: . ,''.'.'. Wxmw wiaa \':.'. ■ ///i)/vr rum i LIBRARY NEW YORK STATE VETERINARY COLLEGE ITHACA, N. Y. mini iiiiiiiiiiiiiniiiimimiriniriimitFiiiriiiiiiiriumiijiiimiiiiiijuiHiiiiiiilMMi j j j 1 1 1 ■b # RC i87.G28 ne,IUn ' Vers " yUbrary T ffl,li!?^,«nsWe,ed as a problem of 3 1924 000 230 502 DATE DUE W3 1 L 1975 , I'QiLM- iSiSrij ' « *■ GAYLORO PRINTED INU.I-A. h Cornell University 9 Library The original of this book is in the Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924000230502 TYPHOID , FEVER CONSIDERED AS AJPPROBLEM OF, SCIENTIFIC MEDICINE THE MACMILLAN COMPANY HEW YORK ■ BOSTON • CHICAGO • DALLAS ATLANTA • SAN FRANCISCO MACMILLAN & CO., Limited LONDON ■ BOMBAY ■ CALCUTTA MELBOURNE THE MACMILLAN CO. OF CANADA, Ltd. TORONTO TYPHOID FEVER CONSIDERED AS A PROBLEM 4 OF SCIENTIFIC MEDICINE BY FREDERICK P. GAY PROFESSOR OP PATHOLOGY IN THE UNIVERSITY OP CALIFORNIA JJro fork THE MACMILLAN COMPANY 1918 AU rights reserved £&&£%»/ Co: Bt THE MACMILLAN COMPANY , Set ap and printed. PubliahedlJanuary, 1918 181 PREFACE This treatise is an attempted exposition of the problem of typhoid fever. It aims to treat historically the development and present status of our knowledge concerning this important malady as viewed from the standpoint of its mechanism. It is not pri- marily designed to aid directly in the clinic or the laboratory, but should serve to point out the relations of one to the other, to indi- cate the dependence of practice on theory, and the happy appli- cability to human need of investigation that may have seemed to aim merely at the gratification of intellectual curiosity. There are numerous admirable clinical treatises on typhoid fever, such as those of Curschmann, of Vincent and Muratet and of McCrae. The purely laboratory and the public health aspects of the disease are well summarized in such works as those of Kutscher, of Chapin and of Whipple. This book aims to strike a balance between these sources of information, following the life history of the typhoid bacillus rather than the manifestations of the disease it produces, in order to gain insight into the nature of the problem as a whole. No attempt has been made to make this work encyclopedic in character, although the references to original sources are suffi- ciently ample to lead a prospective investigator to full sources of information. Although we may have succeeded in maintaining correct proportions in our estimate of the accuracy and value of facts, methods and theories that have been shaken down by time into their proper relations to one another, we shall unconsciously or wilfully have exaggerated the importance of recent contribu- tions. We may well have overemphasized the importance of modern investigations in respect to antityphoid vaccination and specific therapy in typhoid fever through personal enthusiasm. The data on these aspects of typhoid fever are so ample and so recent that a critical summary of their essentials seems desirable, even though somewhat premature. In addition to the use that has been made of all the general treatises and original sources of information to be cited, particular indebtedness is felt to Charles Murchison's "Treatise on the Continued Fevers" as furnishing the backbone of the discus- sion of the earlier historical aspects of typhoid fever. The author wishes to express his thanks to Dr. John N. Force, Miss Ruth Stone and Miss Helen Dunbar for suggestions and aid in preparing the manuscript. TABLE OF CONTENTS CHAPTER I A GENERAL STTBVBY OF THE DEVELOPMENT Or KNOWLEDGE COM CBBN1HG TTPHOIB FEVEB PAG« Progress in the Differential Diagnosis of Typhoid on the Basis of Symp- . tomatology and Morbid Anatomy 1 Development of the Conception of Contagion in Typhoid Fever 6 The Advent of Bacteriology and Its Importance in the Explanation and Prevention of Typhoid Fever 8 CHAPTER II TYPHOID FEVEB AS A CAUSE OF DEATH AND DISABILITY The Significance of Typhoid Fever in Mortality Statistics 13 Chronological Changes in the Typhoid Death Rate 15 Typhoid Fever in Armies 21 The Present Economic Loss from Typhoid 22 CHAPTER III THE TYPHOID BACILLUS Bacillus Typhosus as the Cause of Typhoid Fever 25 The Cultural Characteristics of Bacillus Typhosus 25 Biological Peculiarities Which Serve to Differentiate the Typhoid Bacillus from Other Bacteria 28 The Toxins of Bacillus Typhosus 31 Mutations and Variations in Bacillus Typhosus 34 CHAPTER IV THE MODES OF INFECTION IN TYPHOID FEVEB Transmissibility of Typhoid Fever and General Conceptions of Its Modes of Infection 39 Sources of Infection from the Typhoid Patient 42 The Typhoid Bacillus at Large 45 Routes Followed by the Typhoid Bacillus from one Individual to Another 46 Contact Infections in Typhoid 46 Direct Contact 46 Indirect Contact and Its Several Channels to the Individual 47 Water Infections in Typhoid and Its Several Routes in Reaching the Individual 50 Relative Importance of Various Routes of Infection 56 vii Tiii CONTENTS PAGE General Factors Which Influence the Occurrence of Typhoid Fever 56 Extrinsic Factors 56 Intrinsic Factors 58 CHAPTER V THE PATHOGENESIS OP TYPHOID PEVEB General Symptomatology of Typhoid Fever 61 The Incubation Period 63 The Portal of Entry 66 Localization of the Typhoid Bacillus in the Body During the Course of the Disease 70 The Cause of the Fever in Typhoid 72 Metastatic Foci of Typhoid Bacilli 73 The Bone Marrow in Typhoid 74 The Gall Bladder in Typhoid Fever 75 The Toxins of the Typhoid Bacillus in Their Relation to the Disease Process: 77 The Complications in Typhoid 78 Complications in General and Causes of Death 78 Hemorrhage and Perforation 79 Relapses 81 Experimental Typhoid Fever in Animals 83 CHAPTER VI THE DIAGNOSIS OP TYPHOID PEVEB Clinical Diagnosis and Its Limitations 87 Laboratory Diagnosis of Typhoid Fever 88 Detection of the Typhoid Bacillus in the Body 88 Isolation of the Bacillus from the Blood 89 Isolation of the Bacillus from the Stools 94 Isolation of the Bacillus from the Bile 97 Isolation of Typhoid Bacilli from the Urine 98 The Differential Diagnosis of Bacillus Typhosus 98 Diagnosis of Typhoid Fever Based on Specific Reactions on the Part of the Patient 100 Serum Reactions 100 Agglutination 101 Fixation Reactions in Typhoid 105 The Bactericidal Property of the Serum of Typhoid Patients .. 106 Tropins or Opsonins in Typhoid Serum 106 Methods of Diagnosis Depending on Evidence of Localized Hyper- susceptibility in the Patient 107 Diagnostic Reactions Dependent on Changed Metabolism in Ty- phoid Fever 107 CONTENTS ix PAGE Changes in the Leucocyte Count in the Course of Typhoid Fever. . . 108 Summary of the Diagnostic Value of the Various Laboratory Tests. . 109 CHAPTER VII THE SEQUELS OP TYPHOID FEVER AND THE CARRIER CONDITION Sequels After Bacteriological Cure Ill Typhoid Sequelae Due to Persistence of the Typhoid Bacillus in the Body 113 Localized Pyogenic Foci 113 Gall Bladder Infection 114 Jaundice and Cholecystitis 116 Gall Stones 117 The Carrier State 119 Classification of Typhoid Carriers 120 Urinary Carriers 120 Carriers in Recovered Typhoid Cases 121 Convalescent 121 Chronic 122 Precocious or Incubation Period Carriers 123 Healthy Carriers 124 Importance of Carriers as a Source of Typhoid Fever 126 General Facts in Reference to Carriers 128 The Detection of Carriers 129 CHAPTER VIII GENERAL MEASURES OP PREVENTION OP TYPHOID FEVER The Prevention of Typhoid Fever at Its Source 131 Prevention of the Extension of Typhoid Fever from Typhoid Patients. . 132 Prevention of Extension from Typhoid Carriers 135 The Detection of Carriers 136 General Methods of Dealing with Recognized Carriers 136 Treatment of the Carrier State 138 The Suppression of Typhoid Infection in Its Transit from one Individual to Another 141 Measures of Protecting Possible Victims of Typhoid Infection 142 CHAPTER IX NATURAL AND ACQUIRED RESISTANCE TO TYPHODD FEVER Evidence for Natural, Individual and Racial Immunity from Typhoid. . 145 Immunity from Typhoid Acquired by Recovery from the Disease 147 Recurrence of Typhoid Fever 147 The Nature of Protection Afforded by Recovery from Typhoid. . . . 149 The Typhoidin Test in Typhoid Recoveries 151 x CONTENTS CHAPTER X ARTIFICIAL IMMUNIZATION AGAINST TTPHOID FEVER TA.QU Historical Aspects of Typhoid Immunization 155 Preparations of the Typhoid Bacillus That Have Been Used as Vaccines 156 Killed Cultures of the Typhoid Bacillus 156 Bacterial Extracts 158 Living Cultures of the Typhoid Bacillus 159 Sensitized Cultures of the Typhoid Bacillus 159 Methods of Administration of Typhoid Vaccine 164 The Immediate Effects Following Antityphoid Inoculation 166 CHAPTER XI THE PROTECTIVE VALUE OF VACCINATION AGAINST TTPHOID FEVER Statistical Value of Results of Vaccination Available 172 Vaccination in Armies.. 173 Results in the English Army 174 Results in the French Army 177 Results in the French Navy. 178 Results in the Russian Army 178 Results in the Italian Army 179 Results in the Japanese Army and Navy 179 Results in the German Army 180 Results in the United States Army 181 Results in the United States Navy 182 Antityphoid Vaccination in Institutions 184 Vaccination Among Physicians and Nurses 184 Vaccination Among Laboratory Workers 185 Results of Typhoid Vaccination in Civil Communities 185 Typhoid Fever in the Vaccinated 186 Paratyphoid Fever in Typhoid Vaccinated Individuals 189 Multiple Vaccination 191 Duration of the Protection Afforded by Antityphoid Vaccination 192 CHAPTER XII THE PARATYPHOIDAL INFECTIONS Diseases in Man and Animals Produced by Bacteria of the Paratyphoid Group 198 Clinical Differential Diagnosis of Paratyphoid Fever 202 The Laboratory Diagnosis of Paratyphoid Fever 204 Blood Cultures in Paratyphoid Coxes 205 Diagnosis of Paratyphoid Infections by means of Agglutination Test*. . 208 The Incidence of Paratyphoid Fever 209 Epidemiology in Paratyphoid Infections 211 Prophylaxis in Paratyphoid Infections 212 CONTENTS 3d CHAPTER XIII THE TREATMENT OP TYPHOID FEVER FAQS The Influence of Diet in Typhoid Fever 214 Hydrotherapy in Typhoid Fever 215 Treatment of Typhoid Fever by Means of Sera 217 Use of Serum of Recovered Cases 217 Autoserumtherapy 217 Specific Immune Sera 217 Antiserum of Chantemesse 219 Besredka's Antiserum 219 Rodet's Antiserum 220 Vaccine Treatment in Typhoid 221 Comparative Results with Various Vaccines and Different Modes of Administration 221 Intravenous Vaccine Therapy 222 Non-Specifieity of Vaccine Therapy in Typhoid 235 The Mechanism of Cure in Intravenous Vaccine Therapy 236 CHAPTER XIV SUGGESTED METHODS OF ADVANCE IN SOLVING THE TYPHOID PROBLEM 240 BIBLIOGRAPHICAL INDEX OF REFERENCES QUOTED 245 TYPHOID FEVER CONSIDERED AS A PROBLEM OF SCIENTIFIC MEDICINE TYPHOID FEVER CONSIDERED AS A PROBLEM OF SCIENTIFIC MEDICINE CHAPTER I A GENERAL SURVEY OF THE DEVELOPMENT OF KNOWLEDGE CONCERNING TYPHOID FEVER Progress in medicine depends on the gradual recognition and separation of disease entities. Differential diagnosis must precede all rational means of prevention and therapy, and in each of these phases of progress the older methods of bedside observation and experience have been increasingly supplemented by methods of laboratory precision. No disease illustrates better the successive stages of scientific medical advance than typhoid fever, which as a cause of death and economic loss has been one of the world's greatest scourges. A survey of the useful knowledge that we have gained in respect to this disease is at once of historic interest, as bearing on medical progress, and of promise to those who trust in "Man's redemption of man." PBOGBESS IN THE DIFFERENTIAL DIAGNOSIS OF TYPHOID ON THE BASIS OF SYMPTOMATOLOGY AND MOBBID ANATOMY The disease we now recognize as typhoid or enteric fever is one of those continued fevers which was for centuries confused with other lasting fevers of somewhat similar appearance. Even today mistaken diagnoses are frequent, unless the most modern methods of laboratory aid are resorted to. Among those fevers which may be confused with typhoid may be mentioned recurrent fever, septic infection, malaria, tuberculosis, trichiniasis, and, particularly, typhus fever. The recognition of a disease entity like typhoid is, of course, more readily made in face of an epidemic than in an individual case. In the gradual differential recognition of typhoid fever we find certain characteristics which have been evident from the first. One of the most striking things about typhoid fever is its seasonal occurrence, and we find that Hippocrates, in the course of two successive autumns, met with many cases of a fever l 2 TYPHOID FEVER of the continuous type, characterized by diarrhea, offensive watery stools, bilious vomiting, tympanites, abdominal pain, red rashes, epistaxis, sleeplessness, and in some cases a tendency to coma, delirium and subsultus, irregular remissions, and a lengthened duration, accompanied by increasing emaciation. Galen classified under the larger grouping of Hemitritceus a variety of bilious fever which may also have been typhoid. We may continue our historical survey by dividing the criteria of differentiation into two rather arbitrary groups. First of all, may be cited those criteria which are based on purely clinical, observational grounds, and on the basis of experience, and, secondly, those criteria which depend on the recognition of def- inite changes in anatomic structure. It is obvious that chrono- logically these two groups of observations will overlap to a considerable extent, but the separation may serve to show the limitation of each type of investigative procedure. Following the observations of Hippocrates and Galen, which have been mentioned, Spigelius in 1624 noted the occurrence of a fever characterized by the presence of abdominal pain, diarrhea, with sometimes melena, absence of crisis, and occasional relapses. In 1659 Thomas Willis * of England was first to make an attempt at separation of typhoid fever from typhus or febris pestilens, with which it was still destined for many years to remain confused. He made his differentiation on the basis of the fact that typhoid fever is less contagious, has little or no eruption, an imperfect crisis, and is prone to local complication. In 1734 Ebenezer Gilchrist described typhoid fever under the name of "nervous fever," which he characterized by its long duration, the occurrence of diarrhea, abdominal pain, blood in the stools, epistaxis, and "partial sweats which gave no relief." A further and more com- plete separation between typhus and typhoid fever was made by Langrish in the following year, who separated the two diseases under the headings of "slow, nervous fever," and "malignant, continued fever." A further amplification of this separation was made by Huxham (1739), who described the two fevers as "slow, nervous fever," on the one hand, and "putrid, malignant, petechial fever," on the other. About the year 1850 a discussion arose be- tween Sir John Pringle and Professor De Haen of Vienna, in ref- erence to the advisability of bloodletting in fevers. This discus- sion is now of no particular interest as bearing on treatment, but served to bring forward a point in differential diagnosis between the eruptions of typhus and of typhoid. It appears that Pringle was describing bloodletting in typhus fever, whereas the cases GENERAL SURVEY 3 which De Haen had treated were typhoid. It remained for Pringle to recognize the fact that they had been describing two different forms of disease, and he makes the statement that the miliary fever or typhoid of De Haen occurs in all ranks of people and is characterized by a petechial and miliary eruption, whereas the fever which he had been studying, the malignant fever, occurs only among people who are crowded together in such close and foul places as military hospitals, jails, and transport ships. In 1772 Dr. Macbride of Dublin spoke of "febris nervosa," a pro- tracted fever attended by diarrhea, as different from the putrid, continual fever which was contagious and accompanied by a florid eruption which gradually passed into petechia. We may now turn to the differentiation of typhoid fever on the basis of changes in anatomic structure, at once a surer and more scientific basis of classification. It appears that the lesions of typhoid fever were first referred to by Spigelius in 1624, who called attention to an inflammation and sometimes gangrene and sphace- lus of both large and small intestines. In 1682 Willis 2 made these observations much more definite by describing, in the less contagious of the two diseases which he attempted to differentiate, pustules like those of variola and ulcers in the small intestines, accompanied by swelling of the mesenteric nodes. In 1696 Baglivi called this fever "febris mesenterica" on account of the enlarge- ment of the mesenteric glands which he found associated with the intestinal inflammation. He also separated the disease from typhus or febris pestilens. Hoffmann in 1699 described gangrene and sloughing of the small intestine as associated with typhoid. Lancisi in 1718 first described typhoid perforation, which, how- ever, he incorrectly attributed to the presence of certain lum- bricoid worms in the intestines. In a form of fever which he refers to as Lent or symptomatic fever, Strother in 1729 described in- flammation and an "ulcer fixed on some of the bowels." The characteristic lesions of typhoid were more definitely localized by Riedel in 1748, who described "febris intestinalis," accompanied by gangrene of the lower ileum. A definite and full description of the characteristic intestinal lesions of typhoid fever is usually attributed to two German investigators, Roederer and Wagler (1762). After a careful inspection of the original treatise, we agree with Murchison, however, that it is practically certain that these investigators were not dealing with typhoid at all. In their thirteen cases, the post-mortem appearances of which are de- scribed with great minuteness, we find no description of ulceration of the ileum, whereas the lesions described are almost entirely 4 TYPHOID FEVER confined to the stomach or to the large intestines. It is probable, then, that the German investigators were in reality dealing with an epidemic of typhus, complicated by dysentery, as Murchison has suggested. It appears that the intestinal lesions of typhoid did not escape the keen observation of John Hunter, as is shown by two preparations in his museum at the Royal College of Surgeons, one of which was later figured in a publication by Matthew Baillie. It remained, however, for a group of French investigators in the early part of the nineteenth century to describe with fullness and accuracy the lesions which we now recognize as being char- acteristic of typhoid. In 1804 Prost described ulcerations in the mucosa of the intestines and also a mild type of inflammation, which, however, was in all probability a simple post-mortem change. In 1813 Petit and Serres described in their "Fidvre ent^ro-mesenterique" lesions which were limited to the lower ileum and were specific, differing in many particulars from the ordinary type of inflammation which occurs in simple enteritis. They believed, moreover, that these lesions preceded and were the cause of this fever. In 1826 Bretonneau described typhoid under the name of "dothienenteritis," which he found charac- terized by lesions localized in the agminated and solitary glands of the ileum. He thought, moreover, that this disease was due to a poison, transmissible from the sick to healthy individuals, which suggestion may be regarded as the first definite contribution to the means of transmission in typhoid fever. Bretonneau further made the important observation that there is no definite relation between the severity of the disease and lesions produced. These observations were confirmed and amplified in the same year and independently by Hewitt of London, who also described the lesions of the solitary and agminated follicles. The further ob- servations of Louis in 1829 and of Chomel (1834) served still further to separate typhoid from simple gastro-enteritis, and also to point out the lesions of the lymph follicles. We find, then, at the beginning of the nineteenth century that a pretty clear picture of typhoid fever had been developed, at first on clinical grounds, and later on the basis of post-mortem appearance. There remained, however, for several years confusion between the two diseases, typhus and typhoid, owing largely to the fact that few observers had been able to compare them at first hand. We have mentioned the criteria of differentiation on a purely clinical basis by Willis and Huxham, and other similar observations were also made by Hildenbrand in Germany in 1810, who separated GENERAL SURVEY 5 "contagious typhus" from "non-contagious, nervous fever," a separation which was further amplified by the work of Schoenlein in 1839, who gave names to the two diseases, which still unfor- tunately persist in Germany, namely, "typhus exanthematicus" and "typhus abdominalis." The objection to these terms lies not in their original form but in the abbreviation of "typhus," which is frequently used indiscriminately for typhus and typhoid. The valuable anatomic work of Bretonneau, Louis, and Chomel was not immediately of great service in the separation of typhus from typhoid, owing to the fact that the French investigators had no opportunity of studying typhus fever, a disease which in their time prevailed primarily in England. They were, indeed, inclined to regard typhus in England as identical with the French typhoid fever, and they regret that no careful anatomical observations were made by the English observers. Dr. H. P. Lombard of Geneva in 1836, on the basis of study of fever both in France and England, concluded that in England there were two types of disease present: first of all, the contagious typhus; and, second, a sporadic disease identical with the typhoid fever of the French. It remained, however, for William Gerhard in 1837 to establish beyond doubt the differential criteria between typhus and typhoid fever, on the basis of his own experience in both diseases in France and in Philadelphia. Gerhard maintained that the typhus of Philadelphia was identical with British typhus fever and with the jaL, ship, petechial or spotted fever, and that it is eminently contagious. On the other hand, the enteric or typhoid fever of the French is rarely communicated from one individual to another. He showed that the lesions of Peyer's patches and of the mesenteric glands invariably present in the latter were never found in the former, and remarked that English observers erred in regarding the in- testinal disease as a mere complication of typhus. He insisted on the marked difference between the petechial eruption of typhus and the rose-colored spots of typhoid fever, and he showed that a peculiar train of symptoms very different from those of typhus were associated with the intestinal affection, and that the dis- tinctive characters of the two diseases were such as should not allow them to be confounded in practice. Shattuck of Boston studied cases of both diseases in France and England and separated the two in London. Confirmatory observations were made by Valleix (1839) and by Rochoux (1840) in France, and by Barlow in England (1840). Sir W. Jenner h 2 in London between 1849 and 1851 further confirmed and amplified the distinction between the symptoms of the two diseases as previously laid down by Gerhard 6 TYPHOID FEVER and others. By careful analysis of cases admitted into the London Fever Hospital, he showed that the two fevers did not prevail coincidently and that the one did not communicate the other. He also adduced cases to prove that an attack of either fever pro- tected the patient from subsequent attacks of the same malady but not from the other. Perhaps the most important bearing of these facts is their indication that the two diseases are not only different, but are due to distinct causes. It was possible, then, early in the nineteenth century to recognize typhoid fever as a disease entity on the basis of clinical observation and post-mortem examination. No clear understanding of the exact nature of the disease was, however, possible until the isolation of its specific bacterial cause, nor could the certain recognition of the disease in any particular case be assured in the absence of such knowledge. And, if the individuality and the recognition of typhoid fever is dependent on bacteriology, much more so is accu- rate knowledge concerning its method of transmission and effective prevention. DEVELOPMENT OF THE CONCEPTION OF CONTAGION IN TYPHOID FEVER There were, however, several observations in the pre-bacteriolog- ical days which were of extreme significance, and, indeed, of prac- tical importance in understanding and in controlling this disease. Up to the nineteenth century the general belief was that typhoid fever was not contagious. This relative non-contagiousness was, indeed, one of the earlier differential points in diagnosis between typhus and typhoid. Early in the nineteenth century, however, Leuret (1828), Gendron (1834), and Bretonneau (1829) in turn gave definite reasons for regarding typhoid as transmissible from one individual to another. In 1850 Piedvache summarized the facts, and concluded that the disease is to a limited extent con- tagious. In 1856 William Budd * began a series of publications on the nature and mode of transmission of typhoid fever, which con- stitute one of the most notable contributions to our knowledge of this disease. He not only proved conclusively by careful epi- demiological studies that the disease could be transmitted through the feces of a typhoid patient by means of water or milk con- tamination to healthy individuals, but repeatedly emphasized that this is the usual way in which the disease is propagated. He regards typhoid fever as contagious in the broader sense of the term, using Piedvache's definition that any transmission of a disease from a diseased individual to a healthy individual, what- GENERAL SURVEY 7 ever may be the method, constitutes contagion. The poison of the disease, according to Budd, resides in the diarrheal discharges of the patient, and epidemics are usually caused by contamination of the water supply with such dejecta. "This method of reproduc- tion is not only a characteristic but the master fact in the history of typhoid fever," he says. He discards, after careful discussion, the putrefactive decomposition idea of Pettenkoffer and the pythogenic theory of Murchison, and shows that the disease is essentially self-propagating. He believes he was able to prove this method of contagion, owing largely to the fact that his practice was in the country, where such sewage contaminations are more likely to be traced than with the more complete methods of sewage disposal in cities. Budd, in addition, laid down definite rules which he proved to be effective in checking and preventing epidemics. It is very interesting, moreover, to find that he distinctly foresaw the possi- bility of spread of the disease from the dejecta of those who had entirely recovered from any active manifestations of the malady. In view of this now recognized, important carrier condition, it may be of interest to cite his exact words in this connection. Budd says (p. 118): "The precise date at which the fever patient ceases to give fever to others is not so easy to define. But I have seen so many instances in which fever has broken out in a family living in a previously healthy neighborhood soon after the arrival of a con- valescent, that I am quite sure that patients so far recovered can- not always be safely allowed to mix with others without precau- tion. In the case referred to all traces of actual fever had disap- peared and diarrhea had long ceased." Murchison 2 added certain additional facts to the contagiousness of typhoid fever through the feces, although his theory of trans- mission was marred by the introduction of the idea of a spon- taneous origin of the disease through fermentative processes out- side the body. He further subscribed to the importance of a transmission of typhoid by means of polluted milk. Of historical interest in this connection is the so-called ground- water theory of Buhl and of Pettenkoffer in reference to the spread of epidemics of cholera and typhoid fever. The theory, although no longer accepted in its entirety, doubtless throws some light on the spread of certain epidemics of these diseases. According to Pettenkoffer, the contagion of these two maladies would require a ripening stage in the earth, and the actual spread of the epidemic itself depends on the falling of the ground-water with consequent spread of these ripened contagia from the superficial water supplies. TYPHOID FEVER THE ADVENT OF BACTERIOLOGY AND ITS IMPORTANCE IN THE EX- PLANATION AND PREVENTION OF TYPHOID FEVER The year 1880 may be given as marking the advent of the science of bacteriology, and typhoid fever was one of the first of the human infectious diseases to yield the secret of its specific animate causa- tion. In the few years preceding 1880 several observers had de- scribed the occurrence of certain micrococci in the tissues of cases of typhoid fever. The bacillus, however, which we now recognize as the cause of the disease was not discovered until 1880. The first observations of Bacillus typhosus in the tissues may be attrib- uted to three independent investigators, namely, Eberth, Elebs, and Koch. Credit of priority in the discovery of the micro- organism is generally given to Eberth, but it may well be that injustice has been done in the general acceptance of this priority. It is of interest, therefore, to examine the investigations of these authors in some detail. On April 22, 1880, appeared the first contribution of Klebs 1 on the nature of typhoid, in which he describes his findings in twenty-four fatal cases of the disease. In each of these cases he found short rods, and also in certain places filamentous but unbranching bacterial structures in the various tissues of the body which are peculiarly associated with the malady. He found these organisms in Peyer's patches, in the mesenteric lymph nodes, in the blood vessels, and also in the pia of certain meningeal cases of the disease. The organisms were not found in the intestinal wall of normal cases. They were found in definite relation to what he describes as "a leucocytic proliferation" in the necrotic areas caused by the disease. In July of the same year Eberth x published his findings in typhoid. In the majority of cases of the disease which he inves- tigated he found short bacterial rods in various organs of the body, which diminished in number with the progression of the disease. He states that these rods at times possess spores and do not stain well with the ordinary aniline dyes. From the illustrations which accompany his article it would appear certain that he was dealing with the Bacillus typhosus, although the sporogenous forms which he likewise depicts are misleading. In the year 1881 Koch * published photomicrographs of the bacterial findings in various infectious diseases, among them typhoid fever, in which the characteristic microorganism appears with convincing clearness. Both Eberth 2 and Klebs agree that the bacterial or rodlike forms which each of them had in turn described are identical. The GENERAL SURVEY 9 difference in their findings would seem to rest in the description by Klebs of threadlike forms of from fifty to eighty micra in length, which we do now recognize as characteristic of the growth of the typhoid bacillus, at least in the body. Somewhat similar forms have been described in culture media. This type Klebs regards as a second stage in the development of the rodlike form. Klebs may well have erred in describing a type of microorganism which may have been a secondary invader; it is evident, however, that he really did see the same typhoid bacillus that Eberth describes. Since criticism is made of his description of this threadlike micro- organism, it may also be pointed out that the sporogenous micro- organism described by Eberth is likewise inaccurate. At all events, the threadlike forms described by Klebs seemed to him subsidiary to the rods which alone are mentioned as occurring in the various organs of his twenty-four protocols. Klebs unques- tionably should be credited with suggesting the accepted name (B. typhosus) for the etiological agent in typhoid fever. It would seem also that at least some credit should be given to Klebs for his attempt, and, perhaps, success in cultivating Bacillus typhosus outside of the animal body, although the usual credit for this discovery is given entirely to Gaffky (1884). In Klebs' second communication in 1881 2 he describes his method of pre- paring and sterilizing gelatine culture media, his inoculation of such media from the mesenteric lymph nodes of a case of typhoid fever, and he further notes the occurrence of rodlike forms in the turbid culture growth which results from the inoculation. Gaffky objects to accepting Klebs' results largely on the basis that he had described threadlike forms as existing in the disease, and also owing to the fact that he, Gaffky, failed to produce lesions in animals with his pure cultures similar to those that had already been described by Klebs. Klebs had described the production of hemorrhagic infiltration without ulceration in the cecum of rabbits following injection of his culture of the microorganism. Although Gaffky failed to obtain such results with his cultures, it is now known that they may be produced with pure cultures and toxins of the typhoid bacillus, although they are not specific in nature (Arima, 1 Gay and Claypole 1 ). Klebs, then, may well have grown Bacillus typhosus and, indeed, may have grown it in pure culture, although it remained for Gaffky to demonstrate the purity of the culture, as he was able to do by the employment of solid culture media. Gaffky remarks on the absence of spores in his artificial cultures of the microorganisms, and also comments on its growth on gelatine and potato. 10 TYPHOID FEVER We have discussed hitherto in some detail the historical de- velopment of our knowledge concerning typhoid fever, first on purely clinical grounds, and secondly, on the ground of post- mortem examination. We have further considered the early observations of the typhoid bacillus in the tissues and, secondly, the growth of this microorganism in pure culture. We may now proceed to outline rapidly the successive advances which have followed the complete recognition of a single etiological factor in this disease, leaving more detailed consideration of the method of obtaining such facts and of their significance and applicability to subsequent chapters. It will, we believe, be evident that all significant information concerning the nature of the disease itself and its method of dissemination, as well as all effective means that have been devised to prevent and cure it, have depended on laboratory data and are based on the recognition of the single bacterial causative factor. Following the observations of Klebs, Eberth, Koch and Gaffky that the typhoid bacillus occurs in the various organs that are obviously affected in the disease, and can be isolated from them in pure culture, it was soon shown by A. Pffeiffer (1885) that the organism could also be found in stools, and by Hueppe 1 in the following year in the urine in typhoid fever. One of the most important landmarks in the development of our knowledge concerning typhoid fever and in its diagnosis is the detection of the causative microorganism in the circulating blood. Fraenkel and Simmonds * (1886) are usually credited with this important discovery. They isolated the organism, to be sure, from the blood of the cadaver in one of six fatal cases in that year, but failed then and the year before to obtain it from the blood of living cases. The presence of the microorganism in the blood post mortem, is of course, of interest, but might well be due to a terminal invasion, and for both diagnostic and etiological reasons the greater importance attaches to the discovery of the bacillus in the blood intra vitam. It is apparently Vilchur who in 1887 was first suc- cessful in isolating the typhoid bacillus from the circulating blood, although only in one of thirty-five attempts. Neuhaus had in the previous year obtained the organism from the blood of rose spots in nine of fifteen cases. It is now generally recognized that typhoid fever is primarily a bacteremia and not a disease essentially characterized by in- testinal lesions, which, although they occur in a majority of cases must be regarded rather as incidental and terminal than indica- tions of the true nature of the disease itself. It has already been GENERAL SURVEY 11 pointed out by Louis and others on purely clinical grounds that cases of apparent typhoid fever might occur with absence of any lesions in the intestines. That such cases were indeed typhoid fever and not some disease simulating it, remained, however, to be proven in cases that could be bacteriologically controlled. Such an observation was first made apparently by Terrile, who described a case of typhoid from which he isolated the bacillus in the blood and which showed at death no intestinal lesions. Numerous similar cases have since been described by Chiari 1 and others. Of great significance was the isolation in 1890 by Gilbert and Girode 1 of the typhoid bacillus from the gall bladder in cases of typhoid with acute cholecystitis. Chiari 2 showed a few years later that the microorganism occurs with great regularity in this viscus during typhoid fever. The relation of these observations to our knowledge of the course of the disease and of its sequels will be fully considered in another place. By the year 1890, then, it was generally recognized that no disease could properly be called typhoid fever unless the typhoid bacillus was found somewhere in the body; and, conversely, any case having such an organism in the body, or at least in the blood, must be one of typhoid fever.* Another and almost equally val- uable method of differential diagnosis was introduced into practice by Widal * in 1896. The characteristic property he found in the blood serum of typhoid cases depends upon the important phe- nomenon of agglutination. A clumping occurs when the serum of animals that have been inoculated with or infected by a given bacterium is allowed to act on the provocative microorganism. In the year 1896, Achard and Bensaude reported the first cases which led to separating from the typhoidal fevers a group of maladies now known as paratyphoid infections, similar in most respects clinically to the fever caused by Bacillus typhosus, but each due in turn to a specific microorganism of the paratyphoid or paracolon group. Such organisms, differing in their sugar reac- tions from true typhoid bacilli, were described in two cases by these French authors and were found in one instance in the urine, and in the other in a parotid abscess. In the following year, 1897, Gwyn isolated a similar "paracolon" organism from the circulat- ing blood of a case, the serum of which agglutinated this organism but not the typhoid bacillus, and thereby proved its etiological relation to the disease. In the year 1893, Fraenkel made the first attempt to affect * Exception must be made to the healthy or recovered bacillus carriers. 12 TYPHOID FEVER typhoid fever in a specific manner by the subcutaneous injection of killed cultures of the typhoid bacillus. In 1896, preventive inoculation against typhoid fever was independently attempted by Sir Almoth Wright 1 and by Pfeiffer and Kolle. 1 Attention may now be drawn to certain observations of sig- nificance in relation to the spread of typhoid fever. Reference has already been made to the suggestion of Budd concerning con- tagion from recovered typhoid cases, and the observations of Klebs 3 in 1887 likewise indicate the danger of infection from the feces of afebrile cases or even of healthy individuals. The danger of feces from cases of typhoid fever in spreading the disease was convincingly pointed out by Reed, Vaughan and Shakespeare in their study of the typhoid epidemics in the Spanish-American War (1898). In their report they point out that the spread of the dis- ease in certain regiments bore an undoubted relation to the care- lessness in erecting privies, the exposure of dejecta and the prob- able r61e of flies that had access to these dejecta in contaminating food supplies. Several observers had shown that flies could me- chanically carry bacteria for varying periods of time, and Hamil- ton finally completed the chain of evidence by showing that flies captured in houses in which there were cases of typhoid actually did carry typhoid bacilli. In 1898, Petruschy suggested that people who had recovered from typhoid fever might still be able to infect healthy individuals by means of typhoid bacilli that persisted in their urine. Robert Koch (1903) 2 deserves credit for first specifically calling attention to the danger of the extension of typhoid fever through typhoid bacilli in the excreta of convalescents, or possibly of persons who were apparently healthy. This suggestion was confirmed by Frosch in epidemics in southwest Germany, and led to the es- tablishment of many stations there for the study of such ways of disseminating the disease. This study proved not only the rela- tive infectiousness of stools in different periods of the active dis- ease, but demonstrated that the bacilli persist for varying lengths of time in some four per cent of recovered cases. In 1904, Dri- galski made the important observation that typhoid bacilli may also be found in the feces of some individuals who have apparently never suffered from the disease and that epidemics may be caused by such "healthy" carriers. CHAPTER II TYPHOID FEVER AS A CAUSE OF DEATH AND DISABILITY Our interest in typhoid fever is manifold and compelling. In the first place, we are humanely concerned with the disease as one of the great causes of death and disability, more particularly in the past, but yet to a considerable extent in the present. And it is precisely this rapidly waning seriousness of typhoid that en- hances its interest as a pragmatic problem of preventive medi- cine. The rapidly increasing group of facts that has been gathered through its scientific study, and particularly during the latter years, has led not only to a gratifyingly complete conception of the disease process itself, but has produced practical results of great significance. No human disease, under varying conditions of life, in war and in peace, has been more rapidly checked, and none gives greater promise of eventual complete suppression. THE SIGNIFICANCE OP TYPHOID FEVER IN MORTALITY STATISTICS In the United States, of all nations, our consideration of the typhoid problem is particularly to be desired, since we have hitherto been extremely backward in applying recognized methods of sanitary prevention which have long prevailed in other lands. Typhoid fever remains the ninth contributing cause to the mor- tality statistics * in this country and ranks fifth among the infec- tious diseases, being exceeded as a cause of death only by tuber- culosis, pneumonia, infantile diarrhea and diphtheria. The eco- nomic importance of the disease is even greater than is suggested by these mortality figures, serious as they are, for it is precisely in those years of greatest expectancy and promise that its in- cidence is greatest. After passing through the perilous years of infancy with its characteristic and as yet not wholly avoidable infections, the child, and particularly the young adult, arrives at a period where his chances of usefulness are found to be most assured, and it is during this period that typhoid is most common. About fifty per cent of all cases of the disease occur between the ages of fifteen and twenty-five, and the greater part of these in * Dept. of Commerce Mortality Statistics, 1915. 13 14 TYPHOID FEVER the earlier lustrum (Murchison; 1 Curschmann). Graham, who has studied the incidence of acute infections occurring in children in Philadelphia from 1911 to 1915, finds that typhoid fever ranks next to diphtheria as a cause of death and has the highest mor- tality rate. The actual death rate from typhoid in the United States was in 1900, 35.9 to the 100,000 inhabitants, and in 1913, 17.9, an encouraging diminution of over fifty per cent. Most of the other major causes of death have also diminished during this period, with the exception of cancer and certain chronic diseases, but the rapidity of diminution in typhoid fever has been exceeded by only one other acute infectious disease, namely, diphtheria. Any satisfaction we may feel in these results is, however, lessened on considering that our mortality rate in 1900 had not quite reached the low level in Germany in the five years from 1879 to 1883. The actual number of cases of typhoid fever in the United States in the year 1900 is estimated at 353,790 (Whipple), and the deaths were 35,379. In 1914, the number of cases had diminished to 198,000 and the deaths correspondingly to 19,800 (Dublin). In 1912, the death rate in Germany * was three per 100,000, or actually 2,119 deaths, in a population of over 64,000,000. There may be some satisfaction in finding that the United States re- cently shows a lower typhoid death rate than the two most back- ward continental nations, Spain and Italy, which in 1912 were twenty-seven and twenty-two respectively. No other European nation, however, exceeded nine (Belgium). The occurrence of any given disease in a community is usually estimated from the mortality statistics and not from the actual cases that are supposed to exist. In the case of typhoid the death rate is more accurate and complete, owing to possible errors in diagnosis and failure to report cases that do not terminate fatally. It is, therefore, important to know the percentage mortality which is ordinarily to be expected, and it is generally accepted that in typhoid fever the mortality is now about ten per cent. It is interesting in this connection to note that the mortality rate fell markedly in the latter half of the nineteenth century. In Murchison's statistics from the London Fever Hospital it appears that for the twenty-three years from 1848 to 1870 the mortality varied between 15.63 and 26.97 per cent, the latter figure being the one for the year 1848. The average for this period was 17.26 per cent. This may further be compared with statistics which * Ergebnisse des Todesursachen Statistik im deutsohen Reich fur das Jahr 1912. Springer, Berlin, 1914. TYPHOID AS CAUSE OF DEATH AND DISABILITY 15 Murchison gave from the best hospitals in France, Germany and England, which gave a similar average mortality of 17.45 per cent. It is evident, then, that the decrease in mortality, which is due in large part to better care and probably also to lessened virulence of the infection for the individual, or conversely to in- creased human resistance to this particular disease, must be taken into consideration in estimating the diminution of the disease itself from the mortality statistics. The tendency then in more recent statistics, based on the decreasing mortality rate, is to underestimate the actual number of cases of the disease. It may be noted here that the mortality percentage increases with the age of the patient, ranging from a little over two per cent in in- fants to thirty-five per cent in adults over forty-five years of age. The mortality is undoubtedly higher in hospitals than it is in those private houses where the best facilities for nursing are avail- able (Jochmann; Brouardel and Thoinot). CHRONOLOGICAL CHANGES IN THE TYPHOID DEATH RATE The chronological diminution of typhoid fever has already been suggested. We may express this diminution somewhat more con- cretely by taking first certain figures collected by Seitz 1 in Ger- many towards the end of the nineteenth century (Table I). TABLE I COMPARATIVE MORTALITY STATISTICS FROM TYPHOID FEVER PER 100,000 OF POPULATION IN GERMANY, BAVARIA AND MUNICH AT SUCCESSIVE PERIODS Germany Bavaria Munich 1857-67 — 77 203 1868-78 47 54 123 1879-83 26 26 30 This table, which is representative of many other statistics col- lected over a similar period, illustrates two important facts from which a great hygienic principle of particular import in typhoid fever and some similar diseases may be deduced. It will be noted, first, that the mortality rate during the greater part of this period was consistently and markedly higher in a city than in the state or empire at large, and, secondly, that a sharp diminution in both city and empire occurred about the year 1880. This diminution, it may be noted, continued until in the period 1901-1910 the mortal- ity rate for Munich averaged 2.5 to the 100,000. From these and other similar figures the general statement may 16 TYPHOID FEVER be made that prior to a period, roughly about the year 1880, typhoid fever was a disease the incidence of which varied directly with the density of population, as shown by the increased number of cases in a city like Munich as compared with the larger districts of which it formed a part. Further mortality statistics from the same city of Munich, comparing the incidence of the disease in the Munich garrison as against the general city population, still further and in a more concrete manner illustrate the same principle (Table II). TABLE II COMPARATIVE MORTALITY STATISTICS IN THE MUNICH GARRISON AS COMPARED WITH CITY MORTALITY (FROM SEITZ) City Garrison 1855-1869 204 840 1876-1881 57 190 The great menace which typhoid fever has always been to armies, both in peace and war, is a matter which will be considered separately at a later point. We are concerned at this point not so much with this interesting and striking diminution in the mortality rate itself, as with the causes which underlie it. These causes are, first, the full recogni- tion of water contamination from sewage as the source of trans- mission in typhoid, as had been pointed out some years before by Budd, 2 and the consequent introduction of pure and safeguarded water supplies. And, second, the re-emphasis and rendering con- crete of this first fact when transmission of the disease became typified in its recognized parasitic cause. The recognition of the etiologic importance of a specific bacillus of typhoid fever not only gave greater impetus in protecting water supplies from the dejecta of typhoid patients, but led undoubtedly to greater circumspection in handling the patients themselves and a consequent diminution in contact infections. We may now consider in more detail the direct effect of the purification of water supplies on the mortality incidence of typhoid fever, particularly as it occurs in cities. This may be shown in two different ways: first, by comparing the incidence of the disease as it occurs in cities grouped in accordance with the purity of their water supplies; secondly, by comparing the incidence of the disease in any given city before and after any marked improve- ment in the water supply (Kober). _£ ■oo jC -i -co ^ o if ^ ^ - 5 o> fc j S S o ri =— d-3 ° 3 d o-e d o ° »• d d o_d a> & o s- d d a> q> d o 3- c o is N o T3 2 +f 3 V- Q) CP o n 13 ii) X. tn £ g •a 1 (ii CO t rl rS .C 01 jj > o f* u. <> 1 U) tf) o _1 C ■ft S o -4 t £ UJ £ 0) >■ t > fe t >• 0) CO 1> ■5 -1 & ■H 3 "i u > o v "7 < .> T1 > ■*i o £ H y T3 V 3 f- 01 3 o (I o a. £ +- >- +- ' m ~* •— * y o (L £u >- o o_ o (0 o o «T s 1 sd ^ S rn- 1 d 1 1 ! 1 ^ ^ l T^ S s ^ WT i ^ ^ ^ ^ ^ — « fe SS i w § ^ ^ ^ ^ ■w * ^ i N ^ ^ s ^ 1 ^ i s ^ ^ ^ ^ i ^ ^ ^ x^ ^ 5? 1 ^ ^ ^ ^ $\ ^ ^ i i ^ ^ ^ ^ 1 ^ ^ & $ ^ ^ d 1 ^ I ^ NN Si ^ ^ S ^ ^ # ^ 1 1 ^ §5 ^ ^ ^ ^ ^ ^ ^ ^ d ^ ^ & o iv f; c *• o c 5 - ' f-,d o o o.- 101 3/ o ml — 0) ^.V i V) O) «'. 10/ N, !-. - *L' " 2 ( 1 / o « i/ 2 < o O) i i° \ O / / «/ «/ m 5 02" lO 1 \ a> k «- m ^ \«= o o> — ' \ o / \ 0? %/ o / } CO • (O * CO , G>/ iO S to a CD 3 Ditthorn and Schultz, Csernel and Marton, 1 . 2 Reibmayr, Mazza, McWilliams, Holler, Paulicek, F. Meyer, 2 Rhein, Lentz, Ortiz, Acuna and Belloc; 1916, Faginoli, Petzetakis, Zupnik, Miiller and Leiner, LSvyy, Lucksch and Wilhelm. (4) Authors who have in- jected sensitized vaccine intravenously: 1912, Ichikawa; 1914, Meyer and Altstaedt; 1915, Biedl, 1 - 2 Eggerth, Holler, 1 - 2 Sladek and Kotlowski, Koranyi, Landsberger, Lawy, Lucksch and Wilhelm; 1916, Rohonyi, Galambos; 1917, Caronia. 224 TYPHOID FEVER tainly possess an objective value. We believe that the striking difference in percentage which emerges from the statistical study of these authors and cases that we have mentioned, as between those cases treated subcutaneously by ordinary vaccines and those treated intravenously by sensitized vaccines, a difference of nearly one hundred per cent, represents a conservative rather than an exaggerated statement of the importance that has been made in recent modifications in vaccine therapy in typhoid. A discussion of the actual type of benefit produced, or rather of the results which follow in the actual treatment of cases, should now be more fully presented. The results of our personal experience in the intravenous vac- cine therapy of typhoid fever have not been included in the sum- mary presented in the last table, as it seems advantageous to use them as a separate basis of discussion of the results produced by this method of treatment. Our own results vary only in de- gree from those obtained by the authors we have cited. We were led independently and before the publications of Thiroloix and Bardon and Ichikawa to suggest and later to employ intra- venous vaccine therapy for the following reasons (Gay 2 ). Cer- tain of the experimental studies of Gay and Claypole 4 in the typhoid carrier condition in rabbits brought out the interesting fact that the injection of typhoid bacilli in immunized rabbits gave rise to a grade of leucocytosis which was to some extent specific. The injection of any foreign protein in an animal pro- duces a transitory leucopenia followed by an increase in the polymorphonuclear leucocytes, and the typhoid bacillus or its extractives produces such a result in normal rabbits. When, however, the same number of typhoid bacilli are injected in a rabbit that has been previously immunized against this micro- organism, the degree of leucocytic increase is considerably in- creased over what occurs in the normal animal. This increased leucocytosis would seem to be due to the presence of immune bodies in the serum of such immunized animals, which act as tropins and render the injected bacteria more attractive for the leucocytes. This would seem to be proved by the fact which Gay and Claypole demonstrated, not only with typhoid bacilli but with red blood cells, that a sensitized antigen will give rise to a higher grade of leucocytosis in normal animals than an un- treated antigenic substance. In the case of carrier rabbits it was possible to demonstrate that the production of this specific type of hyperleucocytosis is coincident with the diminution or dis- appearance of bacteria in the body of the carrier, and it was TREATMENT OF TYPHOID FEVER 225 therefore suggested that a similar stimulation of leucocytes might be of advantage in treating cases of typhoid fever which are char- acterized by the diminution in polymorphonuclear leucocytes. It was judged that the type of sensitized vaccine sediment which we had advocated in prophylatic vaccination against typhoid would be most serviceable for therapeutic uses of this sort, not only as stimulating a greater leucocytic response, but as being less toxic than the untreated vaccines. The superiority of sensi- tized over unsensitized vaccines in treatment would appear evi- dent from the summary of the literature which we have already offered. In addition to the agreement as to the higher percent- age of benefit obtained by these vaccines, may be mentioned ob- servations of certain authors who have used both sensitized and unsensitized vaccine in treatment and report better results with the first than with the second preparation. Such conclusions were drawn by Paltauf, Holler, and Feistmantel on the basis of comparative experience with the two vaccines. Our results (Gay, 2 Gay and Chickering, Gay 3 ) with the use of sensitized vaccine sediment, although not compared with the use of other vaccines, would seem as successful as any that have been re- ported. The intravenous injection of sensitized vaccine sediment pro- duces a series of distinct symptoms which vary markedly in in- tensity with individuals and with the dose employed. The usual amount on initial injection has been one-fiftieth of a milligram (corresponding to 150 million bacteria), and a corresponding dose in children, who, as in prophylactic immunization against typhoid, react less markedly than adults to corresponding amounts. We shall later refer to the findings of other investigators who have used other vaccines intravenously and who have described alarming or even dangerous symptoms following their employ- ment. It should be noted, however, that our vaccine, owing to its sensitization and the removal of endotoxins, certainly gives less perturbing, and, so far as we have observed, no really untoward effect. It seems necessary to produce a moderate reaction in order to effect the desired result, and the dosage in successive inoculations has been increased slightly in order to produce a similar train of symptoms on each inoculation, which a continu- ance of the same dose usually fails to do. The injection of the vaccine intravenously is followed in from fifteen minutes to an hour by a chill, which lasts for a few minutes to ten or fifteen. This chill, or shaking, is not accompanied by a feeling of cold- ness, but rather by a sense of involuntary, spasmodic, muscular 226 TYPHOID FEVER contraction. The chill is accompanied by a rise in temperature of one to three degrees, which reaches its height within three hours after injection and then falls. There may be a rise in tem- perature without a chill, or the reverse. The rise in temperature is accompanied by a leucopenia, which may fall as low as 2000 to 3000 to the cubic centimeter. The chill is accompanied by an increase in the pulse rate and may be accompanied by slight cyanosis, slight respiratory distress, and frequently a sense of discomfort. According to Scully, the blood pressure rises during the chill and then falls. The temperature reaches normal or sub-normal in about twelve hours. This fall in temperature is accompanied by sweating, which may be profuse and last for several hours, relaxation, and usually general amelioration of such symptoms as headache, delirium and the like. The patient often feels perfectly well, and this condition, even when transitory, seems beneficial. Co- incident with the fall in temperature there occurs a rise in the leucocytes, which may reach as high as 40,000 and which are characterized by a relative polymorphonuclear increase. We shall later refer, in reviewing the work of others with similar methods, to the dangers that have appeared with slightly different vaccine preparations, and to the contra-indications to such in- jections that undoubtedly exist. We may repeat, however, that in our experience of 1200 injections reactions of this sort have never appeared harmful, either immediately or ultimately, and contra-indications seem, in the light of increasing experience, to grow progressively fewer. No detailed method of procedure can be prescribed for treat- ing any given case of typhoid fever by this method. The best results seem to be obtained by provoking a distinct but not too severe reaction of the type outlined. The dose necessary to pro- duce such a result varies markedly with the individual and the particular balance already established between the typhoid bacillus and the reaction antibodies in the host. The temporary drop of temperature to normal may become permanent and re- main there, in which case no further injections are required, ex- cept for the prevention of relapse. If the temperature again rises over a period of two or three days, the injection should be repeated in slightly increased amount, and so on until the desired result is produced or further injections are judged futile. A con- siderable number of injections may be given with perfect safety. As many as fifteen or sixteen have been given in certain instances, but if no striking result is obtained following three or four injec- TREATMENT OF TYPHOID FEVER 227 tions at two or three day intervals, very little effect from further treatment may be expected. It has seemed wise to us previously to separate our cases into three rather definite groups in respect to the results produced by the vaccine injections. We believe that this grouping, based on results produced, is a conservative one and by no means represents all the benefit that attends this method of treating typhoid fever. We have briefly referred to the fact that the temperature excursion with return to normal is accompanied by subjective feelings of well being, although at times of slight weakness, and would seem to be both immediately and ultimately of benefit to the patient. Such subjective amelioration is, of course, open to error in inter- pretation, but would seem, not only to us but to others who have watched our cases, to be frequent and of a convincing nature. The nurses, for example, in charge of the cases not only volunteer remarks as to the benefit produced by the vaccine injections, but emphasize the lessened care which patients treated in this manner entail. We prefer, however, to base our judgment as to the good results of the method rather on the more objective results that have been produced, the shortening of the duration of the fever, its frequent abrupt termination in an abortive form, the lessening of mortality and of complications in particular. We have classified the three groups of results obtained as abortively recovered, as benefitted, or as unaffected. Cases illustrative of each of these types of result produced by the vaccine injection are given in the reproduced clinical charts in Figures 4, 5, and 6, which are ex- plained in their footnotes. A summary of our ninety-eight cases classified under these three headings proves of interest not only in respect to results achieved, but as bearing on the mechanism by which it is effected. In Table XXV are expressed certain characteristic findings in each of these groups of cases under consideration, which we may briefly refer to in drawing certain conclusions as to their significance. TABLE XXV SUMMARY OF RESULTS IN 98 CASES OF TYPHOID TREATED BY INTRAVENOUS INJECTION OF SENSITIZED VACCINE SEDIMENT No. Widal Titer Blood Treatment No. of Permanen , Days of Age. on beginning Culture. begun. treat- Normal »f Cases. treatment. Positive Day. ments. treatment Aborted 33 26.2 296.0 36.6% 13.4 1.88 20.4 7.0 Benefitted 32 24.2 156.5 70.9 14.8 3.20 30.6 15.8 Unaffected 33 28.8 114.8 84.8 13.7 4.85 46.8 33.1 228 TYPHOID FEVER DAY OF ILLNE53 6 7 8 1 3 10 II 12 13 14 15 16 17 18 19 DAY OF ILLNESS 106' 105° 104° 105 102° ior 100° 39° 38° 37° 106° 105° 104° 103' 102° 101° 100' 39° 98' 37° LJ LJ -J O B.C.+ W.+ 1 B.C.S' W.+ 1 <0~~ J 1 \ 1 1 3; ft r 330 EDO"! J_ ' vU-,-- a a. I 1 1/ \ to A X o 1 r 1 vi i\r V \ ^ \ / T V Fig. 4. — Temperature chart in an abortively cured case of typhoid. The temperatures recorded are rectal and give the forenoon and afternoon maximum of each day. The mark X represents the time at which vaccine injections were given intravenously and the number of million bacteria (200 M) in that par- ticular dose. Above are indicated the results from blood cultures (B. C.) and the strength of the Widal test (W+l-80). Any temperature at or below 100° by the rectum is regarded as normal. TREATMENT OF TYPHOID FEVER 229 In the first place, it will be seen that our cases may be divided into three almost exactly equal groups in respect to results pro- duced. These groups, moreover, are of almost identical age, and it is also found that treatment was begun on the average at prac- tically the same time in the three groups. They differ in prac- tically all other respects. We find, in the first place, that anti- body formation, as evidenced by the Widal or agglutinin titer in the cases before injections were begun, varies markedly in accord- DAY OF .| ( IHNE5S > ii 12 3 14 15 16 17 18 19 20 21 22 25 24 25 2G 27 28 !9 50 DAY OF HI 106' 105' 104' 105' 102" 101' 100' 33' 98' 97' 105* \ v. \A /LUL-- : - V Jj:jwV4 O ....... ..J + _\\ -H P ll M A 3>on| _j_LJ_Jj/_ r M- f\ . I y v \/ V i Fig. 5. — Temperature chart in a benefited case of typhoid fever treated by intravenous vaccine injections. Notations as in Chart 4. ance with the eventual outcome of the case in question. In the abortively cured cases the Widal is found to be on the average over twice as high as in the unaffected cases, whereas the benefitted cases he intermediate between the two groups. A strong Widal is evidence, then, of a good prognosis, not only in respect to these treated cases but probably also in untreated cases, to judge from the experience of others. Inversely correlative with the strength of the Widal is the occurrence of the percentage of positive blood cultures in the three categories under discussion; whereas the cases "tx> *io "-^t- Vo °<^J * — "cd "cri oO *r-~ c3C3c3coCDCDcDcr>cncD o 10 > / CD S i»_ ■ HO <* -^ — 1 _ > ■~~ - —"»»-,_ ,—— - - ID — »v ^ J 10 ^ <■ 091 - 1 +M ■\. 3iiyj LS'D'a CXI v ^ -> M- o 03C- 1 +M + o g o-> 10 > oO 10 10 01r9- 1 + yv\: "rtJ 10 0179-1 + M wnaas X V •«> 8 10 wnaae xv== 01 0*9-1 + M Wfftf2Q XV" 01 + '9 to IO wntras XV K. S 5KI-I + M WflM3S xv •*> s ■1- D a OJ IO IO .> » o IO OSS - 1 + 'M + 'oa CM + -M -s» = E " cS 0921 - 1 + "M Wfl«39 xv ■== 02 ~*| + a £ L "T» wna^s XV =» 1 s 10 OJ 7> x!i Sr 091- [ + M s > IO 091- 1 + M <~ + 'og OJ OJ 091 -1 +M *«£ OJ 08-1 + 'M^ i. o OJ OS -1 + 'M < r- * oa " • §*§ *SS !2 '31 "to «^ "=: "^ 'en *co Y-. Fig. 6. — Temperature chart in a case of typhoid unaffected by intravenous vaccine injections. Notations as in Chart 4. A. T. refers to an antityphoid serum also given intravenously. TREATMENT OF TYPHOID FEVER 231 that respond less well to treatment are found to give positive blood cultures in nearly eighty-five per cent of cases, those that recover abruptly on treatment had positive blood cultures in only 36.6 per cent. The benefited cases, again, he intermediate between the two. These relations between blood cultures and antibody formation we have already referred to as representing a balance established in the patient before intervention between the in- fecting agent and the resisting power of the host. When the re- sisting power is strongly developed, a favorable outcome may be more confidently expected. The group of cases which we have classified as abortively cured or abortively recovered suggest in some respects the mild or abor- tive typhoid cases which are discussed in most extensive mon- ographs on this disease. The typhus levissimus of Griesinger, the typhoidette of Brouardel, or abortive typhoid forms a well recognized group or groups that must occur in every considerable collection of cases of typhoid fever. Estimates vary as to the exact proportion of such cases, as may normally be expected. It is probable, as Curschmann suggests, that at least two groups should be formed, the mild typhoid fevers and the abortive typhoid fevers, the latter more frequently though by no means invariably char- acterized by a somewhat abrupt rise and fall of temperature and an abbreviated fastigium. McCrae in his 1500 cases found three per cent of mild forms of the disease, and, in addition, 0.1 of one per cent of his cases recovered by crisis. Letulle found that these two types of the disease occurred particularly in certain epidemics and in children. He finds something over seventeen per cent in the cases of the disease which he collected. This figure may cer- tainly be regarded as an extreme maximum of occurrence. Accord- ing to Curschmann, the abortive and mild forms frequently have only three to six days of fever and almost never over ten or twelve days, with which statement Hare and Beardsley would agree. At all events, the cases of mild and abortive typhoid together must constitute a relatively small percentage of all, in spite of the figures of Letulle. Hare and Beardsley note that Coleman found only twenty-four such cases in five years' experience at the Bellevue Hospital in New York. At all events, no such number as one-third of all the cases, as in our series, could be found in this way without some type of intervention. It may further be noted that our cases almost invariably have occurred beyond the limit of ten to twelve days set by Curschmann, and have practically invariably been characterized by a critical fall of temperature, and what is more important still, show a direct relation between this critical fall and 232 TYPHOID FEVER the injection of vaccine. Our cases do not represent the mild epidemics of Letulle, nor has any considerable number of them been furnished by children. They have been gathered over three seasons and in widely different localities. As may be anticipated, the abortively recovered cases represent by and large, when es- timated before treatment was begun, the milder cases of the dis- ease in this series. Our characterization of a preponderance of these abortively cured cases as milder has no relation, however, to the small group of mild and abortive forms that have just been discussed. We have endeavored to register our impression as to the severity of each case before treatment was begun, and our results are expressed in Table XXVI, where it is found that many more severe cases occur among those that remain unaffected by treatment, and many more mild cases occur among those that are aborted, whereas the benefitted cases would seem to lie inter- mediate between the two. TABLE XXVI GENERAL CONDITION OP CASES BEFORE TREATMENT Severe Moderate Mild Unaffected 26 6 1 Benefitted 10 17 5 Aborted 4 13 16 It is evident, then, that the milder cases react better to treat- ment than the more severe, but even the most severe ones will in some instances at least be benefited and even aborted. We be- lieve the effects actually produced are best represented by the figures given under "Permanent normal temperature" and "Dura- tion of treatment" in Table XXV. It is found that a permanent normal temperature was obtained in the third of the cases that are called aborted on an average at about the twentieth day. When we consider that the treatment of these cases was not begun until the thirteenth day, the really significant figure of seven days as the average duration of treatment required to restore the patient to an essentially normal condition, so far as the temperature is concerned, is obtained. We find, moreover, that it took on the average a little under two injections to produce this result. The fall of temperature by crisis, which is exemplified in the figure (Figure 4) used to illustrate the abortive cure, is characteristic of this category, although the abrupt fall may not occur in every instance on the first injection. The benefited cases, again, are well typified in the illustrative TREATMENT OF TYPHOID FEVER 233 chart (Figure 5) ; each successive injection of vaccine produces a permanent fall in temperature on the average of one degree, and it may require several, on the average a little over three injections, to reduce the temperature to a permanent normal. The average duration, then, of these cases is found to be 30.6 days, and the duration of treatment the more significant figure, 15.8 days. The cases that have been listed as unaffected, although showing the ordinary temperature excursions following each injection, are characterized by a prompt return of the temperature to its original or nearly its original height. The impression has remained in the minds of many who have seen those cases that they are really benefited, but since we have taken the reduction of temperature as our criterion of results, we prefer not to emphasize any good effect that may have occurred in these cases, beyond the diminu- tion in complications and mortality, to which we shall presently refer. Even in this group of cases the average duration is by no means extraordinary, 46.8 days, although it does exceed somewhat, perhaps, a normal average duration of cases of typhoid fever. It is extremely difficult to estimate what such an average duration usually is. Curschmann regards the mild cases as lasting on an average of twenty-one to thirty-three days. In McCrae's 7 figures the average febrile period was thirty-one days. It should be noted that our figures refer to the total duration of the disease from its initial symptoms, so far as they can be estimated from the patient's history, and not from the known duration of the fever itself. The group of cases, then, that were best affected may reasonably be regarded as having run a distinctly short course, and the average of all cases, which is about twenty-nine days, is not markedly different from McCrae's thirty-one days. The mortality in this series of ninety-eight treated cases is 6.6 per cent, which, when we consider that the cases were treated over a period of three seasons under varying conditions of care in private houses as well as hospitals, and, moreover, treated in different parts of the country, is certainly a very satisfactory figure. The average mortality is usually figured at ten per cent. The cases of death were predominantly due to the accidents of typhoid, three to hemorrhage, complicated with perforation in two instances, two to a combination of laryngitis and broncho- pneumonia, and one only to typhoid toxemia. It should be em- phasized in this connection that treatment was withheld in no case on account of the seriousness of the patient's condition, a fact of significance in considering the low mortality obtained. In two, at least, of our fatal cases the prognosis seemed inevitably 234 TYPHOID FEVER fatal when treatment was begun. The treatment itself in these cases not only seemed to produce no further ill effect, but actually gave rise to a temporary benefit. The complications, again, were few in number, and only thir- teen in all in the entire ninety-eight cases (13.2 per cent). This means, not that thirteen cases showed complications, for there were indeed only eight cases which showed complications, but the total number of complications was thirteen. These com- plications were as follows: pyelitis one case, lobar pneumonia one case, laryngitis two cases, bronchopneumonia two cases, toxemia one case, hemorrhage four cases, perforation two cases. The percentage of hemorrhage (4%+) and of perforation (2%) is certainly below what may be expected as the usual averages for these complications, five to ten per cent for hemorrhage and three to four per cent for perforation. Although the earlier study of vaccine therapy in typhoid certainly led to the impression, particularly when the vaccine was administered subcutaneously, that complications were diminished (Krumbaar and Richardson, Callison), more recent work would seem to show that no distinct effect on the complications can /be expected by the more recent intravenous type of treatment (Szecsy, Wiltshire and MacGilly- cuddy, Reiter, and Guinon and Malarte). The occurrence of relapses in this series of ninety-eight cases is of interest in connection with a supplementary type of vaccine therapy, to which Gay and Chickering referred in their com- munication. It is apparently the experience of several authors, including ourselves, that the intravenous vaccine therapy of typhoid fever, although it may lead to surprisingly successful results in shortening many cases of the disease, is of little value in preventing relapses. In our series of cases there were ten re- lapses (10.2%), which is approximately the number that might be expected. After experiencing several of these relapses we decided to follow up the intravenous therapy by a series of three subcutaneous injections of 0.1 milligram of the vaccine (800 million bacteria), given on alternate days beginning at the point where the patient's temperature had remained normal for twenty- four hours. Thirty-seven cases in the latter part of our series have been treated in this manner and among them relapses oc- curred in only 5.39 per cent, whereas in sixty-nine cases in which the intravenous therapy was not followed by subcutaneous vac- cine injections the relapses occurred in 11.59 per cent. The same method of treatment has since been recommended by F. Meyer, 2 Meyer and Altstaedt, and Wiltshire and MacGillycuddy. TREATMENT OF TYPHOID FEVER 235 Non-Specificity of Vaccine Therapy in Typhoid It has become increasingly evident that the results produced by the administration of typhoid vaccine in typhoid fever can- not be regarded as specific in the narrower sense. The results, however striking they may be, are due primarily to the fact that a foreign protein has been injected more than to the fact that the foreign protein employed is a preparation of the causative agent in the disease in question. In the first place, it has been found that beneficial effects of a very similar nature and characterized by similar reactions to those described have been produced in typhoid fever by the administration of vaccines prepared from bacteria other than the Bacillus typhosus. Kraus was the first to note that he obtained beneficial results on the intravenous in- jection of colon as well as of typhoid vaccines. Ludke 3 and Lucksch both obtained results with colon vaccine, and the latter author obtained a favorable effect by gonococcus vaccines and by sodium nucleinate. Zupnik, Muller and Leiner have utilized a vaccine made from the mouse typhoid bacillus as Jess toxic and as useful as true typhoid vaccine. Reibmayr, who has em- ployed colon and cholera vaccines in typhoid as well as typhoid vaccine, concludes that the former, although beneficial, are not as good as that derjved from the specific microorganism. In a similar manner it has been found that other acute infec- tious diseases may be beneficially affected by the intravenous in- jection of their corresponding vaccines or of other vaccines. Thus, Kraus 2 notes the beneficial effect produced in cases of puerperal sepsis and pyocyaneus infections by the use of a colon vaccine. Rhein notes the beneficial effect in paratyphoid fever of typhoid vaccine. Nolf utilized peptone solutions advantageously in streptococcus infections. Miller and Lusk have employed ty- phoid vaccine by intravenous injection in acute, subacute and chronic arthritis with favorable results. This leads to a consideration of the less complex proteins and, indeed, simple inorganic salts that have been employed with claim to equally favorable results both in typhoid and in other acute infections. Ludke 3 has described the use of deutero-al- bumose in typhoid, Weichardt the employment of albumin solu- tions, and Nolf, as already mentioned, has used one-half a gram of peptone dissolved in 200 cubic centimeters of normal saline and administered intravenously. Baradulin has utilized dextrose solutions in considerable amount in cases of surgical sepsis, and Weichardt and Englander have obtained similar result's with 236 TYPHOID FEVER normal physiological saline alone. The use of colloidal gold (Colibiase) by Letulle and Mage, Barachon, Gay, Labbe" and Moussaud, and Delbet would seem simply another instance of the non-specificity of the reaction that we have described. It should be reiterated that in each and all of these instances the beneficial effects produced, which are undoubted, are brought about by the intravenous injections of a non-specific vaccine, a less complex protein, or even a complex or simple organic or in- organic substance. These injections, moreover, have all been followed by the train of symptoms we have described with ty- phoid vaccines, of chill, temperature excursion, and the results in the nature of critical recovery have been similar, though prob- ably differing in relative percentage. The Mechanism of Cure in Intravenous Vaccine Therapy This proof of the non-specificity of the most favorable results that can be produced by a typhoid vaccine in typhoid fever should not only not discourage us but lead us to inquire further into the mechanism of the reaction on which this benefit depends. In our work (Gay and Claypole, 4 Gay and Chickering) we have been led to attribute significance to two factors, which we believe not only concerned but of importance in the reaction which is pro- duced by intravenous vaccine injections. The first of these fac- tors is the hyperleucocytosis which following our observations has also been found to occur by a number of authors (McWilliams, Holler, Lowy, Lucksch and Wilhelm, Lucksch, Rohonyi, and Scully). It has also been shown that many of the substances which in a non-specific manner may lead to the same effects, as, for example, nuclein (Melnikowa and Wersilowa), and col- loidal gold (Busquet, Barachon, Letulle and Mage), also increase the leucocyte count, to which fact their results have been attrib- uted. As a second factor on which the degree of benefit obtained would seem to depend is the antibody content of the patient. This is indicated in the results cited in Table XXV, where it is found that the strength of the Widal titer seems to increase di- rectly with the benefit that results from injection. This observa- tion, moreover, would agree with the incidental observation of a number of observers that prognosis in general is more or less dependent on the strength of antibodies in the patient, and, particularly, that the prognosis of vaccine injection likewise bears some relation to the degree to which the individual has reacted against the infection. Of like significance is the extremely mild TREATMENT OF TYPHOID FEVER 237 and favorable course of typhoid fever in the vaccinated. Koranyi has found that the opsonic index rises after vaccine injection in typhoid, and Inez Smith in our laboratory has apparently been able to demonstrate a distinct relation in the degree to which the opsonic index increases after intravenous injection and the result produced. In other words, the opsonic index rose much more markedly in the cases that were abortively cured than in either the benefitted or the unaffected cases. We have also fre- quently found that the agglutinin titer rises after the vaccine injection. Our hypothesis as to the mechanism by which cure was effected in the most striking instances has been, briefly, that it was due to a cooperation between the leucocytes that were called out by the injection and the antibodies already present in the patient, which latter substances acting as tropins caused the digestion and destruction of the typhoid bacilli in the body by the increased white blood corpuscles. There are several reasons for regarding this mechanism as probable apart from the now proved relation of the antibody strength and the leucocytic increase to the result obtained. In the first place, it can be shown by blood culture in some, though by no means all, instances that the bacteria disappear rapidly from the peripheral circulation following the injection. Similar results have been obtained by other inves- tigators. This working hypothesis may or may not be the cor- rect or ultimate explanation of the results produced by this non- specific reaction in typhoid fever and in other acute infections. There are other explanations which are probably no more ulti- mate and which, indeed, are not of necessity in any direct con- flict with the one we have presented. Jobling and Petersen have attributed the results produced by the reaction as due to a dis- turbance of ferment, antiferment balance, the antiferment being absorbed and the ferment being allowed to act. Similarly, Nolf speaks of a change in colloidal balance. This explanation is cer- tainly a very attractive one. Teague and McWilliams *■ 2j 3 in recent experiments on rabbits also bring forth certain results which must be taken into consideration in explaining this type of therapy. They find that the injection of vaccine in rabbits produces a refractory condition which renders these animals temporarily more resistant to infection with the typhoid bacillus. They would attribute the results produced in the favorable cases of treatment to an overflowing of bactericidal substances, which are found to be present in the circulating blood, into the remoter lymph spaces which serve as metastatic foci in typhoid fever, 238 TYPHOID FEVER and the consequent destruction of the bacteria that are present in them. It makes very little difference whether we regard the leucocytes or bactericidal ferments in the serum as the cause of the ultimate destruction of the bacteria, with which recovery seems to be as- sociated. It is probable, indeed, that the white blood cells are the source of the ferments, and we see no reason why these various factors and experiments that have been brought out by Teague and McWilliams, Jobling and Petersen and ourselves will not eventually stand in harmony in the ultimate explanation which may soon come. Since the cases in which the least favorable results are obtained seem characterized by the low antibody content in the serum, Gay and Chickering suggested that better results might be ob- tained in them by supplying the deficient antibodies by injec- tions of an artificial serum, and reported one or two cases in which a preparatory injection of the serum of a goat that had been im- munized by repeated injections of typhoid bacilli seemed to render the beneficial results secured by subsequent vaccine therapy more pronounced. Further limited experience with various antisera from goats prepared both by the injection of sensitized and of unsensitized living cultures (Gay 3 ) would not seem to give the anticipated result. The injection of an antityphoid serum of this sort may in itself produce a reaction s imil ar to that evoked by vaccine (Etienne), and it is probable that the effect produced by Rodet and his collaborators, to which we have al- ready referred, is, in part at least, due to the fact that a foreign protein has been employed, since their results were better when the vaccine was given intravenously. The possibility, however, of a combined serum and vaccine therapy is one which we believe should be kept in mind and more extensively tested. Inasmuch as similar therapeutic results to those described following the use of typhoid vaccine can be obtained by the in- travenous injection of almost any protein substance, the question may well be asked as to whether there is any advantage in using typhoid vaccine rather than some other substance. We believe that a typhoid vaccine, particularly of the type we have recom- mended, possesses distinct advantages over other proteins. Such a vaccine, as we employ it, is easily kept indefinitely in dried form and under conditions of strict asepsis, and can readily be introduced in exact amounts. Typhoid vaccine, further, has the advantage over other protein preparations of building up the active immunity of the patient, and a sensitized vaccine TREATMENT OF TYPHOID FEVER 239 will in our experience produce a higher grade of leucocytosis. It is evident from remarks we have made that in our own experience the use of typhoid vaccine intravenously is attended by no real danger and is contraindicated in only those few cases of typhoid fever which are complicated by some profound functional dis- turbance of the heart. The very few individuals who have been led through unfortunate experience to discontinue the intra- venous injection of vaccines, Peutz, Sladek and Kotlowsky, and Deutsch, treated very few cases, and the dangers which they report must be attributed to their inexperience and the excessive amount of vaccine employed. We regard, then, the intravenous vaccine treatment of typhoid fever as the most effective type of therapy hitherto devised to combat this disease. It would seem indicated in nearly every case and at any time during the febrile period. It would seem, moreover, likely that further in- vestigation will enhance the value of this type of therapy. CHAPTER XIV SUGGESTED METHODS OF ADVANCE IN SOLVING THE TYPHOID PROBLEM An attempt has been made in this treatise to express the present status of our effective knowledge concerning typhoid fever. Mat- ters of apparently purely theoretical interest have been treated as fully as those with a practical application, with an appreciation of the fact that such theoretical knowledge will eventually serve directly or indirectly in the practical advances that are to come. It is evident that increasing knowledge of the mechanism by which typhoid fever propagates itself, both within and without the human body, has given us increasing power to diminish the incidence of the disease. As we have shown, both the morbidity and mortality rates from this disease have been enormously re- duced, and the reduction continues. This reduction in the in- cidence of typhoid fever in the larger centers of population is due largely to the appreciation and enforcement of sanitary measures carried out with a thorough knowledge of the life cycle and dis- tribution of the typhoid bacillus. In smaller groups the more recent and effective advance has been in the matter of immuniza- tion in conjunction with the ordinary sanitary precautions. Vac- cination against typhoid, although extremely effective in segre- gated and particularly in completely immunized units, has not so far exerted a fundamental effect on the total morbidity rate from the disease. The advances that have been made in the suppression of typhoid fever cannot but awaken confidence and enthusiasm in the effectiveness of preventive medicine. These advances have been so marked in the case of this disease that we may confidently look forward to its eventual suppression. This suppression will be brought about both through the consistent application of measures arising from the knowledge we already possess as to the pathogenesis and transmission of typhoid fever, and through the acquisition of further knowledge of certain as- pects of the disease. It is the purpose of these closing paragraphs to attempt to outline certain paths along which may come these advances in our knowledge of typhoid fever and in its control. 240 METHODS OF SOLVING THE TYPHOID PROBLEM 241 THE DIAGNOSIS OF CASES OF TYPHOID FEVER One of the most important factors in preventing the extension of typhoid fever lies in the early detection of each individual case. The methods of diagnosis of typhoid fever are so highly perfected that diagnosis can be made at least in the earliest days of the dis- ease, and, indeed, might be made in the incubation period of the dis- ease, if suspicion were directed toward the individual in question. The early diagnosis of typhoid fever depends not only on the co- operation of the laboratory with the practitioner of medicine, but on the willingness and initiative of the practitioner in availing himself of such cooperation as is available. It should be the func- tion of the laboratory not only to accede to the demands of the practitioner but to suggest methods of which the practitioner might and should avail himself. In every well organized commun- ity facilities are at hand for the free diagnosis of blood samples by means of the agglutination test for typhoid fever. These means are made use of by all well informed practitioners and their aid in diagnosis and in protecting the public health is very great. The early diagnosis of the disease is obtained, however, as we have shown, more surely by means of blood cultures, and this method of diagnosis is by no means as available as it should be for the general practitioner. The practitioner has usually neither the experience nor the facilities for making and particularly for study- ing blood cultures, and it should be the duty of every municipal and state laboratory to afford greater faculties, not only for the detection of the typhoid bacillus in blood cultures, but for the actual taking of the cultures themselves. A simple extension of the district nurse system, in cities at least, would provide for this deficiency in the diagnostic aid that is furnished by state and municipal laboratories. A trained nurse could readily be in- structed in the complete technique of obtaining and diagnosing blood cultures, and the additional expense to the community would be inconsiderable. THE MANAGEMENT OF CARRIERS We have sufficiently emphasized the importance of carriers as a means of the further extension of typhoid fever. This method of extension is due in large part to the fact that carriers are unsus- pected. If all carriers of typhoid bacilli were known, the first and most important step would be made in preventing the genesis of secondary cases from this important source. Every effort should 242 TYPHOID FEVER be made, particularly in densely populated communities, to obtain as complete a registration of carriers as may be possible. This may be effected in several ways. In the first place, every recovered case of typhoid fever should have several negative stool examinations before being discharged as healthy. Provision should be made so that such examinations may be carried out not only in hospitals, where at present they are infrequently performed, but also in private cases through cooperation between the attendant physician and municipal laboratories. Recovered cases that remain car- riers would thus be detected and recognized. Their recognition would in most cases in no way interfere with their personal liberty, but would make it possible for a central laboratory to keep in touch with them. Careful instruction should then be given to all such carriers and every effort made to teach them to appreciate their potential danger to the community. If such carriers would sign an agreement to report to the central laboratory for examination, their eventual freedom from typhoid bacilli might be determined. More important still, their relation to any further cases of the disease would be promptly discovered and means taken to prevent additional infection. Legal measures should be available to en- force the compliance of these recovered carriers with such rules as may be laid down for their conduct, and isolation, even, should be possible in recalcitrant or careless individuals. Thorough-going search for and registration of all recovered car- riers will lead eventually to the complete census of all sources of further infection in this category. Such methods, however, will not aid in the detection of carriers who have come from less closely guarded communities, or of the healthy carriers in a most carefully checked community, such as we have outlined. We have already expressed the difficulty or impossibility of detection of all carriers in any general community by the laborious methods of stool examination which at present are necessary to find them. It is increasingly evident that some easier method of detecting typhoid carriers is highly desirable. So far, the only possible test pointing to possible carriers rests on a positive Widal reaction, which, how- ever, is not present in all carriers and is positive in many who are not carriers. The suggestion is made that the possibility of em- ploying the typhoidin test for the purpose of detecting healthy and recovered carriers should be investigated. Most important from the public standpoint, next to the detec- tion of carriers, and more important still from the individual standpoint, is some means of treating them effectively. We have fully considered how inadequate all suggested methods of cure METHODS OF SOLVING THE TYPHOID PROBLEM 243 have been. Further study of the rabbit carrier condition, which presents so close an analogy to the human carrier, is obviously in- dicated. The possible use of chemotherapeutic means of effecting this end by studying the elimination of various dye stuffs and chemical substances through the liver and bile have already sug- gested certain studies with this purpose in view, and definite progress may soon be made in the direction of some specific method of curing the carrier condition. IMMUNIZATION AGAINST TYPHOID FEVER Further practical advances are possible in methods of vaccina- tion against typhoid fever, and theoretical studies as to the nature of the immunity produced by vaccination will doubtless serve toward these advances. We may well question why the protec- tion afforded by vaccination in recognized manners against typhoid fever is less durable than that accomplished through re- covery from the disease. We have already outlined the differences in the expression of this immunity in the blood serum in the two instances and expressed the opinion that recovered typhoid immunity is cellular, whereas artificial typhoid immunity is to a large extent humoral in nature. The exact nature of this durable cellular immunity acquired through recovery is by no means under- stood, and an intensive comparative study of the tissues in re- covered typhoid cases as compared with those vaccinated against typhoid and with normal individuals might afford some informa- tion in this direction. If it could be demonstrated, for example, that certain tissues of recovered typhoid cases, perhaps the tissues of the lymphatic system, contain cellular antibodies in contradis- tinction to normal tissues, great insight as to the nature of this durable immunity would be gained. Whether it is possible to produce a fundamental immunity of this sort by artificial means is extremely doubtful, but at least an appreciation of the differences between this type of immunity and that afforded by vaccination might be expected to aid in further perfecting the latter process. Every effort should be made to stimulate typhoid vaccination in the general community. This may be brought about by prop- aganda of various sorts and by the free distribution of vaccine by municipal, state or even federal laboratories. The inclusiveness of vaccination would seem to increase its efficiency, and every effort should be made to create a typhoid vaccinated community in such a manner as has been done in the case of small-pox. In addition, further investigation is desirable as to the duration 244 TYPHOID FEVER of protection by any method in vogue. We have already suggested the value of the typhoidin test as indicating the failure of individ- uals to respond sufficiently to the vaccine to ensure normal protec- tion, and some systematic method of applying this test, if it proves as reliable as we have anticipated, should be considered. TREATMENT OF TYPHOID FEVER The greatest progress that has been made in the treatment of typhoid fever would seem to be in connection with the protein reaction produced by the intravenous injection not only of typhoid vaccine, but of other protein substances. The nature of this reac- tion is to some extent understood. The relation of leucocytes to the process and the stimulation or mobilization of antibodies induced by this means are repognized. Of the theories that have been advanced to explain the beneficial results that not infre- quently follow this injection of foreign protein, the most attractive would seem to be that of Jobling and Petersen, which is fully in harmony with the ideas of Nolf and others as to fluctuations in the colloidal balance between ferment and antiferment. It would seem desirable, not only for practical ends in connection with protein therapy of this type, but for the purpose of theoretical knowledge that better methods of detecting and complete demonstration of the presence and nature of such ferments should be available. It is particularly desirable from the standpoint of general con- siderations of immunity that further knowledge should be ob- tained as to the relation of ferments of this sort to recognized types of antibodies that have been more circumstantially studied. BIBLIOGRAPHICAL INDEX OF REFERENCES QUOTED (The references are given alphabetically by authors. Where several references to a given author occur, they are cited in order of their occurrence in the text. Any reference in the text without a number refers to the first reference given under that author's name. Subsequent references are numbered consecutively.) Achaed, Ch., and R. Bensatjdb. Infections paratyphoidiqu.es. Bull, et mem. de med. d. h6p., Paris, 1896, jdii, 820. Achaed, Ch., and Ch. Forx. Sur l'emploi des corps gras comme v6hicules des vaccins microbiens. Compt. Rend. Soc. Biol., 1916, lxxix, 209. Albeht and Mbndehall. Reactions induced by antityphoid vaccina- tion. Am. Jour. Med. Sciences, 1912, cxliii, 232. Aldershoff, H. De beteekenis der reactie van Gruber-Widal voor de diagnose "febris typoidea bij de ingeenten." Nederlandsch. Tijd- schrift voor Geneeskunde, 1916, II, 284. Altstaedt. Zur Typhusimmunitat. Berl. klin. Woch., 1915, lii, 681. Alvarez, B. G. Vinegar-water and acid wines in treatment of typhoid and paratyphoid. Siglo Medico, Madrid, 1917, briv, 2. (Jour. Am. Med. Asso., 1917, Mar. 17, p. 885.) Andriescu, Ch. and M. Ciuca. De l'action du s6rum antityphique de Besredka sur Involution de la fievre typhoide. Ann. Inst. Past., 1913, xxvii, 170. Antityphoid Committee (Great Britain), Report of the. T. Fisher Unwin, London, 1913. Aoki, K. Uber die Komplementbindungsreaktion und die hamoly- sehemmende Wirkung des Serums bei Bazillentragerkaninchen. Zeitsch. f. Immunitatsforsch., 1913, xix, 354. Archibald, R. G., G. Hadfield, W. Logan and W. Campbell. Reports of the M. and H. laboratories dealing with the diseases affecting troops in the Dardanelles. Jour. Royal Army Med. Corps, June, 1916. Ardin-Delteil, L. Negre and M. Raynaud. (1) Recherches sur les reactions humorales des malades atteints de fievre typhoide traites par le vaccin de Besredka. Compt. Rend. Soc. de Biol., 1913, lxxiv, 371. (2) Sur la vaccinotherapie de la fievre typhoide. Comp. Rend. Acad. Sciences, 1912, cxl, 1174. 245 246 BIBLIOGRAPHICAL INDEX Arima, R. (1) Ueber die Typhustoxine und ihre pathogene Wirkung. Cent. f. Bakt., 1912, lxiii, 424. (2) Ueber Antikorperbildung gegen Typhustoxine. Cent, f . Bakt., 1912, lxv, 183. Aronbon, Hans. Untersuchungen uber Typhus mit Typhusserum. Berl. klin. Woch., 1907, No. 18, 572. Ascoli, M. (1) Die spezifische Myostagmin Reaktion. Miinch. med. Woch., 1910, lvr. (2) Essai de diagnostic de la fi&vre typhoide au moyen de l'anaphy- laxie passive. Compt. rend. Soc. Biol., 1908, lxv, 611. Ast, Fritz. Praktische Erfahrungen mit der serodiagnostischen Typhus- reaktion nach Mandelbaum. Miinch. med. Woch., 1910, No. 50. 2634. Atlassofp, J. La ftevre typhoide exp6rimentale. Ann. Inst. Past., 1904, xviii, 701. Auche, B. and P. Chevalier. Un cas d'insucc&s de la vaccination anti- typhique. Jour, de m6d. de Bordeaux, 1913, No. 23, 371. Austrian and Bloomfield. The typhoidin reaction. Arch. Int. Med., 1916, xvii, No. 5. Bachmeister. Der Ausfall des Cholesterins in der Galle und seine Beudetung fur die Pathogenese der Gallensteine. Miinch. med. Woch., 1908, lv, 15. Baerthlein, K. Ueber die Mutation bei Bakterien und die Technik zum Nachweis dieser Abspaltungsvorgange. Cent. f. Bakt., 1913, lxxi, 1. Baglivi. Opera omnia. Romae, 1696. Baillie. Plates of morbid anatomy. Fasc. 4, p. ii, Fig. 3. Bainbridge, F. A. The Milroy lectures on paratyphoid fever and meat poisoning. Lancet, 1912, 705, 771, 849. Ballard, E. On a localized outbreak of typhoid fever in Islington during the months of July and August, 1870, traced to the use of impure milk. J. and A. Churchill, London, 1871. Balthazard, V. Toxine typhique et antitoxine typhique. J. B. Bailltere et Fils, 1903. Bandi. Contributo alio studio del tifo sperimentali. Ufficiale sanitorio, 1889, 145 and 193. Banti, G. Sulla localizzazioni atipichi della infezione tifosa. Riforma med., 1887, Oct. (Cit. Baumgarten, 1888, iv, 148.) Barabaschi, P. Importanza dei vermi intestinali nella infezioni di febbre tifioide. Gazz. d. Ospedali e d. Clin., 1910, No. 25. BIBLIOGRAPHICAL INDEX 247 Barachon. L'or colloidal comme adjuvant dans le traitement des e'tats typhoides. Paris. m&L, 1916, vi, 570. Baradulin, G. I. Intravenous infusion of hypertonic solution of grape sugar in treatment of purulent processes. Rusksy Vratch., 1916, xv, 833. (Jour. Am. Med. Asso., 1916, Nov. 25, 1636.) Barlow. On the distinction between typhus fever and dothienenterie. Lancet, 1840; Feb. 29. Bartlett, Elisha. The history, diagnosis and treatment of the fevers of the United States. Blanchard & Lea, Phila., 1856. Battlehner, R. Uber Latenz von Typhusbacillen im Menschen. Diss., Strassburg, 1910. Baumler. Typhusbazillen in den lymphatischen Apparaten des Darmes. Internat. Hyg. Kongress, 1907. (Cent. f. Bakt., Ref. I. Abt., 1908, xli, 230.) Baur, J., P. Abrami and J. Stevestre. La vaccination antitypho- paratyphique. Soc. M6d. des H6p., 1916, Mar. 3. (La Presse MecL, 1916, Mar. 9.) Baur, J., Hautefetjille and J. Stevestre. Germes specifiques dans les vomissements bilieux au cours des maladies typhoides. Soc. MSdicale des H6pitaux, 1916, Jan. 28. (Presse MeU, 1916, Feb. 3, No. 7, 56.) Bech. Fievre typhoide. Reunion meU chir. de la Ire. Arm6e, 1916, Jan. and Feb. (Presse MeU, 1916, Apr. 17.) Bergell and Meter. Uber eine neue Methode zur Herstellung von Bakterien-Substanzen, welche zur Immunisierungszwecken geeignet sind. Med. Klin., 1906, 16. Berget, D. H. The pyrogenic action of bacillus typhosus. Jour. Med. Res., 1915, xxxi, 433. Bernard, L. Les formes legeres de la dothienenterie et l'embarras gastrique febrile. Ann. de MeU, 1916, iii, 32. (2) Les infections typhoides et la vaccination antityphoide. Bull. Acad. MeU, 1915, Sept. 28, 336. Bernard, L. and J. Paraf. Statistiques des infections typhoides chez les sujets vaccines contre la fievre typhoide. Presse MeUcale, 1915, Oct. 11, 399. (2) Les infections typhoides chez les sujets vaccines contre la fievre typhoide. Ann. de MeU, Paris, 1915, Oct. No. 5. Bbsredka, A. Etudes sur le bacille typhique et le bacille de la peste. Ann. Inst. Past., 1905, xix, 477. (2) De rimmunisation active contre la peste, le cholera et l'infec- tion typhique. Ann. Inst. Past., 1902, xvi, 918. 248 BIBLIOGRAPHICAL INDEX (3) Deux ans de vaccination antityphiques avec du virus sen- sibilis6 vivant. Ann. Inst. Past., 1913, xxvii, 607. (4) De l'anti-endotoxine typhique et des anti-endotoxines en general. Ann. Inst. Past., 1906, xx, 449. Beumeb and Peipee. Bakteriologische Studien iiber die atiologische Bedeutung der Typhusbazillen. Zt. f. Hyg., 1887, II, 110. Bezancon, F. and A. Philibeet. Formes extraintestinales de l'infection eberthienne. Jour, de Phys. & Path, generate, 1904, vi, 74. Bezzola, C. and Vallaedi. Contributo alia conoscenza della immunita antitifica naturale. Pathologica, 1912, iv, 353. Biedl, A. Zur Vakzinetherapie des Typhus abdominalis. Letter to Paltauf in Wien. klin. Woch., 1915, xxviii, 125. (2) Therapeutische Verwendung von Typhus-Impstoffen beim Menschen. Prag. med. Woch., 1915, xl, 53. Bieeast, W. Ueber das Bierastische Petrolaetherverfahren zum Nach- weis des Typhus und Paratyphuskeimes in Stuhl. Berl. klin. Woch., 1916, May 15, 532. Billet, A., LeBihan, F., Theeault, Lamande, Luteot and Loins, J. F. L'epidemie de fievre typhoide dans la garnison de St. Brieuc en 1909. Arch, de MM. & Pharm. Milit., 1910, lv, 281. Bindseil. Bakteriologischer Sektionbefund bei einem chronischen Typhusbazillentrager. Zeit. f. Hyg., 1913, lxxiv, 369. Blachstein, 0. G. Intravenous inoculation of rabbits with Bacillus cob* communis and the Bacillus typhi abdominalis. Bull. Johns Hopkins Hosp., 1891, ii, 96. Blandini, P. Profilassi specifica del tifo abdominale. Ann. d'igiene sperimentale, 1905, xv, 295. Blassbeeg, M. Positive Typhusbazillenkultur und Typhugagglutina- tion bei Miliartuberkulose. Wien. klin. Woch., 1915, xxviii, 1314. Blumenthal, Eenst. Ueber das Auftreten von Typhusbacillen in den Gallenwegen nach intravenoser Injektion. Cent. f. Bakt., 1910, lv, 341. Blumenthal, Feanz. Ueber das Vorkommen von Typhus and Para- typhus Bazillen bei Erkrankungen der Gallewegen. Mtinch. med. Woch., 1904, 1641. Boehncke, K. E. Die Vaccina tionsprophylaxe und Therapie des Abdominal typhus. Med. Klinik, 1913, ix, 1690. Bohne, A. Vergleichende bakteriologische Blut-, Stuhl- und Urinunter- suchung bei Typhus abdominalis. Zeit. f. Hyg., 1908, bri, 213. Boinet. Vaccinotherapie de la fievre typhoide par le virus sensibilise' de Besredka. Compt. Rend. Soc. Biol., 1913, bariv, 507. BIBLIOGRAPHICAL INDEX 249 Boldtjan, C. and W. C. Noble. A typhoid bacillus carrier of forty-six years standing, and a large outbreak of milk-borne typhoid fever traced to this source. Jour. Am. Med. Asso., 1912, lviii, 7. Bonhoff and Tsuzttki. Tiber die Schnellimmunisierungsmethode von Fornet und Muller. Zeit. f. Immunitatsforsch., 1910, iv, 180. Bohal, H. Beitrag zur Frage der Typhustherapie mit Besredkas Vakzine. Wien. klin. Woch., 1915, xxviii, 415. Boedet, J. Les leucocytes et les propri6t6s actives du s6rum chez les vaccinas. Ann. Inst. Past., 1895, ix, 462. Boedet, J. and O. Gengou. Sur l'existence de substances sensibilisatrices dans la plupart des senims antimicrobiens. Ann. Inst. Past., 1901, xv, 290. Botez, A. Le violet de methyle comme moyen de differenciation dans la sene typhi-coli. Reun. biol. Bucarest, 1915, July 8. (Compt. Rend. Soc. Biol., 1915, Ixxviii, 489.) Boueges, H., R. Lancelin and P. R. Jolly. Septicemics & mierocoques (diplococcemies). Soc. M&iicale des H6p., 1915, Dec. 10. (2) Infections a l'aspect clinique typhoiide realisees par la presence constante d'un microcoque dans le sang. Soc. de Biol., 1915, Dec. 4, 692. Boueke, Evans and Rowland. Autogenous living vaccine in the treat- ment of enteric fever. British Med. Jour., 1915, Apr. 3. Boycott, A. E. Observations on the bacteriology of paratyphoid fever and on the reactions of typhoid and paratyphoid sera. Jour, of Hyg., 1906, vi, 33. Beand, E. Die Hydrotherapie des Typhus. Stettin, 1861. Beaun, H. and M. Feilee. Ueber Serumfestigkeit des Typhusbacillus. Zeit. f. Immuniz., 1914, xxi, 447. Beetonneau. Notice sur la contagion de la dothienenterite. Arch. gen. de meU, 1829, xxi, Ser. 1. Beiegee, L. Weitere Untersuchungen iiber die Ptomaine. Berlin, 1883. Beiegee, L., S. Kitasato and A. Wasseemann. Ueber Immunitat und Giftbestigung. Zeit. f . Hyg., 1892, xii, 137. Beiegee, L. and Mayee. Weitere Versuche zur Darstellung spezifischer Substanzen aus Bakterien. Deut. med. Woch., 1913, 309. Bhion, A. and H. Kayseb. Neue klinische bakteriologische Erfahrungen bei Typhus. Deut. Arch. f. klin. Med., 1906, lxxxv, 552. Beonnee, C. E. C. Typhusschutzimpfung und Typhusdiagnose bei Geimpften. Medizin. Klinik, Berlin, 1915, xi, 959. 250 BIBLIOGRAPHICAL INDEX Brouardel, P. and L. Thoinot. Pievre typholde. J. B. Bailliere et Fils, Paris, 1905. Broughton-Alcock, W. Vaccination for typhoid fever with living sensitized bacilli. Lancet, 1913, July 12, p. 104. Brown, H. C. Standardization of vaccines. Indian Jour. Med. Res., 1914, I, 71. Bruce, D. Analysis of the results of Professor Wright's method of anti- typhoid inoculation. Jour. Roy. Army Med. Corps, 1905, iv, 241. Bruckner, G. Ueber Typhusverbreitung. Deut. med. Woch., 1912, Aug. 8, 1490. Budd, W. On intestinal fever: its mode of propagation. Lancet, 1856, ii, 618, 694. (2) Typhoid fever: its mode of spreading and prevention. London, Longmans, Green & Co., 1873. (3) Outbreak of fever at the Clergy Orphan School, St. Johns Wood. Lancet, 1856, Nov. 15. (4) On the fever at the Clergy Orphan School, St. Johns Wood. 1856, Dec. 6. Bujioid, O. Die Erzeugung der Impstoffe und Massenimpfungen im Krakau gegen Cholera und Typhus in der Zeit des Krieges. Med. Klin., 1915, xi, 1421. Busquet, H. Etude experimentale sur 1'or colloidal. Presse M6d., 1915, Sept. 16, No. 43, 356. Busse, O. Ueber das Vorkommen von Typhusbazillen im Blute von nicht typhuskranken Personen. Munch, med. Woch., 1908, No. 21, 294. Cade and Vaucher. Les reactions agglutinantes dans les infections typhoidiques et paratphoidiques. Ann. de Med., 1916, iii, 222. Callison, J. G. Therapeutic use of vaccines in typhoid fever. Am. Jour. Med. Sci., 1912, cxliv, 350. Calmette and Salimbeni. La peste bubonique. Etude de l'epidemie de Oporto en 1899. Ann. Inst. Past., 1899, xiii, 865. Cammaert, C. A. Typhoid among Belgian refugees in Holland. Neder- landsch Tijdschrift v. Geneeskunde, Amsterdam, Mar. 4, No. 10. (J. Am. M. A., Apr. 22, 1916.) Canstatt, C. F. Spezielle Pathologie und Therapie von klinischen Standpunkte ausbearbeitet. 3d ed. Enke, Erlangen, 1855. Capaij)i and Proskauer. Beitrag zur Kenntnis der Saurebildung bei Typhusbacillen und Bacterum coli. Zeit. f. Hyg., 1896, xxiii, 452. Carnot, P. and B. W. Weill-Halle. Notes pratiques sur la recherche du bacille typhique dans l'organisme. La Presse Mea\, 1915, xxiii, 89. BIBLIOGRAPHICAL INDEX 251 Cahonia, G. Improved technique for vaccination against typhoid and paratyphoid. Pediatria, Naples, 1917, Jan., No. 1, 1. (Quoted in Jour. Am. Med. Asso., 1917.) Carpano, M. Ueber die Kapselhiille einiger Bakterien. Cent. f. Bakt., 1913, lxx, 42. Castellani, A. On hemolysins produced by certain bacteria. Lancet, 1902, Feb. 16, 440. (2) Sul reperto del bacillo tifico nel sangue. Riforma medica, 1899, 1. (3) Die Agglutination bei gemisohter Infection und die Diagnose der letzteren. Zeit. f. Hyg., 1902, xl, 1. , (4) Observation on typhoid vaccination in men with attenuated living cultures. Cent. f. Bakt., 1909, lii, 92. (5) Typhoid and paratyphoid vaccination with living attenuated vaccines. Lancet, 1912, Mar. 1, No. 4679, 583. (6) Note on typhoid-paratyphoid vaccination with mixed vaccines. Cent. f. Bakt., 1914, lxxii, 536. (7) Typhoid-paratyphoid vaccination with mixed vaccines. Brit. Med. Jour., 1913, ii, 1577. (8) Further remarks on the mixed typhoid and paratyphoid A and paratyphoid B vaccine. Brit. Med. Jour., 1915, May 1, 758. (9) Further researches on combined vaccines. Cent, f . Bakt., 1915, Ixxvii, 63. (10) Brief note on a case of triple infection: typhoid, paratyphoid A and paratyphoid B. Jour. Trop. Med. and Hyg., 1915, xviii, 37. Chambbblain, W. P. Care of troops on the Mexican border. Jour. Am. Med. Asso., 1916, Nov. 25, 1573. Chantemessb, A. L'opthalmo diagnostique de la fievre typhoide. Bull. Acad, de MeU, 1907, 1384. (2) Toxine typhoide soluble et serum antitoxique de la fievre typhoide. Prog, med., 1898, vii, 245. (3) Resultats de la vaccination antityphoidique dans la marine francaise. Bull, de l'Acad. de M6d., 1916, Ixxxvi, 140. (4) Sur la vaccination antityphoide. Bull, de l'Acad. de MM., 1911, Ixvi, 347. (5) Sur le vaccin triple de la fievre typhoide. Presse Mid., 1915, Sept. 2. (6) Vaccinothercipie de la fievre typhoide. Bull. Acad, de M6d., 1913, lxix, 493. Chantemesse and Widal. De l'immunite' contre le virus de la fievre typhoide, conferee par des substances solubles. Ann. Inst. Past., 1888, II, 54. Chapin, C. V. The sources and modes of infection. 2d Ed. Wiley and Sons, 1912. 252 BIBLIOGRAPHICAL INDEX Chabein, M. and H. Roget. Note sur le developpement des microbes pathogenes dans le serum des animaux vaccines. Compt. Rend. Soc. Biol., 1889, xli, 667. Chiabi, H. Ueber atypische Fonnen des Typhus abdominalis. Bericht fiber die Sitzungen der III Section des XII internationalen medicin- ischen Congresses in Moskau. Cent. f. all. Path. & path. Anat., 1897, viii, 790. (2) Ueber Cholecystitis typhosa. Prag. med. Woch., 1893, xvii, 261. (3) Ueber das Vorkommen von Typhusbazillen in der Gallenblase bei Typhus abdominalis. Cent. f. Bakt., 1894, xv, 648. (4) Ueber Typhus abdominalis und Paratyphus in ihnen Bezie- hungen zu den Gallenwegen. Verhand. de deutsch. path. Ges., Dresden, 1907. Chibolanza, R. Experimentelle Untersuchungen liber die Beziehung der Typhusbacillen zu der Gallenblase und den Gallenwegen. Zeit. f . Hyg., 1909, brii, 11. Chomel, A. F. Lecons de clinique m^dicale, I. Fievre typhoide. Paris, 1834. Ciuca, M., D. Combiescu and J. Balleanu. Deux epidemics de fievre typhoide; vaccinations antityphiques au virus sensibilise' vivant de Besredka. Ann. Inst. Past., 1915, xxix, 105. Clarke, C. The presence of B. typhosus in the blood during relapses in enteric fever. Jour. Roy. Army Med. Corps, 1915, xxv, 333. Clee, E. and A. Feeazzi. Sulla presenza del bacillo di Eberth nelle feci di individui sard. Scritti med. in onore di C. Bozzolo, Torinese, 1904. (Cent. f. Bakt., Ref. 1905, xxxvi, 479.) Cole, R. Typhoid fever. Practical Treatment, Musser & Kelly, 1911, II. Coleman, W. The high calory diet in typhoid fever ; a study of 1 1 1 cases . Am. Jour. Med. Sci., 1912, cxliii, 77. (2) Diet in typhoid fever. Jour. Am. Med. Asso., 1909, liii, 1145. (3) Weight curves in typhoid fever. Am. Jour. Med. Sci., 1912, cxliv, 659. (4) The influence of the high calory diet on the course of typhoid fever. Jour. Am. Med. Asso., 1917, bdx, 329. Coleman, W. and B. H. Buxton. The bacteriology of the blood in typhoid fever cases. Am. Jour. Med. Sci., 1907, cxxxiii, 896. Coleman, W. and Dubois. Calorimetric observations on the metabolism of typhoid patients with and without food. Arch. Int. Med., 1915, xv, 887. Collings, H. A. A reasonable treatment for typhoid. Calif. State Jour, of Med., 1915, xiii, 69. BIBLIOGRAPHICAL INDEX 253 Conn, H. W. The outbreak of typhoid fever at Wesleyan University. Report Bd. of Health of Conn., New Haven, 1895, xvii, 243. Conradi,* H. (2) Zur Frage der ragion&ren Typhusimmunitat. Klin. Jahrb., 1907, xvii, 273. (3) Ein Verfarhen zum Nachweis sparlicher Typhusbacillen. Cent. f. Bakt., Ref., 1908, xlii, Beihefte, 47. (4) Quoted from Ledingham and Arkwright, q. v. (5) Ueber sterilisierende Wirkung des Chloroforms in Tierkorper. Zeit. f. Immunitatsforsch., 1910, vii, 158. (6) Ueber losliche, durch aseptische Autolyse erhaltene Giftstoffe aus Ruhr- und Typhusbacillen. Deut. med. Woch., 1903, No. 2. Conkadi,* J. Wann steckt der Typhuskranke an. Deut. med. Woch., 1907, Oct. 10, 1684. Couhmont, P., Chattot and Piekret. Le s&odiagnostique des para- typhoides. Soc. m6d d. H6p., 1916, June 9. Courmont, P. and Rochatx. Immunisation antityphique de l'homme par voie intestinal. Comp. Rend. Acad, des Sci., 1912, cliv, 1829. (2) Etudes experimentales sur la vaccination antityphoiidique. Ann. Inst. Past., 1917, xxxi, 187. Coton, A. and L. Rivet. Etude sur 66 cas de paratyphoiide. Presse Medicale, 1915, Oct. 14. Csernel, E. and A. Marton. Die Therapie des Abdominaltyphus mit nicht sensibilisierte Vakzine. Wien. klin. Woch., 1915, xxviii, 229. (2) Die Behandlung des Typhus abdominalis mit nicht sensibilis- ierte Vakzine. Wien. klin. Woch., 1915, No. 27, 733. Crombie. Some statistics regarding the effect of inoculation against typhoid fever in South Africa. Lancet, 1902, May 3. (Fornet: Kblle & Wassermann, III, 894, ref. 297.) Cummins, W. T. and P. K. Brown. Atypical typhoid infection. Arch. Int. Med., 1913, Oct. Currie. Medical reports on the effects of water as a remedy in fever. London, 1797. Curschmann. Typhoid fever and typhus fever. W. B. Saunders & Co., Phila., 1902. Cushing, Harvey. Typhoidal cholecystitis and cholelithiasis. Johns Hopkins Hosp. Bull., 1898, ix, 91. Daketne, D. I. Agglutination reactions of blood of soldiers inoculated against typhoid. Lancet, London, 1915, II, 529. Dantbz, J. Un microbe pathogene pour les rats. Ann. Inst. Past., 1900, xiv, 193. * Conradi in text without number refers to J. Conradi. 254 BIBLIOGRAPHICAL INDEX Datjmezon, G. Bacille paratyphique aberrant, iso!6 du sang. Bull. Acad. Med., 1915, April 27, 489. (2) Sur la flore typhique et paratyphique du liquide cephalo- rachidien. Bull. Acad. Med., Aug., 1915, 123. Davis, L. Antityphoid vaccination. Jour. Am. Med. Asso., 1912, lviii, 537. Davison, W. C. Report on prophylactic vaccination with Bacillus typhosus, Bacillus paratyphosus A and Bacillus paratyphosus B. Jour. Lab. & Clin. Med., 1917, II, 607. Dawson, G. D. Diagnosis of typhoid fever in inoculated subjects. Brit. Med. Jour., 1915, July 24. Decobeht, C. Du gelo-diagnostic des selles et de son emploi en diagnostie pr6coce de la fievre typholde. Paris Thesis, 1903. de Fkeycinet. Prophylaxie de la fievre typholde dans l'armee. Ann. d'Hygiene, 1891, xxv, 381. De Haen. Theses sistentes febrium divisiones. Vindob. 1760. Dehleb. Zur Behandlung der Typhusbazillentrager. Munch, med. Woch., 1907, 779/ 2134. Dehu, P. Etude sur le r61e du bacille d'Eberth dans les complications de la fievre typholde. These, Paris, 1893, No. 293. Delafield, F. and T. M. Pkudden. A text-book of pathology. 7th Ed., 1914, Wood and Co., N. Y. Delbet, P. L'or colloidal dans le traitement des infections chirurgicales. Soc. des Chirurgiens de Paris, 1916, Jan. 14. Dennemark. Die Griiber-Widalsche Reaktion bei klinischen Gesunden in der Umgebung Typhuskranker. Cent, f . Bakt., 1910, liv, 374. Deutsch, F. Zur Vakzinebehandlung des Typhus abdominalis. Wien. klin. Woch., 1915, No. 30, 810. Deve. Typholde et paratyphoides. La Presse M6dicale, 1915, Nov., No. 53, 437. Ditthoen, F. and W. Schultz. Zur Antigenbehandlung des Typhus. Med. Klinik, 1915, xi, 100. Doekr, R. Experimentelle Untersuchungen Tiber das Fortwuchern von Typhusbacillen in der Gallenblase. Cent. f. Bakt., 1905, xxxix, 624. Donaldson, R. and B. Clabk. Agglutination reactions with Oxford standard agglutinable cultures. Lancet, 1916, ii, 546. Dopfee, W. Uber die Complicationen des lethalen Abdominaltyphus. Munch, med. Woch., 1888, xxxv, 620, 635. Dopter. Vaccination preventive contre la dysentene bacillaire. Ann. Inst. Past., 1909, xxiii, 677. BIBLIOGRAPHICAL INDEX 255 Dbechsfeld. Quoted by Ruhrah, q.v. Dheter, G. Widal's reaction with sterilized cultures. Jour. Pathology and Bacteriology, 1909, xiii, 331. Debtee, G. and A. C. Inman. Persistence of antibodies in blood of inoculated persons as estimated by agglutination tests. Lancet, 1915, II, No. 4796, 225. Debtee, G., E. W. A. Walkee and A. G. Gibson. The detection and identification of B. typhosus and B. paratyphosus. Lancet, 1915, clxxxviii, 643. (2) Agglutination tests in inoculated persons and influence of febrile conditions on inoculation agglutinins. Lancet, 1916, Apr. 8. (3) Typhoid and paratyphoid infection in relation to antityphoid inoculation. Lancet, 1915, clxxxviii, 324. Deigalski. Ueber Ergebnisse bei der Bekampfung des Typhus. Cent, f . Bakt., 1904, xxxv, 776. Deigalski and H. Conbadi. Ueber ein Verfahren zum Nachweis der Typhusbacillen. Zeit. f. Hyg., 1902, xxxix, 283. Deoba, St. Der Zusammenhang zwischen Typhusinfection und Chole. lithiasis auf Grund eines in der Klinik operirten Falles. Wien. klin- Woch., 1899, No. 46, 1141. Dublin, L. Typhoid fever and its sequelae. Am. Jour. Pub. Health, 1915, v, 20. DuBois. The absorption of food in typhoid fever. Arch. Int. Med., 1912. x, 177. Dueham, H. E. On a special action of the serum of highly immunized animals. Jour. Path, and Bact., 1897, iv, 13. Dziembrowski, S. V. Ein Malariarerezidiv nach Typhusschutzimpfung, Deut. med. Woch., 1915, xli, 1331. Ebeling, E. Ueber das Vorkommen von Typhusbacillen im Blut eines "gesunden" Bacillentragers. Berl. klin. Woch., 1914, 689. Ebeeth, C. J. Die Organismen in den Organen bei Typhus abdominalis. Virchows Archiv, 1880, lxxxi, 58. (2) Neue Untersuchungen uber den Bacillus des Abdominal typhus. Virchows Archiv, 1881, lxxxiii, 486. Eggeeth, H. See letter to Paltauf. Wien. klin. Woch., 1915, xxviii, 209. Eichhoest. Klinische Erfahrungen liber wiederholtes Erkranken an Abdominal typhus. Virchows Archiv, 1888, hi, 48. Elmee, W. P. Study of a recent typhoid epidemic with especial reference to the use of antityphoid vaccines. Jour. Am. Med. Asso., 1915, lxiv, 1147. 256 BIBLIOGRAPHICAL INDEX Elsner. Untersuchungen iiber electives Wachsthum der Bacterium coli-Arten und des Typhusbacillus und dessen diagnostische Ver- werthbarkeit. Zeit. f. Hyg., 1896, xxi, 25. Emmehich and Wagner. Typhusschutzimpfung und Infektion im Tierversuch. Medizin. Khnik, 1916, xii, 74. Endo, S. Ueber ein Verfahren zum Nachweis der Typhusbacillen. Cent, f. Bakt., 1904, xxxv, 109. Englander. Ueber intravenose Kochsalzinfusionen bei Typhus ab- dominalis. Wien. klin. Woch., 1915, xxviii, 1227. Ergebnisse der Todesursachen Statistik im deutschen Reiche fur das Jahr 1912. Springer, Berlin. Etienne, E. Similitude devolution de la fievre typhoiide sur Taction de la serotherapie et de la vaccination. Faginolio, A. Nuove osservazioni e considerazioni sulla vaccinoterapia endovenosa nel tifo. Riforma med., 1916, xxxii, 365. Feistmantel, C. Uber Prophylaxie und Therapie des Typhus abdom- inalis mittels Impstoffen. Wien. klin. Woch., 1915, xxviii, 230. Fellner, B. Beitrag zur Therapie des Typhus abdominalis. Med. Klinik, 1915, xi, 1074. Ficker, M. Typhus und Fliegen. Arch. f. Hyg., 1903, xlvi, 274. Findlay, J. W. and R. M. Buchanan. Case of typhoidal cholecystitis in which the usual symptoms of typhoid were absent, in which the Bacillus typhosus was isolated during life from the cystic and in- testinal contents. Glasgow Med. Jour., 1906, lxv, 177. Firth, R. H. A statistical study of anti-enteric inoculation. Jour. Royal Army Med. Corps, 1911, xvi, 589. Firth, R. H. and Horrock, W. H. An inquiry into the influence of soil, fabrics, and flies in the dissemination of enteric infection. Brit. Med. Jour., 1902, ii, 936. Flatten, H. Die Bekampf ung der Einzelen tibertragbaren Krankheiten . Handb. der praktischen Hygiene. Abel. Fischer, 1913, 1, 634. Fleming, A. Typhoid inoculation in the forces. The Practitioner, 1916, Jan., xcvi, 85. Fletcher, J. P. A rational indication for bacterial vaccine in typhoid fever. Jour. Am. Med. Asso., 1911, Apr. 15. Flexner, S. Unusual forms of infection with the typhoid bacillus, with especial reference to typhoid fever without intestinal lesions. Johns Hopkins Hosp. Rep., 1900, viii. Flint, A. Clinical reports on continued fever. G. H. Derby & Co. Buffalo, 1852. BIBLIOGRAPHICAL INDEX 257 Floyd, C. and Barker, W. W. The typhoid cutaneous reaction. Am. Jour. Med. Sci., 1909, cxxxviii, 188. Fogh, R. Ein Fall von posttyphosen supperativen Knockentzundung mit auserordentlich langwierigen Verlaufe. Deut. med. Woch., 1908, xxxiv, 1305. Force, J. N. Institutional vaccination against typhoid fever. Am. Jour. Pub. Health, 1913, III, 750. (2) University of California Bull., ix, No. 6. Annual report of the President of the University, 1914-15, p. 112. Force, J. N. and I. M. Stevens. Further studies on typhoidin. Arch. Int. Med., 1917, xix, 440. Fornet, W. Ein Beitrag zur Zvichtung von Typhusbazillen aus dem Blut. Munch, med. Woch., 1906, 1053. (2) Immunitat bei Typhus. Kolle & Wassermann, 1912, III, 837, Handbuch der path. Mikroorgan. (3) Die Pracipitatsreaktion. Munch, med. Woch., 1906, No. 38. (4) Statistisches tiber den Typhus and die Typhusbekampfung im Stidwesten des Reichs. Arb. kais. Ges., 1912, xli, 448. Fornet, W. and Muller. Zur Herstellung und Verwendung prazip- itierender Sera, insbesondere fur den Nachweis von Pferdefleisch. Zeitschr. f. biol. Techn. u. Meth., 1908, 1, 201. Forster, J. Ueber die Beziehungen des Typhus und Paratyphus zu dem Gallewegen. Munch, med. Woch., 1908, No. 1, 288. Forster, S. and H. Kayser. Ueber das Vorkommen von Typhusbacillen in der Galle von Typhuskranken und Typhusbacillentragern. Munch, med. Woch., No. 31, 147. Foster. Statement in British House of Commons. Jour. Am. Med. Asso., London Letter, 1916, Nov. 18, 1537. Fraenkel, E. Ueber spezifische Behandlung des Abdominaltyphus. Deut. med. Woch., 1893, xix, 985. Fraenkel, E. and P. Kraus. Bakteriologisches und Experimentelles tiber die Galle. Zt. f . Hyg., 1899, xxxii, 97. Fraenkel, E. and M. Simmonds. Die aetologische Bedeutung des Typhusbazillus. Voss. Hamburg and Leipzig, 1886. (2) Zur Aetiologie des Abdominaltyphus. Cent. f. klin. Med., 1885, vi, 737. (3) Weitere Untersuchungen tiber die Aetiologie des Abdominal- typhus. Zt. f. Hyg., 1887, ii, 138. Friedberger, E. Zur Geschichte der Typhusschutzimpfung des Men- schen. Cent. f. Bakt., 1907, xliv, 560. (2) Die Methoden der Schutzimpfung gegen Typhus usw. Kraus and Levaditi Handbuch, 1908, i, 722. 258 BIBLIOGRAPHICAL INDEX Feiedbergeh, E. and S. Mita. Ueber Anaphylaxie. Ztsch. f. Immuni- tatsfor., 1911, x, 216. Friedberger, E. and C. Moreschi. Vergleichende Untersuchungen liber die aktive Immunisierung von Kaninchen gegen Cholera und Typhus. Deut. med. Woch., 1906, No. 49. Frosch, P. Festschrift zur 60 Geburtstage von R. Koch, 1903, 691. Fischer, Jena. (2) Die Verbreitung des Typhus durch sogenannte "Daueraus- scheider und Bacillentrager." Klin. Jahrb., 1907, xix, 507. Frugoni, C. Appunti pratici intorno al tifo di guerra. Policlinico, Rome, 1916, xxiii, 229. Fulton, J. S. Typhoid fever; some unconsidered hindrances in its prophylaxis. Jour. Am. Med. Asso., 1904, p. 73. von Futterer, A. Untersuchungen iiber den Typhus abdominalis. Munch, med. Woch., 1888, No. 19, 315. Gaehtgens, W. Ueber die Erhohung der Leistungsfahigkeit des En- doschen Fuchsinagars durch den Zusatz von Koffein. Cent, f . Bakt., 1905, xxxix, 634. Gaethgens, W. and G. Bruckner. Vergleichende Untersuchungen iiber einige neurere Typhusnahrboden und Erfahrungen iiber den Wert der Agglutination, Blutkultur und Stuhlziichtung fur die Diagnose des Abdominaltyphus. Cent. f. Bakt., 1909, liii, 559. Gaethgens, W. and W. Kamm. Welchen Wert hat die " Fadenreaktion" fur die Diagnose des Abdominaltyphus fur das Auffinden von Typhus- bazillentragern und die Differenzierung von Bakterien der Para- typhusgruppe. Munch, med. Woch., 1910, No. 26, 1389. Gafpt. Zur Aetiologie des Abdominaltyphus. Mitt. a. d. kais. Gesund- heitsamte, 1884, ii, 372. Gaither, J. G. Antityphoid inoculation. Correspondence, Jour. Am. Med. Asso., 1914, Ixiii, 1314. Galambos, A. Die Behandlung des Typhus abdominalis, Paratyphus A und B mit der Besredkaschen Vakzine. Zt. f. klin. Med., 1916, lxxxiii, 127. Garbat, A. L. Studies in typhoid fever. Jour. Am. Med. Asso., 1916, lxvii, 149. (2) Duodenal cultures in typhoid fever as a means of determining complete convalescence. Jour. Am. Med. Asso., 1916, lxvii, 1493. (3) Sensitized versus non-sensitized typhoid bacteria in the prophy- laxis and treatment of typhoid fever. Jour. Am. Med. Asso., 1915, lxiv, 489. BIBLIOGRAPHICAL INDEX 259 Garbat, A. L. and F. Meyeh. Ueber Typhus-Heilserum. Zt. f. ex- perimentelle Path., 1910, viii, 1. Gartner. Ueber die Fleischvergiftung in Frankenhausen am Kyffhauser und den Erreger derselben. Correspondenzbl. des Allg. arztl. Vereins von Thuringen, 1888, No. 9. Gaupp, 0. Erfahrungen mit Krauschem Typhusserum. Beit, zur Klinik der Infektion und Immunitatsforschung. 1914, ii, 131. Gat. Un traitement pratique de la fievre typhoide aux armies. La Presse M6dicale, 1915, Mar. 4, 67. Gat, F. P. Vaccination and serum therapy against the bacillus of dys- entery. Univ. of Penn. Med. Bull., 1902, xv, 307. (2) Abortive treatment of typhoid fever by sensitized vaccine sediment. Jour. Am. Med. Asso., 1915, lxv, 322. (3) Further experience in the treatment of typhoid fever by the intravenous injection of sensitized typhoid vaccine sediment. Jour. Lab. and Clin. Med., 1917, ii, 785. Gat, F. P. and H. T. Chickering. Treatment of typhoid fever by in- travenous injections of polyvalent sensitized typhoid vaccine sed- iment. Archives of Inter. Med., 1916, xvii, 303. Gat, F. P. and E. Clatpole. The typhoid carrier state in rabbits as a method of determining the comparative immunizing value of prep- arations of the typhoid bacillus. Studies in typhoid immunization I. Arch. Inter. Med., 1913, xii, 613. (2) Agglutinability of blood and agar strains of the typhoid bacillus. Studies in typhoid immunization II. Arch. Inter. Med., 1913, xii, 622. (3) Experimental study of methods of prophylactic immunization against typhoid fever. Studies in typhoid immunization V. Arch. Inter. Med., 1914, xiv, 671. (4) Specific hyperleucocytosis. Studies in typhoid immunization IV. Arch. Inter. Med., 1914, xiv, 671. Gat, F. P. and J. G. Fitzgerald. An improved rapid method of pro- ducing precipitins and hemolysins. Univ. of Calif. Pub. in Path., 1912, ii, No. 8. Gat, F. P. and J. N. Force. A skin reaction indicative of immunity against typhoid fever. Studies in typhoid immunization III. Arch. Inter. Med., 1914, xiii, 471. Gat, F. P. and A. R. Lamb. The application of the typhoidin test in a group of nurses and physicians. Jour. Lab. and Clin. Med., 1917, ii, 217. Gat, F. P. and W. P. Lucas. The value of the conglutination reaction as a means of diagnosis of acute bacterial infection. Proc. Soc. Exper. Biol, and Med., 1909, vii, 21. 260 BIBLIOGRAPHICAL INDEX Gendeon. Dothienenterite observee aux environs de Chateau de Loir. Arch. gen. de M6d., 1834, xviii, Ser. 1. Geeaed, P. and Fenestee. Case of paratyphoid A plus typhoid. Prog- res Med., Paris, 1917, xxxii, 61. (Jour. Am. Med. Asso., 1917, lxviii, Apr. 28.) Geehaed, W. W. On the typhoid fever which occurred in Philadelphia in the spring and summer of 1836. Am. Jour. Med. Sci., 1837, xix, 289. Gilbeet, A. and L. Foueniee. Lithiase biliaire expeiimentale. Compt. rend. Soc. Biol, 1897, xlix, 936. Gilbeet, A. and J. Gieode. Contribution a l'6tude bacteriologique des voies biliares. Semaine med., 1890, x, 481. (2) Des angiocholite infectieuses ascendantes suppuratives. Compt. rend. Soc. biol., 1891, xliii, 217. Gilcheist. Essay on nervous fevers. Edinb. Med. Essays and Observa- tions, 1734, iv. Gieoux. Complications genitales des affections paratypholdes. Presse MeU, 1915, No. 42, Sept. 9. Glenabd. Traits de la fievre typhoiide a Lyon. Gazz. Hebd. MSd. et Chir., Paris, 1883. Glinchikopf, V. I. Changes in the leucocytes under the influence of re- peated injections of antityphoid vaccine. Russky Vrach, 1916, xv, 726. (Jour. Am. Med. Asso., 1916). Goebel. Bericht iiber das Sektionsergebnis bei zwei chronischen Typhusbazillentragern. Zeit. f. Hyg., 1914, Ixxviii, 555. Goldscheideb. Impfmilzschwellung und Typhusdiagnose. Deut. med. Woch., 1915, xli, 1177. Goldscheideb and Aust. Uber die spezifische Behandlung des Typhus abdominalis mit abgetoteten Kulturen von Typhusbazillen. Deut. med. Woch., 1915, xli, 361. Goldscheideb and Kbonee. Ueber den Einfluss der Typhusschutzimp- fungen aud die Typhuserkrankungen bei der Armee im Herbst und Winter, 1914-15. Berl. klin. Woch., 1915, lii, 933, 968, 1001. Gbaham. Death rate in acute infections. Jour. Am. Med. Asso., 1916 lxvii, 1272. Geegg, D. A typhoid carrier 52 years after recovery. Boston Med. & Surg. Jour., 1908, cliv, 80. Gbenet, H. and L. Foetineau. Etude de quelques cas de fievre para- typhoide. Reunion Me'dico-Chirurgicale de TAnnee, Jan. 14, 1916. Presse Mddicale, 1916, No. 6, 68. BIBLIOGRAPHICAL INDEX 261 (2) Etude sur un 6pidemie d'infection typhoi'dique. Soc. MeM. des Hopitaux, 1915, Dec. 24. Geimme. Eia unter dem Bilde der Weilschen Krankheit verlaufender Fall von Typhus abdominalis, entstanden durch Autoinfektion von der Gallenblase her. Munch, med. Woch., 1907, liv, 1822. (2) Ueber die Typhusbazillentrager in den Irrenanstalten. Miinch. med. Woch., 1908, lv, No. 1. Ghobl and Hevee. Ueber die Immunkorperbildung bei Impfungen mit verschieden Typhusimpfstoffen. Wien. klin. Woch., 1915, xxviii, 1383. Gkoer, F. v. Zur Frage der sogenannten Vaccine oder Bakteriotherapie: Ergotrope Therapie des Typhus abdominalis. Miinch. med. Woch., 1915, lxii, 1312. Geuber, M. and H. E. Durham. Eine neue Methode zur raschen Erkennung des Cholera Vibrio und des Typhusbacillen. Miinch. med. Woch., 1896, No. 13, 285. Grunbaum, A. S. Some experiments on enteric, scarlet fever and measles in the chimpanzee. Brit. Med. Jour., 1904, Apr. 9, 817. (2) Blood in the identification of bacterial species. Science Prog., 1897. Guinon, L. and Malarte. Quelques cas de bacterioth^rapie anti- typhique chez l'enfant. Bull. Soc. de Pediatric, 1914, xvi, 1. Gwtn, N. On infection with a para-colon bacillus in a case with all the clinical features of typhoid fever. Johns Hopkins Hosp. Bull., 1898, ix, 54. Haendel und Baerthlein. Ueber chininfeste Bakterienstamme. Cent, f. Bakt., 1913, Ref., lvii, Beiheft, 196. Hage and Korfp-Petersen. Typhusschutzimpfung und Typhus- diagnose. Deut. med. Woch., 1915, xli, 1328. Hahn, M. Immunisierung und Heilversuche mit plasmatischen Zell- saften von Bakterien. Miinch. med. Woch., 1897, xliv, 1347. Haibe, A. A propos des infections de laboratoire a bacilles typhiques. Compt. rend. Soc. Biol., 1913, lxxiv, 998. Hailer, E. and W. Rimpau. Versuche tiber Abtotung von Typhus- bazillen im Organismus. Arbeit, aus kais. Gesundheitsamte, 1911 xxxvi, 409. Hall, H. C. Untersuchungen iiber die Bedeutung des Petrolaethers fur den Nachweis von Typhus und Paratyphusbakterien im Stuhl. Berl. klin. Woch., 1915, Dec. 27, No. 52. Hamilton, A. The fly as a carrier of typhoid; an inquiry into the part played by the common house fly in the recent epidemic of typhoid, fever in Chicago. Jour. Am. Med. Asso., 1903, xl, 576. 262 BIBLIOGRAPHICAL INDEX Hare and Beaedslet. Medical complications, accidents and sequels of typhoid. Lea and Febiger, Phila., 1909. Harbison, W. S. Memorandum regarding antityphoid inoculation. Jour. Roy. Army Med. Corps, 1906, vii, 63. Hartsock, Frederick M. Antityphoid vaccination. Jour. Am. Med. Asso., 1910, liv, 2123. Hatchel, F. W. and H. W. Stoner. Inoculation against typhoid. Jour. Am. Med. Asso., 1912, liv, 1364. (2) Inoculations against typhoid in Maryland. Am. Jour. Pub. Health, 1916, vi, 703. Herz, A. Die Behandlung der Bazillentrager. Wien. klin. Woch., 1916, 1290, Oct. 11. Hess, A. The use of a simple duodenal catheter in the diagnosis and treatment of certain cases of vomiting in children. Am. Jour. Dis- eases of Children, 1912, 133, March. Hildenbrand. Ueber den ansteckenden Typhus. Wien, 1810. Hilgerman, R. Ueber Bazillentrager beim Typhus. Klin. Jahrb., 1908, xix, H 3. Hirsch, C. Atypische Verlaufsformen des Typhus im Felde. Berl. klin. Woch., 1915. lii, No. 30. (2) Ueber atypische Verlaufsformen des Typhus im Felde. Wien. klin. Woch., 1915, xxviii, 955. Hiss, Philip H. On a method of isolating and identifying Bacillus ty- phosus based on a study of Bacillus typhosus and members of the colon group in semi-solid culture media. Jour. Exper. Med., 1897, vii, 677. (2) Studies in the bacteriology of typhoid fever, etc. Med. News, 1901, May 11. Hoffmann. Opera omnia physico-medica. 1699. Ed. Schultze, Gen- evae, 1740. Hohlweg. Ueber den Einfluss der Typhusschutzimpfung auf den Nach- weis der Typhusbazillen in kreisenden Blut. Munch, med. Woch., 1915, lxii, No. 16. Holler, G. Zur Vakzinetherapie des Typhus abdominalis. Zt. f. klin. Med., 1915, lxxxi, 462. (2) Erfahrungen iiber Bakteriotherapie des Typhus abdominalis. Med. Klinik, 1915, xi, 639 and 668. Holscher. Ueber die Complicationen bei 2000 Fallen von lethalen Abdominaltyphus. Munch, med. Woch., 1891, xliii, 43. Holt-Harris, J. E. and O. Teague. A new culture medium for the isolation of Bacillus typhosus from stools. Jour. Infec. Dis., 1916, xviii, 596. BIBLIOGRAPHICAL INDEX 263 Homolle. Quoted by J. Minet, q.v. Hooker, Sanfoed B. A comparison of the antigenic properties of dif- ferent strains of Bacillus typhosus. Jour. Immunology, 1916, ii, 1. Howell, K. Observations on the production of antibodies after anti- typhoid inoculation. Jour. Infec. Dis., 1916, xix, 63. Hueppe, F. In remarks on articles by Fodor and Wyssokowitch. Fort- schr. d. Med., 1886, iv, 447. (2) Schutzimpfung bei Typhus and Cholera. Berl. klin. Woch., 1915, lii, 1274. Hunter, W. Roy. Coll. Surg. Path. Catalogue. (See Murchison ')■ Huxham. Essay on fevers. London, 1739. Ichikawa, S. Abortivbehandlung von typhosen Krankheiten. Mitteil. d. medic. Gesellsch. zu. Tokio, 1914, xxviii, H. 21. Ickert, F. Der Einfluss der Typhusschutzimpfung auf der weisse Blutbild. Beitrage z. klin., Infekkrank. und Immunitatsf., 1915, iv, 153. Irwin, T. and T. H. Houston. On a typhoid carrier treated successfully ,,. by the inoculation of typhoid vaccine. Lancet, 1909, No. 5. Jacobsen, K. A. Untersuchungen fiber die Lebensfahigkeit der Cholera- vibrionen im Meerwasser. Cent. f. Bakt., 1910, lvi, 201. Jaffe, R. H. Die Wirkung des Petrolathers auf die Bakterien der Typhus-Koligruppe. Wien. klin. Woch., 1915, xxviii, 418. Jeanneret, L. Skin typhine tests and skin diphtherine tests for typhoid and for diphtheria in young children. Revue Med. de la Suisse Romande, 1916, xxxvi, No. 10. (Jour. Am. Med. Asso., 1916, 1881.) Jenner, Wm. On the identity or non-identity of the specific cause of typhoid, typhus and relapsing fever. Med. Chirur. Trans., xxxiii. (2) Typhus and typhoid: an attempt to determine the question of their identity or non-identity by an analysis of their symptoms and post-mortem appearances. Edin. Month. Jour. Med. Sci., ix, x, 1849, 1850. (3) Fevers and diphtheria. Macmillan & Co., N. Y., 1893. Jez, V. Ueber Typhusbehandlung (Abdominaltyphus) mit einen Anti- typhus Extract. Wien. med. Woch., 1899, 346. Jobling and Petersen. Bacteriotherapy in typhoid fever. Jour. Am. Med. Asso., 1915, lxv, 515- Jochmann, G. Lehrbuch der Infektionskrankheiten. Springer, Berlin, 1914. Joettbv, K. W. Typhusbekamr>fung im Felde durch ein einf aches Verfahren zur Handedisinfection. Deut. med. Woch., 1915, xli, 1388. 264 BIBLIOGRAPHICAL INDEX Johan, B. Ueber eine Typhusvakzine mit milderer Reaktion. Deut. med. Woch., 1915, xli, 826. Johnson, I. P. and A. I. Milne. Combined preventive inoculation against typhoid fever and paratyphoid and bacillary dysentery. Brit. Med. Jour., 1916, Jan. 15, 88. Johnston. A research on the experimental typhoid carrier state in the rabbit. Jour. Med. Res., 1912, xxvii, 177. Josias, A. Serotherapie de la fievre typhoide. Bull, de l'Acad. de m6d. 1906, lv, 301. Josue, 0. and Belloir, F. Autovaccination antityphique. Cent. f. Bakt., Ref., 1914, lx, 212. Kabeshima. Ueber Typhus und Paratyphusschutzimpfung mittela gemischten Typhus und Paratyphus Vaccine und die Ergebnisse der Schutzimpfung in der kaiserlichen Japanisschen Marine. Cent. f. Bakt., 1914, lxxiv, 294. Kalberlan, F. Die Behandlung der Typhusbazillentrager. Med. Klinik, 1915, xi, 581. Kammerer, H. and R. W. Woltering. Typhusschutzimpfung und Milzschwellung. Munch, med. Woch., 1916, lxiii, 57. Karaffa-Korboutt. Contribution a l'6tude du serum des chevaux immunises avec le vaccin antityphique de Besredka. Compt. rend. Soc. de Biol., 1914, lxxvi, 279. Karell, W. and T. Lucksch. Die Befreiung der Bacillenausscheidern von ihrem Uebel durch Behandlung mit homologen Impfstoffe. Wien. klin. Woch., 1916, xxix, No. 7. Kaspar, F. Zur Autoreinfektion des Typhusbacillenwirtes. Mitteil- ungen aus d. Grenzgebieten der Med. und Chir., xxvi, No. 5, 695. Kast, L. and C. Guiig. Ueber Hypoleucozytose beim Abdominaltyphus und anderen Erkrankungen. Deut. Arch. f. klin. Med., Ixxx, 105. Katser, Heinrich. Uber Untersuchungen bei Personen die vor Jahren Typhus durchgemacht haben, und die Gefahrlichkeit von "Bazillen- tragerri." Arbeiten a. d. kais. Gesungheitsamte, 1907, xxv, 223. (2) Ueber die Art der Typhusausbreitung in einer Stadt. Munch. med. Woch., 1909, lvi, 1067, 1130. Keen, W. W. Surgical complications and sequels of typhoid fever. Phila., 1898, W. B. Saunders & Co. Kelly, F. L. Personal communication. Kendall, A. I. Bacteriology, general, pathological and intestinal. Lea and Febiger, Phila., 1916. BIBLIOGRAPHICAL INDEX 265 Kilgohe, E. S. The typhoidin quotient. Arch. Inter. Med., 1916, xvii, 25. (2) A comparison of two methods of vaccinating against typhoid fever. Arch. Inter. Med., 1917, xix, 276. Kibaltfi, G. Die bakteriologische und chemische Untersuchung der Galle "in vivo" bei Typhus abdominalis. Berl. klin. Woch., 1912, 1985. Kisskalt, K. Laboratoriumsinfektionen mit Typhusbazillen. Zt. f. > Hyg., 1915, lxxx, 145. (2) Ein Modification des Typhusimpfstoffes. Deut. med. Woch., 1915, xli, 393. Kitasato, S. Quoted by Lescohier, q.v. Klebs. Der Ueotyphus eine Schistomycose. Arch. f. exp. Path, u Pharmakol., 1880, xii, 231. (2) Der Bacillus der Abdominaltyphus und der typhose Process* Arch. f. exp. Path. u. Pharmakol., 1881, xiii, 381. (3) Die allgemeine Pathologic Fischer, 1887, Part I. Klein, E. Flies as carriers of the Bacillus typhosus. Brit. Med. Jour., 1908, ii, 1150. Klein, H. The opsonins in typhoid immunity. Johns Hopkins Bull., 1907, xviii, 245. Klieneberger, C. Agglutinationstiter bei Infektionskrankheiten im besondere bei Typhus und Paratyphus. Deut. med. Woch., 1914, 1511. Rlingeb, P. tlber TyphusbacUlentrager. Arb. a. d. kais. Ges., 1906. xxiv, 91. (2) Epidemiologische Beobachtungen bei der Typhusbekampfung im Siidwesten des Reichs. Arb. a. d. kais. Ges., 1909, xxx, 584. Kobek, G. M. The general movement of typhoid fever and tuberculosis in the last thirty years. Trans. Assn. Am. Phys., 1909. Koch, J. Typhusbacillen und Gallenblase. Zt. f. Hyg., 1909, bdi, 1. Koch, R. Zur Untersuchung von pathogenen Organismen. Mitt. a. d. kais. Gesundh., 1881, i, 45. (2) Die Bekampfung des Typhus. Vortrag gehalten in der Sitzung des wissenschaftlichen Senats bei der Kaiser Wilhelms Akad- emie am 28 Nov., 1902. Veroffentlichungen a. d. Milit&r- sanitatswesen, 1902, H. 21. Koenigsfeld, H. Eine neue einfache Methode zum beschleunigten Typhusbazillennachweis in kleinen Mengen Blut. Munch, med. Woch., 1915, 130. (2) Ein neues Prinzip der Serumtherapie bei Infektionskrankheiten, mit besondere Beruchtsichtigung des Typhus abdominalis. Munch, med. Woch., 1915, No. 8, 253. 266 BIBLIOGRAPHICAL INDEX Kolle, W. and H. Hetsch. Die experimentelle Bakteriologie und die Infektionskrankheiten. V. I, p. 261, III Auf., 1911, Urban and Schwartzberg, Berlin. Konjajeff. Die bakterielle Erkrankung der Niere beim Abdominal- typhus. Jescheniedielnaia klinitscheskaia Gaseta, 1888, Nos. 33, 35, 36, 37, 38. (Cent. f. Bakt., 1889, vi, 672.) Koranyi, A. V. Zur Vakzinebehandlung des Typhus abdominalis. Wien. klin. Woch., 1915, xxviii, 85. Korczynski, L. von. Paratyphose Erkrankungen. Medizin. Klinik, Berlin, 1916, xii, No. 3. Kossel, H. Ueber Typhusschutzimpf ung. Berl. klin. Woch., 1914, 1857. Kramer, S. P. The pathogenesis of gallstones. Jour. Exp. Med., 1907, ix, 319. Kratjs, R. Bemerkungen liber Schutzimpfung und einer Bakteriotherapie des Typhus abdominalis. Wien. klin. Woch., 1914, xxvii, 1443. (2) Ueber Bakteriotherapie akuter Infektionskrankheiten. Wien. klin. Woch., 1915, 29. Kratjs and Mazza. Zur Frage der Vakzinetherapie des Typhus abdom- inalis. Deut. med. Woch., 1914, xl, 1556. Kraus, R. and R. v. Stenitzer. Uber Gifte des Typhusbazillen und uber Gift neutralizierende Eigenschaften des Immuneserums. Zt. f. Immunitatsforsch., 1909, iii, 646. Krumbhaar and Richardson. The value of typhoid vaccine in the treatment of typhoid fever. Am. Jour. Med. Sci., 1915, cxlix, 406. Krumwiede, C. Fecal examinations of a regiment infected with Bacillus paratyphosus A, with special reference to normal carriers. Jour. Infec. Dis., 1917, xxi, 141. Krumwiede, C., J. Pratt and L. Kohn. Studies on the paratyphoid enteriditis group. I. Jour. Med. Res., 1916, xxxiv, 355. Ktjhn, P. Weitere Beobachtung uber die Ergebnisse des Typhusschutz- impfung in der Schutztruppe fur Sudwestafrika. Deut. Militarartz Woch., 1907, xxxvi. Kuhnemann, G. Ueber Kapselbildung beim Typhusbacillus. Cent, f Bakt., 1911, lvii, 497. Kutscher, K. H. Abdominaltyphus. Kolle and Wassermann: Hand- buch der pathogenen Mikroorganismen. II Auflage. Fischer, Jena, 1913, iii, 717. Kutscher and E. Meinicke. Vergleichende Untersuchungen Qber Paratyphus-, Enteritis- und Mausetyphusbakterien und ihre im- munisatorischen Beziehungen. Zt. f. Hyg., 1906, Iii, 301. BIBLIOGRAPHICAL INDEX 267 Labbe, M. Les infections typhoides et paratyphoides chez les vaccines. Ann. de MeU, 1916, iii, 13. (2) Vaccination et paratyphoides. Presse MeU, 1916, No. 3, 20. (3) Les fievres paratyphoides. Paris Med., 1915, v, 212. Labbe, M. and Moussaud. Traitement de la fievre typhoide par Tor colloidal. Presse MeU, 1916, No. 14, 105. Labor, M. Zu den zytologischen Veranderungen der Typhusimpfung. Wien. klin. Woch., 1916, xxix, 1393. Lampe, R. Ein Beitrag ziun Verlauf des Typhus bei Geimpften. Deut. med. Woch., 1916, 1120. Lamy, M. Fievre typhoide et lithiase biliare. Paris Thesis, 1909. Lancisi. Opera omnia. Genevae, 1718, Lib. 1. Landmann, G. Ueber eine neue Methode der bakteriologischen Typhus- diagnose. Arb. an der Stadt Krankenhaus, Frankfurt, 1896, 243. Landouzt, L. Note sur 600 injections antityphoidiques. Bull. Acad, de MeU, 1915, lxxiv, 79. (2) Fievre typhoide et fievres paratyphoides, etc. Presse MeU, 1914, No. 78, 707. Landsberger, O. Zur Prognosestellung bei Typhus abdominalis. Med. Klinik, 1915, xi, 1078. Langer, R. Untersuchung iiber einen mit Knotchenbildung einher- gehenden Prozess in der Leber des Kalbes und dessen Erreger. Diss., Giessen, 1904. Langrish. Modern Theory and Practice of Physic. London, 1735. Leboeuf, A. and P. Braun. Notes sur la technique de I'hemoculture au cours des 6tats typhoides. L'hemoculture dans rurine. Comp. Rend. Soc. Biol., 1916, Ixxix, 157. Leclainche, E. Sur la serotherapie du rouget du pore. Comp. Rend. Soc. Biol., 1897, xlix, 428. Ledingham, J. C. G. and J. A. Arkwright. The carrier problem in infectious diseases. Longmans, Green & Co., N. Y., 1912. Leger, Abt and Dumont. Documents relatifs aux infections typhiques et paratyphiques. Presse MeU, 1915, No. 53, 437. Leishmann, W. B. Preliminary note on antityphoid vaccine in the treat- l ment of enteric fever. Jour. Roy. Army Corps, 1909, xii, 136. Lemierre, A. and P. Abrami. Cholecystites et pericholecystites hem- atogenes experimentales. Comp. Rend. Soc. Biol., 1907, lxiii, 252. Lentz, O. Ueber chronische Typhusbazillentrager. Klin. Jahrb., 1905, xiv, 475. (2) Uber den Fornetschen Typhusimpfstoff. Hygien. Rund., 1915, xxv, 891. 268 BIBLIOGRAPHICAL INDEX Lbntz, 0. and J. Tietz. Eine Anrechnungsmethode fur Typhus und Paratyphusbaeillen. Munch, med. Woch., 1903, No. 49. Lescohieh, A. W. Duration of Immunity following small-pox vaccina- tion. Jour. Am. Med. Asso., 1913, lxi, 487. Letulle, M. Des pyrexies abortives. Paris, Asselm and Herizean, 1886. Letulle, M. and Mage. Traitement de la fievre typhoide par Tor colloi- dal en injections intraveineuses. Bull. Acad. M£d., 1914, lxxii, 421. Leuchs. Ueber Malachitgrunnahrboden zum Nachweis von Typhus- und Paratyphusbaeillen. Deut. med. Woch., 1906, 1330. Letjret. Memoire sur la dothienenterite a Nancy. Arch. gen. de Mecl., 1828, xviii, Ser. 1. Levt, E. and E. Bruch. Vergleichende experimentelle Untersuchungen zwischen drei Typhusvakzinen, die sowohl Bakterienleibersubstanzen als auch losliche Stoffwechselprodukte enthalten. Arb. a. d. kais. Gesundh., 1913, xliv, 150. Levt, E. and W. Gaethgens. Ueber die Verbreitung der Typhusbacillen in den Lymphdriisen bei Typhusleichen. Arb. a. d. kais. Ges.-Amte, 1908, xxviii, 295. Levy, E. and H. Katsek. Ueber die Lebensdauer von Typhusbacillen die im Stuhl entleert wurden. Cent, f . Bakt., 1902, xxxiii, 489. (2) Bakteriologische Befund bei der Autopsie eines Bacillentragers. Munch, med. Woch., 1906, No. 50, 2434. Levt, E. and P. Levt. Ueber das Hamolysin des Typhusbacillus. Cent, f. Bakt., 1901, xxx, 405. Levy, P. and P. Vallert-Radot. Differentiation pratique du bacille d'Eberth, du paratyphique A, du paratyphique B par un seul milieu: le gelo-gluco-plomb. Presse M6d., 1915, No. 51, 420. Leydhecker, E. Ueber das Verhalten der weissen Blutkorperchen bei Typhusbacillentragern. Diss., Strassburg, 1910. Liebermann, L. v. Vakzinebehandlung der Typhuskranken. Deut. med. Woch., 1915, xli, 937. Liebermann, L. v. and D. Acel. Neuer gefarbter Nahrboden zur scharfen Unterscheidung saurebildender Bakterien von anderen, in besondere der Colibazillus von Typhusbazillus. Deut. med. Woch., 1914, 2093. (2) Uber Antigenewirkung sensibilisierter und nicht sensibilisierter Blutzellen und Typhusbacillen. Deut. med. Woch., 1915, xli, 965. Liebermeister, C. v. Einleitung zu den Infektionskrankheiten und Ty- phus abdominalis. v. Ziemssen's Handbuch der speciellen Pathologie und Therapie, ii, 82, 155. BIBLIOGRAPHICAL INDEX 269 Liefmann. Beitrag zur Behandlung der Typhusbazillentrager. Miinch. med. Woch., 1909, No. 10. Lignieres. Contribution a l'6tude de septicemic hemorrhagique. Buenos Ayres, 1900. Link, R. Ueber Hautreaktionen bei Impfungen mit abgetoteten Typhus- Paratyphus B und Colikulturen. Miinch. med. Woch., 1908, lv, 730. Lipp, H. Das Blutbild bei Typhus- und Choleraschutzimpfung. Miinch. med. Woch, 1915, lxii, 539. Loeffler, F. tjber ein neues Verfahren zur Gewinnung von Antikorpern. Deut. med. Woch., 1904, xxii, 113. (2) Ueber Epidemieen unter den im hygienischen Institute zu Griefswald gehaltenen Mausen und iiber die Bekampfung der Feldmausplage. Cent. f. Bakt., 1892, xi, 129. Lombard. Observations suggested by a comparison of the post-mortem appearances of typhus fever in Dublin, Paris and Geneva. Dublin Jour. Med. Sci., 1836, x. Longcope, W. T. A study of the bone-marrow in typhoid fever and other acute infections. Bull, of the Ayer Clin. Lab., 1905, No. 2, 1. (2) Personal communication. (3) Paracolon infection together with the report of a fatal case with autopsy. Am. Jour. Med. Sci., 1902, 209. Louis, P. C. A. Recherches anatomiques, pathologiques et therapeu- tiques sur la maladie connue sous les noms de fievre typhoide, etc. J. B. Bailliere, 1841. Louis and Combe. Indication et technique de la vaccination antity- phiques par le vaccin bacillaire polyvalent de H. Vincent. Rev. d'Hyg. et de Pol. saint., 1912, xxxiv, 1325. Lowr, J. Zur Symptomatologie der Typhusschutzimpfung. Med. Klinik, 1915, No. 26, 728. Lbwr, R., F. Lucksch and E. Wilhelm. Zur Vaccinatherapie des Typhus abdominalis. Wien. klin. Woch., 1915, xxviii, 756. Lucksch, F. Die Heterovakzinebehandlung des Typhus abdominalis. Wien. klin. Woch., 1915, xxviii, 707. Ludke, H. Ueber den latenten Mikrobisums der Typhusbazillen. Munch, med. Woch., 1909, lvi, 57. (2) Ueber die Gewinnung und Wirkung von Typhusheilserum. Deut. Archiv. f. klin. Med., 1910, xcviii, 395. (3) Behandlung des Abdominaltyphus mit intravenosen Injek- tionen von Albumosen. Miinch. med. Woch., 1915, 321. Ltster, W. Vaccination against typhoid in the United States army. Jour. Am. Med. Asso., 1915, lxv, 510. 270 BIBLIOGRAPHICAL INDEX MacBridb. Introduction to theory and practice of physic. London, 1772. MacFadyean, A. and S. Rowland. Upon the intracellular constituents of the typhoid bacillus. Cent. f. Bakt., 1903, xxxiv, 765. Magendie, F. Quelques experiences sur les effets des substances en putrefaction. Jour, de Physiol., iii, 1823. Mallory, F. B. A histological study of typhoid fever. Jour. Exper. Med., 1898, iii, 611. Mandelbaum, M. Ueber das Bacterium metatyphi. Cent. f. Bakt., 1912, lxiii, 46. (2) Eine neue einfache Methode zur Typhusdiagnose. Munch, med. Woch., 1910, H. 4, 178. Mann, B. L., F. Rainsford and M. Warren. Report of blood cultures examined in the pathological laboratory. Med. and Surg. Rep. Roosevelt Hosp., N. Y., 1915, 231. Marie, A. Immunisation par des melanges de virus rabique et de serum antirabique. Compt. rend. Soc. Biol., 1902, liv, 1364. Marrassini, A. Ueber das Vorhandsein einer den Korper einiger Bak- terien umgebenden Hulle und deren besondere Bedeutung. Cent, f. Bakt., 1913, lxxi, 113. Martin, S. Intracellular constituents of the typhoid bacillus. Brit. Med. Jour., 1898, 1569, 1644. Marx. Die experimentelle Diagnostik, Serumtherapie und Prophylaxc der Infektionskrankheiten, Kapitel Typhus. Bibliothek v. Coler-v. Schjerning, Berlin, 1902. Matthes, M. Versuche zur Immunisierung gegen Typhus; nach Ver- suchen des verstorbenen Herrn Gottstein. Verh. d. Ges. deut. Naturf . u. Arzte, 1908, 80 Vers., 2 Teil, 95. Maurange, M. G. Statistique de 39,215 injections antitypholdiques et antiparatyphoi'diques B. Presse M6d., 1915, No. 58, 479. Maverick, A. Typhoid vaccination and the Widal reaction. N. Y. Med. Jour., 1912, June 15. Mayer, G. Ueber Typhus, Paratyphus und deren Bekampfung. Cent, f. Bakt., 1910, liii, H. 3. (2) Zur Vakzinetherapie des Typhus abdominalis bei den prophy- laktisch Geimpften. Medizin. Klinik, 1916, xii, 13. Mazza, S. Die Bakteriotherapie des Typhus abdominalis. Wien. klin. Woch., 1915, xxviii, 64. McConkey, A. T. Bile salt media and their advantages in some bac- teriological examinations. Jour. Hyg., 1908, viii, 322. BIBLIOGRAPHICAL INDEX 271 McCrae, T. C. Typhoid fever. Osier's System'of Medicine, II. 1st Ed., 70. McWeenet, E. J. The agglutinability of different races of the typhoid bacillus. Lancet, 1899, i, 380. McWilliams, H. I. Treatment of typhoid fever with typhoid vaccine administered intravenously. Med. Rec, N. Y., 1915, lxxxviii, 648. Mehler, F. C. Prophylaxis of typhoid fever (typhoidin skin tests). Jour. Iowa State Med. Soc, 1916, March. Melnikowa, F. J. and Wersilowa, M. A. Zur Lehre von der Toxin- infektion. II. Ueber die Wirkung der Blutgifte zur die Agglutina- tion von Typhusbazillen. Cent. f. Bakt., 1912, lxvi, 525. Mertz. Uber Vaccinetherapie des Typhus abdominalis. Zt. f. Exper. Path, und Therapie, 1915, xvii, 224. Messerschmidt, Th. Bakteriologischer und histologischer Sektions- befund bei einer chronischen Typhusbazillentragerin. Zt. f. Hyg., 1913, lxxv, 411. Metchnikoff, E. Etudes sur l'iinmunite\ Ann. Inst. Past., 1895, ix, 433. (2) Etudes sur l'immunit6. Ann. Inst. Past., 1891, v, 465. Metchnikoff, E. and A. Besredka. Recherches sur la fievre typhoide expenmentale. Ann. Inst. Past., 1911, xxv, 193. (2) Sur la vaccination contre la fievre typhoide. Compt. Rend. Acad. Sci., civ, 112. (3) Des vaccinations antityphiques. Ann. Inst. Past., 1913, xxvii, 597. Meter, F. Intravenose Typhusbehandlung mit sensibilisierten Bacillen- emulsion (Hochst). Berl. klin. Woch., 1915, lii, 870. (2) Spezifische Typhusbehandlung. Berl. klin. Woch., 1915, lii, 677. Meter and Ahreiner. Ueber typhose Pyonephrose. Mitt. a.d. Grenz- gebieten der Med. und Chir., 1908, xix, H. 3. Meter, F. and E. F. Altstaedt. Spezifische Typhusbehandlung. Berl. klin. Woch., 1915, No. 52, 677. Meter, F. and Bergell. Ueber Typhusimmunisierung. Berl. klin. Woch., 1907, No. IS. Meter, K. F. and C. R. Christiansen. The nature and specificity of the typhoidin reaction. Jour. Infec. Dis., 1917, xx, 391. Meter, K. and E. Kilgore. The agglutinins and complement-fixing antibodies in serum of persons vaccinated against typhoid fever. Arch. Int. Med., 1917, Feb. 15. 272 BIBLIOGRAPHICAL INDEX Milian. Lithiase biliare au cours de la fievre typhoitde. Gaz. hebd. de meU, 1896, 1137. Miller and Lusk. The use of foreign protein in the treatment of ar- thritis. Jour. Am. Med. Asso., 1916, lxvii, 2010. Minelli, S. Ueber Typhusbacillentrager und ihr Vorkommen unter gesunden Menschen. Cent. f. Bakt., xli, 1906, 406. Minet, J. Sur les complications des paratyphoiides. Presse M&l., 1916, No. 4, 25. Montefusco. Sulla sieroterrapia antitifica. Jour. Int. d. Chir. Med., 1908, xxx, 1. Moore, J. W. Text-book of the eruptive and continued fevers. Wm. Wood & Co., N. Y., 1892. Morgan, H. de R. Attempts to produce the typhoid carrier state in the rabbit. Jour. Hyg., 1911, 11, 202. Muller, P. T. Search for bacilli carriers. Munch, med. Woch., 1917, Jan. 2, Ixiv, 1. (Rev. Jour. Am. Med. Asso., Mar. 24, 1917, 944.) Muller, R. and H. Graef. Nachweis von Typhusbakterien in ein gesandten Blutproben. Munch, med. Woch., 1906, lxix, 411. Murchison, C. A treatise on the continued fevers of Great Britain. Longmans, Green & Co., 1884, 2ed. (2) Contributions to the etiology of continued fevers. Med. Chir. Trans., March, 1858. (3) Account of a pig fed for six weeks on typhoid dejections. Trans. London Path. Soc, 1858, Nov., x. Naegeli, L. A. Blutkrankheiten und Blutdiagnostik. Veit. 2ed. Leip- zig, 1912. Nauntn, B. Klinik der Cholelithiase. Leipzig, 1892. Neisser, M. and R. Lubowski. Lasst sich durch Einspritzung von agglutinierten Typhusbazillen eine Agglutinproduktion hervorrufen. Cent. f. Bakt., 1901, xxx, 483. Neisser, M. and K. Shiga. Uber freie Rezeptoren von Typhus- und Dysenteriebazillen und uber Dysenterietoxin. Deut. med. Woch., 1913, lxi. Netter, A. Observations. Bull, de l'Acad. de M6d., 1911, Levi, 351. Neufeld, F. and E. A. Lindemann. Beitrag zur Kenntnis der Serum- festen der Typhusstamen. Cent. f. Bakt., Ref. 1912, liv, Beihefte, 229. Netjhaus. Nachweis der Typhusbazillen am Lebenden. Berl. klin. Woch., 1886, xxiii, 89. BIBLIOGRAPHICAL INDEX 273 Nichols, H. J. Experimental observations on the pathogenesis of gall bladder infections in typhoid, cholera and dysentery. Jour. Exper. Med., 1916, xxiv, 497. (2) Observations on antityphoid vaccination. Jour. Exper. Med., 1915, xxii, 780. Nicolle, C. and L. Blaizot. Les vaccins fluorur^s dans les vaccinations preventives et la vaccinotherapie. Arch. Inst. Past, de Tunis, 1914, ix, 1. Nicolle, C, A. Conor, E. Conseil. De l'inoculation intraveineuse des bacilles typhiques morts a rhomme. Compt. rend. Acad. Sciences, 1912, civ, 1036. Nibble. Importing colon bacilli to fight pathogenic intestinal flora. Deut. med. Woch., 1916, xlii, 1181. (Jour. Am. Med. Asso., Dec. 2, 1916, 1702.) Noak. Ueber Typhusimmunitat und Typhusimpfung. Zeit. f. klinik. Med., Berlin, 1915, lxxxii, 132. Noblecourt, P. and M. Peyre. Complications observes au cours des fievres typhoides et paratyphoides. Soc. M6d. des H6p., 1916, xxxii, 152. Nocard, E. and E. Leclainche. Les maladies microbiennes des animaux. 1905, I, 231. Nolp, P. De Faction antithermique et antiinfectieuse des injections intraveineuses de peptone. Compt. rend. Soc. Biol., 1916, lxxix, 649. (2) Parenteral injections of peptone in treatment of infectious diseases. Archives M6dicales Beiges, Paris, 1917, lxx, 97. (Jour. Am. Med. Asso., May 5, 1917, 1349.) Ogan. Immunization in a typhoid outbreak in the Sloane Hospital for Women. N. Y. Med. Jour., 1915, ci, 610. Ohno, K. Paratyphusbacillus ohne Gasbildungsvermogen. Cent. f. Bakt., 1915, lxxv, 288. Olmer. Fievres typhoides eberthiennes et paratyphiques de l'epidemie de guerre. Revue de M6d., 1916, xxxv, 108. Ortiz, E., M. Acuna and L. Belloc. Bacteriotherapie antityphique chez l'enfant. Arch, de MeU des Enfants, 1915, xviii, 573. Ostertag, R. Hanb. der Fleischbeschau. 1904. Park, W. H. Importance of ice in the production of typhoid fever. Jour. Am. Med. Asso., 1907, xlix, 852. (2) Typhoid bacilli carriers. Jour. Am. Med. Asso., 1908, li, 981. Park, W. H. and A. W. Williams. Pathogenic microorganisms. 4th ed. Lea and Febiger, N. Y., 1910. 274 BIBLIOGRAPHICAL INDEX Patrick, A. Agglutination experiments with typhoid bacilli isolated from the body. Jour, of Hyg., 1914, xiv, 163. Paulicek, E. Zur Frage der Typhusheilimpfung. Wi.en. klin. Woch., 1915, xxviii, 759. Peiper, E. Zur Frage der spezifischen Behandlung des Typhus abdom- inahs. Deut. med. Woch., 1915, xli, 605. Penfold, W. J. Studies in bacterial variation. With special reference to the chemical functions of the members of the typhoid-coli group. Jour, of Hyg., 1911, xi, 30. Pensuti, V. Vaccination in typhoid. Policlinico, Rome, 1914, xx, 1805. (Jour. Am. Med. Asso.) Perussia, F. Sulla pretesa azione sterilizzante in vivo del cloroformio nell 'infezione tifosa. Pathologica, 1912, iv, 141. Pescarolo, B. and C. Quadrone. Aktive Immunisation durch sub- kutane Injektion lebender Typhusbazillen. Cent. f. inn. Med., 1908, xxix, 40. Petit and Serres. Traits de la fievre ente'ro-m&enterique. Paris, 1813. Petroviich, M. Traitement de la fievre typhoide par Phemoserotherapie dans I'armee serbe. Presse M6d., 1915, July 29. Petruscht, J. Ueber Massenauscheidung von Typhusbacillen durch den Urin von Typhusreconvalescenten und die epidemiologische Bedeu- tung dieser Thatsache. Cent. f. Bakt., 1898, xxiii, 577. (2) Spezifische Behandlung des Abdominaltyphus. Deut. med. Woch., 1902, xxviii, 212. Petzetakis. Vakzinotherapie antityphoidique intraveineuse. Comp. rend. Soc. Biol., 1916, lxxix, 655. Peutz, J. L. A. Vaccine therapy of typhoid. Bederl. Tijd. v. Geneesk., Amsterdam, 1916, ii, 555. (Quoted in Jour. Am. Med. Asso., 1916.) Pfatjndler, M. Eine neue Form der Serumreaktion auf Coli- und Pro- teusbacillosen. Cent. f. Bakt., 1898, xxiii, 9, 71, 131. Pfeiffer, A. Ueber den Nachweis der Typhusbacillen im Darminhalt. und Stuhlgang. Deut. med. Woch., 1885, July 16, 500. Pfeiffer, R. Untersuchungen tiber das Choleragift. Zeit. f . Hyg., 1892, xi, 393. Pfeiffer, R. and G. Bessatj. Zur Frage der Antiendotoxine bei Typhus abdominalis. Cent. f. Bakt., 1910, lvi, 344. Pfeiffer R. and W. Kolle. Experimentelle Untersuchungen zur Frage des Schutzimpfung des Menschen gegen Typhus abdominalis. Deut med. Woch., 1896, xxii, 735. (2) Ueber die specifische Immunitatsreaction der Typhusbacillen. Zt f. Hyg., 1896, xxi, 203. BIBLIOGRAPHICAL INDEX 275 Piedvache. Recherches sur la contagion de la fievre typho'ide. M6m. de 1 Acad, de MeU, 1850, xv. Posselt, A. Atypische Typhusinfektion. Lubarsch-Ostertag, Ergebn. der allgem. Pathol., 1912, xvi, 184. (2) Beziehungen zwischen Leber, Gallenwegen und Infektions- krankheiten. Lubarsch-Ostertag, Erbegn. d. allgem. Path., 1915, xvii, 719. Peatt, J. H. Typhoid cholecystitis, with observations upon gallstone formation. Am. Jour. Med. Sci., 1901, Nov. Prigge. StudienuberTyphusbazillentrager. Klin. Jahrb., 1909, xxii, 245. (2) Ortliche Ermittelungen iiber den Ursprung der Falle. (Bei wie vielen Fallen gehngt der Nachweis des Herkunfts? Umgebungs- untersuchen. Nachuntersuchungen Fragebogen.) Arb. a. d. kais. Ges., 1912, xli, 179. Prigge and Sachs-Muke. Beobachten bei zwei durch Nahrungsmittel verursachten Paratyphusepidemien. Klin. Jahrb., 1909, xxi, 225. Pringle. Diseases of the army. 4th ed. 1764. Prost. Medicine 6clairee par l'observation et l'ouverture des corps. Paris, 1804. Pulat, E. Diagnostiche Hautreaktion bei Typhusrekonvaleszenten Typhuskranken, und Schutzgeimpften mit "Typhin" nach Gay und Force. Wien. klin. Woch., 1915, xxviii, 1189. Purjesz, B. Der Nachweis von Typhusbacillen im Duodenalinhalt bei Anwendung der Einhornschensonde. Hyg. Rundschau, 1915, xxv, 601. Ramond, F. and G. Goubert. L'autohemotherapie appliqu^e au traite- ment de la fievre typhoide. Bull, de TAcad. de M6d., 1915, lxxiii, 208. Ranque and Senez. Action de l'iode sur le bacille d'Eberth. Compt. rend. Soc. Biol., 1913, lxxiv, 57. (2) L 'immunity spgcifique et Pimmunite' de groupe obtenues contre les bacilles typhiques et paratyphiques A et B par les vaccins iodSs. Bull. Acad, de MeU, 1915, lxxiv, 703. Reading, B. Isolation of B. typhosus from the bile in typhoid fever. Texas State Jour. Med., 1916, xii, 211. Reed, W., V. C. Vaughan and W. O. Shakespeare. Abstract of report on the origin and spread of typhoid fever in U. S. military camps during the Spanish War, 1898. Wash. Govt. Print. Office, 1900. Reibmayr, H. Tiber Impstoffbehandlung des Typhus abdominalis auf intravenosen Wege. Munch, med. Woch., 1915, xlii, 610. Reiter. tJber thereapeutische Typhusvaccination. Deut. med. Woch., 1915, No. 38, 1120. 276 BIBLIOGRAPHICAL INDEX Remlinger, P. Fievre typhoide experimentale par contamination alimentaire. Ann. Inst. Past., 1897, xi, 829. Remlinger, P. and Schneider. Presence du bacilles d'Eberth dans l'eau, , le sol, et les matures fecales, de sujets non atteints de fievre typhoide. Compt. rend. Soo. Biol., 1896, ii, 105. Remond and Minvielle. Traitement de la fievre typhoide par le serum de Rodet. Bull. Acad. MeU, 1915, lxxiii, 321. Renaud, M. Resultats therapeutiques obtenus par l'emploi du vaccin typnique irradie\ Presse Me'd., Paris, 1911, xix, 665. (2) Vaccinotherapie par les vaccins irradtes. Presse Mecl., Paris, 1911, xix, 585. Rhein, M. ZurBakteriotherapiedes Typhus abdominalis. Munch, med. Woch., 1915, lxii, 427. Ribadeau, Dumas and Hartier. Recherches sur 1'elimination des bacilli d'Eberth et des paratyphiques par l'intestin. Compt. rend. Soc. Biol., 1910, lxix, 181. Richardson, M. W. A case of cholecystitis due to the typhoid bacillus. Bost. Med. & Surg. Jour., 1897, cxxxvii, 570. (2) On the rdle of bacteria in the formation of gall stones. Jour. Bost. Soc. Med. Sci., 1899, iii, 79. Richardson, M. W. and L. H. Spooner. Antityphoid inoculation as in- troduced into certain training schools for nurses in Massachusetts. Bost. Med. & Surg. Jour., 1911, clxiv, 8. Riecke. Der Kriegs- und Friedentyphus in den Armeen. Nordhausen, 1850. Riedel. De febribus intestinalibus. Collect. Ballinger, 1776. Rimbaud, L. Diagnosis and prognosis of paratyphoid infection. Presse MeU, 1916, vi, 305. (Jour. Am. Med. Asso., 1916, Nov. 19.) Rist, E. Etudes sur la fievre typhoide. I. L'action de la vaccination antityphique sur la fievre typhoide et les fievres paratypholdes. Ann. de MeU, 1916, iii, 88. Robinson, H. Notes on the clinical characteristics of cases treated as paratyphoid fever. Lancet, 1915, ii, 851. Robinson, A. C. and L. F. Rettger. Studies in the use of brilliant green and a modified Endo's medium in the isolation of B. typhosus from feces. Jour. Med. Res., 1916, xxxiv, 363. Rocek, J. Ueber die Wirkung des Indols auf Typhusbazillenkulturen als Grundlage fur therapeutische Versuche. Cent. f. Bakt., 1915, lxxvii, 100. Rochoux. Le typhus nosocomial et la dothienenterite, sont ils la meme maladie? Arch. gen. de M6d., 1840, Feb. BIBLIOGRAPHICAL INDEX 277 Rodet, A. Sur le propria toxique de la culture de bacille d'Eberth et coli. Compt. rend. Soc. Biol., 1898, 1, 756. (2) Serotherapie antityphoidique. Preparation du serum. Bull. Acad, de MeU, 1916, lxxvi, 85. (3) Serotherapie antityphoidique. Bull. Acad, de Mid., 1916, lxxvi, 114. Rodet, A. and Laghiffotjl. Serotherapie de la fievre typhoiide; resultats cliniques. Compt. rend. Soc. Biol., 1910, lxviii, 605. Rodet, A., Lagriffoul and Wahbt. La toxine soluble du bacille d'Eberth. Compt. rend. Soc. Biol., 1904, lvi, 794. Roederer and Wagler. De morbo mucoso. Gottingen, 1762. Roger, H. Principles of medical pathology. 2d Eng. ed. by Gabriel. Appleton & Co., 1905, N. Y. Rohonyi, H. Untersuchungen liber das Wesen der therapeutischen Typhusvakzinwirkung. Zeit. f. klin. Med., 1916, lxxxiii, 60. Rommel and Herrmann. Klinische Beobachtungen aus der Schneide- miihler Typhusepidemie in Sommer 1911. Veroffentlichungen aus dem Gebiete der Medizinalverwaltung, 1912, i, 29. Roques, E. Contribution a l'Stude de la vaccinotherapie de la fievre typhoi'de par le virus-vaccin sensibilise' antityphique vivant de Besredka. Pub. Ch. Dirion, Toulouse, 1913. Rosenau, M. J. Preventive medicine and hygiene. Appleton & Co., 1913, N. Y. Rosenau, M. J., L. L. Ldmsden and J. H. Kastle. On the origin and prevalence of typhoid fever in the District of Columbia. Bull. No. 52, Hyg. Lab. U. S. Pub. H. & Mar.-Hosp. Serv., 1909. Roth, N. Versuche iiber die Einwirkung des Caffeins auf das Bacterium Typhi und coli. Hyg. Rundschau, 1903, No. 10. Rothberger, C. J. Differentialdiagnostische Untersuchungen mit gefarbten Nahrboden. Cent. f. Bakt., 1898, xxiv, 513. Roux, E. and Chamberlain. Immunity contre le septicemic confer6 par des substances solubles. Ann. Inst. Past., 1887, i, 561. Rovsing, Th. Klinische und experimentelle Untersuchungen iiber die infektiosen Krankheiten der Harnorgane. A. d. Danischen, Berlin, 1898. Ruediger, G. F. and R. Hulbert. Is dried blood as reliable as fresh serum in making the Widal test? Am. Jour. Pub. Health, 1914, iv, 113. Ruhrah, John. Infectious diseases, including acute rheumatism, croupous pneumonia and influenza. Prog. Med., 1916, March, 133. 278 BIBLIOGRAPHICAL INDEX Rumpf, T. Die Behandlung des Typhus abdominalis mit abgetSdteten Culturen des Bacillus Pyocyaneus. Deut. med. Woch., 1893, xix, 987. Russell, F. F. Progress in antityphoid vaccination during 1912. Jour. Am. Med. Asso., 1913, lxi, 665. (2) The isolation of typhoid bacilli from urine and feces with the description of a new double sugar tube medium. Jour. Med. Res., 1911-12, xxv, 217. Sachs, H. Die Schutzimpfung gegen Typhus. Med. Klinik, 1914, 1538. Sacquepee, E. Les porteurs de germes. Bull. Inst. Past., 1910, viii, 1, 49. Sacquepee, E., Burnet and Weissenbach. Etude macroscopique des lesions produites chez l'homme par le bacille paratyphique A, d'apres le protocole de 9 autopsies. Presse Mdd., 1915, Sept. 8. Sacquepee, E. and F. Chevrel. Les bacilles paratyphiques. Bull. Inst. Past., 1907, v, 49. (2) Sur la vaccinotherapie antitypholdique. Soc. m6d. des H6p. de Paris, 1913, 845. Sadler. The antigen treatment of enteric fever. Quart. Jour, of Med., 1912, v, 193. Salmon, E. and T. Smith. On a new method of producing immunity from contagious diseases. Proc. Biol. Soc. of Washington, 1884-6, iii, 29. (2) The bacterium of swine plague. Am. Monthly Microscopical Jour., 1886, Nov., 204. Sanarelli, J. Etudes sur la fievre typhoide experimentale. Ann. Inst. Past., 1894, viii, 193. (2) Etiologie et pathogenie de la fievre jaune. Ann. Inst. Past., 1897, xi, 433. Sarrailhe, A. and J. Clunet. La "jaunisse des camps" et I'gpidemie de paratyphotde des Dardenalles. Bull, et Mem. Soc. M6d. des Hop., Paris, 1916, xl, 45. Sartory, A., L. Spillmann and P. Lasseur. fitats typholdes pendant la campagne 1914-15. Bull. Acad. MeU, 1915, lxxiii, 385. Sawyer, W. A. Ninety-three persons infected by typhoid carrier at pub- lic dinner. Jour. Am. Med. Asso., 1914, lxiii, 1537. (2) A typhoid carrier on shipboard. Jour. Am. Med. Asso., 1912 Iviii, 1336. (3) The disease carrier on train and steamboat. Jour, of Sociologic Medicine, 1916, xvii. (4) The efficiency of various antityphoid vaccines. Jour. Am Med. Asso., 1915, lxv, 1413. BIBLIOGRAPHICAL INDEX 279 Scheller, R. Beitrage zur Typhusepidemiologie. Cent. f. Bakt., 1908, xlvi, 385. Schlager. Kriegesarzte Abend der V. armee am 14 Dez., 1914. Munch, med. Woch., 1914, Dec. 14. Schmitz, K. E. F. Die Brauchbarkeit des Kongorotnahrbodens zur bakteriologischen Typhusdiagnose. Deut. med. Woch., 1915, xli, 425. (2) Ein neuer Elektionahrboden fur Typhusbacillen. Cent. f. Bakt., 1915, lxxvi, 306. Schneider, F. Ueber Leukopenic und Aneosinophilie nach Typhus- schutzimpfung. Deut. med. Woch., 1915, xli, 426. Schoenlein. Allgemeine und specielle Pathologie und Therapie. Frey- burg, 1839. Scholz. Bemerkungen zur Symptomatologie und Therapie des Unter- leibstyphus. Deut. med. Woch., 1915, xli, 1456. Schottmuller, H. Die typhosen Erkrankungen. Handb. der inn. Med., i, 397. (2) Weitere Mitteilungen fiber mehrere das Bild des Typhus bietende Krankheitsfalle, hervorgerufen durch typhusahnliche Bacillen. Zt. f. Hyg., 1900, xxxvi, 368. Schtulern, W. R. De la bacteriemie typhique et ses rapports avec le pouvoir agglutinant du seYum au cours de la fievre typhoiide. Roussky Vratch, 1907, Mar. 23, 339. (Bull. Inst. Past., 1907, v, 433.) Schdder. Zur Aetiologie des Typhus. Zeit. f. Hyg., 1901, xxxviii, 343. Schumacher. Zur Frage der Bazillentrager und ihrer Beziehung zum endemischen Typhus. Klin. Jahrb., 1909, xxii, 263. Schurmann. Zur Beschleunigung und Vereinfachung der Typhus- bazillenzuchtung aus dem Blut. Deut. med. Woch., 1916, xlii, 158. Scott, H. H. An investigation into the causes of the prevalence of enteric fever in Kingston, Jamaica; with special reference to the question of unrecognized carriers. Ann. Trop. Med. and Parasit., 1915, ix, 239. Scully, F. J. The reaction after intravenous injections of foreign protein. Jour. Am. Med. Asso., 1917, July 7, 20. Sedgwick, W. T. Introduction to Whipple's Typhoid Fever, 1908. (2) Reports to Massachusetts State Board of Health, 1892. Sedgwick, W. T. and S. MacNutt. An examination of the theorem of Allen Hazen, that for every death from typhoid fever avoided by the purification of public water supplies, two or three deaths are avoided from other causes. Science, 1908, p. 215, N. S. 28. Seiffert, S. Ueber Mitagglutination de Gaertnerbasillen, ein Hilfs- mittel zur Typhusdiagnose. Munch, med. Woch., 1915, lxii, 1753. 280 BIBLIOGRAPHICAL INDEX Seitz, C. Der Abdominaltyphus nach langjahriger Beobachtung. Stutt- gart, Enke, 1888. Semple, D. and E. D. W. Greig. An enquiry on enteric fever in India. Scientific memoir by officers of the medical and sanitary department of the Government of India. No. 32, Calcutta, 1908. Sergent, E. and L. Negre. Les vaccinations mixtes antityphoidiques et antiparatyphoidiques dans l'armee de PAfrique du Nord. Bull. Acad. Med., 1915, Oct. 26, 469. Shaffer, P. A. and W. Coleman. Protein metabolism in typhoid fever. Arch. Int. Med., 1909, iv, 538. Shattuck. Observations of typhus and typhoid fever. Am. Med. Examiner, Feb. and Mar., 1840. Shimidsu, K. Ueber die Morphologie des Bact. coli, B. typhi abdominalis und der anderen gramnegativen Bacillen. Cent. f. Bakt., 1913, Ixxi, 338. Sick, K. Ueber die klinische Verwendung von Blutnahrboden, ihren Einfluss auf Immunitatsreaktionen und liber das Verhalten der Bakterien (speziell der Tuberkelbacillen) zum Hamoglobin. Cent, f. Bakt., 1912, bdv, 111. Simon, G. Ueber Cholecystitis typhosa als Ursache chronischer Typhus- bazillenausscheidung. Klin. Jahresbericht, 1907, xvii, 363. Sinnhuber. Die Bekampfung der Kriegesseuchen durch Schutzimpfung. Deut. med. Woch., 1915, xli, 637. Sirotinin, W. Die Uebertragung von Typhusbacillen auf Versuchs- thiere. Zt. f. Hyg., 1886, i, 465. Sladek, J. and S. Kotlowski. Zur Vakzinetherapie des Typhus ab- dominalis. Wien. klin. Woch., 1915, xxviii, 389. Smith, F. Antityphoid or anti-enteric inoculation. Jour. Trop. Med., 1904, vii, 271. Smith, H. The typhoid bacillus and typhoid fever. Brit. Med. Jour., 1900, i, 827. Smith, J. H. The identification of the pathogenic members of the typhoid-colon group of bacilli. Brit. Med. Jour., July 3, 1915. Smith, Nathan. Medical and Surgical Memoirs, 1824, p. 47. Smith, T. Active immunity produced by so-called balanced or neutral mixtures of diphtheria toxin and antitoxin. Jour. Exp. Med 1909 xi, 241. ' Southard, E. E. and E. T. F. Richards. Typhoid meningitis: cultiva- tion of Bacillus typhosus from meninges and mesenteric lymph node etc. Jour. Med. Res., 1908, xix, 513. BIBLIOGRAPHICAL INDEX 281 Spigelitxs. De febre semitertiana. Frankfurt, 1624. Spitta. Die Wasserversorgung. Handb. d. Hyg., 11, 39. Rubner, Griiber, Ficker, 1913, Hirzel, Leipzig. Spooneh, L. H. Antityphoid inoculation. Jour. Am. Med. Asso., 1912, lix, 1359. Stenitzee, R. Ueber die Toxine (Endotoxine) der Typhusbazillen, Kraus and Levaditi Handb. d. Immunitatsforsch., 1908, i, 193. Stepp. Die Duodenalsonde zum Nachweis der Typhusbazillen in der Galle von Typhusrekonvaleszenten. Miinch. med. Woeh., 1915. lxii, 1676. Stern, R. Ueber die Wirkung des menschlichen Blutserums auf die experimentelle Typhusinfektion. Zt. f. Hyg., 1894, xvi, 458. Stern, R. and W. Korte. Ueber den Nachweis der bakteriziden Reak- tion im Blutserum der Typhuskranken. Berl. klin. Woch., 1904. Sterzing, P. Ueber Recidive und Nachschube beim Typhus abdom- inalis. Diss., Leipzig. Stokes, A. and C. Clarke. Search for typhoid carriers. Lancet, 1916, 566, 590. Stoner, H. W. Antibody production by typhoid vaccines. Jour, of Immunol., 1916, i, 511. Strong, R. P. Some questions relating to the virulence of microorganisms with particular reference to their immunizing powers. Jour. Exper. Med., 1905, vii, 229. Strother. A very remarkable history of a spotted fever. London, 1729. Stursburg and Klose. Zur Frage der Bewertung der franzosischen Typhusschutzimpfung der Griiber-Widalschen Reaktion bei Typhus- geimpften. Miinch. med. Woch., 1915, lxii, 380. Sutton, J. B. On the diseases of monkeys in the Society's Gardens. Zool. Soc. Proc, 1883, 581. Szecst, E. Die Behandlung des Typhus abdominalis mit Besredkas Vakzine. Deut. med. Woch., 1915, xli, 966. Tanaka, K. Bacteriological investigation of typhoid fever. Korea Med. Soc, 1914, No. 12, 22. (China Med. Jour., 1917.) Tarassevitch, L. Vaccinations antityphiques dans 1'armee russe. Bull. Acad, de Med., 1916, May 9. Taylor. On the communication of fever by ingestion. Ed. Med. Jour., 1858, June. 282 BIBLIOGRAPHICAL INDEX Teague, 0. and H. I. McWilliams. The bacteriolytic power of normal and immune rabbit serum for typhoid bacilli and the influence of the intravenous injection of vaccine upon the same. Jour, of Imm unol., 1917, ii, 167. (2) Experiments with a possible bearing upon treatment of typhoid fever with typhoid vaccine administered intravenously. Jour, of Immunol., 1917, ii, 185. (3) The bacteriolytic power of normal human sera and typhoid patients' sera for typhoid bacilli and an inquiry into the theoretical basis for the treatment of typhoid fever with vac- cine administered intravenously. Jour, of Immunol., 1917, ii, 193. Tehbile, A. (Quoted by Posselt). Atypische Typhusinfektion. Lu- barch-Ostertag Ergebn., 1912, xvi, 184. Thayer, W. S. Two cases of post typhoid anemia with remarks on the value of examination of the blood in typhoid fever. Johns Hopkins Hosp. Reports, 1895, 83. Thiholoix, J. and Baedon. Vaccin typhique intraveineux. Soc. Meet, des Hop., 1913, xxxvi, 108. Tidt, H. L. Influence of febrile conditions on inoculation agglutinins. Lancet, 1916, i, 241. Tolmee and Weissenbach. Un cas de meningite cer^bro-spinale aigue primitive a bacille paratyphique A. Presse M6d., 1915, Sept. 9, No. 42. Tonnel. Etudes des reactions humorales dans la vaccination anti- typhoidique et antiparatyphoidique A et B. Lyon Med., April, 1916, cxxv. Tonnet, F. O., F. C. Caldwell and P. J. Griffin. The examination of the urine and feces of suspect typhoid carriers with a report on elaterin catharsis. Jour. Inf. Dis., 1916, xviii, 239. ToEEEY, J. C. The fecal flora of typhoid fever and its reaction to various diets. Jour. Inf. Dis., 1915, xvi, 72. Townsend, J. H. Antityphoid vaccination. Am. Jour. Pub. Health 1914, iv, 993. Teemoliebes, F., P. Loew and Maillabt. Recherches sur la vaccina- tion antityphoidique par la voie digestive. Bull. Acad. MecL 1915 Oct. 26, p. 477. Trowbridge, E. H., B. A. Finkle and E. M. Barnabd. Report of a typhoid epidemic occurring three months after the use of prophylactic vaccine. Jour. Am. Med. Asso., 1915, Ixiv, 728. Tsuzuki, J. Eine von Bazillentragem hervorgerufene Typhusepidemie in der XV Division von Japan. Arch. f. Schiffs- und Tropenhygiene 1910, xiv, 147. ' BIBLIOGRAPHICAL INDEX 283 Tsuztjki, M. and K. Ishida. Ueber die Beeinflussung der Typhusbazillen bei Typhusrekonvaleszenten durch Kalium jodatum sowie Acidum arsenicosum. Deut. med. Woch., 1910, Sept. 1, 1005. Tubby, A. H. and J. A. B. Hicks. A case of suppurative post-typhoid osteitis thirteen years after an attack of enteric fever. Lancet, 1913, i, 304. Twort, F. W. The fermentation of glucosides by bacteria of the typhoid coli group and the acquisition of new fermenting by Bacillus dys- enteriae and other microorganisms. Proc. Roy. Soc, London, 1907, Ixxix, 329. Uhlenhtjth, P. and E. Hubener. Infektiose Darmbakterien der Para- typhus und Gaertner-gruppe einschliesslich Immunitat. Kolle & Wassermann Handbuch der pathogen. Mikroorganismen. 1913, iii, 1005, Fischer, Jena. Uhlenhtjth, P. and T. Messerschmidt. Versuche Kaninchen zu Typhusbazillentragern zu machen und sie therapeutisch zu beein- flussen. Deut. med. Woch., 1912, xxxviii, 2397. Uhlenhuth, P., Olbrich and T. Messerschmidt. Typhusverbreitung und Typhusbekampfung im Felde. Med. Klinik, 1915, No. 6, 149. Valleix. Considerations sur la fievre typholde. Arch. gen. de Mdd., 1839, Jan., Feb., Oct., and Nov. Vaughan, V. C. The specific treatment of typhoid fever. Am. Jour. Med. Sci., 1908, Sept. (2) Protein split products in relation to immunity and disease. Lea and Febiger, 1913. Venema, T. A. Ueber Agglutination von Bakterien der Typhusgruppe durch Galle. Berl. klin. Woch., 1906, No. 30. Vilchur. Etiology and clinical bacteriology of typhoid fever. Inaug. Diss., St. Petersburg, 1887. Vincent, H. See Vincent and Muratet. (2) Sur la vaccination antityphique. Jour. State Med., 1912, xx, 322. (3) Sur rimmunisation active de l'homme contre la fievre typholde. Compt. rend. Acad, des Sci., civ, 480. (4) Remarques sur la vaccination antityphique. Ann. Inst. Past., 1911, xxv, 455. (5) Sur la vaccination antityphique. Jour. State Med., 1912, xx, 321. (6) Nouvelles remarques sur le vaccin mixte antitypholdique et antiparatyphique. Presse MM., Sept. 2, 1915. (7) Action du vaccin antitypholdique chez les sujets en incubation de la fievre typholde ou infectes au cours de 1 'immunisation. Compt. rend. Acad. Sci., 1913, clvi, 821. 284 BIBLIOGRAPHICAL INDEX (8) Un nouveau cas de la contagion eberthienne de laboratoire prevenu par le vaccination antityphoidique (vaccin polyva- lent). Compt. rend. Soc. Biol., 1914, lxxvi, 32. (9) Reference by Vincent and Muratet, 1. c. 162. (10) R&ultats de la vaccination antityphoidique par le vaccin polyvalent. Bull, de l'Acad. de M6d., Ixxvii, No. 19, 475. Vincent, H. and L. Muratet. Fievres typhoides et paratyphoides. Masson & Co., Paris, 1916. von Behring, E. Ueber ein neueres Diphtherieschutzmittel. Deut. med. Woch., 1913, xxxix, 873. von Jaksch, R. Ueber die Behandlung des Typhus abdominalis mit Blutserum von Typhusrekonvaleszenten. Verhand. d. Kong. f. inn. Med., Wiesbaden, 1895. Wade, E. M. and O. McDaniel. Observations on the Widal reaction following the administration of typhoid vaccine. Am. Jour. Pub. Health, 1915, v, 136. Waitzfelder, E. Treatment of typhoid with bacterins. N. Y. Med. . Jour., 1916, ciii, Feb. 26. Walger, E. Beitrag zur Behandlung des Abdominaltyphus mit mensch- lichem Rekonvalescentenblutserum. Cent. f. inner. Med., 1898, 941. Ward, W. A. Some notes on the results of anti-enteric inoculation. Jour. Roy. Army Med. Corps, 1906, vi, 436. Wassermann, A. tJber Agglutinine und Pracipitine. Zt. f. Hyg., 1903, xlii, 267. (2) Beitrage zur Typhus-Schutzimpfung. Zt. f. Hyg., 1911, lxx, 204. (3) Zur aktiven Immunisierung des Menschen. Festschr. z. 60. Geburtst. von R. Koch, p. 527. Fischer, Jena, 1904. Weichardt, W. Uber die unspezifische Therapie von Infektionskrank- heit. Munch, med. Woch., 1915, lxii, 1525. Weil, P. E. Vaccinotherapie de la fievre typhoide chez l'enfant. Soc. m6d. des h6p. de Paris, 1913, xxxvi, 344. Weinfttrter, F. Experimentalle Typhusbazillentrager bei Kaninchen. Cent. f. allg. Pathol., 1915, xxvi, 367. Weiss, H. Cultural and antigenic differences in strains of Bacillus typhosus and studies in the paratyphoid group. Jour. Med. Res., 1917, xxxvi, 135. Werner, A. Sur la toxine secr^tee par le bacille typhique. Compt. rend. Soc. Biol., 1904, lvi, 882. Whipple, G. C. Typhoid fever: its causation, transmission and preven- tion. Wiley & Sons, 1908. BIBLIOGRAPHICAL INDEX 285 Whittington, T. H. The use of stock vaccine in infection by the Bacil- lus typhosus with an analysis of 230 cases. Lancet. 1916, No. 4832, 759. Widal, F. Serodiagnostic de la fievre typhoide. Bull, et mem. Soc. m&I. d. h6p. ,1896, vi, 26. (2) Reference in Brouardel and Thoinot, 1. c. 29. (3) A propos de la vaccination antityphoidique. Bull. Acad, de MeU, 1915, lxxiii, 363. (4) Sur les vaccinations mixtes antityphoidiques et antiparaty- phoidiques. Bull. Acad. MM., 1915, lxxiv, 249. (5) Etude sur les vaccinations mixtes antityphoidiques et antipara- typhoidiques. Presse M6d., 1915, No. 38, 305. (6) Etudes sur les vaccinations mixtes antityphoidiques et anti- paratypholdiques. Bull. Acad. MeU, Aug. 10, 1915, 149. (7) Resultats de la vaccination antityphique. Presse Mid., 1915, No. 53, 437. Widal, F. and Courmont. Revaccination antityphoidique et vaccina- tion antiparatyphoidique. Presse M6d., 1916, No. 8, 57. Widal, F. and L. LaSouhd. Recherches experimentales et cliniques sur la sensibilitrice dans le sdrum des typhiques. Compt. rend. Soc. Biol., 1901, liii, 841. Whjal, F. and A. T. Salimbeni. Reduction du nombre des injections employees pour la vaccination mixte antityphoidique et antipara- typhoidique A et B. Presse M6dicale, 1917, xxv, 1. Widal, F. and A. Sicabd. Etude sur le serodiagnostic et sur la reaction agglutinante chez les typhiques. Ann. Inst. Past., 1897, xi, 353. Willis. Defebribus. 1659. (2) Opera omnia Amstelodami. 1682. De morbis convulsivis, Cap. 8. Wilman. Detection of typhoid bacilli in search for carriers. Norsk. Magazin for Laegevidenskaben, 1916, lxxvii, 879. (Jour. Am. Med. Asso., 1916). Wilson, W. J. and C. Dickson. A rapid gravimetric method of stand- ardizing vaccines. Jour, of Hyg., 1912, xii, 49. Wiltshire, H. W. and A. MacGillycuddt. Treatment of typhoid by stock typhoid vaccine. Lancet, 1915, ii, 685. Winslow, A. E. Technology Quarterly, 1901, xiv. Wolff-Eisner, A. Die Ophthalmo- und Kutandiagnose der Tuber- kulose. Wiirzburg, 1908. Wolfsohn, G. Appendicitis und Typhus. Berl. klin. Woch., 1915, xli, 872. 286 BIBLIOGRAPHICAL INDEX Woodruff, C. E. Tuberculosis following typhoid fever. Am. Med., 1914, N. S. 9, 17. Whight, A. E. On the association of serous hemorrhages with conditions of defective blood coagulability. Lancet, 1906, ii, 802. (2) Zur Geschichte der Typhusschutzimpfung des Menschen. Cent. f. Bakt., 1908, xlvi, 188. (3) On the protective value of antityphoid inoculation. Lancet, Sept. 6, 1902, 651. Weight, A. E. and Semple. Remarks on vaccination against typhoid fever. Brit. Med. Jour., Jan. 30, 1897, 256. Yagisawa, M. La vaccination antityphique dans l'armee japonaise. Paris Mdd., 1916, vi, 490. Yamanouchi, T. Toxicity du filtrat des cultures en bouillen des bacilles typhiques et paratyphiques. Compt. rend. Soc. Biol., 1909, lxvi, 1050. Ziersch, P. Beobachtungen bei Typhusschutzgeimpften. Munch, med. Woch., 1915, lxii, 1310. Zinssee, H. Infection and resistance. Macmillan Co., N. Y., 1914. Zupnic, L., A. von Muller and K. Leiner. Erfahrungen fiber Praxis und Theorie der Vakzinetherapie. Wien. klin. Woch., 1916, xxix, 33. Printed in the United States of America THE following pages contain advertisements of a few of the Macmillan books on kindred subjects Infection and Resistance An Exposition of the Biological Phenomena Underlying the Occurrence of Infection and the Recovery of the Animal Body from Infectious Disease By HANS ZINSSER, M.D. Professor of Bacteriology at the College of Physicians and Surgeons, Columbia University, New York With a Chapter on Colloids and Colloidal Reactions By Professor STEWART W. 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