article · Tropical Medicine and Infectious Disease
Treating late-stage human African trypanosomiasis with melarsoprol carries a severe risk of encephalopathic syndrome, an immune-related complication that results in death for approximately half of affected patients. A case-control study conducted across six treatment centres in Angola and the Democratic Republic of Congo evaluated sixty-nine patients who developed the syndrome and two hundred and seven who did not. Clinically, the primary presentation involved convulsions followed by coma. Prior to treatment, symptoms such as oedema, bone pain, apathy, and depressed humour correlated with an increased likelihood of developing the syndrome. Furthermore, conditions including abdominal pain, coma, respiratory distress, and the presence of a Babinski sign were linked to increased mortality. Genetic analyses revealed that specific Human Leukocyte Antigen haplotypes, particularly C*14/B*15, significantly elevate the risk of developing this condition, indicating an underlying genetic susceptibility.
Human African trypanosomiasis is a life-threatening infection, but melarsoprol treatment carries a high risk of lethal post-treatment complications. Identifying early clinical indicators and genetic risk markers helps healthcare providers recognise which patients face the greatest danger, supporting better risk assessment and targeted patient monitoring during treatment for this neglected tropical disease.
The discovery of genetic markers linked to melarsoprol toxicity could enable diagnostic developers to design screening tools to identify high-risk individuals prior to therapy. Such tools would serve clinical teams and health programmes treating late-stage sleeping sickness. This research represents early-stage biomarker identification, requiring further validation and development before any diagnostic test could be introduced into routine clinical practice.
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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; <i>p</i>-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.
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DOI: 10.3390/tropicalmed5010005
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