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

• Published in: Malaria Journal
• Main Authors: 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
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2021
• Subjects: Madagascar; Anti-malarial; Artemisinin-based combination therapy; Resistance; Efficacy; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/s12936-021-03935-4; https://doaj.org/article/df32110b281d46a280c7dd012b62afec

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 ...