{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:44:46Z","timestamp":1790239486632,"version":"4.1.0"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The emergence and spread of artemisinin-resistant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium falciparum<\/jats:named-content>\n            is of huge concern for the global effort toward malaria control and elimination. Artemisinin resistance, defined as a delayed time to parasite clearance following administration of artemisinin, is associated with mutations in the\n            <jats:italic>Pfkelch13<\/jats:italic>\n            gene of resistant parasites. To date, as many as 60 nonsynonymous mutations have been identified in this gene, but whether these mutations have been selected by artemisinin usage or merely reflect natural polymorphism independent of selection is currently unknown. To clarify this, we sequenced the\n            <jats:italic>Pfkelch13<\/jats:italic>\n            propeller domain in 581 isolates collected before (420 isolates) and after (161 isolates) the implementation of artemisinin combination therapies (ACTs), from various regions of endemicity worldwide. Nonsynonymous mutations were observed in 1% of parasites isolated prior to the introduction of ACTs. Frequencies of mutant isolates, nucleotide diversity, and haplotype diversity were significantly higher in the parasites isolated from populations exposed to artemisinin than in those from populations that had not been exposed to the drug. In the artemisinin-exposed population, a significant excess of dN compared to dS was observed, suggesting the presence of positive selection. In contrast, pairwise comparison of dN and dS and the McDonald and Kreitman test indicate that purifying selection acts on the\n            <jats:italic>Pfkelch13<\/jats:italic>\n            propeller domain in populations not exposed to ACTs. These population genetic analyses reveal a low baseline of\n            <jats:italic>Pfkelch13<\/jats:italic>\n            polymorphism, probably due to purifying selection in the absence of artemisinin selection. In contrast, various\n            <jats:italic>Pfkelch13<\/jats:italic>\n            mutations have been selected under artemisinin pressure.\n          <\/jats:p>","DOI":"10.1128\/aac.02370-15","type":"journal-article","created":{"date-parts":[[2016,3,22]],"date-time":"2016-03-22T03:45:36Z","timestamp":1458618336000},"page":"3340-3347","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["Little Polymorphism at the K13 Propeller Locus in Worldwide Plasmodium falciparum Populations Prior to the Introduction of Artemisinin Combination Therapies"],"prefix":"10.1128","volume":"60","author":[{"given":"Toshihiro","family":"Mita","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, Tokyo, Japan"},{"name":"Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Culleton","sequence":"additional","affiliation":[{"name":"Malaria Unit, Department of Pathology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine and Parasitology, Dokkyo Medical University, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Tsukahara","sequence":"additional","affiliation":[{"name":"Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University, Tokyo, 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Myanmar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aung S.","family":"Marma","sequence":"additional","affiliation":[{"name":"Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lek","family":"Dysoley","sequence":"additional","affiliation":[{"name":"Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Ndounga","sequence":"additional","affiliation":[{"name":"Laboratoire de Pharmacologie, Centre d'Etudes sur les Ressources Vegetales, Brazzaville, Republic of Congo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mawuli","family":"Dzodzomenyo","sequence":"additional","affiliation":[{"name":"Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University, Tokyo, 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