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dc.contributor.authorArjen M. Dondorpen_US
dc.contributor.authorFrançois Nostenen_US
dc.contributor.authorPoravuth Yien_US
dc.contributor.authorDebashish Dasen_US
dc.contributor.authorAung Phae Phyoen_US
dc.contributor.authorJoel Tarningen_US
dc.contributor.authorKhin Maung Lwinen_US
dc.contributor.authorFrederic Arieyen_US
dc.contributor.authorWarunee Hanpithakpongen_US
dc.contributor.authorSue J. Leeen_US
dc.contributor.authorPascal Ringwalden_US
dc.contributor.authorKamolrat Silamuten_US
dc.contributor.authorMallika Imwongen_US
dc.contributor.authorKesinee Chotivanichen_US
dc.contributor.authorPharath Limen_US
dc.contributor.authorTrent Herdmanen_US
dc.contributor.authorSen Sam Anen_US
dc.contributor.authorShunmay Yeungen_US
dc.contributor.authorPratap Singhasivanonen_US
dc.contributor.authorNicholas P.J. Dayen_US
dc.contributor.authorNiklas Lindegardhen_US
dc.contributor.authorDuong Socheaten_US
dc.contributor.authorNicholas J. Whiteen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherShoklo Malaria Research Uniten_US
dc.contributor.otherFamily Health International, Thailanden_US
dc.contributor.otherChurchill Hospitalen_US
dc.contributor.otherNational Center for Parasitology, Entomology and Malaria Controlen_US
dc.contributor.otherInstitut Pasteur du Cambodgeen_US
dc.contributor.otherOrganisation Mondiale de la Santeen_US
dc.identifier.citationNew England Journal of Medicine. Vol.361, No.5 (2009), 455-467en_US
dc.description.abstractBACKGROUND: Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease. There are recent concerns that the efficacy of such therapies has declined on the Thai - Cambodian border, historically a site of emerging antimalarial-drug resistance. METHODS: In two open-label, randomized trials, we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin, western Cambodia, and Wang Pha, northwestern Thailand: oral artesunate given at a dose of 2 mg per kilogram of body weight per day, for 7 days, and artesunate given at a dose of 4 mg per kilogram per day, for 3 days, followed by mefloquine at two doses totaling 25 mg per kilogram. We assessed in vitro and in vivo Plasmodium falciparum susceptibility, artesunate pharmaco kinetics, and molecular markers of resistance. RESULTS: We studied 40 patients in each of the two locations. The overall median parasite clearance times were 84 hours (interquartile range, 60 to 96) in Pailin and 48 hours (interquartile range, 36 to 66) in Wang Pha (P<0.001). Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients (30%) receiving artesunate monotherapy and 1 of 20 (5%) receiving artesunate-mefloquine therapy in Pailin, as compared with 2 of 20 (10%) and 1 of 20 (5%), respectively, in Wang Pha (P = 0.31). These markedly different parasitologic responses were not explained by differences in age, artesunate or dihydroartemisinin pharmacokinetics, results of isotopic in vitro sensitivity tests, or putative molecular correlates of P. falciparum drug resistance (mutations or amplifications of the gene encoding a multidrug resistance protein [PfMDR1] or mutations in the gene encoding sarco-endoplasmic reticulum calcium ATPase6 [PfSERCA]). Adverse events were mild and did not differ significantly between the two treatment groups. CONCLUSIONS: P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thailand. Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing. Containment measures are urgently needed. ( number, NCT00493363, and Current Controlled Trials number, ISRCTN64835265.) Copyright © 2009 Massachusetts Medical Society.en_US
dc.rightsMahidol Universityen_US
dc.titleArtemisinin resistance in Plasmodium falciparum malariaen_US
Appears in Collections:Scopus 2006-2010

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