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dc.contributor.authorObaldía III, Nicanoren_US
dc.contributor.authorDow, Geoffrey S.en_US
dc.contributor.authorGerena, Luciaen_US
dc.contributor.authorKyle, Dennisen_US
dc.contributor.authorOtero, Williamen_US
dc.contributor.authorMantel, Pierre-Yvesen_US
dc.contributor.authorBaro, Nicholasen_US
dc.contributor.authorDaniels, Rachelen_US
dc.contributor.authorMukherjee, Anganaen_US
dc.contributor.authorChilds, Lauren M.en_US
dc.contributor.authorBuckee, Carolineen_US
dc.contributor.authorDuraisingh, Manoj T.en_US
dc.contributor.authorVolkman, Sarah K.en_US
dc.contributor.authorWirth, Dyann F.en_US
dc.contributor.authorMarti, Matthiasen_US
dc.date.accessioned2016-03-01T19:50:59Z
dc.date.issued2016en_US
dc.identifier.citationObaldía III, N., G. S. Dow, L. Gerena, D. Kyle, W. Otero, P. Mantel, N. Baro, et al. 2016. “Altered drug susceptibility during host adaptation of a Plasmodium falciparum strain in a non-human primate model.” Scientific Reports 6 (1): 21216. doi:10.1038/srep21216. http://dx.doi.org/10.1038/srep21216.en
dc.identifier.issn2045-2322en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:25658525
dc.description.abstractInfections with Plasmodium falciparum, the most pathogenic of the Plasmodium species affecting man, have been reduced in part due to artemisinin-based combination therapies. 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) P. falciparum Thai C2A parasite strain in the non-human Aotus primate model, and across multiple passages. Aotus infections with C2A failed to clear upon oral artesunate and mefloquine treatment alone or in combination, and ex vivo drug assays demonstrated reduction in drug susceptibility profiles in later Aotus passages. Further analysis revealed mutations in the pfcrt and pfdhfr loci and increased parasite multiplication rate (PMR) across passages, despite elevated pfmdr1 copy number. Altogether our experiments suggest alterations in parasite population structure and increased fitness during Aotus adaptation. We also present data of early treatment failures with an oral artemisinin combination therapy in a pre-artemisinin resistant P. falciparum Thai isolate in this animal model.en
dc.language.isoen_USen
dc.publisherNature Publishing Groupen
dc.relation.isversionofdoi:10.1038/srep21216en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754742/pdf/en
dash.licenseLAAen_US
dc.titleAltered drug susceptibility during host adaptation of a Plasmodium falciparum strain in a non-human primate modelen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalScientific Reportsen
dash.depositing.authorDaniels, Rachelen_US
dc.date.available2016-03-01T19:50:59Z
dc.identifier.doi10.1038/srep21216*
dash.authorsorderedfalse
dash.contributor.affiliatedMarti, Matthias
dash.contributor.affiliatedMukherjee, Angana
dash.contributor.affiliatedDaniels, Rachel
dash.contributor.affiliatedWirth, Dyann
dash.contributor.affiliatedDuraisingh, Manoj
dash.contributor.affiliatedChilds, Lauren


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