Controlled Human Malaria Infection Transmission Model - Phase A

Malaria is a disease of major public health importance. The only vaccine available is partially effective and targets the pre-erythrocytic stages of the life cycle. Thus, there is a need to identify other potential vaccine targets as well as to develop models to test vaccine efficacy, especially that of transmission-blocking vaccines. Controlled human malaria infection (CHMI) has been shown to be an important tool for the assessment of the efficacy of novel malaria vaccines and drugs. CHMI also allows for the evaluation of immunity to malaria and monitoring of parasite growth rates in vivo. This is particularly useful in individuals from endemic areas with varying levels of exposure and immunity to malaria. Thus, CHMI in individuals with prior exposure to malaria has potential to accelerate malaria vaccine development. In this study, the aim is to use CHMI in semi-immune adults to develop a model to assess transmissibility of malaria infection to mosquitoes, to study immune responses that are directed against sexual stages that might block transmission, and as a platform to test vaccines. To achieve this, the study will be carried out in two phases A (N=45 participants) and B (N=60 participants) over a period of 4-6months. Parasite dose will be varied in individuals enrolled for CHMI and use of low-doses of anti-malarial drugs to promote the production of gametocytes in vivo (Phase A) and demonstrate transmissibility in mosquito feeding assays (Phase B). Thus, the main outcomes of the study will be: (1) optimisation of sporozoite dose for infections success in individuals with moderate-high malaria exposure; (2) use of sub-curative anti-malaria treatment for induction of gametocytes; and (3) infection of mosquitoes in mosquito feeding assays by induced gametocytes. To achieve this, up to 250 semi-immune adults will be recruited from known areas of malaria endemicity in Kenya with varying exposure to malaria undergo screening procedures after informed consent to enrol 105 individuals to conduct CHMI studies with serial quantitative polymerase chain reaction (PCR) to measure asexual parasite growth and induction of transmission stages in vivo. In addition, comprehensively characterize immunity and identify targets in relation to function assessed by various laboratory assays.