Controlled human malaria infection (CHMI) has revolutionized the development of malaria
vaccines. It involves the administration of either known numbers of sporozoites or infected
erythrocytes to healthy human volunteers under a controlled environment. The use of highly
sensitive molecular malaria diagnostic methods informs treatment decisions before symptom
development and allows the 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 Artemether Lumefantrine 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 gametocytaemia,
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 transmission blocking candidate
malaria vaccine and gametocidal antimalarial drugs before larger, more complex, and expensive
field efficacy studies are conducted. A study done in naïve individual showed 100% success in
establishing a malaria infection using 2800 P. falciparum infected RBCs, while a recent study
(manuscript in development) has demonstrated success in establishing infection in Tanzanian
semi-immune individuals with low malaria exposure using 1000 P. falciparum infected RBCs. We
will use 1000 ALU-sensitive 3D7 P. falciparum infected RBCs to establish an in vivo
transmission model for studying Transmission blocking interventions and assess the efficiency
of two antimalarial drugs regimens (Piperaquine and doxycycline) to induce high levels of
gametocytaemia and mosquito infection rates in healthy African adults. We will also
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