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In Africa,\n                    <jats:italic>K13-<\/jats:italic>\n                    propeller genotyping confirms the emergence of the R561H mutation in Rwanda and highlights the continuing dominance of wild-type K13 elsewhere. Using gene editing, we show that R561H, along with C580Y and M579I, confer elevated in vitro ART resistance in some African strains, contrasting with minimal changes in ART susceptibility in others. C580Y and M579I cause substantial fitness costs, which may slow their dissemination in high-transmission settings, in contrast with R561H that in African 3D7 parasites is fitness neutral. In Cambodia,\n                    <jats:italic>K13<\/jats:italic>\n                    genotyping highlights the increasing spatio-temporal dominance of C580Y. Editing multiple K13 mutations into a panel of Southeast Asian strains reveals that only the R561H variant yields ART resistance comparable to C580Y. In Asian Dd2 parasites C580Y shows no fitness cost, in contrast with most other K13 mutations tested, including R561H. Editing of point mutations in\n                    <jats:italic>ferredoxin<\/jats:italic>\n                    or\n                    <jats:italic>mdr2<\/jats:italic>\n                    , earlier associated with resistance, has no impact on ART susceptibility or parasite fitness. These data underline the complex interplay between K13 mutations, parasite survival, growth and genetic background in contributing to the spread of ART resistance.\n                  <\/jats:p>","DOI":"10.7554\/elife.66277","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T08:00:34Z","timestamp":1626681634000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.66277","source":"Crossref","is-referenced-by-count":170,"title":["Plasmodium falciparum K13 mutations in Africa and Asia impact artemisinin resistance and parasite fitness"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9519-487X","authenticated-orcid":true,"given":"Barbara H","family":"Stokes","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish 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