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Abstract
Controlled human malaria infection (CHMI) studies, where healthy volunteers are infected with Plasmodium falciparum have become a vital tool to accelerate vaccine and drug development. As CHMI trials are carried out in a controlled environment, they allow unprecedented, detailed evaluation of parasite growth dynamics and immunological responses to infection. Though commonly performed in malaria-naïve populations, CHMI trials have rarely been conducted in malaria-endemic regions and to date, have not been used to investigate naturally acquired immunity (NAI) to P. falciparum infection. This thesis describes the first CHMI study in Kenya and the first attempt to use the modern CHMI model to explore the dynamics and mechanisms of NAI. Using samples collected post-CHMI from both UK volunteers and Kenyan subjects with varying prior exposure to P. falciparum, this work reports and compares the findings of key in vitro assays including GIA, ADRB activity and changes in gene expression in order to understand the effect of NAI on these measures.