{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:12:10Z","timestamp":1791306730686,"version":"4.3.1"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005635","name":"Funda\u00e7\u00e3o Calouste Gulbenkian","doi-asserted-by":"publisher","award":["xxxx"],"award-info":[{"award-number":["xxxx"]}],"id":[{"id":"10.13039\/501100005635","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009131","name":"Swiss Agency for Development and Cooperation","doi-asserted-by":"publisher","award":["yyyy"],"award-info":[{"award-number":["yyyy"]}],"id":[{"id":"10.13039\/100009131","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004423","name":"World Health Organization","doi-asserted-by":"publisher","award":["zzzz"],"award-info":[{"award-number":["zzzz"]}],"id":[{"id":"10.13039\/100004423","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondation Roche de Recherche en Afrique","award":["xzxzx"],"award-info":[{"award-number":["xzxzx"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/tropicalmed5010005","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T04:43:03Z","timestamp":1578026583000},"page":"5","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Clinical Study on the Melarsoprol-Related Encephalopathic Syndrome: Risk Factors and HLA Association"],"prefix":"10.3390","volume":"5","author":[{"given":"Jorge","family":"Seixas","sequence":"first","affiliation":[{"name":"Institute of Hygiene and Tropical Medicine, NOVA University, 1349-008 Lisbon, Portugal"},{"name":"Global Health and Tropical Medicine R&amp;D Center, NOVA University, 1349-008 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Atouguia","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Tropical Medicine, NOVA University, 1349-008 Lisbon, Portugal"},{"name":"Global Health and Tropical Medicine R&amp;D Center, NOVA University, 1349-008 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Te\u00f3filo","family":"Josenando","sequence":"additional","affiliation":[{"name":"Instituto de Combate e Controlo das Tripanossom\u00edases, Luanda, Angola"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gede\u00e3o","family":"Vatunga","sequence":"additional","affiliation":[{"name":"Hospital Geral de Luanda, Luanda, Angola"},{"name":"Instituto Superior Polit\u00e9cnico Kalandula de Angola, Luanda, Angola"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin","family":"Miaka Mia Bilenge","sequence":"additional","affiliation":[{"name":"Programme National de Lutte contre la Trypanosomiase Humaine Africaine, Kinshasa, Democratic Republic of the Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Lutumba","sequence":"additional","affiliation":[{"name":"Tropical Medicine Department, University of Kinshasa, Kinshasa, Democratic Republic of the Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Burri","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland"},{"name":"University of Basel, 4001 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/S0140-6736(09)60829-1","article-title":"Human African trypanosomiasis","volume":"375","author":"Brun","year":"2010","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Franco, J.R., Cecchi, G., Priotto, G., Paone, M., Diarra, A., Grout, L., Simarro, P.P., Zhao, W., and Argaw, D. 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