{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T01:49:05Z","timestamp":1789004945399,"version":"build-2803163510"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["CSA 2020NOE-3102"],"award-info":[{"award-number":["CSA 2020NOE-3102"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH","award":["R01AI177791"],"award-info":[{"award-number":["R01AI177791"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The rise of antimalarial drug-resistant\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    threatens malaria elimination efforts. Mutations in the gene\n                    <jats:italic>kelch13<\/jats:italic>\n                    (\n                    <jats:italic>k13<\/jats:italic>\n                    ) confer artemisinin partial resistance (ART-R), compromising the efficacy of frontline artemisinin-based combination therapies (ACTs). The validated mutation\n                    <jats:italic>k13<\/jats:italic>\n                    R622I has emerged and expanded rapidly in the Horn of Africa. We conducted a year-long genomic surveillance study in Gondar Zuria and Tach Armachiho, two ecologically distinct districts in northwestern Ethiopia where R622I was first identified. A total of 903\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    infections were sequenced using molecular inversion probe (MIP) panels targeting major drug resistance mutations and genome-wide informative SNPs. The R622I mutation was found in 44.3% of samples, more frequent in Gondar Zuria than Tach Armachiho (52% vs. 35%;\n                    <jats:italic>p\u2009&lt;\u20090.001<\/jats:italic>\n                    ), and persisted year-round in nearly all sites, indicating stable transmission with minimal seasonal variation. Histidine-rich protein 2 (HRP2) based rapid diagnostic test (RDT) negativity was also prevalent (39.3%), with significant district-level variation (48.7% vs. 27.6%;\n                    <jats:italic>p\u2009&lt;\u20090.001<\/jats:italic>\n                    ). Concerningly, R622I and HRP2-RDT co-occured in 22% of samples, higher in Gondar Zuria than in Tach Armachiho (28.9% vs. 12.9%;\n                    <jats:italic>p\u2009&lt;\u20090.00<\/jats:italic>\n                    1). Overall, HRP2-RDT negativity was significantly more common among R622I mutant parasites than wild-type (48.3% vs. 30.7%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). The\n                    <jats:italic>k13<\/jats:italic>\n                    C580Y mutation was also detected at very low frequency (0.4%) in Gondar Zuria, representing the first report of this mutation in the Horn of Africa. Long-read whole-genome sequencing showed\n                    <jats:italic>k13<\/jats:italic>\n                    flanking haplotypes of C580Y isolates were distinct from Southeast Asian lineages, suggesting a local,\n                    <jats:italic>de novo<\/jats:italic>\n                    emergence of African origin. These findings highlight the increasing prevalence and types of ART-R mutations, persistence of\n                    <jats:italic>k13<\/jats:italic>\n                    R622I and its increasing association with HRP2-RDT negativity, representing a double threat to malaria control and elimination efforts.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013771","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T18:35:29Z","timestamp":1765478129000},"page":"e1013771","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["High prevalence and emerging positive association of kelch13 R622I and HRP2-based RDT negativity in Plasmodium falciparum in northern Ethiopia"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9640-4784","authenticated-orcid":true,"given":"Ayalew Jejaw","family":"Zeleke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abebe A.","family":"Fola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"Tollefson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karamako","family":"Niar\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alec","family":"Leonetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Om","family":"Taropawala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Marglous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Crudale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bokretsion G.","family":"Brhane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashenafi","family":"Assefa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patience","family":"Kiyuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan B.","family":"Parr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asrat","family":"Hailu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mulugeta Aemero","family":"Tegegne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6899-8204","authenticated-orcid":true,"given":"Jeffrey A.","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"ppat.1013771.ref001"},{"key":"ppat.1013771.ref002","doi-asserted-by":"crossref","DOI":"10.4269\/ajtmh.2007.77.181","volume-title":"Artemisinin-based combination treatment of falciparum malaria","author":"F Nosten","year":"2007"},{"key":"ppat.1013771.ref003","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12936-015-1075-7","article-title":"Assessing the potential impact of artemisinin and partner drug resistance in sub-Saharan Africa","volume":"15","author":"HC Slater","year":"2016","journal-title":"Malar J"},{"issue":"8","key":"ppat.1013771.ref004","doi-asserted-by":"crossref","DOI":"10.1093\/jtm\/taad159","article-title":"Out of Africa: increasing reports of artemether-lumefantrine treatment failures of uncomplicated Plasmodium falciparum 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