Efficacy of artesunate-amodiaquine and artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Madagascar, 2018

Abstract Background Since 2005, artemisinin-based combination therapy (ACT) has been recommended to treat uncomplicated falciparum malaria in Madagascar. Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the first- and second-line treatments, respectively. A therapeutic efficacy stu...

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Autores principales:	Catherine M. Dentinger, Tovonahary Angelo Rakotomanga, Antsa Rakotondrandriana, Arinomenjanahary Rakotoarisoa, Marie Ange Rason, Leah F. Moriarty, Laura C. Steinhardt, Laurent Kapesa, Jocelyn Razafindrakoto, Samaly S. Svigel, Naomi W. Lucchi, Venkatachalam Udhayakumar, Eric S. Halsey, C. Arsène Ratsimbasoa
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Madagascar Anti-malarial Artemisinin-based combination therapy Resistance Efficacy Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/df32110b281d46a280c7dd012b62afec
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spelling	oai:doaj.org-article:df32110b281d46a280c7dd012b62afec2021-11-08T11:05:19ZEfficacy of artesunate-amodiaquine and artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Madagascar, 201810.1186/s12936-021-03935-41475-2875https://doaj.org/article/df32110b281d46a280c7dd012b62afec2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12936-021-03935-4https://doaj.org/toc/1475-2875Abstract Background Since 2005, artemisinin-based combination therapy (ACT) has been recommended to treat uncomplicated falciparum malaria in Madagascar. Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the first- and second-line treatments, respectively. A therapeutic efficacy study was conducted to assess ACT efficacy and molecular markers of anti-malarial resistance. Methods Children aged six months to 14 years with uncomplicated falciparum malaria and a parasitaemia of 1000–100,000 parasites/µl determined by microscopy were enrolled from May–September 2018 in a 28-day in vivo trial using the 2009 World Health Organization protocol for monitoring anti-malarial efficacy. Participants from two communes, Ankazomborona (tropical, northwest) and Matanga (equatorial, southeast), were randomly assigned to ASAQ or AL arms at their respective sites. PCR correction was achieved by genotyping seven neutral microsatellites in paired pre- and post-treatment samples. Genotyping assays for molecular markers of resistance in the pfk13, pfcrt and pfmdr1 genes were conducted. Results Of 344 patients enrolled, 167/172 (97%) receiving ASAQ and 168/172 (98%) receiving AL completed the study. For ASAQ, the day-28 cumulative PCR-uncorrected efficacy was 100% (95% CI 100–100) and 95% (95% CI 91–100) for Ankazomborona and Matanga, respectively; for AL, it was 99% (95% CI 97–100) in Ankazomborona and 83% (95% CI 76–92) in Matanga. The day-28 cumulative PCR-corrected efficacy for ASAQ was 100% (95% CI 100–100) and 98% (95% CI 95–100) for Ankazomborona and Matanga, respectively; for AL, it was 100% (95% CI 99–100) in Ankazomborona and 95% (95% CI 91–100) in Matanga. Of 83 successfully sequenced samples for pfk13, no mutation associated with artemisinin resistance was observed. A majority of successfully sequenced samples for pfmdr1 carried either the NFD or NYD haplotypes corresponding to codons 86, 184 and 1246. Of 82 successfully sequenced samples for pfcrt, all were wild type at codons 72–76. Conclusion PCR-corrected analysis indicated that ASAQ and AL have therapeutic efficacies above the 90% WHO acceptable cut-off. No genetic evidence of resistance to artemisinin was observed, which is consistent with the clinical outcome data. However, the most common pfmdr1 haplotypes were NYD and NFD, previously associated with tolerance to lumefantrine.Catherine M. DentingerTovonahary Angelo RakotomangaAntsa RakotondrandrianaArinomenjanahary RakotoarisoaMarie Ange RasonLeah F. MoriartyLaura C. SteinhardtLaurent KapesaJocelyn RazafindrakotoSamaly S. SvigelNaomi W. LucchiVenkatachalam UdhayakumarEric S. HalseyC. Arsène RatsimbasoaBMCarticleMadagascarAnti-malarialArtemisinin-based combination therapyResistanceEfficacyArctic medicine. Tropical medicineRC955-962Infectious and parasitic diseasesRC109-216ENMalaria Journal, Vol 20, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Madagascar Anti-malarial Artemisinin-based combination therapy Resistance Efficacy Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216
spellingShingle	Madagascar Anti-malarial Artemisinin-based combination therapy Resistance Efficacy Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Catherine M. Dentinger Tovonahary Angelo Rakotomanga Antsa Rakotondrandriana Arinomenjanahary Rakotoarisoa Marie Ange Rason Leah F. Moriarty Laura C. Steinhardt Laurent Kapesa Jocelyn Razafindrakoto Samaly S. Svigel Naomi W. Lucchi Venkatachalam Udhayakumar Eric S. Halsey C. Arsène Ratsimbasoa Efficacy of artesunate-amodiaquine and artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Madagascar, 2018
description	Abstract Background Since 2005, artemisinin-based combination therapy (ACT) has been recommended to treat uncomplicated falciparum malaria in Madagascar. Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the first- and second-line treatments, respectively. A therapeutic efficacy study was conducted to assess ACT efficacy and molecular markers of anti-malarial resistance. Methods Children aged six months to 14 years with uncomplicated falciparum malaria and a parasitaemia of 1000–100,000 parasites/µl determined by microscopy were enrolled from May–September 2018 in a 28-day in vivo trial using the 2009 World Health Organization protocol for monitoring anti-malarial efficacy. Participants from two communes, Ankazomborona (tropical, northwest) and Matanga (equatorial, southeast), were randomly assigned to ASAQ or AL arms at their respective sites. PCR correction was achieved by genotyping seven neutral microsatellites in paired pre- and post-treatment samples. Genotyping assays for molecular markers of resistance in the pfk13, pfcrt and pfmdr1 genes were conducted. Results Of 344 patients enrolled, 167/172 (97%) receiving ASAQ and 168/172 (98%) receiving AL completed the study. For ASAQ, the day-28 cumulative PCR-uncorrected efficacy was 100% (95% CI 100–100) and 95% (95% CI 91–100) for Ankazomborona and Matanga, respectively; for AL, it was 99% (95% CI 97–100) in Ankazomborona and 83% (95% CI 76–92) in Matanga. The day-28 cumulative PCR-corrected efficacy for ASAQ was 100% (95% CI 100–100) and 98% (95% CI 95–100) for Ankazomborona and Matanga, respectively; for AL, it was 100% (95% CI 99–100) in Ankazomborona and 95% (95% CI 91–100) in Matanga. Of 83 successfully sequenced samples for pfk13, no mutation associated with artemisinin resistance was observed. A majority of successfully sequenced samples for pfmdr1 carried either the NFD or NYD haplotypes corresponding to codons 86, 184 and 1246. Of 82 successfully sequenced samples for pfcrt, all were wild type at codons 72–76. Conclusion PCR-corrected analysis indicated that ASAQ and AL have therapeutic efficacies above the 90% WHO acceptable cut-off. No genetic evidence of resistance to artemisinin was observed, which is consistent with the clinical outcome data. However, the most common pfmdr1 haplotypes were NYD and NFD, previously associated with tolerance to lumefantrine.
format	article
author	Catherine M. Dentinger Tovonahary Angelo Rakotomanga Antsa Rakotondrandriana Arinomenjanahary Rakotoarisoa Marie Ange Rason Leah F. Moriarty Laura C. Steinhardt Laurent Kapesa Jocelyn Razafindrakoto Samaly S. Svigel Naomi W. Lucchi Venkatachalam Udhayakumar Eric S. Halsey C. Arsène Ratsimbasoa
author_facet	Catherine M. Dentinger Tovonahary Angelo Rakotomanga Antsa Rakotondrandriana Arinomenjanahary Rakotoarisoa Marie Ange Rason Leah F. Moriarty Laura C. Steinhardt Laurent Kapesa Jocelyn Razafindrakoto Samaly S. Svigel Naomi W. Lucchi Venkatachalam Udhayakumar Eric S. Halsey C. Arsène Ratsimbasoa
author_sort	Catherine M. Dentinger
title	Efficacy of artesunate-amodiaquine and artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Madagascar, 2018
title_short	Efficacy of artesunate-amodiaquine and artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Madagascar, 2018
title_full	Efficacy of artesunate-amodiaquine and artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Madagascar, 2018
title_fullStr	Efficacy of artesunate-amodiaquine and artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Madagascar, 2018
title_full_unstemmed	Efficacy of artesunate-amodiaquine and artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Madagascar, 2018
title_sort	efficacy of artesunate-amodiaquine and artemether-lumefantrine for uncomplicated plasmodium falciparum malaria in madagascar, 2018
publisher	BMC
publishDate	2021
url	https://doaj.org/article/df32110b281d46a280c7dd012b62afec
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Efficacy of artesunate-amodiaquine and artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Madagascar, 2018

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