Strategic use of antimalarial drugs that block falciparum malaria parasite transmission to mosquitoes to achieve local malaria elimination.

Abstract

The ultimate aim of malaria chemotherapy is not only to treat symptomatic infection but also to reduce transmission potential. With the absence of clinically proven vaccines, drug-mediated blocking of malaria transmission gains growing interest in the research agenda for malaria control and elimination. In addition to the limited arsenal of antimalarials available, the situation is further complicated by the fact that most commonly used antimalarials are being extensively resisted by the parasite and do not assist in blocking its transmission to vectors. Most antimalarials do not exhibit gametocytocidal and/ or sporontocidal activity against the sexual stages of Plasmodium falciparum but may even enhance gametocytogenesis and gametocyte transmissibility. Artemisinin derivatives and 8-aminoquinolines are useful transmission-blocking antimalarials whose optimal actions are on different stages of gametocytes. Transmission control interventions that include gametocytocides covering the spectrum of gametocyte development should be used to reduce and, if possible, stop transmission and infectivity of gametocytes to mosquitoes. Potent gametocytocidal drugs could also help deter the spread of antimalarial drug resistance. Novel proof-of-concept compounds with gametocytocidal activity, such as trioxaquines, synthetic endoperoxides, and spiroindolone, should be further tested for possible clinical utility before investigating the possibility of integrating them in transmission-reducing interventions. Strategic use of potent gametocytocides at appropriate timing with artemisinin-based combination therapies should be given attention, at least, in the short run. This review highlights the role that antimalarials could play in blocking gametocyte transmission and infectivity to mosquitoes and, hence, in reducing the potential of falciparum malaria transmissibility and drug resistance spread.