African Trypanosomiasis

AFRICAN SLEEPING SICKNESS, lethargus, morbus dormitivus, trypanosomiasis, trypanosis, hydropsia narcotica (Lat.), afrikanische Schlafkrankheit (Ger.), maladie du sommeil, trypanosomiase humaine (Fr.), sleeping sickness (Eng.), a chronic disease prevalent in tropical Africa caused by parasites of the genus Trypanosoma, characterized by irregular fever, enlargement of lymph glands, a rash, and progressive central nervous system disorders, usually leading to death with symptoms of drowsiness and general cachexia.—History. Sleeping sickness has existed in tropical Africa since ancient times in small endemic foci, but the lack of communication routes and constant hostility between small tribes limited its spread. With the invasion of Arabs from the East and especially with the appearance of white conquerors, the construction of roads, increased movement, and the introduction of steam navigation, sleeping sickness gained the opportunity to spread across vast regions. The slave trade led to the appearance of imported cases far beyond Africa. From the end of the 19th century, imperialist powers seeking to expand their possessions and consolidate their power in tropical Africa began to acutely feel the danger posed to them by this terrible disease, which devastated entire native villages and spared not even white colonizers. The large number of victims claimed by sleeping sickness in Portuguese possessions, particularly in Angola, prompted the Portuguese government in the 1890s to equip a special expedition that laid the foundation for the scientific study of sleeping sickness. The rapid spread of sleeping sickness in Uganda and other British colonies served as the impetus for a series of investigations that led to the discovery of the pathogen at the very beginning of the present century. The major scientists of Germany (R. Koch), France, Belgium, and a number of other countries soon joined the competition to study sleeping sickness. Sleeping sickness and the fight against it remain to this day a matter of special concern for colonial countries and attract the attention of major scientists worldwide.—Etiology. The pathogen of sleeping sickness, the blood parasite Trypanosoma gambiense Dutton, 1902 (synonyms: Trypanosoma castellanii Kruse, 1903, Trypanosoma hominis Manson, 1903), was first detected in the blood of a patient in Gambia in 1901 (Forde). In 1902, Dutton found it in another patient and defined it, giving it its modern name. In the same year, Castellani found a trypanosome in the cerebrospinal fluid and blood of a sleeping sickness patient in Uganda, which he named Trypanosoma ugandense (1903). Subsequently, it was established that both trypanosomes are identical and that the disease known as sleeping sickness is the late stage of trypanosomiasis. Trypanosoma gambiense in the blood of patients and laboratory animals appears as: 1) long, narrow forms with a flagellum significantly exceeding the body length, reaching 30 and 40 μ in length; and 2) broader and shorter forms with a flagellum not extending beyond the anterior end of the body. Both extreme forms are connected by a series of intermediate forms. Robertson believes that the narrow, long forms produce short forms upon division, which then grow into long ones. The nucleus occupies a central position, and the blepharoplast is situated at some distance from the posterior end. Volutin granules are frequently found in varying amounts in the cytoplasm. Trypanosoma gambiense is easily inoculated into monkeys, except baboons, and from them into laboratory animals: rats, mice, rabbits, guinea pigs; it is also inoculable into dogs, goats, sheep, horses, and cattle. In Northern Rhodesia and southern regions of East Africa, a distinct variety of the sleeping sickness pathogen is found—Trypanosoma rhodesiense Stephens et Fantham, 1010. In human blood, it is indistinguishable from Trypanosoma gambiense, but upon subculturing into laboratory animals, it demonstrates certain variations in the position of the nucleus, which in a certain percentage of trypanosomes (5–6%) is displaced toward the posterior part of the body, where it lies adjacent to or behind the blepharoplast. Diseases caused by Trypanosoma rhodesiense are characterized by a more acute course and respond less well to drug treatment. On NNN agar and Ponselle's medium, it is possible to maintain Trypanosoma gambiense and rhodesiense for several weeks, but the forms surviving and partially multiplying in these cultures prove to be avirulent.—Geographic distribution. Sleeping sickness is endemic only to tropical Africa; cases outside Africa are imported. Its area of distribution encompasses the coast of the Gulf of Guinea from approximately 15° N latitude to 15° S latitude and some islands of this gulf. Inland, its area of distribution is somewhat narrower (from 10° N to 10° S). In the north, it reaches Senegal and the upper reaches of the Nile; in the south, Northern Rhodesia; in the east, Lakes Victoria and Tanganyika. The World War and its aftermath (military operations, redistribution of colonies and associated population movements, disorganization of medical services, etc.) resulted in a significant increase in the spread of sleeping sickness and the expansion of its borders to the north and east. In French possessions, the infection rate in a number of villages reaches 50–60%; there are areas where up to 97% of the population is infected. Jamot discovered a 100% infection rate among the population of one village. Since 1923, the population of the Djem tribe has dropped from 2,229 to 609 due to sleeping sickness. In Senegambia, Angola, and the Congo, entire villages are dying out from sleeping sickness, and several islands on Lake Victoria-Nyanza have been completely depopulated. The population of one region in Uganda decreased in a short time from 300,000 to 100,000.—Epidemiology. In its distribution, sleeping sickness primarily follows the banks of major rivers and lakes. Its area of distribution coincides with the range of blood-sucking flies of the genus Glossina, mainly the species Glossina palpalis (tsetse fly), as well as Glossina morsitans and Glossina swynnertoni. The role of tsetse flies in the spread of sleeping sickness was suggested by several authors, but it was only in 1909 that Kleine proved it experimentally. Glossina palpalis inhabits shady shores near water, from which it rarely strays more than 100 m. Glossina morsitans is significantly less dependent on water and can spread the disease in villages far from water bodies. Trypanosomes entering the fly's stomach with a patient's blood undergo a long developmental cycle. The forms developing in the stomach during the first 10–15 days are non-infective. Subsequently, the trypanosomes pass from the fly's midgut into the foregut and salivary glands, where so-called metacyclic trypanosomes develop, which resemble the forms found in human blood and are infective to humans. The fly becomes infective approximately three weeks after feeding on infective blood and appears to remain infective for the rest of its life. Transmission by the tsetse fly is the primary route of spread for sleeping sickness; sexual transmission is recognized only as an exception. Several authors have suggested that livestock and wild animals (antelopes) serve as reservoirs for the sleeping sickness virus. However, epidemiological data indicate that the infection spreads from person to person. All ages, both sexes, and all human races are susceptible to Trypanosoma gambiense. Sleeping sickness predominantly affects those population groups whose work and living conditions expose them more to tsetse fly bites. Fishermen, water carriers, rubber gatherers, and boatmen who spend a significant portion of their time near water are affected first and foremost. In tribes where women perform field work along riverbanks and lakeshores, women fall ill more frequently than men. Some data support a relative immunity among residents of areas long affected by sleeping sickness.—Pathological Anatomy. Sleeping sickness is characterized by inflammatory hyperplasia of the lymph nodes (especially occipital, submandibular, and mesenteric), spleen, and to some extent the liver. In later stages, diffuse leptomeningitis, meningoencephalitis, and meningomyelitis are noted, with heavy round-cell infiltration, particularly of the vascular walls and perivascular spaces. Trypanosomes are also found outside the bloodstream—in the cerebrospinal fluid, intercellular spaces of the brain's gray matter, spleen, and heart.—Clinical Picture. The incubation period lasts 2–3 weeks. During the first months, clinical manifestations may be very mild, permitting a prolonged latent phase. This evidently explains the data in older literature regarding an incubation period lasting several years. In the first stage of the disease, an irregular fever of a mostly remittent character is observed, along with enlargement of the lymph nodes, particularly the occipital ones, and a rash consisting of small papules, roseolas, or more rarely a miliary eruption. The febrile period may drag on for weeks and months without giving the impression of a severe illness.

In the second stage, a number of phenomena from the nervous system develop in the patient—marked nervousness, headaches, dizziness, fibrillary muscle twitching, transient paralyses, and speech disorders appear, and patients become sluggish and apathetic. With the onset of the stage of African trypanosomiasis proper, the intellect weakens significantly, the face assumes a motionless expression, patients fall into a state of stupor, and extreme drowsiness develops; left to themselves, patients easily fall asleep, often with a piece of food in their mouth. Simultaneously, severe physical exhaustion, muscle atrophy, and sphincter paralyses develop (see the separate plate to the article Schistosomiasis, Figure 4). Patients die in a state of cachexia, often as a result of a secondary infection (pneumonia, dysentery). The course of the disease is subject to fluctuations. Remissions of varying duration also occur. Diagnosis is made primarily on the basis of detecting the pathogen. In human blood, Trypanosoma gambiense is rarely found in large numbers. Their number is subject to significant fluctuations. It is easier to detect them in the punctate of enlarged lymph glands, mainly the occipital ones. Sometimes, to detect the parasites, inoculations of blood into animals, such as monkeys, are resorted to. In a later stage, trypanosomes are sought in the centrifugate of the cerebrospinal fluid. Pathological examination of the latter allows one to judge the degree of damage to the central nervous system. A certain aid in diagnosis can be the so-called formol reaction of the serum (Napier's aldehyde test, see Leishmaniases), which, however, is also positive in kala-azar and other chronic diseases, as well as the adhesion reaction (Rickenberg phenomenon), which consists in the fact that when the serum of a trypanosomiasis patient is mixed with the blood of an experimental animal containing trypanosomes, the parasites become coated with blood platelets; the Rickenberg phenomenon, however, is not obtained with all strains or in all known patients, and sometimes turns out to be positive with sera from patients with other diseases. In the initial stage of the disease, a differential diagnosis must be made with malaria and relapsing fever. However, one should not forget the possibility of a mixed infection. In later stages, conditions partially resembling kala-azar, pellagra, neurosyphilis and progressive paralysis, leprosy, and beriberi may arise. In the latter disease, unlike African trypanosomiasis, there are lesions of the peripheral nerves, whereas the symptoms observed in trypanosomiasis are caused by damage to the central nervous system.—The prognosis, even in forms that appear mild, is always poor without treatment. However, there are data indicating that in certain localities the natives tolerate the infection relatively easily and can act as parasite carriers. Treatment. Cure of African trypanosomiasis is by no means achieved in all cases. It is easier to achieve good results if treatment is initiated in the initial stage of the disease. Treatment should begin with the removal of hookworms and schistosomes, which are widely prevalent in tropical Africa and whose presence in the organism may cause its increased sensitivity to specific antitrypanosomal agents. Primary among the preparations used for the treatment of African trypanosomiasis is Germanin = Moranyl = Bayer 205 = Fourneau 309, a synthetic preparation that is a sulfonic acid of a very complex aromatic urea derivative. Germanin is used in a 10% solution intravenously or intramuscularly in an amount of 1.0–2.0. This dose is repeated the next day or every other day, then a third time, totaling up to 5.0 per course. After several weeks or months, the course is repeated. As a side effect, albuminuria may occur, usually with a favorable course. Among organic arsenic derivatives, the best result is given by tryparsamide, the sodium salt of N-phenylglycinamide-p-arsonic acid. Tryparsamide is used intramuscularly in a solution no stronger than 20% and intravenously in a solution no stronger than 40% in an amount of 1–3 g per week, for 6 to 8 weeks in a row. Tryparsamide can cause damage to the optic nerve, and in late stages of the disease, a Herxheimer reaction. Tryparsamide crosses the blood-brain barrier and gives good results even after trypanosomes have penetrated the central nervous system. The best results are given by combined treatment with Germanin and tryparsamide. Antimony preparations are also used as a supplement to Germanin. Tartar emetic is used in a 1% solution intravenously in an amount of 6–10 cm³—12 infusions over 3 weeks; such courses are repeated several times with 7–15-day intervals. Stibenyl is also used at 0.05–0.1 intramuscularly or intravenously—the dose is gradually increased to 0.4, and stibosan at 0.2–0.3 intravenously in a 1–5% solution.—Prevention of African trypanosomiasis consists in detecting patients and systematically treating them, restricting movement from infected areas, and controlling the vector (trapping, destroying brushwood in the coastal zone, biological methods). Personal prevention boils down to clothing that protects against fly bites and screening living quarters and latrines. The systematic application of these measures has made it possible to significantly reduce morbidity in a number of sites.

Sh. Moshkovsky.