Artemisinin Resistance in Plasmodium falciparum Malaria

作者：Arjen M. Dondorp, François Henry Nosten, Poravuth Yi, Debashish Das, Aung Pyae Phyo, Joel Tärning, Khin Maung Lwin, Frédéric 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 Day, Niklas Lindegårdh, Duong Socheat, Nicholas John White · 发表于：New England Journal of Medicine · 年份：2009 · DOI：10.1056/nejmoa0808859 · 被引用次数：3510 · 研究领域：Malaria Research and Control、Multiple Myeloma Research and Treatments、Calpain Protease Function and Regulation

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 pharmacokinetics, 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, artesunat...