COLUMBIA LIBRARIES OFFSITE HEALTH SCIENCES STANDARD HX00056987 :'i7Ml i iliilHii WILKINSON fSIHiSl:! iiii] oiPiisii'sieHil II an i PROTOZOA MED. DEPT. eoUege of ^Ijpgitiansi anb ^urseons itibrarp ERRATA. Page II. Insert vertical line under Telosporidia to join transverse line embracing Gregarinida, Hsemosporidia, and Hremogregarinida. Page 51, third paragraph. For " infected " read " infections with." Page 1 18, line 9. " Become " at the beginning of line instead of at the end. Page 130. For " thieleri " read " theileri." Page 137, last paragraph. For " trypanosomes" read " trypanosomiasis." Page 138, fourth paragraph. After "arista" insert "and are." Page 142, last line but one. After " whole of" insert " the." Page 154, first line. After "acute" insert " : " Page 170, third line. After " It is" insert "at." Page 190. For " Chapter XIV. " read " Chapter XV." Page 197, in table, fourth line. For " 1-2 days " substitute " I-2." Page 213, second paragraph, line 3. After " neighbourhood " insert " of." Page 225, first paragraph. For " McAllum " read " McCallura." Page 229, seven lines from bottom. For " chelicera " read "appendage." Page 230, seventh line. For " Ixodinse" read " Ixodse." Page 234, second paragraph. For " veins " read " vein." Fifth para- graph : for " fig. 24" read " fig. 23." Page 246. For " Hsematobia pluvialis " read " Hsematopota pluvialis.' Pages 252 and 258. For " Marchand " read " Marchoux." Digitized by tine Internet Arcinive in 2010 witii funding from Open Knowledge Commons http://www.archive.org/details/tropicalmedicine01dani TROPICAL MEDICINE AND HYGIENE TROPICAL MEDICINE AND HYGIENE BY C. W. DAN I E LS M.B.Cantab., M.R.C.P.Lond. Director London School of Tropical Medicine ; Lecturer on Tropical Diseases, L^ondon Hospital ; Assistant Physician, Albert Dock Hospital, Seamen's Hospital Society ; formerly Director Institute for Medical Research, Federated Milay States; Metnber of Royal Society Malaria Commission, and in the British Guiana, and Fiji Colotiial Medical Services E. WILKINSON F.R.C.S.Eng., D.P.H., D.T.M. & H.Camb., Major I. M.S. Formerly Chief Plague Medical Officer, Punjab; Acting Sanitary Commissioner, Punjab ; and Professor of Hygiene, Medical College, Lahore In Three Parts, with Coloured and other Illustrations Part L DISEASES DUE TO PROTOZOA NEW YORK WILLIAM WOOD AND COMPANY MDCCCCIX V, \ PREFACE. The exigencies of tropical practice require most medical men to be practical sanitarians as well as clinicians. It is with this in view that in the present work, while due attention has been paid to the clinical features, treat- ment and nursing of tropical diseases, special prominence has been given to their etiology and prevention. Owing to the recent advances in the knowledge of the etiology of many tropical diseases the subject of their prophylaxis is a very promising one, since the general principles on which eiiticient and economical preventive measures should be based are now well understood. In the application of such general principles local conditions must be carefully considered, and thus in describing the various methods to be adopted those suitable for certain localities have been given as types. In the spread of many tropical diseases intermediate hosts play an important part, and the life-history of such hosts, often insects, has been considered at some length, as a knowledge of this subject is essential to the proper understanding of the rationale of the preventive measures proposed. An attempt has been made to group the diseases treated of according to their known or probable causation. Thus, in the first part those diseases are dealt with which, like Malaria, are known to be due to Protozoa, and others, such as Yellow Fever, which are probably due to such organisms. In the second part diseases due to the higher forms of animal life are considered. The third part is devoted to bacterial diseases, to the IV. PREFACE effects of certain animal and vegetable poisons and to certain diseases the causation of which is unknown or but imperfectly understood. The advantages of this arrangement are considerable, as the general outline of the prophylactic measures required differs for the diseases described in each part. Thus the measures described in the first part are mostly directed against arthropoda, insects or arachnida, which act as intermediate or alternative hosts for the malarial and other protozoal parasites. The measures described in the third part, including as they do those for dealing with cholera, enteric fever and plague, involve the consideration of the protection of water supplies, the disposal of sewage, disinfection and other sanitary problems ; while the measures dealt with in the second part include some directed against insects, as in the case of filariasis, and others, e.g., those for the preven- tion of endemic hsematuria and ankylostomiasis, dealing with the water supplies and sewage disposal : in both cases, however, involving somewhat different problems from those discussed in the other two parts of this work. Suitable technical methods of a simple character, as well as data and measurements in common use, are given in an appendix to each part. We are much indebted to numerous friends and past students of the London School of Tropical Medicine for valuable hints and aid in revision of proofs. Major J. B. Smith, Major J. H. McDonald, of the I. M.S., Dr. Venis, and Dr. H. B. Newham must be specially mentioned. The charts used for the illustrations are in most instances those of patients at the Albert Dock Hospital of the Seamen's Hospital Society, to which is attached the London School of Tropical Medicine. CONTENTS. PAGK ClTAI'lKR I. Introductory, Classification, and Life History of I'rotozoa ... i Chaptkr II. Sporozoa, General ... ... ... ... ... 12 Chapter III. Malaria, Benign Tertian and Quartan ... ... ... 15 Chapter IV. Subtertian Malaria, Pathology, Treatment, Complications ... 22 Chapter V. Parasites of Malarial Fevers, Varieties and Species ... ... 48 .Chapter VI. Prevention of Malarial Fevers, Mosquitoes ... ... 65 Chapter VII. Black water Fever ... ... ... ... ... 87 Chaptf:r VIII. Piroplasmosis, General ... ... ... ... ... 105 Chapter IX. Yellow Fever, Clinical Course and Prevention of ... ... 109 Chapter X. Flagellata, General ... ... ... ... ... 123 Chapter XI. Human Trypanosomiasis, Sleeping Sickness ... ... 131 Chapter XII. Kala-azar ... ... ... ... ... ... 144 Chapter XIII. Oriental Sore ... ... ... ... ... ... 167 Chapter XIV. Relapsing Fever, Indian, Clinical Course, and Etiology ... 172 Chapter XV. Tick Fever, and other varieties of Relapsing Fever ... ... 190 CtrAPTER XVI. Diseases due to Spirochtetas in the Tissues, Syphilis, Yaws, Granuloma of the Pudenda ... ... ... ... 199 Chapter XVII. Intestinal Diseases due to Protozoa, Amcebina ... ... 217 Appendixes. (i.) Notable Dates — • (ii.) Important Measurements — (iii.) Classification of Diptera — (iv.) Ticks — (v.) Further Sub- division of Diptera ... ... ... ... ... 225 Tropical Medicine and Hygiene CHAPTER I. INTRODUCTORY. The term Tropical Diseases is a convenient one though not capable of logical definition. Few diseases are limited to the Tropics or even subtropical regions. As employed in this work, it is meant to include all diseases which are not commonly seen or recognized in England but which are prevalent in tropical regions, and a few other diseases which present peculiar characters, or require special prophylactic measures in the Tropics. The peculiar distribution of many of the diseases met with in the Tropics is due to the fact that the parasites causing them require special conditions for their extra- corporeal existence. These conditions in the case of parasites such as ankylostomes, which do not require an intermediate host, are mainly warmth and moisture. Where, however, the parasites, like those of malaria, require an alternative host for their development, the conditions determining the distribution of disease are not purely meteorological, but include various other factors affecting the alternative hosts — in that instance, certain species of mosquitoes. The other factors include the presence or absence of special soil, of water suitable for breeding places, of suitable food for larvje, and so forth. The absence of natural enemies of larvae or adults has also to be considered. The distribution of such alternative hosts and, there- fore, of their parasites and the diseases caused by them, has a great tendency to be local and apparently erratic, .2 TROPICAL MEDICINE AND HYGIENE and to vary from time to time without any obvious reason. With closer study the reasons for such varia- tions can sometimes be traced. The varying results of prophylactic measures directed against such diseases, though on the whole satisfactory, are explained by the variations in these factors. The distinction between plants and animals, so obvious in the higher members of these kingdoms, is less definite in the unicellular organisms. Such distinctions as the presence or absence of chlorophyll, the absorption or assimilation of nitrogen and carbon from their inorganic compounds, or only from higher organic compounds, are not conclusive. Those organisms most closely related to the vegetable kingdom and those that appear to be animal may either be motile or non-motile. In so many instances is it impossible to determine whether the lowly unicellular organisms are animal or vegetable, that Haeckel proposes to make a separate kingdom of such forms which he calls Protista. The unicellular organisms approximating in most of their characters to the animal kingdom are known as the Protozoa. In the warmer countries the diseases due to the para- sites with characters in the main animal are of more special importance than those caused by parasites of the same division in cold climates. The protozoa for this reason are first considered. Protozoa are unicellular organisms. The cells may be aggregated together in mass or may occur singly. Frequently parts of the cells are specially modified for special purposes, such as locomotion, so that flagella or cilia are formed, whilst in other instances a part only of the cell is contractile and exhibits amoeboid movement. Many of the protozoa are non-parasitic ; others are parasitic only in the lower animals. Some are parasitic during a portion only of their existence, whilst others are parasitic in entirely different animals during the different stages of development. INTRODUCTORY 3 It is proposed to consider in detail only the protozoa parasitic in man, with brief reference to protozoa parasitic in other animals. The knowledge of disease-causing protozoa is advancing so rapidly that some information as to parasites of other animals may at any time become of importance in human pathology. The Protozoa are divided into four groups : — (r) Sarcodina include all forms which move by the protrusion of protoplasm either as blunt and broad pro- cesses or sharp and thin processes. They may be naked or covered in part with shells. Multiplication is by bud- ding or fission ; occasionally spores are formed. (2) Mastigophora or FlagcUaia are provided with motile apparatus specialized for the purpose and consisting of one or more flagella. All parts of the cell enter into the formation of the flagellum. The body is usually of a well-defined shape and covered with a cuticle or mem- brane. Multiplication is by longitudinal fission. (3) Sporozoa are unicellular parasites living during a portion of their life in cells and multiplying by the division of the whole or part of the protoplasm into young organisms commonly called " spores," more cor- rectly termed " merozoites." (4) CiUata {Infusoria). The motor apparatus is in the form of cilia which may be either simple or united into membranes. These are formed from the ectosarc only. Reproduction is effected by transverse division or budding. Of these classes it will be convenient to consider first the Sporozoa. Recent researches, especially those of Schaudinn, have gone far to throw doubt on this classification, for his work, if confirmed, would prove that the distinction between the flagellata and the sporozoa is not a sound one, as flagellates have a quiescent stage when thev resemble sporozoa. Much more work is necessary in connection with the protozoa and their sexual cycles and transformations before we can safely alter the present 4 TROPICAL MEDICINE AND HYGIENE classification, and any premature attempts at regrouping these organisms are to be deprecated. Development and Life-history. — This is not known in all the genera, but where it is fully known two methods of multiplication can be shown to occur — asexual or vegetative, and sexual. As types of the life-histories and methods of reproduction of the sporozoa those of coccidia and of the parasites of malaria may be taken as examples. In the coccidia entrance to the warm-blooded host is gained through the alimentary canal. The young coccidia spores, sporozoites, are set free from the cyst in which they are contained by the action of the digestive juices and penetrate into the epithelial cells of the intes- tinal mucosa, or of one of the appendages of the intes- tine such as the bile passages and the liver. When the young coccidia have entered such a cell they grow until they have entirely filled and destroyed it. Division of the protoplasm of the coccidium now takes place. The outer part of this has formed a cyst wall, and thus a cyst is formed containing a large number of young coccidia or spores. The cyst wall then ruptures, the young coccidia are liberated and pass into other intes- tinal or hepatic cells. The process is repeated over and over again, and massive tumours are thus formed by the coccidia which have multiplied asexually. Coccidia which develop into asexual forms are known as " schizonts." Some of the spores of young coccidia develop in a dif- ferent manner. No division of the cell contents takes place, but the protoplasm remains undivided with a single nucleus. A weak spot in the cyst wall, known as the micropyle, is present. Such forms are the female forms, inacrogametes, of the coccidia. Again, in other coccidial cells when they have reached their maximum stage of growth, the cell contents divide into a mass of bodies smaller and more actively motile than the spores. The small actively motile bodies are the male fertilizing elements equivalent to spermatozoa, and are known as microgametes. When the cyst containing them ruptures INTRODUCTORY 5 the microgamctes are set free and penetrate through the micropyle of the macrogamete and fertihze it. In the fertihzed macrogamete, now known as the .oocyst, various changes occur and the micropyle is closed so that the cyst wall is complete. The cyst is discharged and passed with the faeces of the host. Development of the contents takes place, the cell mass divides into Fig. I. — Diagram of development of Coccidia. Endogenous life includes the asexual cycle and the fertilization of the macrogamete by the microgamete. The further development does not require an alternate host. It takes place on the ground. four, and in each of these four divisions two spores — " sporozoites "—are formed. This stage of development takes place in the oocysts as they He on the ground, no host being necessary in this stage. This is the sexual form of multiplication. Ultimately when the cyst is 6 TROPICAL MEDICINE AND HYGIENE swallowed by a suitable host the capsule is dissolved, the sporozoites are liberated in the alimentary canal and enter cells in the mucosa or pass up the bile ducts in the liver and there recommence the cycle of events described, multiplying asexually to form massive tumours, or becoming sexual forms, gametocytes, male or female. This protozoal infection is common in rabbits ; it has been described in man, but is certainly extremely rare. It forms a good example of a sporozoal organism, parasitic during its stages of growth and asexual multiplication, but not throughout the whole of its sexual development (fig. I.) The general plan of development of the parasites of malaria resembles this to some extent, but there are important differences. The young parasites introduced by the mosquito into the human blood enter the red corpuscles. In these red corpuscles there is first a stage of growth until the maximum size is attained. No cyst is formed, but the remnants of the red corpuscle act as a cyst wall. When the full size is attained the protoplasm of the parasite divides into a mass of rounded bodies — the spores or " merozoites," which are set free by the rupture of the red blood corpuscles and rapidly enter other red cor- puscles in which the process of development is repeated, ending in a further liberation of spores. This process of asexual multiplication resembles the similar process in the coccidia, with the exception that no cyst wall is formed, and that the host cells, the red corpuscles, are in movement in the blood, so that the parasites are scattered and do not form massive tumours. Asexual multiplica- tion of the parasite of malaria may be continued for years but not indefinitely. A certain number of young parasites do not go on to the formation of spores but become potentially sexual forms — gametocytes. These, when mature, can be recognized as differing more or less in structure and appearance from the parasites which are to divide INTRODUCTORY 7 asexually — sporocytes — corrcspoiidin;^ to the schizoiits of the coccidia. No active sexual processes take place in man. The gametocytes do not undergo development unless re- moved from the human body. When their environ- ment is chans^ed, as it is when the blood is shed, or more certainly when it is sucked up into the stomach of a mosquito, the gametocytes become actively sexual and lose the protection of the remnants of the red blood corpuscles. Some of them, the females or macrogametes, are passive and receptive, and except for the extrusion of small rounded masses, the polar bodies, change little in appearance, whilst .others, the male forms, throw out fiagella which are actively motile and soon separate from the residual protoplasm. These fiagella are the equivalent of spermatozoa and are known as microgametes. They enter the macrogamete and fertilize it ; the fertilized macro- gamete soon becomes motile. It is called the travelling vermicule or ookinet (motile egg) as it differs from the oocyst (encysted egg), formed by the fertilization of the coccidian macrogamete, in that it is motile and not encysted. The ookinet passes into the stomach wall of the mosquito and comes to rest between the epithelial and muscular layers. It is now known as the zygote, is motionless and is enclosed in a cyst wall. Growth takes place, the cell contents of the zygote divide into several masses — zygotomeres — from the outer part of which innumerable thread-like bodies the zygotoblasts, or sporozoites, are formed. The cyst when fully mature is distended with these sporozoites and ulti- mately ruptures, discharging the motile sporozoites into the body cavity of the mosquito. These sporozoites accumulate in the secreting cells of the salivary glands. When a mosquito thus infected bites man, the sporozoites are injected into the wound through the proboscis. The sporozoites thus again reach their warm-blooded host and pass into the red corpuscles. This sexual phase is carried on entirely in the mosquito, the asexual phase entirely TROPICAL MEDICINE AND HYGIENE in man, and the organism of malaria is therefore parasitic in all stages of its development (fig, 2.) The names given to the parasites in various stages are numerous, and a few only are selected as those in most common use. The table appended gives the terms commonly used : — The term alternate host is used when it is not meant to indicate which cycle, sexual or asexual, is carried on in that host. ^"CI Fig. 2. — Development of malarial parasite. The exogenous cycle requires an alternative host — a mosquito. Intermediate and definitive hosts are more precise terms. The definitive host is the host in which the sexual processes of multiplication or reproduction are carried out. In the case of the parasites of malaria the definitive host is the mosquito. Intermediate hosts are those in which the asexual method of multiplication is carried out ; e.g., man is the intermediate host of the malaria parasite. INTKODUCTORY 9 Insects or other alternate hosts are not required for the propagation of all the various protozoa which cause disease, as in some, such as the coccidia and AuucJxl coll, part of the development takes place in earth (jr in water without an alternative host. Invertebrate hosts : The commonest alternative hosts, either intermediate or delinitive, are insects, but some of the ticks, ixodince and argasinae, may also serve as hosts. Table showing Comparative and Equivalent Terms used in the Description of the Stages in 'ihe Development of Protozoa. Scientific terms Schizogony Schizont... Merozoite (spore) Gameiocyte Microgameie Macrogamete Sp07-ogony Ookinet ... Oocyst . . . Sporoblast Sporozoite Description The asexual or endogenous cycle ... The parasite of the asexual cycle ... The young parasites resulting from asexual division The potentially sexual forms, male and female The fertilizing element or elements, "spermatozoa" discharged from the male gametocyte The female sexual form The sexual or exogenous cycle The motile fertilized macrogamete The non-motile fertilized macro- gamete, applied whether origin- ally motile or not The primary division of the proto- plasm of the oocyst (zygote) The final product of the sexual development formed from the sporoblasts or blastophores Terms commonly used in descriljing the develop- ment of the parasites of malaria Cycle in man. Sporocytes. Spores. Gametocyte. " Cres- cents " in subter- tian malaria Flageilum or micro- gamete. Macrogamete. Cycle in mosquito. Travelling vermicule. Zygote. Blastophore. Zygotoblasts, blasts, or sporozoites. Insects are infected with animal parasites in various ways : — (i) The blood-sucking nisects draw up with the blood any small parasites present in that fluid, such as the parasites of malaria. These parasites developing in the insect host are ultimately injected into a warm-blooded host — man in this instance — and multiply in that host. (2) In other cases, as in the development of piro- plasmata and the spirochasta in ticks, the development lO TROPICAL MEDICINE AND HYGIENE of the parasites taken up with the blood is continued in the eggs of the host, and the full development does not take place till the eggs are hatched and the young ticks are sufficiently developed to bite a warm-blooded host, when they will transmit the infection. (3) The parasites drawn up with the blood may develop in the lumen or walls of the alimentary canal and the sporozoites may be discharged with the faeces. (4) The larvae of the invertebrate host living in water become infected directly through their food with protozoa. These then develop and, as in the case of a monocystis described by Ross, multiply after encystment, so that when the insect has attained its perfect form — the imago — it harbours very numerous parasites which are deposited with the excrement and then live an indepen- dent existence till they re-enter other larvae. It is possible that many of the flagellata are thus transmitted. Protozoa are not the only parasites for which inverte- brates act as hosts. Several of the metazoa are conveyed in a similar manner. Bacteria also can be conveyed by such hosts. In some instances the insects merely act as mechanical carriers. Thus the ordinary house-fly may, after alighting on the excreta of a typhoid patient, carry the bacilli to human food, such as milk, directly. In other instances, blood-sucking insects take up bacteria, such as those of plague and leprosy, and may, in the former case at least, infect other animals. The bacteria present in the water in which larvae live are taken up by such larvae, and in some instances, e.g., Bacillus pyocyanetis, the bacteria continue to live during the various stages of development of the larvae and may be widely distributed by the adult insect or imago. The conveyance of vegetable organisms by insects will be more fully considered in Part III. Origin of Parasites. The question is sometimes raised as to the origin of parasites, and particularly of such parasites as are INTRODUCTORY II found only in so recent (geoUj^ically) a development as man. No direct genealogy can be diawn up for these parasites; they must be derived from pre-existing non- parasitic forms which gradually became parasitic during one, probably the sexual, cycle, and later parasitic thr(nigh- out their entire cycle. Possibly, this change first took place in birds or bats, and by development from them those parasites, which are now parasitic in man only, were developed. The intervening links are lost and any explanation can be merely hypothetical. Protista — Unicellular organisms. Characteristics mainly those of the veget- able king- dom, &c. Bacteria to be con- sidered, Tart III. Protozoa Characteristics mainly those of the animal kingdom. Sarcodina — represe nted by the Amaba coli. Mastigophora — including Spi- rochjet3e,Leish- man -Donovan bodies, Try- pa nosomes, Trichomonas and Lamblia in man. Sporozoa— Telosporidia Metazoa I Animal Parasites, Part II. Infusoria — represented in man by the Balantidizini coli. Neosporidia Gregarinida — Parasitic in earth-worms and many invertebrata. Coccidia : parasiiic in many animals, very common in rabbits. Have been observed in man. Species (?) Sarcosporidia Myxosporidia. Hsemosporidia Hcemo- gregarinida — In reptiles and few mammals. Babesia or Piroplasma — Hjemamceba — Parasitic in cattle, horses, Including H. relicta (proteosoma) sheep, dogs, &c. in birds and at least three species, the cause of malaria in man. 12 CHAPTER II. The classification of the Sporozoa is still in dispute, and various schemes have been propounded from time to time. There is no authoritative classification at present. The scheme here given is a useful one, but is not to be regarded as final or as even univ^ersally accepted. Sporozoa. (a) Those in which the entire protoplasm, with the exception of dead residual masses, divides into spores, the parent protozoon disappearing in the process. Telosporidia, e.g., parasites of malaria, coccidia, &c. In this group are included the sporozoa that cause the most important diseases of man and the lower animals — malaria, Texas fever, &c. The group is variously divided by different authors and protozoologists. The classification here given is con- venient for the purpose : (i) Gregarinida ; (2) Coccidia; (3) Hcemosporidia ; (4) H cemogregarinida. (i) Gregarinida. — The body is of a constant elongated form. They are distinguished by their peculiar creeping movements. They are parasitic in cells of the intestinal walls of the various invertebrates during the early part of their existence, and later are free in the intestinal cavity or its appendages, where they become encysted, and the cell contents have been shown in rare instances to undergo division into spores. Reproduction. — Sexual reproduction by the conjugation of two cells which resemble each other. (2) Coccidia. — Of a spherical or oval shape, and con- tained in definite cyst walls when mature ; only the youngest forms are motile. Fecundation by the con- jugation of dissimilar cells. They are parasitic in cells SPOKOZOA 13 of warin-blooclcd animals and invertebrates, and fre- quently form massive tumours. They have been deseribed in man, but little is known at present of human diseases caused by them. Very common in rabbits. (3) Hcvinosporidia or Hcvinocylozod. — Parasites of the red blood corpuscles of warm-blooded animals ; do not form cysts in such hosts; are parasitic throu-^hout their whole existence, the sexual phase taking place in inverte- brates, e.g., insects or ticks. The young forms have active amoeboid movement. They are divided into two main groups : — {a) Ha'inamcebcc, which form pigment, and usually divide into a large number of spores. The definitive hosts are mosquitoes. Fig. 3. — Piroplasmata. (b) Piroplasmata (fig. 3), which do not form pigment ; divide into two or more spores. Ticks are the definitive hosts. Piroplasmata have been described in man, probably erroneously; common in cattle, sheep, horses, dogs, &c., and usually lead to extensive blood destruction, e.g., Texas fever in cattle, and hasmoglobinuria in sheep and dogs. (4) Hcemogregarinida are, by many authors, included in the Hccmosporidia. The young forms are found in red corpuscles of reptiles (fig. 4), and in few instances in red blood corpuscles of mammals, as in the Indian rat and the African jerboa. They may also be found in leucocytes, as in the dog and in the palm squirrel. Older forms moving like gregarines are found free in the blood plasma. Sporulation takes place in cells of solid viscera, such as the liver and in the bone-marrow. It appears to be doubtful what are the definitive hosts ; M TROPICAL MEDICINE AND HYGIENE in the dog hcemogregarine they are ixodhia. They do not form pigment, and differ from the Jicsinosporidia, in the restricted sense, in the structure of the nucleus of the young parasite. The nucleus stains with basic stain, and the chromatin is distributed in fine granules throughout the nucleus. Segmentation does not take place whilst the parasites are present in the blood. No Jiccniogregarines are known to occur in man, and it is only recently that they have been found in mammals and birds (fig. 4 and Plate II.) Fig. 4. — Haetnogregarines of frog. (B) Only a portion of the protoplasm of the cell divides into spores. The parent protozoon still remains alive, further growth takes place, and again, part of the new protoplasm divides into spores. This process, repeated indefinitely leads to the formation of large masses composed of spores enclosed in the much dis- tended parent cells. Neosporidia, e.g., Sarcosporidia. — The Neosporidia are too little studied to be fully considered at present. They are divided into Myxosporidia, which occur in fishes and in silkworms, and Sarcosporidia, which are very common in the muscles of domesticated animals, and are rarely found in man. They are not known to cause any human disease. 15 CHAPTER III. DISEASES CAUSED BY H^MOSPORIDIA IN MAN. Malaria. (Synonyms : Ague, Fever, Marsh Fever, Puliulisiii, Intermittent Fever, &c.) Malaria is the general term applied to the diseases caused by the human haemosporidia commonly known as the parasites of malaria. The prominent symptoms are those of febrile disturbance ; the fever may be regu- larly periodic, irregularly intermittent, or remittent, and later visceral changes, especially enlargement of the spleen, and pigmentation of the spleen and liver, may occur. The febrile symptoms yield readily to treatment by quinine. The parasites are conveyed from man to man by various species of mosquitoes, belonging to the sub- family Anophcllna. There are at least three species of parasites and the symptoms differ according to the species of the parasite with which the patient is infected. Geographical Distribution. — Malaria occurs in most tropical and sub-tropical countries, with the exception of certain groups of islands, such as the Seychelles in the Indian Ocean, Fiji, the Society and Friendly Islands in the South Pacific, Barbados and St. Helena in the Atlantic Oceans. In temperate regions the distribution is more irregular, and is frequently limited to low-lying country, and the course of rivers or their estuaries. Elevation has a decided effect in temperate regions, but in equatorial districts malaria may be still common 4,000 or 5,000 feet above the sea. The topographical distribution of malaria is affected bv many conditions, such as density of population, but is 1 6 TROPICAL MEDICINE AND HYGIENE mainly determined by the species of mosquito present, and the abundance of suitable breeding places for such mosquitoes. Clinical Varieties of Malaria, and Species Associated with these Varieties. Benign tertian ; Tertian Fever. Geographical Distribu- tion. — It occurs in all the malarial tropical countries, but is rarer in Africa than in the East, In sub-tropical and temperate countries a larger proportion of the cases are benign tertian and it occurs further north than the other forms of malaria. It used to be common in some parts of Great Britain and, rarely, cases still occur. The clinical course of an attack of benign tertian malaria is regular, though in a first attack of a severe type the periodicity may not be well marked. The attacks of pyrexia are short, lasting some six or eight hours. The temperature rises suddenly, and there is a rigor, often so severe that the bed on which the patient is lying is shaken. The temperature rises to 105° F. or more, and the pulse is quick and bounding. The urine presents the usual febrile characters. The skin is cold and the features pinched, whilst the lips may have a bluish tinge. Following the cold stage is the hot stage, and during this the patient still has fever, usually high, severe head- ache, and the skin is dry. This stage may last for two or three hours, and is succeeded by a sweating stage during which the temperature rapidly falls. With the onset of the diaphoresis the patient becomes much more comfortable, and the temperature rapidly falls to or below normal, when, beyond a certain amount of debility, or sometimes a mild form of collapse, the patient will feel well and be able to resume his occupation. The next day, and till forty-eight hours after the occurrence of the rigor, the patient remains to all appearances in normal health. At the end of this period DISEASES CAUSED I5Y HA<:M0^P()]<\1)\A IN MAN 17 there is another siinil;ii" jiyrexial attack, aiul on eacli alternate day in an untreated case tliese attacks of pyrexia recur. Even without active treatment, sooner or later the paroxysms diminish in severity, and gradually dis- appear altogether, and the temperature may remain normal or subnormal for two or three weeks, when another series of febrile paroxysms on alternate days will occur. These attacks of tertian fever alternating with apyrexial intervals may continue for two or three years. During the whole time the patient is suffering from infection with parasites of malaria, and visceral changes, especially enlargement of the spleen, are likely to occur, as well as anaemia and general debility. Death is unusual even if treatment be neglected, and in fatal cases there is usually concomitant disease. TIME M E M E ^ 1 E M E ^ n E M E M E M E M E M "e^ M E M E M E F° 105 104 103 1 02 10 1 100 99 98 97 I \ \ ' t 1 , \ \ 1 I. N \ I \ 1 ^ V "^1 V ^i V V. *^ i ^ ^ J V * V. -V >*- y" Fig. 5. — Simple Benign Tertian. In a simple benign tertian the character of the pyrexial attacks and the regular periodicity of their recurrence enables diagnosis to be made readily. Blood examina- tion showing the presence of the parasites confirms this diagnosis, and it is the only way in which it can be made if the patient is seen during the apyrexial attack. In many cases of the disease the fever is quotidian, that is, a pyrexial attack occurs every day. This is the so- calied double tertian, and is due to the co-existence of 2 15 TROPICAL MEDICINE AND HYGIENE two generations of the parasite maturing on alternate days. Sometimes the double character of the infection is obvious clinically, as the pyrexial attacks vary in severity, being alternately severe and mild (fig. 6). In a double TIME M E M . M I . M f : M E M E M E M E M E 105 I04 I03 I02 lOI lOO 99 98 97 1 ' A \ \ r^ [} \/ V V '\ ^ r ^ / ^r^ V V Fig. 6.— Double Tertian. tertian the more frequent recurrence of the pyrexia causes more rapid development of anaemia and debility, and the prognosis therefore is more serious. The nature of the disease may be suspected from the completeness of the apyrexial intervals, from the character of the pyrexial attacks, and in some cases because the pyrexia occurs in the morning, whilst in most forms of quotidian intermittent fever, the pyrexia is in the evening. A cer- tain diagnosis cannot be made without an examination of the blood. 7*; t;;=: ■3= =3 ER m Fig. 7. — Quartan Fever. Quartan Malaria. — Clinically, this form closely re- sembles benign tertian, but differs from it in that in a simple infection the pyrexial attacks occur with an interval of two days between them (fig. 7). The character of CLINICAL DIAGNOSIS IN MALARIAL KLVKK' 9 each attack is similar to that of beni.^n tertian. Quartan malaria is less widely distributed than benign tertian, but also occurs throughout the Tropics. In some districts cases are as numerous as those of benign tertian, or even more so. As a rule in such countries quartan will be commoner amongst the poorer classes and tertian amongst the well-to-do, but no race or class is exempt. The reason for the irregular distribution of quartan is not known. Double and triple infections of quartan malaria occur, due to two or three generations of the parasite being present in the same patient, and reaching maturity at intervals of twenty-four hours. With three generations the fever would be quotidian, with two TIME M E M E M E M E M e: M E M E M E F° 104 I03 I 02 10 1 1 00 99 98 37 K f, ^ \ \ \ It , A \, y I L -,/ \ N J \ V \ ^ V Fig. 8. — Double Quartan. generations there would be fever on two days and then a day free from fever, followed again by two days with fever and so on (fig. 8). The effects of quartan malaria are very similar to those of benign tertian, but it is more dangerous to life, especially in cases of dis- turbed cardiac action, such as in beri-beri. It persists for a longer time, and often yields less readily to quinine. Clinical Diagnosis. — The single and double infections are easy because of the peculiar periodicity. In a triple infection the quotidian periodicity may not only be confused with double tertian, but with any diseases in which quotidian fever occurs. Prognosis is good in uncomplicated cases if well treated. 20 TROPICAL MEDICINE AND HYGIENE Pathology. — The malaria parasites of both the benign tertian and quartan fevers circulate freely in the blood throughout the body. When the parasites are full-grown they have a tendency to remain in the splenic sinuses, probably because the red corpuscles containing such parasites are so altered as to adhere to the walls of the smaller vessels. This tendency is more marked in benign tertian than in quartan, but in both numerous full-grown forms will also be present in the peripheral blood. The rigor follows shortly after sporulation. For some unknown reason, with both species of parasites, the stages of growth are completed either all about the same time, or at periods differing by twenty-four hours from each other, consequently parasites of intermediate ages are rarely met with. The sporulation of these parasites leads to rupture of the red corpuscles, when the spores together with the remains of the parasites, pigment, and any other products are set free in the plasma. The simplest explanation of the observed clinical phenomena is that amongst these varied products are (i) toxins that act on the heat-controlling centre, and (2) hjemolytic toxins, variable in amount ; and (3) toxins affecting innervation. Blood serum taken before a rigor and passed through a Berkefeld filter will, when injected into a healthy man, cause a febrile paroxysm similar to that which occurs in malaria. Of the bodies set free, the spores rapidly enter other red corpuscles, and recom- mence the cycle, or failing to do this are destroyed by phagocytes or by the blood plasma, and this destruction IS facilitated by the action of quinine. The pigment is taken up by the leucocytes, usually by the large mono- nuclear or hyaline cells, and ultimately deposited in the spleen, which becomes, in a chronic case, of a deep slate black colour. It is also deposited in the connective tissue cells of the liver. In an earlier stage the spleen may merely appear to be congested, but on microscopic examination abundant deposits of pigment will be seen even then. TREATMENT IN MALARIAL FliVli\i 21 TreaUncnl. — Quinine in any form and in moderate doses will rapidly relieve the symptoms, but to pievent relapses must be continued in diminished doses for months. Tiie patient should be kept in bed, not only during the pyrexial period, but in the intervals, for t\V(j or three days after a pyrexial attack. Quinine is far more effective in a person kept at a uniform temperature in bed and on light diet. The bowels must be kept open. Simple rest and diet will often, without any medicine, cause temporary disappearance of the symptoms. 22 CHAPTER IV. SUBTERTIAN MALARIAL FEVER. Malignant tertian, subtertian, aestivo-autumnal, and tropical malaria are some of the names applied to the re- maining forms of malaria, viz., those due to infection by parasites, which pass the greater part of their asexual stage in the visceral capillaries. Young forms and gametocytes are found in the peripheral blood. The gametocytes are the sausage-shaped bodies known as "crescents." It is not certain whether there is more than one species of these parasites. The geographical distribution of this is more limited than of other forms of malaria. It is the commonest form in the Tropics, and was called by Koch tropical fever. In temperate regions it is not found as far north as benign tertian, and in the south of Europe it occurs later in the year than other forms of malaria, i.e., in the summer and early autumn, and was, therefore, called by the Italians cestivo-autumnal. Clinically it has a less regular and definite course than the other forms, and the stages of the pyrexial attack are ill-defined, whilst the periodicity is uncertain. There is a great liability to sudden onset of pernicious symptoms, often fatal, even in cases apparently not very severe. Hence the name malignant tertian. Sometimes before the fever there are aching pains in the back and legs; these myalgic pains may become worse with the onset of the fever, or in other cases disappear, , The pyrexia presents few diagnostic characters. The tendency so marked in tertain and quartan for the parasites all to sporulate about the same time is less constant. Subtertian parasites of all ages may be found at the same time in blood removed from the viscera. SUHTERTIAN MALARIAL KLVKK 23 though a majority may be abcjut tlic same age. The pyrexial attack following sporulation is therefore neces- sarily less defined, as the toxin is being formed during a far longer period. The cold stage is less often marked by a rigor, frequently merely by a feeling of chilliness ; the hot stage is prolonged and the sweating stage is often intermittent, consisting of a series of attacks of dia- phoresis with hot dry intervals ; the whole pyrexial period may last for more than twenty-four hours. The interval in such cases is short, as the whole cycle of development of the parasite appears to be under forty-eight hours (figs. 9 and 10). TIME A.M. P.M. A.M. P.M. A.M. P.M. A.M. P.M fiy.M. PM. A.M. P.M A.M P.M. A.M, P.M. a.mJpm.] F° 105 104 103 ro2 1 01 too 99 98 97 96 K ^ ■1, ) \ 1 ^ i \ v \ r V t( -1 , \, J V \ \ f u V, V , \ 1 V / \/ y \ v\ V \. 4 / V vv J V V l^ v "h If Fig. 9. — Subtertian Malaria with definite Tertian Periodicity. In other cases the pyrexial attack is still more pro- longed, and the interval correspondingly shortened. Xot uncommonly in a severe attack there is no interval during which the temperature is normal, but merely a remission. Such a fever is therefore not intermittent, but remittent (tig. 11). Vomiting is common and may be persistent. When exceptionally severe and bilious, particularly if asso- ciated with jaundice, it is often popularly called bilious remittent fever. Constipation is the rule, but there are exceptions. In many of the cases of this form of malaria the temperature is not high, sometimes not exceeding 100^ or loi'^ F. (tig. 12). 24 TROPICAL MEDICINE AND HYGIENE In benign tertian, in spite of the severe attacks of fever, the patient may be in good health during the intervals. In subtertian this is exceptional. The patient may be able to be up and force himself to attend to business or pleasure, but these attempts at "lighting the fever" are responsible for many serious errors of judgment, as well as causing serious risk to the patient. Children are said by some to suffer little or not at all, and there is a certain amount of truth in this as they may, whilst harbouring the parasites, be capable of playing about and taking interest in their surroundings. Careful enquiry, however, will usually show that during a great part of the day they are listless, do not take food, or otherwise show signs of ill-health. They have usually a definite enlargement of the spleen. Labial herpes is common in malaria, but as a rule does not occur till late in the attack, and frequently occurs when the fever begins to subside. The great peculiarity of subtertian fever is the liability, with little or no warning, to the so-called pernicious manifestations. These are in the main due to blood stasis in different organs of the body, caused by the numbers of red corpuscles containing the parasites ad- hering to the walls of the capillaries, and obstructing the circulation in that organ. This may occur in any organ, and the effects and clinical manifestations vary accordingly. (i) When stasis of the blood occurs in the capillaries of the central nervous system the danger is great, and a large number of deaths are due to this condition. The symptoms vary in adults and in children. In adults the patient usually has a flushed face and appears to be dull and stupid with slow speech and uncertain gait. In appearance and demeanour he is not unlike a man in the early stages of intoxication. This stupor may pass off in mild cases, but in others rapidly increases, and a condition of coma supervenes. There are no convulsions in the great majority of cases and no localizing symptoms. In a fatal case the coma deepens. vSUBTERTIAN MALAKIAL KKVER 25 Fig. 10. — Subterlian Malaria. Periodicity still definite. TIME A.M P. M A.M. P.M. A.M. PM A M |PM A.M. P.M. A M P M A.M P.M. 103 1 02 10 I 1 00 99 98 97 96 P , \. M r 1/ \ n \ \ r \ V, / \ n fN \ V I \ / V \ \ , ' { A r i V 1 \ \1 V M" — r 11 l Fig. II. — Subtertian Malaria. Periodicity indefinite. TIME M E M E M E M E M E M E M E F° 104 1 03 1 02 1 ) 1 00 99 99 97 A A r .'^ A / \ / s V ^ V V V V /^ V Fig. 12. — Subtertian Malaria (un- treated). Slight fever only. No definite periodicity. Diagnosis based on blood examination. TIME A.M. P.M A.M PM A.M. P.M. A.M P.M. F° t06 105 1 0^ 1 03 102 1 1 1 00 99 96 97 A, 1 \ V / \ 1 J / \ \ V V \ \ y \ 1 \ \ 1 \ 1 i Y "^.A W Fig, 13. — Severe Subtertian Malaria (treated). 20 TROPICAL MEDICINE AND HYGIENE the breathing becomes stertorous and the conjunctivae insensitive. Even at this stage recovery may occur with energetic treatment, or rarely even without it. Recovery when it occurs is rapid and complete, the patient in twenty-four hours may appear to be in fair health. There is no more striking instance of the effects of vigorous treatment than in a case of this kind. If untreated and the patient recovers, the attack usually recurs and is then fatal ; very rarely does he survive two attacks at short intervals without antimalarial treatment. In children the onset is less gradual, usually the first thing noticed is a convulsion. When this has occured other convulsions rapidly follow, the child remains coma- tose between the convulsions, and death occurs in four to twelve hours from the first attack. Even when the convulsions have continued for two or three hours, recovery is the rule with energetic treatment, and is complete. Such convulsions are the usual evidence of cerebral malaria up to the fifth year of life. After this period coma without convulsions begins to be more common, and after the tenth year convulsions are highly excep- tional. Epistaxis is common. In these cerebral cases the temperature may be little raised, or temperature up to 105° F. may be noted. Hyperpyrexia is said occa- sionally to occur. (2) The lungs may be a preferential site, and there is increased rapidity of breathing. Provided that the con- dition of the heart and lungs is sound there is compara- tively little danger. The congestion of the lungs induced, though it may give rise to suspicion of pneumonia, does not seem to be serious in itself. In any condition of cardiac disease, or in pulmonary conditions such as emphysema and bronchitis, the danger is greater, as the effect of such diseases is aggravated. In cases of tuber- culosis there is often haemoptysis. (3) If the abdominal viscera, and particularly the intestinal capillaries are blocked, the congestion induced SUIiTEKTIAN MALAKMAI. I f V \ A r •>^ > ' \ \ ' \ N <1 V '\ y \ I V \ -\ k, A ' -^ s S ( /\ ^ / s/' \ V Ou •at ?/> I/'. fe/ 70^ '0^ '" Fig. 30.— Blackwater Fever, severe attack ; hsemoglobinuria, two and a half days. Jaundice, or a yellow staining of the skin and, con- junctiva, can be observed a few hours after the onset of the haemoglobinuria, and deepens during its continuance. The stools are always dark, the urine does not contain bile, and enlargement or tenderness of the liver does not usually occur. The duration of this stage of hcemo- BLACKWATIiR FEVIiK 9 1 glohiniiria varies ^n-eally ; it may last only two or three hours, but is usually in a moderately severe case from two to three days. If it lasts more than three days tlie pro^s^nosis is very ^rave. There is usually much mental anxiety, partly on account of the reputation of tlie disease, but still more because of the large amount of blood-like urine that is being passed. The mental faculties are quite clear, and beyond the debility there is little actual distress. The amount of haemoglobin passed steadily diminishes, though still sufficient to render the urine opaejue. The last urine passed in this' stage often contains no oxyhaemo- globin, but methaimoglobin only, the urine changing from a red-black to a dark brown colour. As the urine clears the temperature falls to normal or subnormal. Profuse sweating may occur several times in one day. The change from the hasmoglobinuric period to the non-haemoglobinuric is less abrupt than would be judged by mere superficial examination of the urine. The haemolytic process has ceased, and the waste products are being rapidly eliminated. As the haemo- globin disappears the diuresis diminishes, so that even when abundant fluid is supplied the rate of secretion of urine may fall to much below normal. This is prob- ably merely the result of the over-stimulation of the renal cells, so that secretion becomes slow. If any urine at all is passed, a fall in the rate of secretion to less than half the normal is to be expected and should cause no alarm, though fluid must still be supplied freely. The rate of secretion in a favourable case soon increases. The urine is clear and of normal colour, but contains a small amount of albumin and some casts. The patient remains in an extremely weak condition, and the anaemia may show a slight increase, though the appearance of the blood corpuscles is more natural. The temperature may remain normal or commence to rise. After a day or two the temperature rises, usually above normal, and for several days there may be irregular pyrexia, secondary 92 TROPICAL MEDICINE AND HYGIENE fever. This varies a great deal in severity. In some cases it is very slight, the temperature rising in the evening to ioo° F. or even less (figs. 29 and 30). More frequently the nocturnal rises are to 101° and 102° F., the temperature falling nearly to normal in the morning. In other cases it is much more severe, and occasionally there is fatal hyperpyrexia in this stage. The usual duration of this stage is three to four days, and it may be protracted to two or three weeks. The urine in this stage remains free from haemoglobin and usually from albumin. No further blood destruction is taking place, and the red corpuscles and haemoglobin are rapidly in- creasing at a rate sometimes of 400,000 or 500,000 corpuscles per c.mm, per week. The secondary fever is probably associated with the metabolic changes due to the absorption and assimila- tion of some of the waste products of the haemolysis, which have been stored up in various organs. The icterus rapidly disappears. After this secondary fever has subsided, convalescence is rapid and usually unin- terrupted. It is highly exceptional for anyone who has had blackwater fever to have any malaria attacks for a prolonged period; probably the corpuscles containing parasites are amongst the first to be destroyed, and so a " cure " of the malaria results. Sometimes, as in a few cases in England, an attack of malaria may occur shortly after the blackwater fever, though a new infection has not occurred. There are few sequelae, but the debility and anaemia persist to some extent for several weeks, and fatal cardiac failure has occurred during convalescence. If fluid is not freely supplied the history is very different. The urine, whilst still loaded with haemo- globin, diminishes in amount, and vomiting becomes incessant. The amount of urine continues to diminish so that only an ounce or less is passed per diem. This urine may become free from haemoglobin and even from albumin, the temperature becomes normal, the BLACKWATKR KKVKK 93 aiiiomiii diminislics, but unless the flc^w of urine is rapidly restored death is certain. This usually (occurs in four or five days or less, hut life may be protracted up to ten days. There is no delirium, no convulsions, the mind is clear, and beyond headache, whicli is not necessarily severe, there are none of the ordinary symptoms associated with renal disease or uraemia ; vomiting is persistent. The condition more closely resembles that due to blockage of the ureters. This is the commonest cause of death, and if it can be avoided the mortality from blackwater fever is low. Duygiiosis. — The diagnosis is made on the character of the urine. This is dark red, practically black. If diluted the red colour appears and the urine is clear and trans- parent. On shaking the urine the froth that forms on the surface is red. If allowed to stand a thick deposit soon forms, but this is not present when the urine has been recently passed. The deposit in the quite fresh urine is scanty. A few casts may be found, and later in the course of the disease are more abundant ; some may still be found weeks after the urine is free from albumin. These casts are usually granular and contain bright yellow granules, not uric acid, similar to those found in the organs ; blood cells are rarely found ; bladder epithelium may be moderately abundant after the first day. When the urine is kept much deposit is formed; this is composed usually of casts, coagulum and altered haemoglobin. The urine in paroxysmal haemoglobinuria is similar, and that disease w^ould certainly be diagnosed as black- water fever if a case occurred in a blackwater district. If methaemoglobin only be passed the difficulty in diagnosis is much greater, as the brown urine is not very unlike some high-coloured normal urine, and may be mistaken for bile-stained urine. In all cases if the urine be boiled the albumin coagulated will be a dark brown colour. a E C I) El. F 75:70; ; I feS 63 55 50 4>0 ii: ;l ri m Tr 4^ Tl M M Fig. 31. — I, Oxyhemoglobin; 2, reduced hEemoglobin ; 3, CO. hsemo- globin ; 4, methsemoglobin ; 5, meihgemoglobin (after addition of alkali) ; 6, alkaline hsematin ; 7, acid heematin (etherial solulion); 8, hsematopor- phyrin (acid) ; 9, hsematoporphyrin (alkaline) ; 10, bilirubin. BLACKWATICK KEVER 95 The best test to apply is the speeti'oscopie one: Ix^lh the hcemoglobin ;ind methcemoglobin can be recognized at once and with certainty by the use of any of the simplest and cheapest direct vision spectroscopes. The addition of ammonia will cause the colour to change so that it becomes red, something like the colour of haemoglobin. (Spectra, fig. 31.) The absence or great rarity of blood corpuscles readily distinguishes this disease from any of the forms of hasma- turia. Without microscopic examination the transparency of the diluted urine in blackwater fever distinguishes it from the smoky opalescent urine of haematuria. Prognosis. — If suppression of urine is averted the prog- nosis is good. Constant vomiting and hiccough are of unfavourable import, and great care has to be exercised in order to prevent syncope or cardiac failure. Recurrences of the haemoglobinuric attacks sometimes occur at short intervals. Such a relapse may take place within twenty-four hours of a serious attack, or be delayed for three or four days ; it is rare after that period. As each attack runs its own course, a fatal degree of anaemia may be induced, and in each attack there is the same liability to suppression of urine. A person who has once had blackwater fever appears to be specially liable to it, and, if he remains in or returns to a country where the disease exists, will probably have other attacks. These are usually of a similar character to his first attack, so that, if his first attack was a mild one, subsequent attacks will probably be of the same nature. Cases are known of twelve, or even more, such attacks in one person. If, however, the first attack is severe, so will subsequent attacks be, and few persons will survive the third or fourth attack. Pathological Anatomy. — No specific organism has been discovered. Malaria parasites are present when the blood is examined before the onset of the disease ; thev dis- appear in these cases very shortly after the onset of the haemoglobinuria. In the great majority of cases of 96 TROPICAL MEDICINE AND HYGIENE blackwater fever, those examined only after the onset of the disease, no parasites are found. In fatal cases on microscopical examination of the liver and spleen, finely divided intracellular black pigment will be found as in recent malaria. Frequently it is not abundant enough to be seen on inspection with the naked eye. No parasites are found in the organs, but sometimes pigmented leucocytes are present. The blood examination shows an increase in the large mononuclear elements, such as is found in malaria, but this also occurs in other protozoal diseases. No piro- plasmata have been found, and the blood and organs are sterile as regards bacteria. The organs show all the usual evidences of blood destruction. In the hepatic cells, in the convoluted tubules of the kidneys and in the spleen, are abundant deposits of haemosiderin, and other granules not pigmented are present which give the reaction of iron in inorganic combination. This evidence of blood destruction occurs to a less marked extent in some cases of malaria and in other diseases attended with hzemolysis ; it is marked in the piro- plasmosis of cattle. The kidneys in all cases show casts in the tubules. When death has occurred from suppression these casts are very numerous. They usually show evidence of the presence of iron in inorganic combination. The renal cells, except for the presence of hsemosiderin, are singularly little affected. The epithelium is neither detached nor necrotic, but usually shows cloudy swelling and sometimes fatty degeneration. The spleen may be enlarged or not. The liver, beyond the evidence of haemolysis and a certain amount of cloudy swelling, is normal in appearance and structure. Subserous haemor- rhages and haemorrhages into either solid or hollow viscera are exceptional. Treatment. — No drugs have any specific action. The depth of colour of the urine passed early in the attack enables a fairly accurate estimate of the duration of the liLACKWATKR FICVKR 97 hiumolysis to be made, and tliis is not shortened bv treatment with quinine or any other drug used. Though we cannot deal with the essential cause, as this is un- known, much may be done to avoid the main dangers of the disease. The failure to recognize these essential features has caused the adoption of injurious measures from time to time. The disease is not a haimorrhagic one ; it is a hccmolytic one. The actual disease occurs in the blood-vessels, and the red corpuscles, once broken up, set free the haemo- globin in the plasma, and there it is injurious and has to be disposed of. The liver and other organs can absorb it in part only, but the capacity of these organs is limited and the greater proportion is discharged with the urine. This discharge must not be checked, but aided by the free supply of water. If considered as haemorrhage it would be natural to attempt to diminish this discharge. The patients themselves notice that they fill chamber- pot after chamber-pot with what looks like almost pure blood, and are anxious that the loss should be diminished, as they fear that they are bleeding to death. The medical attendant requires a firm faith in the soundness of his pathological views, and his action should be to main- tain, and if possible increase, the total amount of the bloody urine discharged. The dilution of the urine makes no obvious difference in its appearance, and, from the point of view of the patient and his friends, the measures that should be taken will only increase the loss. Free administration of water is necessary to maintain this flow, otherwise there is danger of such extensive coagulation in the renal tubules that suppression will occur. The drugs used have belonged to manv classes. Haemostatics, such as ergotin, have been extensivelv used, but can have no good effect. Water has been withheld in order to stop the loss, and this practice is responsible for much of the mortality. Stimulating diuretics, such as turpentine, have been employed, but the haemo- globin in itself acts as so powerful a diuretic that it is 7 9o TROPICAL MEDICINE AND HYGIENE unnecessary to employ any additional one. Quinine should not be given unless parasites of malaria are found, and even then must be given very cautiously. Quinine in large doses usually has no effect at all. Patients may recover whilst taking 60 grains a day, but it does not shorten the duration of the disease. In these doses it may increase the tendency to vomiting, and as in some cases it actually causes further haemoglobinuria it should not be given. Good results are claimed for the frequent adminis- tration of boracic acid in solution, and of carbonate of soda in moderate doses, with perchloride of mercury in minute doses frequently repeated. They all have the advantage of increasing the amount of fluid taken by the patient, and perchloride of mercury and carbonate of soda given as in yellow fever seems to check the vomiting and also acts in the late stages as a bland diuretic. This treatment has been practised by Hearsey with excellent results. Carbonate of soda... ... ... ... ... 5 grains. Perchloiide of mercury ... ... ... ... g'j grain. Water ... ... ... ... ... ... 2 oz. This dose should be given every hour till the urine clears. The most uniformly successful treatment consists in giving frequent rectal enemata, 6 to 8 oz. at a time, of normal saline solution ; water alone is not retained. These must be repeated every hour, or every half-hour, according to the severity of the case, till the haemo- globinuria ceases. The injection of large quantities of sterilized normal saline into loose cellular spaces such as the axilla is preferred by some. This cannot be repeated so often as the rectal injections, but must be employed in cases where there are both vomiting and rectal irritability. The great point is to commence the treatment early. If this is done from the onset, fluid by the mouth only will suffice, as the vomiting is to a great extent due to the renal obstruction, and if the latter can be prevented, or only a few tubules are blocked, the vomiting can be controlled. BLACKWATER FEVEK 99 If suppression has set in, recovery does not take place, but there is just the possibiHty that the free supply of fluids may enable a sufftcient flushing to take place to dislodge some of the casts and so restore the functional activity of a part of the kidneys. Alcoholic stimulants are required in all severe cases, but their use should not be commenced too early ; strychnine also should be given. The patient is usually constipated ; but active purga- tion is probably injurious, as it diverts into the intestine the fluid that we wish to pass through the kidneys. During convalescence good, easily digested food must be given. The digestive powers are usually good. The bowels should be kept freely open with salines. Iron and arsenic may be taken with benefit in the later stages, but there is no advantage in giving them early, as all the actively metabolic organs are at that time overloaded with iron. For the secondary fever free purgation seems to be the most effective. Quinine has no beneficial action and may provoke a relapse. Phenacetin and other anti- pyretics are to be avoided ; their action is temporary and the danger of cardiac failure is great. In hyperpyrexia during this stage hot packs, cold packs, or cold baths may be resorted to, but the prognosis is most un- favourable. Relapses must be treated in the same way as the primary attack. In the exceptional cases where an attack of malaria follows blackwater fever, quinine should be given in small but gradually increasing doses, commencing with •|-grain doses. Nursing. — Duiing the first day of the illness the main precaution to be taken is to administer fluid frequently, so that a considerable quantity, at least equal to that of the urine passed, is taken. As there is always a tendency to vomiting, water must be given in small quantities at a time. Though there is thirst, the amount of water that 100 TROPICAL MEDICINE AND HYGIENE must be taken is in excess of that which the patient desires. Tepid sponging after the perspirations is required, and great care must be taken to avoid a chill. This treatment must be continued throughout the attack, but after the first day, though the muscular strength may be considerable, the patient must not be allowed to leave his bed or even raise himself in it without assistance. Any necessary movement must be made very slowly. These precautions become more and more necessary, not only whilst the blackwater persists, but for several days after. The urine should be measured after each act of micturition, as it is of the utmost importance to obtain information as to any diminution in the rate of secretion. The vomiting must be checked; if not restrained by sinapisms or hot applications to the epigastrium, hypodermic injections of morphia should be administered and all fluid given in teaspoonfuls if necessary. Patients must never be worried to pass urine ; they all know the danger of suppression, and any concern shown by the attendant as to this will still further increase their anxiety. The danger is suppression, and if no urine is in the bladder it can do no good for the patient to attempt to micturate. Retention does occur occasion- ally, so that if there is undue delay in micturition the abdomen above the pubes should be examined to make sure that the bladder is not distended. If the vomiting cannot be checked, or sufficient water cannot be administered by the mouth, rectal injections of normal saline solution, '2 per cent., should be given hourly. As the frequent administration of such enemata leads to an irritable condition of the rectum, great care is required. The enemata should be given very slowly and should be at blood heat. The blankets and clothing must be replaced by warm, dry clothing as often as required. If the tendency to syncope becomes marked, the lower end of the bed must ]u.ackwati<:k fever ioi be niised, hot-water bottles applied to the axilla, and the legs bandaged from the feet upwards, and stimulaiits given freely by the mouth, rectum, or by hypodermic injections. Transfusion througii the veins has not been successful, as hyperpyrexia may occur either whilst hccmo- globinuria is present or afterwards during the secondary fever. The temperature should be taken frequently and hourly when it is above 104° F. The hyperpyrexia after the urine has cleared is the more dangerous. Where the patient is so situated that there is no skilled nursing available, the danger is greatly increased. Atten- tion to the general principles will be of service, and if the patient has to leave the bed his movements must be as slow as possible and the head held low. He must crawl, not walk or hold himself upright under any cir- cumstances. Any expressions of despondency must be discouraged. It is useless to attempt to minimize the danger, but the patient's courage must be sustained as much as possible. Under these circumstances the advis- ability of removing the pa,tient to a place where he can receive skilled care has to be considered. If moved at all, he should be moved early, in the first day of the disease. Later the risk of collapse is enormously increased by a prolonged journey. The risks, on the whole, of moving are about as great as the advantages resulting from the more careful attention would be. If moved, the patient must be carried in a recumbent position. A hammock is as good a method as any. He must be well wrapped up and receive water frequently whilst on the road, and food in addition if the journey be a long one. Food must be fluid and nutritious : it is well digested. During convalescence great care must still be exercised both to prevent chill and exposure, for fear of relapses, and to avoid over-exertion or anything that may throw any strain on the heart, as fatal syncope mav occur during this period. Constipation during the early stages is not of much 102 - TROPICAL MEDICINE AND HYGIENE importance ; later the bowels must be kept open, prefer- ably by mild saline aperients. Etiology. — The true cause of blackwater fever is unknown. It occurs in both sexes, but is not known in early childhood. It does occur in negroes, but not in natives in an area where the disease is endemic. In proportion to their numbers it is more common amongst Europeans than amongst Asiatics. In Euro- peans it rarely occurs during the first six months of residence in an endemic area, but after that period becomes more common, and is most common in the second and third year of residence. First attacks are very rare after ten years' residence. A person who has not had blackwater fever in an area in which the disease is endemic may have his first attack after leaving that area, sometimes up to six months after leaving it. Generally speaking, in Africa, it is most prevalent where malaria is most prevalent, and by many persons malaria is considered to be essential for the development of the disease. As the disease is not known in some countries where malaria is prevalent, it has either to be assumed that there is a special variety of the malarial parasite implicated, or that there is some special condition under which this extreme haemolysis takes place. So far all experiments that have resulted in a decrease in the amount of malaria have been associated with a reduction in the number of cases of blackwater fever. This seems to hold whether the reduction is due to attacking the carriers of malaria, anophelines, or to steady administration of quinine. No morphological differences have been observed in the malarial parasites in a malarious country where black- water fever is endemic and in malarious countries where it does not occur. The carriers differ in the different countries, and in Africa Myzoinyiafiinesta is the commonest carrier in places where blackwater fever is prevalent. The special condition that has been considered to be the immediate exciting cause is quinine poisoning. BLACKWATER FEVKK 103 The advocates of this hypothesis contend that in some individuals, after they have been exposed to the endemic influences, the blood is so altered that quinine produces haemolysis. There are cases in which a dose of quinine, even a small one, may bring on an attack of hsemo- globinuria; this has been proved in many instances. There are reasons for considering that this, though an occasional cause of blackwater fever, is not an essential or even the common cause. In many countries where large doses of quinine are given, after and during fever, no such effects take place. In analysing the cases in an endemic area there is no close relation, either as regards dose of quinine or interval between taking quinine and the onset of haemoglobinuria, as might have been anticipated if the quinine acted as the determining cause. In a few instances quinine has not been taken. In many the dose taken is no larger than, or not as large as, that the person was in the habit of taking, and after the onset of h?emoglobinuria further administration even of large doses of quinine does not usually cause fresh haemolysis. Exposure to cold and wet seems to often act as the determining cause, but a few of the cases occur amongst persons who have no chance of such exposure. Various hypotheses have been formulated in the attempt to explain why a disease which appears to be closely connected with malaria is not directly due to the malarial parasite. A want of balance between the pro- duction of h^emolysins and antihaemolysins dependent partly on the parasites and partly on blood changes in the host as a result of the formation of antibodies appears to be the inost promising. Seqiiclcv. — In the majority of cases recoverv is com- plete, and there are no persistent ill-effects bevond a liability to subsequent attacks. Sometimes a malarial attack will occur, but as a rule there is freedom from such attacks. In rare cases there mav be persistent albuminuria. Parotiditis has been known to occur, and retinal haemorrhages or haemorrhages into the vitreous 104 TROPICAL MEDICINE AND HYGIENE may lead to impaired vision, but in such cases complete recovery of sight is usual. Plroplasma. — Piroplasmata have been frequently looked for but never found, as has been already mentioned. There is no relation known between the distribution of any species of tick and blackvvater fever, but more work in this direction is required. The distribution of Ornithodoriis monhata does not correspond with that of blackwater fever. Prophylaxis. — The close relationship in Africa between the distribution of blackwater fever and of great liability to malarial affection points to the desirability of dealing with the malaria. Persons in whom quinine produces haemoglobinuria are unsuited for residence in a malarial country. In such persons it is sometimes possible to treat the malaria with quinine, if small doses of quinine very gradually increased are employed. Persons who have never had blackwater fever in Africa are still liable to an attack for some months after their arrival in England. It is therefore advisable that the prophylactic use of quinine should be continued, not only on the voyage home, but for two or three months after arrival in England. Such persons must also avoid exposure to chill, over-fatigue, or any depressing influences. A previous attack of blackwater fever appears to pre- dispose to other attacks. A single severe attack or two milder attacks should be considered as disqualifying that person for residence in an endemic area. I05 CHAPTER VIII. PIROPLASMOSIS. Piropliisniosis. — " Malaria " of cattle, horses, clogs, &c. Piroplasmosis is the term sometimes applied to the affec- tion caused by certain sporozoal blood paiasites which, being commonly pear-shaped, are called piroplasmata. The piroplasmata differ from the haemamoebce in that, (i) they do not form pigment ; (2) division is usually into two, sometimes into four, and the young forms are not immediately set free, but continue to grow in the red corpuscle in which they live. Ultimately they escape from these red corpuscles. It is probable that a large proportion of their nutriment is derived by osmosis from the blood plasma and less from the haemoglobin than in the haemamoebje. The free parasites may be found in the plasma, actively motile before they enter other cor- puscles ; (3) they are conveyed in all known instances by ticks of various genera. The diseases are transmitted not by the tick that feeds on the infected animal, but by the second and sometimes the third generation of these ticks, as the parasites are transmitted to the eggs and develop in the young ticks. The piroplasmata in the early stage have no definite vesicular nucleus, though a clear non-staining space or vacuole is present. The chromatin is frequently in two equal or unequal masses, and though it divides to some extent the complete fragmentation and diffusion observed in the malaria parasite does not occur. Division is more by a process of budding than of breaking up into spores. The pear-shaped body after escaping from a red corpuscle enters another and then becomes a rounded amoeboid mass. In this stage it does not escape from the red corpuscle. After a time two iG6 TROPICAL MEDICINE AND HYGIENE processes or buds are formed at the periphery of this rounded body, and these gradually increase in size, the chromatin divides, and half enters each of these buds. The increase in size in the buds is by absorption of the original protoplasmic mass, which is reduced to a mere thread connecting the two bodies, and this finally is absorbed and the two pear-shaped bodies lie free in the red corpuscle. They may remain in the red corpuscle for some time, and when they escape enter in turn red corpuscles, before they again become amoeboid and divide and so repeat the cycle. Piroplasmata occur in most of the domesticated animals and cause serious disease, and frequently death, in cattle, sheep, horses and dogs. They have been described in man, but their occurrence is very doubtful. By some observers Leishman-Donovan bodies, now known to be a resting stage of a flagellate, were con- sidered as piroplasmata. In all the diseases of domes- ticated animals pyrexia occurs, not showing definite periodicity. A common character is haemoglobinuria, so much so that the popular name of the disease in cattle is " red-water fever," in sheep '' heart fever." In dogs the disease they cause is called epidemic jaundice, on account of the haemotogenous colouring of the conjunctiva from the haemolysis. Although haemolysis is a common result of piroplasma infection, haemoglobinuria is by no means always a prominent symptom. Red-water does not occur, for example, in Rhodesian or East Coast cattle fever, and although piroplasmosis is common in cattle throughout the East, yet haemoglobinuria is rarely met with except in animals suffering from serious intercurrent disease, such as rinderpest, or among those imported from countries where piroplasmata do not occur. An infection with piroplasma in cattle appears to last during the whole life of the animal, but the clinical "evidence of the presence of the parasites disappears, and though the animals harbour the parasites in small numbers they seem to have acquired a degree of toler- PIHOPLASMOSIS 107 ance that enables them to prevent the miUtiphcatifMi of the parasites and to resist the effects of their presence. Such animals, liowever, though in s^ood health themselves, are able to infect ticks. The non-recognition of the practically universal infection of native cattle has in several instances led directly to the destruction of im- ported animals, as in the process of immunizing against rinderpest virulent blood has been injected into newly imported animals, which have then died from "red-water." Human Piroplasniosis. — Several observers have de- scribed piroplasmata in human blood ; so far, however, without confirmation. A very fatal form of fever, occurring in the Rocky Mountains and called locally spotted fever, was attributed to the presence of a piroplasma in the blood, and infec- tion was thought to be due to a tick {perinoccntor reticu- laris). Subsec|uent observers have failed to find the piroplasma, but confirm the opinion that it is a disease carried by ticks which can be communicated to lower animals. The disease occurs chiefly in the spring and affects white races only ; it is more common in persons under than over forty, and in males than females. The incubation is short, symptoms commencing two to five days after the bite of a tick. The onset is gradual and the general symptoms resemble those of typhus fever, but are more severe, and a rash appears on the second to the fifth day. The rash appears first on the ankles or back, but soon becomes general. It is at first vesicular, but later petechial, jaundice is usual and des- quamation occurs in patients who survive. The mortality is very high, between 70 and 80 per cent, of the patients dying, usually between the sixth and eleventh da^^s. In patients who survive recovery is gradual, and commences about the end of the second week. Quuiine is said to be the only drug which does good, and the avoidance of tick-bites is suggested as a preventive. Post-iiioiicm examination shows a considerable enlarge- I08 , TROPICAL MEDICINE AND HYGIENE ment of the spleen and acute parenchymatous degenera- tion of other intestinal organs. There is no ulceration of the intestine. By many the disease is believed to be typhus. The term " human piroplasmosis " has sometimes been applied in India to cases of kala-azar, but it will be seen that this disease is due to a parasite of a different nature. Piroplasmata have also been described in the blood of a cowherd suffering from fever during the presence of Texas fever amongst cattle in India. This observation also lacks confirmation. Bodies resembling piroplasmata, but easily distinguish- able upon careful examination, have been described by Cropper working in Palestine, and by Smith working in America, as occurring in the blood of persons suffering from severe forms of malaria. The bodies have a rota- tory but no amoeboid movement ; their nature is unknown. They do not stain with basic stains. The edges, probably the edges of the haemoglobin, are sometimes stained irregularly. Similar bodies have been found by Nuttall in the blood of dogs. They are probably not parasites. J 09 CHAPTER IX. YELLOW FEVER. The parasitology of this disease is unknown. It is in no way connected with malaria, but as it has been proved to be carried' by a mosquito, Stegoniyia fasciata (S. calopns), and as there is further proof that time has to elapse after the infection of the mosquito before it in turn becomes infective, development must take place in the mosquito. On these grounds the disease is here included with the probably protozoal diseases. Yellow Fever is characterized by fever, intense headache, jaundice, and albuminuria increasing steadily in amount ; by tendency to haemorrhages from mucous and some- times from cutaneous surfaces, and by haematemesis — "black vomit." In fatal cases there is frequently suppression of the urine. It is conveyed from man to man by mosquitoes belonging to the genus Stegouiyia. Geographical Distribution. — It is essentiallv a disease of the New World, and occurs endemically or as epidemics in the West Indies and along the Atlantic coast from New York down to Rio de Janeiro. It has been described on the West Coast of Africa, and has occurred in South Europe, on the Atlantic coast as an imported disease, and on board ship. It has spread to a small extent even in English ports in the vicinitv of infected ships, during summer months. It is usually limited to the larger settlements on the coast in the Tropics. Ship epidemics were common in the past, but are now rare. ■no TROPICAL MEDICINE AND HYGIENE Clinical Course. — The onset of the disease is sudden, but not invariably with a rigor. The temperature rises rapidly, there is violent headache, most intense over the frontal region. The eyes are much injected and often described as ferrety. Jaundice soon appears ; the con- junctiva and skin are at first lemon-coloured, but soon deepen to a bright yellow colour. Vomiting is a promi- nent symptom ; at first, merely of food, then watery, then " acid vomit," and later almost black — " black vomit." The act of emesis is performed with little or no effort, and the amount ejected is surprising. The vomit seems rather to gush out than to be forcibly expressed. There is a feeling of marked and decided relief after each evacuation of the stomach. Epigastric pain and tenderness occur early and are intensified by pressure. There is usually an intensely acid or bitter taste in the mouth. The course of the disease is best considered divided into three stages as described by Blair, During the first stage the temperature is high and the pulse quick and bound- ing. The headache and epigastric pains are severe, and the vomit is free from blood till towards the close of the period. The urine contains albumin, and the jaundice appears and progressively deepens. The duration of this stage is from three to four days. The passage into the second stage is rapid, though not exactly by crisis. The temperature falls to normal or subnormal, the pulse-rate is reduced, the restlessness, pain, and delirium disappear, and the patient feels much relieved, and often quite well. The general appearance of well-being in the second stage is deceptive and death may occur, in such a patient, and he, even while he is sinking, may feel quite well. In some cases — the mild ones — this remission is the end of the disease and the patient steadily continues to improve, and passes into the stage of convalescence with- out secondary fever. YELIXnV VKVKU III In other cases, after a short apyrexial peri(jd or period with a moderate temperature, the tempera- ture again rises — secondary fever — the vomiting recurs, and the vomit if not previously mixed with blood is so now. The urine becomes more and more loaded with albumin, and diminished in amount, and the distressing symptoms again recur. This is the most dangerous stage and may last for about a week or more. In cases progressing favourably the symptoms gradually subside, the tempera- ture gradually falls and the amount of urine increases whikst the albumin decreases and convalescence is estab- lished. The diagnosis of an epidemic of yellow fever is TIME M E M E M E M E M E M E M E M E M E M E M ■ E M , E _MJE M E F° 105 t 04 I03 102 1 1 1 00 99 98 /\ / ^ / V -" / I A A \ \ / ^/ \ \ A 1 U A ,A, ! \ A V V ^\ \ [a A 'a I J V V V '\ V A lV '\ r V V ■¥ Fig. 32. — Yellow Fever. Severe attack. not difficult. The fever, severe headache, increasing albuminuria and jaundice, with the occurrence in a pro- portion of the cases of " black vomit," render the diagnosis certain. The limitation of the disease to certain quarters, or even streets of a town, and the dependence of one case on preceding cases are all aids in this diagnosis. The diagnosis of isolated cases is more difficult. Acute yellow atrophy of the liver may closely simulate the severe forms of the disease, malaria with jaundice, and Weil's disease have each manv points of resemblance. There are certain points of resemblance between yellow 112 TROPICAL MEDICINE AND HYGIENE fever and blackwater fever that have in the past led to a confusion between the two diseases^ so much so that both have been considered to be manifestations of malaria, and are still often mistaken for " bilious remittent fever " with jaundice. The points of similarity are the jaundice, liability to suppression of urine, and vomiting; the temperature charts are not unlike in the two diseases, as in both there is a remission in the pyrexia between the primary and secondary fever. Clinically there are important differ- ences. Haematemesis is very rare in blackwater fever, and common in yellow fever. Haemoglobinuria or metlijemoglobinuria is invariable in blackwater fever and very rare in yellow fever, though there may be haema- turia. In neither disease are malarial parasites found in the blood, during the attack, and in yellow fever the increase in the relative number of the large mononuclear leucocytes is not found. The intense headache in the early stages of yellow fever is not present in blackwater fever, and the repeated rigors so common in blackwater fever are usually absent in yellow fever. Treatment. — A preliminary purge seems to be of great importance, and calomel is frequently used for this purpose. Many drugs have been employed, and a treat- ment for which great success was claimed was by large doses of calomel and quinine, 20 grains of each being given. All later work shows that quinine has no effect on the disease. Carbolic acid, in drop doses every hour, and other intestinal antiseptics have also enjoyed a great reputation. There does not appear to be any drug with a specific action. The present treatment is that introduced by Sternberg, well diluted bichloride of mercury and car- bonate of soda being given frequently in small doses. Nursing. — Careful nursing is of great importance. The room must be kept very quiet and dark, as there is great intolerance of light. Vomiting must be checked if pos- sible, and opium is contraindicated. All food, drinks, YELLOW FEVER II3 and medicines must be given in small quantities at a time. Ice-bags or cold compresses to the abdomen give more relief in most cases than hot applications. Protection from the bites of mosquitoes must be very carefully attended to in order to prevent the spread of the disease and the infection of the attendant, especially dur- ing the iirst stage of the disease. The danger is greatest at night, as one of these mosquitoes which has once fed becomes a feeder at night mainly. The bed must be always screened off in a mosquito net sufficiently large for the attendant also to be inside it, and any mosquitoes that obtain entrance to the net must be caught and killed, as otherwise they may become infective in ten days. The netting must not be too coarse, as the S. fasciata can pass through a mesh of 15 to the square inch. All the evidence is opposed to the belief that any discharges from the patient are infective. Mosquito larvae in the room should be destroyed, and no breeding-places — flower- vases, water-jugs, &c. — allowed to remain in the room. Pathology and Morbid Anatomy. — The organism that causes yellow fever has not been isolated. It is present in the blood of the patient during the first three days of the disease, and is so minute that blood serum of such a patient retains its infectivity after passage through a Berkefeld filter. This serum if injected into a non- immune subject will cause an attack of the disease, not merely a toxemia, as the blood of this person is infective, showing that he also harbours the parasite. The morbid changes due to the action of this unknown organism result in liability to haemorrhages, congestion of viscera, and extreme fatty degeneration of the cells in the liver, kidneys, and elsewhere. This fatty degeneration is so marked that the liver and kidneys are pale yellow in colour and extremely friable. There will be no malarial pigment unless there have been previous attacks of malaria. The stomach is always congested, submucous haemorrhages 114 TROPICAL MEDICINE AND HYGIENE are common, and the contents of the stomach and ah- mentary canal are black and tarry, even when there has been no black vomit. Subserous haemorrhages are always present and the serous membranes are stained with bile. All attempts at isolating an organism that can be regarded as the cause of the disease have failed. From time to time organisms have been described, and the one that for some years attracted considerable attention was a bacillus described by Sanarelli. This organism, one of the coli group, has been showai to be that of hog-cholera. Though the cause has not been discovered, it is now known, as the result of the experimental work of Reed and Caroll, fully confirmed by numerous observers, that the infective agent is imbibed with the blood of patients by certain mosquitoes, and that such mosquitoes after a definite period of ten to twelve days are in turn capable of infecting non-immunes. These experiments have shown : — (i) That neither in the vomit, black or otherwise, in the faeces, or sweat, or other discharges from the patients is any infective agent contained, but that it is contained in the blood during the first three days of the attack. (2) That mosquitoes {S. fasciata) can convey the disease, and that the other common and domestic mosquitoes do not so carry the disease. The conditions necessary for the conveyance of the disease by these mosquitoes are : — {a) That the mosquito must have fed on the blood of a yellow fever patient during the early stage, first, second or third day of the disease. (6) That the mosquito must have lived for ten days after this feeding. (c) That the person bitten in the second instance must be susceptible. This series of events shows that the parasite of yellow fever requires development in the mosquito before it can be injected into man, and that it is not simply a transference of the organisms from one man to another. YELLOW FEVER II5 M.'irclioux and Simond claim that the mosquitoes may transmit the organism to their offspring, though the more extensive observations of Kosenau and Goldbergcr have failed to confirm these results, and the method in which yellow fever is spread is in more accoidance with tlie transmission by the adults than in this manner. The period of incubation of yellow fever after the bite of an infective mosquito varies little and is usually from three to four davs, very rarely over five. In persons partially immune a longer period of incubation may be met with. The early cases in an epidemic are twelve to fifteen days after a case is introduced, as the mosquitoes have to be infected and become infective, which takes ten days, and then the person infected by them will not develop the disease for two, three or four days. The incubation period for an epidemic is therefore about two weeks. Most of the etiological factors connected with yellow fever are closely related to the conditions favour- able for the life and multiplication of S. fasciata, but this insect is more widely spread than yellow fever, and is only of importance in this connection when persons with yellow fever are present or are imported. Prophylaxis. — The carrier of yellow fever is known, and for eflfective prophylaxis thorough knowledge of the habits of this insect is required, and the means of identification. It is possible that other members of the same group may carry yellow fever. The subfamily of the Culicidce to which the St ego my la belongs is the Citllcina, characterized by a straight or nearly straight proboscis adapted for piercing, by a nude metanotum, by a trilobed scutellum, and by having the palpi short in the female and long in the male. The scales on the wings, thorax, head and scutellum vary in the different members of this subfamilv, and these varia- tions are made the basis of the subdivision of the Cullclna into a large number of genera. The genus Stegomyla diit'ers from the other Culicinas in that there are no narrow curved scales on the head or ri6 TROPICAL MEDICINE AND HYGIENE scutellum. They are small mosquitoes and usually black with brilliant silver-white markings. These markings, especially those on the thorax, serve to distinguish the different species, and in S.fasciata there is a faint central, narrow silver line on the dorsum, and on each side of this a more conspicuous curved line. The S. fasciata (S. calopiis) is commonly known as the " tiger mosquito," because of the brilliant striping of the legs and abdomen. The breeding-places and habits of the Stegomyia in general, and of S. fasciata in particular, differ greatly from those of the Culicidae already considered, and the prophylactic measures must be varied accordingly. Stegomyia eggs are laid singly, and have no lateral air- floats. They are covered with a thick shell. They float for a time on the surface of the water, but ultimately sink and lie at the bottom of the water in which they were deposited. These eggs are not killed by immersion in water, nor are they destroyed by prolonged desiccation. This extraordinary vitality of the eggs is the cause of the great variety of breeding-places, and of the wide dissemination of this mosquito. In the first place eggs are often deposited in quite small receptacles, shallow pools, gutters of houses, old tins used for preserved foods, broken bottles, empty cocoanut shells, &c., and it is immaterial if this deposition takes place at the end of a spell of wet weather, as the eggs will remain alive even if the water dries completely. With the next rain, either there will be sufficient rain to moisten the eggs, or there will be an excessive amount, so that these receptacles overflow. In the first case the eggs will hatch where they were laid ; in the second, they will be washed away into some larger and perhaps more permanent col- lection of water. Eggs that have fallen to the bottom of a pond remain alive, and if in taking water, as on board a ship, the bottom is at all disturbed, the eggs will be taken with the water, and hatch out and develop in the water-barrels. YELLOW KKVER 117 Old wooden barrels in which water has been kept, if not well cleansed, will often be found full of larv;e within twenty-four hours if refilled with water. Such bai-)-eIs are often used for storage of watei" on a small scale and for catching roof water, and whether kept indoors or out (jf doors are most prolilic breeding-places. With the onset of the wet season these species of mosquitoes very rapidly become abundant. The mature eggs are present in old beds of dried puddles, and in every receptacle that will hold even a few drops of water, and these hatch out with the first rain, and if rain continues the pupae will form in a week, and a day or two later the imagines emerge. Light is not necessary for the development of these larvae, so that cisterns and tanks are suitable breeding grounds. The larvae have a respiratory syphon or tube attached to the eighth abdominal segment. This syphon is present in all the Culicinae, but varies greatly in length. In the Stegomyia it is a short, broad, stumpy syphon, shorter than in most of the commoner Culiciiuv. The mouth-parts are simple, the clumps of hairs — the brushes — situated on each side of the mouth are short, stiff, and not very abundant. The mandibles and maxillje are powerful. These larvae feed at the bottoms or sides of the water in which they live, and mainly on lower forms of animal and vegetable life. They require abundant food and serve to keep down algae. They can remain under water for a long time, and often escape notice in that way. When breathing or resting they hang with their heads down from the surface of the water, and in butts and barrels are often numerous enough to blacken the surface of the water. Any slight disturbance appears to alarm them, as the whole lot will then immediately dive to the bottom of the barrel, and may remain there for some time, and the surface of the w^ater be free from larvae. The larvae are very hardy, active in their move- ments, and less readily killed by desiccation than most larv^. The larvae live well on board ship. They require a fairly high temperature, and are killed when frozen. Il8 TROPICAL MEDICINE AND HYGIENE They do not occur outside tropical and sub-tropical regions. The adults — imagines — are hardy mosquitoes, and most species feed readily on man. Some jungle species bite by day only, many feed both at night and by day, but S. fasciata at first will feed by day or night, but after once feeding continue to feed at night only. Many species are jungle mosquitoes, but some of these, as S. scntellaris, much more numerous in settlements in the vicinity become of jungle, and readily become domesticated. S. fasciata is far more abundant on the sea-coast, and in many countries, such as the Guianas and the Malay Peninsula, is rarely met with except in coast settlements and towns. Though strong, active mosquitoes, they do not take extensive flights, or go far .from their breeding-places. It follows that when these mosquitoes are numerous, the breeding-places are close at hand. As a rule, the breeding-places of the mosquitoes are in the immediate surroundings of a house, and destruction of these breed- ing-places will result in the freedom of that house from these mosquitoes. The places to look for breeding-places of S. fasciata are : — (i) The back of servants' quarters, as behind these empty tins, bottles, and broken crockery of all kinds are allowed to accumulate. If there is long grass these receptacles are hidden by it, and thus sheltered from the sun, retain water for a long time. (2) Tanks, barrels, water-butts, used for collecting or storing water. The largest as well as the smallest are common breeding-places. Wooden receptacles are perhaps the most likely to harbour the larvae. The warning that any incautious movement is to be avoided in examining such places must be remembered, as the larv^, if they are not on the surface, cannot be seen. Badly graded gutters are also fertile breeding-places. The ordinary roof-gutter is apt to sag, and even if properly graded is liable to be blocked by leaves and YELLOW FEVER II9 other debris, so that pools, permanent in the wet season, are formed. Moreover, egjL^s deposited on their extensive surface are carried down into the water-tanks and there develop. Some authorities condemn roof-flutters for these reasons, but there is no reason why roof-gutters should not be properly graded and kept clean, and it is of little importance that eggs are washed down if the mosquitoes that develop in the tank cannot escape from it. (3) In houses, bath-tubs, vessels for holding flowers, flower-pots, even filters, such as the drip stone filters, water-coolers, and every receptacle for water will serve as a breeding-place. These are frequently found in unoccupied rooms. As these mosquitoes can breed in foul water, they may be present in the receptacles for kitchen refuse, and even cesspits. Stable cesspits, stable buckets and drains are often the breeding-places of these mosquitoes. In preventing the spread of yellow fever, a knowledge of their breeding-places is essential. In any country into which yellow fever may be introduced the extermination of these mosquitoes will render the spread of the disease impossible ; and in all countries their extirpation will greatly increase comfort. In a scattered settlement it is an easy and inexpensive matter to render a house free from this species of mosquito, but constant care is required. The important point is that in such a place the breeding-places are in the immediate surroundings of the house. The occupier breeds his own mosquitoes. In a more crowded settlement continued efforts are re- quired, and it should be made compulsory for each occupier to free his own property from breeding-places ; or the whole work may be done by the municipality at the common expense. A combination of these methods is most effective. It should be compulsory on the occupier to free the actual premises from breedmg- places, and to have his water-tanks so protected that mosquitoes cannot escape from them, and to see tliat I20 TROPICAL MEDICINE AND HYGIENE no accumulation of empty tins and bottles is present in his compound. The municipality should remove such bottles, and inspect and report on the condition of drains, gutters, tanks, and stable surroundings as to their freedom from larvae, and should make recom- mendations to the occupier and enforce the carrying out of such recommendations. The gutters must be well graded and kept clean. The pipes supplying water to the tanks must be long enough to reach the bottoms of such tanks, otherwise the mosquitoes as they hatch out will escape through this pipe. The manhole must be kept covered, and it is better to have a double covering, an inside one of gauze, and the ordinary solid one over it. It is useless to attempt to render the supply pipe impervious to mosquitoes by placing a gauze diaphragm in any part of it, as the meshes soon become clogged and the water will not pass through. An inspection and collection of any portable breeding-places, e.g., bottles, &c., should be made twice a week, and any foul drains or cesspits should be treated with crude petroleum, or better, some such poison as tuba root {Derris elliptica.) With a good organization, with the active support of the intelligent section of the community, and stringent regulations well enforced, the cost of extirpation of this mosquito is not prohibitive. Roof water forms the best available supply of drinking water in many places, so that measures that prevent its infection cannot be overlooked. In a town not so protected, or only partially protected so that some mosquitoes of the species Stegomyia fasciata are present, the introduction of a patient with yellow fever is a source of danger to the whole community. This danger can, by energetic measures, be reduced to a minimum, (i) All cases of fever must be at once reported and enquired into. Any that are yellow fever must be at once isolated. In a port where yellow fever is likely to be introduced, the machinery for the registration, identi- YELLOW FEVEK 121 fication, and isolation of cases must be kept in working order, and form a department or bureau that is at all times available. (2) If there is a case of yellow fever the patient must be removed to another room and placed inside a mos- quito net, and kept there night and day till convalescent. (3) The room from which the patient has been re- moved must be at once closed, and all places where mosquitoes can escape blocked. The room must then be fumigated with burning sulphur i| lb., or pyrethrum 2 lb., to each 1,000 cubic ft. As soon as possible after the fumigation the floor must be swept, and the sweepings at once burnt, as mosquitoes may revive after such a fumigation. The attendants, those engaged in fumigation or mosquito destruction, and any persons having business in the house, must be protected by suitable clothing from mosquitoes. (5) In adjoining houses every effort should be made to destroy the mosquitoes, as some may have escaped to them. If the case of yellow fever is detected early, when these precautions are adopted there is frequently no spread of the disease, because the mosquitoes, as in malaria, are not capable of infecting human beings in less than ten days after biting the patient. Where the first case is not detected early, and the disease has spread, each case as it is reported must be treated in the same manner as an original case. The success of the measures depends on each case being reported early, and a thoroughly efficient central bureau is therefore essential. When an outbreak does occur measures for the destruction of the larv^ must be most energetically pushed. For the success that has attended such prophylactic measures the reader is referred to the reports as to the sanitation of Havana, New Orleans, and the Panama Canal Works. Importation of disease is usually by ship. Either 122 , TROPICAL MEDICINE AND HYGIENE infected mosquitoes are introduced or infected persons. Infected mosquitoes may be brought in with the cargo or in private baggage, and in that case the focus of the epidemic is the place where the baggage is opened. Ship Epidemics. — S. fasciata can thrive on board ship, and can be transported for long distances by sea as eggs, larvae, or adults. The adult mosquitoes may be infected in one port and only become infective after reaching a second port, and then may give rise to an epidemic in the vicinity of the wharves. It is quite possible in a voyage of a week or less that the crew of the ship might escape infection, and the source of infec- tion of the port would not then be known. It is different in cases where the mosquitoes become infective whilst at sea. In such a case a large proportion of the sus- ceptible crew may acquire yellow fever. The mosquitoes need not be numerous, but every attempt must be made by fumigation of one part of the ship after the other to destroy any mosquitoes, and the sweepings as on land must be burnt at once. S. fasciata become torpid with cold, and consequently such epidemics subside four or five days after reach- ing colder latitudes, but in summer may continue to develop as far north as England, and may spread in the vicinity of the wharves as the mosquitoes escape from the ship. In some cases the infection has remained in the ship for several months, even when it has not been occupied for this period. In a sheltered warm part of a ship these mosquitoes may live for that period. 123 CHAPTER X. FLAGELLATA. The Mastigophora or Flagcllata form a group of organ- isms that have long been known both 21s free-living as well as in parasitic forms. The main characteristic is the modification of a part of the cell to form an apparatus for locomotion consisting of one or more motile flagella. The essential part of this fiagellum is not attached to nor does it arise from the ectosarc, but it is derived from a portion of the chromatin mass contained in the endosarc. The nucleus is not vesicular and contains abundant chromatin, which is diffused throughout it. A second more compact but smaller chromatin mass, the inicro- nucleus, cenirosoine, or blepJiaroplast, is contained in the endosarc, and the fiagellum, which also contains chro- matin, arises in relation to this mass. In the presence of the fiagellum, the absence of amoeboid movements, in the character of the nucleus, as well as in the method of multiplication by longitudinal fission, the flagellates would appear to be absolutely distinct from the haemosporidia. Recent work, however, shows that the distinction is not so absolute as was supposed. Flagellates may have a resting form in which they become rounded and lose their flagella, and are then not unlike some of the lijemosporidia, though even then the two unequal chromatin masses serve as a distinction. Schaudinn considered that he had proved that certain of the trypanosomes could assume a gregarine form after losing the flagella and then closely resemble the product of the fertilization of the macrogamete of a hcemo- sporidium by a microgamete. His work on the subject illustrates the extreme complexity of the problem, but has not been confirmed in many important respects. The most important part of his work was with the halteridium. 124 TROPICAL MEDICINE AND HYGIENE Special interest attaches to the halteridium, a parasite in the red corpuscles of many species of birds, partly because it was in a species of this parasite that McCallum first observed the fertilization of a female gamete by a male gamete, resulting in the formation of an ookinet or travelling vermicule, and partly because of Schaudinn's work on a species occurring in the little owl, Athene nodiia;. The halteridium has long been considered as being a hsemamoeba, closely allied to the malarial para- sites of man, but Schaudinn believes that it is but a stage in the life-history of a trypanosome which he calls Trypanosoma noctiice. Schaudinn's opinions have not received universal acceptance, some observers saying that the owl harbours a trypanosome in addition to halteri- dium, and that Schaudinn confused the changes occurring in the two classes of parasites. A brief epitome of them is given here, as there are many points in which further information as to the full life-history of trypanosomes is required. Schaudinn's views (condensed, modified, &c.) are therefore here briefly considered. It will be convenient to start with the ookinet of the halteridium resulting from the fertilization of the female gametocyte by the male gamete, and to trace the life-cycle of the organism back to this stage again. The ookinet is formed in the stomach of the gnat in which union of the sexual forms of the halteridium occurs very shortly after the ingestion of infected blood. It corresponds closely with the similar stage of the malarial parasite and is a fusiform body, containing in its cytoplasm the nucleus re- sulting from the fusion of the male and female elements, some reserve materials, a few pigment granules and vacuoles. When first formed all ookinets are similar in appear- ance, but they soon become distinguishable into three forms, indifferent (hermaphrodite), male and female, recognizable by variations in their cytoplasm, nucleus, reserve material, and relative size and shape. KLAOKLLATA 125 A process common to some fcjrms oi 0(jkincts, though it may not be completed until after differentiation has occurred, is the extrusion of pigment and residual material. Before the different forms become distinguish- able certain ciianges have occurred, chiefly affecting the nucleus. The nucleus, as has been seen, consists of b(;th male and female elements. Each of these is subdivided into a trophic portion and a kinetic portion, concerned respectively with the nutrition and movement of the organism. In all forms, the trophic and kinetic portions of the nucleus become separated eventually, the former be- coming the tropho-nucleus and the latter the kineto- nucleus of a trypanosome. In the indifferent ookinet the nucleus soon becomes divided into two portions, the larger of which is the tropho-nucleus, and undergoes at this stage little further change. The smaller part, which remains connected with the larger by a fine thread, the remains of the axial spindle, passes towards the outer part (ectoplasm) of the ookinet, and at the same time towards the pointed anterior end, where it again divides, and part of it ulti- mately forms the free edge of the undulating membrane (the membrane itself being formed by the flattening of the anterior part of the organism) and the flagellum. The other part remains on the kineto-nucleus of the trypanosome, and makes towards the posterior part of the organism, drawnng with it the central end of the flagellar apparatus. In this way a trypanosome is formed with its small kineto-nucleus posterior to the larger tropho-nucleus, and with an undulant membrane ex- tending nearly the whole length of the organism. When thus fully developed, the indifferent trypanosome multiplies by fission. The nuclei first divide, then the motor apparatus is duplicated, and finally the cytoplasm divides into two trypanosomes. This multiplication by fission, which is limited to indifferent forms, mav occur several times and may give rise, in the later multiplica- 126 TROPICAL MEDICINE AND HYGIENE tions at any rate, to male and female as well as to indifferent trypanosomes. After a certain time this form of multiplication ceases and the trypanosomes become attached to the epi- thelial cells of the gnat's stomach, and these assume a resting gregariniform stage. The flagellum may be reduced to a short rod, or may disappear altogether, and the parasite becomes rounded and inactive. Binary fission may now occur, and large masses of gregarini- form parasites thus result. From this gregariniform stage trypanosomes are again developed, the kineto-nucleus giving rise to a flagellum and the cytoplasm becoming elongated. The male ookinets are much smaller than the indifferent forms, their cytoplasm is clearer and hyaline, and contains no reserve material. The nucleus is relatively large, and instead of dividing into trophic and kinetic portions, as in the case of the indifferent ookinet, it divides into a male and a female half. The latter is the larger but undergoes no further development and eventually disappears. The male half of the nucleus breaks up into eight smaller nuclei, which become distributed radially in the peripheral portion of the ookinet, which has now become rounded and is termed a microgametocyte. Prominences, each contain- ing one of the nuclei, grow out from the periphery of the microgametocyte and gradually assume the shape of a trypanosome. The trophic and kinetic portions of the contained nucleus become separated and from the latter a large flagellum is produced in the same manner as in the " indifferent " trypanosomes. Eight male trypano- somes are thus formed, they become free and very active, the motor apparatus being much more developed than in the indifferent or female forms. The male trypano- somes are easily distinguishable by their minute size and great activity. They undergo no further development and die off if no opportunity for copulation occurs. Female ookinets are the largest of the three forms. The SCHAUDINN S VIKWS I27 cytoplasm is dense, the nucleus relatively small, and the reserve material plentiful. Like that of the male, the nucleus of the female separates into male and female portions, and in a similar manner the male portion disappears, while the female portion divides into tropho- and kineto-nuclei, the last forming a flagellar apparatus in the same manner as in the indifferent form. The female trypanosome thus formed resembles the indifferent form, but is larger, rounder, and contains much more reserve material. The flagellum is shorter and its movements are much less active. The female form never divides longitudinally, but may enter a gregariniform stage, and on account of its relatively large amount of reserve material it can resist unfavourable influences much longer than can the indifferent form. It can thus survive a winter, and can infect the larvae of a gnat resulting from eggs laid in the following spring. It can further undergo parthenogenesis and thus gives rise to either form of trypanosome. The changes so far described occur in the mosquito. When the mosquito bites an owl, all three forms of trypanosomes are injected into the bird's blood. The indifferent trypanosomes divide by longitudinal fission into very small forms, which become attached to red corpuscles, they lose their flagella and have the appear- ance of young halteridia. They do not penetrate the corpuscles but become deeply embedded in their sub- stance, from which they absorb hzemoglobin, and in twenty-four hours exhibit pigment granules in their interior. At night flagella are formed and the halteridium becomes a trypanosome again, while during the day the halteridium is again formed and is again attached to a red corpuscle. This process is repeated for six days, during which grow^th occurs and full size is attained. The trypanosome then again divides into small forms and the process just described is repeated. The changes occur chiefly in the internal organs, especiall)^ in the spleen and bone-marrow, in which the circulation is 128 TROPICAL MEDICINE AND HYGIENE slower. Schaudinn suggests that the considerable lower- ing of the temperature of the owl which occurs at night brings about the changes from halteridium to the trypanosome form. As will be seen later, the spirochaetae were also con- sidered by Schaudinn to be the result of rapid longi- tudinal fission of trypanosomata and should therefore be included in the flagellata. Leishman had early pointed out the close resemblance of the Leishman-Donovan bodies to degenerate trypano- somes, and Rogers, by showing that in artificial media these bodies become elongated and acquire a flagellum, has proved that these parasites must also be included in the flagellata. Considering the uncertainty resulting from these rapid advances in our knowledge, it is not advisable to attempt to classify the various parasites belonging to, or probably belonging to, the flagellata. The list appended gives the main groups with which we are concerned. (i) Trypanosoma. — Body elongated and terminating as a conical, blunted, or pointed extremity, at the end in which the centrosome is placed. The flagellum passes along the length of the body, emerging at the opposite end to that from which it arises. A portion of the edge of the body on the side in which the flagellum lies is thinned out with a motile membraneous edge, the undulatory membrane. This membrane may be smooth or crimped up and is largely concerned in locomotion. (2) Trypanoplasma of fish and Herpetomonas differ from the Trypanosoma in that there is no undulatory mem- brane, and the flagellum or the flagella emerge from the body at the end from which they arise, namely, that in which the centrosome is situated. Many of the Herpeto- monas are parasitic in the intestines of dipterous insects, as flies, mosquitoes, and fleas. (3) Leishman-Donovan bodies appear to be a resting stage of a flagellate, probably of Herpetomonas. TRYPANOSOMrASIS I29 (4) Trcponciiui have lon,!^, s[">ii-al bodies, and are very thin and cylindrical. No unduhitory membrane is present. There is a sinj^le ilaj^ellum at each end. Multi- phcation is by longitudinal fission. The known specimens stain u^ith basic stains with diBiculty. To this group is now assigned the organism believed to be the cause of syphilis, and described as the Spirocliccta pallida, and probably the similar organisms found in yaws by Castellani and in granuloma pudendi by Wise. (5) Spirocliivtcv are elongated spiral bodies with no flagella. Tiiey are usually pointed at the ends. Accord- ing to Schaudinn there is an elongated nucleus, and mul- tiplication is by longitudinal division. Some observers believe that multiplication is by transverse division, and doubt the protozoal nature of these organisms. The Spirodicvta oberinelcri and S. duttoni, the causal organisms respectively of relapsing fever and of African tick fever, belong to this group. The spirochastas found commonly in the mouth, as well as those sometimes found in the faeces, and those described in the lungs, and by some believed to be a cause of bronchitis, are also members of this group. Spirohactcria are organisms that are not protozoal but which either constantly or occasionally assume a special form, such as the vibrio of Asiatic cholera. These are not considered in this part of the work, as they definitely belong to the division of the Protista with vegetable affinities. Trypanosomiasis. This is a general term used to designate the diseases caused in the higher animals by the presence of trypano- somes in the blood. Trypanosomes are found in many classes of animals, but while they cause disease in most of the mammalia, those in fish and amphibia are, as far as we know, harmless. The effects of trypanosomes vary, both according to the species of the parasite and of the host. 9 130 TROPICAL MEDICINE AND HYGIENE The first of the mammahan trypanosomes discovered was that of the rat, T. lewisi, which may often be found in enormous numbers in rats. They appear to be harmless in adults, but in young rats may cause fatal disease. Trypanosoma bnicei was shown to be definitely patho- genic, and was proved by Bruce to be the cause of the fatal " fly disease " (nagana) of South Africa. This disease is rapidly fatal to horses, and more slowly causes death of cattle, monkeys, and dogs. It is fatal to rats in from three to five days. T. evansi causes a very similar disease to* nagana in many parts of the East. The disease is known in India as surra. It is chiefly fatal to horses, but cattle, buffaloes, &c., though less affected, often harbour the parasites, and may die after a prolonged illness. They probably are the main agents in spreading the disease to horses. T. equiperdum is the cause of the peculiar disease known as " dourine." It is of special interest, as the parasites are discharged with the semen, and the disease is spread from males to females by coitus. There are in human trypanosomiasis so many analogies with syphilis that this mode of communicating disease is of theoretical importance, though it is fairly certain that human trypanosomiasis is not spread in this manner. T. thieleri occurs in cattle in South Africa. T. dimorphon. — Blunt-ended trypanosomes that vary a great deal in size. In the same specimen both large and small are usually found together. Occurs in cattle and horses, and most of the laboratory animals are susceptible. These various trypanosomes are, so far as we know, not inoculable in man. One human trypanosome is well known ; this was first found by Ford in Gambia, and was first identified and described by Button as T. gambiense. A second, T. cruzi, has been recently discovered in South America. It causes fever, enlargement of spleen, and oedema in various parts of the body. It may be fatal. 131 CHAPTER XL HUMAN TRYPANOSOMIASIS. A DISEASE due to the presence in the blood of T. ganibiense. It manifests itself as a long-continued fever, at first of a severe type, but later a low form of hectic fever and associated with enlargement of the lymphatic glands, especially the cervical ; evanescent rashes, and often splenic enlargement. It terminates fatally with cerebral symptoms, usually of the form long known as sleeping sickness. Geographical Distribution. — The disease is only known in Tropical Africa as an indigenous disease, but many cases have been reported in Europe, all in persons who had resided in Africa within the last few years. As judged by the distribution of its terminal phase — sleeping sickness — the disease has within recent years been spread- ing rapidly across Africa. It is still unknown on the Zambesi and south of it, and it is not known in the neighbourhood of Lake Nyasa or east of these lakes. It is prevalent throughout the Congo, but is rare on the Gold Coast, in Lagos, and in Nigeria. It has been introduced into the neighbourhood of Victoria Nyanza within the last few years, and now extends throughout that district and down the Nile some 200 miles. There is every probability that it will become more widely diffused in Africa, though it is less prevalent in some places, such as Liberia, where at one time it was common. The intermediate hosts belong to the genus Glossiua, and the species implicated are Glossina palpalis and possibly G.fusca. Glossinje are only found in Africa and Arabia, and suitable species to act as alternate hosts are not 132 TROPICAL MEDICINE AND HYGIENE present in South Africa and South America, and though the disease has been introduced there it has not spread. Clinical History. — Little is known as regards the onset of the disease in man. The period of incubation in monkeys is about fourteen days. The onset in man appears to be often confounded with malaria, but in some cases there is high and continued fever as in typhoid, and in some cases there is no marked fever. At this stage there appear to be no characteristic symp- toms, but sometimes trypanosomes are found abundantly in the blood. The temperature after this early stage may fall to normal, and remain so, but even in these cases the diurnal variation is usually increased, so that when the temperature is taken frequently, though it may rarely exceed 99" F., there may be a variation at different times of the day of as much as 2° F. More frequently there is slight irregular fever, the temperature rising to 100° or loi'^^ F. every day. At times, in such cases, there will be definite pyrexia, the temperature rising to 103° or 104° F., or even more, for several days, falling gradually to normal or a little above it. Some of the lymphatic glands are soon found to be enlarged and are soft to the touch. They are not acutely painful but are tender on pressure. The glands at the base of the neck are those most commonly enlarged. In Europeans a rash is usually present. It is evanes- cent but appears as erythematous rings surrounding an area sometimes slightly discoloured by blood pigments.. This discoloration may amount to an actual bruised appearance. The rings are not raised to the touch. The chest, abdomen and covered portions of the body are the usual sites for this eruption, but it may occur on any other parts of the body, such as the forehead and face. There is progressive muscular weakness, some loss of flesh, and some anaemia. Even in the early stages a slight blow may cause prolonged muscular pain — Grissoli's symptom. The cardiac action is very rapid HUMAN TRYPANOSOMIASIS I33 and unduly subject to irregularities as a result of slight exertions. A line muscular tremor is often perceptible in the hands in late stages. The appetite is good, and unless there is much pyrexia the tongue is moderately clean and the bowels regular. The disease runs a very chronic course, and with the subsidence of the fever the general condition shows some improvement, and the patient may be able to go about his work and believes that he is recovering. This con- dition may last for two or three years. During this period trypanosomes will only be found in the blood after prolonged search : they may be more abundant during a pyrexial period in those cases in which definite attacks of fever recur. They are much more readily found in the soft enlarged glands, but in old hard glands, though they be still enlarged, the trypanosomes may not be more numerous than in the peripheral blood. Injections of considerable amounts, 2 c.c. or more, of the blood of such patients into monkeys or other sus- ceptible animals will result in the infection of such animals, and the trypanosomes can be found in number in their blood, and the animals will die shortly after. Rats may be infected in this way, but the results are uncertain, and the period of incubation may be prolonged to months. Sooner or later in a patient who may have been free from fever, and in whom the presence of parasites may only be shown by the infection of animals with the patient's blood, terminal cerebral symptoms supervene. The cerebral symptoms vary in character ; they may take the form of a rapidly fatal coma or of a series of epileptiform convulsions, or of the progressive lethargic condition known as sleeping sickness or negro lethargy. In this condition, which is the most common termina- tion of the disease, the patient passes into a peculiarly lethargic state, so that while the total amount of sleep obtained may be little above normal he is always drowsy, and frequently falls asleep even at meals or when in the act of performing some ordinary occupation. Before the .134 TROPICAL MEDICINE AND HYGIENE onset of these symptoms there is usually marked fine tremor and dull headache. The temper is frequently un- certain, and there may be mental irritability. This irrita- bility, as the disease progresses, becomes more marked and mental deficiency occurs. There is a general aspect of misery about the patient and he is apt to be neglectful of his person, and dirty and careless in his habits. Muscular weakness is extreme, and unless the patient is regularly fed he rapidly emaciates and dies, partly of starvation. Even when well fed and carefully nursed there is rapidly progressive emaciation. The termination of the disease may be associated with diarrhoea, or the patient dies comatose. Diagnosis. — The disease may be mistaken in the early stages for malaria and typhoid fever and possibly pell- agra. In the later with any of the chronic forms of intermittent, remittent, or " low fever," such as kala-azar. As the disease is confined to Tropical Africa, suspicion may be excluded in patients who have not resided in that country. The presence of enlarged gfands and the fugitive circinate eruptions are of great value in the diagnosis. Certainty can only be obtained by finding trypanosomes in the blood or fluid obtained by hypodermic puncture of one of the enlarged glands, or by the results of the injection of the blood into monkeys or other susceptible animals, but with some of these, such as rats, the period of incubation may be indefinitely prolonged. In the terminal stage the epileptiform convulsions and the comatose condition might readily be mistaken for other diseases. When this stage shows the peculiar lethargy of sleeping sickness mistakes could hardly occur. When cerebrospinal symptoms have set in try- panosomes may not be found in the blood, but only in the cerebrospinal fluid. This should be drawn off by lumbar puncture, and centrifugalized, as the parasites are usually scanty. Prognosis. — The terminal stage, sleeping sickness, is HUMAN TRYPANOSOMIASIS I35 invariably fatal. The earlier sta^L^es of the disease, when there is merely a trypanosome infection of the blood and lymphatic system, are amenable to treatment, and there is good reason to believe that complete and permanent recovery may ensue. The disease is a serious one, and the prognosis, even when all the symptoms have disappeared, and the parasites cannot be found in either glands or blood, must be guarded, as cerebrospinal symptoms may occur years after the original infection. Pathological Anatomy. — Little is known of the patho- logical anatomy of the early stages of the disease in man. In monkeys and the lower animals the condition is mainly one of visceral congestion, but enlargement of the spleen and intense congestion, sometimes h^emorrhagic of the lymphatic glands and extreme congestion of the brain are also met with. In sleeping sickness there is formation of round cells in the perivascular spaces of the cerebral capillaries, closely resembling that found in general paralysis of the insane. Treatment. — The drugs most distinctly useful in malaria, quinine and methylene blue, have no effect in this disease and do not alleviate the symptoms or reduce the number of trypanosomes. Arsenic long had some reputation in the treatment of the early stages of sleeping sickness, and experiments with various trypanosomie infections in lower annuals showed that this drug had a decided controlling effect, and that the number of parasites could be reduced, and life much prolonged by its administra- tion. The effects were not permanent ; if the arsenic were pushed the animals died from arsenical poisoning, whilst if given in smaller amounts the trypanosomes became tolerant of the drug and the animals died of trypanoso- miasis. In human trypanosomiasis it was soon found that only a few persons could tolerate arsenic given by the mouth in sufficient quantities for the parasites to be affected. 136 TROPICAL MEDICINE AND HYGIENE Various forms of injection of arsenic were tried, cacody- lates and the like, but arsenic in the form of atoxyl appears to be both the safest and most promising. In the lower animals very large doses seemed to effectively con- trol the disease without producing arsenical poisoning. In man smaller doses have to be used or arsenical poison- ing will result. The most successful method is to use a freshly made 10 per cent, solution of atoxyl in normal saline. The solution must be sterilized before use and injected whilst still warm into one of the large muscles, such as the gluteus maximus : 20 minims every alternate day can always be borne, and the dose should be gradually increased and given more frequently till a decided effect is produced, 2^ to 3 grains of atoxyl will usually suffice ; in some persons symptoms of poisoning are produced by 25 minims, but a larger dose is better and in most cases can be taken. In some, 70 minims or more may be well borne ; 30 minims every other day appears to be an effective dose, the parasites diminish in number and ultimately cannot be found. The glands become small and hard, the temperature normal, and the eruption ceases to appear. The general health also is completely restored. Relapses occur, particularly if there be any intercurrent disease. The atoxyl treatment should be continued for at least a year after the symptoms have disappeared. Sufficient time has not yet elapsed for certainty as to the completeness and permanency of the recovery, and particularly whether all possibility of the recurrence of the cerebral symptoms or of sleeping sickness has been obviated. It is somewhat unfortunate that a different line of treat- ment has been adopted on a large scale. This plan, introduced by Koch, was to use large doses and repeat them a fortnight later. The immediate effects were good, so much so that the method was widely advertised, and has been extensively employed. Further experience has shown that the effects are temporary, relapses the rule, and optic atrophy common. These results have to some extent discredited the use of atoxyl. HUMAN TRYPANOSOMIASIS I 37 The attempt to treat many diseases by a few heroic doses has often failed, as in syphilis by mercury, and malaria by quinine, whilst the same drugs in moderate doses continued for a long time have a permanent bene- ficial effect, and the same appears to hold good with atoxyl in trypanosomiasis. Alternate treatment with atoxyl and mercury has been advocated, but the results in man have been no better than with atoxyl alone. Injections of preparations of antimony have a more powerful effect on the trypanosomes than atoxyl or any other arsenical preparations, but the antimony prepara- tions used cause much pain and local gangrene unless very dilute. Nursing. — No special precautions are required. The disease is a chronic one and good feeding is necessary. On account of the cardiac condition sudden movements or exertion on the part of the patient must be discouraged. When the general condition of the patient permits it he should be allowed to live an ordinary healthy life. But over-fatigue and any risk of intercurrent disease must be carefully guarded against. When taking atoxyl or any other preparation of arsenic, any digestive disturbance such as nausea, vomiting, or abdominal pains must be carefully noted. Any com- plaint of dryness of the mouth, and pain or irritation of the eyes, must also be reported. Increasing muscular tremor, headache, and disturbed sleep are premonitory signs of the onset of sleeping sickness. When this supervenes, all that can be done is to feed the patient at regular intervals, and to keep him clean, warm and comfortable. There is no object in en- deavouring to prevent him from sleeping. Etiology. — There are certain points of analogy between trypanosomes and some cases of S3'philis. In both there is a latent period followed by a more or less marked febrile stage, and associated with glandular enlargement and cutaneous eruptions and terminating in the formation of diffuse lymphoid growths around the cerebral vessels. 138 TROPICAL MEDICINE AND HYGIENE The mode of propagation of one of the trypanosome diseases in the horse is by sexual intercourse. With human trypanosomiasis the disease is not spread in this manner, but, as far as is known, by the bites of certain flies belonging to the genus Glossina. From the distribution of the disease, and the corre- sponding distribution of the flies, G. palpalis is beheved to be the important carrier, whilst G. fiisca and possibly G. tachinoides may also be carriers. The commonest of the tsetse-flies, G. morsitans, though it carries the trypano- some of nagana, is probably not a carrier of T. ganibiense. The Glossinas are a genus limited to Africa and the shores of the Arabian Gulf, and are easily distinguished from other biting flies. They are dipterous insects, and closely resemble many of the Muscidae, but are distmguished by the long, straight proboscis, by the arista or spine which arises from the third joint of the antennae being plumose on the one side only, by the palps being the same length as the proboscis and grooved on the inner sides, so that together the two palpi form a sheath for the proboscis. There are hairs only on the convex side of the arista compound. The wings are crossed, so that when at rest their tips overlap each other — "scissor" wings — and project beyond the abdomen. The fourth longitudinal vein is bent twice, once to meet the transverse vein, and a second time to approximate tothe third longitudinal. Glossinae are pupiparous, the larvae attain their full growth in the ovary, and after being passed do not feed but pass into the ground and become pupae. G. palpalis can be easily distinguished from other common Glossinae, as the last four joints of the hind legs are entirely black. Two other species have this character, G. pallicera and G. maculata, whilst in G. tachinoides the last four joints though black are not entirely so. The commoner species, G. morsitans, has only the last two joints of the hind legs black. Without going into detail, then, Glossinas are flies which, HUMAN TKYPANOSOMIASIS J 39 when alive, are readily recognized by the slraif^ht, long proboscis projecting out in front of the head, and i)y the crossed position of the wings of the insect when at rest. These wings are always longer than the abdomen, and projecting beyond it give the insect the appearance of being longer than it really is (lig. 33). Glossinas bite mainly in the daytime, though some species also bite at night. The bite is painful at the time, feeling more like a sharp sting, but not producing any subsequent local effects. They will bite a man or other animal Fig. 33. — Glossina morsitans. while he is in motion, and seem to bite almost as soon as they alight on him. G. palpalis is often found in boats and canoes, sheltering under the thwarts. Very frequently it will crawl out and bite the legs, and in other cases, as they often keep low, will alight on the legs and bite, whereas G. morsitans more frequently attacks the upper part of the body, the head or neck. They are usually found in narrow belts near water on the edge of forest land, and may in such situations be present in large numbers for a few hours, whilst at other 140 TROPICAL MEDICINE AND HYGIENE times few or none may be found. They are also found in well-wooded country, in forest clearings, and near forests. The larvae are deposited in the neighbourhood of rotting vegetation, and particularly near the roots of certain plants, such as bananas, as well as many other plants and trees. The pupae are usually found in banks covered with trees near open water, lakes, or streams. Extensive clearings, therefore, form an important part of prophylaxis. By the formation of such clearings and the burning off of refuse vegetation in the vicinity of settlements, the actual habitations may be kept clear of these flies. It has been suggested that keeping and breeding fowls, or the importation of jungle fowls from India, might aid in the destruction of such larvae. It is doubtful, however, whether such fowls would have any chance of continued existence at any distance from human habitations, and the larvae are deposited away from the uncleared tracts or in plantations. More hope of the destruction of the flies in their adult form may be entertained by the introduction or cultiva- tion of insectivorous insects and other animals, such as dragon-flies. Koch believes that their most important source of food is the crocodile, and advocates the extermination of that reptile. Protection from the bites of flies is very difficult, not only fly-proof houses must be made, but fly-proof clothing must be worn when out- side such houses. Such measures should be taken when living in an endemic area close to native settlements where sleeping sickness is prevalent. Biting flies belonging to other families are not to be altogether ignored, as the trypanosomes of Asia are carried by some of these, such as Stomoxys. Attention in Africa has been almost entirely directed to Glossinae. It is not known how the Glossinae convey trypanoso- miasis. There is direct evidence that occasionally they convey the parasites by feeding first on an infected animal and very shortly after feeding on another susceptible HUMAN TRYPANOSOMIASIS 141 animal. Such transmission is direct. Usually attempts at transmission in this manner fail, and Kleine has recently shown that flies again become infective eighteen days or more after they have fed on infected animals. All attempts to demonstrate a definite cycle of develop- ment of trypanosomes in the Glossin^c have failed. The Fig. 34. enquiry is difficult because flagellates are so common in the alimentary canal of flies. Minchin has suggested that the encysted trypanosomes which he found in the intes- tines of Glossinae were the developmental stage and that the trypanosomes, after development, \vere passed per 142 TROPICAL MEDICINE AND HYGIENE reduin and possibly subsequently deposited on food which was devoured by man, who then became infected. The biting method of infection appears to be the more probable, and the contamination method has not met with much support. In mammals they multiply asexually by longitudinal division (fig. 34). Small resting forms, according to some observers, may be produced. • Prophylaxis amongst Europeans is comparatively simple. Districts where sleeping sickness is prevalent should be avoided as much as possible European habitations should not be near water nor placed where Glossinae are plentiful. The houses should be fly-proof, and as far as possible from native settlements. When travelling fly-proof clothing should be worn and boots after the style of mosquito boots ; veils also should be worn and loose gloves. Prophylaxis for natives is very difficult, (i) Segregation of the infected; (2) deportation of the non-infected to a fly-free area ; (3) destruction of the fly along ordinary routes of travel ; (4) treatment of infected persons to reduce the number of trypansomes where it is impossible to isolate them in a fly-free country, are the most promising measures. (i) Segregation of the infected is not likely to be thorough, as the symptoms are for a long time indefinite and the prolonged search of the blood necessary to find trypanosomes is impracticable for a large collection of persons. Examination for enlarged glands is not conclusive, as glandular enlargement is so common from other causes. A combination, however, of the examination for enlarged glands and microscopic examination of the fluid obtained by gland puncture is of value in preventing the introduc- tion of diseased persons into a community. The segre- gation camps must be in a district free from the fly or they may form a focus for the spread of infection. (2) Deportation of the whole of uninfected population to a fly-free area is the most satisfactory of the present HUMAN TRYPANOSOMIASIS I43 methods. The old station must he Ininit, the gardens destroyed, and patrols established, or some of the people will return and may become infected. (3) Destruction of the fly along known trade routes is important. The points of special danger are ferries, fords and watering places, as at such places many travellers pass and the fly is often present. Extensive clearing of the jungle along the banks of the rivers for 100 yards from the edge of the water and on each side of the path in the vicinity of water will greatly reduce the number of flies present. (4) Treatment with atoxyl will greatly reduce the number of trypanosomes present in the blood and thereby chminish the probability of infection of the fly, even in cases where the course of the disease is little afifected. 144 CHAPTER XII. KALA-AZAR. KALA-DUKH. DUM-DUM FEVER. TROPICAL SPLENOMEGALY. Definition. — A chronic infective febrile disease due to a flagellate protozoal organism found in its resting, non-flagellate form in the spleen, liver, intestines and other organs. The disease is characterized by long- continued fever, enlargement of the spleen and liver, wasting, debility and anaemia, and by a very high mortality. It occurs both endemically and in epidemics. Geographical Distribntion. — The principal seat of kala- azar is Assam, in parts of which it has long been prevalent, though it was first mentioned in 1882. Its name, signi- fying the " black disease," refers either to the terrible mortality attending the epidemics which for many years devastated district after district of Assam, or to the dark- ening of the skin observed in many of those suffering from it. Epidemics have occurred in Lower Bengal, where the disease is also endemic, and the name " Dum-Dum fever " was given to attacks of it contracted at this station by British soldiers, many of whom have died of it in England. Kala-azar also occurs in Madras, and sporadic cases have been met with in Bombay and other parts of India, also in Burmah and Ceylon. Cases have also been described as occurring in China, the Straits Settlements, the Phihppines, Panama, Northern Africa, and the Soudan. The population of some of the places named is drawn from so many sources, that it is not possible to say at present whether the disease is endemic in them or not. KALA-AZAR I45 Clinical Course. — Tlic cliniciil picture of a case of kala- azar of some months' duration is very strikinj^. The patient, even if up and about, is obviously ill. He is a wretchedly thin, tired-looking man, with a big abdomen and shrunken limbs, and complains of having had fever off and on for months, and that in spite of quinine and various other medicines he has become gradually thinner and weaker, while his abdomen has got bigger and bigger. A very slight examination of the patient's distended abdomen will show that his spleen is enormously en- larged, that his liver is also increased in size, and perhaps that there is a little ascites present ; possibly the superficial abdominal veins will be noticeably prominent, and if attention be turned to the feet some oedema of the ankles and dorsum will be found. Besides being thin, the patient is also anaemic, and his skin, especially that of the face, is darkened or pigmented. His hair is dry and lustreless and may fall out in quantities, leaving him almost bald. He is very easily tired and any little exer- tion causes breathlessness. His intellect is generally ■clear, and he may make little complaint except of his gradually increasing weakness and wasting ; he may, or may not, complain of present fever, but even in its absence may say that he is disturbed at nights by violent ■sweats, but for which he probably sleeps well. Not infrequently, however, patients at this stage of the ■disease suffer from attacks of epistaxis, or of bleeding from the gums or from other mucous surfaces. Some- times, too, petechiae appear, more commonly in the axillae than elsewhere. Attacks of bronchitis or sore throat are not uncommon. Less common symptoms, but of sufficient frequency to require mention, are jaun- dice, rheumatic pains in the joints, and ulcers on the skin. It is noteworthy that in spite of their serious illness the appetite of patients suffering from kala-azar is usually very good, sometimes it is even voracious, leading to ■over-eating and consequent dyspepsia. But for this and 10 146 TROPICAL MEDICINE AND HYGIENE for a rather undue degree of thirst, there are usually no symptoms referable to the digestive system until later in the disease. The tongue is clean and the bowels are inclined to be constipated. Later on, however, diarrhoea or dysentery sets in, the latter being the most common immediate cause of death. Less commonly the patient dies, after several months of illness, of asthenia, or some intercurrent disease, such as pneumonia, carries him off. In places where the disease is epidemic, patients will not infrequently be met with who say that several of their relations have died of a similar disease within a year or two. The incubation period of kala-azar is not definitely known, though it is probably long, some months having elapsed in many instances between the departure of patients from infected places and the onset of symptoms- Considerable difficulty in determining the incubation period arises from the circumstance that sometimes the onset of the disease is very insidious, while in many cases the earliest symptoms are mistaken for those of malarial fever, or of typhoid fever. Three stages of the disease are commonly recognized : those of the initial fever, of the secondary low fever, and of cachexia. These stages are not sharply marked off from one another, for the acute pyrexial attacks of the initial period become gradually less severe, until they emerge into the chronic irregular fever of the secondary period, and after this has persisted for some months the cachectic con- dition is established. There is a gradual loss of ground throughout the course of the disease, though periods of temporary improvement may occur. The initial fever may resemble typhoid fever (fig. 35), or,, in other cases malarial remittent fever, commencing with chills, or less commonly with a rigor, mounting to a considerable height, and after several hours falling several degrees, the fall being accompanied by profuse perspira- tions. These febrile attacks recur daily. At first the type is remittent, but may soon. become intermittent, the. KALA-AZAK 147 daily range of temperature being c(>nsideral)le, varying between 97° and 103° F. (fig. 36). The rise of temperature usually occurs in the evening, but not uncommonly there is a double or even a treble rise and fall in the twenty-four hours. Some- times there are short periods of apyrexia, followed by further outbursts of fever. TIME M E M E M E M E M E M c M E M E M E M E M E M E M E M E f" 104 103 1 02 1 1 100 99 98 97 ^ A A A 1 /^ V V V \ A y Y \l\ V A V V 'V' y '\ \ A It _ _ _ _ _ V ^ P r V V ^ V 7^ V 7^ V y Fig. 35. — Kala-azar. Simulating typhoid. Fig. 36. — Kala-azar. Later showing intermittent type. After the fever has lasted a short time, the spleen becomes enlarged and tender ; enlargement and tender- ness of the liver also occur, but are less marked. Wast- ing, anemia, and debility are early symptoms of the disease, and sometimes darkening of the skin is observed at this stage. 148 TROPICAL MEDICINE AND HYGIENE Headache sometimes accompanies the fever, but there is very httle, if any, digestive disturbance, the tongue remains clean, and the appetite good, except in cases where high fever has persisted for some time. The first stage usually lasts about a month, but the duration may vary from ten days to two months. It is followed, either directly or after an interval of apparent health, by a stage in which low fever persists for weeks or, more frequently, for months. Sometimes the course of this secondary fever is very irregular. It is rarely high, though there may be occasional attacks of TIME M E M E M E M E M E M ri"^ M F M- E wT 1? M E M E M E M E M € 104 103 102 1 01 100 9 9 99 97 '^It I / V^ v\ A A ^ / V if A A « / \ n V V ^ /\ / V J V 7 V I A ^ r\ ' '^Z V V \ ^ V V A V V V Fig. 37. — Kala-azar. Undulating type. high fever, lasting for some days, while, on the other hand, there may be days or weeks of apyrexia (fig. 37). In some cases the course of the fever may be remarkably regular, the temperature rising and falling to exactly similar points at the same hours day after day for weeks. Fre- quently also the course of the temperature chart shows a double daily rise and fall. The fever at this state often causes but little discomfort, and but for profuse sweating the patient may be unaware that he has any. Sweating, especially at night, may, however, occur without any rise in the temperature. The liver and spleen continue to enlarge, the latter often attaining enormous dimensions. Emaciation, anaemia and debility are progressive until the condition KALA-AZAk 149 iilready described is attained, and the stage of cachexia supervenes. As the end approaches the patient's condition is wretched in the extreme. He is terribly emaciated, and so weak that he can hardly move, he suffers from diarrhoea or dysentery, though his appetite may be ravenous to within a day or two of death. By this time the fever may have given place to subnormal tempera- ture, and the spleen and liver, though still considerably enlarged, may be smaller than formerly. Death is most commonly due to dysentery, which appears to be an integral feature of the last stage of the disease, rather than an added complication. As already stated, however, patients sometimes die from mere asthenia, while not uncommonly death is due to some intercurrent disease, of which lobar pneumonia, phthisis, and cancrum oris are those most frequently met with. The duration of the disease varies from three or four months to two years, but is most commonly a year or eighteen months. Of this period the stage of initial fever lasts a month or two, and that of low fever six months to a year. While the description given above applies to most cases of kala-azar, variations from this type of the disease are met with. In some instances the period of initial fever seems to be absent, the patient gradually becoming weak and ill without any definite symptoms beyond loss of flesh and enlargement of the liver and spleen. In other cases the onset may be very acute, and the patient may be carried off by fever or dysentery before the development of cachexia. For so serious a disease the symptoms other than those mentioned are remarkably slight. Besides headache, those referable to the nervous system are chiefly a diminution of nervous energy and occasional muscular tremors, resulting, for example, in inability to write, in educated patients. Cases are said to be met with in the endemic area in which the symptoms throughout are of a mild nature. 150 TROPICAL MEDICINE AND HYGIENE The symptoms referable to the circulatory system are chiefly dependent upon anaemia. In the early stage the pulse is less rapid than might be anticipated from the height of fever present, while later, owing to the anaemia, its frequency is out of proportion to the temperature, and is full, though very soft. Pulsation of the carotids is often noticeable, and haemic murmurs are common, as also is palpitation on exertion. Anaemia is a constant symptom of kala-azar. Its degree varies in different cases and at different periods of the disease, but is usually considerable, though not extreme. It commences early in the disease and there is a progressive reduction in numbers of both red corpuscles and leucocytes. Instead of the usual 5,000,000 red cor- puscles to the cubic millimetre, only half that number may be present, though 3,000,000 or 3,500,000 are more common counts. The haemoglobin value of the red corpuscles is only slightly reduced. The diminution of leucocytes is normal or more marked than that of the red corpuscles, their numbers varying from 3,000 down to 1,000, or even to only 500 to the cubic milli- metre. This marked leucopenia is, according to Rogers, diagnostic of kala-azar. The decrease chiefly affects the polymorphonuclear leucocytes, while the mononuclear elements show a considerable relative increase. The results of differential blood counts are commonly as follows, the figures given representing percentages : polymorphonuclears, 40 to 60 ; lymphocytes, 20 to 30 ; large mononuclears, 13 to 16. Although the specific parasite may be met with in the peripheral blood, it occurs so sparingly, especially in the early stages of the disease, that the diagnosis can rarely be made by blood examination. It occurs in the polymorphonuclear and in the large mononuclear leucocytes, and the method which affords the best chance of finding it is to centrifugalize 2 or 3 c.c. of blood, and after separating the red corpuscles to again centrifugalize the remainder and prepare films from it. Another KALA-AZAR 151 method is to in;ikc blootl lilins Icnniiiatin^ in a thick edge ; leucocytes accumulate at this edge, and search for the organism is thus faciHtated. By this method a skilled observer may be able to make his diagnosis certain by examination of the peripheral blood alone. Unless the case is complicated by malaria, no malarial parasites or pigment will be present in the blood. Among the results of the blood changes are the haemor- rhages from mucous surfaces already mentioned. Of these epistaxis is the most common form, and is some- times profuse and difficult to control; in other cases slight but persistent oozing of blood from the nasal mucous membrane occurs ; bleeding of the gums is not uncommon, and sometimes intestinal haemorrhages occur, quite apart from those met with during the dysenteric attacks of the final stage. Haematuria is occasionally- observed. Mention may here be made of the occasional presence of slight general anasarca ; this and the transitory oedemas sometimes met with are probably due to the condition of the blood. The anasarca may be most marked in the face, and may mask the emaciation. Digestive System. — There is little to add to what has already been said of symptoms referable to the digestive system. During the early stages they are slight or absent, this being in contrast to the condition usually met with in malaria. While diarrhoea or dysentery are usually symptoms of the final stage, attacks may appear at any period of the disease. In some instances, indeed, soldiers have been invalided from India to England for dysentery, and the symptoms of kala-azar have supervened. The enlargement of the liver and spleen is usually pain- less, though these organs are often tender, especially in the early stage of the disease. Sometimes, however, there is considerable pain in the liver, which has led to the mistaken diagnosis of hepatic abscess. While the enlarge- ment is usually progressive until towards the end, variations 152 TROPICAL MEDICINE AND HYGIENE in the size of the liver and spleen sometimes occur, diminution being usually coincident with temporary- general improvement in the patient's condition. The slight degree of ascites not infrequently met with is probably due, at least partly, to the obstruction to the circulation caused by the enlargement of the liver and spleen. The urine is normal in most cases of kala-azar, though towards the end it may contain a little albumin. Hasma- turia is a rare complication. Respiratory System. — A liability to congestion of the respiratory passages, as evidenced by sore throat or by slight bronchitis, is common in patients suffering from kala-azar, and there seems to be a special liability to pneumonia during the later stages of the disease ; the pneumonia is of the ordinary lobar type. True tuber- cular phthisis is one of the causes of death in kala- azar. The parasites may occur in the lungs, and in that case nodules resembling tubercles will be present. Cutaneous System. — Darkening or pigmentation of the skin is sometimes very marked, especially among dark- skinned patients. The skin of Europeans suffering from this disease often has a dull, dirty appearance. Except for occasional petechias, there are no special skin erup- tions in kala-azar. Cancrum oris is frequently met with in the last stages of kala-azar, especially in children. Although nearly always fatal, cases have been recorded in which its appearance has been followed by great improvement in the general symptoms and even in subsequent recovery. Diagnosis.— With, regard to the diagnosis of kala-azar it may at once be said that this cannot be made with certainty except by the demonstration of the specific parasite. In Assam, where the disease was first recog- nized, medical practitioners who have been familiar with it for many years admit that in the early stage kala-azar cannot be readily distinguished clinically from malaria, and that even in the later stages a consideration of the KALA-AZAR 1 53 history of the patient is necessary before any conchision can be arrived at. Should the patient be from an infected house or village, and should the development of his cachexia have been more rapid than is usual in malaria, he is considered to be suffering from kala-azar, (otherwise the diagnosis of his disease is likely to be malarial cachexia. In Madras, too, all of the patients in whom the earliest discovery of the parasite had been made during life had been considered to be suffering from malarial cachexia, and this in spite of the fact that no malarial parasites could be discovered by repeated examination of their blood. Of the early investigators of the disease, one beUeved that it was ankylostomiasis, others that it was a special epidemic form of malaria, while yet another believed it to be Malta fever. An important feature for the clinical differentiation of kala-azar from malaria is the resistance of the former disease to quinine, and should this resistance be definitely proved, the latter may be excluded. It is important to note, however, that the two diseases may co-exist, and that therefore the demonstration of malarial parasites in the blood and their disappearance following the adminis- tration of quinine cannot be considered as definitely excluding in suspicious cases the diagnosis of kala-azar. In such cases, should the temperature show a double or triple daily curve, and should there be little or no diges- tive disturbance, the likelihood of their being kala-azar is considerably increased. It is only in the early stages that kala-azar is likely to be mistaken for enteric fever, from which the points just mentioned should serve to distinguish it. The examination of the blood is an essential preliminary step in the diagnosis of kala-azar. The combination of marked leucopenia with relative increase in the number of mononuclear leucocytes at once differentiates it from a number of diseases which at some stage or other resemble it in some respects, but in which this condition is absent. Such are enteric fever and Malta fever among 154 TROPICAL MEDICINE AND HYGIENE acute and splenic anaemia (Banti's disease) and spleno- meduUary leucocythemia among chronic diseases, in all of which the spleen may be considerably enlarged, and a varying degree of anaemia present, but in which the number of leucocytes is increased — in the chronic anaemias very greatly so. In patients suffering from tropical abscess of the liver there is usually leucocytosis. This may not be marked in some cases, but there is no leucopenia. A blood count would differentiate the two diseases, the total number of leucocytes being in excess in hepatic abscess and diminished in kala-azar. The diseases other than kala-azar in which leucopenia is combined with a relative mononuclear increase are malaria and trypanosomasis. In malaria, how^ever, leuco- penia is less marked than in kala-azar, the relative pro- portion of white and red corpuscles remaining the same as in normal blood, about i to 750. In kala-azar, on the contrary, the diminution of white corpuscles is much greater than that of the red, the proportion falling as low as I to 1,500, or even as i to 3,000. In ankylostomiasis there is leucocytosis with marked eosinophilia. Examination of the blood alone should not, however, unless the specific parasites of these diseases are recog- nized, be relied upon to differentiate them from kala-azar. To place the diagnosis beyond doubt the demonstration of the parasite of kala-azar is necessary. The parasite is most readily obtained by puncture of the liver or spleen. The risk of haemorrhage following puncture of the spleen may be great in kala-azar and has been fatal. It is preferable to puncture the liver. The method of puncture is as follows : — The syringe and needle must be sterilized dry, as any admixture with water may cause a breaking up of the parasite. The skin over the site selected for puncture must be thoroughly sterilized and the needle plunged deep into the liver with a slight rotatory movement. When well in the liver the syringe will move with the KALA-AZAR 1 55 respiratory movements. The needle should be kept in position for about a minute and sh^iitly \vith(h"a\vn before gentle aspiration is attempted. Tiie less blood that is present the more satisfaetory is the operation, as the parasites are not in the blood, and any blood present only serves to dilute the fluid and render it more difficult to find the parasite. The fluid withdrawn should be blown out on to a series of slides, making as thin films as possible. These films when dry may be stained with Leishman's method, or with dilute, i in 4, freshly filtered carbol-fuchsin after fixation. The parasites may be numerous in such films, or scanty, and several films should be examined before a negative diagnosis is given. They can be recognized by the presence of two chromatin masses, one small, rod-like and deeply staining, the other larger, oval, and staining less deeply. Prognosis. — The mortality of kala-azar is very high. In Assam the mortality was estimated at 96 per cent., but it is most likely that the remaining 4 per cent, of the patients were suffering from malarial cachexia, the difficulty in the differentiation of which from kala-azar by clinical methods alone has already been mentioned. In Madras the case mortality is recorded as 98 per cent. One recovery has been known of a patient invalided to England in whom the diagnosis was fully confirmed by examination by liver puncture, and in whom parasites were also found in leucocytes in the peripheral blood. Rogers, however, believes that a fair proportion of the cases recover if properly treated. PatJiological AnaioJiiy. — The most noticeable feature in the morbid anatomy of kala-azar, apart from the great emaciation, is the enlargement of the spleen and liver. Besides this, inflammation and ulceration of the large intestine, and some degree of ascites or cedema are common. The spleen is almost invariably very greatly enlarged, often weighmg over 80 oz. ; it is of hrm consis- tence, retaining its shape on removal. There is usually 156 TROPICAL MEDICINE AND HYGIENE no thickening or inflammation of the capsule. On sec- tion the surface is dark red, and the spleen substance is firm and friable; should, however, the examination have been delayed, especially in warm weather, the spleen substance will be found to be soft. There is no malarial pigmentation, and there are no infarcts. Microscopical examination reveals great dilatation and enlargement of the splenic capillaries, with reduction in the lymphoid elements. Scattered irregularly throughout the organ are enormous numbers of parasites, the Leishman bodies. These are contained chiefly in the cells lining the lymph spaces and in the endothelial cells of the capillaries. They also occur in the spleen cells themselves, and in leucocytes, chiefly in the mononuclear, but also in some of the polymorphonuclear cells. They are not met with in the Malpighian corpuscles or lymphatic follicles. The enlargement of the liver is usually less propor- tionate than that of the spleen. Like the spleen, the liver is of firm consistence and friable. It is usually rather paler than normal and presents a nutmeg appearance, this being due partly to the growth of mononuclear cells, chiefly in the centre of the lobules, and partly to fatty degeneration of the liver cells. Parasites are numerous in the endothelial cells of the capillaries and lymphatics, and are also met with in free mononuclear cells, but do not occur in the liver cells themselves. Haemosiderin is present both in the hepatic cells and in the spleen pulp. Next to the spleen and liver the bone-marrow is the principal seat of the parasites, which occur chiefly in the large mononuclear cells ; the marrow appears to be increased in amount and is redder than normal. Should death have been brought about by dysentery, as is so commonly the case, the large intestine will be found thickened and inflamed, the descending colon and sigmoid flexure being chiefly affected. The inflammation sometimes affects the whole length of the large intestine, and may involve the lower part of the small intestine. There is great inflammatory infiltration of all the coats KALA-AZAR 1 57 of the bowel, and frequently there are ulcers extending from the mucous to the serous coat, or even causing per- foration ; sometimes the mucous membrane is covered with a tough film of exudation. The inflammation of the intestine does not appear to be directly clue to the Leishman body, for but few of these organisms are usually found in its coat; they occur chiefly in the endothelial cells of the capillaries. In uncomplicated cases the other organs of the body appear to be healthy, but even in this case parasites may be found, though sparingly, in the endothelial cells of the capillaries and lymph spaces of various organs, e.g., lungs, kidneys, suprarenal capsules, and lymphatic glands. Sometimes the mesenteric glands are enlarged, and contain the specific parasites in large numbers. In spite of the wide distribution of the parasite in the body it has never been found in any of the secretions or excre- tions during life. The difficulty of finding the organism in the blood has already been alluded to. In fresh unstained preparations the parasites of kala- azar are difficult to see. They appear as rather retractile, motionless bodies of indefinite outline, almost colourless or of a light greenish tinge, and may be mistaken for blood platelets. The organisms are best seen when stained by Roman- owsky's method. So stained, they appear as sharply defined, round or oval bodies, between 2 /j, and 3 //. in diameter, of a faint blue colour, and containing two masses of chromatin ; one large, round, of a light violet colour, the other small and rod-shaped, and staining a deep red, almost black. The two chromatin masses are usually situated in the shorter diameter of the oval- shaped parasites, the larger at one pole, the rod at the other, with its length directed at the larger mass across the body of the parasite. The rod is usually sharph^ defined, but is sometimes reduced to a mere dot of deeply staining chromatin. The organisms are remark- ably uniform both in size and appearance ; they appear 158 TROPICAL MEDICINE AND HYGIENE to possess a strong cell wall which resists distortion, and the relative size and position of the chromatin masses are very constant. The cytoplasm of the parasite shows little or no structure, but sometimes vacuoles are seen in it. Besides, by Romanowsky's method, the parasites can be stained by many of the basic aniline dyes, weak carbol-fuchsin and carbol-thionine perhaps giving the best results. Fig. 38. In smears obtained from the liver and spleen during life the parasites may either be free or contained in cells or embedded in a matrix. The matrix is not seen in smears made from organs after death, nor in sections in which the parasites always appear to be intracellular. In the great majority of cases the cells containing the parasites appear to be endothelial cells of capillaries and lymph spaces, either unaltered or of large size and irregular shape, constituting macrophages. The macro- phages often contain large numbers of parasites, upon which they appear to exert no phagocytic action. On the contrary, under the influence of the parasites the macrophages undergo gradual disintegration, and in all KALA-AZAK 1 59 probability furnish the matrix seen in antc-uiorletii smears. Next to the endothelial cells the large mononuclear leucocytes most frequently harbour the parasites, and a few are found in the polymorphonuclear leucocytes; they also occur in the myelocytes of bone-marrow, but are not met with in parenchymatous cells. When obtained post morteni, and especially if several hours have elapsed since the death of the patient, many of the parasites show changes indicative of development. They are larger, 3 /a to 5 yu- in diameter, the chromatin masses show signs of division and may even be re- duplicated, and commencing cleavage of the cytoplasm is seen, each half containing a large and a small chromatin mass. In sections, owing to shrinkage, the parasites appear much smaller than in smears ; the chromatin masses are closer to each other and the smaller has frequently lost its rod-shaped appearance. Etiology. — The etiology of kala-azar is of special in- terest, both because of the repeated failures which have attended the investigations undertaken for its elucida- tion, and because of the remarkable series of observations which have resulted in the discovery of the cause of the disease and the nature of the specific parasite, and probably of its mode of transmission and prophylaxis. The great mortality caused by epidemics of kala-azar in Assam, during the last two decades of the nineteenth century, prompted the Government of India to send one medical officer after another to investigate the disease, and if possible to discover its cause and devise methods for its prevention. All the investigations so undertaken, although carried out with great care, failed in their object. One observer, influenced by the ana2mia of the patients and by the discovery that man}- of them harboured ankylostomes, considered that the disease was essentially ankylostomiasis. Another came to the conclusion that kala-azar was malarial fever, which had l6o TROPICAL MEDICINE AND HYGIENE acquired an intense and communicable form; and a third investigator, while noticing the absence of malarial parasites in the blood and of melanin pigment, thought that it was a form of malaria with marked incidence on the liver and spleen, and with a mortality enhanced by the concurrence of ankylostomiasis or of dysentery. The subject stood thus when, in May, 1903, Leishman published in the British Medical Journal a short note entitled " On the Possibility of the Occurrence of Trypanosomiasis in India." A few years previously, in 1900, he had noticed in smears made from the spleen of a soldier, who had died at Netley of tropical cachexia and dysentery, contracted near Calcutta, enormous numbers of the small, round, oval bodies, with the two characteristic chromatin masses already described. As to the meaning of these bodies Leishman was at a loss. In 1903, however, he found almost exactly similar bodies in the spleen of a white rat, which forty-eight hours previously had died of infection with the trypanosome of Nagana. Up to the time of its death the blood of this rat was swarming with trypanosomes, and experi- ments proved that it was possible to trace every step in the degenerative changes which lead to the formation of the small rounded bodies, the two chromatin masses of which represented without doubt the macro- and micro-nuclei of the trypanosomes from which they had been formed (fig. 39). This second observation gave a clue to the explanation of the first, and Leishman felt himself justified in suggesting not only that the soldier had suffered from trypanosomiasis, but that " some of these severe tropical cachexias, such as Dum-dum fever, as well as kala-azar and sleeping sickness, might be due to trypanosomiasis. These suggestions have been justi- fied to the extent that the parasites have been proved to develop flagella. In July, 1903, Donovan announced that some months previously he had seen the bodies described by Leishman in the spleens of several patients, who had died at Madras KALA-AZAR l6l of what was considered to be chronic maluria, but lie was not aware of their nature until he had seen Leishman's paper, and that he had since found identical bodies in the blood, obtained by puncture, of the spleen durinjf the life of a patient suffering from irregular pyrexia, and in whose blood no malarial parasites could be found. In the following January, Bentley discovered similar bodies in spleen smears from living patients suffering from kala-azar in Assam, and since then numerous similar observations have been made as regards cases presenting similar symptoms, where the disease was con- tracted in or near Calcutta, and in certain other places in India and elsewhere. It may, however, be noted here that the parasite has not been discovered in patients Fig. 39, — a, Trypanosomes and the altered forms found in culture ; b, Leish- man-Donovan bodies and the altered forms found in culture. suffering from " malarial cachexia and enlarged spleen " in the Punjab where organisms morphologically similar have been shown to occur in Delhi boils. A further stage in the etiology of the disease was reached in November, 1904, when Rogers announced that he had observed the development from the parasite of flagella, leaving, as he said, " but little room for doubt that the human parasite belongs to the flagellates." Rogers's observations have been confirmed by others, including Leishman (fig. 39). The flagellate organism into which the Leishman II l62 TROPICAL MEDICINE AND HYGIENE body develops differs from a true trypanosome in that it does not possess an undulating membrane, and that its flagellum and micro-nucleus are situated at the blunter, posterior end of the parasite. It thus resembles a her- petomonas. Similar forms have, however, been observed in the so-called cultivations of true trypanosome, and Rogers noticed forms in his cultures similar to those described by Bradford and Plimmer as occurring in the lungs of animals artificially infected with Trypanosoma brucei. Mention may be made of the opinion expressed by Laveran and Mesnil that the Leishman body is a piro plasma, and of Ross's suggestion that it belongs to a new genus which he named Leishmania, calling the parasite Leishmania donovani. Both these opinions, however, were expressed before the development into flagellaie forms had been observed. Rogers found that when the blood obtained by spleen puncture of patients suffering from kala-azar was mixed with sterile sodium citrate solution, and kept at a temperature of 22° C. for a few ciays, developmental forms occurred. The cytoplasm of the parasites increased in size, became granular, and the body became elongated, the macronucleus enlarged and the micronucleus migrated to the thicker end of the organism from which a flagellum arose. The protrusion of the flagellum was preceded by the formation in the cytoplasm surrounding the micronucleus of a rounded mass which stained with eosin, the rest of the cytoplasm staining blue with Leish man's stain. In one instance, long, flagellate forms were developed within twenty-four hours, these chiefly occurring in pairs. In later experiments (1905) Rogers has found that the development of flagellated forms from kala-azar parasites takes place more freely and with greater regu- larity in an acid than an alkaline medium, and that sterility of the medium is e'ssential. This has led him to suggest that the intermediate host of the parasite might be the bed-bug, the intestinal contents of which KALA-AZAK 163 he found supplied these conditions. Working on this hypothesis, Patton has announced that he has been able to trace the complete cycle of the parasites up to com- pletely developed flagellates in certain tropical bed-bugs, and that in his opinion there is no doubt that the Indian bed-bug, Cimex rotundatus, transmits the disease. The rarity of the occurrence of the parasites in the peripheral blood has been advanced as an argument against this method of infection. Donovan has, how- ever, shown that they occur in the peripheral blood in the leucocytes intermittently in all cases of kala-azar, and at times may be fairly numerous. It must also be re- membered that trypanosomiasis can often be transmitted by the injection of blood, the microscopical examination of which fails to reveal any parasites. In the Assam epidemics kala-azar spread slowly from village to village along the lines of communication. Isolated villages, or those to which persons from outside were not admitted, remained free from attack, and the common history of infected villages was that some person had arrived there suffering from the disease ; after a short time the members of his household were attacked and the disease gradually spread from house to house. Rogers reports that he has observed a similar house or family incidence among his hospital cases of kala-azar at Cal- cutta. All these facts, as well as the success which has attended attempts to stamp out epidemics of kala-azar in Assam by the isolation of patients, coupled with the burning of infected huts, is in favour of the view that the disease is transmitted by some house-infesting parasite, such as a bug. A suggestion based upon the consideration of the low^ temperature at which the flagellate forms are developed ill vifiv from the oval forms obtained from the spleen, is that the parasites escape in the faeces and undergo a stage of development in some cold-blooded animal, a ilsh or mollusc, and that they obtain entrance into the human ±64 TROPICAL MEDICINE AND HYGIENE body by the ingestion of such alternative hosts, either direct or through the water supply. There is, however, no experimental evidence in support of this suggestion, and the circumstances that the parasites cannot be found in the faeces, and that a sterile medium is required for the development of flagellate forms, are opposed to it. The seasonal prevalence of kala-azar, as shown by the number of fresh attacks, is greatest in the cold weather months, November to April, in Assam and Lower Bengal. The "cold weather" temperature in this area ranges between 60° and 75° F., and Rogers points out that it is only within these limits that developmental forms of the parasite are obtainable in vitro. He suggests that epidemics of kala-azar have been due to a succession of periods of prolonged cold weathers, which have extended the conditions favourable to the extra-corporeal develop- ment of the parasite. He further suggests that the more severe cold weather of North-west India accounts for the absence of kala-azar there. As has been seen, kala-azar when epidemic may carry off entire households, persons of either sex and all ages being liable to attack. Rogers states that males and females are attacked in equal proportion, and that infants and old people are less liable than others to the disease, while it is commonest among children and young adults. As to race, kala-azar is comparatively rare among Europeans in India and occurs chiefly among the poor whose domestic hygiene in places like Calcutta resembles that of natives. In Assam it has been noticed that in- fection of Europeans is often traceable to cohabitation with natives, or to occur in missionaries and others whose duties bring them into close contact with natives. Rogers has pointed out that, in contrast to the case of enteric fever, kala-azar occurs more commonly among Euro- peans who have lived some years in India than in newcomers. Treatment. — Once kala-azar has become well developed,. KALA-AZAR 1 65 no treatment seems to liave any effect upon the course of the disease. It is claimed by some that quinine in very large doses may arrest the disease at a very early stage, but it is possible that cases responding to quinine are malarial. Besides quinine a very great number oi drugs have been tried — arsenic, the salicylates, and also bone-marrow — but with little effect. More recently atoxyl has been given, but the results are not rapid, though in one case so treated recovery has taken place. It is possible that careful attention to the general health of the patient, coupled, in the case of Europeans, with residence in a temperate climate, may prolong life a little, and it is important that such measures should not be neglected, for they at any rate add greatly to the patient's comfort, and throughout the disease treatment must be symptomatic. The marked improvement in the condition of kala-azar patients who have recovered from an intercurrent attack of some inflammatory affection suggests the trial of measures for inducing leucocytosis. The diet should be liberal, but it is important to avoid overfeeding and foods difficult of digestion, for, as has been seen, the voracious appetite of kala-azar patients, if unchecked, frequently results in digestive troubles. Prevention. — In view of the part played in all prob- ability by the Eastern bed-bug, Ciinex rotimdatiis, in the transmission of kala-azar, cleanliness, domestic and personal, is the best safeguard against the disease. In countries where the disease prevails every effort should be made to rid houses of these parasites. Old bug- infested houses should be abandoned and burnt, as it is very difficult, if not impossible, to free such houses from bugs by milder measures. In other circumstances, should the disease appear, the patients should be isolated, the infected houses thoroughly fumigated with sulphur or pyrethrum, all beds and furniture likely to harbour bugs soaked in boiling carbolic solution or similar disinfectant, and all clothes and bedding similarly disinfected. l66 TROPICAL MEDICINE AND HYGIENE Segregation of patients and the burning of infected huts have proved successful for dealing with outbreaks of kala-azar in Assam. Varieties. — The specimens of the parasites obtained by Durling in Panama present certain differences, in that the parasites are larger and the ectoplasm more definite and thicker. In this form the lungs are more frequently attacked. It may be a different species. 1 67 CHAPTER XIII. ORIENTAL SORE. Aleppo Evil, Aurangzebe, Bouton de Baghdad, Clou de Biskra, Date Sore, Delhi Boil, Fron- tier Sore, Orient Buele, Yemen Ulcer. The various names mentioned above, and many others, are given to ulcers occurring in Algeria, Egypt, Asia Minor, the Levant, Cyprus, Arabia, Persia, Northern India, and other subtropical countries, and characterized by the thick crusts which form on their surface, and by their great chronicity. The affection begins as a small red, itching papule, resembling the effect of a mosquito bite. This soon increases in size, becomes shiny and transparent, and surrounded by a red areola. Later there is a serous discharge which, together with desquamated epithelial scales, form a crust which is often studded with small yellow points. Underneath the crust ulceration takes place, until the crust giving way, an indolent ulcer is exposed, which slowly spreads. The surface of the ulcer is studded with flabby red granulations, which bleed readily on pressure ; its base is freely movable over the subjacent tissues, and its edges' are raised, irregular and slightly indurated. There is always a considerable amount of thin, serous or purulent discharge which coagulates, forming dirty yellow crusts. The degree of pain varies ; often there is little or none, but sometimes, especially if irritated, or if the discharge be pent up by thick scabs, the ulcer is very painful and the edges acutely tender. l68 TROPICAL MEDICINE AND HYGIENE The ulcer slowly spreads in an irregular manner for some time, often for several months, and either of itself or by coalescing with similar ulcers forms a large open sore an inch or two in diameter. After a time the ulcer ceases to spread and slowdy heals, the healing process being often interrupted by the retention of the discharge beneath the crusts. Depressed, pitted, and pigmented but superficial scars are left which may be mistaken for those of syphilis. These ulcers are most common on exposed parts of the body, especially on the face, neck, wrists, and on the back of the hands and dorsum of the feet. They may be single, but are more commonly multiple, and are irregularly distributed. There is usually no enlargement of the lymphatic glands. As a rule, there is no constitutional disturbance, but if numerous and severe the ulcers lead to gradual impairment of the health. Pathological An atomy. — Oriental sore is essentially an infective granuloma. The proper elements of the skin and its accessories, the hair and sebaceous follicles, and the sweat glands are invaded and destroyed by granulation tissue, which extends deeply into the corium and necroses superfically, thus producing an ulcer. In the early stage, before an ulcer is formed, there is proliferation of the cuticular cells leading to the formation of papules ; later this proliferation extends a little in advance of the edges of the ulcer. The cells composing the granulation tissue are almost exclusively of the mononuclear type. They are large rounded cells with prominent nuclei, and are apparently of endothelial origin. The appearance is thus very different from that of simple ulceration of the skin, in which polymorphonuclear cells predominate. A few of these cells also occur in Oriental sore, but giant cells, such as those seen in tubercular and some syphilitic affections of the skin, are not met with. Scattered throughout the granulation tissue, but chiefly contained in the large mononuclear cells, are vast numbers of parasitic organisms, very similar to those occurring in OKIKNTAL SOKK I 69 kala-azar, Tlicsc bodies were lirsl described as occurring in Oriental sore by Wright, of Boston, in 1903. He discovered them in an ulcer contracted in Armenia some months previously. The discovery was confirmed as regards similar sores contracted at Delhi, Lahore, Quetta and other places in Northern and Western India by James in 1904, and as regards Egypt by Billot. 'l"he parasites are indistinguishable morphologically from those of kala- azar, a description of which will be found on p. 157. James described the occurrence in some of the parasites of a third chromatin mass — a rod tapering towards the micronucleus and at- right angles to it. He believed it not to occur in the organism of kala-azar, but it has since been shown to do so. Etiologv. — From the great abundance throughout the cells composing the granulation tissue of Oriental sore of the binucleated organisms described by Wright and James, it seems highly probable that these are the cause of the disease. How they enter the body is unknown, but long before their discovery the malady was considered to be of a parasitic nature, and various parasitic bodies were described as occurring in the affected tissues. Among these mention should be made of the bodies described in 1885 by Cunningham, and considered by him to be monadina. From his description and figures there can be little doubt that the bodies he considered to be parasites were the large endothelial cells containing the organisms described by Wright and James, the magnifica- tion and staining methods at his command not admitting of more precise differentiation. It may be added that Cunningham's description of the histological appearances of the sores is in close agreement with those of Wright and James. While many of the earlier observers agreed that water was in some way responsible for these sores, some attri- buted them to its chemical contents, and others to its con- taining parasites which were ingested or entered through abrasions in the skin. Other suppositions are that these 170 TROPICAL MEDICINE AND HYGIENE sores are the result of bites of mosquitoes or of sandflies or other biting flies, or that the parasites exist in the soil and are directly inoculated by accidental abrasions. It is least possible that infection may be carried directly from an Oriental sore to simple ulcers or wounds by flies so common in places where the disease is prevalent. The circumstance that these sores are most common on parts of the body not protected by clothes, and especially on the face and neck which are not particularly liable to abrasions, is in favour of the view that the parasite is introduced by some biting insect, the nature of the organism favouring this view. It has been suggested that true Oriental sore only occurs in countries in which camels are in common use, and that infection is in some way derived from camels. The disease, however, is more prevalent among town- dwellers than among those who have especially to do with camels or who usually lead a nomadic life. It has been shown that Oriental sore can be directly inoculated in man and there is a strong popular belief that recovery is followed by immunity, so much so that in certain places it is the practice to inoculate children on unexposed parts of their bodies with matter taken from such sores, with the object of avoiding disfigure- ment of the face. Attempts have been made to inoculate dogs and other animals with pus from Oriental sore, but without success. Sores occurring in dogs at Delhi, and locally believed to be of the same nature as Delhi boils in man, were shown by James to contain numerous spirilla, but no Leishman bodies. In places where Oriental sore is very prevalent, children are the principal sufferers, and newcomers are specially liable to attack. Where less common, persons between 15 and 30 are most affected. Otherwise, age, sex and race appear to be without influence. The seasonal prevalence varies in different places, but the attacks appear to be most common at the beginning and end of the hot weather. ORIENTAL SORK 17I Diagnosis. — Tlie description given above should be a sufficient guide to the nature of the affection, and the diagnosis can be established by the discovery of the specific parasite. Syphilis is the disease for which Oriental sore is most likely to be mistaken. The absence of the other symptoms of syphilis and the failure of anti- syphilitic treatmeht should enable a correct diagnosis to be made. The treatment of Oriental sore, unless thoroughly carried out, is very unsatisfactory. Internal medication has no effect. If protected from irritation they heal very slowly, but with slight scarring. Of local applica- tions, copper sulphate solution i to 4 per cent, gives perhaps the best results. If the diseased tissues are com- pletely destroyed healing is more rapid but the scar may be greater. In the early stage complete excision may be possible, but failing this, the surface and edges of the ulcer should be thoroughly scraped and ordinary anti- septic dressings applied. Should scraping be considered inadvisable some caustic application, preferably strong carbolic acid, may be applied. Others use caustic alkalies, such as potassa fusa. Change of air is often of great benefit in obstinate cases. Prevention. — In the present state of knowledge concern- ing the manner in which Oriental sore is contracted it is not possible to give precise directions for its avoidance. The proved inoculability of the ulcers suggests the import- ance of measures to avoid direct contagion, these includ- ing, besides personal cleanliness, the covering of the sores with some antiseptic application. Until it has been shown that the water of places in which the disease prevails is innocuous, it would be well to boil it before use, either for drinking" or washing. Similarly the bites of insects and contamination by flies are to be avoided. 172 CHAPTER XIV. RELAPSING FEVER. Famine Fever ; Spirillum Fever ; French, Fievre A Rechutes ; German, Ruckfallsfieber. An acute infective fever characterized by the presence of spirilla in the blood and by the common occurrence of relapses. Relapsing fever was formerly common in the British Isles, especially in Ireland, where the associa- tion of its attacks with famine gave it the name of " famine fever." Epidemics, also associated with scarcity, have occurred in several countries of Northern Europe, most commonly in Russia, where there have been recent outbreaks. There was also an outbreak in Austria in 1Q03. In its epidemic form the disease is now most common in India, more particularly in the Bombay Presidency. Outbreaks have also occurred in recent years in Northern China and in Egypt, and cases have been met with in various parts of the world, including Mexico, New York, Cuba, London, Northern Africa, the Sudan, Palestine, Hong Kong, and the Philippines. The disease is probably much more common than is supposed, for without systematic examination of the blood isolated cases are almost certain to escape recognition. With such examination it would probably be recognized at any large seaport among the crews of vessels arriving from the Tropics. Incubation. — The most common duration of the incuba- tion period of relapsing fever is two to five days. The extremes which have been noted are twelve hours and eight days. KliLAPSKNG KEVKK I73 The course of an attack of relapsiniL^ fever is commonly as follows : — Clinical Course. — After a few hours of malaise the patient is suddenly seized with chills, and in two or three hours he is sulTermg from higli fever, with a hot, dry skin, with rapid pulse, severe frontal headache, and great pain in the back and limbs. Bilious vomiting sets in, acc(jmpanied by much thirst and by pain and tenderness of the upper part of the abdomen. Considerable prostration ensues, and by the second day of his illness, if not earlier, the patient takes to his bed. Here he lies for about a week, his tongue becomes dry and coated, his bowels consti- pated, and his liver and spleen enlarged and tender. Jaundice may supervene, and slight bronchitis is common at this stage. The patient is troubled with sleeplessness (the insomnia resembling that of a patient with delirium tremens), or he may be delirious. His aspect is weary, his face livid, and his condition appears to be very serious. On or about the seventh day, however, a crisis occurs. Following a brief increase in the severity of the symptoms, copious perspiration sets in, the temperature falls very rapidly, and symptoms of collapse may follow, not infre- quently accompanied by diarrhoea or even dysentery. In a favourable case, however, the collapse is not serious, the patient falls asleep and wakes after a few hours, apparently convalescent. After about a week of this seeming convalescence the patient is subjected to another attack of fever commencing almost as suddenly as the first. The symptoms of the relapse are similar to those of the initial attack, but milder, though the fever may be higher and the debility more pronounced. The duration is, however, shorter. A second crisis occurs on or about the fifth day, and is usually followed, after a short con- valescence, by complete recovery. Sometimes, however, a second, and in decreasing frequency a third, fourth, or fifth relapse may occur. On the other hand, there may be no relapse, even in cases not cut short by death. 174 TROPICAL MEDICINE AND HYGIENE The suddenness of the rise and fall of temperature is a startling feature of relapsing fever. Within a few hours the temperature in the axilla reaches 103° F. or beyond. While usually showing a diurnal variation of about 2° F., being lowest in the morning, the temperature remains at a high level throughout the initial attack, with an upward tendency as the crisis is approached. At the acme of the fever a temperature of 105° F., 106° F., or even higher is not uncommon, but as it is not long maintained is of less serious import in this than in most other acute fevers. The crisis, while usually occurring on the seventh day of the primary attack, may often be accelerated or delayed TIME M E M|E M E |M E M|E MEMEMEME M^MEMEMEME M E MEMEMEMEMEME .lUSi^^ ~X-Ai i 1 iti \ 72. A / N " -" ^-^^\ i vW^ *- -^ -^ ^ \- V_, ji _ \l\ " -V 'Z '- \ ~ " 97 - J^^ ^ A^-"* -f- ^t _L Fig. 40. — Relapsing Fever. Indian. a day. Rarely the crisis occurs on the ninth day, or still more rarely on the fourth. Whenever it occurs the critical fall of temperature is usually very sudden, reach- ing the normal point or, more commonly, a degree or two below it within twelve hours. The temperature remains subnormal for two or three days, then rises to the normal point, where it remains until a relapse occurs. The course of the fever in relapses is similar to that of the initial attack, tending, however, to be less abrupt in its onset, to show greater daily oscillations and to be of shorter duration. In fact, all the symptoms of a relapse are less typical than those of the initial attack. The interval between each sue- KKLAl'SING KI':VKF>: I75 cessive relapse also tends to be longer. Thus, while the ordinary duration of the initial attack is seven days, and of the first apyrexial interval also seven days, the first relapse usually lasts five days and the third only two days, while the interval between them is commonly nine days. It will be evident that an attack of relapsing fever with only one relapse lasts nearly three weeks. Considerable variations may occur in the temperature of relapsing fever. Instead of by crisis, for example, the fever may subside by lysis, and in some cases a secondary rise may abruptly succeed the critical fall. The pulse during relapsing fever follows the course of the temperature, though with a tendenc}', more marked with each successive relapse, to lag behind. It rapidly increases in frequency' with the onset of the fever and continues to rise, though less slowly, as the crisis is approached. Its rate commonly reaches 120 per minute during the first day of the disease — rather more than that in women and children — and by the third or fourth day of fever it may be 130 or even 140 per minute. With the crisis the pulse-rate falls, though less rapidly than the temperature. It may be unusually slow for a day or two following the crisis, after which it returns to normal until the relapse sets in. Although at first bounding, the pulse of relapsing fever soon becomes soft and compressible, these features (which are almost invariable) becoming more marked in proportion to the duration of the disease. Corresponding with the condition of the pulse, the heart almost invariably shows signs of weakness. The impulse soon becomes weak and the first sound pro- longed and booming. In rare instances, and these almost always met with during the acme of the initial attack, sudden heart failure occurs, causing fatal syncope. Respiration in an uncomplicated case of relapsing fever corresponds with the pulse. There is commonly slight bronchial conj^estion evidenced bv couo'h and frothv expectoration. With no further complications than this, 176 TROPICAL MEDICINE AND HYGIENE the breathing may be very rapid and the patient may suffer from acute dyspnoea at the acme of the fever, which, however, is quickly reheved with the fall of temperature. A frequent and serious complication of relapsing fever is pneumonia, which may be either of the lobar type or more commonly lobular. The relation of the two conditions is liable to be over- looked, for while on the one hand the indications of serious pulmonary inflammation may be so slight as to be only discovered after death, on the other hand pneu- monia may be the most prominent feature of the illness and may modify the crisis or obscure the onset of a relapse. The onset of pneumonia is most common towards the end of the initial attack, but may be earlier or not until the commencement of a relapse. It may sometimes be indicated by a diminution in the severity of the general symptoms shortly before the crisis is due. The temperature and pulse-rate fall, breathing becoming more frequent, and working of the alae nasi may be observed. The headache and bodily pains diminish and there is less epigastric discomfort. Examination of the chest will reveal the ordinary physical signs of pneumonia. There is, however, less tendency to involvement of the bases of the lungs than in primary pneumonia. It is always accompanied by pleurisy. Reference has been made to the thirst, vomiting, and epigastric discomfort of relapsing fever. The severity of the thirst is often a striking symptom. It is associated with a dry tongue, which quickly becomes coated with brown fur, except at the tips and edges. Following the crisis the tongue soon becomes clean and the thirst diminishes. Vomiting is a variable symptom. It is usually not serious, but the irritability of the stomach may render feeding difficult and aggravate the thirst. The vomited matter is usually greenish, a mixture of bile and mucus, occasionally containing streaks of KELAPSING FEVEK 177 blood. In rare instances "black vomit" has been observed. The epigastric discomfort which is so common a symptom is due to catarrhal inflammation of the stomach, partly also to active congestion of the liver and spleen. While the constipation of the early period of relapsing fever is constant enough to be of some diagnostic value, severe diarrhoea not infrequently occurs at the crisis, the stools sometimes containing blood. Occasionally there is actual dysentery, depending prob- ably upon previous infection. Pain and tenderness of the liver and spleen are early symptoms. Both organs are enlarged, the spleen ■especially, and both rapidly diminish in size after the crisis. Frequently associated with enlargement and tender- ness of the liver is jaundice, though this symptom is more common in some epidemics than in others. It usually commences about the fifth day of the initial attack, disappearing a few days after the crisis. Its intensity varies greatly, but while usually slight and transient it may sometimes be very intense. The urine is dark and scanty during the febrile stages of relapsing fever, and also during the early part of the apyrexial period. It is of rather low specific gravity (loio to 1015), and contains an excess of urea. A small amount of albumin may occur, and granular casts may be found ; blood is uncommon. When jaundice is present the urine contains biliary pigments. Mention has been made of the hot, dry skin of the febrile stage and of the sweating at the crisis of relapsing fever. The skin, though dry, does not feel so hot as might be expected from the bodily temperature, thus dift'ering from the condition observed in certain other acute febrile diseases, pneumonia for example. The critical sweats are usually very profuse, even more so than in malaria, and may saturate the clothes and bedding. 12 1 78 , TROPICAL MEDICINE AND HYGIENE Night sweats sometimes occur after the crisis, and during relapses the skin may often be moist. While there is usually no rash in relapsing fever, facial herpes is not uncommon. In certain cases small rose- coloured spots, something like those of enteric fever, but smaller, are met with. They come out in crops, which^ commencing near the crisis of fever, may continue into the apyrexial period. These papules are most common on the front and sides of the chest and abdomen. They are never very numerous, last only a few days, and disappear on pressure without leaving a stain. Sudamina are common, and in rare cases petechias are met with. Desquamation, except in the form of minute branny scales following sudamina, is uncommon. Complications. — The more important complications of relapsing fever are pneumonia, severe diarrhoea, or dysen- tery, and have already been dealt with. Mention may here be made of the liability of a small! proportion of cases to haemorrhages. Epistaxis at the acme of fever is the most common example. Haema- temesis may also occur, and more rarely cerebral haemorrhage, always fatal, has been observed. Swelling and inflammation of the parotid gland and of lymphatic glands, most commonly those of the inguinal regions, have been observed occasionally. This is of importance in connection with the differentiation of the- disease from plague. Inflammatory affections of the eye and ear sometimes- occur, but are rarely serious in the Indian variety. Inflammation of serous membranes are rare, but slight painful swelling of some of the joints, most commonly those of the upper limb, are not uncommon. Pregnant women always abort; the abortion is gener- ally followed by recovery. The coexistence of relapsing fever with malaria, small- pox, measles, plague, and diphtheria has been noticed, and in certain epidemics, following famines, with scurvy. RELAPSING FEVER 179 There are no special seqnehc of relapsinj:^ fever, though mental and bodily weakness frequently persist for some time. Propjwsis. — The prognosis of an uncomplicated case of relapsing fever is good. The mortality varies in different epidemics, probably depending upon the con- dition of the infected population. When the disease prevailed in Great Britain the mortality was estimated at about 4 per cent. A similar rate is said to be common in Russia. In Bombay, however, Vandyke Carter found that the mortality was 18 per cent. His statistics were, however, based upon hospital experience. The death-rate amongst cases treated in the municipal hospital in Bom- bay during the last ten years has been much higher than this, something like 30 to 40 per cent., and Choksy re- cords 2,832 deaths out of 9,275 cases, from 1898-1907, an average mortality of 30'6, but in the northern parts of India the mortality is not high. Death is most likely to occur during the acme of the initial attack and may be due to collapse or to heart failure, or may occur during collapse following the crisis. The risk is greater in the first attack. As might be expected, extremes of age are unfavourable. The case mortality is slightly higher among women than among men, though abortion is usually followed by recovery. In cases complicated by pneumonia the prognosis is unfavourable, recovery being rare. Severe jaundice also renders the prognosis unfavour- able, and, as has been seen, cerebral haemorrhage is alwavs fatal. Diagnosis. — While a typical case of relapsing fever is easily recognized, instances occur in which it is impossible to arrive at a correct diagnosis by means of the clinical signs alone, and the real nature of the disease may quite easily be overlooked, even at the autopsy. It can be understood, also, that a patient seen for the first time at the acme of the fever or at the crisis might be thought to be suffering from malaria, while, but for the occurrence l8o TROPICAL MEDICINE AND HYGIENE of the crisis, the diagnosis in severe cases might well be that of septicaemic plague, especially should death ensue. It may be added that the pneumonic form of plague may resemble that of relapsing fever, though it is usually much more severe, and the very abundant prune juice sputum, seen in pneumonic plague, is characteristic when it occurs. It is quite possible that cases of relapsing fever accom- panied by severe jaundice and bloody vomiting, occurring in countries in which yellow fever prevails, might easily be mistaken for that disease. The discovery of the Spirillum obernieieri in the blood is therefore sometimes the only means by which a positive diagnosis can be arrived at. It is essential, therefore, that all cases in which the diagnosis of relapsing fever is doubtful the blood should be carefully examined for this parasite. Moreover, in view of the differences which have been described in the spirilla of relapsing fever cases occurring in different parts of the world, and of the discovery of a similar parasite in the blood of persons suffering from African tick fever, the examination of the blood in cases in which the clinical diagnosis has been well established is of great interest and importance. It should be remembered that the spirillum can usually be found in the blood only during the febrile period, as it disappears at the crisis and reappears only with the onset of a relapse. This state- ment is not absolute, however, for cases are not infrequent in which spirilla have been discovered, though in greatly diminished numbers, in the blood of patients during the early part of the apyrexial period. For the discovery of the spirilla, either fresh, unstained, or dry-stained films may be used. In either case the search may be easy or difficult, depending upon the number of parasites present, this varying greatly. In some cases they may be so numerous as to make the whole of the field of the microscope seem in active motion, while in others careful search of stained films is necessary to discover any. The best staining method is probably Leishman's or RELAPSING FEVER lOI other modification of Romanovvsky's stain. Failin^f this, gentian violet or carbol-fuchsin may be used. The spiril- lum is described under the heading of Etiology, p. 183. The blood of patients suffering from relapsing fever shows a condition of leucocytosis. The number of both polymorphonuclear and mononuclear leucocytes is in- creased. Sometimes this is very marked, and as there is also a diminution in the number of red corpuscles the excess of these over the leucocytes is greatly reduced. The spirillum has not been demonstrated in any of the patient's secretions or excretions. Morbid Anatomy. The bodies of patients dying of uncomplicated relapsing fever do not show any very characteristic gross changes. The condition is that of a general septicaemia with en- largement of the spleen and liver and catarrhal inflamma- tion of the stomach — often also of the intestines and of the bronchi. Subserous haemorrhages under the peritoneum, pericardium, and pleura are common. The enlargement of the spleen is usually very considerable, its weight sometimes reaching 5 lb., and its size exceed- ing the normal by five or six times. The splenic capsule is distended and smooth, and the whole organ is rounded. The spleen substance shortly after death is firm and dark mottled with small white spots, which are the enlarged Malpighian corpuscles ; these may sometimes be breaking down into minute abscesses. Large wedge-shaped infarcts are common, usually having their base at the capsule, though they may be met throughout the organ. When recently formed they are of a dark red colour, but later they become pale and may be found breaking down into pus. Microscopically the hypertrophy of the spleen is found to be due both to proliferation of its cellular elements — especially of the Malpighian corpuscles — and to vascular engorgement. Spirilla may be found in the spleen both free and in polymorphonuclear cells, often in great profusion. l82 TROPICAL MEDICINE AND HYGIENE The enlargement of the hver is often marked and the weight may be as much as 5 lb. Though sometimes dark and congested, it is more commonly pale and mottled. Its substance is soft and the lobules are in- distinct. There is cloudy swelling of the cells. Besides the conditions mentioned, the heart is usually found to be pale and soft, the muscular fibres showing signs of cloudy swelling and sometimes fatty degenera- tion. The kidneys and other abdominal organs are also in the condition of cloudy swelling. The inflammation of the intestinal tract is often considerable. The stomach is the part most commonly affected and there are usually numerous small haemorrhages beneath the mucous membrane. . In cases complicated by diarrhoea or dysentery there is intense congestion of the ileum and colon, which may even be superficially ulcerated. A certain amount of bronchial catarrh is usually found, but in uncomplicated cases the lungs are pale. Two forms of pneumonic consolidation may be met with. The more common form is that in which patches of consolidation, often of considerable size, are scattered through both lungs ; they may be met with in any part of the lobes and are not more common at the bases than elsewhere. The other form of consolidation is similar to that of ordinary croupous pneumonia. While inflammation of the brain or its meninges is rare in relapsing fever, passive congestion as shown by venous engorgement and serous exudation is not uncommon. Etiology. — Relapsing fever is remarkable in being the first disease shown to be due to a micro-organism. During an epidemic in Berlin, in 1868, Obermeier dis- covered in the blood of patients suffering from relapsing fever a spirillum, which since the publication of the discovery in 1873 has been accepted as the cause of the disease. These spirilla are now commonly termed spirochaetae. . The Spirillum obenneieri or S. recurrentis is a delicate KELAPSING FEVEK 183 wavy thread measuring between 15 ^ and 40 /x in len^^th by about '25 fju in breadth at its widest part. The num- ber of spirals varies greatly, as also does their contour. A common number of spirals is eight, but often two spirilla are joined together, giving the appearance of one long form with sixteen spirals. Sometimes the spirals may be short, giving a corkscrew appearance, or they may be only slight undulations. In thick films the spirilla may be in bold curves or figures of eight, with few or no undulations (fig. 41), Fig. 41. No details of structure can be made out except that it has tapering pointed ends, and that, especially when stained by Romanowsky's method, slight difference in the degree of staining of different parts can be noted, the central part staining least. Some observers have de- scribed a delicate terminal flagellum ; the presence of flagella is denied by most observers. A striking feature of the organism is its extraordinary motility, which is 184 TROPICAL MEDICINE AND HYGIENE progressive as well as rotary and lateral. It is best stained by aniline dyes, especially by some modification of Romanowsky's stain, and also by carbol-fuchsin and gentian violet. It is decolorized by Gram's method. When faintly stained by Romanowsky's method the parasite is blue, if the staining is prolonged it becomes red. All attempts to cultivate it have failed, but it can be kept alive in citrated blood outside the body for several days. Tictin found the spirillum in bugs fed upon patients suffering from relapsing fever and showed that they could survive in them for seventy-seven hours. He also succeeded in infecting monkeys with the fluids of such bugs crushed immediately after feeding, but when bugs had been killed forty-eight hours after feeding their fluids were not infective, although the S. obermeieri could be found in stained preparations. Karlinsky, in infected houses, found the spirillum in bugs, and that the spirilla could live in these for thirty-nine days. Blood containing the spirillum has been frequently inoculated into man, both deliberately and by accident, and has caused relapsing fever. Various kinds of monkeys have also been successfully inoculated. Until recently man and monkeys were considered to be the only susceptible animals, but Novy and Knapp have recorded the successful inoculation of white mice in which relapses occurred, and of white rats. The incubation period following inoculation in man is usually between thirty and thirty-six hours. There has been a good deal of speculation as to the interdependence between the presence of spirochaetes and the different phases of relapsing fever. An early view was that the fever resulting from the presence of the parasite in the blood caused its destruction and that relapses were due to the development of further generations of spirilla from spores. The existence of spores of S. obermeieri has, however, not been demonstrated. The blood of a patient during the apyrexial intervals will still infect monkeys if injected RELAPSING FEVER 1 85 into tlieiii. Another view attributed tiie disappearance of spirilla to the formation in the blood of some bacteri- cidal a^^ent at this crisis, while a more modern view is that the spirilla are destroyed by phagocytosis, this destruction occurring chiefly in the spleen. Th:OCH/KT.l': 201 The discuses believed to be remc^lely due lo syphilis in En^dund ;ire pnictically unknown in 1lic Tropics amon^fst the natives; these are the parasyphilides — ,L;eii('ial paralysis of the insane, and tabes dorsalis. In the treatment of syphilis amongst natives it must be remembered that mercury is not well borne by anaemic persons and that pyorrhoea alveolaris, so common in native races, is often increased by mercury, and must therefore be treated independently. In dealing with large bodies of men intramuscular injections are specially valuable, as a weekly injection insures sufficient treatment. The method in use in the Army is essentially that intro- duced by Colonel Lambkin. A cream is made of metallic mercury in lanolin : — Hydrargyri ... ... ... ... ... ... ... Ji. Adipis lanre ... ... ... ... ... ... ... o''^'- Paraffin liquid! (with 2 per cent, carbolic acid) ... ad 5X. The mercury and lanolin are by weight, the liquid paraffin by volume. Great care must be taken to obtain a thorough mixture of the mercury. It should be stored in small quantities, as if kept in bulk the mercury will settle at the bottom. Ten minims of the mixture contain I grain of mercury. Injections must be made into the muscle, preferably the gluteus maximus, and never into the subcutaneous cellular tissue. The skin must be care- fully sterilized before the injection. An all-glass syringe should be used ; this may be sterilized by drawing up olive oil at a temperature of 160° F. Between the injections the point of the needle should be dipped into the heated oil, and the needle should be wiped with a sterilized cloth so that none of the mercury cream is left along the track of the needle. It is important that the patient should not take any violent exercise for some hours after the injection, and care must be taken that no injection is given in a place where there is any induration as a result of previous injections. The advantages of the method are : (i) An attendance once a week only is required ; (2) there is no 202 TROPICAL MEDICINE AND HYGIENE uncertainty as to whether the mercury is regularly taken ; (3) though the rate of absorption varies, still the mercury is certainly absorbed. The disadvantage is that the injection is slightly painful, that a certain amount of induration and tenderness may be left, and that, rarely, abscesses may form. Much depends on the confidence the natives have in their medical ofBcer. Congenital syphilis is not common, but it is probable that syphilis is an important factor in the causation of the large number of abortions and stillbirths, and is respon- sible for much of the sterility of the native. It must be remembered that the negro is fertile earlier in life when the effects of the virus are most marked, but ceases to be fertile in many cases at an earlier age than the European, and therefore has few children at ages when the most fatal effects of the disease are less likely to occur. Prophylaxis. — Prophylactic measures are similar to those required in England. The local labour supply is usually insufficient for the large plantations, mines and other enterprises of Europeans. Large numbers of men are therefore imported from other districts and countries or attracted by the superior rate of pay. Men as a rule come in great excess of women, who are of less value as labourers, and many of these women are or become prostitutes. With such gangs of men, whether soldiers or labourers on plantations, it is often possible to find the infecting agent or agents. A certain proportion of women should always be imported with the men, and this is arranged for in Indian immigration ordinances. Every encouragement should be given to men bringing their wives, and labour of a suitable kind should be pro- vided for women as well as men, even if it is not directly remunerative to the employer. Under any circumstances the immigrant system usually results in a larger or smaller proportion of the men becoming infected, and these, having earned a considerable supply of money, often disseminate the disease on their return to their native villages. The disease is then propagated in the YAWS 203 same mannci-, and unless the human canici-s of tlic disease are isolated or segregated reliance is only to he placed on personal prophylaxis. Regular inspection of men as well as women, detention and treatment until the most infective stage is passed, will greatly reduce the prevalence of the disease. Legislation and increased powers in dealing with such cases are much to be desired. A warning is necessary to missionaries and others as to interference with native customs too quickly. Amongst most natives, women are jealously guarded and their movements restricted in many ways. This condition is sometimes considered by Europeans as " slavery." An unfortunate result of too speedy liberation from their accustomed restraints is a great increase in the amount of promiscuous intercourse and the rapid spread of syphilis and other venereal diseases. Other Granulomata. Amongst the large class of diseases known as infective granulomata, two of the purely tropical ones are asso- ciated with the presence of spirochjeta, yaws and granu- loma pudendi. But similar organisms have been found in many forms of ulcers. Yaws. Yaivs. — Franiboesia tropica. Native names : Piirii (Malay), Coko (Fijian), Paraiighi (Ceylon), &c. This disease is characterized by the appearance of successive crops of raised granulomatous nodules covered with thin or thick sulphur-yellow crusts and subsiding without deep ulceration or the formation of any but superficial scars. The usual duration of the disease is two or three years, but on the parts of the body where the epidermis is thick, such as the soles of the feet, it may persist for much longer. Destructive ulceration of the mucous surface and a lupoid eruption on the face are by some considered to be sequelae, and onychia mav also occur, Geograpliical Distribiifion. — As an indigenous disease it 204 TROPICAL MEDICINE AND HYGIENE was probably limited to the West Coast of Africa, to the aborigines of the Malay Peninsula, possibly Ceylon, and to the Pacific Islands. Introduced by the slave:, into the West Indies and South America, it has been firmly established there for over a century. An outbreak has also occurred in Assam, probably introduced by labourers returning from Fiji or the West Indies. Cases are occa- sionally seen in many tropical ports, and to a limited extent it has spread amongst the inhabitants of such ports. It does not occur on the East Coast of Africa and is very rare in the central plateau. Outside the Tropics it does not seem to spread. Fig. 44. Clinical Course. — Experimental inoculations have shown that there is a period of incubation of about twenty-eight days. In such experiments there need be no primary sore ; a primary yaw is, however, common in accidental inoculation. It may appear at the edge of an ulcer or in a clean-cut wound, but is more common at or near the junction of the skin and mucous membranes, such as the angle of the mouth. When there is a primary sore it is a raised granulomatous mass similar to the YAWS 20 = siibsct|ucnt eruptions. Tlic i^cnci'alizcd eruption iii;iy ;ippe;u- in any part of the body and is associated with febrile symptoms. Sometimes the temperature is 103' or 104° F. There are achin<4 pains in the hmbs, and particularly in tlie back and loins, sometimes severe enougii to raise the suspicion of small-pox. The erup- tion may be abundant, but in other cases there may only Fig. 45. be a few yaws limited to the lower part of the face, the chest, or the genitals (fig. 47). When there are few yaws they are more common near mucous orifices ; when abundant the whole body and limbs may be involved (tig. 45). On the extensor surfaces the eruption tends to be more abundant. The scalp and axillae are rarelv involved, and the palms and soles only in the later eruptions. The actual duration of each vaw is three or four weeks, and 206 TROPICAL MEDICINE AND HYGIENE fresh yaws may appear before the subsidence of the earher ones. On moist surfaces, as in the perinaeum and at the angles of the mouth, httle or no crust is formed on the yaw, but in drier parts the pecuHarly yellow scab is always FiG. 46. present. This scab is detached with difficulty, and a slightly milky fluid is found beneath it. The exposed surface bleeds very readily. The glands are not enlarged unless the yaw is injured or secondarily ulcerated. Ulcer- ation may take place in parts exposed to much movement LATE YAWS 207 or to friction, and secondary deeper ulceration sometimes, but rarely, occurs. The eruption may recur for two or three years, but the later crops are usually scanty, and in this stage are frequently under thick, hardened epideiinis, such as the sole of the foot (fig. 46). Fig. 47. The granulomata in such situations cannot grow to any great size, and are compressed by the thickened epidermis and very painful. These painful granulomata on the soles of the feet may persist for years after all 2o8 TROPICAL MEDICINE AND HYGIENE other manifestations of the disease have ceased — "crab yaws." Sequelae attributed to yaws are numerous, but the evi- dence that they are related to that disease is inadequate. A destructive ulceration of the mucous membrane of the mouth, palate, pharynx, and nares is common in Fiji, and occurs in other countries where yaws is common. It is a disease which occurs usually in early adult life, many years after the last definite manifestation of yaws. It occurs in persons who have not had syphilis, and if not a sequela of yaws is probably a separate and distinct disease and will be described separately. Associated with this disease is sometimes a lupoid ulceration of the skin of the face, extending by continuity from the ulcera- tion of the nares. Periostitis, and chronic ulcers of the legs and elsewhere have been described as sequelae of yaws. If they are results of this disease they are very rare ones. Gummata probably do not occur. Diagnosis. — At the onset of the general eruption, and whilst the granulomata are still small, in cases where the muscular and back pains are severe and the temperature is high, the disease has been mistaken for small-pox ; such errors are very rare. The disease in the majority] of cases has to be diagnosed from syphilis and other skin diseases. In a single case the diagnosis from a fram- boesial syphilide may be impossible ; from any other syphilide it is easy. The absence of ulceration, the raised granulomatous tumour and the sulphur crust with the milky fluid underneath it differentiate the disease from rupia or similar tertiary syphilitic lesions. Where the case is under observation the close similarity of the successive eruptions is unlike that in syphilis. The exposure to contagion, the occurrence of other cases, and the absence of any other signs of syphilis all aid in the diagnosis. Prognosis. — Death may occur in children under one year, or in debilitated persons, but even in such cases a fatal termination is exceptional. Good feeding, cleanli- YAWS AND SYl'HII.IS 209 ncss, and protection from irritation of the yaws dinunish the habihty to ulceration but do not shorten the course of the disease. Pathological Anatomy. — The lesions are limited to tlie skin and subcutaneous tissues. Essentially the i^rowth is a vascular granuloma, and there is no tendency to caseation, necrosis or suppuration. The epidermis is softened, and the distinction between the various layers is lost. Pigment is either not formed or irregularly distributed in the deeper layers or subcutaneous tissue. Keratinization is imperfect and the superficial layers of epidermis are cast oiif, and form the scab covering the granuloma. The cause of the peculiar yellow colour is unknown. In moist situations in the neighbourhood of the genitals or mouth there is little or no scab formation, and superficial ulceration is common. r7-(sa/;/;6'///. —Probably no drug influences the duration of the disease. Mercury and arsenic certainly do not. Potassium iodide is uncertain in its action. The erup- tions will sometimes disappear rapidly when iodides are given, but even in such cases when the use of the drug is continued fresh eruptions appear. The use of iodides is therefore limited. Local applications that merely sei-ve to keep the granuloma clean are valuable, but eschar- otics and irritants, though they may destroy the yaws are likely to cause the formation of scars. The painful granulomata on the feet are best destroyed by the action of nitric acid, acid nitrate of mercury, or silver nitrate. Etiology. — Most observers who have had extensive experience of the disease known as yaws consider it to be a clinical entity. Some eminent authorities, and especially Hutchinson, believe it to be syphilis, and that the differences from the common manifestations of that protean disease as seen in temperate regions are due to the effect of climate, race, and heredity in the Tropics. The similarity of the two diseases will be admitted by all. In both there is a rather prolonged period of incu- bation with a primary sore, rarely absent in syphilis, 14 ■2IO TROPICAL MEDICINE AND HYGIENE commonly absent in yaws, and a series of cutaneous eruptions lasting for months or years, with later manifesta- tions usually of a destructive character, which are common in untreated syphilis, and also in yaws if the lupoid diseases of the mucous membrane are correctly attributed to the antecedent yaws. The parasitic cause of syphilis is now generally believed to be a spirochaete, Spirochceta pallida, and a spirochjete morphologically indistinguish- able from S. pallida has been found by Castellani in yaws, S. pertenuis. That the diseases belong to the same class is clear ; that they are identical is a different matter, and is open to serious question. The manifestations of yaws for at least the first three years of the disease are all of the same character, the primary sore and each successive eruption differing slightly in moist parts, or when under thickened epi- dermis. Syphilitic cutaneous manifestations are poly- morphic. Yaws may be universal in a population, but if uninfected newcomers of any race — Europeans, Portu- guese, Chinese, Negro, Malays, Indians — are introduced into such a community and are infected, the disease they acquire is yaws, and resembles in all its characters the disease in the native population. From a single source of infection in a negro the disease has been acquired in the same form in a whole family of Portuguese, and in an Indian servant. Yaws therefore breeds true. Syphilis, when acquired by members of the same races, presents the usual characters of that disease. Syphilis is little modified in persons resident in the Tropics. The formation of gummata and the extensive and destructive bone lesions do not occur in yaws. It is sometimes urged by those with little experience of some of the native races, amongst whom the disease is common, that the over- crowding and filth of the native houses favours the wide diffusion of the disease, and that therefore the fact that all the children have " yaws " is no argument against the disease being syphilis. A closer study of these races will convince anyone that as regards personal cleanliness and YAWS PKOl'lIYLAXIS 211 absence of overcrowding unci morals they compare very favourably with the lower classes of Europeans, amongst whom syphilis does not become universal in the children. Yaws does not protect from sypliilis nor syphilis from yaws. The relationship between yaws and syphilis, in the sense of both diseases being due to organisms of the same genera, is admitted and was predicted, but the relationship is like that between variola and varicella, not that between variola and vaccinia. Prophylaxis. — Infection can be carried from man to man by direct contact, and the virus is contained in the discharges from the granulomata. The frequency of the early yaw in the neighbourhood of the mouth suggests that food is a frequent source of infection. The com monest ages for infection, 3 to 5 years, are ages at which children frequently exchange partially eaten pieces of food. Probably flies are also direct carriers of infected material, and the frequency with which ulcers and wounds become infected is probably explicable in this manner. The chigoe {Sarcopsylla penetrans) is by some believed to be an important carrier. There is no evi- dence that the virus can enter through the unbroken skin, but cracks about the mouth, small ulcers as a result of insect-bites, or other sources of irritation are so common in the Tropics that possibilities of infection are numerous. There is little risk to well-clad Europeans, even if stopping in the same house as persons with the disease, but amongst European and half-caste children who play about with native children cases of infection are common. It is well to carefully cover up even superficial wounds, and to prevent, if possible, children from having access to natives in a country where yaws is endemic, and to take sufficient precautions to prevent the inter- change of partly eaten articles of food with native children. " Guam " disease in most respects corresponds to the description given of the destructive ulcerations about the 212 TROPICAL MEDICINE AND HYGIENE naso-pharynx so common in Fiji, and there considered to be tertiary framboesia. Those who consider it a separate .disease call it granuloma gangrenosa. It is said to be most common in places where yaws is rare, and to be very rare in some places where yaws is very common. Probr ably it is the same condition as the Fijian " kanailoma.'" FiG. 48. Granuloma of the Pudenda. Serpiginous Ulceration of the Genitalia. (McLeod) ; Ulcerating Granuloma of the Puden- dum ; Sclerosing Granuloma of the Pudenda. — The disease manifests itself as a chronic indurated super- licial growth on or near the genitalia, male or female. It is slow growing and extends along moist surfaces, whilst, the older and deeper portions of the growth are converted, into a dense fibrous mass of tissue. It is very vascular. Geographical Distribution. — It occurs in many islands of the West Indies, in Tropical South America, on the West Coast of Africa, and either it or a similar disease GRANULOMA OF THE PUDIiNDA 213 occurs in India, Northern Austi'alia, and many oi the Pacific Islands. Clinical Course. — This differs to some extent in different races, and in the two sexes. It usually commences in the male on the penis, and extends in the neighbourhood that organ ; if situated on the skin it is very slow growing, but is more rapid when the glans is attacked, and the granulations may then be very large and coarse ; it extends for a fraction of an inch up the urethra, and causes very serious stricture. It rarely extends by direct continuity down the penis ; more often the inguinal folds Fig. 49. or other places with which the penis may rest in contact become infected (fig. 49), and from such a point extension by continuity along the fold of the groin (fig. 49), and back- wards on the inguino-scrotal fold, takes place, and from that directly backwards on the perineum surrounding the anus, and extending up it into the lower part of the rectum (fig. 50). Sometimes both groins are affected. Frequently the penis and scrotum become slightly ele- phantoid, probably from compression of the lymphatics by the indurated subjacent tissue. 214 TROPICAL MEDICINE AND HYGIENE In the female the early growth is on the inner surface of the labia majora or nymphse, which may become elephantoid, and the growth extends upwards into the vagina, and rarely into the bladder. It also extends over the labia majora, and backwards along the perineum, surrounding and extending up the anus. In such cases, where both the vagina and rectum are involved, incurable Fig. 50. recto-vaginal fistulas are common. The growth may continue for many years, and the general health of the patient is not affected. The lymphatic glands are not en- larged, though there is evidence of lymphatic obstruction. There is always a considerable formation of hard fibrous tissue beneath the growth, and when healing occurs GRANULOMA OK THK PUDKNDA 215 natui'.'illy the growth is entirely converted into dense fibrous tissue. Very rarely complete cicatrization takes place ; more frequently it is partial and extension of the growth at the edges takes place. Spontaneous healing of the mucous surfaces does not take place. The diagnosis has to be made from other diseases of the same part. On the penis it is frequently mistaken for epithelioma. In the groin it may be mistaken for any form of ulceration, syphilitic or otherwise. In the vagina it is usually mistaken for chronic gonorrhoea. The chronicity of the growth, the dense fibrous base, and the absence of glandular enlargement are important points in the diagnosis. In cases of doubt, microscopic examination will exclude epithelioma. Prognosis as regards life is good. The growth is not malignant. Natural cure is highly exceptional, and it is only when complete removal of the growth can be effected that recovery is probable. The most troublesome complications are stricture of the meatus of the urethra, which can only be treated effectually by amputation of the glans penis ; recto-vaginal fistulas, which are not suited for operations, as the tissue between the rectum and vagina is mainly composed of the growth ; and stricture of the anus with ulceration of the lower part of the rectum. If the growth does not extend too high, excision, of the rectum gives good results in the last complication. Pathological Anatomy. — The growth is a vascular granuloma. The cells are round cells with a single rounded nucleus. There are no giant cells. There is no tendency to caseation, necrosis, or suppuration, and the epithelium is usually present over the growth, though softened and thickened. Treatment. — Mercury and potassium iodide in the majority of cases have no effect. In a few, where the tendency to natural cure is strong, large doses of iodides seem to aid this tendency. Cleanliness and antiseptic dressing favour rather than 2l6 TROPICAL MEDICINE AND HYGIENE retard the growth. Escharotics, such as chloride of zinc, nitrate of mercury, and saHcyhc acid, are rarely effective ; complete excision of the growth where that is possible is highly satisfactory, but the dense fibrous tissue should be excised as well. The raw surface left is always more extensive than the growth removed. Where excision is impossible, scraping and the use of escharotics may give satisfactory results. Good results have been obtained by the use of the Rontgen rays. In Dr. McLeod's case the use of these rays converted the granulomatous tissue into a cheesy mass, which was readily scraped away, and healing then took place rapidly. Etiology. — The occurrence on the genitalia and the different situations in the two sexes are strongly in favour of the view that the disease is conveyed by venereal inter- course ; it does not seem to be highly contagious, as there are cases where the husband only is infected and the wife escapes. Spirochcetes resembling S. pallida and S. refringens have been described by Wise as occurring in these granulomata. 217 CHAPTER XVII. Intestinal Protozoa, &c. Many protozoa are found in the intestines, and may be discharged with the faeces. In coccidia infections either of the Hver or intestinal mucosa the fertihzed macrogametes are discharged in this manner. The more important of the human intestinal protozoa are those associated with diarrhoea and dysentery. These diseases are so often due to bacterial infections, and the prevention of such diseases so closely connected with the disposal of sewage and the provision of a good water supply, that they are best considered at the same time as the similar diseases due to vegetable organisms in Part III. Only a brief reference to these parasites and the diseases they cause will be given here. The protozoal organisms described as concerned in the production of intestinal diseases are Sarcodina, such the Ainceba coli ; Flagellata, as Tricliomojias hoiiiinis, Lamblia intestinaUs and various spirochseta; and Infusoria (Ciliata), as the Balantidiiun coli (fig. 51). Of these the most important is the Anuxba coli — Ent ainceba histolytica (Schaudinn). Other protozoa, especially Bahmtidiiim coli, which invades the tissues, may cause ulceration and all the symptoms of dysentery. Lamblia intestinaUs is probably pathogenic. It does not invade the tissues, but lies closelv applied bv its sucker-like aspect to the mucosa, both in the small and large intestine, and is associated with chronic enteritis. The symptoms are of a chronic recurrent diarrhoea, with abundant discharge of mucus, often bile-stained, and sometimes there is also blood. When there is diarrhcea 2l! TROPICAL MEDICINE AND HYGIENE the parasite may be found in abundance ; at other times the encysted forms only will be found. These are easily recognized by their oval shape and the pair of nuclei situated near one extremity. The treatment is not very satisfactory. Free purgation to remove the mucus, followed by intestinal antiseptics such as kerol, seems the most promising line of treatment. The Amoebina. — An order belonging to the Rhizopoda Fig. si. or Sarcodina. The members of this order are either naked masses of protoplasm or enclosed in a simple shell, either secreted by the organism or formed from some foreign substance. They have blunt, lobulated or finger-shaped pseudopodia and a single nucleus. Many of them live in fresh or salt water, and are abundant where there is moist decaying vegetation ; some are parasitic. In the genus Amoeba the body is always naked, and usually there is a marked distinction between the outer part, ectosarc, and the interior, endosarc. The former is clear and INTESTINAL PROTOZOA, AMGiHA 219 tninsparcnt but viscid, whilst the latter is more liquid and granular, and frequently contains foi-eign bodies taken in as food. The compact nucleus and a contractile vesicle are contained in the endosarc. Asexual multiplication by simple division of nucleus and cytoplasm. Fig. 52. — Scheme of Development of Amreba. Multiplication in encysted forms (autogamous). ? sexual multiplication. The early stages of division of the nucleus [a—d) and conjugation of the divided nuclei in pairs (e), followed by further division of these products of conjugation, first into two and then into four each {/—z). The thick wall of the cyst in the later stages indicates the hardening of the cyst wall during the stages when the cysts are outside the body. When active the amcebas are constantly changing shape, and throw out blunt processes or pseudopodia. The number and shape of these are points to consider in the differentiation of species. When motionless or dead the amoebae assume a spherical form, and are difficult to 220 TROPICAL MEDICINE AND HYGIENE distinguish from other mononuclear cells. Propagation takes place by budding, division, or segmentation. Amoeba coli. — This is a large amoeba, frequently '05 mm. in diameter, though smaller forms are common. The ectosarc can be readily seen when pseudopodia are thrown out, but it is difficult to see in the resting animal. The pseudopodia are very broad and only one or two are protruded at a time. Movement is active at or near blood-heat, but is retarded or stopped at lower tempera- tures. Multiplication of the amoeba may take place by simple division ; the nucleus divides, and the protoplasm then divides so that two equal individuals are produced. This is the asexual method of reproduction, and takes place readily where the conditions for existence are favourable. The second method may be considered as a rudimentary sexual process, though the conjugation is by fusion of two chromatin masses derived from one nucleus and not of two separate cells. If considered as a sexual process it would be an instance of autogamy. In this method the amoeba becomes encysted. The nucleus divides into two, and each of these nuclei after extruding polar bodies again divides into two. The four nuclei thus produced conjugate in pairs, so that the number of nuclei is again reduced to two. These two nuclei each divide into two and then again divide so that there are eight nuclei, and these with the protoplasm segmented round them form eight young amoebae which are still contained in the cyst (fig. 52). These quasi-sexual encysted forms are resistant, and it is probably in this form only that is capable in the para- sitic amoebaj of retaining vitality in a free form under ordinary meteorological conditions. These encysted forms are therefore the important ones, as the infective agents in amoebic infection. In some of the parasitic amoebae in the lower animals the active amoebae are only found in the small intestine. The changes described take place in the large intestine. The amoebae passed in the faeces are all encysted. In such INTESTINAL PROTOZOA, AMOCIiA 221 animals, if the intestinal contents were passed rapidly through the alimentary canal, as aftei" purgatives (;r in diarrhoea, active amoebae will be passed with the stool. In man encysted amcebcX3 may be found in apparently healthy stools, but the hosts from time to time have attacks of diarrhoea or dysentery and then the active amo^hcc are present in the stools. AmcEb?e parasitic in the internal organs of man are sometimes called Eiitanicebcv. Morphologically there is no real diiference between these and other amoebae beyond the absence of a contractile vesicle. There are said to be three species, one occurring in the mouth, A. hnccalis, in some persons with dental disease, and two in the large intestine. One of these, the A. coli, or Entanioeha coli, is not found in other parts of the body and the life-cycle is as described by Schaudinn. According to the same author it is distinguishable by its appearance as the ectosarc or ectoplasm, is not visible as a distinct layer, and the nucleus is large and rich in chromatin, so that it stains deeply in stained preparations. This amoeba is not considered to cause disease. It may be present in the small intestines as an active motile amoeba, and only the encysted forms found in the stools unless there is diarrhoea. The other intestinal amoeba, Entmnoeha histolytica, has a more distinct ectoplasm and the pseudopodia are entirely formed by it at first, so that they are tougher and stronger than those of the A. coli. The nucleus is not readily visible and is poor in chromatin, and therefore does not stain deeply in stained preparations. Schaudinn describes the multiplication as different from the E. coli. The whole cell does not form a cyst, but a series of buds are formed externally, each of which becomes a latent encysted form. These observations have not been confirmed, and by many the distinctions between E. coli E. histolytica are doubted. The E. histolytica may enter the subcutaneous tissues and be carried to various Darts of the body, such 222 TROPICAL MEDICINE AND HYGIENE as the liver, spleen, and kidneys, and there cause the formation of abscesses. These abscesses are slowly formed and may attain enormous size, containing many pints of pus. They are usually single, but two or three are not rare. The pus in such abscesses is white, yellow, or may be chocolate in colour. It is a very thick, slimy pus. The walls of the abscess are rugged, and as a rule there is little formation of fibrous tissue around, though there is an area of intense congestion. In the pus from such an abscess no bacteria are found, either on examina- tion or by culture, in the majority of cases. In others, the minority, there are bacteria, but these are not of any uniform species. This fact is taken to show that the amoebae are pyogenic, and that for the formation of pus no bacterial aid is necessary. Others particularly state that in early abscesses bacteria are to be found, but admit the possibility that they have been carried by the amoebae, and that in the large sterile abscesses these bacteria have died out. The amoebae are very scanty in the pus in the abscess, so that they are rarely to be found. In the walls of the abscess, in scrapings from the walls, and in the pus dis- charged a few days after the abscess is opened, they are usually present in very large numbers. An abscess may become quiescent and encapsuled or be reduced to a putty-like mass. More commonly they continue to increase in size, and bursting through the liver may extend in the cellular spaces almost anywhere. Frequently they burst into the lungs or intestines and a natural cure results. The treatment and symptomatology of hepatic abscess will be more fully considered with other forms of hepatitis and with dysentery (vol. iii.). Ipecacuanha is again coming into favour in cases of amoebic hepatitis when there is no evidence of the formation of pus. A. coll die if left in the faeces as soon as putrefaction occurs. Reproduction takes place by simple division whilst they are parasitic, but transference from one host HEPATIC AliSCKSS 223 to another is believed to be by the encysted forms. In these the organism becomes spherical, is covered with a thickened cyst wall, and the contents divided. Amoebic dysentery will be fully considered later, with otiier forms of that disease. Here it is sufficient to state that the disease may be acute, and rapidly fatal perforation in this form in the most severe cases is not uncommon. In the common form the onset may be sudden, but more frequently is insidious, sometimes the patient is not even laid up. It runs a very protracted course : attacks of diarrhoea with the passage of a little mucus and blood, alternating with periods of constipation, when the hard fasces are sometimes coated with blood or mucus, or the TIME A.M. P.M. A.M. P.M A.M P.M. A.M. P.M. A.M. P.M. A.M. P.M. A.M. P.M. 104- 103 1 02 1 1 1 00 99 98 97 >. \ 1\ K \ N \, N / \ \ p >i\ b f 1a / A J \ ^ V \ 1 \r J v^ ,/ A sl 1 \ ^1 J y J V Fig. 53. — Hepatic abscess. stool may be apparently normal. This relapsing, or rather remittent, type of dysentery, for the stools are rarely normal, is usually associated with the amoeba indistin- guishable from A. colt or E, histolytica. Associated with this type of dysentery is hepatic abscess, and rarely abscesses in other organs, such as the spleen. These abscesses are usually sterile as regards bacterial growth, but in the walls of the abscesses the amoebje will be found in abundance. The possibility of this condition must always be considered in any person who has had chronic dysentery, however mild, and in any person from the Tropics with a chronic irregular fever (fig. 53). There is nothing characteristic about the temperature and there 224 TROPICAL MEDICINE AND HYGIENE may be periods of apyrexia. The liver is enlarged and often tender, but the enlargement is not always marked. Leucocytosis occurs, but may be slight, and is often only to the extent of 12,000 to 15,000 leucocytes. The poly- morphonuclear cells form 75 to 80 per cent, of the total, as a rule. In hepatic abscess of this kind there may be two or more abscesses, but usually there is only one. Solitary hepatic abscess may occur in England, and in the Tropics, and may be due to other causes, e.g., Ascaris hunbricoides and Clonorchis sinensis. When due to amoebae the associated dysentery may be very mild and in many cases no history of dysentery can be obtained, but in these either amoebse are found in the stools or ulceration of the caecum is found at the post-mortem examination. In some countries where hepatic abscess is said to be rare, as in the West Indies, at post-mortem examinations it is found to be common ; clinically, the condition is often overlooked. 225 APPENDIX. I. — Notable Dates. Malaria. — Discovery of the parasites, Laveran, November 6, 1880.— Differentiation of species and asexual life-cycle, Golgi and others, autumn of 1885, and onwards. — Conjugation of sexual forms, McAllum, 1897-8.— Sexual cycle, Ross, 1897-8. Redwaier Fever. — Piroplasma discovered by Babes in 1888. — Mode of transmission. Smith and Kilburne, 1893. — Mode of transmission of yellow fever, Reed and Carroll, U.S. Army Commission, igoo-i. Trypanosomes. — In fish, Valentine, 1841. — In frogs, Gruby, 1843. — In rats, Lewis, 1878. As a cause of disease (Surra), Evans, 1880. — As a cause of disease (Nagana), Bruce, 1894. — In man, Nepveu described a trypanosome, 1890. — In man Ford discovered and Dutton described T. gamhiense, 1901. — In man, in sleeping sickness, Castellani discovered the same trypanosome in the cerebro-spinal fluid, 1902. Spirochcsta obermeieri or Spirochata recmventis, discovered by ■Obermeier, 1873, named S. recurrentis , 1874, and 5. obermeieri, 1875. SpirochiBta duttoni. — P. Ross, 1904. SpirochcBta pallidum or Treponema pallidum. — Schaudinn, spring of 1905. Spirochata pertcnnis. — Castellani, June, 1905. — Spirochseta in granuloma pudendi. Wise, 1906. Leishman-Donovan Bodies. — Leishman and Donovan indepen- dently in kala-azar, 1900. — In Delhi boil, Wright, 1903. — Rogers proved their flagellate stage, 1904. Amoeba coli first found in stool by Lambl, i860, and recognized as the cause of dysentery by Losch, 1875. — Trichomonas, Donne, 1836. — Lamblia intestinalis , Lambl, 1859. — Balantidium coli, Malmsten, 1857, recognized as a cause of dysentery by Strong and Musgrave, 1902. This list, though giving the names of the actual discoverers and the dates, does not necessarily imply that the only or even the main credit is due to the actual discoverers. 15 226 TROPICAL MEDICINE AND HYGIENE Most discoveries are founded on antecedent ones ; the part played by mosquitoes in carrying malaria is based on the previous observations of Manson on the transmission of filaria. Improvement in methods of technique leads directly to further discoveries, and the introduction of a simple rapid method of staining for chromatin by Leishman led to the discovery of the Leishman-Donovan bodies and their relation- ship to flagellates. Irl other cases, discoveries have been made independently by two or more workers nearly at the same time. The SpirochcBta diittoni was discovered indepen- dently by Dutton and Todd very shortly after P. Ross. In trypanosomiasis, though Castellani discovered the para- site in cases of sleeping sickness, the fuller confirmation of the causal connection and the mode of transmission is mainly due to Bruce and others. It is rare to find that the credit of any discovery is due to one man only. Nor can the influence of the English Tropical Schools^ founded in iSgg, be ignored, nor their founders, including Sir Patrick Manson, Mr. J. Chamberlain and Sir Alfred Jones, II. — Important Measurements. I ^(micron) ... = o'ooi millimetre or sy-Joo °^ ^^ inch nearly. I millimetre ... = 0*04 or Jg- ^'^*^-^' 25 millimetres ... =1 inch. I centimetre ... = 0-39 of an inch. I gramme ... = 15*432 grains. 28 grammes ... =1 ounce, nearly. I cubic centimetre — 16-23 minims, and weighs at 4° C. I gramme. 28 cubic centimetres = i ounce nearly. I litre ... ... = i| pints or 35 ounces, nearly. Normal blood : Weight about J§- of the body weight, say,. 9 pints or 5,000 cubic centimetres. Red corpuscles : About 5,000,000 per cubic millimetre. Leucocytes : 6,000 to 8,000 per cubic millimetre. Of these 65 to 75 per cent, are polymorphonuclear leucocytes. ,, 5 ,, 10 ,, ,, large mononuclear. ,, 15 ,, 25 ,, ,, lymphocytes, but number varies according to the stage of digestion. ,, I ,, 3 ,, ,, eosinophiles. APPENDIX 22 Malaria diameter of " spores " or merozoites : — Benign tertian ••• 1-5 M- Quartan ... ... 175^. Subtertian ... 07 M. Full-grown parasite, sporocyte or schizont : — Benign tertian ... 8-5 M. Quartan ... ... 6^. Subtertian ... ... 4-5^. Full-grown zygote -= 50 to 60 fx. Sporozoite - HA'. Leishman-Donovan body ... = 2-5 to 3-5 M X ['5 to 2 ^ A mceha coli ... Up to 50 M. Encysted form ... ... 15 to 20 fx. Lamhlia intcstinalis ... Up to 15 M in length. Encysted form ... 13 M X 7m. Trichomonas hominus ... 3 M to 20 M. Encysted form ... - . Up to 15 fx. III. — Classific.*lTion of Diptera. Suborder I. OrthorrhapJia. — The adult imago escapes from the pupal case through a longitudinal anterior or posterior T-shaped slit. As there is no ptilinum there is in the imago no frontal lunule. Antennae usually project in front of the head. They are divided into Nematocera (thread-like antennae) and Brachycera (short antennae). Nematocera. — Antennae have many joints — always more than six ; the segments, except the one at the base, are similar to each other ; palps, usually four or five joints. Nematocera vera. — Joints of the antenna are long, and frequently have whorls of hairs, legs long and slender, abdomen usually long, e.g., Culicidae (mosquitoes). Nematocera anomala. — Antennae composed of many segments ; but these are all short, and, as a rule, without whorls of hair. The abdomen is usually stout, and the legs are shorter and thicker than in N. vera, e.g., Simulidse, or sand-flies. 228 , TROPICAL MEDICINE AND HYGIENE Brachycera. — The number of true joints in the an- tennae is less than six ; palps, one or two joints. Brachycera vera. — Third joint of antennae is not ringed, and usually terminates in a bristle or style, e.g., Asilidae, or robber-flies. Brachycera anomala. — Terminal joint of antennae com- posed of several short segments fused together. These fused segments appear as rings, e.g., Tabanidae. Suborder II. Cyclorrhapha. — A circular cap is pushed off the pupal case by the bladder-like protrusion, ptilinum, which forms on the anterior part of the head, and the imago escapes through the circular opening thus made. In the imago a curved scar is left when the ptilinum contracts. This scar is the lunule, and the presence of this scar shows that the insect belongs to the Cyclorrhapha. Antennae are short, usually three- jointed, and more or less flattened against the head or dependent. The third segment has at the base a bristle or style, arista. (i) AscHizA. — The extremities of the lunule are not continued as sutures on each side of the face, e.g., Syrphidae, or hover-flies. (2) ScHizoPHORA. — The extremities of the lunule are continued as lines on each side of the face, so as to separate off the antennae and mouth-parts from the rest of the face. These lines form the frontal suture, e.g., Muscids, Glossinas, Stomoxys. Suborder III. Pupipava. — Larva nourished within the parent and changed into a pupa without feeding. Some are wingless, in others the wing venation is im- perfect. Antennae are small rounded masses show- ing no division into joints, with one or more stiff hairs ; the claws are powerful and much curved, e.g., Hippoboscidae and sheep-ticks. Suborder IV. Siphonaptera, or fleas, are by some considered to be wingless diptera; but, if so, they are so much modified that they are best considered separately, and will be considered in Part III. in connection with plague. APPENDIX 229 Of the other insects that are blood-suckers and are possibly carriers of disease are several that belong to tlie Hemiptera, or bugs. The Hemiptera are readily distinguished from otlier insects by the peculiar moutli-parts. IV.— Ticks. Blood-suckling Arthropods are found also amongst the Arachnidse, which in the adult stage are readily distinguished from the insects, even from the wingless insects, by the presence of four pairs of legs and the absence of antennse, whilst the orifice of the mouth is a small slit. The blood-sucking groups are the Ixodid^. Fig. 54. — Mouth-parts of Ixodes. IxoDiD^ have either a hard and chitinous or thick, leathery skin. The mouth-parts consist of a central hypostome armed with teeth projecting backwards, and on each side a powerful chelicera, also armed with teeth projecting backwards, clicliccrcB, enclosed in a sheath. There are a pair of four- jointed palps or pedipalps. The opening of the genitalia is on the under aspect near the head, and respiration is conducted by a pair of sieve-like openings in the respiratory areas, situated close to the bases of the fourth pair of legs. 230 TROPICAL MEDICINE AND HYGIENE There are two great groups of the IxodiD/E, Ixodinm and ArgasincB. IxoDiN/E. — The rostrum projects from the anterior extremity of the body. The palps are deeply grooved on their inner aspects and act as a sheath to the rostrum. The last joint of the palps is a small projection from the third. The second joint is long in one division, Ixodinae (fig. 54), and shorter, as broad as long, in another : Rhipicephalge (fig. 55). On the Fig. 55. — Mouth-parts of Rhipicephaliis. dorsal aspect is a hard chitinous plate, dorsal shield, covering the entire dorsum in the male but only the anterior part in the female. The Ixodince are important as the carriers of piro- plasma in the lower animals. They are not proved to carry any disease to or from man. Argasin^ differ from Ixodinae in that (i) the rostrum is on the under surface of the body ; (2) the palps do not form a sheath for the rostrum ; (3) they have no dorsal shields, but a thick leathery covering ornamented with knobs or bosses, making a regular pattern. There are two genera : — A rgas. — Body with sharp edges. The pattern of the marking close to the edge differs from that on the rest of the dorsum. Species of this genus carry the avian spirochsetes. Omithodonis. — Body with rounded edges. No difference in the pattern of the marking on the edge from that of the rest of the dorsum. APPENIJIX 231 Oniithodorus moiibaisa carries Spivochcvta diUloni, the cause of the African form of relapsing fever. V. — Subdivision of the more Important Groups OF THE DiPTERA. Of the groups into which the Diptera are divided the Nematoceva vera and the Cyclovrhapha schizophora are of the most importance to us, as some of them are proved to be carriers of important diseases. Many of the others are blood-suckers, others are important as mechanical carriers of baciliary diseases, and others, both of the dipterous and other insects, Fig. 56.— Mouth-parts of Ornithodorus. are important as destroyers of larvae of dangerous species and in many cases do much injury to growing crops, to fruit, grain, &c. Nematocera vera are subdivided according to their wing vena- tion mainly. This venation varies greatly in the members of the group, and the family known as the CuHcidae are charac- terized by having scales on the veins of the wings and by the forking of the 2nd, 4th and 5th longitudinal veins. These characters of the wings separate the Culicidae from all other Nematocera vera. The subdivision of the Culicidas is made on variations of the mouth-parts mainly into subfamilies, and at this point various difficulties arise and other schemes have been proposed, some based on larval characters and others on those of the eggs. Each of these methods would lead in somo ■23- TROPICAL MEDICINE AND HYGIENE cases to quite a different grouping and in others would make very little difference. It must always be borne in mind that any grouping founded on a single character is unsatisfactory, the larger the number of the characteristics that show a marked difference the sounder is that classification. The important subdivisions of the Culicidae are : — CoRETHRiN^. — Proboscis adapted for suction and not for penetration. Fig. 57. — Neuration of wing characteristic of Culicidae (Theobald). Megavhinina. — Proboscis very long and curved. Palps long, ist fork cells in wings very short. Scales on veins of wings small. Scutellum, lateral lobes very small. Larvae are lar- viverous. Very short respiratory siphon. Eggs oval, thick shelled. Anophelina. — Proboscis straight. Palps same length as the proboscis in both sexes, clubbed in male. Scutellum not lobed. Scales on veins of wings usually lanceolate. Scales on thorax and abdomen rarely abundant. Larvae asiphonate. Eggs with lateral air-floats. Culicina. — Proboscis straight. Palps short in female, in male as long or longer than the proboscis. Wing scales variable. Scales on thorax and abdomen abundant. Scutellum trilobed. Larvae always siphonate ; the siphon may be long or short. Eggs variable ; may be in rafts or thick-shelled eggs, deposited singly. ^Sdina. — Proboscis straight. Palps short, often very short in both sexes. Scutellum trilobed. In some genera hairs on Al'lM';NiJlX 233 Probosc Basal _ lobes of Q ^^ V Ma Basal lobes. Clasper.. n u ^Headof9 Proboscis. Palpi Antennae -W(---¥///Clype Basallobesofanlennae ^^^ P~VT^ yr Frons.... Vertex... Eyes Occiput. Nope -- Fig. 5S. 16 --5^ tarsal '234 TROPICAL MEDICINE AND HYGIENE metanotum. Wing scales variable. Scales abundant on thorax and abdomen and often very long hairs on thorax. Larvae always siphonate, in some the siphon is very short, and these lie flat on the surface of the water and much like Anopheline larvae, in others siphon is long. Eggs often in loose rafts, but may be laid singly. There are two other subfamilies, Heptaphlebomyina and Joblotinci. In the former there are scales on the 7th or accessory veins, and in the latter scales and hairs on the metanotum. Nothing is known as to the pathogenic properties of the ^dina ; many of them are vicious day biters. In jungle, in mangrove swamps and elsewhere they are common mosquitoes. Culicincs are subdivided into many genera by the character of the scales on the head, scutellum, wings and elsewhere. Other points, such as the character of the palps, of the male genitalia and antennae, also serve for the purpose of sub- dividing a group that is too large to be convenient. In some genera the wing scales are most characteristic, as in Mansonia and Mucidiis (fig. 24) ; in others, the scales on the head and scutellum ; and it is the characters of these scales that separate the Stegomyia, as there are only square-ended scales on the scutellum, instead of narrow-curved scales as in Culex, and square-ended scales with a few upright scales on the head, instead of narrow-curved scales, upright scales, and at the sides only square-ended scales as in Culex. AnophelincB are subdivided also on scale characters ; but with this group it is the scales on the thorax, abdomen and ventral surface of the abdomen that are of most importance, though variations in the wing scales are a subsidiary aid. Anopheles are devoid of scales on thorax and abdomen, and the scales on the wings are all the same colour. Myzomyia. — No scales on abdomen, scale-like hairs on the thorax— more like scales on the anterior margin of the thorax ; but the scales of the wings are of two colours and smaller and narrower than in Anopheles. Pyvetophonis. — Upright fork and narrow-curved scales on head, narrow-curved scales on thorax, hairs only on abdomen, wings scales are bluntly lanceolate. AI'PENDIX 235 Fig. 59. — Types of scales, a to k. Head and scutellar ornamentation, i to 5 : I, Head and scutellum of Stegomyia, &c. ; 2, of Culex ; 3, of ^des, &c. ; 4, of Megarhinus, &c. ; 5, of Cellia and some other Atiophelina (Theobald). Cellia. — Numerous scales on abdomen, and fusiform scales on thorax. On the ventral aspect of the abdominal segments are tufts of long dark scales which project laterally ; these may arise only from the ventral surface or from the latere- ventral aspect. 236 TROPICAL MEDICINE AND HYGIENE Nyssovhynchiis. — Upright fork and narrow-curved scales on head, narrow-curved and spindle-shaped scales on thorax, last one or two segments of abdomen scaled dorsally, latero-dorsal patches of scales over rest of abdomen and ventral scales. Myzovhynchiis. — Numerous upright fork scales and a few narrow-curved scales on head, narrow-curved scales on thorax, and dense tufts of upright scales on pro- thoracic lobes, last two segments of abdomen scaled, tuft on last segment ventrally, densely scaled palps and proboscis. Fig. 60. — Hamatopota pluvialis. Nematocera anomalainclvides several biting flies, such as sand- flies. Wing venation is in this group also of prime importance in dividing them into families, but other points are considered. Brachycera anomala also includes many biting flies, as the Tabanidae. The antennae, and particularly the relative length of the 2nd joint and the form of the 3rd joint, is the point of importance ; though the mouth -parts, the colouring or mottling of the wings and the character of the proboscis are all used to aid the division into genera. The wing venation APPENDIX 237 in most of the genera Tahamis, Ilcvmatopola, &c., is similar, and in these there is a central closed discal cell (fig. 61). The Cyclorvhapha schizopliora include many important genera. These are divided into those in which the halteres are covered viAith a semilucent plate or scale — the squama ; these are called calyptvata ; when there are no such covers to the halteres the insect is said to be acalyptrate. Fig. 61. — Wing of a Tabanus. The important division of the calyptvate schizophora is the MuscidiB. In these the antennae are dependent, the wing venation is simple, there is no closed central discal cell and the marginal cells are all open (fig. 62). They can be divided into those with mouth-parts formed for penetration and into those only capable of suction. These latter include the common house-fly, Miisca domestica, and also several genera which deposit their larvae in wounds on the skin. Fig. 62. — Wing of Stonioxys calcitrans. Those with mouth -parts formed for penetration are subdivided by the character of the penetrating parts, by the palps and the hairs on the arista of the antennas, as well as by minor differences in the wing venation and particularly in the 4th longitudinal vein. 238 TROPICAL MEDICINE AND HYGIENE Stomoxys. — The proboscis is elbowed at the base, is thick and comparatively short. The palps are short and thin and do not form a sheath to the proboscis. The hairs on the arista are on the upper side of the arista only, whilst the 4th longitudinal vein is not abruptly bent, but slightly curved. Glossina. — The proboscis is long and projects straight out from the head. The palps are thick, the same length as the proboscis and grooved on their inner aspects. Together they form a sheath for the proboscis. The hairs on the arista are compound and are on the upper surface only. The 4th longi- tudinal vein is angled twice. INDEX. PAGE Abdomen, distension of, in kala-azar ... ... ••. ... •■• I45 Abortion : — Spontaneous, in malarial fever, prevention 43' 44 Subtertian 29 In relapsing fever ... ... ... ... ••■ ••• •■ 178 Abscess of liver associated with amoebic dysentery 223,224 Abscesses, 'mtei-na.], due to Eu^amaia kzsto/yiica ... ... ... ... 222 Africa : — Blackwater fever, prevalence in malarious districts ... ... ... 102 South, trypanosomes found in ... ... ... •. ••. -.- 13° Tropical, blackwater fever prevalent in ... ... ... ... 87 Human trypanosomiasis ... ... ... .•• ••■ •■• 131 Agnottidce : see Dragon-flies. Albuminuria : — In subtertian malaria ... ... ... ... ••• ••• 28, 30 Toxic effect of malarial parasite ... ... ... ... ... 64 In yellow fever 109,110,111 Alimentary canal, invasion by coccidia ... ... ... ... •.■ 4 Alkaloid, percentages of, in salts of quinine 34 Amblyopia in malarial cachexia ... ... ... •■• ••■ ••■ 46 Amaindcc ... ... ... ... ... ••• •■■ ••• ••• 5^ Amceba ... ... ... ... ... ... •■• ••• ■•• ••• 218 Scheme of development 219 Autogamy in ... ... ... .. ... ••■ ••• ■•• 220 Date of discovery ... ... ... ... ••■ ••• ••• 225 Encysted forms ... ... ... ... ■■• ••• ■- ••■ 220 Infective agents ... ... ... .•• ... ■•• ••• 220 Amcebina ... ... .- ... ... ••• ••• ••• ••• 218 240 INDEX Ansemia : — In blackwater fever In kala-azar In malarial cachexia ... Masked by bronzing of skin Anasarca in kala-azar .. . Anopheles Anophelina Anophelines : — Breeding places of, important ... Conveyance of malaria parasites from man to man by Determination in given localities of malaria-carrying species Species of, carriers of malaria ... Points of distinction from other mosquitoes Antimony injections : — In human trypanosomiasis Appetite in kala-azar ... Argas ... persicus. Spirillum gallinarum transmitted by Argasina Arsenic, effect of, in human trypanosomiasis See also Atoxyl. Arthropods Aschiza... Assam : — Kala-azar in Mortality from excessive . . . Athene nodiice, see Oivl {^Little). Atoxyl, injections of, in human trypanosomiasis ... Atrophy, acute yellow, of liver simulating yellow fever Bacillus typhosus, conveyance by flies Bacteria, conveyance by insects Balantidium coli Date of discovery Barbados, freedom from malaria Bath-tubs, hatching place for eggs of Stegoniyia fasciata Baths, cold, in reduction of high temperature in malaria Bed-bug, Indian, probable carrier of kala-azar parasite Bentley, etiology of kala-azar Birds, halteridium in ... Black vomit : — In relapsing fever In yellow fever ... Blackwater fever In Africa, in areas of greatest malarial prevalence Ansemia in Causal organism undiscovered ... 01 150 44 45 151 234 232 80 15 "84 ,85 67 68 137 145. 165 230 185 194. 230 135 229 228 144, 152 159 136 III 10 10 217 225 66 119 41 •63, 165 i6i 124 177 no 87 102 89,95 9i INDEX 241 Black water fever : — I'AfiR Caution in giving quinine to malarial patients previously the subjects of ... ... ... ... ... ... ... 44 Clinical course ... ... ... ... ... ... ••• ■•■ 87 Close connection with malaria ... ... ... ... ... 95> '°3 Danger from suppression of urine ... ... ... ... 93> 95» ''^ Deposits of hcxmosiderin in kidney, liver, and spleen 96 Diagnosis ... ... ... ... ... •■• ■•• ••• ••■ 93 Differential, from yellow fever 111,112 Made from state of urine ... ... ... ... •• ••. 93 By spectroscopic test ... ... ... .. ■•. 94)95 Discharge of hemoglobin in urine should be aided, not checked ... 97 Etiology "32 Quinine poisoning, hypothesis discussed 102,103 Examination of urine in 88,91 Geographical distribution 87 Hemolysis in 91,92-96,97 Hiccough in 89,95 Jaundice in 89,90 Liability to subsequent attacks ... ... ... ... ... ■•• 95 Afyzomyia funesta in vfoxst districts ... ... ... ... ... I02 Nursing 99 Pathological anatomy ... ... ... ... ... ••■ ••• 95 Pigment present in liver and spleen 9^ Piroplasma not associated with ... ... ... ... •■• 87,104 Prevention of relapse ... ... ... ... ■•• ••• ••• 1°^ Prognosis... ... ... ... ••• ••• ■•• ■•• •■• 95 Prolonged immunity to malaria conferred by attack of 92 Prophylaxis I04 Recurrent attacks ... ... ... ■•• ••• ••• ••■ 95 Risks of travelling during attack loi Secondary fever in ... ... ... ••• ••• ■•• ••• 92 Sequelae '°3 Treatment 9^ Diuretic 98 By drugs, without specific action 96.97 By rectal enemata of saline solution .. 98,100 Urine in, colour similar to that of urine in paroxysmal ha;moglobinuria 93 Vomiting in 89,93,100 Blair, on stages of yellow fever no Blood, examination of, in diagnosis of kala-azar 150,153,154 of malaria ... ... ■•. ...30,31 In relapsing fever ... ... ... ••. .•• 180 Diminution in kala-azar 15° Blood-films, in examination of malarial parasites 49 Appearances seen ... ... ... ... •■• •■• ^2, 03 Schiltiner's dots 61 Stained ... ... ..• ••• ••• ■•• ■•• ■ • ^^ Blood-serum from yellow-fever patient, infectivity 113,114 17 • 242 INDEX PAGE Blood-stasis in subtertian malaria, abdominal ... ... ... 26,27 Cardiac... ... ... ... ... 28 Convulsions in ... ... 26 Cerebral ... ... ... 24, 26 Pulmonary ... ... ... ... 26 Rarity in Benign fevers ... ... 24 Bombay, mortality from relapsing fever at ... ... ... ... ... 179 Bone-marrow, a seat of parasite in kala-azar ... ... ... ... 1 56 Boophilus decoloraius, Spirilliiai theile?-i ix^nsmitttAhy ... ... ... 185 Boracic acid, in treatment of black water fever ... ... ... ... 98 Brackycera ... ... ... ... ... ... ... ... ...227-8 anomala ... ... ... ....... ... ... ... 228, 236 vera ... ... ... ... ... ... ... ... ... 228 Brain, histological changes in sleeping-sickness ... ... ... ... 135 Breinl, on tick fever ... ... ... ... ... ... ... ... 191 British troops in India, severity of syphilis greater than among native ... 200 Bronchitis : — In kala-azar ... ... ... ... ... ... ... 145, 152 In tick fever ... ... ... ... ... ... ... ... 192 Cachexia : — Of kala-azar ... ... ... ... ... ... ... 146, 149 Malarial ... ... ... ... ... ... ... ... ... 44 Diagnosis of kala-azar from ... ... ... ... ... 153 Enlargement of liver and spleen in ... ... ... ... 45 Ocular disturbances in ... ... ... ... ... ... 45 Symptoms associated with.. ... ... ... ... ... 45 Treatment of ... ... ... ... ... ... 45> 4^ Climatic ... ... ... ... ... ... ... 46 Dietetic... ... ... ... ... ... ... ... 45 " Caledonia" S.S., relapsing fever on board ... ... ... ... 187 Cancrum oris in kala-azar ... ... ... ... ... ... ... 152 Carroll and Reed, infective agent in yellow fever... ... ... ... 114 Cattle :— Piroplasmosis in ... ... ... ... ... ... ... 105, 106 Inoculation against rinderpest leading to infection ... ... 107 Universal infection ... ... ... ... ... ... ... 107 See also Red-water fever. Trypanosoma diniorphon... ... ... ... ... ... ... 130 Trypanosoma theileri ... ... ... ... ... ... ... 130 Cellia ... ... ... ... ... ... ... ... ... ... 235 Cerebro-spinal fluid, trypanosomes in sleeping sickness ... ... ... 134 Cess-pits, hatching place for eggs of 6". ya.ff /a/a ... ... ... ... 119 Chamberlain, Right Hon. J., one of the Founders of English Tropical Schools ... ... ... ... ... ... ... ... 226 Chigoe {SarcopsyUa penetrans), csmitr of yzws ... • ... ... ... 211 Children :— Convulsions during attacks of subtertian malaria ... ... ... 26 INDEX 243 Children : I'AGK Determination of n^c at which larfje.st proportion of, arc infected by malaria ... ... ... ... ... ... ... 82 Oriental sore affeclinj^ ... ... ... ... ... ... ... 170 Subtertian malaria in ... ... ... ... ... ... ... 24 (Jiliata ... ... ... ... ... ... ... ... ... ... 3 Ciniex rotundaius (Indian bed-bug), as carrier of kala-azar ... 163, 165 Cisterns : — Cleansing of in prophylaxis of yellow fever ... ... ... ... 120 Hatching place of eggs of .S'/^^iJwj/m/aj-r^a/a... ... 117, 118, 119 Climate in malarial cachexia ... ... ... ... ... ... 46 Coccidia : — Development and life history ... ... ... ... ... ... 4 Reproduction and hosts ... ... ... ... ... ... ... 12 Coko : see Yaws. Cold compresses, application in yellow fever ... ... ... ... 113 Coma, malarial, treatment by hot packs ... ... ... ... 40, 41 Congo district, human trypanosomiasis ... ... ... ... ... 131 Convulsions in subtertian malaria in children ... ... ... ... 26 Coolie lines, separation from European quarters in prevention of malaria 80 Copper sulphate solution in treatment of Oriental sores ... ... ... 171 Corethrincc ... ... ... ... ... ... ... ... ... 232 Corpuscles, " brassy "... ... ... ... ... ... ... ... 51 " Crescents" of subtertian malarial fever ... ... ... 22, 30, 57, 62, 63 Cropper, bodies in severe forms of malaria... ... ... ... ... 108 Cw/zV/afe, neuration of wing characteristic of ... ... ... ... 232 Cidicina 232, 234 Characteristics ... ... ... ... ... ... ... ... 115 Cunningham, parasite of Oriental sore ... ... ... .. ... 169 Cyclorrhapha ... ... ... ... .. ... ... ... ... 228 schizophora ... ... ... ... ... ... ... 231, 237 Cj//;7«ort(7«//^fr, destruction of mosquito larvK by ... ... ... 78 Deafness caused by quinine in malaria ... ... ... ... ... 46 Delhi boil : see Oriental sore. Diarrhoea associated with Ztzwi^/zfl! ?'«/'£5'/?Via/?i' ... .. ... ... 217 In kala-azar ... ... ... ... ... ... ... I46, 151 Diet :— In kala-azar ... ... ... ... ... ... ... ... 165 In malaria ... ... ... ... ... .. ... ... 43 During convalescence ... .. ... .-. ... ... 43 In malarial cachexia ... ... ... ... ... ... 45j 4^ In relapsing fever ... ... ... ... .-■ ... •■■ 18S Diptera : — Classification of ... ... ... ... .. ... ... ... 227 Subdivision of more important groups of ... ... ... -. 231 Dirt and overcrowding favourable to spread of relapsing fever ... ... 187 Diuretic treatment of blackwater fever ... ... ... ... ■-. 98 244 INDEX PAGE Dogs : — Piroplasmosis in ... ... ... ... ... ... ... 105, 106 See also Jaundice epidemic. Donovan : see Leishman- Donovan bodies. Dourine... ... .. ... ... ,.. ... ... ..... 130 Dragon -flies, larvae of, destruction of larvae of mosquito by ... ... 78 Drainage, extermination of malaria-carrying mosquitoes by ... ... 75"77 Of settlements and plantations in extirpation of mosquitoes ... 78-80 Drinks in malaria ... ... ... ... ... ... ... ■ 43 Dum-dum fever : see Kala-azar, Dutton, on cause of tick fever ... ... ... ... ... 190,191 Dysentery, abscess of liver associated with... ... ... ... 223,224 Amoebic 223 In kala-azar ... ... ... ... ... ... ... 146, 151 Frequent cause of death ... ... ... ... ... 146, 149 Malarial patients prone to ... ... ... ... ... ... 47 Dyspepsia, atonic, chronic, caused by quinine ... ... ... 46 Chronic, mistaken for malarial cachexia ... ... ... ... 44 Endemic Index in Malaria, determination of 81 Methods 81-86 Enemata of saline solution in treatment of blackwater fever ... 98, 100 English tropical schools, influence of ... ... ... ... ... 226 Entamceha buccalis ... ... ... ... ... ... ... ... 221 hystolitica ... ... ... ... ... ... ... ... 221 Internal abscesses due to ... ... ... ... ... ... 222 EntamabcB ... ... ... ... ... ... ... ... ... 221 Epistaxis : — In kala-azar ... ... ... ... ... ... ... 145, 15 1 In relapsing fever ... ... ... ... ... ... ... 178 In subtertian malaria ... ... ... ... ... ... ... 26 Epithelioma of penis, diagnosis of pudendal granuloma from ... ... 215 European quarters, separation from coolie lines in prevention of malaria 80 Europeans : — Incidence of tick fever ... ... ... ... ... ... ... 192 Ftotecl'ion horn OmiiAodorus mozibaia ... ... ... 196,197 Eye, diseases of, complicating malarial cachexia ... ... ... 45)46 Famine fever, relapsing fever described as ... ... ... ... 187 Fever, initial, in kala-azar ... ... ... ... ... ... ... 146 Fiji, reason for absence of malaria in ... ... ... ... ... 66 Fish, species of, destruction of mosquito-larvae by... ... ... ... 78 Fish-poison, destruction of mosquito-larvse by ... ... ... .-77-78 Trypanoplasma of ... ... ... ... ... ... ... 128 Fistula, recto-vaginal, accompanying granuloma of pudenda 214 Flagellata ... ... ... ... ... ... ... ... ... 123 Flagellum of ... ... ... ... ... ... ... ... 123 lO INDKX 245 Flagellata :— ^'^^^ (Jroiip of protozoa ... ..• ■.• ••• ••• ••• •• -^ Inclusion of parasite of kala-azar in 161,162 Flagellate, resting-stage of 106,128 Flagellum ... ... .• ••• ••• ••• ■• •■■ ■" ^ Flies, conveyance of typhoid bacillus by Food : see Diet. Frambcssia : see Yaws, Gametocytes of subtertian malaria Sausage-shaped bodies (crescents) Geese, septicoemia in, produced by Spirillum anseniu Geographical distribution : — Of blackwater fever Of granuloma of pudenda Of relapsing fever Of tropical diseases, dependence on parasites producing them Of yaws ... Of yellow fever ... Glossina... Bites Carrier of human trypanosomiasis 131 Description and varieties Destruction in prophylaxis against human trypanosomiasis Habitat of... fiista ^31 maciilata ... vioi'sitans ... palpalis tachinoides Glycosuria in subtertian malaria Gonorrhoea, chronic, diagnosis of granuloma of pudenda from Granuloma gangrenosa Granuloma of pudenda Clinical course Diagnosis... from epithelioma from gonorrhoea Geographical distribution Pathological anatomy Prognosis ... Recto-vaginal fistulre accompanying Treatment Granuloma of yaws Gregarinida Origin of ... Reproduction Grissoli's symptom in human trypanosomiasis " Guam " disease 57 57, 62, ,63 185 87 212 172 I 203, 204 109 131, 238 139 I, 138, 140 138 -142 143 139 I, 13S, 139 138 138, 139 131, 138 138 28 215, 212; 212 213 215 215 215 212 215 215 214 215 207 12 II 12 132 211,213 246 INDEX PAGE H/EMAMCEBA, origin of II Points of difference of piroplasma from ... ... ... ... 105 Reproduction and hosts ... ... ... ... ... ... ... 13 Hismatobia pluvialis ... ... ... ... ... ... ... ... 236 Hcematopota ... ... ... ... ... ... ... ... ... 237 Heematuria in kala-azar ... ... ... ... ... ... ... 151 IlEcmocytozoa : see Hcemosporidia. Haemoglobin, discharge in urine in blackwater fever ... ... ... 97 Hsemoglobinuria : — Mortality, principal cause ... ... ... ... ... ... 93 (Paroxysmal), similarity of urine to that in black water fever ... 93 In piroplasmosis ... ... ... ... ... ... ... ... 106 Endemic : see Blackwater fever . Hsemogregarinida, origin of ... ... ... ... ... ... ... 11 Reproduction of ... ... ... ... ... ... ... I3) 14 Hsemolysis : — In blackwater fever ... ... ... ... ... 91, 92, 96, 97 In piroplasmosis ... ... ... ... ... ... ... ... 106 Toxic effect of malarial parasite ... ... .. ... ,.. 63 Haemorrhage : — From mucous surfaces in kala-azar ... ... ... ... 145, 151 In subtertian malaria ... ... ... ... ... ... ... 28 (Cerebral), fatal in relapsing fever ... ... ... ... ... 178 Haemosiderin, deposits of, in kidney, liver, and spleen in blackwater fever 96 Haemosporidia : — Diseases caused by, in man ... ... ... , . . ... ... 15 Origin of . . . ... ... ... ... ... ... ... ... 11 Reproduction and hosts ... ... ... ... ... ... ... 13 Halteridium ... ... ... ... ... ... ... ... 123, 124 Fertilization of ... ... ... ... ... ... ... ... 124 Life-history of ... ... ... ... ... ... ... 124, 125 Ookinet of ... ... ... .. ... ... ... ... 124 Havana, prophylactic measures against yellow fever at ... ... ... 121 Headache in yellow fever ... ... ... ... ... ... no, 112 Hearsey, treatment of blackwater fever ... ... ... ... ... 98 Heart : see Blood-stasis, cardiac. Heart failure in relapsing fever ... ... ... ... ... ... 175 Treatment ... ... ... ... ... ... ... ... 188 In subtertian malaria ... ... ... ... ... ... ... 29 Heart fever (piroplasmosis with haemoglobinuria), in sheep ... ... 106 Hepatitis, amoebic ... ... ... ... ... ... ... ... 222 Treatment by ipecacuanha ... ... ... ... ... ... 222 Heptaphlebotiiyiiia ... ... ... ... ... ... ... ... 234 Herpes, labial, in subtertian malaria ... ... .,, ... ... 24 Zfer/e/^;;/^«aj-, difference from trypanosomes ... ... ... ... 128 Hiccough in blackwater fever ... ... ... ... ... •••89,95 Horses : — Piroplasmosis in ... ... ... ... ... ... ... 105, 106 Trypanosojua di77iorphon \.x\ ... ... ... ... ... ... 130 INDEX 247 I'AGR Hosts, intermediate, of parasites 1,8 Hot packs in treatment of malarial coma 40i4i Ice-bags, application to abdomen in yellow fever H3 Immunity to malaria after blackwater fever 92 Slowly acquired by repeated attacks 81 To relapsing fever, acquirement of '85 India : — Distribution of kalaazar in '45 Epidemic pmha.h\y due to Feduulus vesitmeniorum 185 Possibility of human trypanosomiasis in 160 Infusoria, origin of ... ... .■• ■•■ ••• ••• ••• ••• '^ See also Ciliala. Insects : — Conveyance of bacteria by ... ... ... ••• ■•■ ••• 1° Development of metazoa in ... ... ... .•• ... .•• 10 Of protozoa in ... ... .■■ •■■ ••• ■■• •■• ^^ Infection with animal parasites 9 Methods 9. 1° Insomnia in malarial cachexia ... ... ... ••• •■• ••■ 45 Intestine, inflammation of, in kala-azar 156,157 Intestines, protozoa found in... ... .• ••• ••• ••• ••■ 217 Intramuscular injections of metallic mercury in treatment of syphilis ... 201 Of quinine in malaria ... •■• ••• ■■• ••• 3"' 37 Intravenous injections of quinine in malaria ... ... ... .. 37 Ipecacuanha in treatment of amoebic hepatitis .. .. .. •■ 222 Irrigation systems, avoidance of harbourage of mosquitoes in 80 /xijfl^ifj, mouth-parts of ... ... ••• ••• ■•■ •■■ ••■ 229 Ixodida 229 Ixodina 194,230 Jaundice in blackwater fever 89,90 epidemic (piroplasmosis with hcemoglobinuria), in dogs ... 105, 106 Malaria with, simulating yellow fever iil In relapsing fever ... ... ... •■• ••• ••• ■•• ^77 In yellow fever 109,110 Joblotina 234 Jones, Sir A., one of the founders of English tropical schools 226 Kala-azar 144-167 Abdominal distension in... ... ... ■•• •■ •• ■■• I4S Age incidence ... ... ■• ■■• ••■ •■ ••• ••• '64 Anaemia in ... ... ... ■•• ■■• ■•• •■ •■• '5° Anasarca in ... ... ... ■•. ••■ ■•• ■■• ■•• 15^ Appetite good or voracious in ... ... ■•• •• 145,165 Bronchitis in I45, ^52 Cachexia of 146,149 Cancrum oris in ... ... ... ••• •■• .•• •■■ •• 152 Clinical course ... ... ... ... ■■• ••• '45 stages of ... ... ... ... ... ••• ••• ••• ^46 248 INDEX Kala-azar : — Cutaneous pigmentation in Definition ... Diagnosis ... By blood-examination By demonstration of parasite By diminished number of leucocytes From malaria, by quinine test From malarial cachexia Diarrhoea or dysentery in Duration ... Dysentery, frequent cause of death Enlargement of liver and spleen in ... ... 147 Epistaxis in Etiology ... Mistakes in ... ... Geographical distribution Hsematuria in Hemorrhage from mucous surfaces in ... Incubation period Intestinal inflammation in Mortality excessive Parasites of ... ... ... ..: History of discoveries relating to ... Probable carrier Similarity of parasite of oriental sore to Staining for ... Pathological anatomy Pneumonia in Prognosis ... Prophylaxis Race incidence ... Relation to trypanosomiasis Seasonal prevalence Spread by house infection Treatment.., Dietetic Induction of leucocyto.sis ... Tubercular phthisis in Kala-duakh : see Kala-azar. Kanailoma Karlinsky, experiments with spirillum Kidney, fatty degeneration in yellow fever ... Hsemosiderin deposited in tubules of, in blackwater fever Kinghorn on tick fever Koch, atosyl injection in human trypanosomiasis Experiments as to cause of tick fever . . . Labour gangs, working strength badly affected by malaria Lambkin, Colonel, treatment of syphilis in Army... 150. 153. 150. 44, 152, 146, 146, 151. 155. 145. 145. PAGE •52 156, 156, 160, 57, 60, INDEX '•^49 I'AOR Laniblia iiileslinalis ... Date of discovery -" Diarrhrt-a associated with ... ... ■• • ■• •■■ ' Lanolin, metallic mercury in, intra-muscular injections 201 Larvre: see DI^gon■mes, Mosqukoes, .S/e.s^omyia /ascia/a. Leishman, W. B., possible occurrence of trypanosomiasis in India ... 160 Leishman's method of staining for malarial parasites 3° Modification of Romanowsky's stain 49. 59. '02 Description of 59. Leislimania donovani Leishman-Donovan bodies ... TA- f ... 160, 161 Discovery ot T-. ^ ... 225, 226 Date ... ... ■■• ■■• ••• ••• ■■■ -" Resemblance to trypanosomes • '^ Resting-stage of flagellate '°^' '^^ Lemon grass tea as drink in malaria "^3 Leucocytes, mononuclear, large, in diagnosis of malaria ... ... •■■ 3' Pigmented, discovery by blood examination, aid to diagnosis of malaria ... .•■ ■• ••■ ••• •■• ■■' ■' -^ Leucocytosis, induction of, in treatment of kala-azar io5 Leucopenia in kala-azar ... ... ■■• ••■ ••• •• 5 > 54 Lips : see Hei-pes, labial. Liver, abscess of, associated with amcebic dysentery 223,224 Acute yellow atrophy of, simulating yellow fever "i Enlargement in kala-azar 147,148.151.156 In malarial cachexia ... ... •.• ••• •■■ •■ 45 In relapsing fever 177. i'52 In tick fever '9^ Fatty degeneration in yellow fever ^'3 Hemosiderin deposited in cells of, in blackwater fever 96 Pigment present in, in blackwater fever ■•■ 32. 33. 9^ Puncture of, to obtain parasite of kala-azar '55 Seat of parasite in kala-azar '5" London, Port of, relapsing fever in ••■ •■• ^°7 Lumbar puncture, discovery of trypanosomes in cerebrospinal fluid during sleeping sickness by ... ... ■•• •■• ■•• •• 'j4 Lungs, pneumonic consolidation of, in relapsing fever 182 See also Blood-stasis, pulmonary ; Pneumonia. Lymphatic glands, enlargement in trypanosomiasis 132 Swelling and inflammation in relapsing fever 178 Important in diagnosis from plague 178 McCallum, on fertilization in halteridium 124 Mackie : — Difterences in parasites of varieties of relapsing fever 198 School epidemic probably due to Pedicultis vcstiinento) itvt 185 Macrogametes : — Of coccidia ... ... ••• ••• , ••• ••■ ••• ••■ 4 Of malarial parasites ... ... ... ••• ••• •■■ ••■ 55 250 INDEX 153 PAGE 77 102 44 74. 75 Macrogametes : Micropyle of Madras, kala-azar in ... Malaria : — Absence of, on plantations well managed and well drained., Blackwater fever in Africa in areas of greatest prevalence of Cachexia following Carriers of, species of Myzomyia See also Anophelines, Mosquitoes, malaria-carrying, Myzomyia funesta. Classes liable to attack in regions of prevalence ... ... 72,73 Clinical varieties of ... ... ... ... ... ... ... 16 Close connection with blackwater fever ... ... ... 95, 103 Co-existence with kala-azar ... ... ... ... ... ... 153 Coma in, treatment ... ... ... ... ... ... 40,41 Complicated by pregnancy ... ... ... ... .. ... 43 Determination of age at which largest proportion of children are infected by Diagnosis of relapsing fever from .., ... ... ... 179, Diminution by reduction of mosquitoes Enlargement of spleen in ; examination for, method of testing endemic index ... Etiology ... Transmission of parasite by mosquito Freedom from, ensured by protection from bite of mosquitoes Geographical distribution ... ... ... Immunity to Prolonged, conferred by attack of blackwater fever Slowly acquired by repeated attacks Incubation period With jaundice simulating yellow fever... Management of cases Nursing in Occupation of patients during apyrexial periods Onset of human trypanosomiasis confounded with ... Parasites of Date of discovery ... Development of Endogenous cycle Exogenous Sexual in mosquito Asexual in man Period of residence or exposure before attack develops, measure of endemic index Pigment deposits in, proportion of bodies showing, determination of endemic index by ... ... ... ... ... 8, Prevalence of, in localities Dependent on existence of mosquitoes capable of trans- mitting Estimation of : see also Ejidemic index. 82 180 66 83,84 65-86 65 66 15 73 92 81 III 38 39-41 38, 39 132, 134 48, 64 225 6, 8 8 8 7. 8 7, 8 INDEX 2^1 Malaria :— TAOE Prevention of, on settlements, by separation of European quarters 80 Propagation of, requirements for ... ... ... ... 68 Prophylactic measures against ... ... ... ... ... ... 72 Isolation of travellers or gangs of workers from mosquito haunts 72, 73 Universal and continuous administration of quinine among possibly infected persons Reduction in amount of, methods should be as complete^as possible Of temperature by cold bathing .. Topographical distribution Treatment Dietetic By quinine Methods of administration Vomiting in, due to oral administration of quinine ... ... 41 Treatment ... Working strength of labour gangs affected by Quartan ... Diagnosis Pathology Toxins of Treatment ... Subtertian Albuminuria in Algide form .. Blood-stasis in Abdominal Cardiac... Cerebral Pulmonary In children ... Complications and sequelae Convulsions in, in children... "Crescents" Diagnosis By blood examination... Effects of repeated congestion Epistaxis in ... Glycosuria in Haemorrhages in Heart failure in Labial herpes in Nephritis in ... Neuralgia in... Neuritis in Paraplegia in Pathological anatomy Accumulations of parasites in capillaries of organs... ... 33 Deposit of pigment in. liver and spleen ... ... •■32i 33 74 80 41 15 34-38 43 34 35-37 42 40 81 18 19 20 20 21 28, 30 27 24 26, 27 28 24, 26 26 24 28 26 22, 30, 57, 62. 63 30 30 29 26 28 28 29 24 28 29 28,30 29 32.34 252 INDEX Malaria : Subtertian : — page Pernicious manifestations of ... ... ... ... ... 24 " Petit mal" in 29 Prognosis ... ... ... ... ... ... ... ...31. 32 Pyrexia of ... ... ... ... ... ... ... ...22,23 Toxic effects... ... ... ... ... ... ... ...29,30 Treatment by quinine ... ... ... ... ... ... 34 Vomiting in ... ... ... ... ... ... ... ... 23 Tertian, benign ... ... ... ... ... ... ... ... 16 Diagnosis ... ... ... ... ... ... ... 17 Geographical distribution ... ... ... ... ... 16 Pathology ... ... ... ... ... ... ... 20 Symptoms ... ... ... ... ... ... ... 16 Toxins of ... ... ... ... ... ... ... 20 Treatment ... ... ... ... ... ... ... 21 Man, intermediate host only known for malarial parasites ... ... 68- Manson, Sir P., K.C.M.G., F.R.S., one of the founders of English tropical schools ... ... ... ... ... ... ... 226 Mansonia ... ... ... ... ... ... ... ... ... 234 Marchand and Simond on transmission of yellow-fever organism ... 115 Mastigophora, origin of ... ... ... ... ... ... ... Ill See also Flagellata. Megarhinina ... ... ... ... ... . . ... .. ... 232 Mental depression in malarial cachexia ... ... ... ... ... 45 Mercury, bichloride, with carbonate of soda, in treatment of yellow fever 112 Metallic, in lanolin, intramuscular injections of, in syphilis ... ... 201 Perchloride of, in treatment of blackwater fever ... ... ... 9S Merozoites ... ... ... ... ... ... ... ...» ... 54 Metazoa ... ... ... ... ... ... ... ... ... 11 Development in insects ... ... ... ... ... ... ... la Methylene blue, altered (red), in Leishman's stain ... ... ...60, 61 Unaltered, in Leishman's stain ... ... ... ... ... 60 Microgametes, of coccidia ... ... ... ... ... ... .,. 4 Of malarial parasites ... ... ... ... ... ... 55 Micropyle of macrogamete ... ... ... ... ... ... ... 4,5 Milk, and milk and barley water, in malaria ... .,. ... ... 43 Minchin, development of trypanosomes ... ... ... ... ... 141 Mines, gangs at, prevention of syphilis among ... ... ... ... 202 Monadina ... ... ... ... ... ... ... ... ... 169 Mosquitoes, conveyance of malaria parasites from man to man by ... 15 Development of malaria parasite in ... ... ... ... ... 7 Sexual ... ... ... ... ... ... ... ... 7, 8 Existence of species capable of transmitting malaria determines endemic prevalence of disease ... ... ... ... 66 Extirpation of, methods for ... ... ... ... ... ...77-80 Harbourage by irrigation systems, avoidance of ... ... ... 80 Haunts of, prophylaxis of malaria by avoidance of ... ... ...72,73 Larvae of, methods of destruction in water ... ... ... •••77)78 Malaria-carrying, extermination, methods of .. . ... ... .••74j7S Drainage ... .„ ... ... ... •••75"77 INDEX Mosquitoes : — Propagation of malaria l)y, proofs Geographical distribution of species Success of prophylactic measures Protection from bite of ... Ensures freedom from malaria Trypanosomes in... Mouth, nose, and pharynx, destructive ulceration of, following yaws Mouth-parts of Ixodes Of Oniithodorus ... Oi Rhipicephalus... ... ... ... ... Mucidtis Musca doinestica MuscidtT Myxosporidia, origin of Myzomyia Species of, carriers of malaria ... fmiesta, commonest carrier of malaria in blackwater fever loca' Myzorhynchus... i; 253 66 66 67 72 66 26, 127 , 208 229 231 , 230 234 • 237 237 II ■ 234 74. 75 ities 102 ... 2;6 Nagan A, causal organism, Trypanosoma brucei ... ... ... ... 130 G. morsitans, carrier of . . . ... ... ... ... ... . ■ • 138 Nematocera ... ... ... ... ... ... ... ... ... 227 aiiomala ... ... ... ... ... ... ... ... 227, 236 vera ... ... ... ... ... ... .. ... 227,231 Neosporidia, origin of... ... ... ... ... ... ... ... 11 Reproduction of ... ... ... ... ... ... ... ... 14 Nephritis in subtertian malaria ... ... ... ... ... ... 28 Neuralgia in malarial cachexia ... ... ... ... ... ... 45 Neuration of wing of C^^/zV/i/fZ ... ... ... ... ... 232 Neuritis in subtertian malaria ... ... ... ... ... 28, 30 New Orleans, prophylactic measures against yellow fever at ... ... 121 Nose, pharynx, and mouth, destructive ulceration following yaws ... 208 Nyssorhynchus... ... ... ... ... ... ... ... ... 236 Obermeier, discovery of parasite of relapsing fever Edina ... Oocysts Ookinet .Formation of Motile eggs Nucleus of Oriental sore ... Diagnosis ... From syphilis Etiology ... Inoculation against Mode of onset ... 182 232, 234 ... 5> 7 59. 126 124, 126 7 125, 126 167 171 171 169 170 16S . 254 INDEX Oriental Sore : — page Parasite of ... ... ... ... .., ... ... ... 169 Similarity to that of kala-azar ... ... ... ... ... 169 Pathological anatomy ... ... ... ... ... ... ... 168 Prevalence in children ... ... ... ... ... ... ... 170 Prophylaxis against ... ... ... ... ... ... ... 171 Treatment... ... ... ... ... .. ... 171 By copper-sulphate solution ... ... ... ... ... 171 Ornithodorns "... ... ... ... ... ... ... ... ... 230 Mouth- parts of 231 Moubata, description of... ... ... ... ... ... 194, 196 Distribution does not correspond with that of blackwater fever 104 Prophylaxis against... ... ... ... ... ... 196, 197 'Yx2.\\%xm'i&\oxi oi Spirochata duttoni \yy ... ... ... ... 185 Transmission of tick fever by ... ... ... 190, 191, 193 Savignyi ... ... ... ... ... ... ... ... ... 195 Orthorrhapha ... ... ... ... ... .;. ... ... ... 227 Overcrowding and dirt favourable to spread of relapsing fever ... ... 187 Panama canal works, prophylactic measures against yellow fever at ... 121 Paralysis, facial, following tick fever ... ... ... ... ... 192 General, of insane, similarity of cerebral changes in sleeping sickness to those of ... ... ... ... ... ... 135 Paranghi : see Yaws. Paraplegia in subtertian malaria Parasites, animal, infection of insects with... Methods Influence distribution of tropical diseases Intermediate hosts of, distribution Malarial Accumulations in capillaries of organs found posi inortem Determination of proportion of inhabitants infected with Discovery by blood examination ... Man the only known intermediate host for Preparation of blood-films for examination of ... Ring form ... Vesicular nucleus ... Subtertian ... Classification ... Differences from other forms... ... ... Sexual development ... Toxic effects ... Tertian (benign), quartan and subtertian, differences between, table showing And quartan, benign ... ... ... ... Chromatin nodules seen in .., Sexual multiplication ... ... ... ... Sexual phase ... 29 9 ... 9, 10 I I ...48-64 ■•• 33 ... 81 ... 31 ... 68 ... 49 ... 61 ... 61 ...56-59 ...62,63 .-■ 57 •■.58,59 ...63,64 ... 56 ...50-54 ... 61 ..■; 54 •.•- 54 INDEX -DD Parasites : Malarial :— vack x\sexual development ... .. ... ... ... •■•52,53 Measurements of... ... ,.. .. ... ... ... 226-227 Origin of 10, 1 1 See also iindei- names of species and under names of diseases. Parotid gland, swelling and inflammation in relapsing fever ... ... 178 Important in differentiation from plague ... ... ... ... 178 Pediculus veslimentorum ... ... .. ... ... ... ... i86 Presumed cause of epidemic among school cliildren in India ... 185 Pellagra, human trypanosomiasis mistaken for in early stages ... ... 134 " Petit nial " in subtertian malaria ... ... ... ... ... ... 29 Petroleum, destruction of mosquito larva; by ... ... ... ... 77 Pharynx, mouth and nose, destructive ulceration following yaws ... 208 Pigment, deposits in liver and spleen found /^5/ mortem in malaria •••32, 33 Percentage of bodies showing deposits of, determination of malarial endemic index by . ... ... ... ... ... ... ..84,85 Presence of in liver and spleen in black water fever ... ... ... 96 Pigmentation, cutaneous in kala-azar... ... ... ... ... ... 152 Piroplasma ... ... ... ... ... ... .. ... ... 108 Life history of ... .. ... ... ... ... ... ... 105 In native cattle, universal infection ... ... ... ... ... 107 Not associated with blackwater fever ... ... ... ... 87, 104 Origin of ... ... ... ... ... ... ... ... ... 11 Points of difference from hremamoeba .. ... ... ... ... 105 Reproduction and hosts ... ... ... ... ... ... ... 13 Piroplasmosis ... ... .., ... ... ... ... ... 105- 108 Affecting cattle, immunization against rinderpest leading to ... 107 Affecting cattle, sheep, horses and dogs ... ... ... 105, ic6 See also liedwater fever. Heart Fever, Jaundice, epidemic. Htemoglobinuria in ... ... ... ... .. ... ... 106 Hemolysis in ... ... ... ... ... ... . . ... 106 Transmission by ticks ... ... ... ... ... ... ... 103 Plague, differential diagnosis from relapsing fever... ... ... 17S, iSo Plantations, absence of malaria on, under efficient drainage ... .. 77 Drainage of, in extirpation of mosquitoes ... ... ... "]%, 79 Prevention of syphilis on ... ... ... ... ... ... 202 Pneumonia in kala-azar ... ... ... ... ... ... ... 152 In relapsing fever ... ... .. ... ... ... 176, 178 In tick fever ... ... ... ... ... ... ... ... 192 See also Lung, pneumonic consolidation. Pregnancy during malaria ... ... ... ... ... ... ... 43 Prevention of abortion ... ... ... ... ... 43, 44 Protista 11 Protozoa ... ... ... ... ... ... ... ... ... 2, 11 Development and life history ... ... ... ... ... ... 4 In insects ... ... ... ... ... ... ... ... 10 Groups of... ... .., ... ... ... ... ... ... 3 Infection of rabbits by ... ... ... ... ... ... ... 6 Intestinal ... ... .. ... ... ... ... ... ... 217 256 INDEX Protozoa : — PAGE Multiplication, asexual and sexual ... ... ... ... ... 4 Spirochetes classed as ... ... ... ... ... ... ... 186 Unicellular organisms ... ... ... ... ... ... ... 2 See also Ciliata (Infusoria), Sarcodina, Flagellata (Mastigophora), Sporozoa. Pudenda, granuloma of : see also tmder Granuloma ... ... ... 212 Puru : see Yaius, Pupipara ... ... ... ... ... ... ... ... ... 228 Pyretophortis ... ... ... ... ... ... ... ... ... 234 Quinine, administration, universal and continuous among possibly infected persons in prophylaxis of malaria Poisoning by, supposed exciiing cause of black water fever ., Prophylactic value against malaria Resistance to effects of, means of diagnosing kala-azar from Salts of, equivalent doses Percentages of alkaloid Solubility in water ... In treatment of blackwater fever, sometimes injurious When only permitted ... Of malaria ... Dosage : restriction in patients previously sufferin blackwater fever ... Ill-effects of prolonged use .. Methods of administration ... Injections, intramuscular Precautions Intravenous ... By mouth ... By rectum... Of human trypanosomiasis, useless Of yellow fever, no effect ... Bihydrobromate .., Bihydrochlorate, administration by rectal injections in mal Ethyl carbonate, advantages of... Hydrobromate Hydrochlorate, administration by injections in malaria Rabbits, protozoal infection of Rats, presence of Trypanosoma lewisi in enormous numbers in Rectal injections of quinine in malaria Red-water fever, date of discovery ... In cattle ... Produced by immunizing process against rinderpest Reed and Carroll, infective agent in yellow fever ... Relapsing fever Abortion in Blood examination in Clinical course Complications 102, malaria 74 103 72 153 34 • 34 34 97, 98 98 37 g from 44 . 46 • 34-37 36, 42 37 37 35 ■35.36 • 13s 112 35 35 34 35 35 6 • 130 ■ 35-,36 . 225 106 107 . 114 189 178 180 173 178 172 178, i8o, 179. 178, 181, INDICX Relapsing fever : Diagnosis ... ]5y discovery of Spirillitin ohcniicieri in hlood From malaria From plague Enlargement of liver and spleen in ... ... ... 177, Epigastric discomfort in ... Etiology ... Geographical distribution Hoemorrhage (epistaxis and hccmatemesis) in ... Heart failure in ... Immunity to, acquirement of ... Interdependence between presence of spirochtetes and differen phases of Jaundice in Liability to attack of attendants on sick Morbid anatomy ... Mortality from Parasite of ... ... ... ... ... ... ... 129, Pneumonia in ... ... ... ... ... ... ... 176, Pneumonic consolidation in Prevalence greatest among unclean and overcrowded populations Prognosis ... Unfavourable when complicated by pneumonia or jaundice Prophylaxis against By disinfectant measures ... Pulse in ... Quarantine of patients ... Resemblance of tick fever to ... ... ... ... ... 19 Ship infection in ... Sweating during crisis ... Swelling and inflammation of parotid gland and lymphatic glands Symptoms of relapse Temperature in, sudden rise and fall ... Thirst in ... Treatment 187, Dietetic Of heart failure in ... Urine in ... Varieties of, contrasted ... Differences in parasites Vomiting in ... ... .. .. ... ... ... 173, African : see Tick fever. Remittent fever, bilious, with jaundice, blackwater and yellow fevers mistaken for Rhipicephalus , mouth parts of Rinderpest, immunization against, in cattle leading to piroplasmosis in- fection Ring form of malarial parasites 18 79 82 80 80 82 77 82 72 78 75 85 [84 177 [87 [81 (79 182 [78 [82 t87 [79 [79 '75 .89 192 [87 [77 [78 [72 '74 [76 188 [88 1 88 177 167 198 [76 112 230 107 61 258 , INDEX Rogers, L., diagnosis of kala-azar ... Etiology of kala-azar Seasonal prevalence of kala-azar Romanowsky's method of staining ... For parasite of kala-azar ... Leishman's modification... Roof gutters, cleansing in prophylaxis of yellow fever ... ... ... 120 Hatching place for eggs of 6". /aji^/fl/fl; ... ... ... ... ... 119 PAGE ... 150 161, 162 ... 164 183, 184 157,158 ... 49 St. Vincent, prevalence of malaria in, reason for ... ... ... 66 Saline solution, rectal enemata of, in treatment of blackwater fever 98, 100 Sanarelli, bacillus associated with yellow fever, discovered by ... ... 114 Sarcodina ... ... ... ... ... ,., ... ... ... 3 Group of protozoa ... ... ... ... ... ... ... 3 Origin of ... ... ... ... ... ... ... ... ... 11 Sarcopsj///a peneirans {chigoe) cati'ier oi ya.v/s ... ... ... ... 211 Sarcosporidia, origin of ... ... ... ... ... ... ... il Schaudinn, classification of protozoa... ... ... ... ... ... 3 Discovery oi Spirochceta pallida as causal agent of syphilis ... ... 186 On halteridium ... ... ... ... ... ... ... 123,124 Spirochsetes classed as protozoa by ... ... ... ... ... 186 On trypanosomes .. ... ... ... ... ... ... ... 124 Schizogony ... ... ... ... ... ... ... ... ... 54 Schizonts ... ... ... ... ... ... ... ... ... 54 Asexual forms of coccidia ... ... ... ^ ... ... ... 4 Schizophora ... ... ... .., ... ... ... .. ... 228 Schiiffner's dots seen in benign tertian ... ... ... ... ... 61 Settlements, drainage, clearance and cultivation in extirpation of mosquitoes ... ... •••78,79 Prevention of malaria in, by separation of coolie lines and European quarters... ... ,., ... ... ... ... ... 80 Septicaemia in geese produced by 6'/^>27/2^OT a;^^^;/;/? ... ... ... 185 Serum of hyperimmunized animals in treatment of relapsing fever ... 188 Sheep, piroplasmosis in ... ... ... ... ... ... 105,106 See also Heart fever. Ship, epidemics of yellow fever on board ... ... ... ... ... 122 Importation of yellow fever usually by... ... ... ... 121,122 Ship-infection in relapsing fever ... ... ... ... ... ... 187 Simond and Marchand on transmission of yellow-fever organisms ... 115 Siphonaptera ... ... ... .. ... ... ... ... ... 228 Skin, bronzing of, in malarial cachexia ... ... ... ... ... 45 Diseases of, and malaria ... ... ... ... ... ... 47 Sleeping sickness, cerebral changes ... ... ... ... ... ... 135 Discovery of trypanosomes in cerebrospinal fluid by lumbar puncture 134 Fatal cerebral symptoms of ... ... ... ... 131, 133, 134, 135 Terminal stage of human trypanosomiasis ... ... 131, 133, 134, 135 See also Trypanosomiasis, human. 2.S9 I'A';k 1 08 112 . 98 94. 95 . 185 . 185 ... 185 182, 183 129, 182 ... 225 ... 180 ... 185 190, 191 225, 226 210 225 210 186, 22: of INDEX Smith, on bodies resembling piroplasma, found in severe forms of malaria Soda, carbonate of, with perchloride of mercury In treatment of yellow fever In treatment of black water fever Spectroscope, aid in diagnosis of blackwater feve Spirillum, species of, conveyed by bite of ticks anserini cause of septicemia in geese ... duttoni : see SpirocJuvla duttoiti. gailinarum transmitted Ijy Argas pcrsiais obernieieri, description of Causal organism of relapsing fever Date of discovery .., Presence in blood diagnostic of relapsing fever /A«?VeA-2 affecting cattle ... Spirochata duttoni ... ' ... ... ... ... ... 129, 1^5, Date of discovery pallida, causal organism of syphilis Date of discovery ... pertenuis, association with yaws Date of discovery ... Spirocha;t£e Classed as protozoa Interdependence between presence of and different phases relapsing fever Present in blood in tick fever ... In tissues, diseases associated with See also Granuloma of pudenda, Syphilis, and P Spleen, deposits of hemosiderin, in blackwater fever Of pigment found post mortem in malaria Enlargement of, examination for, method of testing endemic index in malaria Percentage error in application of test for . In human piroplasmosis ... ... ... ... ■•• 107, In kala-azar 147,148,151,155, In malaria ... ... ... ... ... ... ... .•■ 33 In malarial cachexia ... ... ... .. ••• ■•. 45 In relapsing fever ... ... ... ... ... ... I77> iSi Chronic, in subtertian malaria ... ... ... ... ... 29 In tick fever 192 Pigment present in, in blackwater fever Seat of parasite in kala-azar ... ... ... ... ••• ■•. 156 Splenomegaly (tropical), see Kala-azar, Sporogony 59 Sporozoa, classification of ... ... ... ... ... ..• ■•■ 12 Group of protozoa ... ... ... ... ••• -. ••• 3 Origin of... ... ... ... ... ... ••. ••• ••• n Sporozoites 7, 59 Formation in coccidia ... ... ... ... ... ... ... 5 . 184 ■ 193 199 • 96 32, 33 83, 84 . 86 108 165 26o • INDEX PAGE Staining, processes of, in preparation of blood-films ... ... ... 50 See also Romanoivsky' s method. 6'/if^(?;;y?'(2, genus, characteristics of ... ... ... ... ... ... 115 Stegotnyia fasciata, breeding places ... ... ... ... 116, 117, 118, 119 Knowledge of, essential in prevention of spread of yellow fever ... 119 Characteristics of ... ... ... ... ... ... ... 116 Destruction by fumigation on board ship ... ... ... ... 122 Eggs of 116 Extreme vitality ... ... ... ... ... ... ... 116 Habitats of 118 LarvEe of ... ... ... ... ... ... ... 117 Protection from bites of ... ... ... ... ... ... ... 113 Transmission of yellow fever by 109,114 Conditions necessary for ... ... 114 Stomach, congested state of in yellow fever 113,114 Stomoxys .. ... ... ... ... ••. ... 238 calcitrans ... ... ... ... ... ... ... ... ... 237 Surra 130 Sweating in relapsing fever during crisis 177 Syphilis, treatment by intramuscular injections of metallic mercury in lanolin ... ... ... ... ... ... ... ... 201 Causal organism (presumed), Spirochata pallida ... 129, 186, 210 Diagnosis of oriental sore from ... ... ... ... ... ... 171 Of yaws from ... ... ... ... .. ... ... 208 Does not protect from yaws ... ... ... ... ... ... 211 In Indian army ... ... ... ... ... ... ... ... 200 Secondary and tertiary fever in... ... ... ... ... ... 200 Points of similarity to yaws ... ... ... ... ... .. 209 Recurrence induced by malarial cachexia ... ... ... ... 45 In Tropics, prophylaxis ... ... ... ... ... ... .. 202 Nature of ... ... ... ... ... ... ... ... 199 Spread among women ... ... ... ... ... 202,203 Treatment 201 Tabanus, wing of ... ... ... ... ... ... 237 Tanks, clearing of, in prophylaxis of yellow fever... ... ... ... 120 Hatching place for eggs oi S. fasciata... ... ... 117, 118, 119 Tea, hot, as drink in malaria ... ... ... ... ... ... 43 Telosporidia ... ... ... ... ... ... ... ... , . . 12 Origin of ... ... ... ... ... ... ... ... ... il Thirst in relapsing fever ... ... ... ... ... ... ... 176 Tick fever 190-198 Bronchitis and pneumonia in ... ... ... ... 192 Causal orgSLuism, Splroc/icFla dttllom ... ... ... 129,185, 190, 191 Diagnosis ... ... ... ... ... ... ... ... ... 192 Enlargement of liver and spleen in ... ... ... ... ... 192 Etiology ... ... ... ... .. ... .. ... ... 193 Facial paralysis after ... ... ... ... ... ... ... 192 INDEX 261 Tick fever : — I'Agk Historical account of ... ... .. ... ... ... ... 190 Incidence on Europeans... ... ... ... ... ... ... 192 Incuhalion period ... ... ... ... ... ... ... 192 /WA/ywr/ew appearances in animals ... ... .. ... ... 193 Prophylaxis ... ... ... ... ... ... ... ... 194 Resemblance to relapsing fever ... ... ... ... 191, 192 Spirochfctes present in blood ... ... ... ... 192, 193, 194 Symptoms ... ... ... ... ... ... .. 191, 192 Tisinsmiss'ion hy Omi^/iodorus Motidaia ... ... 190, 191, 193 Points of importance respecting ... ... ... ... ... 194 Treatment.., ... ... ... ... ... ... .. ... 194 Ticks ... ... ... ... ... ... ... ... ... ... 229 Transmission of piroplasmosis by ... ... ... ... ... 105 Tictin, on experiments with spirillum ... ... ... ... ... 184 Todd, on course of tick fever ... ... ... ... ... 190, 191 Toxins, effects of, in subtertian malaria ... ... ... ... 29, 30 Trade routes, destruction of (7/(?j'JzV;rt along ... ... ... ... 143 Treponema, description of ... ... ... ... ... ... ... 129 palliduju : see Spirochata pallidutii. Trichofiionas, date of discovery ... ... ... ... ... ... 225 Tropical fever : see Malaria, subtertian. Trypanoplasma of fish Trypanosoma brucei ... Causal organism of nagana (Tr^^sz found in man dimorphon occurs in cattle and horses... e(('? fi*? U 14. 12. 13 15 # 16 . 18. 20 . .-. ' '•'■■ ' ■ »-V"».' '-^ 19 A.Terzi del 21 . Bai.e A-Danielsson L'-.^ Mi. COLUMBIA UNIVERSITY LIBRARIES This book is due on the date indicated below, or at the expiration of a definite period after the date of borrowing, as ' provided by tlie rules of the Library or by special arrange- ment with the Librarian in charge. DATE BORROWED DATE DUE DATE BORROWED DATE DUE 1 ^ — C\ ■"''' CZ8(n4l)M100 ^C9 61 Daniels «^edi cine and hyg lene /f^^^/ K^w^'*^