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Simple assays to monitor parasite drug response in direct patient samples (<jats:italic>ex vivo<\/jats:italic>) can detect drug resistance before it becomes clinically apparent, and can inform changes in treatment policy to prevent the spread of resistance.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Parasite drug responses to amodiaquine, artemisinin, chloroquine and mefloquine were tested in approximately 400 <jats:italic>Plasmodium falciparum<\/jats:italic> malaria infections in Thi\u00e8s, Senegal between 2008 and 2011 using a DAPI-based <jats:italic>ex vivo<\/jats:italic> drug resistance assay. Drug resistance-associated mutations were also genotyped in <jats:italic>pfcrt<\/jats:italic> and <jats:italic>pfmdr1<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Parasite drug responses changed between 2008 and 2011, as parasites became less sensitive to amodiaquine, artemisinin and chloroquine over time. The prevalence of known resistance-associated mutations also changed over time. Decreased amodiaquine sensitivity was associated with sustained, highly prevalent mutations in <jats:italic>pfcrt<\/jats:italic>, and one mutation in <jats:italic>pfmdr1<\/jats:italic> \u2013 Y184F \u2013 was associated with decreased parasite sensitivity to artemisinin.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Directly measuring <jats:italic>ex vivo<\/jats:italic> parasite drug response and resistance mutation genotyping over time are useful tools for monitoring parasite drug responses in field samples. Furthermore, these data suggest that the use of amodiaquine and artemisinin derivatives in combination therapies is selecting for increased drug tolerance within this population.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1475-2875-12-441","type":"journal-article","created":{"date-parts":[[2013,12,6]],"date-time":"2013-12-06T22:01:12Z","timestamp":1386367272000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Changes in drug sensitivity and anti-malarial drug resistance mutations over time among Plasmodium falciparum parasites in Senegal"],"prefix":"10.1186","volume":"12","author":[{"given":"Daria","family":"Van Tyne","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baba","family":"Dieye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarissa","family":"Valim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel F","family":"Daniels","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Papa Diogoye","family":"S\u00e8ne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda K","family":"Lukens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mouhamadou","family":"Ndiaye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy K","family":"Bei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaye Die","family":"Ndiaye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth J","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar","family":"Ndir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Souleymane","family":"Mboup","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":"Daouda","family":"Ndiaye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,12,6]]},"reference":[{"key":"3041_CR1","doi-asserted-by":"publisher","first-page":"e1000406","DOI":"10.1371\/journal.pmed.1000406","volume":"8","author":"PL Alonso","year":"2011","unstructured":"Alonso PL, Brown G, Arevalo-Herrera M, Binka F, Chitnis C, Collins F, Doumbo OK, Greenwood B, Hall BF, Levine MM, Mendis K, Newman RD, Plowe CV, Rodriguez MH, Sinden R, Slutsker L, Tanner M: A research agenda to underpin malaria eradication. 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