Effects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand: a prospective study

Background Worsening drug resistance in Plasmodium falciparum malaria is a major threat to health in tropical countries. We did a prospective study of malaria incidence and treatment in an area of highly multidrug-resistant P falciparum malaria. Methods We assessed incidence of P falciparum malaria and the in-vivo respo nses to mefloquine treatment over 13 years in two large camps for displaced Karen people on the northwest border of Thailand. During this time, the st andard mefloquine dose was first increased, and then combined artesunate an d mefloquine was introduced as first-line treatment for uncomplicated P fal ciparum malaria. Findings Early detection and treatment controlled P falciparum malaria init ially while mefloquine was effective (cure rate with mefloquine [15 mg/kg] and sulphadoxine-pyrimethamine in 1985, 98% [95% CI 97-100]), but as mefloq uine resistance developed, the cure rate fell (71% [67-77] in 1990). A simi lar pattern was seen for high-dose (25 mg/kg) mefloquine monotherapy from 1 990-94. Since the general deployment of the artesunate-mefloquine combinati on in 1994, the cure rate increased again to almost 100% from 1998 onwards, and there has been a sustained decline in the incidence of P falciparum ma laria in the study area. In-vitro susceptibility of P falciparum to mefloqu ine has improved significantly (p=0.003). Interpretation In this area of low malaria transmission, early diagnosis an d treatment with combined artesunate and mefloquine has reduced the inciden ce of P falciparum malaria and halted the progression of mefloquine resista nce. We recommend that antimalarial drugs should be combined with artemisin in or a derivative to protect them against resistance.