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Evaluation of Artesunate-mefloquine as a Novel Alternative Treatment for Schistosomiasis in African Children (SchistoSAM): protocol of a proof-of-concept, open-label, two-arm, individually-randomised controlled trial
INTRODUCTION: Alternative drugs and diagnostics are needed for the treatment and control of schistosomiasis. The exclusive use of praziquantel (PZQ) in mass drug administration programmes may result in the emergence of drug resistance. PZQ has little activity against Schistosoma larvae, thus reinfec...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231067/ https://www.ncbi.nlm.nih.gov/pubmed/34168029 http://dx.doi.org/10.1136/bmjopen-2020-047147 |
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author | Roucher, Clémentine Brosius, Isabel Mbow, Moustapha Faye, Babacar Thiendella De Hondt, Annelies Smekens, Bart Arango, Diana Burm, Christophe Tsoumanis, Achilleas Paredis, Linda van Herrewege, Yven Potters, Idzi Cisse, Badara Mboup, Souleymane Polman, Katja Bottieau, Emmanuel |
author_facet | Roucher, Clémentine Brosius, Isabel Mbow, Moustapha Faye, Babacar Thiendella De Hondt, Annelies Smekens, Bart Arango, Diana Burm, Christophe Tsoumanis, Achilleas Paredis, Linda van Herrewege, Yven Potters, Idzi Cisse, Badara Mboup, Souleymane Polman, Katja Bottieau, Emmanuel |
author_sort | Roucher, Clémentine |
collection | PubMed |
description | INTRODUCTION: Alternative drugs and diagnostics are needed for the treatment and control of schistosomiasis. The exclusive use of praziquantel (PZQ) in mass drug administration programmes may result in the emergence of drug resistance. PZQ has little activity against Schistosoma larvae, thus reinfection remains a problem in high-risk communities. Furthermore, the insufficient sensitivity of conventional microscopy hinders therapeutic response assessment. Evaluation of artesunate-mefloquine (AM) as a Novel Alternative Treatment for Schistosomiasis in African Children (SchistoSAM) aims to evaluate the safety and efficacy of the antimalarial combination artesunate-mefloquine, re-purposed for the treatment of schistosomiasis, and to assess the performance of highly sensitive novel antigen-based and DNA-based assays as tools for monitoring treatment response. METHODS AND ANALYSIS: The SchistoSAM study is an open-label, two-arm, individually randomised controlled non-inferiority trial, with a follow-up of 48 weeks. Primary school-aged children from the Richard Toll district in northern Senegal, an area endemic for Schistosoma mansoni and Schistosoma haematobium, are allocated to the AM intervention arm (3-day courses at 6-week intervals) or the PZQ control arm (single dose of 40 mg/kg). The trial’s primary endpoints are the efficacy (cure rate (CR), assessed by microscopy) and safety (frequency and pattern of drug-related adverse events) of one AM course versus PZQ at 4 weeks after treatment. Secondary endpoints include (1) cumulative CR, egg reduction rate and safety after each additional course of AM, and at weeks 24 and 48, (2) prevalence and severity of schistosomiasis-related morbidity and (3) malaria prevalence, incidence and morbidity, both after 24 and 48 weeks. CRs and intensity reduction rates are also assessed by antigen-based and DNA-based diagnostic assays, for which performance for treatment monitoring is evaluated. ETHICS AND DISSEMINATION: Ethics approval was obtained both in Belgium and Senegal. Oral assent from the children and signed informed consent from their legal representatives was obtained, prior to enrolment. The results will be disseminated in peer-reviewed journals and at international conferences. TRIAL REGISTRATION NUMBER: NCT03893097; pre-results. |
format | Online Article Text |
id | pubmed-8231067 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-82310672021-07-09 Evaluation of Artesunate-mefloquine as a Novel Alternative Treatment for Schistosomiasis in African Children (SchistoSAM): protocol of a proof-of-concept, open-label, two-arm, individually-randomised controlled trial Roucher, Clémentine Brosius, Isabel Mbow, Moustapha Faye, Babacar Thiendella De Hondt, Annelies Smekens, Bart Arango, Diana Burm, Christophe Tsoumanis, Achilleas Paredis, Linda van Herrewege, Yven Potters, Idzi Cisse, Badara Mboup, Souleymane Polman, Katja Bottieau, Emmanuel BMJ Open Infectious Diseases INTRODUCTION: Alternative drugs and diagnostics are needed for the treatment and control of schistosomiasis. The exclusive use of praziquantel (PZQ) in mass drug administration programmes may result in the emergence of drug resistance. PZQ has little activity against Schistosoma larvae, thus reinfection remains a problem in high-risk communities. Furthermore, the insufficient sensitivity of conventional microscopy hinders therapeutic response assessment. Evaluation of artesunate-mefloquine (AM) as a Novel Alternative Treatment for Schistosomiasis in African Children (SchistoSAM) aims to evaluate the safety and efficacy of the antimalarial combination artesunate-mefloquine, re-purposed for the treatment of schistosomiasis, and to assess the performance of highly sensitive novel antigen-based and DNA-based assays as tools for monitoring treatment response. METHODS AND ANALYSIS: The SchistoSAM study is an open-label, two-arm, individually randomised controlled non-inferiority trial, with a follow-up of 48 weeks. Primary school-aged children from the Richard Toll district in northern Senegal, an area endemic for Schistosoma mansoni and Schistosoma haematobium, are allocated to the AM intervention arm (3-day courses at 6-week intervals) or the PZQ control arm (single dose of 40 mg/kg). The trial’s primary endpoints are the efficacy (cure rate (CR), assessed by microscopy) and safety (frequency and pattern of drug-related adverse events) of one AM course versus PZQ at 4 weeks after treatment. Secondary endpoints include (1) cumulative CR, egg reduction rate and safety after each additional course of AM, and at weeks 24 and 48, (2) prevalence and severity of schistosomiasis-related morbidity and (3) malaria prevalence, incidence and morbidity, both after 24 and 48 weeks. CRs and intensity reduction rates are also assessed by antigen-based and DNA-based diagnostic assays, for which performance for treatment monitoring is evaluated. ETHICS AND DISSEMINATION: Ethics approval was obtained both in Belgium and Senegal. Oral assent from the children and signed informed consent from their legal representatives was obtained, prior to enrolment. The results will be disseminated in peer-reviewed journals and at international conferences. TRIAL REGISTRATION NUMBER: NCT03893097; pre-results. BMJ Publishing Group 2021-06-24 /pmc/articles/PMC8231067/ /pubmed/34168029 http://dx.doi.org/10.1136/bmjopen-2020-047147 Text en © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Infectious Diseases Roucher, Clémentine Brosius, Isabel Mbow, Moustapha Faye, Babacar Thiendella De Hondt, Annelies Smekens, Bart Arango, Diana Burm, Christophe Tsoumanis, Achilleas Paredis, Linda van Herrewege, Yven Potters, Idzi Cisse, Badara Mboup, Souleymane Polman, Katja Bottieau, Emmanuel Evaluation of Artesunate-mefloquine as a Novel Alternative Treatment for Schistosomiasis in African Children (SchistoSAM): protocol of a proof-of-concept, open-label, two-arm, individually-randomised controlled trial |
title | Evaluation of Artesunate-mefloquine as a Novel Alternative Treatment for Schistosomiasis in African Children (SchistoSAM): protocol of a proof-of-concept, open-label, two-arm, individually-randomised controlled trial |
title_full | Evaluation of Artesunate-mefloquine as a Novel Alternative Treatment for Schistosomiasis in African Children (SchistoSAM): protocol of a proof-of-concept, open-label, two-arm, individually-randomised controlled trial |
title_fullStr | Evaluation of Artesunate-mefloquine as a Novel Alternative Treatment for Schistosomiasis in African Children (SchistoSAM): protocol of a proof-of-concept, open-label, two-arm, individually-randomised controlled trial |
title_full_unstemmed | Evaluation of Artesunate-mefloquine as a Novel Alternative Treatment for Schistosomiasis in African Children (SchistoSAM): protocol of a proof-of-concept, open-label, two-arm, individually-randomised controlled trial |
title_short | Evaluation of Artesunate-mefloquine as a Novel Alternative Treatment for Schistosomiasis in African Children (SchistoSAM): protocol of a proof-of-concept, open-label, two-arm, individually-randomised controlled trial |
title_sort | evaluation of artesunate-mefloquine as a novel alternative treatment for schistosomiasis in african children (schistosam): protocol of a proof-of-concept, open-label, two-arm, individually-randomised controlled trial |
topic | Infectious Diseases |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231067/ https://www.ncbi.nlm.nih.gov/pubmed/34168029 http://dx.doi.org/10.1136/bmjopen-2020-047147 |
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