Clinical evidence of Kelch13-dependent and -independent malaria treatment failure with Artemether-Lumefantrine

Clinical evidence of Kelch13-dependent and -independent malaria treatment failure with Artemether-Lumefantrine | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Clinical evidence of Kelch13-dependent and -independent malaria treatment failure with Artemether-Lumefantrine Jacob Souopgui, Sandra Fankem, Jean-Bosco Mbonimpa, Edgar Kalimba, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6958044/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Malaria remains a major public health threat, particularly in sub-Saharan Africa. In Rwanda, Artemether-Lumefantrine (AL; Coartem) has been the primary treatment for uncomplicated malaria, though its efficacy is increasingly in question. Using clinical data and Plasmodium biobanks from King Faisal Hospital Kigali, we analyzed 23 selected samples from patient with recurrent malaria. Genotyping confirmed recrudescence rather than reinfection. Following the initial AL treatment, 56.5% (microscopy) and 83.3% (qPCR) remained positive, with symptoms persisting. After a second treatment, positivity declined but was still notable. Sequencing analysis revealed widespread MDR1 Y184F mutations and cumulative Pfkelch13 mutations, including H384R in the BTB/POZ domain, associated with treatment failure. Four failing strains lacked kelch13 mutations, indicating alternative resistance mechanisms. These findings support the need for expanded genetic surveillance to preserve ACT efficacy. Health sciences/Diseases/Infectious diseases/Malaria Biological sciences/Genetics/Genotype/Haplotypes Full Text Additional Declarations There is NO Competing Interest. Supplementary Files supplementaryfigureFankemNS.pdf Figure S1, Figure S2, Figure S3, Figure S4, Table S1, Table S2 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6958044","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":490419008,"identity":"4e3bc6f2-edc8-4734-8cee-8d6f2fd9ae1b","order_by":0,"name":"Jacob Souopgui","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIiWNgGAWjYBAC9gYGBmYGhjoo18CGgU+CgQ2vFkaIlsMwLWkMbERqOQDjHyZCS/vhh48LGA7IGRzvPfyap+B8Ypt0A9uDD/i09KQZG89gqDM2OHMuzZrH4HZim8wBdsMZeB2WwybNw8CcuOFGjpkxWItEAkgEj5b+NyhazkG0/MGjRXAGwhbjxzwGByBa8HlfWuIZ0C8Gh40lgX5hnGOQbNwmc7DdsAePFj7+ZGCIVdTJ8QFD7MObP3ay/dLNxx78wGcNGBiACB5gjED810BQAxTwMOOLjVEwCkbBKBjBAADVFUh1aeu7VwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-1526-4431","institution":"Universite Libre de Bruxelles - 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