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

Abstract

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.

qRT-PCR versus IFA-based Quantification of Male and Female Gametocytes in Low-Density Plasmodium falciparum Infections and Their Relevance for Transmission

“…To what extent such low-density infections can sustain malaria transmission is not clear, as scanty parasitemia diminishes the likelihood of a mosquito bloodmeal harboring both male and female gametocytes, a prerequisite for infectiousness to mosquitoes. The density of gametocytes in the host’s blood, the maturity of gametocytes, and proportion of male gametocytes are critical determinants for successful transmission to the mosquito [ 4 , 5 ]. Mosquito feeding assays (MFA) are ideally used to assess the infectiousness of a parasitemic host to mosquitoes [ 6–9 ], but integrating MFAs into large epidemiological field studies is logistically and technically challenging.…”

A whole parasite transmission-blocking vaccine for malaria: an ignored strategy

“…Burkina Faso) it is estimated that almost one-third of all transmission occurs from people with sub-microscopic levels of gametocytaemia [40]. Recent data demonstrating that asexual parasites can inhibit the infectiousness of gametocytes ( possibly through the activation of the mosquito immune system by hemozoin) [41] may, in part, explain these observations. In a low transmission setting, Churcher et al [37] argue that if an intervention can keep gametocyte levels below 200 per μl, then this may be sufficient to eliminate disease.…”