Depicting Plasmodium falciparum sexual conversion in natural infections: role of host immune responses and parasites genetic factors

Malaria is an infectious life-threatening disease caused by a protozoan parasite of the genus Plasmodium, which is transmitted through the bite of an infected Anopheles mosquito. The disease is caused by several species, but infection by Plasmodium falciparum is the most severe and represents 99.7% of estimated malaria cases in the WHO African region.
Malaria parasites in human blood need to undergo sexual commitment and produce gametocytes in order to transmit infection to mosquitoes. At each replication cycle within erythrocytes, a proportion of asexual parasites converts into non-replicative sexual stages. Sexual conversion rate (SCR) is the proportion of parasites that differentiate into gametocytes at every replication cycle. This conversion can happen during a spontaneous commitment (basal sexual conversion) of asexual parasites to gametocytogenesis. Basal sexual conversion rates are usually less than 1% but can increase significantly (up to 20%) (to induced sexual conversion) in response to hostile and stressful environment in the host.
In recent years, impressive progress has unraveled the molecular mechanisms driving sexual development in P. falciparum in vitro cultures; however, the triggers of sexual conversion in natural human P. falciparum infections are not fully understood. This PhD proposes an integrated study combining novel tools for (molecular) quantification of sexual conversion, immunological profiling, and genomic analysis of parasite isolates from both symptomatic and asymptomatic individuals in a malaria-endemic setting. Results will advance our understanding of malaria transmission biology and may inform the development of targeted interventions, including transmission-blocking strategies.