- ture to assign to the serum treatment a directly antidotal action. Prac- tically, a very great difficulty is met with in the treatment of tetanus by this method ; that is, the disease is fully established before the treat- ment is resorted to. From Behring's experiments on animals referred to above it is clear that the immune serum is only effective when it is administered very soon after the first appearance of the symptoms. There is every reason to believe that the same holds good in the human subject, and that to be effective it should be used early (within a few hours). TREATMENT. 943 It has l)een (jiiestioned whether tlie aiitituxie .seruiii iicl.s (jji th(! .saiuo tissues as the tetanus poison. Tiie action of the latter is chiefly on the central nervous system when the (liseas*(> is fully established, while it is contended that the serum has no direct iiiHiience on these tissues. If these eontentions were true, it would fully exj)laiu why (he results are so slij2;ht once the disease is fully estahlished. In carrying out the treatment of tetanus with antitoxin Tizzoni- Cattani's preparation has been chiefly employed, for the reason that it is a much more stabile compound than others. It is an aseptic serum in a desiccated state. It can be kejit for an indefinite length j)rcdik'cti<)n of age or sex, but selects by j)ret"erence newcomers to the island. Regarding the nature of the disease we are uncertain. It is possible tliat it is a modified form of typhoid fever, but many observers who have studied it believe that it is a specific fever with a definite poison of its own. The infection of the disease is apparently conveyed tiirough the air. There is no evidence that it is communicated by food or drinking water. Pathological Anatomy. — There are no characteristic lesions found after death. The lesions of typhoid fever are not present. Bruce has found in the spleen a micrococcus which has been called micrococcus Melitensis. This has been cultivated, and by it the disease has been reproduced in monkeys. Symptoms. — The period of incubation is about fourteen days. The onset is gradual. There are malaise, headache, anorexia, and sleeplessness. These may last from one to four weeks. Then follows a period of improvement, during which the patient apparently enters upon convalescence. In a few days, however, the symptoms recur and with greater severity. The headache now is intense. There may be chills. The temperature is from 101° to 104° F. The temperature curve is very irregular. It may be remittent in type, or it may be intermittent, or it may resemble closely that of typhoid fever. The tongue is coated and moist. There is anorexia. There may be nausea and vomiting. In some cases there is diarrhoea. Sometimes there are cerebral symptoms, apathy, or delirium. Headache is generally well marked. After continuing from five to six weeks there is a remis- sion of the above symptoms, and again the patient begins to convalesce. After from ten to twelve days there may again be a relapse. In many cases the remissions and relapses are less clearly marked. The disease shows a tendency to continue for from one to six months. There are generally very marked anaemia and debility. Late in the course of the disease there are commonly very severe neuralgic pains in the back and limbs. These are often the most pronounced features. There may be swelling of the joints. Convalescence when it sets in is often very slow, and in many cases two or three years elapse before the patient regains his normal good health. The death rate is about 2 per cent. The average stay in hospital is from seventy to eighty days. The prognosis is fairly good. The mortality is about 2 per cent. The treatment consists of rest in bed and fluid diet, and in some cases quinine has been given in considerable doses. Miliary Fever ; Sweating Fever. Definition. — An infectious disease occurring in epidemics of vary- ing intensity and duration. The disease was first described in 1485 in London, where a severe epidemic occurred in that year. It was called 948 INFECTIOUS FEVERS OF OBSCURE NATURE. sudor Anglicus. In this outbreak it was characterized by symptoms of great severity, and a large proportion of the cases were fatal. It occurred several times in the seventeenth century in France and Ger- many. In 1887 a severe epidemic of the disease took place in France in the department of Vienne. Etiology. — The etiology of the disease is unknown. It is supposed to be due to a micro-organism. The period of incubation is variable, and may be very short, less than twenty-four hours. Susceptibility is universal, and is the same for all ages and both sexes. One attack does not produce future immunity. Symptoms. — The attacks generally begin with acute gastric distress and a sense of lassitude. These in some cases precede the appearance of the other symptoms by several days. Generally, however, in the night following the onset of these prodromata the patient is awakened by a profuse perspiration. In the early stages there are fever, sweating, great debility, and a variety of nervous symptoms. There is often paroxysmal dyspnoea, with no discoverable lesion of the lungs. There may be a sense of constriction in the epigastrium. Sometimes there are restlessness and delirium. There may be muscular cramps. The tongue is coated, the appetite is absent, and the bowels are constipated. Later, there is generally cough, and in some cases epistaxis, w^hich is sometimes profuse. An eruption generally appears on the fourth day, and with this the other symptoms are apt to become less marked. The eruption itself con- sists of a rash which may be in crescentic patches, resembling that of measles, or may be diffuse and like that of scarlatina, or it may be pur- puric. But in each case there is superimposed upon it the miliary eruption proper, consisting of numerous miliary pa])ules which gradually change to vesicles that then discharge and desquamate. As the eruption becomes more marked the sweating diminishes, the temperature falls, and the debility and headache become less. At this time the cough commonly becomes more frequent, and bronchial rales are heard on auscultation. Constipation persists. The urine is dimin- ished, but contains no albumin. In some cases there are hsemoptyses. In a few eases intestinal hemorrhage occurred. Next following comes the stage of desquamation. Convalescence begins on the ninth or tenth day, and generally proceeds slowly. It is marked by great prostration and anemia, and is often much prolonged. Cases of miliary fever differ much in their severity. Sometimes the patient is not ill enough to have to go to bed. In other cases the disease begins suddenly and with great severity, and is rapidly fatal. Anomalous forms of the disease are described in which the eruption and sweating are wanting. The PROGNOSIS depends probably upon the character of the epidemic. In some epidemics the death rate is very high. The TREATMENT is entirely symptomatic. Simple Continued Fever. Definition. — From time to time cases of disease are met with in which an elevation of the temperature is the only symptom or is the SIMPLE CONTINUED FEVER. 949 most prominent symptom, and which ilo in^t achnit of heing classed with any of the well recognized diseases. It has become the habit of many observers to gronp these cases together under the name simple continued fever, and to assume that they represent a -^peciilc disease of unknown causiition, but admitting of classification u])on a purely clinical basis. Hence in medical literatnre are found a luuuber of descriptions, in more or less detail, of a disease variously called simple continued fever, febric- ula, ephemeral fever, or catarrhal fever. Clinical study of the cases thus named and of the literature of the subject discloses the fact that thev are far from uniform in their manifestations, and brings the conviction that so-called simple continued fever in most cases is not a specific disease, but is a group of clinical phenomena comprising irregular cases of many different maladies. Etiology. — Many of the cases thus described are typhoid fever of mild or abortive type ; others are ptomaine-poisoning from the intestine ; others are cases of mild tuberculosis where the tubercular focus is not to be found by clinical investigation. Then there are the many kinds of poisoning by the streptococcus pyogenes, where the local symptoms may be so little marked that they are entirely overshadowed and masked by the general syiliptoms. This is especially apt to occur in a streptococcus inflammation of the throat, where sometimes the local trouble may be entirely unnoticed by the patient, and may be discovered only by a searching examination of the fauces. These cases sometimes present the clinical picture of so- called simple continued fever. Leaving out of consideration all of the above mentioned cases, there are left remaining a considerable number of instances of continued fever whose causation cannot be explained. These cases, however, vary so much in their mode of onset, their duration, and their associated conditions that it is impossible to regard them as one and the same dis- ease. For clinical purposes they may be divided into three groups, according to their duration : First, those of short duration, lasting only a few days ; Second, those of moderately long duration, from one to three weeks ; Third, those of long duration, lasting for many weeks or months. Symptoms. — The first set of cases is very often met with, especially in hospital practice. The patients complain of lassitude, sometimes of headache. The temperature is from 100° to 102° F. The pulse is moderately rapid, 80 to 90. The symptoms regularly subside in from two to five or six days if the patient remains in bed. Many of these cases, especially as met with in hospitals, are appar- ently due to fatigue or exposure — some to exposure to heat, but not severe enough to give rise to sunstroke. This moderate disturbance of the heat-regulating function of the body seems capable of being brought about by a large variety of causes. These cases require only rest in bed and good nursing. The second set of cases, those of longer duration, are less often seen. In these the onset is gradual. The patient complains of malaise and headache. The tongue is coated. The bowels may be moderately con- stipated. The temperature is slightly elevated in the morning, 99.5° to 100.5° F. It is from one to two degrees higher in the afternoon. The 950 INFECTIOUS FEVERS OF OBSCURE NATURE. pulse is somewhat more rapid than normal. The spleen is not enlarged. There is no eruption. The examination of the blood is normal. The disease la.sts for from one to three weeks or sometimes longer, and the symptoms disappear gradually. At no time is the patient very ill. The course of the disease is not influenced by quinine. The nature of these cases is obscure. Some of them may be cases of very mild typhoid fever. In many epidemics of typhoid, cases of mild fever like the above are met with, or they may be cases of infec- tion with the poison of influenza. It is believed by some observers that they form a specific disease produced by a special poison, probably a micro-organism. The cases of the third variety, those of long duration, seem to depend upon locality. They have been described by Delafield as occur- ring in New York City. The patients feel tolerably well in the morn- ing, at which time the temperature is normal or it may be slightly above normal. In the afternoon there are lassitude and slight headache. The pulse is moderately rapid. The temperature is from 100° to 101° F., or it may be a little higher. There is no marked loss of weight nor of strength. The patients regularly go about their usual occupa- tions, but feeling always not perfectly well. The tongue may be coated, and there may be some dyspepsia and constipation. The disease is not affected by quinine or other medication. The duration is indefinite. The symptoms -generally continue until the patient is removed to a different climate. The nature of the disease is entirely unknown. It is often supposed to be malarial, but there is no reason for supposing that it is due to the malarial poison. It has also been ascribed to sewer-gas poisoning and to chronic poisoning by arsenic, as from wall paper. The only treatment that avails is the removal of the patient from the place where he acquired the disease. INDEX. ABATTOIRS and tuberculosis, 839 Abbott on enteric fever, 170 on malarial pigment, 22 on pyamia, 47 S Abdominal scrofula, 764 symptoms of dysentery, 365 tenderness in enteric fever, 189 typhus. See Enteric Fever. Abortion and syphilis, 915 Abortive enteric fever, 183, 200 Abscess of liver, dysenteric, 353 of lung in dysentery, 354 metastatic, in pvwmia. 488 in plague. 395, 396 in pyfemia, 480 in relapsing fever, 263 in typhoid fever, 197 Acclimatization and yellow fever, 274 Achalme on erysipelas, 452, 453 Acid, hydrochloric, in cholera, 327 Acquired svphilis. 849 Acute hydrocephalus. See Tuberculous MeningUi.*. miliary tuberculosb, 751 and peritonitis, 771 tuberculosis. See Miliary Tubereulom. tuberculous meningitb, 754 Adenitis, tuberculous, 760 Adenoid growths and tuberculosis, 840 Adeno-typhoid. See Malta Fever. _ Adhesive tuberculous pleurisy, 767, 768 ^ Adirondack Sanitarium and tuberculosis, 742 Adirondacks and tuberculosis, 843 Adrenal glands in malaria, 89 .£stivo-autumnal fever, 99, 106 blood in, 119, 126 diagnosis, 141 leucocytosis, 126 prognosis, 144 quinine in, 151 parasites, 35, 36, 47 Afanassiew on pertussis, 714 Afebrile enteric fever, 200 Age and cholera, 304 dysentery, 340 enteric fever, 168 influenza, 404 measles, 625 parotiditis, 725 pertussis, 713 relapsing fever, 259 revaccination, 565 rubella, 639 scarlet fever, 579 Age and smallpox, 515 tetanus, 937 tuberculosis, 745 typhus fever. 236 varicella, 569 Ague, 17 cake, 89 dumb, 17 Air, exposure to, in malaria, 145 Aitken on dvsentery, 369 Alabama Insane Hospital and tuberculosis, 742 Albumin in tuberculosis, 841 Albuminuria in enteric fever, 195 and erysipelas, 468 in malaria, 123 and measles, 633 in tvphus fever, 248 in yellow fever, 285, 290 Alcohol in enteric fever, 213-215 and syphilis, 896 and tuberculosis, 841 Algid pernicious malaria, diagnosis, 142 ', tvpe of pernicious malarial fever, 115 Alimentary canal in cholera, 314 system, tuberculosis of, 810 Alopecia, syphilitic, 866 Altitude and malaria, 81 and tuberculosis, 843 and yellow fever, 269 Ambulatory typhoid, 199 Amceba dysenterica, 344 Amoebie coli, plate of, 348 in dysenteric stools, 364 of malaria, 37, 44, 48 Amcebic dysentery, clinic-al course, 361 dysentery, symptoms, 361 Amceboid bodies in malaria 26 j hvaline bodies in malaria. 58 I Amyloid degeneration after malaria, 131 1 in chronic malaria. 95 in malarial kidneys, 94 I Anaemia, chronic, in malaria, 130 I and chronic phthisis, 786 ! complicating dysentery, 366 in dysentery, 363 in enteric fever, 186 explanation of, in malaria, 71 and influenza, 418 of malarial cachexia, 93. 94 of malarial fever, 125 malarial, treatment of, 153 post -malarial, 130 diagnosis of, 143 951 952 INDEX. Ansemia of scarlet fever, 624 secondary to malaria, 130 Anatomy. See Pathological Anatomy. morbid, of fibroid phthisis, 804 of phthisis, 775 of septicemia, 500 of tubercle, 746 of tuberculosis, 731 Anders on erysipelas, 456 Anaesthesia in leprosy, 927 Ansesthetic leprosy, 922 Angelini on malarial fever, 57 Angina in enteric fever, 186 and rubella, 642 scarlatinal, 588, 589 Animal inoculations of diphtheria, 651 Animals, dysentery in, 346 scarlet fever in, 586 tuberculosis in, 731, 738 Anorexia in chronic phthisis, 802 in enteric fever, 187 Anthrax and septicemia, 498 Antipyretics in enteric fever, 216 in influenza, 422 in septicfemia, 511 in yellow fever, 297 Antipyrine and pertussis, 723 Antisepsis, intestinal, in enteric fever, 222 Antiseptic treatment of cholera, 326 Antiseptics in dysentery, 384 in erysipelas, 474 in pyemia, 493 in smallpox, 550 Antitoxic blood in diphtheria, 668 Antitoxin in diphtheria, 692, 693 beneficial results, 700 conclusion, 707 ill effects, 701 limitations of, 702 for erysipelas, 472 mortality in diphtheria, 697, 699, 700 serum in tetanus, 942 in yellow fever, 295 Antoiisei on malaria, 34, 42, 57, 62, 71 Anuria in cholera, 316 Anus, syphilis of, 880 Apathy in enteric fever, 192 Aphasia in enteric fever, 194 Appendicitis and enteric fever, 206 Appendix in enteric fever, 175 Armies and dysentery, 341 Army, data of revaccination, 557 Arning on leprosy, 923, 925 Arsenic in malaria, 153 and tuberculosis, 845 Arsenical poisoning and cholera, 321 Arsenious acid in leprosy, 930 Arterial sclerosis, syphilitic, 874 Arteries, gummata of, 873 tuberculosis of, 833 Arthritic pains in dengue, 160 Arthritis, pyemic, 483 Arthropathies, dysenteric, 372 Ascites and tuberculous peritonitis, 773 Ascoli on malaria, 127 Asheville and tuberculosis, 843 Asia, cholera in, 321 Asiatic cholera, 301 Asphyxia, choleraic, 321 and tuberculosis, 809 Asthenia in enteric fever, 219, 221 in influenza, 415 and tuberculosis, 809 Astringents in dysentery, 383 Ataxia, acute, after malaria, 132 Atmosphere and tuberculosis, 843 Atrophy of gastro-intestinal mucosa after malaria, 131 Atropine in tuberculosis, 846 Aufrecht on cerebro-spinal meningitis, 447 Auscultation in chronic phthisis, 797 Autopsies of cholera cases, 313 in tuberculosis, 834 Autumnal fever, 17, 106 BABES on diphtheria, 648 Baccelli on estivo-autumnal fever, 111 toxic theory of malaria, 71 Bacilli in cerebro-spinal meningitis, 425 in erysipelas, 451, 452 of miliary tuberculosis, 751 tubercular, in chronic phthisis, 790 in yellow fever, 272 Bacillus coli communis, 272 comma, 305-311 of Koch, 301 of diphtheria, 647 growth of, 668 life outside of the body, 668 of enteric fever, 169 of influenza, 406 lepre, 922, 924, 925 of pertussis, 714 pseudo-, of diphtheria, 658 pyocyaneus, cultures in enteric fever, 230 in septicemia, 497, 498 of syphilis, 852, 853 tuberculosis, 733 biology, 733 deleterious agents, 736 methods of growth, 735 morphology, 733 staining reaction, 733 tussis convulsive, 714 typhi abdominalis, 169 typhosus, 169, 233 of typhus fever, 233 Bacteria in cholera, 308 of erysipelas, 451-455 of pyemia, 478 pyogenic, 498 in septicemia, 496-500 in yellow fever, 281 Bacteriology of pseudo-diphtheria, 670 of smallpox, 518 of yellow fever, 271 Bacterium coli commune in scarlet fever, 589 of syphilis, 852 Baer on tuberculosis, 742 Baginsky on diphtheria, 697, 698 Ball on dysentery, 339, 369, 381 Balanitis, syphilitic, 874 Barallier on typhus fever, 246 INDEX. 953 Barker on cerebru-spinal meningitis. A'l^\ on malarial cirrhosis, 96 spleen, 86 on tuberculosis, 810 Barthez on tuberculosis, 763, 764 Bastianelli on malarial fever, 49, 53, 57, 61, 62 germs, 68 pigment, 67 Baths, cold, in relapsing fever, 264 in scarlet fever, 616, 617 in smallpox, 549 in typhus fever, 254 water, in enteric fever, 222-229 hot, in cholera, 334, 335 Batt on enteric fever, 224 Baumgarten on dysentery, 316 on tuberculosis, 737, 738, 821 Bayle on chronic phthisis, 788 Beck on diphtheria, 656 B^court on tuberculosis, 817 Bedding, disinfection of, in tuberculosis, 839 Bedor on mammary tuberculosis, 833 Bedsores and enteric fever, 197, 220 Beebe on diphtheria. 650 Behring on tetanus, 942 Beinstock on tubercle bacillus, 734 Beneke on tuberculosis, 745 Benoit on malarial kidneys, 87 Berenger Feraud on yellow fever, 282, 285 Bergmann on septictemia, 495 Bernheim on tuberculosis, 739 Beulenpest, 391 Bible on leprosy, 921 Bignami on liver in chronic malaria, 92 on malaria, 25, 27, 53. 61, 62 on malarial germs, 37, 49, 51, 57, 68, 73 pigment, 67 on quinine in malaria, 147 Bilious fever and yellow fever, 288, 291 haemoglobinuric fever, 117 type of pernicious malarial fever, 115 typhoid, 262 Billings on antitoxin, 701 on malarial leucocytosis, 126 Biniodide and syphilis, 902 Binz on malaria, 146 Birds and malarial pai'asites, 74, 75 and tuberculosis, 739 Bismuth in dysentery, 384 Bisulphate of quinine in malaria, 149 Black measles, 631 Black vomit, 267, 276, 286 Bladder, catarrh of, in enteric fever, 177 syphilis of, 876 tuberculosis of, 821 Blair on vellow fever, 273 Blattern,"513 Blaxall on malaria, 97 Blood in cestivo-autumnal fever, 119 antitoxic, in diphtheria, 668 and bacillus leprae, 924 in cholera, 317 in chronic malaria, 129 phthisis, 801 corpuscles in malaria, 21, 25, 71, 72 examination of, in malaria, 137 Hlood, examination of, in miliary tubercu- losis, 753 in intermittent fever, 103 in malarial cachexia, 93 fevers, 125 in pernicious malarial fever, 119 in pyaimia, 479 in quartan fever, 105 in (luotidian intermittent fever, 104 in septicu'mia, 501 serum of horse, 848 in tetanus, 942 transfusion in enteric fever, 230 tubercle bacilli in, 753 tubercular infection through, 819 in urine in vesical ttil)erculosis, 825 of yellow fever, 275 Bloodletting in cerebro-spinal meningitis, 446 Bloodvessels in enteric fever, 177 in tetanus, 938 syphilis of, 872, 873, 891 Blumer on tuberculosis, 731 on urine in enteric fever, 196 Bock on relapsing fever, 258 Bollinger on tuberculosis. 818 Boltz on tuberculosis, 738 Bone diseases in enteric fever, 197 marrow in chronic malaria, 93 in malaria, 54, 55, 64, 89 Bones, syphilis of, 881 Boophilus bovis, 82 Botazzi on malarial urine, 124 Bouchard on cholera. 326 on intermittent fever, 102 Boulay on cerebro-spinal meningitis, 426 Boulland on tuberculosis, 774 Bouveret on enteric fever, 229 Bovine lymph, 549 Bowditch, Vincent, on tuberculosis, 744, 844 on tuberculous pleurisy, 765 Bradycardia in enteric fever, 186 Brain in cerebro-spinal meningitis, 433 in cholera, 311 in malaria, 83 syphilis of, 884 tuberculosis of, 831 in yellow fever, 276, 292 Brand on enteric fever, 222, 226 Break-bone fever, 155 Brehmer on tuberculosis, 844 Bribram on tuberculosis, 831 Brieger on enteric fever, 229 on erysipelas, 454 on tetanus, 937 British Leprosy Commission, report, 923 Medical Association, tuberculosis com- mittee, 743 Bromoform and pertussis, 723 Brompton Consumption Hospital, 742 Bronchi in chronic phthisis, 784 in phthisis, 776 Bronchial glands and tuberculosis, 742, 760, 762 Bronchitis and chronic phthisis, 786, 800 in enteric fever, 186, 220 954 INDEX. Bronchitis and influenza, 415, 416 and miliary tuberculosis, 754 and pertussis, 718 in relapsing fever, 263 and tuberculosis, 745 Broncho-pneumonia in enteric fever, 187 and influenza, 415, 416 with malaria, 132 in measles, 632 and pertussis, 720 Broncho-pneumonic form of phthisis, 777, 779 Brown on diphtheria intubation, 691 Browne, Sir -Thomas, on tuberculosis, 795 Brun on dengue, 160 Brunton on cholera, 315 Bubo, 851, 856 plague, 391 Buboes in plague, 395, 396 Buchanan and tuburculosis, 744 on typhus fever, 248 Bullae in leprosy, 926 CACHEXIA, chronic malarial, 89, 128 malarial, dinguosis of, 143 treatment, 154 Calcareous fragments in chronic phthisis, 790 Caley on enteric fever, 207 Calmette on leprosy, 932 Calomel in cholera, 326 in dysentery, 382 fumigation in diphtheria, 686 and syphilis, 902 Cameron on yellow fever, 268 Canalis on a?stivo-autumnal fever, 121 on malaria, 22, 27, 37, 47, 57 Cancer and syphilis compared, 869 Cantani on cholera, 328 Carbuncle and septicaemia, 507 Carbuncles in plague, 396 Cardialgic tvpe of pernicious malarial fever, 115 Cardio-vascular svstem in chronic phthisis, 801 Caries, dry syphilitic, 881, 883 Carmack on relapsing fever, 258 Carreau on lepros}', 930, 932 Carter on enteric fever, 230 on relapsing fever, 259 Caseation, 749 Caseous degeneration. 749 pneumonia. See Phthisis. Cases of cholera, 333-337 of typhus fever, 244-246 Castor oil in dysentery, 382 Catarrh of bladder in enteric fever, 177 in influenza, 413 Catarrhal bronchitis and tuberculosis, 745 dysentery, acute, 347 clinical course, 357 symptoms, 357 laryngitis in enteric fever, 187 Caustics in diphtheria, 684 Cavities of phthisis, 782, 798, 799 Ceci on cholera, 313 Celli on malaria, 21, 22, 30, 32, 35, 37, 47 Cells, giant, 748 of leprosy, 924 Celsus on intermittent fever, 18 on leprosy, 921 Cephalic tetanus, 939 Cerebral meningitis, diagnosis from typhus, 251 paralysis, malarial, 131 symptoms of pernicious malaria, 115 Cerebro-spinal fever, 425 meningitis, 425 abortive cases, 441 cause of death, 442 in children, 437, 438 complientions of, 441, 447 counter-irritants in, 446 definition, 425 diagnosis, 443 etiology, 425 eyes in, 438 fever in, 439 fulminant cases, 441 herpes in, 439 history, 425 incubation, 436 and influenza, 444 joints in, 440 and meningitis, 444 ordinary form, 436 pathological anatomy, 433 prognosis, 445 pulse in, 440 remission in, 441 sequelae, 441 symptoms, 436 synonyms, 425 treatment of, 445 and typhoid fever, 443 and typhus fever, 444 varieties, 436 venesection in, 446 Cervical glands and tuberculosis, 762 Cervix uteri, tuberculosis of, 830 Chancre, 850, 854 dry papule, 857 of ear, 889 erosion, 856 extra-genital, 856 forms, 856 genital, 856 induration, 856 mixed, 858 of mouth, 868 pustule, 858 sites, 855 of tongue, 868 of tonsil, 869 treatment of, 897 ulcer, 858 Chancroid, 893 Channing on tuberculous peritonitis, 772 Chapin on typhus fever, 255 Chaplin on fibroid phthisis, 805 Chapparo amargoso in dysentery, 389 Charles on dengue, 160 Chaulmoogra oil and leprosy, 930 Cheeseman on typhus fever, 234 INDEX. 955 Cheyne-Stokes breathing in cerebro-spiiial meningitis, 440 and meningeal tuberculosis, 758 in niiliarv tnliereiilosis, 753 in pernicious malaria, 114 Chiari on tubercle, 747 Chickiilioniiny (Harrhcea, 356 Chicken-pox. See Varicella. Children, cerebro-spinal meningitis in, 437, 438 intermittent fever in, 102 prognosis of dysentery in, 376 and yellow lever, 293 Childhood mortalitv in enteric fever, 207 syphilis of, 914-919 and yellow fever, 274 Chill in erysipelas, 459 in phthisis, 777 in py:¥niia. 484, 485, 488 in smallpox, 523 of tertian fever, 100 in yellow fever, 281 Chills and fever, 17. See Malaria. Chincon, Del, 18 Chisholm on leprosy, 932 Chloral in tetanus, 944 Chlorate of potash in leprosy, 930 Chloride of iron and diphtheria, 685 Cholera, 301 and age, 304 algid stage, 301, 314 in Asia, 321 Asiatic, 301 bacteriological diagnosis, 308 brain in, 311 climate, 304 collapse in, 317 complications of, 319 convalescence, 318, 332 definition, 301 diagnosis, 319 disinfection, 322, 323 duration, 319 etiology, 304 heart in, 311 history, 301 hydrochloric acid in, 327 infectiosa, 301 intestines in, 312 kidnevs in, 312 liver in, 312 lungs in, 312 maligna, 301 mortality, 303 pathological anatomy, 311 predisposing causes, 304 premonitory stage, treatment, 314, 326 prognosis, 321 prophylaxis, 322 and quarantine, 324 and race, 305 and raw food, 323 reaction in, 314, 318 season, 304 sequelae, 319 and sex, 304 sicca, 317 Cholera, splocn in, 312 stage of asphyxia, 314 of collapse, 314 of reaction, 332 of serous (liarrha?a, 314 stinuilation in, 332 stomach in, 312 stools, 307 symptoms, 314 synonyms, 301 systematic treatment, 326 treatment of, 325 collapse stage, 327 Choleriform tvpe of pernicions malaria, 116 Cholerine, 301, 303, 319 Chorea and enteric fever, 198 Choroiditis, syphilitic, 889 Chromatin in malarial germs, 62 Chronic anannia in malaria, 130 dysentery, jjost-mortem appearances, 356 malarial cachexia, 89, 94, 128 diagnosis of, 143 treatment, 154 phthisis, 780 and dyspnoea, 792 haemoptysis in, 790 pleura in, 784 pulmonary tuberculosis. See Phthisis, Chronic. Cicatrices of smallpox, 552 tubercular, 835 of varicella, 571 Cicatrix of vaccinia, 562 of vaccination, 564, 565 Cicatrization of enteric ulcers, 174 Ciliary body, syphilis of, 888 Cinch onism, 152 Circulation and pyaemia, 482 Circulatory apparatus and diphtheria, 678 system in enteric fever, 185 and scarlet fever, 599 Cirrhosis, malarial, 95, 131 Civil War, dysentery in, 341, 349, 370 Clark on fibroid phthisis, 805 on intermittent fever, 19 Clements on yellow fever, 294 Cleanliness in cholera, 322 Climate and cholera, 304 and dysentery, 340 and enteric fever, 168 influence on dengue, 156 and malaria, 79 and tuberculosis, 842, 843 and yellow 'fever, 269, 270 Climatic treatment of tuberculosis, 842 Clinical cases of dipbtlieria, 700 of pseudo-diphtheria, 708 course of acute catarrhal dysentery, 357 of diphtheritic dysentery, 359 of enteric fever, 179 of secondary dysentery, 365 history of dengue, 159 of fibroid phthisis, 805 Cloisters and tuberculosis, 742 Clothing, disinfection of in cholera, 323 Cnopp on tuberculosis, 738 Cod-liver oil in syphilis, 918 956 INDEX. Cod-liver oil and tuberculosis, 841, 845 Cohnlieim on tuberculosis, 811 Cold bathing. See Baths. Coley on typhus fever, 234 Collapse in cholera, 315 in enteric fever, 219 in relapsing fever, 262 stage of cholera, 327 Colles' law, 914 Colon bacillus in yellow fever, 281 inflammation of, 339 photograph of dysenteric, 349 plate of transverse section in dysentery, 348 Colorado and tuberculosis, 843 Coma, malarial, 114 Comatose malarial fever, 114 pernicious fever, diagnosis, 142 Combined infections with malarial para- sites, 122 Comma bacillus, 305-311 Communicability of pseudo-diphtheria, 670 Complications of cerebrospinal meningitis, 441, 447 of cholera, 319 of chronic phthisis, 799 of dengue, 162 of diphtheria, 679 of enteric fever, 198 treatment of, 215 of erysipelas, 467 of influenza, 415 of malaria, 127 of measles, 632 of parotiditis, 729 of pertussis, 718 in the pleura in chronic phthisis, 800 pulmonary, of malaria, 132 of relapsing fever, 262 in rubella, 643 of scarlet fever, 597 of secondary dysentery, 366 of smallpox, 538 of typhus fever, 248 of vaccinia, 561 of varicella, 573 of Weil's disease, 946 Condylomata of ear, 890 syphilitic, 862 Confederate army, dysentery in, 341 Confluent variola, 531 Congenital scarlet fever, 580 Conjunctiva in cholera, 315 in smallpox, 535 syphilis of, 887 Conjunctivitis and scarlet fever, 619 Constipation and dysentery, 342 in enteric fever, 217 Consumption, 780. See Phthisis. pulmonary. See Tuberculosis. Contagium of diphtheria, 647 of dysentery, 344 of enteric fever, 169 of erysipelas, 455 of leprosy, 922 of plague, 393 of scarlet fever, 582 Contagium of smallpox, 518, 519 of syphilis, 850 of typhus fever, 234 of varicella, 570 Continued fever, 948 Convalescence in cholera, 332 of dengue, 159 of diphthei'ia, 664 of diphtheritic dysentery, 361 of dysentery, 358 of enteric fever, 221 of influenza, 423 of plague, 396 of relapsing fever, 262 of smallpox, 554 Convulsions in enteric fever, 193 in meningeal tuberculosis, 757 and pertussis, 7 1 8 in scarlet fever, 597, 623 in smallpox, 550 in tetanus, 938, 939 Cooper on tuberculosis, 832 Copland on scarlet fever, 577 Coplin on enteric fever, 179 Cord, syphilis of, 885 tuberculosis of, 831 Cornea, syphilis of, 887 Cornet on tuberculosis, 741, 837 Cornil on cerebro-spinal meningitis, 431 Corpulency in enteric fever, 207 Corrosive sublimate in diphtheria, 684 in dysentery, 384 in syphilis, 902 Coryza and measles, 629 syphilitic, 916 Cough in chronic phthisis, 787 in influenza, 413, 423 in pertussis, 716 in tuberculosis, 846 Councilman on amoebic dysentery, 352-354 on crescents, 57 on flagella, 27 on malarial pigment, 22 on yellow fever, 278, 280 Counter-irritants in cerebro-spinal menin- gitis, 446 Courmont on erysipelas, 454 Course of syphilis, 849 Cowpox, 555, 561 Cramps in cholera, 317 relief of, 331 Creasote and tuberculosis, 845 Creoles and yelloAv fever, 274, 293 Creolin in cholera, 330 Crescentic bodies in malaria, 21, 27, 54, 60 Crimean War and dysentery, 369, 370 Crises in relapsing fever, 26l Croup. See Pseudo-diphtheria. Croupous pneumonia and enteric fever, 187, 206 _ Cryptogenetic infection, 455 septicEemia, 508 Culture media, diphtheritic, 651 of tetanus germs, 935, 936 Cultures of amoeba dysenterica, 345 of cholera bacteria, 308-310 of erysipelas germs, 452 INDEX. 957 Ciinissct on yellow fever, 276 Ciinningliaui on dysentery, 345 Cure, spontaneous, of tnbereulosis, 834 Curry on enteric lever, 'I'l'l Curselunann on smallpox, 516 Cyanosis in eiiolera, 333, 334 and chronic phthisis, 793 Cystitis in enteric fever, 177 syphilitic, 888 Czerny and tuberculosis, 741 DA COSTA on enteric fever relapse, 203 Dairies, ins{>ection of, 839 Daland on cholera, 333 Dandy fever. See Denc/ue. Danielewsky on malaria, 56, 74 Dantes on yellow fever, 277 Davidson on typhus fever, 235 Davis on cerebro-spinal meningitis, 447 Deafness in cerebro-spinal meningitis, 442 in enteric fever, 193 D'Aquin on dengue, 159 Death rate. See Mortality. Decomposing vegetation and dysentery, 343 D'Espine on diphtheria, 648 Definition of cholera, 301 of diphtheria, 647 of dysentery, 339 of enteric fever, 167 of erysipelas, 451 of intiuenza, 399 of leprosy, 921 of measles, 625 of miliary fever, 947 of parotiditis, 725 of pertussis, 713 of plague, 391 of pyaemia, 477 of relapsing fever, 257 of rubella, 639 of scarlet fever, 577 of septicemia, 495 of simple continued fever, 948 of smallpox, 513 of syphilis, 849 of tetanus, 935 of tuberculosis, 731 of vaccination, 555 of Weil's disease, 945 of yellow fever, 267 Degeneration, amvloid, in chronic malaria, 95 after malaria, 131 caseous, 749 of tubercle, 749 Deglutition pneumonia in enteric fever, 187 Dejecta, choleraic, 308, 324 of dysentery, 377 Delafield on enteric fever, 207 on simple continued fever, 950 Delavan on erysipelas, 467 Del Chinchon and quinine, 145 Delirium in ajstivo-autumnal fever, 141 in enteric fever, 181, 192, 215 ferox, 529 and meningeal tuberculosis, 757, 758 in smallpox, 529 Delirium in tertian intermittent fever, 101 in typhus fever, 248 Dengue, 155 clinical history, 159 communicable, 158 complications, 162 course of fever, 160 definition, 155 diagnosis, 162 eruption of, 160 etiology, 155 glandular injections, 161 hemorrhages in, 161 liistory, 155 and influenza, 420 medicinal treatment, 164 muscular and arthritic pains, 160 pathological anatomy, 158 prognosis. 164 relapses, 161 seqnelse, 162 specific causes, 156 symptoms, 159 treatment of, 164 varieties of, 161 and yellow fever, 291 Denguis maligna, 162 DeEenzi on cholera, 316 Dermatitis gangrenosa, 573 and scarlet fever, 608 Dermatosis and scarlet fever, 607 Desquamation in enteric fever, 197 in measles, 630 of rubella, 643 in scarlet fever, 593 Desiccation stage of smallpox, 530 De Toma on tubercle bacillus, 736 Dewevre on dysentery, 372 on enteric fever, 178 Diabetes and enteric fever, 198 and tuberculosis, 746 Diagnosis of acute pneumonic phthisis, 778 of sestivo-autumnal fever, 142 of cerebro-spinal meningitis, 443 of cholera, 319 of chronic phthisis, 803 of dengue, 162 of diphtheria, 654, 655, 680 of dysentery, 374 of enteric fever, 205 of erysipelas, 470 of fibroid phthisis, 806 of influenza. 419 of leprosv, 928 of malaria, 136 of measles, 634 of meningeal tuberculosis, 759 of miliary tuberculosis, 754 of parotiditis, 729 of pernicious malaria, 142 of pertussis, 719 of plague, 396 of pyaemia, 491 of relapsing fever, 263 of rubella, 644 of scarlet fever, 604 of septicfemia, 508, 509 958 INDEX. Diagnosis of smallpox, 540 of syphilis, 892 of tetanus, 940 of tuberculosis, 839 of tuberculous adenitis, 764 pericarditis, 770 pleurisy, 768 of typhus fever, 249 of varicella, 574 of Weil's disease, 946 of yellow fever, 287 Diapedesis in malaria, 73 Diaphoretics in scarlet fever, 621 Diarrhoea in amoebic dysentery, 363 Chickahominy, 356 choleraic, 327 in enteric fever, 180, 188 and scarlet fever, 599 serous, in cholera, 315 in tuberculosis, 846 Diazo-reaction in enteric fever, 195 in malaria, 141 Dickson on dengue, 158 Dicrotism in enteric fever, 185, 219 Diet of amoebic dysentery, 387 in cerebro-spinal meningitis, 449, 450 in cholera, 326 convalescence, 332 in diphtheria, 685 in dj'sentery, 385, 386 and enteric fever, 171, 212, 226 errors of, and dysentery, 342 in erysipelas, 473 in influenza, 421, 422 in malaria, 145 in malarial cachexia, 154 in measles, 636 in pyaemia, 494 in relapsing fever, 264 in scarlet fever, 613 in septicaemia, 512 in syphilis, 895 in tuberculosis, 840 in typhus fever, 253 in yellow fever, 300 Dietetic treatment of tuberculosis, 840 Differential diagnosis. See Diagnosis. Digestive system and diphtheria, 678 and enteric fever, 187 in influenza, 413 tract and syphilis, 871 in typhus fever, 247 Di Mattel on malarial inoculation, 75 Dionisi on malarial blood, 125 Diphtheria, 647 antitoxin, 692 conclusions, 707 bacilli, 647 in healthy throats, 663 sources of, 666 summary, 663, 664 circulation in, 678 complications, 679 convalescence and bacilli, 664 cultures, 651-653 definition, 647 diagnosis, 654, 655, 680 Diphtheria, diet in, 685 digestion in, 678 and enteric fever, 198 epidemics, 669 general condition, 678 treatment, 685 heart in, 674 failure in, 679 immunization, 692, 696 intubation, 686, 689 instruments, 687, 688 irrigation in, 683, 684 joints in, 679 kidneys in, 674 laryngeal, 677 treatment, 685 local treatment, 683 lymph glands in, 679 malignant cases, 676 nervous system in, 675, 678 . paralysis in, 679 pathological anatomy of, 673 pharyngeal, 675 mild cases, 675 symptoms, 675 pneumonia in, 679 prognosis, 681 prophylaxis, 682 pseudo-, bacteriology of, 670 relapses, 679 and scarlet fever, 609 and septic infection, 508 severe cases, 675 skin in, 679 symptoms in detail, 678 temperature, 678 tracheotomy, 686 treatment, 682 urine in, 679 Diphtheritic dysentery, 349 pathological anatomy of, 349 symptoms, 359 Diplococci in cerebro-spinal meningitis, 426 Diseases associated with pulmonary tuber- culosis, 807 Disinfectants in diphtheria, 684 Disinfection of cholera patients, 322 of cholera stools, 323 of dj'senteric stools, 377 of enteric stools, 208 in erysipelas, 472 in scarlet fever, 611, 612 in smallpox, 546, 547 of tubercular sputum, 837 in typhus fever, 252 Distribution of malaria, 77, 79 of tubercle bacillus, 736, 737 Diuretics in scarlet fever, 622 in yellow fever, 299 Dobie on dysentery, 380 Dock on dysentery, 346, 353, 362, 364, 374 on malarial germs, 23, 29, 66 Doehle on scarlet fever, 586 Domestic animals, tuberculosis in, 731 Donnet on yellow fever, 290 Double quartan intermittent fever, 105 Dowler on yellow fever, 274 INDEX. 959 Drainage and enteric fever, 210 anil malaria. 79 Drake on inlerniittent fever, 19 Drepanidiuni Kavanun in malaria, 74 Drinking water and dysentery, 342 and enteric fever, 209 and malaria, 81 pathogenic micro-organisms in, 343 and relapsing fever, 259 Dropsy of the brain, 754 Drug eruptions and measles, 635 and scarlet fever, 606, 607 rashes and smallpox, 542 Dry cholera, 317 Dubar on tuberculosis, 832 Dubini's disease after malaria, 132 Duffin on scarlet fever, 582 Dunham's culture method, 308, 309 Duration of cholera, 319 of pulmonary tuberculosis, 836 of relapsing fever, 262 Dust and tuberculosis, 741 Dysenteric am«ba, 354 arthropatiiies, 372 paralyses, 373 Dysentery, 339 abdominal symptoms in, 365 abscess of liver in, 353 of lung in. 354 acute catarrhal, 347 clinical course, 357 pathological anatomy, 347 symptoms, 357 and age, 340 amoebic, 340 clinical, 361 masked forms, 361 pathological anatomy of, 351 symptoms, 361 and ansmia, 366 antiseptics in, 384 in armies, 341 calomel in, 382 castor oil in, 382 catarrhal, 340 chronic, post-mortem appearances, 356 circulation in, 362 and climate, 340 complications, 366 contagium, 344 definition, 339 diagnosis, 374 diphtheritic, 340 clinical course, 359 symptoms, 359 and drinking water, 342 etiology, 340 fever in, 365 follicular ulceration, 356 gangrenous form, 363 and hepatic abscess, 367-369 ipecac in, 379 and malaria, 143, 370 opium in, 380 and peritonitis, 366 in pneumonia, 369 prognosis, 375 Dysentery, prophylaxi.s, 376 purgatives in, 382 rectal medication, 385 in relapsing fever, 263 respiration in, 365 and season, 340 secondary, 340, 355 clinical course, 365 pathological anatomy of, 355 symptoms, 365 sequeiie, 374 and scurvy, 370 and sex, 340 sporadic, 340 tenesmus in, 365 treatment of amoebic, 387 of catarrhal, 385 of diphtheritic, 386 of, in general, 376 tropical, 340 and tuberculosis. 369 and typhoid fever, 371 and typhus fever, 371 urine in, 365 Dysidi'osis and leprosy, 929 Dyspepsia and chronic phthisis, 786 and tuberculosis, 841 Dyspnoea in chronic phthisis, 792 in influenza, 414 in miliary tuberculosis, 753 EAK and erysipelas, 468 in smallpox, 539 syphilis of, 889 Eberth on cerebro-spinal meningitis, 425 on enteric fever, 169 Eberth's bacillus, 169, 177, 197 Echinacea augustifolia, 255 Eczema of syphilis, 894 Edward 11. and smallpox, 550 Efinsion, sero-fibrinous in pleurisy, 767 Eggs in enteric fever, 226 and tuberculosis, 841 Ehrlich's diazo-reaction in enteric fever, 195 in malaria, 141 Elastic tissue in phthisical sputum, 789 Electric chorea after malaria, 132 Electrolysis, 329-331 Emaciation in cerebro-spinal meningitis, 441 in chronic phthisis, 795 in enteric fever, 181 Emboli in pyemia, 480, 483, 487 Emetics in yellow fever, 295 Emphysema in chronic phthisis, 800 Endarteritis obliterans, syphilitic, 873 tuberculous, 756 Endocarditis and chronic phthisis, 808 in enteric fever, 186 and erysipelas, 469 malignant and cerebro-spinal meningitis, 442 in pya?mia, 484, 490 and scarlet fever, 604 Endophlebitis in pysemia, 481 Enemata in dysentery, 385 960 INDEX. Enemata in yellow fever, 297 Enteric (or typhoid) fever, 167 abdominal tenderness in, 189 abortive form, 200 afebrile type, 200 and age, 168 in the aged, 203 albuminuria in, 195 ambulatory, 199 anaemia in, 186 angina in, 188 antipyretics in, 216 aphasia, 194 and appendicitis, 206 asthenia in, 221 bacillus, 169 and bedsores, 197, 220 bloodvessels in, 177 and bronchitis, 186, 220 and broncho-pneumonia, 187 cardiac asthenia in, 219 and catarrhal laryngitis, 187 central nervous system in, 179 circulatory system in, 185 and climate, 168 collapse in, 219 complications, 198 constipation in, 217 convalescence, 221 convulsions in, 198 and croupous pneumonia, 1 87, 206 cutaneous hyperesthesia, 194 cystitis in, 177 deafness in, 193 definition, 167 delirium in, 192 and desquamation, 197 diagnosis, 205 from typhus, 249 diarrhoea in, 188 diet in, 212, 226 differential diagnosis, 206 and digestive system, 187 dilatation of pupils, 193 disinfection of stools, 208 and en tero- colitis, 207 epidemics, 171 and epistaxis, 187, 219 eruption in, 196 and erythema, 196 etiology, 167 and furuncles, 197, 221 general clinical course, 179 management of patient, 211 geographical distribution, 168 headache in, 192 heart in, 177 hemorrhage in, 175 hemorrhagic type, 200 and herpes, 197 hydrotherapy in, 222 incubation, 179 and influenza, 410 insanity in, 194 intercurrent and concurrent diseases, 198 intestinal hemorrhage in, 189, 218 Enteric fever, intestinal perforation in, 21& intestines in, 173 jaundice in, 192 kidneys in, 177 latent form, 199 liver in, 176 localized tenderness of muscles, 194 and malaria, 205 mesenteric glands in, 175 mild form, 199 mortality, 207 muscular weakness in, 193 and nervous system, 192 neuralgia in, 194 neuritis, 194 organs of special sensation, 193 and osseous s^'stem, 197 otitis media in, 188 pancreas in, 178 parotiditis in, 221 pathological anatomy, 173 perforation in, 175 of intestine in, 190 peripheral neuritis in, 222 peritonitis in, 191, 206, 218 physiognomy, 197 and pleurisy, 187 and pregnancy, 203 and prognosis, 207 prophylactic inoculations, 229 prophylaxis, 207 and pulmonary tuberculosis, 807 pulse in, 185 pyuria in, 196 recrudescence, 204 reduction of temperaturCj 220 and relapses, 203 respiratory organs in, 178 respiratory system, 186 retention of urine in, 219 salivary glands in, 178 and season, 168 second attacks, 205 serum inoculations, 230 and sex, 169 skin in, 196 somnolence in, 192 special management of individual cases, 214, 215 specific treatment, 222 spleen in, 176, 191 sporadic cases, 173 and sudamina, 197 symptoms, 179 synonyms, 167 and synovitis, 198 temperature chart, 180, 182-185, 189, 199-202, 204 thi-ombosis in, 222 tongue in, 187 transfusion of blood in, 230 treatment, 207 of complications, 215 tremor in, 193 and trichinosis, 206 and tuberculosis, 206 tympanites in, 189, 217 INDEX. 961 Enteric fever, iiJceiation in, 174 urinary system in, 194 urine in, 194, 217 and nrticaria, 197 varieties, 198 vertigo, 19o voluntary nniscles in, 178 Vdiniliui;- in, 188 and weatlier, 1(38 Entero-et)litis and enteric lever, 207 Environment and tuberculosis, 743 Epidemic catarrhal fever, 399 cerebro-spinal meningitis. See Cerebro- spinal Men iiM/itis. cholera, 301 parotiditis. See Parotiditis. Epidemics of cholera, 301-304 of diphtheria, 669 of dysentery, 349 of iiiHueiizaV 399-405 of scarlet fever, 577 of smallpox, 513 of typhus fever, 233, 242 of yellow fever, 267 Epidermis in erj'sipelas, 456, 457, 460 Epilepsy and enteric fever, 198 Ej)istaxis in enteric fever, 187, 219 in relapsing fever, 263 in typhus fever, 247 Epizootics and influenza, 404 Erb on syphilis, 885 Ernst on enteric fever, 170 Eruption of dengue, 160 of enteric fever, 180, 181, 196 of erysipelas, 460, 470 of leprosy, 926 of measles, 627-629 of pyaemia, 482 of relapsing fever, 261 of rubella, 641, 642 of septic infection, 506 of smallpox, 525, 526 of typhus fever, 241, 242 of varicella, 572 of varioloid, 537 Erysipelas, 451 afebrile, 461 and albuminuria, 468 ambulant, 463 antiseptics in, 474 bullous, 463, 464 and chronic phthisis, 807 complications, 467 definitions, 451 diagnosis, 470 diet, 473 and enteric fever, 198 erratic, 463 etiology, 451 of face, 465 gangrenous, 464 hemorrhagic, 463 incubation, 459 of the larynx, 466 and lymphangitis, 470 migrating, 463 of mucous membranes, 465 Vol. I.— 61 Erysipelas of nose, 466 cedematous, 463 patliological anatomy, 456 patliology, 451 pemphigoid, 463 petecliial, 163 and pharynx, 466 phlegmonous, 464 prognosis, 471 and scarlet fever, 606 sequela?, 467 of special regions, 465 stimulants in, 474 symptoms, 459 synonyms, 451 transmission of, to foetus, 467 treatment, 472 and vaccinia, 562 variations in local lesion, 403 wandering, 463 Erysipeloid, 471 Erythema in enteric fever, 196 scarlatiniforme, 607 Erythemata in sestivo-autumnal fever, 141 Erythematous syphiloderni, 894 Escherich on diphtheria, 659, 660 Esmarch on cholera, 309 Etiology of cholera, 304 of dysentery, 340 of enteric fever, 167 of erysipelas, 451 of influenza, 404 of leprosy, 922 of malaria, 77 of Malta fever, 946 of measles, 625 of meningeal tuberculosis, 755 of miliary fever, 948 of parotiditis, 725 of pertussis, 713 of plague, 392 of pyiemia, 477 of relapsing fever, 257 of rubella, 639 of scarlet fever, 577 of septicsemia, 495 of simple continued fever, 949 of smallpox, 513 of syphilis, 852 of tetanus, 935 of tubercle, 746 of tuberculosis, 731 of typlius fever, 233 of vaccinia, 557 of varicella, 569 of Weil's disease, 945 of yellow fever, 267 Eucalyptus globulus and malaria, 79 Ewart on dysentery, 379 Examination of malarial blood, 137 of syphilitic patients, 893, 894 Exanthem. See Eruption. of enteric fever, 196 in smallpox, 524, 525 Exanthemata and malaria, 135 and measles, 634, 635 and scarlet fever, 585 962 INDEX. Exostoses, syphilitic, 882, 884 Expectoration. See Spulum. in chronic phthisis, 788 Exudate, diphtheritic, 653, 654, 673, 680, 681 Eye symptoms in cerebro-spinal meningitis, 438 syphilis of, 886 Eyelids, syphilis of, 886 Eyes and erysipelas, 468 in smallpox, 539 FACE in erysipelas, 465 Fades of cholera, 320 Fseces and dysentery, 364, 377 and enteric fever, 172, 208, 209 in yellow fever, 272 Faget on yellow fever, 283 Fagge on cerebro-spinal meningitis, 430, 434 on dysentery, 343 Faggioli on malarial germs, 69 Falk on tubercle bacillus, 736 Falkenstein and tuberculosis, 844 Fallopian tube, tuberculosis of, 819, 830 Famine fever, 258 and typhus fever, 235 Febris carnis, 184 Fehleisen on erysipelas, 451, 456 Feletti on hsemoproteus, 75 on malaria, 81 on malarial germs, 38, 57, 61 Fermentative fever, 495, 498, 502 Fever, sestivo-autumnal, 99, 106 diagnosis of, 141 African, 17 and ague, 17 aseptic, 498 autumnal, 17 Batavia, 17 black water, 17 break-bone, 155 of cerebro-spinal meningitis, 439 Chagres, 17 in chronic phthisis, 793, 794 course of, in dengue, 1 60 in dysentery, 365 enteric, 167 treatment, 207 famine, 258 fermentative, 495, 498, 502 hsematuric, 117 Hungarian, 17 infectious, of obscure nature, 945 of influenza, 410 intermittent, 17 diagnosis, 136 irritative, 498 malarial, with long intervals, 120 malignant tertian, 107 Malta, 946 Mediterranean, 946 and meningeal tuberculosis, 757, 758 miasmatic, 17 miliary, 947 tuberculosis, 753 Neapolitan, 946 Fever, Panama, 17 periodical, 17 pernicious malarial, 113 of plague, 395 quartan, 99, 105 quotidian intermittent, 99, 104 relapsing, 257 resorption, 498 rock, 946 simple continued, 948 swamp, 17 sweating, 947 tertian, 99 intermittent, 99 of tuberculosis, 846 typhoid and malaria, 133 typho-malarial, 134 typhus, 233 Walcherian, 17 yellow, 267 Fibroid phthisis, 804 tuberculosis and peritonitis, 772 Fiesinger on scarlet fever, 595 Fievre bileuse melanurique and yellow fever, 291 Filehne on erysipelas, 455 Finger on dysentery, 342 Fisher's Island epidemic of diphtheria, 669 Fissui'es, syphilitic, 870 Fixed cells and tubercles, 748 Flagella of malaria, 21, 27-29, 47 Flagellation, 76 Flexner on cerebro-spinal meningitis, 426 on diphtheria, 648 on enteric fever, 177 on malaria, 73 on septicaemia, 498 on tuberculosis, 812 Flick on tuberculosis, 742 Flies and enteric fever, 172 Flint on cholera, 315 on dysentery, 358, 359 on tuberculosis, 835 Foetus, smallpox in the, 515 Follicular ulceration in dysentery, 356 Food. See Diet. raw, and cholera, 323 Foster on dengue, 160 Foudrovante cerebro-spinal meningitis, 441, ■ 442 Fowler on phthisis, 780 on tuberculosis, 738 Fowler's solution in malarial anaemia, 153 Fox on chronic phthisis, 788 Fragmentation of malarial parasite, 30 Friinkel on enteric fever, 229, 230 on phthisis, 775 on tetanus, 937 Eraser on leprosy, 932 Frerichs on malarial cachexia, 94 pigment, 73 on tuberculosis, 811 Fresh air and tuberculosis, 842 Friedlander on cerebro-spinal meningitis,430 on tuberculosis, 829 Fulminant cerebro-spinal meningitis, 441, 442, 445 INDEX. 963 Fiiniit-ation after scarlet fever, Oil, 612 tvpliiis t'ovi'r, 'J'l'J, '!•'>?> local, of sypiiilis, 1)09 ami pertussis, I'l'l in sypiiilis, W,\ Furbriiio Niemeyer on chronic phthisis. 791 Nikiforoff on relapsing fever, 259 Nikiforofl's method of blood examination, 139 Nitro-glycerin in cholera, 333 Nodes, syphilitic, 882 Noma and enteric fever, 198 Northru|) on tubercular bronchial glands, 763 Nose and erysipelas, 466 Nothniigel on cholera, 329 Nununular sputum, 788 Nursery and Child's Ho.spital and diph- theria, 703 Nurses and tuberculosis, 742 Nuttall on tubercle bacillus, 737 on tuberculosis, 837 OAKES on dysentery, 343 Occupation and malaria, 81 and scarlet fever, 581 and tuberculosis, 745 Odor of yellow fever, 284 ©"Dwyer on diphtheria intubation, 687, 691 (Esophagus, perforation of, in tuberculosis, 763 syphilis of, 871 tuberculosis of, 812 Ointments in ervsipehis, 473 in syphilis. 910, 911 Old age and tuberculosis, 809 Omental tumoi"s in tuberculous peritonitb, Onychia, syphilitic, 867 Ophthalmia in relapsing fever, 263 Opisthotonos in tetanus, 938 Opium in dysentery, 380, 381 Optic neuritis, syphilitic, 889 Orbit, syphilis of, 886 Orchitis in parotiditis, 728, 729 syphilitic, 876 Organisms of malaria, 35, 36 Orth on pysemia, 483 on tubercular prostate, 826 0.sler on cerebro-spinal meningitis, 442 on dysentery. 346, 371 on enteric fever, 210, 229 on pyfemia, 490 Osseous system in enteric fever, 197 Osteomyelitis in pyaemia, 489 and septic infection, 504, 505 Osteo-jieriostitis, 881 Os uteri, syphilis of, 876 Otitis and cerebro-spinal meningitis, 432 and scarlet fever, 598, 619 Otitis, syphilitic, 890 media in enteric fever, 188 and inliuenza. 417 and meningeal tuberculosis, 759 Ovary, tuberculosis of, 831 Overcrowding in ty[)hus fever, 235 Ovum and tuberculosis, 739 Oysters and enteric tever, 172 Ozjena, .syphilitic, 913 PAGET on scarlet fever, 585 on tuberculosis, 810 Pain, abdominal, in enteric fever, 189 in chronic phthisis, 793 relief of, in cholera, 331 in smallpox, 524 Paine on dengue, 158 Painter on diphtheria, 669 Palate, syphilis of, 869 tuberculosis of, 211 Palpation in chronic phthisis, 796 Paludism. See Maloria. Pancreas in enteric fever, 178 tuberculosis of, 817 Papules, moist syphilitic, 862 in smallpox, 520, 521 syphilitic, 860 Paquin on serum-therapy, 84S Paralyses, dysenteric, 373 Paralysis in cerebro-spinal meningitis, 442 in diphtheria, 679 in leprosy, 928 malarial, 131 and meningeal tuberculosis, 758 scarlatinal, 603 syphilitic, 885 Parasite, Eestivo-autumnal, 35, 36, 47 of sestivo-autumnal fever, 76 of dengue, 156, 157 of malaria, 23, 24 of quartan fever, 76 of tertian fever, 76 Parasites, differential diagnosis, 58 of malaria. classificatif)n, 35, 36 intimate structure, 60 and quinine, 146 varieties, 58 malarial, in combined infections, 122 localization of, 72 quartan, 35, 36, 40 tertian, 35, 36, 44 Parasitology of malaria, 20 Paris hospitals and tuberculosis. 742 Morgue and tuberculosis, 834 Parke on typhus fever, 248 Parkes on yellow fever, 271 Paronychia, syphilitic, 868 Parotiditis, 725 age, 725 complications, 729 definition, 725 diagnosis, 729 in enteric fever, 221 etiology, 725 incubation, 726 initial stage, 720 orchitis in, 728, 729 972 INDEX. Parotiditis, pathological anatomy, 726 pathology, 726 prognosis, 730 prophyhixis, 730 recurrence, 729 relapse, 729 in relapsing fever, 263, 265 season, 725 sequelae, 729 stage of swelling, 727 symptoms, 726 synonyms, 725 treatment, 730 Parotitis. See Parotiditis. Paroxysm of sestivo-autumnal fever, 107 of pei'tussis, 716, 717 of tertian fever, 100 Parry on relapsing fever, 258 Pasteur on cholera, 307 on septicaemia, 497 Pathogenesis of malaria, 69 Pathological anatomy of acute cataiThal dysentery, 347 of amoebic dysentery, 351 of cerebro-spinal meningitis, 433 of cholera, 311 of chronic phthisis, 780 of dengue, 158 of diphtheria, 673 of diphtheritic dysentery, 349 of enteric fever, 173 of ei'ysipelas, 456 of influenza, 407 of malaria, 83 of Malta fever, 947 of meningeal tuberculosis, 755 of parotiditis, 726 of plague. 394 of pyajmia, 482 of relapsing fever, 259 of scarlet fever, 587 of secondary dysentery, 355 of smallpox, 520 of syphilis, 890 of tetanus, 937 of typhus fever, 239 of vaccinia, 559 of varicella, 571 of Weil's disease, 945 of yellow fever, 275 Pathology of erysipelas, 451 of leprosy, 924 of measles, 626 of parotiditis, 726 of pertussis, 714 of phthisis, 775 of rubella, 640 Peiper on enteric fever, 230 Pellarin on malarial kidneys, 87 Pelvic organs in cholei'a, 314 Pemberton on tuberculosis, 818 Pemphigus gangrenosa, 57 and leprosy, 929 Penis, syphilis of, 874 Pensuti on malarial urine, 124 Penzolt on tuberculosis, 812 Percussion in chronic phthisis, 797 Perforation in enteric fever, 175 intestinal and dysentery, 366 of intestine in enteric fever, 190, 219 of lymph glands in tuberculosis, 763 Pericarditis, acute tuberculous, 769 chronic tuberculous, 769 in enteric fever, 186 tuberculous, 769 diagnosis, 770 Pericardium, tubercular, 769 in yellow fever, 276 Periodical fever, 17 Periodicit}' of malaria, 70 of scarlet fever, 577 Periostitis, syphilitic, 881, 882 Peripheral nerves, syphilis of, 885 neuritis after malaria, 132 Peritoneum in cholera, 312 tubercular infection through, 819 tuberculosis of, 770 Peritonitis, acute tuberculous, 754 and dysentery, 366 in enteric fever, 191, 206, 218 and scarlet fever, 600 tuberculous. See Tuberculous Pei-itonitis. Pernicious ansemia and influenza, 418 Pertussis, 713 age, 713 catarrhal stage, 716 complications, 717 definition, 713 diagnosis, 719 and enteric fever, 198 etiology, 713 general treatment, 723 hygiene, 721 incubation, 715 local treatment, 721 mortality, 720 paroxysmal stage, 716 pathology, 714 prognosis, 720 prophylaxis, 720 recurrence of, 719 relapse, 719 and scarlet fever, 600 sequelse, 718 sex and, 713 stage of decline, 717 symptoms, 715 synonyms, 713 treatment, 720 Peruvian bark in malaiia, 146 Pest, 391 Pestilentia, 391 I Petechia? in enteric fever, 197 in relapsing fever, 260 I Petechial typhus, 168 Pettenkofer on enteric fever, 172 Pever's patches in enteric fever, 174 Pfeiffer on influenza, 406, 407 Phagocytes in malaria, 65, 67, 69, 73 Piiagocytosis, 76 in sestivo-autumnal fever, 120 in erysipelas, 458 in malaria, 43 Pharyngeal diphtheria, 675 l\J)j:x. 973 Pharynx and erysipelas, 466 in smallpox, ;").'{2 syphilis of,