Current Organisation

Ifakara Health Institute

Current Job Title

Senior Research Scientist

Biography

Project Title

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

EDCTP Project Call

Senior Fellowship (SF)

Host Organisation

Project Objectives

Primary objectives: To determine the safety of two different P. falciparum blood-stage CHMI models adapted for transmission studies in semi-immune healthy adults residing in Bagamoyo, Tanzania. To select the most efficient P. falciparum blood-stage CHMI model adapted for transmission studies for induction of stable gametocytaemia at densities detectable by qRT-PCR.

Study Design

Controlled Human Malaria infection (CHMI)

Project Summary

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 candidate malaria vaccines, 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 (Sulfadoxine-pyrimethamine, doxycycline and their combination) 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. Finally, I will assess the utility of this model for evaluating the in vivo gametocytocidal activity of Pfs25-Matrix M candidate transmission blocking vaccine as an exploratory objective in a small phase Ib trial in healthy African adults. A PhD studentship will be established in malaria immunoepidemiology to undertake the studies described in the this proposal.