Efficacy and safety of atovaquone-proguanil compared with mefloquine in the treatment of nonimmune patients with uncomplicated P. falciparum malaria in Japan

Malaria treatment is becoming increasingly difficult due to the widespread drug resistance of Plasmodium falciparum. In Japan, only three antimalarials are approved for treatment: oral quinine, sulfadoxine-pyrimethamine, and mefloquine. Recently, however, the Research Group on Chemotherapy of Tropical Diseases introduced atovaquone-proguanil for treating drug-resistant P. falciparum malaria. This research group had also introduced mefloquine before it was licensed nationally. Using data obtained from the research group, we analyzed the efficacy and safety of atovaquone-proguanil, as compared with mefloquine, in nonimmune patients with uncomplicated P. falciparum malaria. Cures were attained in all (100%) of 20 atovaquone-proguanil-treated and 49 (98%) of 50 mefloquine-treated adults. The mean fever clearance time (FCT) and parasite clearance time (PCT) appeared to be longer in the atovaquone-proguanil group than in the mefloquine group, but the differences were not statistically significant. Three (15%) of the 20 atovaquone-proguanil-treated adults had adverse events (AEs), all of which were transient elevations of liver enzymes, while 19 (38%) of the 50 mefloquine-treated adults had AEs, including dizziness in 8 (16%) and nausea/vomiting in 7 (14%). All 3 children treated with atovaquone-proguanil were cured without developing AEs. Despite the limitations of this study in not being a formal clinical trial, atovaquone-proguanil seemed to be at least equal to, or even better than, mefloquine for the treatment of uncomplicated P. falciparum malaria in nonimmune patients, including children. Its marketing in Japan could be beneficial in offering an alternative therapeutic option. However, vigilance should be maintained on the possible occurrence of rare but severe AEs, and also of the possible spread of drug resistance.