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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/27999
Title: Artemisinin resistance in Plasmodium falciparum malaria
Authors: Arjen M. Dondorp
François Nosten
Poravuth Yi
Debashish Das
Aung Phae Phyo
Joel Tarning
Khin Maung Lwin
Frederic Ariey
Warunee Hanpithakpong
Sue J. Lee
Pascal Ringwald
Kamolrat Silamut
Mallika Imwong
Kesinee Chotivanich
Pharath Lim
Trent Herdman
Sen Sam An
Shunmay Yeung
Pratap Singhasivanon
Nicholas P.J. Day
Niklas Lindegardh
Duong Socheat
Nicholas J. White
Mahidol University
Shoklo Malaria Research Unit
Family Health International, Thailand
Churchill Hospital
National Center for Parasitology, Entomology and Malaria Control
Institut Pasteur du Cambodge
Organisation Mondiale de la Sante
Keywords: Medicine
Issue Date: 30-Jul-2009
Citation: New England Journal of Medicine. Vol.361, No.5 (2009), 455-467
Abstract: BACKGROUND: 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. (ClinicalTrials.gov number, NCT00493363, and Current Controlled Trials number, ISRCTN64835265.) Copyright © 2009 Massachusetts Medical Society.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=68049123592&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/27999
ISSN: 15334406
00284793
Appears in Collections:Scopus 2006-2010

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