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Ethiopia, once a success story in case reduction, is now experiencing a resurgence. Here we examine key drug resistance genes (\n                    <jats:italic>Pfmdr1<\/jats:italic>\n                    ,\n                    <jats:italic>Pfcrt<\/jats:italic>\n                    ,\n                    <jats:italic>Pfk13<\/jats:italic>\n                    ,\n                    <jats:italic>Pfdhfr<\/jats:italic>\n                    and\n                    <jats:italic>Pfdhps<\/jats:italic>\n                    ) and mitochondrial genomes from 605\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    isolates collected across 15 districts in Ethiopia with varying transmission intensity and\n                    <jats:italic>Plasmodium vivax<\/jats:italic>\n                    co-endemicity. Although chloroquine was withdrawn for\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    long ago, it remains the first-line treatment for\n                    <jats:italic>P. vivax<\/jats:italic>\n                    ; this overlapping use may shape selection pressure in co-endemic settings that influences resistance markers to artemether\u2013lumefantrine, the current first-line therapy for\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    . A dominant\n                    <jats:italic>Pf<\/jats:italic>\n                    MDR1 NFSND haplotype, associated with reduced lumefantrine susceptibility, was identified alongside near fixation of the chloroquine-resistant\n                    <jats:italic>Pf<\/jats:italic>\n                    CRT CVIET haplotype in specific areas. Concerningly,\n                    <jats:italic>Pf<\/jats:italic>\n                    K13 variants associated with partial artemisinin resistance, R622I (10%), A675V (1.7%) and P441L (1.1%), were expanding. Multilevel models demonstrated robust, independent associations of R622I with\n                    <jats:italic>Pf<\/jats:italic>\n                    CRT CVIET and\n                    <jats:italic>Pf<\/jats:italic>\n                    DHFR AICNI, while ecological predictors were weaker and less consistent. These findings highlight genetic co-occurrence of\n                    <jats:italic>Pfcrt<\/jats:italic>\n                    and\n                    <jats:italic>Pfk13<\/jats:italic>\n                    mutations in\n                    <jats:italic>P. vivax<\/jats:italic>\n                    \u2013\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    co-endemic settings and can inform antimalarial policy in Ethiopia.\n                  <\/jats:p>","DOI":"10.1038\/s41564-026-02420-5","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:01:21Z","timestamp":1785920481000},"page":"2577-2588","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genomic surveillance reveals co-occurrence of Plasmodium falciparum drug resistance variants across diverse transmission settings in 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