Modulation of transmission success of Plasmodium falciparum gametocytes (sexual stages) in various species of Anopheles by erythrocytic asexual stage parasites

During malaria infection, a small proportion of erythrocytic asexual stages undergo sexual differentiation. Male and female gametocytes ingested in the blood meal initiate the sexual development of malaria parasites in the mosquito midgut. During blood feeding on a host, a mosquito ingests, in addition to mature gametocytes, host immune factors present in the blood, as well as large excess of erythrocytic asexual stages. In the current study we addressed the impact of the presence of large excess of asexual stages, hitherto not known or even suspected to influence, on the infectivity of gametocytes in the mosquito. Asexual stages resulted in a dose-dependent inhibition of infectiousness of gametocytes, and some of this could be explained by the presumed effect of hemozoin and other unknown asexual-stage components on the mosquito immune system, affecting survival and maturation of parasites in the mosquito midgut. Interactions between asexual and sexual stages, maturity and ratio of male and female gametocytes, host immune factors and mosquito innate immune factors are some of the variables that determine the infectiousness of gametocytes in the mosquitoes and ultimately malaria transmission success. Understanding of determinants affecting malaria transmission will be critical to approaches directly targeting the transmission process for malaria elimination.