Clinical Study on the Melarsoprol-Related Encephalopathic Syndrome: Risk Factors and HLA Association.

Journal: Tropical medicine and infectious disease

Volume: 5

Issue: 1

Year of Publication: 

Affiliated Institutions:  Institute of Hygiene and Tropical Medicine, NOVA University, - Lisbon, Portugal. Instituto de Combate e Controlo das Tripanossomíases, Luanda, Angola. Hospital Geral de Luanda, Luanda, Angola. Programme National de Lutte contre la Trypanosomiase Humaine Africaine, Kinshasa, Congo. Tropical Medicine Department, University of Kinshasa, Kinshasa, Congo. Swiss Tropical and Public Health Institute, Basel, Switzerland.

Abstract summary 

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; -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.

Authors & Co-authors:  Seixas Jorge J Atouguia Jorge J Josenando Teófilo T Vatunga Gedeão G Bilenge Constantin Miaka Mia CMM Lutumba Pascal P Burri Christian C

Study Outcome 

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Statistics
Citations :  Brun R., Blum J., Chappuis F., Burri C. Human African trypanosomiasis. Lancet. 2010;375:148–159. doi: 10.1016/S0140-6736(09)60829-1.
Authors :  7
Identifiers
Doi : 5
SSN : 2414-6366
Study Population
Male,Female
Mesh Terms
Other Terms
adverse event;association study;encephalopathy;human African trypanosomiasis;human leukocyte antigen;melarsoprol;treatment
Study Design
Study Approach
Country of Study
Democratic republic of Congo
Publication Country
Switzerland