Abstract
Melarsoprol administration for the treatment of late-stage human African trypanosomiasis (HAT) is associated with the development of an unpredictable and badly characterized encephalopathic syndrome (ES), probably of immune origin, that kills approximately 50% of those affected. We investigated the characteristics and clinical risk factors for ES, as well as the association between the Human Leukocyte Antigen (HLA) complex and the risk for ES in a case-control study. Late-stage Gambiense HAT patients treated with melarsoprol and developing ES (69 cases) were compared to patients not suffering from the syndrome (207 controls). Patients were enrolled in six HAT treatment centres in Angola and in the Democratic Republic of Congo. Standardized clinical data was obtained from all participants before melarsoprol was initiated. Class I (HLA-A, HLA-B, HLA-Cw) and II (HLA-DR) alleles were determined by PCR-SSOP methods in 62 ES cases and 189 controls. The principal ES pattern consisted in convulsions followed by a coma, whereas ES with exclusively mental changes was not observed. Oedema, bone pain, apathy, and a depressed humour were associated with a higher risk of ES, while abdominal pain, coma, respiratory distress, and a Babinski sign were associated with higher ES-associated mortality. Haplotype C*14/B*15 was associated with an elevated risk for ES (OR: 6.64; p-value: 0.008). Haplotypes A*23/C*14, A*23/B*15 and DR*07/B*58 also showed a weaker association with ES. This result supports the hypothesis that a genetically determined peculiar type of immune response confers susceptibility for ES.
Highlights
Human African trypanosomiasis (HAT, sleeping sickness) is a neglected tropical disease (NTD) caused by the protozoan parasites Trypanosoma brucei gambiense (Gambiense human African trypanosomiasis (HAT), endemic in West and Central Africa) and Trypanosoma brucei rhodesiense (Rhodesiense HAT, endemic in Eastern and Southern Africa)
Three patients were less than 10 years old, and two patients were above 60 years
All but five patients had parasitologically confirmed HAT. These five patients had been previously treated with pentamidine; late-stage HAT diagnosis was established according to a positive card agglutination test for trypanosomiasis (CATT) and more than 5 white blood cell count (WBC)/mm3 in cerebrospinal fluid (CSF)
Summary
Human African trypanosomiasis (HAT, sleeping sickness) is a neglected tropical disease (NTD) caused by the protozoan parasites Trypanosoma brucei gambiense (Gambiense HAT, endemic in West and Central Africa) and Trypanosoma brucei rhodesiense (Rhodesiense HAT, endemic in Eastern and Southern Africa). HAT cases are still being reported in more than 20 countries in intertropical Africa. Most of the reported cases (98%) are of Gambiense HAT, which usually causes a chronic form of infection and in which humans are the main reservoir of the parasite. Rhodesiense HAT, a zoonotic disease that occasionally affects humans, usually causes a more acute form of disease and accounts for the remaining number of cases. HAT has been targeted by WHO for sustainable elimination by 2030. The essential component of the elimination strategy is the treatment of all diagnosed cases in order to deplete the parasite’s reservoir [2,3]
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