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However, artemisinin resistant parasites have recently emerged in South-East Asia. Novel intervention strategies are therefore urgently needed to maintain the current momentum for control and elimination of this disease. In the present study we characterize the phenotypic and genetic properties of the multi drug resistant (MDR) <jats:italic>P. falciparum<\/jats:italic> Thai C2A parasite strain in the non-human <jats:italic>Aotus<\/jats:italic> primate model, and across multiple passages. <jats:italic>Aotus<\/jats:italic> infections with C2A failed to clear upon oral artesunate and mefloquine treatment alone or in combination, and <jats:italic>ex vivo<\/jats:italic> drug assays demonstrated reduction in drug susceptibility profiles in later <jats:italic>Aotus<\/jats:italic> passages. Further analysis revealed mutations in the <jats:italic>pfcrt<\/jats:italic> and <jats:italic>pfdhfr<\/jats:italic> loci and increased parasite multiplication rate (PMR) across passages, despite elevated <jats:italic>pfmdr1<\/jats:italic> copy number. Altogether our experiments suggest alterations in parasite population structure and increased fitness during <jats:italic>Aotus<\/jats:italic> adaptation. We also present data of early treatment failures with an oral artemisinin combination therapy in a pre-artemisinin resistant <jats:italic>P. falciparum<\/jats:italic> Thai isolate in this animal model.<\/jats:p>","DOI":"10.1038\/srep21216","type":"journal-article","created":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T11:39:37Z","timestamp":1455622777000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Altered drug susceptibility during host adaptation of a Plasmodium falciparum strain in a non-human primate model"],"prefix":"10.1038","volume":"6","author":[{"given":"Nicanor","family":"Obald\u00eda III","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey S.","family":"Dow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Gerena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis","family":"Kyle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Otero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre-Yves","family":"Mantel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Baro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Daniels","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angana","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren M.","family":"Childs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Buckee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manoj T.","family":"Duraisingh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah K.","family":"Volkman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dyann F.","family":"Wirth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Marti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,2,16]]},"reference":[{"key":"BFsrep21216_CR1","doi-asserted-by":"publisher","first-page":"e1000406","DOI":"10.1371\/journal.pmed.1000406","volume":"8","author":"PL Alonso","year":"2011","unstructured":"Alonso, P. 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