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This study assessed the efficacy of these artemisinin-based combinations, proportion of day 3 positive patients, proportions of molecular markers associated with <jats:italic>P. falciparum<\/jats:italic> resistance to anti-malarial drugs and variable performance of HRP2-based malaria rapid diagnostic tests (RDTs).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A single-arm prospective study assessing the efficacy of AS\u2013AQ and AL at three sites (Doba, Kelo and Koyom) was conducted between November 2020 to January 2021. Febrile children aged 6 to 59\u00a0months with confirmed uncomplicated <jats:italic>P. falciparum<\/jats:italic> infection were enrolled sequentially first to AS\u2013AQ and then AL at each site and followed up for 28\u00a0days. The primary endpoint was PCR-adjusted adequate clinical and parasitological response (ACPR). Samples collected on day 0 were analysed for mutations in <jats:italic>pfkelch13<\/jats:italic>, <jats:italic>pfcrt<\/jats:italic>, <jats:italic>pfmdr-1<\/jats:italic>, <jats:italic>pfdhfr, pfdhps<\/jats:italic> genes and deletions in <jats:italic>pfhrp2\/pfhrp3<\/jats:italic> genes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>By the end of 28-day follow-up, per-protocol PCR corrected ACPR of 97.8% (CI 95% 88.2\u2013100) in Kelo and 100% in Doba and Kayoma were observed among AL treated patients. For ASAQ, 100% ACPR was found in all sites. All, but one patient, did not have parasites detected on day 3. Out of the 215\u00a0day 0 samples, 96.7% showed <jats:italic>pfkelch13<\/jats:italic> wild type allele. Seven isolates carried nonsynonymous mutations not known to be associated artemisinin partial resistance (ART-R). Most of samples had a <jats:italic>pfcrt<\/jats:italic> wild type allele (79% to 89%). The most prevalent <jats:italic>pfmdr-1<\/jats:italic> allele detected was the single mutant 184F (51.2%). For <jats:italic>pfdhfr<\/jats:italic> and <jats:italic>pfdhps<\/jats:italic> mutations, the quintuple mutant allele N51I\/C59R\/S108N\u2009+\u2009G437A\/540E responsible for SP treatment failures in adults and children was not detected. Single deletion in the <jats:italic>pfhrp2<\/jats:italic> and <jats:italic>pfhrp3<\/jats:italic> gene were detected in 10\/215 (4.7%) and 2\/215 (0.9%), respectively. Dual <jats:italic>pfhrp2\/pfhrp3<\/jats:italic> deletions, potentially threatening the efficacy of HRP2-based RDTs, were observed in 5\/215 (2.3%) isolates.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The results of this study confirm that AS\u2013AQ and AL treatments are highly efficacious in study areas in Chad. The absence of known <jats:italic>pfkelch13<\/jats:italic> mutations in the study sites and the high parasite clearance rate at day 3 suggest the absence of ART-R. The absence of <jats:italic>pfdhfr\/pfdhps<\/jats:italic> quintuple or sextuple (quintuple\u2009+\u2009581G) mutant supports the continued use of SP for IPTp during pregnancy. The presence of parasites with dual <jats:italic>pfhrp2\/pfhrp3<\/jats:italic> deletions, potentially threatening the efficacy of HRP2-based RDTs, warrants the continued surveillance.<\/jats:p>\n                <jats:p><jats:italic>Trial registration<\/jats:italic> ACTRN12622001476729<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12936-023-04644-w","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T10:03:03Z","timestamp":1692784983000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Therapeutic efficacy of artesunate\u2013amodiaquine and artemether\u2013lumefantrine for the treatment of uncomplicated falciparum malaria in Chad: clinical and genetic surveillance"],"prefix":"10.1186","volume":"22","clinical-trial-number":[{"clinical-trial-number":"actrn12622001476729","registry":"10.18810\/anzctr"}],"author":[{"given":"Mahamat Souleymane","family":"Issa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Warsame","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moussa Hassane Taisso","family":"Mahamat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issakha Diar Mahamat","family":"Saleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kodbsse","family":"Boulotigam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honor\u00e9","family":"Djimrassengar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Haggar","family":"Issa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ousmane","family":"Abdelkader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manah","family":"Hassoumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mbanga","family":"Djimadoum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Doderer-Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Bosco","family":"Ndihiokubwayo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Rasmussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Menard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,23]]},"reference":[{"key":"4644_CR1","volume-title":"Guidelines for malaria","author":"WHO","year":"2023","unstructured":"WHO. 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