SummaryWe assessed the efficacy of mefloquine monotherapy and mefloquine-artesunate (MQ-AS) combination therapy for the treatment of Plasmodium falciparum malaria at four sites in the Bolivian Amazon region.Patients with uncomplicated P. falciparum infections between 5 and 60 years of age were randomly assigned to be treated with either MQ (15 mg/kg in a single oral dose) or MQ (15 mg/kg) plus AS (4 mg/kg daily for 3 days). A total of 143 patients were enrolled and followed for 28 days. None of the 73 patients who received MQ alone or the 70 patients who received MQ-AS combination therapy had recurrences of parasitaemia during the 28-day follow-up period. Asexual parasite densities fell significantly more rapidly and the proportion of patients with gametocytes was significantly lower on days 7-28 in patients treated with MQ-AS than in those treated with MQ alone. All patients tolerated the medications well. After this study, the Bolivian Ministry of Public Health changed its treatment policy for uncomplicated P. falciparum malaria in the Amazon region to combination therapy with MQ-AS to slow or prevent the development of resistance.

Abstract. The World Health Organization (WHO) has developed guidelines for in vivo antimalarial drug efficacy testing for Plasmodium falciparum and Plasmodium vivax in areas with low-to-moderate transmission, such as the Americas. These guidelines are used widely by ministries of health and national malaria control programs to assess the efficacy of their first-line and second-line drugs for the treatment of malaria and to provide the information necessary to update national malaria treatment policies. Following the WHO guidelines, we have conducted in vivo efficacy trials with a variety of drugs and drug combinations against P. falciparum and P. vivax at 13 sites in Peru, Bolivia, and Ecuador. Based on these experiences, we have identified several modifications that we believe should be made in the WHO recommendations to make them more suitable to the relatively low levels of P. falciparum transmission in the Americas and to the logistic challenges of carrying out such studies in sparsely populated areas, such as the Amazon Basin. These include changes in inclusion and exclusion criteria, in enrollment and follow-up procedures, and in the measurement of study outcomes.