CHAPTER III

THE TRYPANOSOMIASES

DEFINITION AND SYNONYMS

=Definition.=—African trypanosomiasis is an important protozoal disease of Central and West Africa, due to a flagellate, _Trypanosoma gambiense_, and transmitted by a tsetse fly, _Glossina palpalis_. The trypanosome undergoes a developmental cycle in the fly which does not become infective until after about twenty days. The period of incubation is about two or three weeks, after which an irregular fever with approximately normal morning temperature and high evening rise appears, attended with a rapid pulse rate at all times. This is called the stage of trypanosome fever and may show trypanosomes in the peripheral blood. Later on the glands enlarge and gland juice shows trypanosomes. With the appearance of a fine tremor of the tongue, a state of apathy or lethargy, known as sleeping sickness, sets in, attended with trypanosomes in the cerebro-spinal fluid. Gradually increasing mental deterioration marks the almost invariable course to death. A more virulent type of trypanosomiasis is found in Rhodesia.

In Brazil there is a disease caused by a flagellate, _Schizotrypanum cruzi_, which resembles a trypanosome and is transmitted by a bug, _Lamus megistus_. The disease runs an acute course with a high fever and great mortality in infants showing chiefly manifestations of involvement of brain or thyroid gland. In adults it runs a chronic course showing neurological manifestations or signs of myxoedema or even of Addison’s disease.

=Synonyms.=—Sleeping sickness; Negro lethargy. French: Maladie du sommeil. German: Schlafkrankheit. For the Brazilian trypanosomiasis, Schizotrypanosomiasis; Chagas’ disease.

HISTORY AND GEOGRAPHICAL DISTRIBUTION

=History.=—In describing sleeping sickness, in 1803, Winterbottom brought out the importance of enlargements of the posterior cervical glands (Winterbottom’s sign).

In 1880 Evans had found a trypanosome in the blood of horses affected with surra and several years afterward Bruce discovered that nagana, a fatal disease of cattle, was due to a trypanosome, _T. brucei_. In 1890 Nepveu found a trypanosome in the blood of a man in Algeria but owing to vagueness of description the discovery did not attract attention.

[Illustration: FIG. 25.—Geographical distribution of African trypanosomiasis.]

In 1901, Forde found a parasite in the blood of a patient in the River Gambia Colony who had a fever and in 1902 Dutton recognized the parasite as a trypanosome and gave it the name _T. gambiense_. In 1902, Castellani, finding a trypanosome in the cerebro-spinal fluid of a patient with sleeping sickness, brought about the establishment of the connection between the trypanosome in the blood (trypanosome fever) and the trypanosome in the cerebro-spinal fluid (sleeping sickness). In 1903, Bruce and Nabarro reported that this disease was spread by a tsetse fly, _Glossina palpalis_.

In 1910 Stephens and Fantham brought forward the existence of a more virulent trypanosome, _T. rhodesiense_.

=Geographical Distribution.=—The disease exists on the West Coast of Africa, from Senegal to Mossamedes. It is also present in the Congo basin and particularly in Uganda. The more virulent form is found in Rhodesia.

ETIOLOGY AND EPIDEMIOLOGY

=Etiology.=—The African trypanosomiases follow infection with two species of trypanosomes; the more virulent type of the disease, occurring in South Central Africa, being due to _Trypanosoma rhodesiense_, transmitted by _Glossina morsitans_ and that of less severe type, but of more general distribution, being due to _T. gambiense_ and transmitted by _Glossina palpalis_. The very important _Trypanosoma brucei_, which is the devastating agent in the African horse, dog and cattle disease, nagana, is also transmitted by _Glossina morsitans_ and there exists the opinion that this trypanosome is identical with _T. rhodesiense_.

Macfie has reported a new trypanosome, _T. nigeriense_, from young persons in Nigeria. It is said to be less virulent than _T. gambiense_, and to be transmitted by _Glossina tachinoides_.

[Illustration: FIG. 26.—_Trypanosoma gambiense_ (slide presented by Professor F. G. Novy) (From Todd.)]

Bruce considers _T. nigeriense_ as being _T. gambiense_. Macfie noted many short stumpy forms in animals inoculated with _T. nigeriense_.

These trypanosomes are blood flagellates and are typical of the Binucleata in possessing two chromatin-staining areas, the larger and more centrally situated mass being the tropho or macronucleus and the smaller, but more deeply staining one, the kineto or micronucleus (Blepharoplast). Trypanosomes have a fusiform or fish-shaped body which stains blue. Near the less pointed, nonflagellated end, usually called the posterior end, is the deeply stained blepharoplast. Adjoining this is a vacuole and, taking origin from this part of the trypanosome, is the flagellum. This borders an undulating membrane attached to the body and then, carried along to the other extremity, projects free as a long, whip-like flagellum.

In fresh preparations the body of the trypanosome progresses in the direction of its flagellated end, although occasionally it will be observed to move in the opposite direction.

Some trypanosomes show granules at certain stages and it has been observed that the extrusion of these granules precedes disintegration of the trypanosome. It has been suggested that such granules might be infective, explaining the infectivity of blood from which trypanosomes were absent. In the separation of trypanosomes into groups and species Bruce relies upon morphology, action on animals, and manner of development in the tsetse fly. He does not consider serum diagnosis and cross inoculation methods as reliable for differentiation. The human trypanosomes are polymorphic.

_T. gambiense_ varies much in length and breadth. The normal type, as found in the blood, varies from 14 to 20 microns, while longer forms, 20 to 24 microns, are growth ones and, in the longest ones (23 to 33 microns), we have those preparing to divide longitudinally. The normal short forms are the ones from which the development takes place in the tsetse fly. In width these flagellates are from 1.5 to 2 microns. The blepharoplast is oval and the nucleus situated about the center.

[Illustration: FIG. 27.—_Glossina palpalis_ in natural resting position and with wings outstretched. (MacNeal after Doflein.)]

With _T. rhodesiense_ the nucleus is typically located almost adjacent to the blepharoplast. As a matter of fact it may require the passage of this trypanosome through rats to bring out these “posterior nuclear forms,” the nuclear location being at times almost entirely that of _T. gambiense_. In addition to the characteristic of nucleus being near the blepharoplast, this trypanosome is more virulent for laboratory animals than _T. gambiense_, agreeing in this respect with the more severe clinical course in man.

When the tsetse fly, _Glossina palpalis_, feeds on a man in whose peripheral circulation there are normal type trypanosomes we have an accumulation of such forms in the middle and posterior portions of the gut. From the eighth to the eighteenth day long, slender forms develop and pass forward into the proventriculus. None of the intestinal forms can cause infection when injected into animals. These proventricular types work their way into the salivary ducts and thence into the salivary glands, where further development takes place. Here we have shorter forms developing, which are similar in morphology to the normal blood type. It is at this stage that the fly becomes infective by the passing of these trypanosomes down the salivary ducts and through the channel in the hypopharynx to the subcutaneous tissues of the person bitten. High temperatures, 75 to 85°F., are favorable to development, while low temperatures, 60 to 70°F., are inimical to development, but do not kill the ingested trypanosomes. This explains the long period which at times elapses before a fly becomes infective. Under favorable conditions a fly becomes infective in twenty to thirty-four days and remains infective the rest of its life, up to 185 days. The infection is not transmitted to the pupa. This is an inoculative, cyclical or indirect type of infection. It is usually considered that a tsetse fly whose proboscis has just been contaminated with trypanosome blood is capable of transferring the infection for a few hours. This would be a mechanical or direct method of infection and such power for infection only lasts for a few hours.

There are other groups of trypanosomes, not important for man, in which the cyclical development does not include the salivary glands. In the _T. pecorum_ group of small monomorphic trypanosomes development takes place only in intestines and proboscis, while in the _T. vivax_ group this occurs in the proboscis alone.

[Illustration: FIG. 28.—_Glossina morsitans_ before and after feeding. Lateral view. (From Doflein after Austin.) MacNeal.]

When tsetse flies feed on animals infected with trypanosomes only from 2 to 6% become infective. Again, it has been shown that where the wild animals on which tsetse flies feed may show an infection of from 16 to 50% yet not more than 2 out of every 1000 tsetse flies, caught and tried out on susceptible animals, show themselves infective.

Both of the human trypanosomes of Africa have been cultured by using the N.N.N. medium in which rat’s blood was substituted for that of the rabbit. Human blood will also serve as a substitute. Growth however is not constant.

=Epidemiology.=—Practically the only method of transmission of the disease is by the bite of infected tsetse flies. The female gives birth to a single, yellowish brown, motile larva, which is almost as large as the mother and which, upon reaching the ground, bores its way into a coarse, sandy soil for a depth of about two inches and then becomes a pupa. The larval stage in the mother lasts about two weeks and the pupal stage about a month.

The tsetse fly is much like _Stomoxys_, but has a branching of the feathering of the arista, long palps, a bulb to the proboscis and a characteristic upbending of the fourth longitudinal vein to meet the mid-cross vein. The female deposits her larva near a shady place upon loose, dry, sandy soil. Moisture and sunlight are not favorable for pupal development, the sun being particularly injurious, so that pupae, buried only an inch deep and away from shade, are killed. This fact has been utilized in prophylaxis by cutting down the trees. The trouble is that the bush growth which soon follows is favorable as providing shade for the pupae.

Male and female flies bite and transmit the disease. They bite in the daytime, usually from 9 A.M., to 4 P.M., and will bite in the sunlight.

It has been stated that tsetse flies are attracted by persons wearing khaki clothing.

With a view to eradication of the disease certain areas have been depopulated, but upon examining the flies caught in the district a year or more later, infected flies have been obtained. This would indicate some other reservoir than man. It is now generally conceded that the trypanosome strain in the antelope is the same as _T. rhodesiense_, both being transmitted by _G. morsitans_.

Taute, however, believes them different as he not only injected blood containing such trypanosomes into himself, with negative result, but also allowed flies which had fed on antelopes, which were infective for laboratory animals, to feed on himself, likewise with negative result. It is a well-known fact that men in good condition are refractory to trypanosome infection so that this courageous experiment does not prove the antelope strain to be different from the human one.

One measure that has been proposed is to kill off the big game from a certain area with a view to depriving the flies of their main source of infection.

The probabilities of an animal reservoir for _T. gambiense_ however is not so well settled. Many think that we may have trypanosome carriers and that such persons in the enjoyment of health may act as reservoirs of the virus. Koch suggested that crocodiles were important factors in the life of the tsetse flies and recommended the destruction of the crocodile eggs.

Koch noted the infection of 15 women in a fly-free district and considered their infection as coming from sexual intercourse with their husbands, who had returned home from fly districts where they had contracted trypanosomiasis.

This same method of infection of prostitutes has quite recently been brought to notice by Bernard.

It will be remembered that dourine, a trypanosome disease of horses, caused by _T. equiperdum_, is transmitted by the sexual act.

All observations however indicate that the spread of the disease is almost exclusively through the medium of the tsetse fly. Professor Lanfranchini was infected in his laboratory by a strain which was supposed to be _Trypanosoma brucei_.

PATHOLOGY

The chief pathological findings are the enlargements of the lymphatic glands. The dura mater may be adherent in places and the pia mater may show areas of thickening. The cerebro-spinal fluid is increased in amount. The pathological process is a chronic polyadenitis which is followed by a chronic inflammation of lymphatics of brain and spinal cord.

We have a meningo-encephalitis in which the most characteristic feature microscopically is a widespread perivascular infiltration of small round cells surrounding the vessels of the pia-arachnoid of both brain and cord. The process is most marked about vessels of pons and medulla. The nerve cells are but little affected other than those of the bulbar nuclei.

[Illustration: FIG. 29.—Temperature chart of trypanosome fever.]

SYMPTOMATOLOGY

_The Period of Invasion._—After an incubation period which may be as short as ten or twelve days, following the bite of an infective tsetse fly, the trypanosomes may be found in the blood or in gland juice. One case has been reported where an official of the Belgian Congo showed trypanosomes less than four weeks after his arrival in the colony. His first symptoms were noted about ten days after his arrival.

In natives, trypanosomes may be present in the blood for long periods of time during which they may do heavy work; thus 7 of Koch’s 52 native porters showed trypanosomes. In Europeans however the course of the disease is rarely so insidious but rapidly enters upon the stage of trypanosome fever.

_The Stage of Trypanosome Fever._—Although fever may be absent in natives until the onset of the period of sleeping sickness, yet in Europeans there are usually noted febrile paroxysms, lasting for a few days, and followed, by afebrile periods varying from a few days to two or three weeks.

The temperature curve is of a markedly remittent type, approaching normal in the morning and going up to 103°F. or higher in the evening—a wide daily range. Very characteristic is a low-tension rapid pulse which often is as rapid when the temperature approximates the normal as when it is higher. Early in the disease there are evidences of involvement of the nervous system, as shown by headache insomnia, difficulty of concentration for mental work and cardiac instability.

[Illustration: FIG. 30.—Rash of human trypanosomiasis. (Photo: R. McKay.) By permission from Manson’s Tropical Diseases.]

_Winterbottom Sign._—Very important are the glandular enlargements,

## particularly of the glands of the posterior cervical triangle

(Winterbottom’s sign), which upon puncture may show trypanosomes when the blood examination fails to reveal them. The glands are discrete, soft, usually painless and may show but very slight enlargement. Oedematous swellings, especially about the eyes or joints or in localized areas upon the trunk, may be rather prominent in some cases. In Europeans pinkish erythematous rings appearing early in the infection may make one think of syphilis. These erythematous patches are not visible on the skin of natives. A dryness of the skin is rather constant and, especially in natives, papules which itch greatly may be present. Rarely such manifestations as orchitis or choroiditis may be observed.

[Illustration: FIG. 31.—Swelling of the glands of the posterior cervical triangle—Winterbottom’s sign. (Ruge and zur Verth after Koch.)]

_Kérandel Sign._—Recently great prominence has been given to a deep hyperaesthesia, which shows itself as a lively pain, often retarded, after some slight blow upon a bony projection of the body. Kérandel, who suffered from trypanosomiasis, noted that the fear of striking against objects became with him an absolute obsession. It is called the Kérandel sign. It is during this first stage, when the trypanosomes are to be found only in the blood or gland juice that the disease would appear to be curable. Upon the appearance of the trypanosomes in the cerebro-spinal fluid (second stage) we have practically a hopeless prognosis.

There may be a latent period of several months in which health seems normal, to be followed by the sleeping-sickness stage. It has also been noted that untreated cases, as well as those receiving more or less treatment, may remain in good health for periods up to several years. There is therefore reason to believe that certain cases may not enter upon the sleeping sickness stage.

[Illustration: FIG. 32.—Cases of trypanosomiasis showing the edema especially about eyes. (Ruge and zur Verth after Koch.)]

_The Stage of Sleeping Sickness._—In this stage the mentality becomes more weakened. The native from being happy and willing to work becomes morose and apathetic. This change of disposition is frequently the first thing to be noted in a patient by his family. There is a tendency to gaze into the distance. The speech is rather low and tremulous like that of a tired, sleepy child. The tongue especially shows a decided tremor which may also be present in the lips and hands.

The gait is one of weakness and apathy—a shuffling gait. The reflexes may be exaggerated. Romberg’s sign may be present but the Argyll-Robertson pupil has not been noted. There may be an alternation of periods of crying and laughing which with the occasional exhibition of intention tremor and rarely nystagmus may make one think of multiple sclerosis. The patient tends to sleep even when lying in a bright sunlight. Again he may go to sleep with a morsel of food in his mouth. Notwithstanding the apparent stupid state of the patient, he will, when aroused, answer fairly intelligently but with apathy and retardation. The hebephrenic and catatonic manifestations of dementia praecox may be exhibited in some cases.

Finally the patient becomes weaker and more emaciated. The pulse becomes rapid and feeble, the blood pressure being extremely low. The mouth becomes dry, the teeth covered with sordes and bed sores develop. There may be convulsions. The coma and general weakness become more marked and the patient dies. Frequently terminal pneumonias or dysenteries bring about the end.

The sleeping sickness stage rarely lasts longer than a year and even with treatment not more than two years.

The Symptoms in Detail

_The Nervous System._—Headache and lack of mental concentration may be early features of the disease. Deep hyperaesthesia, or Kérandel’s sign, often present. Patients tend to be morose and apathetic. Tremor of tongue and lips are rather constant signs about the commencement of the stage of sleeping sickness. Early insomnia gives way to the drowsiness that characterizes the second stage. There is very little disturbance of sensory or motor functions until near the end. Epileptiform convulsions may be late manifestations. Coma deepens as the end approaches.

_The Temperature Curve._—The febrile paroxysms, which may not be present in natives until the sleeping-sickness stage, show great irregularity of course and a marked remission in the morning. The fever may be absent for several weeks to return later. Trypanosomes are more apt to be present in the peripheral circulation during the fever than when the temperature is normal.

_The Circulatory System._—The pulse tends to run from 90 to 120 beats per minute and is fast even without fever. The tension is low and the systolic pressure tends to be extremely low during the later stages of the disease.

_The Lymphatic System._—Most important in diagnosis is the enlargement of the lymphatic glands, especially those of the posterior cervical triangle (Winterbottom’s sign). Other enlarged glands may be the supraclavicular, epitrochlear and axillary glands. The inguinal glands suffer enlargements so frequently as the results of wounds and infections of the foot that their enlargement is of less diagnostic value. The natives of certain parts of Africa not only attach great diagnostic importance to gland enlargement but they imagine they cure the disease by removing the glands with various primitive cutting tools. The glands are not painful, do not become matted together and rarely suppurate. Our best means of diagnosing trypanosomiasis is by withdrawing gland juice with a syringe and examining the smears.

_The Skin._—Erythematous areas may be present in Europeans. Localized oedemas are rather marked features. The skin may be very dry and itch markedly.

_Other Manifestations._—The spleen may be enlarged, the respirations may be more rapid than normal and the blood show a secondary anaemia. In a blood examination the large mononuclears show an increase with a normal white count.

The eye may show keratitis or irido-cyclitis in trypanosomiasis.

Trypanosomiasis seems to favor abortion and still-births, in this respect resembling syphilis.

DIAGNOSIS

In making a survey of a native population Schwetz considers gland palpation as almost as reliable as gland puncture and of course more expeditious. The typical gland should be large and soft or elastic although he admits trypanosomes may be found in small hard glands.

When the glandular enlargement is distinct, with the erythema and headache, there is much that suggests syphilis. Another point of confusion is that positive Wassermann tests are often obtained in sleeping sickness.

The increase in large mononuclears goes with malaria, kala-azar and syphilis as well as with trypanosomiasis so that such findings are of little assistance in differential diagnosis.

An early history of attacks of fever, with marked fluctuation of temperature, associated with rapid pulse, even with the apyrexial morning fall, is suggestive. Then with the glandular enlargements we think immediately of laboratory examinations. As with pellagra the history is very important in the diagnosis of trypanosomiasis.

_For the laboratory diagnosis_ we may use peripheral blood with some thick film method. The examination of preparations from the peripheral blood is usually very discouraging. Very much better results (in fact some prefer this method to any other) can be obtained by taking 10 to 20 cc. of blood in about 25 cc. of citrated salt solution, centrifuging 2 or 3 times and examining the sediment of the third centrifugalization. Dutton and Todd prefer to centrifuge citrated blood and to collect the leucocyte layer for examination as is done in opsonic work.

_Gland Puncture._—The English workers usually prefer the gland puncture method, using a sterile but dry hypodermic needle. Water in the needle distorts both leishman bodies and trypanosomes.

In the sleeping-sickness stage trypanosomes can almost constantly be found in the cerebro-spinal fluid.

In a diagnostic study of 336 cases Broden obtained 87% of positives from gland puncture, 80% from centrifugalizing the supernatant fluid left from the second centrifugalization of the blood and 4.5% from spinal fluid examinations.

Some prefer to inoculate susceptible animals, particularly the guinea pig or monkey, with blood or gland juice from the suspected case. A very satisfactory material is an emulsion from an excised gland which may be inoculated intraperitoneally into white rats. The further course, after animal inoculation, is the examination of the blood of these animals for trypanosomes. Usually at the time the guinea pigs die we find numerous trypanosomes.

Other tests are: (1) Trypanolysis, when unheated suspected serum and trypanosomes are incubated together for one hour. Normal serum may occasionally cause disintegration and treated cases give it in only about 45% of cases. Unfavorable untreated cases give it in about 80% of cases.

(2) The so-called auto-agglutination test is not of much value. In this the red cells of the blood of a trypanosomiasis case come together in clumps when one makes a wet preparation. It is not a rouleaux formation. (3) The attachment test is made by making a mixture of inactivated serum, leucocytes and trypanosomes and allowing them to be in contact for 20 minutes. A positive test shows attachment of the trypanosomes to the leucocytes.

PROGNOSIS

If the patient cannot be removed from the infected district or cannot receive the atoxyl or atoxyl-tartar-emetic treatment the prognosis is almost surely that of a prolonged but fatal end.

There is very little hope of cure if the disease has gone on to the sleeping-sickness stage.

PROPHYLAXIS AND TREATMENT

=Prophylaxis.=—The question of depopulation of districts and destruction of the big game therein, when the area is infected with _Glossina palpalis_, has been fully considered under epidemiology.

Isolation, in the fly-free districts, of infected natives has not proven a very practical measure but that of rendering their peripheral blood free of trypanosomes by atoxyl injections would seem more desirable. In this we aim to cure the patient as well as render him safe to others.

The most practical measure is that employed in Uganda of clearing the plant and tree growth for at least fifteen feet from the streams of water, it having been noted that the tsetse flies confine themselves to a narrow strip not more than fifteen feet from the water’s edge. The tsetse fly requires considerable moisture for its existence.

The catching of flies in traps or with a sticky lime does not offer much encouragement.

As regards personal prophylaxis, white clothes are to be worn as the tsetse fly, along with mosquitoes, prefers dark-colored garments. The legs should be protected by leggings and possibly one could consider the wearing of gloves or veils. As a matter of fact, however, the heat of the tropics precludes these latter measures. As the fly only bites in the daytime one should choose the night for going about, if practicable.

=Treatment.=—The general opinion is that trypanosomiasis is only curable at a time prior to the appearance of trypanosomes in the cerebro-spinal fluid. Consequently, the stage of sleeping sickness offers little chance of cure by treatment.

Such cases have been treated with injections of 10 cc. of 1 to 1000 solution of neosalvarsan into the spinal canal, after withdrawing about 15 cc. of spinal fluid, but without appreciable curative effect. On the assumption that trypanosomes invading the central nervous system are protected from drug action, Marshall proposed the injection of salvarsanized serum intrathecally. Three hours after the administration of 0.6 gm. of salvarsan enough blood is withdrawn from a vein to give about 20 cc. of serum. Following the withdrawal of a slightly greater amount of cerebro-spinal fluid from 5 to 20 cc. of the serum is injected in its place. Yorke in a critical article on the claims for this treatment is of the opinion that there is no satisfactory evidence that such a method sterilizes the infected cerebro-spinal fluid. He cites cases where the trypanosomes disappeared from the spinal fluid after ordinary treatment and where cases lived for extended periods after trypanosomes were found in their spinal fluid. Corbus and associates have described a new method of obtaining a high medicinal content in the cerebro-spinal fluids. Their work was done with neo-arsphenamine, but there seems to be no reason why other drugs may not be similarly administered.

The basis of the method is the observation that hypertonic salt solution, injected intravenously, will dehydrate the central nervous system, and that restoration of fluid begins at about the sixth hour. If a drug is injected into the circulation just at the time when the restorative formation of spinal fluid is taking place, it appears that a large quantity is carried into the subarachnoid spaces with the fluid, as on a flood tide.

Method:

1. 8 A.M. Patient is put to bed.

2. 10 A.M. Intravenous injection of 100 cc. of 15% saline, warmed and administered slowly by gravity. The symptoms produced by this injection are mild and transitory.

3. No food is permitted at midday.

4. 4 P.M. Neo-arsphenamine is injected with the usual technic.

5. 8 P.M. Light nourishment is allowed. Patient is kept under observation, preferably in bed, for the ensuing thirty-six hours.

_Atoxyl._—The first drug to offer hope of cure was sodium arsanilate, atoxyl, which contains about 26% of As. This is best given in doses of about 0.5 gram (7½ gr.) in about 15 cc. of sterile distilled water intramuscularly. Several cases of optic neuritis were reported but the drug is still a standard treatment. We give the atoxyl at intervals of five days, Manson gives 3 grains every third day.

Probably the best treatment is one in which three doses of atoxyl are followed by from 10 to 15 daily or every other day injections of 0.1 gram (1½ gr.) of tartar emetic. The course is repeated after an interval of three weeks. It is advisable to give a hypodermic of caffein a few minutes before the tartar emetic to lessen depression. Kérandel received the atoxyl-tartar-emetic double treatment and ascribed his cure to the tartar emetic. Tartar emetic is also given intravenously, 0.1 gram in 150 cc. water.

Intravenous injection of arsenophenylglycin, in doses of about 1.0 gram. (15 gr.) intravenously has been highly recommended. Recent reports from German East Africa state that of 35 treated with this drug six died of the effects of the drug. Salvarsan and neosalvarsan have been used but apparently without particular success.

A combination of treatments in which salvarsan, sodium salicylate and ethyl-hydrocuprein (a quinine derivative) have been used has been favorably reported by Morganroth where the action of a single drug was of little value.

Very remarkable claims in experimental animals have been made for “trixidin,” a preparation of antimony trioxide which is given intramuscularly. Even inunctions with this preparation have been quite successful in curing infected mice. In larger animals abscess formation is an objection.

Daniels has reported good results from the injection of oxide of antimony. The preparation used is Martindale’s injectio antimonii oxidi given subcutaneously in 30 minim doses (1/20 grain of the oxide). Masters gives this preparation intramuscularly and notes its greater efficiency than any other drug or combination of drugs. He gives 3/100 grain every other day until 40/100 grain has been given. If trypanosomes continue present he gives a .77 gram dose of soamin. Soamin is a drug similar to atoxyl but said to be less toxic.

In the treatment of 18 cases of _T. rhodesiense_ infections Newham notes that tartar emetic alone was as effective as the combined treatment with atoxyl. He gave the tartar emetic injections twice weekly intravenously commencing with 1 grain and going up to 3 grains. An organic antimony preparation, “Stibenyl,” has been recommended. See kala-azar.

Very favorable reports have been made from the use of galyl and ludyl, arsenical compounds.

A drug which is reported to have exceptional trypanocidal effect on animals infected with both human trypanosomes is “Bayer 205.” Dogs infected with the dourine parasite and showing oedema and eye symptoms have been cured by the injection of the drug intravenously. A dose of 0.5 mg. causes disappearance of parasites in mice. It is stated that the drug produces a protection against reinfection which lasts for months.

BRAZILIAN TRYPANOSOMIASIS

=General Considerations.=—In 1909, Chagas reported the finding of a flagellate in the intestines of _Conorhinus megistus_ or, more properly, _Lamus megistus_. He was also able to transmit the flagellate to laboratory animals and could culture it on blood agar.

[Illustration: FIG. 33.—_Schizotrypanum cruzi_ in blood of child with acute type of Brazilian trypanosomiasis. (MacNeal from Doflein after Chagas.)]

In investigating the matter of the importance of this flagellate, _Schizotrypanum cruzi_, in Minas Geraes, Brazil, where the above-named bug was present in great numbers in the cracks of the houses of the poor he associated this flagellate infection, which he at first considered trypanosomal, with a disease of the children of that section.

The bug is a vicious feeder and, from its biting chiefly about the face, has been called barbeiro or barber by the natives. Both the male and female of _Lamus_ bite and can transmit the disease and although the parasite is not transmitted hereditarily the nymph is capable of sucking blood and becoming infected.

[Illustration: FIG. 34.—_Conorhinus megistus_, the insect carrier of _Schizotrypanum cruzi_. (From Doflein after Chagas.)]

It requires several months for the insect to go through the egg, larval and pupal stage to maturity. Some consider this bug to belong to the genus _Triatoma_. The insects may live for more than a year and tend to remain in the same house where they may have become infected but leave such house if it be abandoned by man. Brumpt thinks that the bedbug may also transmit the disease. A large proportion of armadillos in the endemic areas are infected with _S. cruzi_ but do not seem to be affected thereby. It has been suggested that this animal may be a reservoir of virus.

[Illustration: FIG. 35.—_Schizotrypanum cruzi_ developing in the tissues of the guinea pig. 1. Cross-section of a striated muscle fibre containing _Schizotrypanum cruzi_: Note dividing forms. 2. Section of brain showing a _Schizotrypanum_ cyst within a neuroglia cell, containing chiefly flagellated forms. 3. Section through the supra-renal capsule, fascicular zone. 4. Section of brain showing a neuroglia cell filled with round forms of _Schizotrypanum_. (From Low, in Sleeping Sickness Bulletin, after Vianna.)]

_S. cruzi_ is found in the blood of children during the acute febrile stage but at other times in children, and as a rule in adults, it is rarely present in the peripheral blood. The early blood forms are narrow and very motile. They increase in size and slacken in motility when they become about 20 microns long. _S. cruzi_ is characterized by a very large blepharoplast. Dividing forms are never seen in the blood. The common site of multiplication is in the cells of the voluntary muscles and heart and also in the cells of the central nervous system, adrenals, and bone marrow. In these tissues the flagellate takes on a rounded form and undergoes binary division. Continued division converts the infected cell into a cyst. It is this process going on in various important structures that accounts for the extreme variation in symptomatology and pathology.

Chagas thinks that the gametes for the cycle in _Lamus_ arise from parasites developing in the lungs of the vertebrate host. Flagellated parasites enter the lungs, lose the flagellum and become oval in shape, later on dividing into 8 parts. These assume an elongated form and enter the red cells of the host. Against this is the statement of various observers that the flagellates are only to be found free in the plasma, never within red cells. The forms taken up by _Lamus_ multiply in the intestine and then pass to the salivary glands after about 8 days. The bug is then infectious when it bites. Brumpt notes that infection may occur from inoculation of the faeces passed by the bug, especially through the conjunctiva.

=Symptomatology.= _Acute types._—This form of the disease usually occurs in children under one year of age. The period of incubation is about ten days. It is attended by a high continued fever which may show a slight morning drop. There is marked puffiness of the face and enlargement of the thyroid. The lymphatic glands and spleen are also enlarged. The case may give the picture of a meningitis in which form the disease is exceedingly fatal. During the febrile period parasites are to be found in the blood but in the afebrile intervals which alternate with the febrile ones parasites are not present.

_Chronic Types._—The type of the disease as seen in adults is mainly chronic. They often show enlargement of the thyroid and manifestations of myxoedema. The lymphatic glands are enlarged. Where the adrenal is attacked we have the syndrome of Addison’s disease.

In the cardiac types there are present various forms of cardiac irregularities.

In the cerebral types various neurological manifestations may be noted.

An irregular fever may accompany the signs of involvement of the various important organs.

The disease is attended by a marked anaemia.

=Diagnosis.=—In the laboratory diagnosis of those cases not showing the flagellates in the blood the usual method is to inoculate a guinea pig with the blood and in about two weeks _S. cruzi_ may be found in the blood of the animal. The parasites may not appear, however, in the blood, when one should resort to culturing the guinea pig’s blood or more surely examine sections of muscle of the animal for the forms in the muscle cells undergoing binary division.

Brumpt has recently advocated the xenodiagnostic method. Thus, in a number of guinea pigs infected with _S. cruzi_, parasites could not be found, but by having third stage larvae of _Conorhinus_ feed on these animals the parasites developed in the bugs. He regards the alimentary tract of these bugs as a most favorable culture medium.

=Prophylaxis and Treatment.=—Other than destroying the bugs by sulphur fumigation or whitewashing there is little to note. The bugs show a liking for leather articles, as old harness.

The same plan of treatment as for African trypanosomiasis may be tried but such treatment is not effective with infected animals.

In the myxoedema types thyroid extract is indicated.

NOTE: Escomel has reported the finding of a trypanosome 20 to 40 microns by 3 to 4 microns which had a flagellum as long as the body and with a very small but distinct blepharoplast (unlike _S. cruzi_) in the blood of a native of Peru. The patient at the time of the blood examination was afebrile and showed a generalized firm oedema. There was noted anaemia, prostration and somnolence. This may be a new species.

TRYPANOSOMIASES OF ANIMALS

=Trypanosoma brucei.=—This trypanosome causes a surely fatal disease in horses and one from which few cattle recover. It is called “nagana” or the fly disease, from being transmitted by the tsetse fly, _Glossina morsitans_. All animals except man and possibly the goat seem susceptible. The disease is characterized by fever, oedematous areas about neck, abdomen and extremities, progressive anaemia and emaciation. It is an important disease of domesticated animals of many parts of Africa.

=Trypanosoma evansi.=—This is the cause of a very fatal disease of horses in India and the Orient and known as “surra.” It also affects camels and even cattle. It is thought to be transmitted by biting flies (_Stomoxys_). The symptoms are fever, emaciation, oedematous areas and great muscular weakness.

=Trypanosoma equinum.=—This trypanosome causes a fatal disease in horses in South America. There is paralysis of the hind quarters of the horse which gives the disease the name “mal de caderas.”

=Trypanosoma equiperdum.=—This trypanosome causes a disease of horses in many parts of the world. It is known as “dourine” and is transmitted by coitus. The genital organs show marked oedema which is followed by anaemia and paralysis.

=Trypanosoma dimorphon.=—This trypanosome causes a disease of horses in Gambia. It is also found in horses and cattle in other parts of Africa. The parasite shows marked variation in morphology.

=Trypanosoma lewisi.=—Rats in many parts of the world show this infection which is rarely fatal to them. It is transmitted by the rat flea by a process of regurgitation. It can also be transmitted by the rat louse.

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