Show simple item record

dc.contributor.authorVenkatesan, M
dc.contributor.authorGadalla, N. B.
dc.contributor.authorStepniewska, K
dc.contributor.authorKironde, Fred
dc.date.accessioned2017-05-30T10:12:07Z
dc.date.available2017-05-30T10:12:07Z
dc.date.issued2014
dc.identifier.citationVenkatesan, M...et al (2014) Polymorphisms in Plasmodium falciparum Chloroquine Resistance Transporter and Multidrug Resistance 1 Genes: Parasite Risk Factors that Affect Treatment Outcomes for P. falciparum Malaria after Artemether-Lumefantrine and Artesunate-Amodiaquine. Research Article.en_US
dc.identifier.urihttp://hdl.handle.net/20.500.12309/186
dc.description.abstractAdequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter ( pfcrt) and P. falciparummultidrug resistance1(pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemetherlumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 – 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36–17.97, P < 0.001) were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.en_US
dc.language.isoenen_US
dc.subjectArtemether-Lumefantrineen_US
dc.subjectArtesunate-Amodiaquineen_US
dc.subjectPolymorphismen_US
dc.subjectGenesen_US
dc.subjectP. falciparum Malariaen_US
dc.subjectMalariaen_US
dc.subjectParasiteen_US
dc.subjectChloroquineen_US
dc.titlePolymorphisms in Plasmodium falciparum Chloroquine Resistance Transporter and Multidrug Resistance 1 Genes: Parasite Risk Factors that Affect Treatment Outcomes for P. falciparum Malaria after Artemether-Lumefantrine and Artesunate-Amodiaquineen_US
dc.typeArticleen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record