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Ngodhe island, Kenya, presents a unique malaria profile, with lower <jats:italic>P. falciparum<\/jats:italic> incidence rates than the surrounding region, and a high proportion of sub-microscopic and low-density infections. Here, using custom dual-indexing and Illumina next generation sequencing, we generate resistance profiles on seventy asymptomatic and low-density <jats:italic>P. falciparum infections<\/jats:italic> from a mass drug administration program implemented on Ngodhe island between 2015 and 2016. Our assay encompasses established molecular markers on the <jats:italic>Pfcrt<\/jats:italic>,<jats:italic> Pfmdr1<\/jats:italic>,<jats:italic> Pfdhps<\/jats:italic>,<jats:italic> Pfdhfr<\/jats:italic>, and <jats:italic>Pfk13<\/jats:italic> genes. Resistance markers for sulfadoxine-pyrimethamine were identified at high frequencies, including a quintuple mutant haplotype (<jats:italic>Pfdhfr\/Pfdhps<\/jats:italic>: N51I, C59R, S108N\/A437G, K540E) identified in 62.2% of isolates. The <jats:italic>Pfdhps<\/jats:italic> K540E biomarker, used to inform decision making for intermittent preventative treatment in pregnancy, was identified in 79.2% of isolates. Several variants on <jats:italic>Pfmdr1<\/jats:italic>, associated with reduced susceptibility to quinolones and lumefantrine, were also identified (Y184F 47.1%; D1246Y 16.0%; N86 98%). Overall, we have presented a low-cost and extendable approach that can provide timely genetic profiles to inform clinical and surveillance activities, especially in settings with abundant low-density infections, seeking malaria elimination.<\/jats:p>","DOI":"10.1038\/s41598-023-38481-3","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T18:02:28Z","timestamp":1689357748000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Drug resistance profiling of asymptomatic and low-density Plasmodium falciparum malaria infections on Ngodhe island, Kenya, using custom dual-indexing next-generation sequencing"],"prefix":"10.1038","volume":"13","author":[{"given":"Ashley","family":"Osborne","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jody E.","family":"Phelan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wataru","family":"Kagaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chim","family":"Chan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mtakai","family":"Ngara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Kongere","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyoshi","family":"Kita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesse","family":"Gitaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana","family":"Campino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taane G.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,7,14]]},"reference":[{"key":"38481_CR1","doi-asserted-by":"publisher","DOI":"10.30875\/6c551ba0-en","volume-title":"World Malaria Report 2021","author":"World Health Organization","year":"2021","unstructured":"World Health Organization. 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