{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T10:30:52Z","timestamp":1777631452229,"version":"3.51.4"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000200","name":"United States Agency for International Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000200","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Malar J"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antimalarial drug resistance leads to increased treatment failures, prolonged illness, and increased mortality. The World Health Organization (WHO) recommends malaria-endemic countries regularly (ideally biennially) assess the efficacy of commonly used antimalarials. An evaluation of Sierra Leone\u2019s first and second-line antimalarials assessed artemether-lumefantrine (AL) in three sentinel sites\u2014Bo, Bombali, and Kenema\u2014and artesunate-amodiaquine (ASAQ) in two sites\u2014Bo and Bombali. Children 6\u00a0months to 5\u00a0years old with uncomplicated malaria were enrolled in the 28\u00a0day in vivo efficacy study using the WHO-recommended protocols. Genotyping at three markers (msp1, msp2 and the PolyA microsatellite) and match counting using the WHO 3\/3 algorithm were used to distinguish recrudescence from new infection, PCR-uncorrected and corrected efficacy results were calculated, and molecular markers of antimalarial resistance were analyzed. Of 1777 children screened, 496 reached a study endpoint. Kaplan\u2013Meier uncorrected efficacy for AL was 89.5% (95%  CI 84\u201395%) in Bo, 96.1% (95%  CI 92\u2013100%) in Bombali, and 93.2% (95%  CI 89\u201398%) in Kenema; for ASAQ, estimates were 92.0% (95%  CI 86\u201398%) in Bo and 94.5% (95%  CI 90\u201399%) in Bombali. PCR-corrected Kaplan\u2013Meier efficacy was 100% in all AL arms, 100% for ASAQ in Bo, and 99.1% (95%  CI 97\u2013100%) for ASAQ in Bombali.<\/jats:p>\n                  <jats:p>\n                    New infections accounted for 72.7% (16\/22) and 63.6% (7\/11) of recurrent parasitemia in the AL and ASAQ arms, respectively. No validated or candidate Pfk13 mutations were detected, and while some\n                    <jats:italic>Pfmdr1<\/jats:italic>\n                    and\n                    <jats:italic>Pfcrt<\/jats:italic>\n                    polymorphisms were observed, no clear pattern of association with treatment failure was evident. Therefore, our study provides evidence that AL and ASAQ remain efficacious for treatment of\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    infection in Sierra Leone.\n                  <\/jats:p>","DOI":"10.1186\/s12936-026-05850-y","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T12:14:08Z","timestamp":1775736848000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) for the treatment of uncomplicated Plasmodium falciparum malaria among children 6\u201359\u00a0months in three sentinel sites of Sierra Leone, 2021\u20132022"],"prefix":"10.1186","volume":"25","author":[{"given":"Irene","family":"Cavros","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisca","family":"Abanyie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anitta Renitta Yokoe","family":"Kamara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fay","family":"Chalobah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelson","family":"Fofana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jehan","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwabena","family":"Larbi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Culzean","family":"Kennedy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Breanna","family":"Horton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marko","family":"Bajic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mashanika","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryce","family":"Matlock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"McCaffery","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santigie","family":"Kanu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Schnabel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Temitayo S. A.","family":"Labor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelby","family":"Cash","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mateusz","family":"Plucinski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James P.","family":"Komeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Musa","family":"Sillah-Kanu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"5850_CR1","unstructured":"World Malaria Report 2024. World Health Organization."},{"key":"5850_CR2","doi-asserted-by":"publisher","DOI":"10.1093\/jtm\/taad159","author":"ES Halsey","year":"2023","unstructured":"Halsey ES, Plucinski MM. Out of Africa: increasing reports of artemether-lumefantrine treatment failures of uncomplicated Plasmodium falciparum infection. J Travel Med. 2023. https:\/\/doi.org\/10.1093\/jtm\/taad159.","journal-title":"J Travel Med"},{"issue":"24","key":"5850_CR3","doi-asserted-by":"publisher","first-page":"2619","DOI":"10.1056\/NEJMc0805011","volume":"359","author":"H Noedl","year":"2008","unstructured":"Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM. Evidence of Artemisinin-resistant malaria in Western Cambodia. N Engl J Med. 2008;359(24):2619\u201320. https:\/\/doi.org\/10.1056\/NEJMc0805011.","journal-title":"N Engl J Med"},{"issue":"5","key":"5850_CR4","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1056\/NEJMoa0808859","volume":"361","author":"AM Dondorp","year":"2009","unstructured":"Dondorp AM, Nosten F, Yi P, et al. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009;361(5):455\u201367. https:\/\/doi.org\/10.1056\/NEJMoa0808859.","journal-title":"N Engl J Med"},{"issue":"5","key":"5850_CR5","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1056\/NEJMc0900231","volume":"361","author":"H Noedl","year":"2009","unstructured":"Noedl H, Socheat D, Satimai W. Artemisinin-resistant malaria in Asia. N Engl J Med. 2009;361(5):540\u20131. https:\/\/doi.org\/10.1056\/NEJMc0900231.","journal-title":"N Engl J Med"},{"issue":"8","key":"5850_CR6","doi-asserted-by":"publisher","first-page":"4719","DOI":"10.1128\/AAC.00835-15","volume":"59","author":"R Leang","year":"2015","unstructured":"Leang R, Taylor WRJ, Bouth DM, et al. Evidence of Plasmodium falciparum malaria multidrug resistance to Artemisinin and Piperaquine in Western Cambodia: Dihydroartemisinin-Piperaquine open-label multicenter clinical assessment. Antimicrob Agents Chemother. 2015;59(8):4719\u201326. https:\/\/doi.org\/10.1128\/AAC.00835-15.","journal-title":"Antimicrob Agents Chemother"},{"issue":"7481","key":"5850_CR7","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/nature12876","volume":"505","author":"F Ariey","year":"2014","unstructured":"Ariey F, Witkowski B, Amaratunga C, et al. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature. 2014;505(7481):50\u20135. https:\/\/doi.org\/10.1038\/nature12876.","journal-title":"Nature"},{"issue":"8","key":"5850_CR8","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1016\/S1473-3099(21)00142-0","volume":"21","author":"A Uwimana","year":"2021","unstructured":"Uwimana A, Umulisa N, Venkatesan M, et al. Association of Plasmodium falciparum kelch13 R561H genotypes with delayed parasite clearance in Rwanda: an open-label, single-arm, multicentre, therapeutic efficacy study. Lancet Infect Dis. 2021;21(8):1120\u20138. https:\/\/doi.org\/10.1016\/S1473-3099(21)00142-0.","journal-title":"Lancet Infect Dis"},{"issue":"13","key":"5850_CR9","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1056\/NEJMoa2101746","volume":"385","author":"B Balikagala","year":"2021","unstructured":"Balikagala B, Fukuda N, Ikeda M, et al. Evidence of Artemisinin-resistant malaria in Africa. N Engl J Med. 2021;385(13):1163\u201371. https:\/\/doi.org\/10.1056\/NEJMoa2101746.","journal-title":"N Engl J Med"},{"key":"5850_CR10","unstructured":"WHO. Methods for surveillance of antimalarial drug efficacy. 2009. https:\/\/www.who.int\/publications-detail-redirect\/9789241597531. Accessed 14 April 2024."},{"key":"5850_CR11","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.actatropica.2018.06.016","volume":"185","author":"SJ Smith","year":"2018","unstructured":"Smith SJ, Kamara ARY, Sahr F, et al. Efficacy of artemisinin-based combination therapies and prevalence of molecular markers associated with artemisinin, piperaquine and sulfadoxine-pyrimethamine resistance in Sierra Leone. Acta Trop. 2018;185:363\u201370. https:\/\/doi.org\/10.1016\/j.actatropica.2018.06.016.","journal-title":"Acta Trop"},{"key":"5850_CR12","unstructured":"National Malaria Control Programme, Statistics Sierra Leone, college of medicine and allied health services, University of Sierra Leone, Catholic relief services, ICF. Sierra Leone Malaria Indicator Survey, 2016. https:\/\/dhsprogram.com\/pubs\/pdf\/MIS25\/MIS25.pdf."},{"issue":"2","key":"5850_CR13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056677","volume":"8","author":"NW Lucchi","year":"2013","unstructured":"Lucchi NW, Narayanan J, Karell MA, et al. Molecular diagnosis of malaria by photo-induced electron transfer fluorogenic primers: PET-PCR. PLoS ONE. 2013;8(2):e56677. https:\/\/doi.org\/10.1371\/journal.pone.0056677.","journal-title":"PLoS ONE"},{"key":"5850_CR14","unstructured":"WHO. Methods and techniques for clinical trials on antimalarial drug efficacy: Genotyping to identify parasite populations. 2007. https:\/\/www.who.int\/publications-detail-redirect\/9789241596305. Accessed 14 April 2024."},{"key":"5850_CR15","unstructured":"MaRS Protocol. 2023. https:\/\/cdcgov.github.io\/MaRS\/."},{"issue":"4","key":"5850_CR16","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1056\/NEJM200101253440403","volume":"344","author":"A Djimd\u00e9","year":"2001","unstructured":"Djimd\u00e9 A, Kayentao K, Su XZ, Wellems TE. A molecular marker for chloroquine-resistant falciparum malaria. New Engl J Med. 2001;344(4):257\u201363.","journal-title":"New Engl J Med"},{"key":"5850_CR17","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1086\/322858","volume":"184","author":"TE Wellems","year":"2001","unstructured":"Wellems TE, Plowe CV. Chloroquine-resistant malaria. J Infect Dis. 2001;184:770\u20136.","journal-title":"J Infect Dis"},{"key":"5850_CR18","doi-asserted-by":"crossref","unstructured":"Sisowath C, Petersen I, Veiga MI, et al. In vivo selection of plasmodium falciparum parasites carrying the chloroquine-susceptible Pfcrt K76 allele after treatment with Artemether-Lumefantrine in Africa. 2009.","DOI":"10.1086\/596738"},{"issue":"9","key":"5850_CR19","doi-asserted-by":"publisher","first-page":"3714","DOI":"10.1128\/AAC.00358-10","volume":"54","author":"K Beshir","year":"2010","unstructured":"Beshir K, Sutherland CJ, Merinopoulos I, Durrani N, Leslie T, Rowland M, et al. Amodiaquine resistance in Plasmodium falciparum malaria in Afghanistan is associated with the pfcrt SVMNT allele at codons 72 to 76. Antimicrob Agents Chemother. 2010;54(9):3714\u20136.","journal-title":"Antimicrob Agents Chemother"},{"issue":"4","key":"5850_CR20","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.meegid.2005.09.001","volume":"6","author":"G Holmgren","year":"2006","unstructured":"Holmgren G, Gil JP, Ferreira PM, Veiga MI, Obonyo CO, Bj\u00f6rkman A. Amodiaquine resistant Plasmodium falciparum malaria in vivo is associated with selection of pfcrt 76T and pfmdr1 86Y. Infect Genet Evol. 2006;6(4):309\u201314. https:\/\/doi.org\/10.1016\/j.meegid.2005.09.001.","journal-title":"Infect Genet Evol"},{"key":"5850_CR21","unstructured":"National Malaria Control Programme. Guidelines for case management of malaria. 2015."},{"key":"5850_CR22","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-018-2370-x","author":"K Banek","year":"2018","unstructured":"Banek K, Webb EL, Smith SJ, Chandramohan D, Staedke SG. Adherence to treatment with artemether\u2013lumefantrine or amodiaquine\u2013artesunate for uncomplicated malaria in children in Sierra Leone: a randomized trial. Malar J. 2018. https:\/\/doi.org\/10.1186\/s12936-018-2370-x.","journal-title":"Malar J"},{"key":"5850_CR23","unstructured":"Global Malaria Programme. Multiple first-line therapies as part of the response to antimalarial drug resistance: an implementation guide. World Health Organization; 2024."},{"key":"5850_CR24","unstructured":"Community Health Worker Hub. National Community Health Worker Policy, 2021."}],"container-title":["Malaria Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12936-026-05850-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-026-05850-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-026-05850-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:32:02Z","timestamp":1777433522000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12936-026-05850-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,9]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["5850"],"URL":"https:\/\/doi.org\/10.1186\/s12936-026-05850-y","relation":{},"ISSN":["1475-2875"],"issn-type":[{"value":"1475-2875","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,9]]},"assertion":[{"value":"21 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All co-authors consent for publication of the included results.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"182"}}