The mosquito transmission of malaria: the effects of atovaquone-proguanil (Malarone (TM)) and chloroquine

Despite its recognized importance, the prevention of patients with malaria from continuing to infect mosquitoes after treatment is not always achieved in practice. An inevitable consequence of the prolonged life-span and rela tive metabolic stasis of the mature gametocytes of Plasmodium falciparum; i s that they are not cleared by most antimalarials, and few antimalarials bl ock infection in the mosquito vector. Previous research on the constituents of Malarone(TM), a new 'combined antimalarial', suggested that the active components, atovaquone and proguanil, might inhibit infectivity of gametocy tes to mosquitoes. We contrast here the impact of atovaquone-proguanil and chloroquine on the transmission of P. falciparum and P. berghei. While chlo roquine enhanced infectivity of P,falciparum, atovaquone-proguanil caused a significant reduction. Surprisingly, sporontocidal activity against the ro dent parasite persisted long after the levels of the constituent drugs woul d have been expected to have fallen below effective plasma concentrations o n the basis of the established pharmacokinetics of atovaquone and proguanil . The P. berghei model may thus have provided a sensitive bioassay, detecti ng drug(s) at levels below that normally found with the usual chemical assa ys.