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

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...

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Autores principales: Seixas, Jorge, Atouguia, Jorge, Josenando, Teófilo, Vatunga, Gedeão, Miaka Mia Bilenge, Constantin, Lutumba, Pascal, Burri, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157710/
https://www.ncbi.nlm.nih.gov/pubmed/31906333
http://dx.doi.org/10.3390/tropicalmed5010005
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author Seixas, Jorge
Atouguia, Jorge
Josenando, Teófilo
Vatunga, Gedeão
Miaka Mia Bilenge, Constantin
Lutumba, Pascal
Burri, Christian
author_facet Seixas, Jorge
Atouguia, Jorge
Josenando, Teófilo
Vatunga, Gedeão
Miaka Mia Bilenge, Constantin
Lutumba, Pascal
Burri, Christian
author_sort Seixas, Jorge
collection PubMed
description 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.
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spelling pubmed-71577102020-04-21 Clinical Study on the Melarsoprol-Related Encephalopathic Syndrome: Risk Factors and HLA Association Seixas, Jorge Atouguia, Jorge Josenando, Teófilo Vatunga, Gedeão Miaka Mia Bilenge, Constantin Lutumba, Pascal Burri, Christian Trop Med Infect Dis Article 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. MDPI 2020-01-01 /pmc/articles/PMC7157710/ /pubmed/31906333 http://dx.doi.org/10.3390/tropicalmed5010005 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Seixas, Jorge
Atouguia, Jorge
Josenando, Teófilo
Vatunga, Gedeão
Miaka Mia Bilenge, Constantin
Lutumba, Pascal
Burri, Christian
Clinical Study on the Melarsoprol-Related Encephalopathic Syndrome: Risk Factors and HLA Association
title Clinical Study on the Melarsoprol-Related Encephalopathic Syndrome: Risk Factors and HLA Association
title_full Clinical Study on the Melarsoprol-Related Encephalopathic Syndrome: Risk Factors and HLA Association
title_fullStr Clinical Study on the Melarsoprol-Related Encephalopathic Syndrome: Risk Factors and HLA Association
title_full_unstemmed Clinical Study on the Melarsoprol-Related Encephalopathic Syndrome: Risk Factors and HLA Association
title_short Clinical Study on the Melarsoprol-Related Encephalopathic Syndrome: Risk Factors and HLA Association
title_sort clinical study on the melarsoprol-related encephalopathic syndrome: risk factors and hla association
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157710/
https://www.ncbi.nlm.nih.gov/pubmed/31906333
http://dx.doi.org/10.3390/tropicalmed5010005
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