Project: Adaptation of blood-stage CHMI for evaluation of transmission blocking malaria interventions in endemic countries.

Acronym	Blood-CHMI-Trans (Reference Number: TMA2018SF-2475)
Duration	01/01/2020 - 31/12/2023
Project Topic	Controlled human malaria infection (CHMI) has revolutionized the development of malaria vaccines. It involves administration of either known numbers of sporozoites or infected erythrocytes to healthy human volunteers under controlled environment. Use of highly sensitive molecular malaria diagnostic methods informs treatment decisions before symptom development, and allow characterization of parasite growth dynamics. Sporozoite CHMI has safely been used in six countries in Africa providing a platform to assess the efficacy of malaria vaccine candidates, and study the natural immunity to malaria. Blood stage CHMI involves administration of known number of chloroquine sensitive infected erythrocytes in healthy volunteers, and it is a more sensitive model for modelling parasite growths and study the efficacy of blood-stage malaria vaccines. It has been safely used in Australia and Europe but not in Africa. Adaptation of this model by administration of combination of suboptimal and optimal antimalarial drugs lead to increased gametocytemia, and infection rates in mosquitoes following standard membrane feeding assay. Such adaptation allows the model to be used to study parasite transmission from human to mosquitoes, and evaluate transmission blocking malaria interventions. There is an urgent need to establish an in vivo model for early-stage clinical evaluation of transmission blocking interventions (TBI) in volunteers living in malaria endemic countries. This would allow rapid and cost-effective way to down-select candidate malaria vaccine and drugs before larger, more complex and expensive field efficacy studies are conducted. I will use an ideal dose of chloroquine-sensitive infected erythrocytes to establish an in vivo transmission model for studying TBI. I will assess the efficiency of two antimalarial drugs regimens  Sulfadoxinepyrimethamine and doxycycline) to induce high levels of gametocytemia and mosquito infection rates in healthy African adults. I will investigate the determinants of successful transmission to mosquitoes including underlying immune responses to both asexual and sexual malaria antigens, asexual parasite dynamics and gametocyte burden, sex ratio of male and female gametocytes, and the relationship between gametocyte density and mosquito infection rate. A PhD studentship will be established in malaria immunoepidemiology to undertake the studies described in this project. Finally, as a long term plan I will seek for additional funding from other sources to test the utility of this model for evaluating the in vivo gametocytocidal activity of a candidate transmission blocking vaccine as a proof of concept in a small phase Ib trial in healthy African adults.
Network	EDCTP2
Call	Senior Fellowships 2018

Project partner

Number	Name	Role	Country
1	Ifakara Health Institute Trust	Coordinator	Tanzania