Tropical Diseases/Chapter 10
CHAPTER X
TRYPANOSOMIASIS OF MAN*[1]
Definition.—— Morbid conditions produced by parasites belonging to the genus Trypanosoma, including irregular chronic fever, skin eruptions, local œdema, adenitis, physical and mental lethargy, and, in a large proportion of cases, death.
History.—— Although its true etiology was not apprehended until quite recently, sleeping sickness, the terminal phase of African trypanosomiasis, has been known for over a century.
The occurrence of trypanosomes in animals has been recognized for at least sixty years, first in cold-blooded vertebrates, later in mammals. The best-known and first-described mammalian species is that of the rat (Trypanosoma lewisi). It was discovered by Lewis, in 1879, in Calcutta. In the following year Evans described a similar parasite (T.evansi) in the blood of horses in India; he found that it also infests camels, elephants, buffaloes, and dogs, and that it is the cause of the disease called " surra," which, from time immemorial, the natives of India have ascribed to the bite of certain blood-sucking flies. Fifteen years later Bruce showed that nagana, the " fly disease " of horses, bovines, and other species of domestic mammals in Africa, is due to the same kind of organism (T. brucei). Since these discoveries were made trypanosomes have been found in many species of mammals, as well as in numerous birds, fishes, and reptiles. Though differing in degree of virulence, they all, at least in mammals, give rise to a more or less similar type of disease.†[2] In 1890 Nepveu, in the course of researches in Algeria on malaria, encountered these flagellates in the blood of man. He appears to have been the first to do so; but, unfortunately, his original description is vague, and his illustrations are crude. He established no definite relationship between the organisms he alluded to and the associated morbid conditions; onsequently, his observations did not receive the attention their significance deserved, although, later, he emphatically affirmed that a trypanosome has to be reckoned with as a factor in human tropical pathology.
In 1901 Forde encountered a flagellated parasite in the blood of a European suffering from an irregular non-malarial fever, in the River Gambia Colony. This parasite he showed to Button (1902), who recognized it to be a trypanosome. Later, Button found a similar organism in the blood of a native of the same colony, and suggested the name T.gambiense, which the parasite now bears. Subsequently many cases were described, both in Europeans and natives, and the association of the parasite with a peculiar form of febrile cachexia was quickly and satisfactorily established.
A great impulse was given to the study of the subject by the discovery of trypanosomes in the cerebro- spinal fluid, as well as in the blood of cases of sleeping sickness, by Castellani in Uganda in 1902. Castellani's suggestion that the parasite is the cause of sleeping sickness has been fully confirmed by Bruce, Nabarro, and other investigators, who have also shown that in Uganda the tse-tse fly, Glossina palpalis, is the transmitter of the infection, an hypothesis already advanced on analogical and epidemiological grounds by Sambon and Brumpt. Then (1909) came the important discovery by Kleine that the tse-tse fly was no mere mechanical transmitter of the trypanosome, as had been supposed, but was a true intermediate host. Later, on morphological and clinical grounds, Stephens and Fantham established the existence in Rhodesia of another species or variety of trypanosome (T. rhodesiense), which Kinghorn and Yorke have since proved to be transmitted by Glossina morsitans.
Meanwhile Chagas had associated a disease, occurring in Brazil, with a peculiar species of trypanosome, Schizotrypanum cruzi, having a special transmitter, Lamus (Conorhinus) megistus. (See p. 188.)
Geographical distribution.—The presence of T. gambiense has been definitely ascertained for the west of Africa from the Senegal in the north to Mossamedes and the upper reaches of the Lualaba in the south. Also in the Niger and Congo basins, and in Uganda, where it must have been introduced only recently, apparently about the end of the nineteenth century. Throughout this vast area the infection is not uniformly distributed. It occurs
Fig. 43.—Schema of trypanosoma, with nomenclature.
in a patchy way, principally along the banks of the rivers and shores of the lakes, conformably to the distribution of certain tse-tse flies, and apparently being influenced also by the frequency and nature of the intercourse and by the occupations of the inhabitants. There is strong reason for believing that the recent influx of Europeans into tropical Africa and the consequent increased movement of the natives is spreading the disease, and that this extension has by no means reached its limit. As regards the eastern side of the continent, the disease has not extended beyond the shores of the Victoria Nyanza. In this locality its present limits are Wadelai on the Nile to the north, and the southern end of Lake Tanganyika to the south. There is every reason to apprehend that, in time, the distribution of trypanosomiasis will become coextensive with that of the appropriate tse-tse flies.
Etiology.——In common with other trypauosomes, T. gambiense, as seen in fresh blood, is an active, wriggling organism, having a spindle-shaped body, which is slightly compressed laterally. It is provided with a delicate, wavy membrane——the undulating membrane——which fringes the convex dorsal edge of the body, and terminates in a free, whip-like filament, the flagellum. Suitably stained specimens show a nucleus about the centre of the body, and a minute, deeply staining chromatin mass, the blepharoplast (kinetonucleus), generally near one pole. The extremity of the body which encloses the blepharoplast is regarded by recent authorities as the posterior extremity; it varies greatly in shape and may be pointed or obtuse. The opposite end, the anterior extremity, tapers to a point, to which the flagellum is attached. Adjoining or surrounding the blepharoplast is a small non-staining area, the vacuole. The free border of the undulating membrane is somewhat thickened; this thickened border springs from the blepharoplast at one end, and its continuation at the other constitutes the flagellum. In certain specimens the cytoplasm is homogeneous; in other specimens comparatively faintly staining granules are visible. In comparing and measuring a large series of specimens, it becomes apparent that there is great diversity in the dimensions of the body of the parasite, the nucleus, and the flagellum (Fig. 46). Thus, some are short and stumpy, with short or no flagellum, measuring from 14 to 20 μ in length; others are long and slender 23 to 33 μ; others again are of intermediate dimensions 20 to 24 μ in length by 1.40 to 2 μ in breadth.
In certain instances evidences of multiplication by longitudinal division are seen. The process commences most frequently in the blepharoplast, which elongates, and then divides. The nucleus divides almost simultaneously, sometimes before the blepharoplast. The division of the blepharoplast is followed by the duplication of the thickened margin of the undulating membrane, beginning at its blepharoplast attachment; this, in its turn, is followed by longitudinal division of the whole body. According to Miss Muriel Robertson an accomplished protozoologist working in Uganda——only a portion of the flagellum is split off with the daughter individual. The fission of the body is effected dorso-ventrally, but the resulting forms do not separate along the ventral border until the new flagellum has appeared, the final separation proceeding antero-posteriorly; parasites still adhering by their posterior extremities are occasionally encountered. The division forms are usually of about equal size, and slightly smaller than the parent form.
Crithidia-like forms have been found in the cerebro-spinal fluid and, according to Breinl and Fantham, latent encysted forms in the lungs, spleen, and bone marrow. Granule- shedding, similar to that described by Balfour in pathogenic spirochætes, has been observed by Fry and Ranken in the liver, spleen, bone marrow, and lymphatic glands. Wolbach has shown that in experimental animals trypanosomes are found in all organs, including the brain.
Although we are accustomed to observe the parasites in the blood, there is reason to believe that this is not their only principal habitat. As suggested, by Mott, and proved by Greig and others, they are generally more easily found in the lymphatic glands, which are often markedly enlarged. They occur also in the cerebro-spinal fluid, and probably in the fluid of the serous cavities; facts pointing to the lymphatic system as an important habitat of the trypanosoma. As regards the blood, there is no uniformity in the number of parasites present : sometimes they are fairly abundant, one or two in each field of the microscope; at other times and in the same patient it may be difficult or impossible, even after prolonged search, to find a single specimen. In some cases they tend to recur cyclically at intervals of a week or more. On the whole, although this is by no means invariable, the parasites are most abundant in the blood during the febrile attacks to which these patients are so subject.
Formerly many attempts were made to cultivate T. gambiense on artificial media, but without marked success, notwithstanding that the parasite is readily communicated to monkeys, dogs, rats, guineapigs, and many other animals, though amphibia and reptiles are immune. Success was not attained till a suitable medium, termed the N.N.N. medium,*[3] was discovered. On this medium Novy and McNeal have shown that T. lewisi and other trypanosomes multiply rapidly in the water of condensation, and that in many species subcultures can be carried on through an indefinite number of generations. Thus, T. gambiense has been cultivated for four generations; T. rhodesiense is much more difficult to cultivate. Unfortunately, T. gambiense is somewhat refractory and does not multiply readily in this culture medium. In such cultures, however, the trypanosome form may be lost, the flagellum springing directly from the anterior extremity and no undulating membrane developing. Cultivation is now utilized as a diagnostic method of demonstrating trypanosomes, if very scarce in the peripheral blood.
Interesting observations have been made by Laveran and others on a very striking phenomenon exhibited by trypanosomes, in certain circumstances, both in the blood and in artificial cultures. Upon the advent of unfavourable biological conditions in these media, such as the influx of sera of non - susceptible animals, increasing scarcity of nutriment (as in the alimentary tube of an appropriate invertebrate host), lowering of temperature, or the addition of chemical solutions to artificial cultures, the trypanosomes tend to congregate in bunches in which the posterior extremities of the parasites are apposed, the flagellated extremities remaining free (Fig. 44). One such group is termed a "primary" agglomeration, and may be composed of upwards of a hundred individuals. In many cases these primary clusters themselves become grouped together to form still larger tangled masses known as " secondary " agglomerations. Agglomeration does not of itself seem to have any ill effect on the constituent parasites, which may again disperse, apparently quite unaltered. Sometimes all the individuals forming a cluster become disagglomerated; at other times
water for twenty-four hours. After sterilization the agar is pipetted off into test-tubes and one-third volume of fresh rabbit's blood added. After sloping, the tube must be incubated to test sterility. the break-up is only partial, a certain number of the more feeble and less mobile parasites remaining together and slowly dying. The significance of this phenomenon has yet to be ascertained. Some authors believe that it indicates a recuperative molecular interchange between the associates.
In cultures, in many instances, trypanosomes acquire a spherical form and undergo multiple division.
Fig. 44.—Agglutination of Trypanosoma lewisi in the defibrinated blood of an immunized rat. (After Laveran.)
They lose their flagella in the process, certain of the division forms subsequently acquiring such an organ, which now invariably springs, as already mentioned, directly from the blepharoplast. These culture forms possibly represent a stage in the life of the parasite which, in normal conditions, is passed in the vertebrate host, or, more probably, in the insect host.
How long a trypanosome infection may persist in the human body has not been definitely determined, but there is direct evidence that it may continue for several—three or four—years. From what we know of the incubation period of sleeping sickness it is not improbable that this period is sometimes greatly exceeded, and may extend to seven years or longer.
Extrusion of granules and their further development.—Fry and Ranken have recently described under this title a remarkable phenomenon which may have an important bearing on the life-history
Fig. 45.—Trypanosomes shedding granules. (After Fry and Ranken, "Proc. Roy. Soc.")
of the trypanosome (Fig. 45). Balfour describes a similar process in spirochætosis. It is especially observable in those more chronic forms of trypanosomiasis of man and animals, in which the trypanosomes disappear from the blood for considerable periods at a time, and may explain the occasional infectivity of blood in which the parasite cannot be detected with the microscope.
The observers referred to state that trypanosomes may or may not contain two kinds of granules, one kind being of the nature of food material, the other, which is a sharply defined refractile body, being concerned in the process they describe. Their description refers to T. gambiense,but they have witnessed a similar process in other species of trypanosomes.
Referring to T. gambiense, they write:——
" In this species the granules are multiple and move rapidly backwards and forwards in the long axis of the trypanosome. They exhibit also a dancing movement and appear to throw themselves against the periplast and rebound from it. Sometimes the .granules approach the surface, and in doing so may actually cause a slight protrusion on the covering membrane. This seems to be preliminary to extrusion, as afterwards the granule may be shot out with a certain degree of force into the free fluid to some distance from the host. In this species extrusion is not as a rule effected from the extremity (as in T. nanum) but from some point near the middle of the trypanosome body.
" Extrusion of granules, if occurring generally, apparently heralds a disappearance of trypanosomes from the blood and is, in fact, the precursor of a trypanolytic crisis. Under favourable circumstances, e.g. after treatment, extrusion is followed by rapid disintegration of the trypanosomes."
As regards the granules, they state that there is "a definite sequence of events during an exacerbation of the disease: (1) Trypanosomes without granules; (2) trypanosomes showing granules which gradually become larger and very evident; (3) many free granules; (4) many trypanosomes but no granules; (5) trypanolytic crisis, or death of the animal. "
After extrusion the granules, which are now motile, if they escape the phagocytes, undergo the developmental change illustrated in Fig. 46.
Rôle of the tse-tse fly.—— An important practical point is the question of the transmission of the parasite. As already mentioned, the well- and long-known role of the tse-tse fly*[4] in the transmission of the trypanosome of nagana suggests that the corresponding parasite of man is transmitted by a corresponding insect, a suggestion borne out by considerations of distribution, and by experiment.
Minchin, Gray, and Tulloch have shown that when Glossina palpalis was half fed on a rat infected with the cattle trypanosome of Uganda (probably T. brucei), and immediately transferred to complete its meal on a healthy rat, in four out of five experiments the healthy rat contracted the infection; but if the transference was delayed, for an hour even, the experiment failed. As similar experiments with other blood-sucking flies (Stomoxys, for example) which, apparently, have no biological connection with T. brucei, succeeded to some extent, and as such a method of feeding can only occur exceptionally in nature, it is reasonable to infer that the closely allied T. gambiense is not usually
Fig. 46.—Trypanosoma gambiense: various forms from blood and cerebro-spinal fluid.
a, Elongated posterior extremity; b, blunt ditto: c, d, and e, dividing forms and h, probably sexual forms; g, small round forms from cerebro-spinal fluid.
communicated in this purely mechanical way. We know that the malaria parasite can be communicated by the direct inoculation of malarial blood, but it is universally admitted that direct inoculation is not the natural method of transmission. The idea that the glossina inoculated trypanosomes in this direct way originated, undoubtedly, with the interpretation that has been placed on Bruce's experiments with nagana, an interpretation which may be incorrect. It is true that both Bruce and Minchin communicated trypanosoma infection to monkeys and other animals by means of tse-tse flies caught in the jungle. It is manifest, however, that before these tse-tse flies could have fed on the experimental animals an interval of many hours must have elapsed since their previous blood-feed. Therefore, in view of Minchin's failure to communicate the disease by insects that had been kept for only a short time after being fed on trypanosoma-infected animals, it is reasonable to conclude that there could have been no direct inoculation by these jungle-caught flies.
A more probable interpretation of the experiments, and one based upon what we know of the transmission of other hsemoprotozoa, is to the effect that glossina serves as an alternative host in a truly biological sense, and not as a simple mechanical transmitter; that the trypanosome, after entering the intestinal canal of the insect (Fig. 47), undergoes developmental changes requiring a considerable space of time for their completion, developmental changes which enable it subsequently, when the opportunity occurs, to effect a lodgment in the human or other vertebrate host. That this view of the role of the tse-tse fly is correct has been established by Kleine, who, after feeding G. palpalis on animals infected with T. brucei, set the same flies to bite fresh animals at various intervals. Up to twenty (possibly sixteen) days the flies failed to convey the infection, but from that period onwards to the forty-seventh day, when the experiment concluded, they communicated the trypanosome to eight animals. Bruce and others have confirmed Kleine's results and have ascertained that they apply to T. gambiense and other trypanosomes. It is estimated that 0-03-0-34 per cent, of wild G. palpalis in Uganda are infective; but in captivity, if fed on trypanosome-infected blood, 5-6 per cent, of flies become infective, and, according to Miss M. Robertson, a still greater proportion (21 per cent.) if the flies are starved after feeding. More recently Bruce and his co-workers have found that in Nyasaland 1 -35 per cent, of all wild tse-tse flies are infected with one or other of the disease-producing trypanosomes. It is to be noted that the trypanosome at intervals, not as yet
Fig. 47.—General view of digestive tract of Glossina palpalis. (After Minchin, Report on Sleeping Sickness to the Royal Society.)
ascertained, is incapable of infecting the fly. For this observation also we are indebted to Miss M. Robertson.
The trypanosome-infected contents of the stomach of a glossina if injected into a susceptible animal do not communicate the infection, although the parasites may be alive at the time of the injection. Possibly the multiplying forms in the stomach are of the same sexual nature as those of malaria in the mosquito gamete forms and therefore incapable of multiplication in a vertebrate host. Koch for T. brucei, and Minchin, Gray and Tulloch for T. gambiense, state positively that the parasites show marked sexual differentiation within the stomach of the insect host.
The discovery by some of the above-mentioned investigators that jungle-caught tse-tse flies harbour a variety of species of trypanosome " wild forms," while only a small proportion of them convey T. gambiense (sometimes as many as a thousand of these insects were required before a successful infection of monkeys was obtained), makes it evident that extreme precision and care must be observed in order to eliminate sources of fallacy. That the tse-tse fly conveys the trypanosome is certain, and Koch's observation that trypanosoma forms may sometimes be observed in the blood-free droplet of clear fluid which can be expressed from the proboscis, as well as the conditions observed in experimenting, indicate that the infection is conveyed by the bite of the fly. But, even assuming that glossina has been proved to be the proper transmitter of T. gambiense, much remains to be done: the history of the trypanosome, from the time of its removal from one vertebrate by the glossina to its introduction into another vertebrate, has not been completed.
Minchin, having discovered encysted developmental forms of trypanosomes in the lower gut of the tse-tse fly, conjectured that the infection might be transmitted by the droppings of the fly when swallowed by man or other vertebrates. Further observation has not supported this conjecture.
Dealing with the entire life-history of T. gambiense, Miss Robertson summarizes her conclusions as follows; " 1. T. gambiense undergoes an endogenous cycle of development in the vertebrate in the circulating blood. This cycle is of irregular duration and is repeated many times in the course of the disease.
"2. The short forms may be regarded as the adult blood-types; the intermediate types are growthforms, proceeding to the long individuals, which are those about to divide. The products of division give rise, directly or indirectly, to the adult forms. The adult forms appear to be alone responsible for carrying on the cycle in the transmitting host.
" 3. The multiplication occurs in the circulating blood.
" 4. Multiplication of the parasites was never found within the cells of the liver, spleen, or lungs in monkeys.
" 5. Rounded non-flagellate types were found on one occasion in the lung, liver, and spleen of a virulently infected monkey. They appear for the most part to be destined to destruction, but it is not excluded that they may survive in small numbers as latent forms.
" 6. In the fly the trypanosomes are first established in the posterior part of the midgut. Multiplication occurs and trypanosomes of very varying sizes are produced.
"7. From the tenth or twelfth day onwards slender long trypanosomes are to be found in increasing numbers. These finally move forwards to the proventriculus and are the dominant, though not the only, type seen there. The proventriculus becomes infected as a rule between the twelfth and twentieth days.
" 8. The salivary glands become infected by the slender proventricular types. They reach the salivary glands by way of the hypopharynx; arrived in the gland, they become attached to the wall and assume the crithidial condition. Multiplication occurs, and finally small trypanosomes are produced, closely resembling the blood type. The passage through the crithidial stage is characteristic of the salivary development, and the trypanosome forms just mentioned are derived from the crithidial types. The development in the salivary gland takes from two to five days before the forms are infective.
"9. The fly is never infective until the glands are invaded. Trypanosomes from the proventriculus when injected into a monkey never produce infection. Trypanosomes may be found in the salivary glands as early as the sixteenth day of the cycle. An early infection of the salivary glands is always preceded by a very virulent and rapid gut infection.
" 10. The trypanosomes are never attached to the wall of the alimentary canal, and there is no intracellular multiplication in the gut cycle. A crithidial stage does not occur in the gut cycle. The trypanosomes are never found in the body cavity nor are they ever established in the rectum.
"11. Conjugation has not been observed, nevertheless the fly cycle as a whole has the biological significance of conjugation."
Considering the bionomics of glossina, it seems not improbable that some of the trypanosomes, after undergoing certain unknown changes, may enter the larva, and be thus transmitted by heredity to the vertebrate host. This has been suggested by Sambon. So far, however, such hereditary transmission has not been established. Yet it may be pointed out that it would conform in a remarkable manner to the habits of the babesise in relation to their invertebrate transmitters.
To settle these and other questions of great practical importance in connection with the role of the tse-tse fly in trypanosomiasis, experiments with laboratory- reared insects are indispensable; and, further, observations should be extended to all the species of the genus. We have no assurance that Glossina palpalis and G. morsitans are the only efficient transmitters. Direct infection through breaches of surface or through mucous membranes (e.g. during coitus, as has been suggested by Koch) cannot be entirely excluded as a possibility.
Predisposing causes.—— Neither age, sex, occupation, nor race per se has any influence on the susceptibility to trypanosoma infection, except in so far as they conduce to opportunity. Thus occupations (boatmen, fishermen, water-carriers) which imply a frequenting of the waterside haunts of the glossina conduce to infection.
Incubation period.—— The incubation period of the glossina-conveyed disease and that resulting from direct artificial inoculation seem to be about the same, from two to three weeks in the case of dogs, horses, and monkeys. As regards man, observations are too few to warrant anything like a definite statement on the point, but in one or two instances circumstances seem to point to a similar incubation period.
Symptoms.—— Without being too definite on the point, and basing the statement on the experience of a limited number of cases, I would suggest that the bite of an infected glossina is followed, in a proportion of cases, by a degree of local irritation of greater or less severity. This subsides in the course of a few days, to be followed, sooner or later, by fever which may last a week or longer, and which may be accompanied by the appearance, in Europeans at all events, of a peculiar type of erythema and a certain amount of serous infiltration of the connective tissue. A form of hypersesthesia, known as " Kerandel's symptom," is usual, though not invariable; if the patient strikes a limb against any hard object, a degree of discomfort amounting to actual pain is experienced, the sensation being slightly delayed. In time the fever subsides more or less completely, to recur at irregular intervals of days or weeks. The fever is sometimes mild, sometimes severe, and occasionally hyperpyrexial (106.6° F.), the evening temperature being always the higher. The fever may last for weeks; the apyretic period may be equally prolonged. On the other hand, the fever may be continuous, or the apyretic period may last for months. Irregularity of degree and duration is a feature of the fever and, also, of the other clinical manifestations of trypanosomiasis. In time the patients become debilitated, anaemic, feeble both intellectually and physically. Headache is very often complained of. The heart's action is generally rapid and easily excited. The cervical glands and the glands of other parts of the body enlarge and may become tender. It may be that only one gland is visibly involved, or there may be a recognizable general polyadenitis, including the abdominal glands. The implicated glands may be very prominent, or they may not be easily felt. In the early stage of the infection they are soft, later they are indurated. Sometimes they, are painless, sometimes distinctly painful and tender, rarely suppurating. This condition of irregular fever, of debility, of polyadenitis, of slight anæmia, may go on for months, or even, in some instances, for years.
There is reason to hope that in a proportion of cases the disease may terminate at this stage. I know and have seen three cases in which after many months of illness the symptoms entirely disappeared, and have been absent for several years, during which the parasite could no longer be found in the blood, whether tested by microscope or by animal injection (two cases). But, considering that the disease may present at various stages periods of quiescence which, in some instances, may be very prolonged, it would be rash to say whether in any instance of apparent recovery we are dealing with a radical cure, or merely with one of these long periods of latency. Experiments and observations by Laveran and others in other forms of trypanosoma infection, as well as cases of the disease in Europeans, justify the belief that occasionally the parasite does die out, either spontaneously or as a result of treatment.
It would appear that in a given area and in a given population there is a tendency for the virulence of the local trypanosome to i decrease with lapse of time. Thus, the trypanosome of Southern Nigeria, where sleeping sickness presumably ms been long endemic, is less virulent and much more amenable to treatment than that of Uganda, where it is of quite recent introduction.
Remarkable features of human as well as of animal trypanosomiasis are the skin affections and the local œdemas. In many of the lower animals affected with their special trypanosomes, in addition to fever and physical lethargy, papular and pustular eruptions are not uncommon; and in man, especially in negroes, an exceedingly itchy papular eruption is a
Fig. 48.—Rash of human trypanosomiasis. (From photo by R. McKay.)
common symptom. In the European, and possibly in the negro, but in the latter in consequence of his colour not so evident, extensive skin areas are affected with a fugitive, patchy, frequently annular erythema (Fig. 48), usually most evident on the chest and back, but also very often on the face and elsewhere. This erythema seems to occur most frequently and most distinctly in the earlier stages of the infection. Some of the patches may extend to six inches or even to a foot in diameter, their margins fading off insensibly into the surrounding normal skin. Sometimes the erythema takes the form of large rings, occasionally complete, more frequently interrupted and irregular. Erythema nodosum sometimes occurs. Pressure or any irritation of the skin gives rise at once to transient congestion from vaso-motor paralysis of the skin capillaries.
In some of the lower animals a usual feature is redema of certain parts of the body, especially the sheath of the penis, the under surface of the abdomen, and the neck. Similar though less extensive œdemas ccur in man, in whom they are most apparent about the face and about the site of the erythema. In many instances there is a general fullness of the features, which, together with concomitant flushing of the face, is apt to convey a false impression of sound health.
Neuralgic pains, cramps, formication, and paræsthesiæ of different kinds are not uncommon. In two of my European cases recurring orchitis, accompanied by an increase of parasites in the blood, was a feature. Painful local inflammatory swellings, which after a time subside without suppuration, I have seen in three cases; periostitis of tibiae once. Irido-cyclitis and choroiditis are sometimes met with.
In most cases the spleen is enlarged, sometimes enormously enlarged, the swelling fluctuating with the fever. The liver also may be enlarged. As the patients affected with trypanosomiasis are usually the subjects of malarial disease, it is not always possible to say whether the splenic enlargement is entirely or partly attributable to the trypanosome.
According to Greggio, trypanosoma infection is not as a rule transmitted to the fostus; nevertheless, the abortion-rate in the infected is increased from the normal 7 per cent, in Congo natives to 31.7 per cent., and the infant mortality from 29 per cent, to 50 per cent. Death from intercurrent disease, or from rapidly developing cerebral implication causing convulsion, the status epilepticus, coma, etc., may supervene at any stage of trypanosomiasis. Usually the case gradually drifts into the stage known as "sleeping sickness."*[5]
Sleeping sickness.—— The condition known as sleeping sickness may be regarded as the terminal stage of trypanosoma infection. Sometimes it exhibits acute features, sometimes it is exceedingly chronic. From the commencement of the infection to the development of this terminal stage, in a proportion of instances an interval of many years, possibly seven, may elapse. In the majority of cases the march of events is much more rapid. The characteristic terminal symptoms depend on implication of the nervous system either by the parasite itself or by its toxins.
According to Low and Castellani, the average duration of this stage of trypanosomiasis in the African is from four to eight months, not infrequently less; very chronic cases with a course of more than a year's duration are rare. Other observers refer to cases running on for three years, or even longer, and presenting occasionally temporary ameliorations.
Generally the first indications of the oncoming of sleeping sickness are merely an accentuation of the debility and languor usually associated with trypanosoma infection. There is a disinclination to exertion; a slow, shuffling gait; a morose, vacant expression; a relaxation of features; a hanging of the lower lip; a puffiness and drooping of the eyelids; a tendency to lapse into sleep or a condition simulating sleep; a slowness in answering questions; a shirking of the day's task. Dull headache is generally present. Later there may occur fibrillary twitching of muscles, especially of the tongue, and tremor of the hands, more rarely of the legs, indicating a definite implication of the motor centres.*[6] By this time the patient has taken to bed, or he lies about in a corner of his hut, indifferent to everything going on around him, but still able to speak and take food if brought to him. He never spontaneously engages in conversation or even asks for food. As torpor deepens he forgets even to chew his food, falling asleep perhaps in the act of conveying it to his mouth, or with the half-masticated bolus still in his cheek. Nevertheless, such food as he can be got to take is digested and assimilated. Consequently, if he is properly nursed, at this stage there may be no general wasting. As time goes on he begins to lose flesh, tremor of hands and tongue becomes more marked, and convulsive or choreic movements may occur in the limbs or in limited muscular areas. Sometimes these convulsions are followed by local temporary paralysis. Sometimes there is rigidity of the cervical muscles and retraction of the head. Bedsores tend to form; the lips become swollen, and the saliva dribbles from the mouth. Gradually the lethargy deepens, the body wastes, the bedsores extend, the sphincters relax, and finally the patient dies comatose or sinks from slowly advancing asthenia. Possibly he succumbs to convulsions, hyperpyrexia, pneumonia, dysentery, or other intercurrent condition.
The manifestations described are subject to considerable variations. Mania is not uncommon; delusions may present themselves, or psychical and physical symptoms not unlike those of general paralysis of the insane are developed.
During the whole course of the nervous stage of trypanosomiasis the other symptoms already described as characteristic of the infection may be in evidence. The knee-jerks, though lost towards the end, are active at first; the fundus oculi is normal; the sphincters, until towards the end, are controlled; the urine is normal, and the bowels, although generally tending to constipation, act with more or less regularity. Mortality.—Although spontaneous recovery may take place in the early stages of trypanosomiasis, when the disease has arrived at the stage of sleeping sickness death, it is believed, is inevitable. Corre has told us how native villages in Senegambia have been depopulated. What has occurred on the Congo, in Angola, and recently in Uganda, bears out this estimate of the gravity of the disease when it appears
Fig. 49.—Transverse section of vessel in the brain in a case of sleeping sickness. (From photo after Bettencourt.)
in epidemic form. We know that many islands on the Victoria Nyanza have been completely depopulated; and if it be true for a large part of the country, as Bruce has shown to be the case at Entebbe and its neighbourhood, namely, that 30 per cent. of the population harbour trypanosomes, the outlook for Uganda and neighbouring countries is grave indeed. The population of the implicated districts of Uganda, originally about 300,000, was reduced in six years to 100,000 by sleeping sickness.
Morbid anatomy (Fig. 49).—— No gross lesions of the nerve centres, or of any other organ, have been described as invariably present; but in every case indications, principally microscopical, of an extensive meningo - encephalitis can be demonstrated. In a proportion of instances congestion of the meninges, effusion of lymph, increase and turbidity of cerebrospinal fluid, are found. In all cases, as first pointed out by Mott, there is an extensive small-cell infiltration of the perivascular lymphatic tissue throughout the brain, cord, and meninges, varying in amount in different cases and in different anatomical regions. This, the essential pathological feature of sleeping sickness, recalls the very similar condition in general paralysis of the insane.
The nervous elements exhibit secondary degeneration changes.
Similar changes are described by Mott in the nervous system in dourine, and chronic trypanosomiasis in the monkey. Mott has also pointed out that the lymphatic tissues throughout the body are similarly affected.
Bettencourt and other Portuguese observers, as well as Castellani, have described a diplococcus in the brain in sleeping sickness. This organism is in no sense causally related to the disease; it must be regarded merely as a terminal and non-essential epiphenomenon. Similarly, Filaria perstans (which at one time, in consequence of considerations of frequency of concurrence and geographical distribution, was regarded as being possibly the cause of the disease), the various intestinal worms, and Schistosomum hœmatobium, though often met with in sleeping sickness, are present only as accidental concurrences.
Diagnosis.—— Chronic irregular fever, more especially if associated with enlarged cervical glands and, in the European, erythema multiforme, in a patient who has resided in tropical Africa at any time during the previous seven years, but more especially recently, suggests a tentative diagnosis of trypanosomiasis and detailed examination with this possibility in view. Diseases with which trypanosomiasis might be confounded are malaria, kala-azar, pellagra, syphilis, leprosy, and, in its later stages, beriberi, Malaria, syphilis and leprosy are easily excluded. As regards beriberi, there should be no difficulty if it be borne in mind that it is a disease of the peripheral, whilst trypanosomiasis is a disease of the central nervous system; that beriberi is non-febrile, and that trypanosomiasis is febrile. Kala-azar and trypanosomiasis, especially in their earlier stages, may be more difficult to differentiate; but the presence of enlarged glands, local oadema, and erythema multiforme in trypanosomiasis, and their absence in kala-azar, suffice for distinction. Blood or gland-lymph examination, or, if this be negative, hepatic or splenic puncture, should establish the diagnosis.
In pellagra the erythema is of a characteristic type. It is not ringed or fugitive as that of trypanosomiasis, and it affects principally the exposed parts of the body; the disease is of a much more chronic character, and, instead of lethargy, the mental condition, if implicated, is more that of insanity melancholia alternating with mania and terminating in dementia. Further, in pellagra, the symptoms are aggravated at particular seasons spring and autumn.
General paralysis of the insane,*[7] cerebral tumour, forms of meningitis, have features in common with trypanosomiasis and must be considered in diagnosis.
The microscopical diagnosis of trypanosomiasis is sometimes difficult. Anæmia as well as a large mononuclear leucocytosis occurs in trypanosomiasis. A wet blood preparation exhibits, even to the naked eye, a remarkable clumping of the red corpuscles. Held up to the light, such a preparation has a peculiar granular appearance, produced, as can be seen on microscopical examination, by agglomeration of the corpuscles into heaps and clusters, the usual rouleaux arrangement being absent. Such a disposition of corpuscles is significant of, though not peculiar to, trypanosoma infection. As a rule, the parasites in the peripheral circulation are few in number, many fields having to be hunted before a single example is discovered. Sometimes none can be found; rarely are they abundant. In the same case they are sometimes present, sometimes absent. Centrifuging the blood is not of much assistance. Dutton and Todd have emphasized the value of lymphatic-gland puncture and examination of the aspirated lymph, particularly in the earlier stages of the disease when the glands are soft and before they have become sclerosed; then the trypanosomes are fairly abundant in the lymph. An ordinary hypodermic syringe suffices to aspirate a sufficiency of lymph. Films of the lymph so obtained are prepared and stained in the ordinary way. Cerebro-spinal fluid, obtained by lumbar puncture and centrifuged, affords another though not always a practicable means of finding the parasite.
Failing discovery of the parasite by blood or lymph examination, recourse must be had to animal inoculation, 10 to 20 c.c. drawn from a vein being used for that purpose. Of the ordinary laboratory animals the most susceptible, and therefore reliable, are the guineapig, the rat, the dog, and certain monkeys——Macacus and Cercopithecus. Such inoculations are of value as a test of recovery, as well as for diagnosis.
The trypanosome is easily stained by most dyes; convenient stains are those in use for malaria work. A sixth objective suffices to find the parasite.
Treatment.—— Although something may be done to relieve symptoms and delay the fatal issue in the sleeping-sickness stage of trypanosomiasis, it is only in the earlier stages of the infection and by the persistent and energetic use of arsenic or antimony, or both, that a cure can be effected, and that in a proportion of cases only. Other drugs have been shown to have some influence on the trypanosome infections of the lower animals, but their therapeutic value in those of man is practically negligible.
The effects of the administration of arsenic compounds on a heavily infected animal are very marked, after a preliminary and marked increase in the number of parasites in the peripheral circulation. According to Thomas, in from three to seven hours an adequate dose of atoxyl causes the trypanosomes to become swollen, deformed, and almost motionless, their cytoplasm taking on a peculiar ground-glass appearance, becoming vacuolated, and presenting large dark granules. After seven or eight hours, coincidently with a marked increase of leucocytes—— especially phagocytes—— the parasites become rapidly fewer, and by the sixteenth or eighteenth hour completely disappear.
Arsenic, in the form of Fowler's solution or of orpiment, is sometimes given by the mouth; but this way of administering the drug, especially in Europeans, has been quite superseded by the intramuscular injection of a variety of relatively feebly toxic preparations, including atoxyl, soamin, arseno-phenylglycin, arsacetin, salvarsan,*[8] etc.
Atoxyl, a meta-arsenic-anilin compound, introduced by Thomas, is probably the best of these, and the one most usually employed. Unfortunately it has one serious drawback—— in large doses it is apt to give rise to optic neuritis, arid consequent atrophy and blindness. The drug, therefore, must at once be stopped on the slightest threatening—— dimness of vision or congestion of the disc—— of such a calamity. Gastro-iiitestinal irritation and peripheral neuritis are also indications that it has to be suspended, at least temporarily, arid the subsequent dose reduced.
Atoxyl is best given intramuscularly in 10 per cent, solution in sterile normal saline. The solution should be freshly made and free from precipitate. The individual dose should not exceed 7 or 8 gr. The practice as regards dosage and the times and frequency of administration varies. Some advocate a 7-gr. dose once every fifth day until symptoms subside. After a few weeks, similar courses, lasting for a month and repeated at short intervals, are kept up for at least one year. My practice has been to give an injection of 3 gr. every third day, and to keep this up uninterruptedly for two years, unless symptoms of arsenical poisoning show themselves, when the course is temporarily intermitted. I have seen excellent results from this method of giving atoxyl, both alone and in combination with tartar emetic by mouth or intravenously.
Antimony in the form of sodium tartrate hypodermically has been shown by Plimmer and Thompson to cause, without the production of serious local irritation, almost immediate and often permanent disappearance of T. lewisi in infected rats. In two cases of trypanosomiasis in man in which I used this drug intramuscularly the consequent local pain and irritation (culminating in tissue necrosis) were so excessive that in this form the treatment had to be abandoned. One of the patients, however, continued the drug by mouth to the extent of 1½ to 2 gr. daily, very highly diluted, a little being given in all his food and drink, and along with atoxyl injections, for over two years. He appears to be quite well.
The value of antimony (tartar emetic) in the treatment of trypanosomiasis is so marked that, if possible, it should be employed in every case. It is far too irritating for intramuscular injection. It can be given, freely diluted in normal saline, per rectum; but the efficacy of this method of administration has not been proved. Though troublesome and not free from risk, the intravenous method is the best and the one now generally adopted. The dose is ½ gr., gradually increased to 1½ gr., in 6 oz. or thereabouts of sterile normal saline.
The solution must be slowly introduced, and great care taken that none of it escapes into the connective tissue surrounding the vein. Pain and swelling, and perhaps abscess, are apt to follow such an accident. With this in view it is well, before pouring the emetic solution into the receiver of the transfusing apparatus, to place in the latter an ounce or two of plain saline, and, when the emetic solution has nearly all run through, a similar quantity of saline.
Not infrequently during the progress of the transfusion the patient is seized with a fit of coughing, or with feelings of constriction of the chest and faintness. If these are severe they may be regarded as indications for stopping the flow of fluid. Usually, though not always, the transfusion is followed by smart fever which soon subsides. A similar occurrence may follow intramuscular injection of atoxyl, and has been attributed to toxins liberated from the trypanosomes killed by the drug.
As with atoxyl, there are differences in the methods of employing antimony injections. Some give them daily in courses of fifteen days at intervals of fifteen days; others, once a week; others, again, according to indications supplied by temperature and the microscopical examination of the blood. After the short fever which may ensue, the administration of antimony is usually followed by marked relief of symptoms.
Unless contraindicated, atoxyl and antimony treatment should be combined or alternated. One or both should be instituted immediately the diagnosis of trypanosomiasis is established.
As pointed out by Ehrlich, certain strains of trypanosomes are "arsenic- fast," that is, they resist the action of the drug—— a property which becomes hereditary and is continued in sub- inoculations into the lower animals. This undoubtedly accounts for the failure of arsenical treatment in a large proportion of cases. Presumably there are strains having a similar resisting power to antimony. As the atoxyl-fast trypanosomes may respond to antimony, and vice versa, both drugs should be employed in every case. In the face of so grave a disease great risks are justified.
Recently, Daniels and Newham report favourably on treatment of Rhodesian trypanosomiasis by intramuscular injections of 30 minims of Martindale's injectio antimonii oxidi given twice daily and kept up for some time. The injections are painless and cause no necrosis. This method of giving antimony is worth further trial. The dose mentioned is equivalent to 1/20 gr. of tartar emetic. According to Laveran, Roudsky, Kudicke, and Werbitzski, at times the acquired drug resistance is accompanied by a change in the morphology of the trypanosome. In T. bruceithis resistance to parafuchsin and oxazine is accompanied by a disappearance of the blepharoplast, and this feature persists on sub-inoculation in untreated animals (even as far as the 140th sub-inoculation), but is lost immediately the trypanosome is passed through the appropriate definitive host.
In the treatment of trypanosomiasis, concurrently with the use of drugs, every effort should be made to keep the patient in good general health. Rest, warmth, and residence in a cool and healthy climate, the systematic use of quinine for any concurrent malarial infection, and the avoidance of fatigue and everything that might depress, should be insisted on.
The idea of cure must not be entertained until the patient has been free from all symptoms for many months, nor until the repeated injection of several cubic centimetres of his blood has failed to induce trypanosomiasis in susceptible animals.
Immunisation.—— Attempts have been made to procure a curative and immunizing serum, but, although a certain amount of success has attended these efforts in respect to the lower animals, as regards man they have failed.
Prophylaxis.—— The indications for prophylaxis are based principally on the habits of Glossina palpalis and the existing conditions as regards the presence of the infection in a locality.
In endemic regions the fly areas should be located and avoided. If such regions have to be traversed the journey should be made during dark nights when tse-tse flies do not feed, or with such precautions as are used by the natives for the protection of their cattle in nagana-infected spots. Those who are compelled to live in tse-tse regions should have their houses and persons carefully guarded against the fly. Manifestly it is desirable ——whether it is feasible is another question—— to avoid localities in which the natives are affected, and to prevent the infection of the local tse-tse flies by surrounding people having trypanosomes in their blood with mosquito netting; or by other measures, such as removing them from the usually very limited fly area to some neighbouring fly-free spot. Movements of infected individuals towards hitherto uninfected countries must necessarily be attended with great risk of the introduction of the disease. Whether such movements can be prevented in savage lands depends greatly on local circumstances. Wherever possible they should be prevented. Dutton and Todd suggest that an easily ascertained condition, more or less general in trypanosomiasis, namely, enlargement of the cervical glands, should be employed in eliminating dangerous individuals. Many years ago slave-dealers adopted such a method to shield themselves from loss. As a rough test it has some value. But in some cases of trypanosomiasis the glands are not appreciably enlarged at all times. Moreover, as they are often enlarged in other conditions, an injustice might be done in enforcing such a measure.
Hodges and his colleagues in Uganda inform us that the fly ground proper is always a very narrow strip indeed, not more than ten to fifteen yards, and always along the water's edge; and that the insects very rarely extend their feeding beat beyond sixty yards of this, whether on the land side or on the water side. It is true they may follow with great persistency a man who has just passed through this narrow belt, for several hundred yards, rarely as far as half a mile; but it is obvious that if the ten or fifteen yards at the water's edge be made unsuitable for the fly, as can readily be done by clearing it of jungle, there will soon be no flies to follow, and the place will become safe. Therefore, where feasible, fly spots, where there are landing-places, ferries, wells, or roads, should either be avoided altogether or be cleared of jungle for some yards—— to be safe, thirty——from the water's edge. This is a practical measure of proved value in Uganda.* [9] Brilliant results have attended the efforts of the Portuguese to combat sleeping sickness in the island of Principe, where the annual mortality from the disease amounted to 83 per thousand of the population, and the local industry (cocoa) was threatened with extinction. In addition to jungle clearing, drainage, blood examinations and segregation of infected, and destruction of possible animal reservoirs of the trypanosome, coolies, dressed in white and carrying on their backs a dark cloth smeared with bird-lime, were sent into the jungle, and every night the flies caught were removed and counted. In three years 470,000 glossinæ were caught. As a consequence of this combination of sanitary measures the fly and the sleeping sickness were exterminated. Of course it was only the complete 'isolation and the limited size of the island that made such a result possible.
Koch, from observations in Uganda, suggested that trypanosomiasis may be communicated by the male during coitus. The phenomena of dourine and recent animal experiments support the idea, although the experiments referred to indicate that the risk is not great.
A. complete scientific prophylaxis can be indicated with certainty only when we have full knowledge (1) of the habits of the tse-tse flies and of the reasons for their restriction to very limited and apparently capriciously distributed areas; (2) as to what vertebrates under natural conditions are normally hosts of T, gambiense. Experiment has shown that the glossina will bite any vertebrate, and that it can infect a large variety of mammals with the trypanosome. If this be the case in the laboratory it is reasonable to suppose that it is the case in nature also. Therefore, in the endemic regions of trypanosomiasis, the vertebrate fauna has to be reckoned with as a source and reservoir of infection.
In Uganda and elsewhere, principally with a view of preserving the hitherto uninfected from trypanosome infection, Government removed the entire population of the Sesse Islands and neighbouring shore of Lake Victoria Nyanza to fly-free areas in the interior. It was hoped that, the human source of trypanosome supply being thus denied them, the tse-tse flies would cease to be infective. Unfortunately, this hope has been disappointed. Three years after depopulation of the districts involved, Bruce ascertained that the local flies could still convey the disease to laboratory animals. Manifestly, T. gambiense can flourish under natural conditions in vertebrates other than man. The large game is now regarded as a probable reservoir for T. gambiense, as it is known to be for the T. brucei of nagana.
The introduction of T. gambiense into other countries is a grave possibility. It is true that it must have been frequently introduced into America in the days of slave importation and that it did not spread there; but as regards India and other Asiatic countries, which hitherto have had little or no communication with the West Coast of Africa, no introduction on a large scale has occurred, and we have no assurance that, if introduced, the parasite would not find some appropriate transmitter. According to some authorities, nagana and surra are the same disease; if so, the causal trypanosome can be transmitted by blood-sucking flies other than the tse-tse. What holds good for T. evansi and T. brucei might equally apply to T. gambiense. Furthermore, the possibility of the introduction of the fly host of the trypanosome of sleeping sickness, G. palpalis, into other tropical countries must not be lost sight of.
TRYPANOSOMA RHODESIENSE
The discovery by Stephens and Fantham that the trypanosome found in sleeping-sickness cases originating in Nyasaland and Rhodesia presented certain peculiarities when passed through the rat, that it was associated with a highly virulent and resistant form of the disease,*[10] that animals immunized against T.gambiense succumbed to the Rhodesian trypanosome, and especially, as proved by Kinghorn and Yorke, that it was transmitted by Glossina morsitans, justifies the conclusion that, if not a distinct species, Trypanosoma rhodesiense, as it has been named, is a very definite variety, and that in practice it must be regarded as such.
In human blood (Fig. 50), T. rhodesiense is morphologically indistinguishable from T. gambiense; but if it is passed through the rat a small but variable proportion of the parasites, especially the stumpy forms, will be seen to have their nuclei located posteriorly to the blepharoplast, that is to say, at the non-
Fig. 50.—Trypanosoma rhodesiense. (After Laveran.)
1 and 2, Normal forms in blood of man; 3-6, various stages of posterior displacement of the nucleus; 7, a dividing form.
flagellar end of the organism. It also, as occasionally in man, exhibits a marked periodicity, disappearing from the blood-stream for weeks at a time.
Glossina palpalis has not been met with in Rhodesia and Nyasaland; its rôle as regards the trypanosome is filled by Glossina morsitans.
According to Kinghorn and Yorke, the peculiarities in the range, distribution, and fly intermediary of T. rhodesiense receive their explanation in the circumstance that the developmental cycle is dependent on atmospheric temperature. High temperatures (75°-85° F.) favour development in the fly, low temperatures (60°-70° F.) are against it.
The same observers have ascertained that the large game of the country is a reservoir of the parasite. In view of this, Yorke has advocated as an experimental sanitary measure the extermination of this interesting fauna. Seeing that this terrible disease is spreading, and that it has already crossed the Zambesi, that the range of G. morsitans extends as far south as Zululand, that this species of glossina is not so circumscribed topically as G. palpalis, and that it is believed to be in great measure dependent on these animals, the destruction or driving back of the large game in morsitans countries seems to be the only measure likely to avert what might otherwise prove to be an immense calamity.
Later experiments by Bruce and his, co-workers have shown that T. brucei, when injected into rats, exhibits the same proportion of posterior-nucleated forms as T. rhodesiense. From this and other facts these observers suggest that T. rhodesiense is none other than T. brucei, that 37 per cent, of the wild game in the fly-country harbour pathogenic trypanosomes, and that the waterbuck, hartebeest, reedbuck, and duikerbuck are a source of danger to man.
Taute, who has recently carried out much research work 011 this important subject in Portuguese Nyasaland, does not agree in all respects with the views of Kinghorn, Yorke, and Bruce. He points out that the trypanosomes in naturally infected game or domestic animals can be regarded as a potential cause of sleeping sickness only if they are actually shown to be pathogenic to man; and he maintains that the wild game and domestic animals do not play any part in the spread of sleeping sickness, at all events in the sense of Kinghorn and Yorke. Merely to infect laboratory animals with a trypanosome morphologically identified with T. rhodesiense does not prove that this trypanosome is T. rhodesiense, or that the district from which the trypanosome came is a sleeping-sickness area. He says that in East Nyasaland T. brucei can be distinguished from the trypanosome of sleeping sickness only and solely by the fact of its non-pathogenicity to man. Taute supports these views by some very significant experiments. G. morsitans fed on animals infected with T. brucei were subsequently fed to two men; the result was negative, though a number of control animals fed simultaneously died. Taute injected himself with 2 c.c. of blood from a trypanosome-infected dog, the trypanosomes being of the Rhodesian type; there was no bad effect. Fourteen days later he injected 90 c.c. of his own blood into susceptible animals; these animals did not become infected—— showing that the human organism has the power to kill this particular trypanosome. Whether Taute is right or wrong in his views, it must be conceded that he has the courage of his opinions.
Atoxyl and antimony, generally so potent against T. gambiense infection, seem to be relatively powerless in the sleeping sickness of Rhodesia.
TRYPANOSOMA CRUZI (SCHIZOTRYPANUM CRUZI)
Chagas has shown that a form of trypanosomiasis, especially common in children, is endemic in parts of the state of Minas Geraes in Brazil, and that it is transmitted to man and the domestic animals by a species of bug, Lamus megistus (at first erroneously supposed to belong to the genus Conorhinus). Allied species and certain other biting insects appear to have the power of transmitting the infection, at all events under experimental conditions.
Symptoms.—— The disease assumes a variety of aspects according to the organs more particularly affected by the parasite, individual susceptibility, and the occurrence of reinfection. It is frequently fatal, and in those who recover is apt to entail conditions, physical and mental, resembling cretinism.
Chagas recognizes acute and chronic types. In the former, shortly (ten or more days) after the bite of the transmitting insect, which is painful, high fever supervenes together with enlargement of the thyroid gland, lymphatic glands (especially the cervical), spleen, and liver, myxœdematous swelling of the face, and transient œdemas in different parts of the body. There may be indications of meningoencephalitis. These symptoms come and go during a variable period, and terminate either in death, or in recovery, or in the chronic form lasting for years.
Fig. 51.—Trypanosoina cruzi. (After Chagas.)
Figs. 1-6.—Forms in human blood:
1, 2, Supposed endocorpuscular forms; 3, 4, trypanosomes adhering to red cells; 5, 6, so-called male and female forms.
7 and 8.—Schizogony in the endothelial cells of pulmonary vessels in man:
(Diagrammatic representation of the pulmonary cycle, cyst formation and liberation of young trypanosomes. It is doubtful whether ♂ and ♀ cycles as described by Chapras really exist.)
9-14.—Forms found in Lamus megistus:
9 and 10, Forms from midgut showing development of flagellum; 10 and 11, forms from the hindgut; 12, simultaneous division of nucleus and centrosome; 13 and 14, forms from salivary gland, under a lower magnification.
In the chronic form there is well-marked enlargement of the thyroid, with accompanying myxœdematous symptoms, as loss of hair, mental debility, etc. The lymphatic glands are always enlarged. In some instances there is marked bronzing of the skin, as in Addison's disease, depending on implication of the suprarenal capsules. In others, where the brunt of the infection has fallen on the heart, there is great irregularity in the action of this organ. In yet others aphasia, ataxia, spasm, athetosis, tremor, or other nervous symptoms indicate that brain, or spinal cord, or both have become implicated. Generally there is a combination of several of these conditions. Throughout, an irregular fever comes and goes, and there is always pronounced anæmia.
The chronic form is that most commonly encountered in youths or adults; it is probably carried on from infancy or childhood, or kept up by reinfection.
The parasite.— During the febrile attacks the parasite (Fig. 51) in variable numbers is to be found in the blood, free or, rarely, partially included in red blood-corpuscles (Chagas). It averages about 20/u in length and has the usual trypanosome characters. The undulating membrane is narrow and the nucleus and blepharoplast are large. It is easily cultivated.
After ingestion by the insect intermediary the trypanosomes multiply in the gut. Some pass out with the faeces, which thus become infective if inoculated into a wound, or if applied to a mucous surface as the conjunctival sac (Brumpt). This, however, is not the normal way in which the infection is conveyed to man. In the midgut of the lamus, crithidia forms and, at a later stage, minute trypanosoma forms develop. It is the latter that, passing into the salivary glands, become the agents by which the infection is established. Eight days elapse after feeding on infected blood before the bug itself becomes infective.
Arrived in the human body the parasite multiplies, not in the blood (dividing forms are never found there), but in the cells of various organs, including the striped muscular fibres, especially of the heart, back, and lower extremities; also in the bone marrow, the thyroid gland, suprarenal capsules, nerve fibres and cells, testes, connective tissue, and other organs. Arrived in these it assumes a leishmania form (Fig. 56), divides and subdivides, distending the including cell till this becomes a mere cyst in which the parasites revert to the trypanosoma form. The cyst then bursts and the trypanosomes escape into the tissues, ultimately finding their way into the blood concurrently with an attack of fever. This is the form of schizogony by which the infection is kept up in the individual.
According to Chagas the gamete providing for the exogenous cycle in the insect arises from certain trypanosomes which, lodging in the lungs, lose their flagella and, approximating their extremities, form a ring, and then a sphere in which the nucleus divides, giving rise to eight daughter spheres. These elongate and, escaping, enter the red blood-corpuscles and become male and female trypanosomes, thus providing for the exogenous cycle in the insect (Fig. 51).
In the insect the parasite is not transmitted hereditarily, but the nymph, as well as the mature lamus, is capable of harbouring and transmitting the parasite. In the endemic districts all the bugs and many domestic animals are infected. Chagas considers that the armadillo, whose burrows are haunts of lamus, is the normal host of the parasite and a principal reservoir for the infection.*[11]
Pathological anatomy.—— Inflammatory and consequent degenerative changes, the result of the presence of the parasite, are in evidence in most of the affected organs. Under the microscope the cyst like distended cells containing the parasite are to be found, particularly in the striated muscular fibres, and especially in those of the heart. The thyroid is enlarged, often sclerosed, with cystic cavities containing colloid material. The lymphatic glands and the spleen are also enlarged, the liver is fatty, serous effusions in pleura and peritoneum are common, and there may be evidences of meningo-encephalitis with infiltration about the vessels.
Prophylaxis.—— This should be directed principally to the suppression of the insect concerned—— Lamus megistus (Plate III.). It is a large black insect belonging to the family Reduviidæ, with numerous symmetrically arranged red markings; it is well known to the natives, who call it " barbeiro." The nymphs bite and can convey the infection, but the adults, having wings, are more dangerous. During the day time they live in the grass walls and roofs of the dirty native houses, coming out after dark in search of their food—— blood. Their habits indicate better and cleanlier housing, sleeping off the ground, and protection by mosquito-netting.
Treatment.—— We know of no specific remedy. Arsenicals and antimony have failed in experimental animals. Treatment, therefore, must be on general lines.
OTHER FORMS OF TRYPANOSOMIASIS IN MAN
Seeing that most of the trypanosomes hitherto studied experimentally are capable of living in a variety of vertebrate hosts, it seems probable that other members of this group of parasites, in addition to T. gambiense, T. rhodesiense, and T. cruzi, may find in man at times a suitable host. Apparently T. lewisi, T. evansi, and T. brucei do not generally thrive in man, but that circumstance does not warrant the inference that he is completely immune against these and all other species.
CERTAIN OP THE COMMONER TRYPANOSOMES OP MAMMALS
Lamus megistus. (After Chagas.)
Plate III.
It must be remembered that T. brucei, T. gambiense, and T. evansi exhibit a wide range of pathogenicity for many species of animals.
Fig. 52.—Trypanosomes of mammals, x 1,000.
a, T. equinum; b, T. brucei; c, T. equiperdum; d, T. lewisi; e, T. evansi.
Our knowledge of the trypanosomes is still incomplete. Any attempt, therefore, at classification must be merely tentative. Bruce's classification of the pathogenic African species (p. 194), founded on very large experience in the field, has the merit of being of practical value. It is based mainly on three points—morphology, location of development of infective form in the tse-tse fly, and action on animals. Bruce divides the parasites into three groups—(A) T. brucei group, (B) T. pecorum group, (C) T. vivax group.
Of the trypanosomes of mammals the best known and most important are the following (Fig. 52):—
T. lewisi (Kent, 1879) is a parasite of rats (Mus decumanus, M. rattus, M. rufescens). Similar parasites in hamsters, guineapigs, rabbits, etc., probably belong to different species; it has been held that T. lewisi is not capable of living in these animals, but subsequent work seems to contradict this.
On account of the facility with which it can be procured in most countries, T. lewisi offers the best opportunity for study of the genus. In many places from 2 to 50 per cent. of the local rats harbour it, often in such abundance that, viewed
| Bruce's Classification of Pathogenic African Trypanosomes | |||||||
| Form | Cytoplasm | Micro- nucleus |
Undulating Membrane |
Movement | Development in Tse-Tse |
Susceptible animals | |
| A. Trypanosoma Brucei Group, including T. Brucei—T. Gambiensi T. Evansi T. Equiperdum |
Polymorphic including short and stumpy forms |
Contains dark- staining granules |
Small and as a rule, at some distance from posterior end |
Well developed and in bold folds |
Active | Completed in salivary glands |
Many species of mammals |
| B. Trypanosoma Pecorum Group, including T. Pecorum T. Simiæ |
Mono- morphic and small |
Non- granular |
Prominent and sub- terminal |
Well developed |
Active | Completed in pro- boscis and hypo- pharynx. Never found in salivary glands |
Cattle—very fatal to pigs |
| C. Trypanosoma Vivaz Group, including T. Vivax T. Capræ T. Uniformi |
Mono- morphic |
Non- granular |
Large and terminal |
Little development and simple |
Very rapid | Completed in pro- boscis and hypo- pharynx. Never found in salivary glands |
Affects only horse, cattle, goats and sheep. Ordinary laboratory animals immune |
T. lewisi measures, on an average, including the flagellum, 24-25 μ by 1.5 μ; the posterior extremity is said to be more pointed than in the other known mammalian trypanosomes. The nucleus is situated in the anterior half or third of the body; the cytoplasm is very clear and free from granules. There is evidence that it is conveyed from rat to rat by the rat-louse and rat-fleas, which are now known to be its true alternative host. It is not, apparently, transmitted by the salivary glands of the insect, but multiplies in the hindgut of the flea, and, after assuming various crithidial forms, escapes in the excreta, and is thus inoculated into the wound made by the flea's proboscis.
In experimental rats it has been found possible to transmit infection to other rats through the unbroken skin by rubbing on cultures of this trypanosome.
It is generally held that T. lewisi is non-pathogenic. Certainly, infected rats usually exhibit a remarkable tolerance towards this parasite, but occasionally they do sicken and die.
The fact that the rat is susceptible to laboratory inoculation with the trypanosomes of man and cattle indicates the possibility of finding other species of trypanosomes in the blood of wild rats.
T. evansi (Steel, 1885); length, 22-30 μ; breadth, 1-2.5 μ. This parasite was discovered in 1880 by Griffith Evans in the Punjab, in the blood of horses suffering from surra, a disease which the natives of India ascribe to the bite of certain horse-flies (Tabaindae). T. evansi is not limited to horses and mules, but attacks also camels, elephants, buffaloes, and dogs. Experimentally it has been transferred to monkeys, rabbits, rats, mice, and guineapigs ; in nature, infection of dogs by feeding on animals dead of surra has frequently been observed. It has a very wide distribution in Southern Asia and in Malaya. It has been recently imported into Mauritius and the Philippines. We have no positive knowledge as to the definitive host or hosts of this trypanosome. Various blood-sucking flies belonging to the genera Stomoxys, Haematobia, and Tabanus have been incriminated. In Mauritius the epidemic is thought to have been spread by Stomoxys nigra.
The disease known as "Mbori," occurring among drome-daries coming from the Sahara into the Soudan (Timbuctoo, etc.), which is apparently also conveyed by a tabanus, is considered both by Vallee and Panisset, and by Laveran and Mesnil, to be a milder form of surra, the parasite which causes it being a "variety" of T. evansi.
T. brucei (T.pecaudi) (Plimmer and Bradford, 1899); length, 28-30 μ; breadth, 1.5-2.5 μ. The anterior extremity is usually bluntly rounded. The cytoplasm often contains in the posterior half large, deeply staining granules. This parasite was discovered by Bruce in 1895 in the blood of horses suffering from nagana, the fly disease of Africa. The normal intermediary hosts of T. brucei are probably some of the African Antelopidae, such as the wildebeest (Catoblepas gnu), the koodoo (Strepsiceros capensis), and the bushbuck (Tragelaphus scriptus sylvaticus), perhaps also buffaloes. Bruce's researches and experiments led to the belief that the disease was transmitted in a mechanical way by Glossina morsitans. Mr. Austen has shown that the tse-tse -flies with which Bruce made his experiments belonged chiefly, if not entirely, to the species G. pallidipes, and now we know that other glossinae, such as G. fusca, may also convey the disease, and that the role played by these flies is probably that of true alternative host. The development in the fly is identical with that described for gambiense. The fly does not become infective till the eighteenth, and remains so till the sixty-sixth day, or probably longer.
With the exception of certain strains of donkey and goat, all domesticated mammals hitherto experimented with, on inoculation with blood containing the parasite, acquire nagana.
After inoculation of an animal with nagana blood, in from one to two days trypanosomes begin to appear in the blood, and persist therein till death, which, in the vast majority of species, is inevitable. In some species (rats, mice) the trypanosomes become very numerous; in others (the rabbit, guineapig) they are scanty and may be hard to find with the microscope, although their presence may readily be proved by the symptoms and by injection of the suspected blood into the rat. After inoculation death occurs in rats and mice in from two to three days, in rabbits in from five to twelve days, in guineapigs in about fifty days (extremes twenty to 183 days), in dogs in from twenty-two to twenty-six days, in monkeys in fifteen days, in horses and donkeys in from one week to three months, in goats and sheep in several months, and in cattle in from one week to six months, a proportion recovering. Thus resistance varies within wide limits.
In those animals in which death occurs within a few days of infection the parasites become very numerous, and, after one or two oscillations of temperature, death occurs suddenly. In those animals in which death is delayed a very striking cachexia is established. There is a chronic recurring fever, the numbers of parasites visible in the blood being greatest during the febrile accessions; there is also a peculiar firm oedema from infiltration of coagulable lymph into the connective tissue of the neck, abdomen, sheath of penis, genitals, and limbs; with intense anaemia, wasting, skin eruptions, and, often, blindness. On post-mortem examination the spleen is in most instances found to be enlarged, ecchymoses may be present in various viscera, and the lymphatic glands corresponding to the point of inoculation are swollen.
T. brucei is considered by Bruce and several other observers to be the cause of Rhodesian sleeping sickness, and therefore identical with T. rltodesiense. Other trypanosomes, more or less allied to T. brucei, and possibly representing only varieties of the same parasite, have been observed in German East Africa and Togoland among cattle, horses, and other animals. Again, the disease known as "aino," which occurs in Somaliland among dromedaries, and which Brumpt believes to be transmitted by G. longipennis, locally termed the "aino," is probably a variety of nagana.
T. equiperdlim (T. rougeti) (Dofl., 1901); length, 25-28 μ; breadth, 1½-2 μ; differs from T. brucei in not having prominent granules in the cytoplasm. It is the cause of a peculiar disease in stallions, brood mares, and donkeys, occurring in South Europe, North Africa, Chile, and probably in the United States, and known as dourine or mal du co'it. The latter name it has received from the fact that, as a rule, the infection is communicated through coitus. It is not yet certain whether the parasites have any alternate insect host into which they must pass at intervals in order to complete the life-cycle. Fleas have been suggested as possible intermediaries.
Symptoms appear in from ten to twenty days after infection. They begin in the case of the stallion with oedema of the sheath and some inflammation of the end of the penis and discharge from the urethra; in the mare there is a similar oedema of one or both labia and a muco-purulent vaginitis. Concurrently with increase of these symptoms oedema of the limbs and of the abdominal walls sets in, together with pro- gressive anaemia, wasting, muscular weakness, flexion of the fetlocks, and skin eruptions. The appetite is preserved. Fever, except at the outset (40° C.), rarely exceeds 39° C. The disease continues for many months four to ten. Before death weakness increases, the cornea may ulcerate, and there may be complete paraplegia from softening of the spinal cord.
The trypanosome of dourine occurs in the blood, but in numbers so scanty that to communicate the infection with certainty by this medium it may be necessary to inject from 10 to 15 c.c. Hence the improbability of infection by biting insects. On the other hand, it occurs in great abundance in the oedematous tissues, in the skin lesions, in the lymph, and in the discharge from the genitals.
In marked contrast with T. brucei, T. equiperdum is but feebly pathogenic to rats and mice, some of the former being quite refractory. In the rabbit and dog the disease resembles that in the horse, and is communicable by coitus. Monkeys, goats, sheep, and bovines are said to be insusceptible.
Although in many respects the parasites of dourine and nagana resemble each other, the differences in susceptibility of various animals as regards the two parasites indicate specific difference.
T. equinum (Voges, 1902); length, 22-55 μ; breadth, l.5-2 μ. This parasite is clearly distinguished from the above-mentioned species by the very minute size of its blepharoplast. The cytoplasm contains granules, but not so numerous as in T. brucei. Its normal vertebrate host is probably the capybara, Hydrochcerus capybara, a large water mammal of South America belonging to the family Caviidae. Nothing positive is known about its transmitting agent; Stomoxys calcitrans and Stomoxys nebulosa have been blamed. T. equinum causes in horses a deadly disease known as "mal de caderas " in Brazil, Argentina, and Central South America.
T. theileri.—Laveran (1902) reports the discovery by Theiler in the Transvaal of a trypanosome twice the size of any of the foregoing, and peculiar to cattle; so far, other domestic animals have been found to be immune. Theiler regarded it as producing an acute pernicious anaemia without poikilocytosis, and with only slight accompanying fever. He considers "that there exists a natural immunity in cattle against this trypanosome." Theiler believed that the transmitter of this parasite was a spider-fly, Hippobosca rufipes. Another species, H. maculata, recently imported with cavalry from India, is believed to be aiding in spreading the parasite. The disease is known as "galziekte," or bile-sickness, in the Transvaal. More recently, however, Theiler has altered his views, and now believes the disease to be due to a small piroplasm, Anaplasma marginale.
THE TSE-TSE FLIES (Plate IV.)
(Genus Glossina, Wiedemann, 1830)
The Glossinae are sombre-coloured, narrow-bodied flies from about 8 to 12 mm. long, with a thick proboscis (i.e. proboscis enclosed by the palpi) projecting horizontally in front of the head. Their wings are large, of a brownish hue, and present a characteristic venation (Plate IV.) somewhat resembling that of the warble-fly (Hypoderma). The most striking peculiarity in the wing is the course of the fourth longitudinal vein, which about the middle of the wing bends abruptly upwards to meet the short and very oblique anterior transverse vein; here, describing a right angle, it runs obliquely downwards to meet the posterior transverse vein, and then turns upwards to reach the margin of the wing well in front of the apex. When the tse-tse is at rest its wings overlap on the back, crossing each other like the blades of a pair of scissors. This resting attitude of the wings, besides giving the fly a peculiar elongated appearance, renders it readily distinguishable from those other blood-sucking diptera with which it might be confounded, such as the stinging-fly (Stomoxys} and the cleg (Haematopota). Stomoxys is smaller in size, has short palpi not protecting the proboscis, and its wings diverge at an angle when resting. Haematopota presents prominent antennae and its wings are tectiform, i.e. they meet together at the base like the roof of a house and diverge slightly at the tips. In some species of Glossina the abdomen is crossed by sharply defined dark brown stripes, interrupted at the middle line. In the males, beneath the end of the abdomen, the external genitalia
form a conspicuous knob-like protuberance which renders the sexes easily distinguishable. 
Tse-tse flies.
1. Glossina palpalis; 2, G. morsitans.
Plate IV.
The palpi are long, slightly grooved on their inner sides, and closely applied to the proboscis, which they almost entirely conceal, the only uncovered portion being a peculiar large bulb-like expansion at the base. The proboscis consists of three parts (Fig. 54), labrum, hypopharynx, and labium.
The genus Glossina belongs to the family Muscidæ. The nearest related genera are Stomoxys, Lyperosia, Hamatobia; but on account of its limitation to Africa, its peculiar structural features (bulb at the basis of proboscis, remarkable male genitalia, characteristic venation of wings), and its aberrant mode of reproduction, it presents a marked individuality.[12]
The genus at present comprises fourteen species, though this number must not be considered final, as new species are discovered from time to time. Austen arranges the genus into four groups. (See the Table on p. 200.)
Distribution.—With the exception of one species, G. tachinoides, which occurs in the vicinage of Aden, tse-tse flies are confined to continental Africa. Some species, such as G. fusca and G. morsitans, have a very wide range throughout the greater part of intertropical Africa. G. palpalis is also widely distributed, ranging from the Senegal to Angola on the west, and throughout the Lualaba-Congo system to the Victoria Nyanza, Tanganyika, and Upper Nile at least as far north as Moolo in the Soudan. Glossina morsitans extends south in Bechuanaland, North-Eastern Transvaal, and Zululand. G. longipalpis ranges through West Africa as far south-west as the Senegal and south to the Katanga district on the Congo. G. pallidipes is found throughout East Africa from Zululand to the northern boundary of East Africa. Other species appear to be more restricted. G. longipennis is found in Somaliland and adjacent regions; G. tachinoides has a wide range in tropical Africa; G. pallicera ranges to the Ivory Coast; G. fusca ranges from Sierra Leone to Uganda; G. brevipalpis is common in South, Central, and East Africa; G. caliginea is found in Southern Nigeria. Knowledge of their topographical distribution is an important matter. The Glossing are never found on mountains; they are seldom seen above 3,000 feet; they are absent from extensive plains or other open places; they are rarely found in close cultivation. Their usual habitat is in the neighbourhood of open water along the banks of rivers, brooks, and springs, round the coasts of lakes, on low riverine islands, in swamps and mires, with open pools and sandy banks, especially at the foot of
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GENUS GLOSSINA Hind tarsi not entirely dark brown or blackish brown r~ -^ Upper surface of abdomen not banded I Hind tarsi entirely dark brown or blackish brown (all joints more or less dark) Wings fairly dark, palpi long and slender Wings pale, palpi short Upper surface of ab- domen distinctly banded "1 Chara icteris- tic thoracic markings (spots and stripes) dis- tinct Dorsum of ab- domen buff,3rd and other seg- ments exhibit- ing interrupted broad trans- verse bands mountains. A sudd- covered or sedgy-banked river or lake shore or sedgy swamp they do not frequent. They are most numerous along the water's edge; they become scarcer and scarcer as one advances inland, and (except in the case of certain species) during the rainy season disappear entirely within a few miles of the water. The places they occupy are sharply defined and, as a rule, permanently established. These places or stations are called "fly belts," and the natives know the limits of these belts precisely. The fly belts vary greatly in disposition and extent. Not infrequently they occur on one side of a stream but not on the other. These fly patches are usually confined to strips of jungle, to banana grounds coming down to the water's edge, or to areas of mosani or mimosa forest. In short, the essential condition of a tse-tse station are—— the presence of open water, a wooded district, and a loose soil. As a rule, the fly patches are in sandy ridges or where there are overhanging or jungle-shaded banks.
The limitation of the tse-tse to definite tracts or " belts " has given rise to much speculation. The prevalent opinion is that the fly waits near water to feed on the animals that come to drink. Austen ascribes it to a characteristic social tendency which is exhibited very frequently amongst Diptera. Sambon suggests that it may be related to some food habit ——possibly to a connection with air-breathing fish, of which there are several genera with numerous species in the rivers and lakes of Africa; the fly either feeding directly on the fish or on some mammal or bird which feeds on these fish. Such an association with air-breathing fish might explain the peculiar patchy distribution of certain species of tse-tse fly, their limitation to the neighbourhood of water, and the sandy and thickly wooded nature of their haunts. In the dry season air-breathing fish are obliged to bury themselves in the mud or to excavate burrows from which they come out towards evening in quest of food; they must therefore necessarily congregate in such places as offer conditions suitable to these habits.*[13] It is very important to ascertain the exact reason for the singular topical limitation of the fly, for it may be that through knowledge of this the prophylaxis of fly-transmitted disease could get its opportunity.
Reproduction.—— The Glossinœ do not lay eggs as do the majority of the Diptera, but, as in the case of forest-flies (Hippoboscidœ), the eggs hatch, and the larvæ feed, develop, and moult within the body of the parent, so that when extruded they have practically reached the pupa stage. In fact, the extruded larva becomes almost immediately a pupa, the larva skin becoming a dark, rigid puparium. When extruded, the fully grown larva is nearly as large as the abdomen of the mother; it is a yellowish ovoid body composed of twelve segments and presenting two small hooks at the anterior pole, and two protuberances at the posterior extremity, which is black. The perfect insect emerges from its pupa-case in about six weeks. In the case of G. palpalis the pupa has been found in Uganda buried in the loose earth about the roots of banana trees (Bagshawe) and similar situations.
Habits.—Tse-tse flies are voracious blood-suckers, exhibiting great persistency in their attacks on man and animals. They bite almost exclusively during the day, though some of the larger species bite at night, and one of them, G. brevipalpis, is stated to be definitely crepuscular in its habits. Contrary to what is the case among horse-flies (Tabanidæ) and mosquitoes (Culicidæ), of which the females alone suck blood, in the tse-tse both sexes are blood-sucking, and with some species the males are more voracious, or more pertinacious, than the females.
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| Fig. 53. Tse-tse fly. |
Fig. 54. Mouth parts. |
Fig. 55. Pupa stage. |
- ↑ * Laveran and Mesnil in their "Trypanosomes et Trypano- somiases, 1912," have given a very complete and accurate account of this subject. For full details up to date of publication the student is referred to this work.
- ↑ † For a brief description of the trypanosomes of mammals the reader is referred to p. 192.
- ↑ * The composition of this is as follows: Agar 14 grm., salt 6 grm., distilled water 900 c.c.; macerate carefully with fresh
- ↑ * For a brief description of the tse-tse flies, see p. 197.
- ↑ * It is customary to state that the development of the sleeping-sickness stage in tiypanosomiasis concurs with and is dependent on the entrance of the parasite into the cerebro-spinal canal.
- ↑ * In German East Africa, out of 55 patients in the last stages of the disease only 5 had sleep symptoms. Exophthalmos was noted 16 times.
- ↑ * The Wassermann reaction is of little avail, as unfortunately the sera of most cases of trypanosomiasis give a positive result.
- ↑ * Broden and Rodhain report good results on the Congo by intravenous injection of salvarsan; they insist that it is only of benefit in those cases where invasion of the spinal cord is negatived by microscopical examination of the spinal fluid.
- ↑ * Duke has tried the injection of prophylactic doses of arseno-phenylglycin in the monkey and subsequent development of the trypanosome in the tse-tse fly. He finds that a monkey thus injected cannot be subsequently infected by a positive fly, and that the development of the trypanosome in the tse-tse fly is inhibited by imbibing drug -containing blood.
- ↑ * No enlargement of the lymphatic glands is said to occur in the victims of this infection.
- ↑ * Brumpt has recently observed development of T. cruzi in Cimex lectularius and C. boucti.
- ↑ Prof. Newstead has (1912) adopted a classification of species of glossina based on a study of the male genitalia, which in this genus are characteristic. If macerated in potash the hypopygium can be turned backwards so as to display various complicated structures, namely, the superior claspers, the editum, the inferior claspers, the harpes, the juxta or penis sheath, the median process, and the connecting membrane. All these vary in shape in different groups; the median process and counecting membrane are found only in some of them.
- ↑ * It is interesting to note in connection with this suggestion that trypanosomes of the mammalian type have been found by Dutton, Todd, and Toby in Clarias angolensis at Leopoldville, and by Montel in another air-breathing fish of undetermined species.