van der Pluijm RW, Tripura R, Hoglund RM, et al. - In view of the observation that malaria control and elimination are majorly threatened by artemisinin and partner-drug resistance in Plasmodium falciparum, researchers here examined if triple artemisinin-based combination therapies (TACTs), which combine existing co-formulated ACTs with a second partner drug that is slowly eliminated, might result in effective treatment and delay in emergence of antimalarial drug resistance. They conducted a multicentre, open-label, randomized trial, recruiting 1,100 patients with uncomplicated P falciparum malaria at 18 hospitals and health clinics in eight countries between Aug 7, 2015, and Feb 8, 2018. Random assignment of participants (1:1) to one of two therapies was performed depending on their location: in Thailand, Cambodia, Vietnam, and Myanmar, patients were administered either dihydroartemisinin–piperaquine or dihydroartemisinin–piperaquine plus mefloquine; at three sites in Cambodia, they received either artesunate–mefloquine or dihydroartemisinin–piperaquine plus mefloquine; and in Laos, Myanmar, Bangladesh, India, and the Democratic Republic of the Congo, they received either artemether–lumefantrine or artemether–lumefantrine plus amodiaquine. All drugs were orally administered and there was variation in doses by drug combination and site. Outcomes suggest that for uncomplicated P falciparum malaria, dihydroartemisinin–piperaquine plus mefloquine and artemether–lumefantrine plus amodiaquine TACTs are efficacious, well tolerated, and safe therapies, even in areas with artemisinin and ACT partner-drug resistance.