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We assessed the association of\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            polymorphisms and\n            <jats:italic>ex vivo<\/jats:italic>\n            drug susceptibility with clinical effectiveness. Patients enrolled in an effectiveness trial comparing artemether-lumefantrine (\n            <jats:italic>n<\/jats:italic>\n            = 96), fixed-dose artesunate-amodiaquine (\n            <jats:italic>n<\/jats:italic>\n            = 96), and sulfadoxine-pyrimethamine (\n            <jats:italic>n<\/jats:italic>\n            = 48) for the treatment of uncomplicated malaria 2007 in Benin were assessed.\n            <jats:italic>pfcrt<\/jats:italic>\n            ,\n            <jats:italic>pfmdr1<\/jats:italic>\n            ,\n            <jats:italic>pfmrp1<\/jats:italic>\n            ,\n            <jats:italic>pfdhfr<\/jats:italic>\n            , and\n            <jats:italic>pfdhps<\/jats:italic>\n            polymorphisms were analyzed pretreatment and in recurrent infections. Drug susceptibility was determined in fresh baseline isolates by\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium<\/jats:named-content>\n            lactate dehydrogenase enzyme-linked immunosorbent assay (ELISA). A majority had 50% inhibitory concentration (IC\n            <jats:sub>50<\/jats:sub>\n            ) estimates (the concentration required for 50% growth inhibition) lower than those of the 3D7 reference clone for desethylamodiaquine, lumefantrine, mefloquine, and quinine and was considered to be susceptible, while dihydroartemisinin and pyrimethamine IC\n            <jats:sub>50<\/jats:sub>\n            s were higher. No association was found between susceptibility to the ACT compounds and treatment outcome. Selection was observed for the\n            <jats:italic>pfmdr1<\/jats:italic>\n            N86 allele in artemether-lumefantrine recrudescences (recurring infections) (4\/7 [57.1%] versus 36\/195 [18.5%]), and of the opposite allele, 86Y, in artesunate-amodiaquine reinfections (new infections) (20\/22 [90.9%] versus 137\/195 [70.3%]) compared to baseline infections. The importance of\n            <jats:italic>pfmdr1<\/jats:italic>\n            N86 in lumefantrine tolerance was emphasized by its association with elevated lumefantrine IC\n            <jats:sub>50<\/jats:sub>\n            s. Genetic linkage between N86 and Y184 was observed, which together with the low frequency of 1246Y may explain regional differences in selection of\n            <jats:italic>pfmdr1<\/jats:italic>\n            loci. Selection of opposite alleles in artemether-lumefantrine and artesunate-amodiaquine recurrent infections supports the strategy of multiple first-line treatment. Surveillance based on clinical,\n            <jats:italic>ex vivo<\/jats:italic>\n            , molecular, and pharmacological data is warranted.\n          <\/jats:p>","DOI":"10.1128\/aac.01790-12","type":"journal-article","created":{"date-parts":[[2013,10,8]],"date-time":"2013-10-08T03:08:58Z","timestamp":1381201738000},"page":"1-10","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["Plasmodium falciparum Polymorphisms Associated with\n            <i>Ex Vivo<\/i>\n            Drug Susceptibility and Clinical Effectiveness of Artemisinin-Based Combination Therapies in Benin"],"prefix":"10.1128","volume":"58","author":[{"given":"Sabina","family":"Dahlstr\u00f6m","sequence":"first","affiliation":[{"name":"Institut de M\u00e9decine et d'Epid\u00e9miologie Appliqu\u00e9e, Bichat-C. Bernard Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Aubouy","sequence":"additional","affiliation":[{"name":"Institut de Recherche pour le D\u00e9veloppement (IRD), UMR 216 Mother and Child Face to Tropical Infections Research Unit, Paris, France"},{"name":"PRES Paris Sorbonne Cit\u00e9, Paris Descartes University, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oumou","family":"Ma\u00efga-Ascofar\u00e9","sequence":"additional","affiliation":[{"name":"Institut de M\u00e9decine et d'Epid\u00e9miologie Appliqu\u00e9e, Bichat-C. Bernard Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Faucher","sequence":"additional","affiliation":[{"name":"Institut de Recherche pour le D\u00e9veloppement (IRD), UMR 216 Mother and Child Face to Tropical Infections Research Unit, Paris, France"},{"name":"PRES Paris Sorbonne Cit\u00e9, Paris Descartes University, Paris, France"},{"name":"Department of Infectious Diseases, Besan\u00e7on University Medical Center, H\u00f4pital Minjoz, Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abel","family":"Wakpo","sequence":"additional","affiliation":[{"name":"CERPAGE Laboratory, Cotonou, Benin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e8m","family":"Ezinm\u00e8gnon","sequence":"additional","affiliation":[{"name":"CERPAGE Laboratory, Cotonou, Benin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achille","family":"Massougbodji","sequence":"additional","affiliation":[{"name":"CERPAGE Laboratory, Cotonou, Benin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Houz\u00e9","sequence":"additional","affiliation":[{"name":"AP-HP, Saint-Louis Hospital Biochemistry Laboratory, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Kendjo","sequence":"additional","affiliation":[{"name":"AP-HP, Parasitology Laboratory\u2013French National Malaria Reference Centre, Bichat-C. Bernard Hospital, Paris, France"},{"name":"Institute of Tropical Medicine, University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Deloron","sequence":"additional","affiliation":[{"name":"Institut de Recherche pour le D\u00e9veloppement (IRD), UMR 216 Mother and Child Face to Tropical Infections Research Unit, Paris, France"},{"name":"PRES Paris Sorbonne Cit\u00e9, Paris Descartes University, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Le Bras","sequence":"additional","affiliation":[{"name":"Institut de M\u00e9decine et d'Epid\u00e9miologie Appliqu\u00e9e, Bichat-C. Bernard Hospital, Paris, France"},{"name":"Institut de Recherche pour le D\u00e9veloppement (IRD), UMR 216 Mother and Child Face to Tropical Infections Research Unit, Paris, France"},{"name":"PRES Paris Sorbonne Cit\u00e9, Paris Descartes University, Paris, France"},{"name":"AP-HP, Parasitology Laboratory\u2013French National Malaria Reference Centre, Bichat-C. Bernard Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Houz\u00e9","sequence":"additional","affiliation":[{"name":"Institut de Recherche pour le D\u00e9veloppement (IRD), UMR 216 Mother and Child Face to Tropical Infections Research Unit, Paris, France"},{"name":"PRES Paris Sorbonne Cit\u00e9, Paris Descartes University, Paris, France"},{"name":"AP-HP, Parasitology Laboratory\u2013French National Malaria Reference Centre, Bichat-C. 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Global report on antimalarial efficacy and drug resistance: 2000\u20132010. 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