The combination of mefloquine-sulfadoxine-pyrimethamine was developed for therapeutic use on the basis of the observation that its components display at least additive activity and that their combination might delay the emergence of parasite resistance (109). It has not been recommended for general use by malaria control programmes for either chemoprophylaxis or treatment since 1990 because of concerns of the risk of severe adverse reactions to the sulfadoxine component, and because it did not appear to be justified to introduce mefloquine on a large scale to areas where sulfa drug-pyrimethamine was still effective. It was considered that its hypothetical effect on the development of resistance in natural human parasite populations could not counter its documented toxicity (110). The use of this drug as a first-line treatment for uncomplicated P. falciparum infections in Thailand was temporally associated with a period of rapid development of resistance to mefloquine, perhaps related to the 15 mg/kg dose of mefloquine in the combination (158), the existing high resistance to sulfadoxine-pyrimethamine (327) or the long half-life of mefloquine, which led to a long duration of subtherapeutic concentrations unprotected by sulfadoxine-pyrimethamine (328). As a result, mefloquine resistance developed within six years of deployment of this combination (329, 330).