Trypanosome spliced leader RNA for diagnosis of acoziborole treatment outcome in gambiense human African trypanosomiasis: A longitudinal follow-up studyResearch in context

Summary: Background: Detection of spliced leader (SL)-RNA allows sensitive diagnosis of gambiense human African trypanosomiasis (HAT). We investigated its diagnostic performance for treatment outcome assessment. Methods: Blood and cerebrospinal fluid (CSF) from a consecutive series of 97 HAT patien...

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Main Authors: Ipos Ngay Lukusa, Nick Van Reet, Dieudonné Mumba Ngoyi, Erick Mwamba Miaka, Justin Masumu, Pati Patient Pyana, Wilfried Mutombo, Digas Ngolo, Vincent Kobo, Felix Akwaso, Médard Ilunga, Lewis Kaninda, Sylvain Mutanda, Dieudonné Mpoyi Muamba, Olaf Valverde Mordt, Antoine Tarral, Sandra Rembry, Philippe Büscher, Veerle Lejon
Format: Article
Language:English
Published: Elsevier 2022-12-01
Series:EBioMedicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2352396422005588
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author Ipos Ngay Lukusa
Nick Van Reet
Dieudonné Mumba Ngoyi
Erick Mwamba Miaka
Justin Masumu
Pati Patient Pyana
Wilfried Mutombo
Digas Ngolo
Vincent Kobo
Felix Akwaso
Médard Ilunga
Lewis Kaninda
Sylvain Mutanda
Dieudonné Mpoyi Muamba
Olaf Valverde Mordt
Antoine Tarral
Sandra Rembry
Philippe Büscher
Veerle Lejon
author_facet Ipos Ngay Lukusa
Nick Van Reet
Dieudonné Mumba Ngoyi
Erick Mwamba Miaka
Justin Masumu
Pati Patient Pyana
Wilfried Mutombo
Digas Ngolo
Vincent Kobo
Felix Akwaso
Médard Ilunga
Lewis Kaninda
Sylvain Mutanda
Dieudonné Mpoyi Muamba
Olaf Valverde Mordt
Antoine Tarral
Sandra Rembry
Philippe Büscher
Veerle Lejon
author_sort Ipos Ngay Lukusa
collection DOAJ
description Summary: Background: Detection of spliced leader (SL)-RNA allows sensitive diagnosis of gambiense human African trypanosomiasis (HAT). We investigated its diagnostic performance for treatment outcome assessment. Methods: Blood and cerebrospinal fluid (CSF) from a consecutive series of 97 HAT patients, originating from the Democratic Republic of the Congo, were prospectively collected before treatment with acoziborole, and during 18 months of longitudinal follow-up after treatment. For treatment outcome assessment, SL-RNA detection was compared with microscopic trypanosome detection and CSF white blood cell count. The trial was registered under NCT03112655 in clinicaltrials.gov. Findings: Before treatment, respectively 94.9% (92/97; CI 88.5–97.8%) and 67.7% (65/96; CI 57.8–76.2%) HAT patients were SL-RNA positive in blood or CSF. During follow-up, one patient relapsed with trypanosomes observed at 18 months, and was SL-RNA positive in blood and CSF at 12 months, and CSF positive at 18 months. Among cured patients, one individual tested SL-RNA positive in blood at month 12 (Specificity 98.9%; 90/91; CI 94.0–99.8%) and 18 (Specificity 98.9%; 88/89; CI 93.9–99.8%). Interpretation: SL-RNA detection for HAT treatment outcome assessment shows ≥98.9% specificity in blood and 100% in CSF, and may detect relapses without lumbar puncture. Funding: The DiTECT-HAT project is part of the EDCTP2 programme, supported by Horizon 2020, the European Union Funding for Research and Innovation (grant number DRIA-2014-306-DiTECT-HAT).
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spelling doaj.art-dd066076d06b4e58ab678a33a34d95022022-12-22T04:20:51ZengElsevierEBioMedicine2352-39642022-12-0186104376Trypanosome spliced leader RNA for diagnosis of acoziborole treatment outcome in gambiense human African trypanosomiasis: A longitudinal follow-up studyResearch in contextIpos Ngay Lukusa0Nick Van Reet1Dieudonné Mumba Ngoyi2Erick Mwamba Miaka3Justin Masumu4Pati Patient Pyana5Wilfried Mutombo6Digas Ngolo7Vincent Kobo8Felix Akwaso9Médard Ilunga10Lewis Kaninda11Sylvain Mutanda12Dieudonné Mpoyi Muamba13Olaf Valverde Mordt14Antoine Tarral15Sandra Rembry16Philippe Büscher17Veerle Lejon18Department of Parasitology, Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the CongoDepartment of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, BelgiumDepartment of Parasitology, Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the CongoProgramme National de Lutte contre la Trypanosomiase Humaine Africaine (PNLTHA), Ministry of Health, Kinshasa, Democratic Republic of the CongoDepartment of Parasitology, Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the CongoDepartment of Parasitology, Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the CongoProgramme National de Lutte contre la Trypanosomiase Humaine Africaine (PNLTHA), Ministry of Health, Kinshasa, Democratic Republic of the CongoProgramme National de Lutte contre la Trypanosomiase Humaine Africaine (PNLTHA), Ministry of Health, Kinshasa, Democratic Republic of the CongoProgramme National de Lutte contre la Trypanosomiase Humaine Africaine (PNLTHA), Ministry of Health, Kinshasa, Democratic Republic of the CongoProgramme National de Lutte contre la Trypanosomiase Humaine Africaine (PNLTHA), Ministry of Health, Kinshasa, Democratic Republic of the CongoProgramme National de Lutte contre la Trypanosomiase Humaine Africaine (PNLTHA), Ministry of Health, Kinshasa, Democratic Republic of the CongoProgramme National de Lutte contre la Trypanosomiase Humaine Africaine (PNLTHA), Ministry of Health, Kinshasa, Democratic Republic of the CongoProgramme National de Lutte contre la Trypanosomiase Humaine Africaine (PNLTHA), Ministry of Health, Kinshasa, Democratic Republic of the CongoProgramme National de Lutte contre la Trypanosomiase Humaine Africaine (PNLTHA), Ministry of Health, Kinshasa, Democratic Republic of the CongoDrugs for Neglected Diseases Initiative, Geneva, SwitzerlandDrugs for Neglected Diseases Initiative, Geneva, SwitzerlandDrugs for Neglected Diseases Initiative, Geneva, SwitzerlandDepartment of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, BelgiumMixed Research Unit 177 Intertryp, Institut de Recherche pour le Développement, Centre de Coopération Internationale en Recherche Agronomique pour le Développement, University of Montpellier, Montpellier, France; Corresponding author. Institut de Recherche pour le Développement, UMR 177 – Intertryp, Campus International de Baillarguet, 34398 Montpellier Cedex 5, France.Summary: Background: Detection of spliced leader (SL)-RNA allows sensitive diagnosis of gambiense human African trypanosomiasis (HAT). We investigated its diagnostic performance for treatment outcome assessment. Methods: Blood and cerebrospinal fluid (CSF) from a consecutive series of 97 HAT patients, originating from the Democratic Republic of the Congo, were prospectively collected before treatment with acoziborole, and during 18 months of longitudinal follow-up after treatment. For treatment outcome assessment, SL-RNA detection was compared with microscopic trypanosome detection and CSF white blood cell count. The trial was registered under NCT03112655 in clinicaltrials.gov. Findings: Before treatment, respectively 94.9% (92/97; CI 88.5–97.8%) and 67.7% (65/96; CI 57.8–76.2%) HAT patients were SL-RNA positive in blood or CSF. During follow-up, one patient relapsed with trypanosomes observed at 18 months, and was SL-RNA positive in blood and CSF at 12 months, and CSF positive at 18 months. Among cured patients, one individual tested SL-RNA positive in blood at month 12 (Specificity 98.9%; 90/91; CI 94.0–99.8%) and 18 (Specificity 98.9%; 88/89; CI 93.9–99.8%). Interpretation: SL-RNA detection for HAT treatment outcome assessment shows ≥98.9% specificity in blood and 100% in CSF, and may detect relapses without lumbar puncture. Funding: The DiTECT-HAT project is part of the EDCTP2 programme, supported by Horizon 2020, the European Union Funding for Research and Innovation (grant number DRIA-2014-306-DiTECT-HAT).http://www.sciencedirect.com/science/article/pii/S2352396422005588Human African trypanosomiasisTrypanosoma brucei gambienseTreatment outcomeRelapseRNADiagnosis
spellingShingle Ipos Ngay Lukusa
Nick Van Reet
Dieudonné Mumba Ngoyi
Erick Mwamba Miaka
Justin Masumu
Pati Patient Pyana
Wilfried Mutombo
Digas Ngolo
Vincent Kobo
Felix Akwaso
Médard Ilunga
Lewis Kaninda
Sylvain Mutanda
Dieudonné Mpoyi Muamba
Olaf Valverde Mordt
Antoine Tarral
Sandra Rembry
Philippe Büscher
Veerle Lejon
Trypanosome spliced leader RNA for diagnosis of acoziborole treatment outcome in gambiense human African trypanosomiasis: A longitudinal follow-up studyResearch in context
EBioMedicine
Human African trypanosomiasis
Trypanosoma brucei gambiense
Treatment outcome
Relapse
RNA
Diagnosis
title Trypanosome spliced leader RNA for diagnosis of acoziborole treatment outcome in gambiense human African trypanosomiasis: A longitudinal follow-up studyResearch in context
title_full Trypanosome spliced leader RNA for diagnosis of acoziborole treatment outcome in gambiense human African trypanosomiasis: A longitudinal follow-up studyResearch in context
title_fullStr Trypanosome spliced leader RNA for diagnosis of acoziborole treatment outcome in gambiense human African trypanosomiasis: A longitudinal follow-up studyResearch in context
title_full_unstemmed Trypanosome spliced leader RNA for diagnosis of acoziborole treatment outcome in gambiense human African trypanosomiasis: A longitudinal follow-up studyResearch in context
title_short Trypanosome spliced leader RNA for diagnosis of acoziborole treatment outcome in gambiense human African trypanosomiasis: A longitudinal follow-up studyResearch in context
title_sort trypanosome spliced leader rna for diagnosis of acoziborole treatment outcome in gambiense human african trypanosomiasis a longitudinal follow up studyresearch in context
topic Human African trypanosomiasis
Trypanosoma brucei gambiense
Treatment outcome
Relapse
RNA
Diagnosis
url http://www.sciencedirect.com/science/article/pii/S2352396422005588
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