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Human African trypanosomiasis: presence of antibodies to galactocerebrosides.

Improvements were made in the immunodetection of anti-galactocerebroside (anti-GalC) antibody in sera of patients with human African trypanosomiasis by thin-layer chromatography, enzyme-linked immunosorbent assay, and immunoadsorption. Rabbit anti-GalC antibodies were used to standardize these techniques and demonstrate their specificity. Anti-GalC antibodies were found in the sera of 42.8% of 63 patients with human African trypanosomiasis. Thirty-four control subjects living in the same endemic area were also tested. Anti-GalC levels were higher in human African trypanosomiasis patients with neurologic disturbances compared with patients without such disturbances. These antibodies were distributed mainly between the IgG and IgM classes, but 28% of the patients with human African trypanosomiasis had increased IgA levels without anti-GalC antibody activity.

Agglutination Tests↗

[Trypanosomiasis and trypanocidal treatments in Ndama calves in a glossina infected area (the ranch of Madina-Diassa in Mali)].

This work aims at contributing to the knowledge of trypanosomiasis epidemiology in calves of trypanotolerant breeds and at defining an appropriate treatment to improve the survival of such calves in a tsetse infested area. The first study was a parasitological survey of 100 calves from the day of birth to the age of one year. According to the results of this survey, the period from birth to three months is a "critical" moment in the life of the calves, due to a high infection rate and mortality related to trypanosomiasis. The purpose of the second study was to investigate the possible interference of early trypanocidal treatments with the further expression of trypanotolerance. For this purpose three groups of over one-year old animals were established. The groups had different trypanosomiasis history due to the different treatments they had undergone during their first year of life. All the animals had been exposed to trypanosomiasis without treatment and followed up parasitologically and clinically during the second year. The results showed no interference of early trypanocidal treatments (including preventive ones) with the expression of resistance in potentially trypanotolerant animals.

Animals↗

African trypanosomiasis and S. intercalatum infection in Equatorial Guinea: comparative epidemiology and feasibility of integrated control.

The integration of schistosomiasis control with the activities of different endemic disease control or health programmes has been endorsed by a WHO Expert Committee on the Control of Schistosomiasis (WHO 1985). Endemic countries face increasing economic and manpower constraints which limit the coverage and effectiveness of control activities. Integration would be expected to optimize available resources for control. The feasibility of integration can be assessed by a comparative evaluation of: the epidemiology and distribution of the health problems; the techniques and methodology of control; and the requirements for maintenance and their relative health importance. This report presents a preliminary assessment of trypanosomiasis and schistosomiasis in Equatorial Guinea. The background and implementation of the operational national trypanosomiasis control programme are summarized. Population-based epidemiological investigations undertaken by the staff of the trypanosomiasis control programme are reported from a rural village and an urban suburb of Bata, Equatorial Guinea. The distribution and morbidity of S. intercalatum are compared, the public health importance of S. intercalatum is reviewed and the feasibility of integration of control of trypanosomiasis and schistosomiasis are assessed.

Adolescent↗

A field comparison of seven diagnostic techniques for human trypanosomiasis in the Luangwa Valley, Zambia.

One serological and six parasitological techniques for diagnosing human trypanosomiasis were compared with regard to sensitivity, specificity, positive and negative predictive values, and practicality in field application in the Luangwa Valley of Zambia. Seven (0.64%) trypanosomiasis cases were diagnosed parasitologically in a survey of 1093 people from 19 villages. The indirect fluorescent antibody test (IFAT) was more sensitive but less specific than the parasitological techniques, detecting 71% of the confirmed cases in the first round of testing. Rat inoculation, the Giemsa stained thick film and miniature anion-exchange/centrifugation (mAEC) were all more sensitive than wet blood film examination, microhaematocrit centrifugation and wet film examination of the buffy coat after microhaematocrit centrifugation. The comparison indicated that the most effective, practical combination of techniques for survey in the Luangwa Valley was IFAT screening followed by examination of seropositive patients by rat inoculation and the mAEC (or stained thick film) in parallel format. Calculation of positive and negative predictive values showed that trypanosomiasis point prevalence measured in this way would still be underestimated by approximately 60%, indicating the need to improve IFAT specificity and parasitological sensitivity. Although only one of the seven patients diagnosed in the survey presented with signs and symptoms indicating possible trypanosomiasis, no evidence of a population of "healthy carriers" was found.

Adolescent↗

Importance of L-tryptophan metabolism in trypanosomiasis.

African trypanosomiasis or sleeping sickness is caused by extracellular trypanosomes. The presence of seric antibodies directed to a tryptophan-like epitope in trypanosome infected patients and animals led us to investigate the roles of tryptophan in trypanosomiasis. These antibodies are directed against a tryptophan-rich conserved sequence inside the major parasite surface glycoprotein. In vitro, a rapid uptake of tryptophan by trypanosomes is measured. Seric tryptophan levels are decreased during trypanosomiasis. This decrease may be linked with an increase in indoleamine 2,3-dioxygenase (IDO) induced by Interferon-gamma. In vivo inhibition of IDO by norharman provokes a dramatic increase in circulating parasite number. All these data show the essential role of tryptophan in parasite growth. Moreover, antibodies against tryptophan, the decreased concentration of the neurotransmitter serotonin in the brain following infection and the tryptophan metabolites (tryptophol) produced by trypanosomes may participate to the pathophysiological mechanisms provoking sleeping sickness.

Animals↗

Notes on the routine intravenous use of isometamidium in the control of bovine trypanosomiasis on the Kenya coast.

Various chemotherapeutic regimes were used to control trypanosomiasis in 3,000 Boran cattle on an estate on the Kenya coast. Recently the therapeutic use of isometamidium by the intravenous route was adopted to treat individual trypanosome-infected cattle. This was in order to overcome tissue reactions encountered after intramuscular injection and also to control a "thin cow" syndrome attributed to chronic trypanosomiasis. Toxic side effects were eliminated by careful attention to the intravenous technique which was safely used in calves, pregnant cattle and bulls. Weekly blood sampling and treatments of infected individuals resulted in a reduction of cases from 2,187 to 208 out of 46,495 and 46,329 samples examined in 1985 and 1986 respectively. The standard of management was very high and although this routine successfully controlled bovine trypanosomiasis on this estate its application elsewhere is likely to be limited.

Animals↗

Trypanosomiasis control.

In July 2000, Heads of State of the 36th Session of the Organisation for African Unity signed a potentially important declaration on African trypanosomiasis, urging member states "to act collectively to rise to the challenge of eliminating the problem through concerted efforts in mobilising the necessary human, financial and material resources required to render Africa tsetse-free within the shortest time possible". To many, such an ambitious dream is received with some scepticism, recalling the doubts that surrounded a similar declaration signed in Brasilia in 1991, which paved the way for the Southern Cone Initiative against American trypanosomiasis (Chagas disease). True, the two diseases are quite different. But the operational challenges are quite similar, and there are sufficient biological parallels to suggest that the Latin American experience in controlling Chagas disease may provide a useful model for the control of African trypanosomiasis.

Africa South of the Sahara↗

Cattle migration and stocking densities in relation to tsetse-trypanosomiasis challenge in The Gambia.

The local migration of village N'Dama cattle between two study sites, Niamina East and Bansang, 40 km apart in the inland region of The Gambia, West Africa, is described. The consequences of seasonal variations in local stocking densities on the epidemiology of African animal trypanosomiasis are reported. Tsetse abundance at each study site was monitored throughout the study period from trap catches, and cattle censuses at each site were carried out on a monthly basis. Detailed ecological, productivity and health data, including dietary intake and trypanosomiasis prevalence, were collected from selected study herds resident at the two sites and from a third group of (four) herds that migrated annually between the two areas to spend the late dry season period in Niamina East. It was shown that the migration strategy allowed migrants to maintain a high level of green grazing in the diet throughout the year. Cattle were moved to the area of highest tsetse density in the region to obtain this grazing, but it appeared that individual risk of trypanosome infection was diminished by a dilution effect created by locally high livestock densities. Trypanosomiasis prevalences in resident cattle at Niamina East were best correlated with the tsetse catch/trap/day 2 months previously, once this index of tsetse abundance had been corrected to allow for changes in relative stocking density.

Animal Husbandry↗

Genetic resistance to African Trypanosomiasis.

Genetic resistance to African trypanosomiasis occurs in certain breeds of livestock, many species of wildlife, some strains of mice, and possibly humans. The term trypanotolerance is used to describe this trait, which in domestic livestock is best exhibited by the indigenous West African taurine breeds of cattle, N'Dama and West African Shorthorn, that have been in Africa for 5,000 to 7,000 years. Confirmation not only that these breeds are genetically resistant to trypanosomiasis but also that they are at least as productive as other indigenous breeds is currently leading to their increased use in livestock-development projects in tsetse-infested areas. Trypanotolerance appears to be related to the control of parasitemia, a capacity associated with an event that regulates parasite growth and determines how rapidly the immune response is triggered. Identification of the factors that regulate this event and definition of their genetic basis may have important implications for the development of novel strategies for control of African trypanosomiasis.

Anemia↗

Natural resistance to African trypanosomiasis.

Glossina infected with African trypanosomes infest 10(7) Km2 of intertropical Africa. Ten thousand cases of human sleeping sickness are officially recorded each year and 35 X 10(6) human beings are at risk. Animal trypanosomiasis impedes the use of 7 X 10(6) Km2 of land adequate for cattle raising and constitutes a major constraint to increasing protein production in Africa. Several approaches are used to combat trypanosomiasis (a) vector eradication has been successful in certain defined situations but cannot be realistically extended to the whole area at risk, (b) prophylactic drugs, which are too toxic for humans, are widely used to protect cattle. This practice has led to field resistance to many drugs used in the past (reviewed in Holmes & Scott 1982) and the appearance of resistance to the last available prophylactic drug, isometamidium, is being reported (Bourn & Scott 1978, Küpper & Wolters 1983, Pinder & Authié 1984), (c) the hope for a vaccine has been largely abandoned, in the present state of knowledge, due to the considerable extent of antigenic diversity in trypanosomes (reviewed in Doyle 1977, Turner 1982, Roelants & Pinder 1984), (d) consequently, the possible use of certain West African breeds of cattle, which appear resistant to trypanosomiasis, has been emphasized as a solution to this problem in domestic animals. The analysis of this natural resistance is the subject of the present essay.

Animals↗

Cerebral trypanosomiasis in cattle with mixed Trypanosoma congolense and T. brucei brucei infections.

Six Boran steers were infected simultaneously with Trypanosoma congolense and T. brucei brucei while another group of 3 was inoculated with T. b. brucei one year after infection with T. congolense. Three further steers were infected with T. b. brucei alone. Whereas, the six animals which received simultaneous infections developed clinical signs of cerebral trypanosomiasis as evidenced by depression, ataxia and occasional circling, those infected with T. b. brucei alone did not. At necropsy, 4 out of the 6 simultaneously infected animals had a mild to severe disseminated non-suppurative meningoencephalitis. Trypanosoma b. brucei was isolated from the cerebrospinal fluid (CSF) of three out of the four animals with histological lesions. Two of the cattle superinfected with T. b. brucei one year after infection with T. congolense also developed both clinical and histological evidence of cerebral trypanosomiasis. Trypanosoma congolense was isolated from the CSF of one of these 2 animals. Specific antibodies to the variable surface glycoproteins (VSGs) of the infecting T. b. brucei and T. congolense clones were found in the CSF of the 8 animals that developed cerebral trypanosomiasis. In these animals however, there was neither temporal nor quantitative correlation between VSG-specific antibodies in serum and in CSF, implying a de novo synthesis of antibodies to the infecting trypanosomes in the CSF.

Animals↗

[Defense mechanisms in trypanosomiasis].

Quantitative and functional alterations in macrophages are observed in trypanosomiasis. Two molecules from macrophages exert potent anti-microbial effect: Nitric Oxide (NO) and Tumor Necrosis Factor-alpha (TNF-alpha). The role of NO in trypanosomiasis is investigated at first on a murine parasite. Trypanosoma musculi, at first and then on Trypanosoma brucei gambiense and T. brucei brucei. Macrophages from T. musculi-infected mice synthesize NO and their trypanostatic activity is correlated with NO production. In vitro activation of macrophage NO synthase by IFN-gamma induces a trypanostatic activity and TNF-alpha is involved in NO synthase induction. High serum levels of TNF-alpha are correlated with disease severity in human African trypanosomiasis. TNF-alpha is increased in supernatants of leucocyte and trypanosome cocultures. TNF-alpha exerts a strong anti-trypanosomal effect. Messengers RNA of TNF-alpha are detected in monocytes after 8 hours of coculture with trypanosomes. Macrophage effector molecules participate with other immune effector mechanisms in resistance of host to trypanosomes.

Animals↗

African trypanosomiasis in an American hunter in East Africa.

An American citizen acquired African trypanosomiasis while on a hunting safari in Sudan, East Africa. His travel history and rapid onset of symptoms, including fever, chills, headache, lethargy, and weight loss, were suggestive of Trypanosoma brucei rhodesiense infection, and trypanosomes were demonstrated in routine blood smears and buffy-coat preparations. Despite the presence of headaches, nuchal rigidity, and CSF pleocytosis, he was treated for non-CNS African trypanosomiasis, based on a normal CSF IgM level. This case report, along with a review of previously reported cases of imported African trypanosomiasis, illustrates the importance of clinical consideration of this rare, but often misdiagnosed, tropical illness in febrile patients returning from Africa.

Adult↗

Effect of melarsoprol treatment on circulating IL-10 and TNF-alpha levels in human African trypanosomiasis.

The pathogenesis of human African trypanosomiasis (HAT) has been the object of considerable research interest but has remained incompletely understood. The importance of cytokines in the pathophysiology of this protozoan infection is now widely recognized, but the full spectrum of cytokines involved has yet to be determined. In the present investigation we compared the plasma concentrations of TNF-alpha and IL-10 in normal African controls and patients suffering from advanced meningocephalic (late-stage) Trypanosomiasis brucei (T.b.) gambiense infections, before and after treatment with the arsenical trypanocide melarsoprol. We found that patients with late-stage T. b. gambiense exhibit chronically elevated circulating levels of both of these cytokines, and that these levels quickly decline following melarsoprol treatment. These findings confirm that TNF-alpha is involved in the immunopathogenesis of late-stage African trypanosomiasis and suggest that IL-10 may also play an important regulatory role in this disease.

Adolescent↗

Pancarditis with valvulitis in endomyocardial fibrosis (=emf) and in human African trypanosomiasis (= hat). A comparative histological study of four Ugandan cases.

The study compares the histotopographical lesions of two cases of endomyocardial fibrosis with those of two hearts in sleeping sickness, all of them from Uganda. There was considerable overlapping of the fibrosed zones in endomyocardial fibrosis and the corresponding sites occupied by the chronic inflammatory process in trypanosomiasis. There was a tendency towards fibrosis in the hearts of trypanosomiasis while, in endomyocardial fibrosis, there were mild focal chronic cellular infiltrations. This overlapping and to some extent similarities would suggest that the two conditions may only differ in evolution in time and intensity and that they may be the result of the same inflammatory process. Stipulating a cardiac tropism for African trypanosomes, it is suggested that some African cases of endomyocardial fibrosis may be merely burnt-out lesions of trypanosomal pancarditis. Previous descriptions of carditis in human African and American trypanosomiasis are briefly reviewed, and the present findings are discussed in view of a possible trypanosomal aetiology in some African cardiomyopathies.

Endomyocardial Fibrosis↗

Pathological aspects of human African trypanosomiasis (HAT) in Uganda. A post-mortem survey of fourteen cases.

The pathological features of 14 cases of human African trypanosomiasis (HAT) occurring in Uganda over an 8 year period are described. Three cases were clinically proven and in all 14 cases a chronic meningoencephalitis was found. In 2 cases there was histological evidence of ganglion radiculitis and in one of these chronic choroiditis and peripheral neuritis associated with chronic myositis were present. The cardiac lesions consisted of a chronic pancarditis of varying degree in 8 cases and in 3 a generalized valvulitis was observed. In 2 cases, specially investigated, generalized lesions of the conducting system were noticed. Previous histopathological descriptions of HAT are briefly reviewed. The present findings are compared with some of those recorded in human american trypanosomiasis and experimental African trypanosomiasis.

Adolescent↗

Evaluation of an indirect fluorescent antibody test, enzyme-linked immunosorbent assay and quantification of immunoglobulins in the diagnosis of bovine trypanosomiasis.

An indirect fluorescent antibody test (IFAT), a microscale version of the enzyme-linked immunosorbent assay (microELISA) and determination of IgM levels in serum were assessed for their comparative diagnostic value in the detection of bovine trypanosomiasis. Serum samples from drug-treated N'dama cattle and untreated N'dama and Zebu cattle from Liberia were examined for the presence fo antibodies to trypanosomes. In the untreated Zebu cattle, infections with T. vivax predominated and the prevalence of infection was higher than that found in untreated N'damas in which infections with T. congolense predominated. The proportion of animals which showed serological evidence of trypanosomiasis in the untreated Zebus was slightly higher than that found in the untreated N'damas. The prevalence of infection was low in N'dama cattle which had been treated with diminazene aceturate and homidium chloride but 50% of the animals showed serological evidence of trypanosomiasis. More serologically positive animals were detected by microELISA than IFAT, but both tests were equally sensitive in detecting antibodies in cattle in which trypanosomes were demonstrated by examination of peripheral blood. With both IFAT and microELISA it was necessary to carry out tests using antigens prepared from T. brucei, T. vivax and T. congolense in order to detect all serologically positive animals. Increases in serum IgM occurred in both N'dama and Zebu cattle but the levels were raised in only approximately half of the known infected animals. Overall, more animals gave positive reactions with IFAT and microELISA than showed raised IgM levels.

Animals↗

Bovine trypanosomiasis in southern Tanzania: parasitological and serological survey of prevalence.

In a survey for bovine trypanosomiasis blood smears from 1,617 cattle at 72 sites were examined. Trypanosomes were found in 93 cattle, representing 16% of the cattle in herds in which trypanosomiasis was confirmed. Of the positive cattle 56% had infections with T. congolense, 17% T. vivax and 2.2% T. brucei. Five cattle had mixed infections and in 18 cattle the species was not identified. Sera from 1,352 cattle were tested using microelisa. Ten out of 16 sites, at which no trypanosomes were found in blood smears and at which trypanocides were in use, had over 15% seropositive cattle compared with five of 19 sites at which trypanocides were not in use. It was concluded that the microelisa was a useful aid to the diagnosis of bovine trypanosomiasis and that there is a need for accurate records of drug use and livestock movements to be kept. The serious risk of drug resistant strains of trypanosomes emerging due to the uncontrolled use of trypanocides is emphasised.

Animals↗