An open, randomized comparison of artesunate plus mefloquine vs. dihydroartemisinin–piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in the Lao People’s Democratic Republic (Laos) M. Mayxay 1,2 , V. Thongpraseuth 3 , M. Khanthavong 3 , N. Lindega ˚rdh 4,5 , M. Barends 5,6 , S. Keola 7 , T. Pongvongsa 8 , S. Phompida 3 , R. Phetsouvanh 3 , K. Stepniewska 4,5 , N. J. White 1,4,5,6 and P. N. Newton 1,4 1 Wellcome Trust – Mahosot Hospital – Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao PDR 2 Division of Postgraduate Studies and Research, Faculty of Medical Science, National University of Laos, Vientiane, Lao PDR 3 Centre of Malariology, Parasitology and Entomology, Vientiane, Lao PDR 4 Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, UK 5 Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand 6 Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand 7 Phalanxay District Clinic, Savannakhet Province, Lao PDR 8 Savannakhet Provincial Malaria Station, Savannakhet Province, Lao PDR Summary objective To determine the efficacy and safety of oral dihydroartemisinin–piperaquine (DP, Artekin TM ) in the treatment of uncomplicated Plasmodium falciparum malaria in southern Laos. methods An open, randomized clinical trial of oral artesunate–mefloquine (AM) vs. DP in 220 patients with acute uncomplicated falciparum malaria in Savannakhet Province, Laos. results The 42-day cure rates (95% CI), as determined by survival analysis and adjusted for rein- fection, were excellent and similar for the two groups [99 (94–100)% and 100 (100–100)% for AM and DP, respectively]. The median (range) fever and parasite clearance times for the AM and DP groups were also similar [20 (4–63) h and 2 (1–4) days vs. 20 (7–57) and 2 (1–4) days, logrank P ¼ 0.4 and 0.17, respectively]. There were more patients with at least one potential side effect following treatment in the AM group when compared with the DP group [64/110 (58%) vs. 48/110 (44%), respectively, P ¼ 0.031]. conclusion Dihydroartemisinin–piperaquine did not have superior efficacy to AM for the treatment of uncomplicated falciparum malaria in Laos but was associated with fewer adverse effects. keywords Plasmodium falciparum, malaria, artemisinin-based combination therapy, dihydroartemis- inin–piperaquine, Laos Introduction Plasmodium falciparum malaria remains an important public health problem in the Lao PDR (Laos). The inexpensive and readily available antimalarials, chloroqu- ine (CQ) and sulphadoxine–pyrimethamine (SP, Fansidar TM , Hoffman La Roche, Basel, Switzerland), are used alone or in combination in the treatment of uncom- plicated P. falciparum malaria in Laos, despite their low efficacies when used as monotherapy (Pillai et al. 2001; Guthmann et al. 2002; Mayxay et al. 2003a,b; Schwobel et al. 2003). The Lao Government is introducing artemis- inin-based combination therapy (ACT), and to provide evidence as to which combination would be the most appropriate for use in Laos, we recently compared the efficacy of artesunate + mefloquine (AM), artemether– lumefantrine (AL) and CQ + SP in the treatment of uncomplicated falciparum malaria in Savannakhet Prov- ince, southern Laos. Cure rates at 42-day follow-up were 100% for AM, 97% for AL and 92% for CQ + SP (Mayxay et al. 2004). A similar clinical trial in northern Laos demonstrated 42-day follow-up cure rates of 100% for AM and 94% for AL (Stohrer et al. 2004). Although in terms of failure rates, AM and AL seem to be the optimum choices, the high cost of these drugs (approximately 3.5 and 2.4 US$/adult treatment course, respectively) will limit their use in a developing country such as Laos. Addi- tional potential disadvantages of AM include the Tropical Medicine and International Health doi: 10.1111/j.1365-3156.2006.01671.x volume 11 no 8 pp 1157–1165 august 2006 ª 2006 Blackwell Publishing Ltd 1157