A randomized clinical trial to compare P. falciparum gametocytaemia and infectivity following blood-stage or mosquito bite induced controlled malaria infection

For malaria elimination efforts, it is important to better understand parasite transmission to mosquitoes and to develop models to allow early clinical evaluation of transmission-blocking interventions. We previously described a Controlled Human Malaria Infection protocol for induction of gametocytemia in malaria naïve volunteers by mosquito bite (CHMI-trans) (Reuling et al., 2018).  Here, we compared gametocyte production and infectivity in the CHMI-trans model after bites of Plasmodium falciparum (Pf)- infected mosquitoes  to that after intravenous administration of  Pf-infected-erythrocytes.  Volunteers received (sub) curative treatments with gametocyte-permissive piperaquine or sulfadoxine-pyrimethamine. Blood-stage inoculation induced considerably higher gametocyte densities compared to mosquito bitesthat was predicted by PfAP2-G transcripts indicative of gametocyte commitment, and resulted in Pf-positive mosquito infections in 9/12 volunteers versus 0/12 volunteers after mosquito bite inoculation. Current findings firmly establish the CHMI-trans with intravenous administration of asexual parasites as a model for early clinical evaluation of interventions that aim to interrupt Pf-transmission.