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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-11-01
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| Series: | Malaria Journal |
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| Online Access: | https://doi.org/10.1186/s12936-021-03935-4 |
| _version_ | 1819041067028185088 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T09:19:06Z |
| format | Article |
| id | doaj.art-df32110b281d46a280c7dd012b62afec |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-21T09:19:06Z |
| publishDate | 2021-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-df32110b281d46a280c7dd012b62afec2022-12-21T19:09:04ZengBMCMalaria Journal1475-28752021-11-0120111110.1186/s12936-021-03935-4Efficacy of artesunate-amodiaquine and artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Madagascar, 2018Catherine M. Dentinger0Tovonahary Angelo Rakotomanga1Antsa Rakotondrandriana2Arinomenjanahary Rakotoarisoa3Marie Ange Rason4Leah F. Moriarty5Laura C. Steinhardt6Laurent Kapesa7Jocelyn Razafindrakoto8Samaly S. Svigel9Naomi W. Lucchi10Venkatachalam Udhayakumar11Eric S. Halsey12C. Arsène Ratsimbasoa13Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, US Centers for Disease Control and PreventionNational Malaria Control Programme, Ministry of HealthNational Malaria Control Programme, Ministry of HealthNational Malaria Control Programme, Ministry of HealthNational Malaria Control Programme, Ministry of HealthMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, US Centers for Disease Control and PreventionMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, US Centers for Disease Control and PreventionUS President’s Malaria Initiative, USAIDUS President’s Malaria Initiative, USAIDMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, US Centers for Disease Control and PreventionMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, US Centers for Disease Control and PreventionMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, US Centers for Disease Control and PreventionMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, US Centers for Disease Control and PreventionNational Malaria Control Programme, Ministry of HealthAbstract 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.https://doi.org/10.1186/s12936-021-03935-4MadagascarAnti-malarialArtemisinin-based combination therapyResistanceEfficacy |
| spellingShingle | 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 Malaria Journal Madagascar Anti-malarial Artemisinin-based combination therapy Resistance Efficacy |
| title | 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_short | 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 |
| topic | Madagascar Anti-malarial Artemisinin-based combination therapy Resistance Efficacy |
| url | https://doi.org/10.1186/s12936-021-03935-4 |
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