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

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

doi:10.1016/j.ebiom.2022.104376

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

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

Trypanosoma

Research output: Contribution to journal › A1: Web of Science-article › peer-review

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Abstract

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).

Original language	English
Article number	104376
Journal	EBioMedicine
Volume	86
Number of pages	12
ISSN	2352-3964
DOIs	https://doi.org/10.1016/j.ebiom.2022.104376
Publication status	Published - 2022

Keywords

Animals
Antiprotozoal Agents/therapeutic use
Follow-Up Studies
Humans
RNA, Spliced Leader
Treatment Outcome
Trypanosoma
Trypanosoma brucei gambiense/genetics
Trypanosomiasis, African/diagnosis

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Ngay Lukusa, I., Van Reet, N., Mumba Ngoyi, D., Mwamba Miaka, E., Masumu, J., Patient Pyana, P., Mutombo, W., Ngolo, D., Kobo, V., Akwaso, F., Ilunga, M., Kaninda, L., Mutanda, S., Mpoyi Muamba, D., Valverde Mordt, O., Tarral, A., Rembry, S., Büscher, P., & Lejon, V. (2022). Trypanosome spliced leader RNA for diagnosis of acoziborole treatment outcome in gambiense human African trypanosomiasis: a longitudinal follow-up study. EBioMedicine, 86, [104376]. https://doi.org/10.1016/j.ebiom.2022.104376

Ngay Lukusa, Ipos ; Van Reet, Nick ; Mumba Ngoyi, Dieudonné ; Mwamba Miaka, Erick ; Masumu, Justin ; Patient Pyana, Pati ; Mutombo, Wilfried ; Ngolo, Digas ; Kobo, Vincent ; Akwaso, Felix ; Ilunga, Médard ; Kaninda, Lewis ; Mutanda, Sylvain ; Mpoyi Muamba, Dieudonné ; Valverde Mordt, Olaf ; Tarral, Antoine ; Rembry, Sandra ; Büscher, Philippe ; Lejon, Veerle. / Trypanosome spliced leader RNA for diagnosis of acoziborole treatment outcome in gambiense human African trypanosomiasis: a longitudinal follow-up study. In: EBioMedicine. 2022 ; Vol. 86.

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title = "Trypanosome spliced leader RNA for diagnosis of acoziborole treatment outcome in gambiense human African trypanosomiasis: a longitudinal follow-up study",

abstract = "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).",

keywords = "Animals, Antiprotozoal Agents/therapeutic use, Follow-Up Studies, Humans, RNA, Spliced Leader, Treatment Outcome, Trypanosoma, Trypanosoma brucei gambiense/genetics, Trypanosomiasis, African/diagnosis",

author = "{Ngay Lukusa}, Ipos and {Van Reet}, Nick and {Mumba Ngoyi}, Dieudonn{\'e} and {Mwamba Miaka}, Erick and Justin Masumu and {Patient Pyana}, Pati and Wilfried Mutombo and Digas Ngolo and Vincent Kobo and Felix Akwaso and M{\'e}dard Ilunga and Lewis Kaninda and Sylvain Mutanda and {Mpoyi Muamba}, Dieudonn{\'e} and {Valverde Mordt}, Olaf and Antoine Tarral and Sandra Rembry and Philippe B{\"u}scher and Veerle Lejon",

note = "FTX; DOAJ; (CC BY-NC-ND 4.0)",

year = "2022",

doi = "10.1016/j.ebiom.2022.104376",

language = "English",

volume = "86",

journal = "EBioMedicine",

issn = "2352-3964",

publisher = "Elsevier",

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Ngay Lukusa, I, Van Reet, N, Mumba Ngoyi, D, Mwamba Miaka, E, Masumu, J, Patient Pyana, P, Mutombo, W, Ngolo, D, Kobo, V, Akwaso, F, Ilunga, M, Kaninda, L, Mutanda, S, Mpoyi Muamba, D, Valverde Mordt, O, Tarral, A, Rembry, S, Büscher, P & Lejon, V 2022, 'Trypanosome spliced leader RNA for diagnosis of acoziborole treatment outcome in gambiense human African trypanosomiasis: a longitudinal follow-up study', EBioMedicine, vol. 86, 104376. https://doi.org/10.1016/j.ebiom.2022.104376

Trypanosome spliced leader RNA for diagnosis of acoziborole treatment outcome in gambiense human African trypanosomiasis: a longitudinal follow-up study. / Ngay Lukusa, Ipos; Van Reet, Nick; Mumba Ngoyi, Dieudonné; Mwamba Miaka, Erick; Masumu, Justin; Patient Pyana, Pati; Mutombo, Wilfried; Ngolo, Digas; Kobo, Vincent; Akwaso, Felix; Ilunga, Médard; Kaninda, Lewis; Mutanda, Sylvain; Mpoyi Muamba, Dieudonné; Valverde Mordt, Olaf; Tarral, Antoine; Rembry, Sandra; Büscher, Philippe; Lejon, Veerle.

In: EBioMedicine, Vol. 86, 104376, 2022.

Research output: Contribution to journal › A1: Web of Science-article › peer-review

TY - JOUR

T1 - Trypanosome spliced leader RNA for diagnosis of acoziborole treatment outcome in gambiense human African trypanosomiasis: a longitudinal follow-up study

AU - Ngay Lukusa, Ipos

AU - Van Reet, Nick

AU - Mumba Ngoyi, Dieudonné

AU - Mwamba Miaka, Erick

AU - Masumu, Justin

AU - Patient Pyana, Pati

AU - Mutombo, Wilfried

AU - Ngolo, Digas

AU - Kobo, Vincent

AU - Akwaso, Felix

AU - Ilunga, Médard

AU - Kaninda, Lewis

AU - Mutanda, Sylvain

AU - Mpoyi Muamba, Dieudonné

AU - Valverde Mordt, Olaf

AU - Tarral, Antoine

AU - Rembry, Sandra

AU - Büscher, Philippe

AU - Lejon, Veerle

N1 - FTX; DOAJ; (CC BY-NC-ND 4.0)

PY - 2022

Y1 - 2022

N2 - 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).

AB - 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).

KW - Animals

KW - Antiprotozoal Agents/therapeutic use

KW - Follow-Up Studies

KW - Humans

KW - RNA, Spliced Leader

KW - Treatment Outcome

KW - Trypanosoma

KW - Trypanosoma brucei gambiense/genetics

KW - Trypanosomiasis, African/diagnosis

U2 - 10.1016/j.ebiom.2022.104376

DO - 10.1016/j.ebiom.2022.104376

M3 - A1: Web of Science-article

C2 - 36436279

VL - 86

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

M1 - 104376

ER -