Plasmodium falciparum bottlenecks to improve intervention effectiveness in Kenya
Fall 2019 Graduate Student Award in Pathogenic and Commensal Organisms
Malaria is a large global health issue with over 200 million cases reported in 2017. Recently, GlaxoSmithKline has developed a vaccine for malaria prevention; however, the vaccine does not provide protection for a long period of time and differs by study site, probably due to variability in the vaccine’s target, a highly diverse Plasmodium falciparum malaria protein. High variability in this protein has arisen because of evolutionary processes during malaria’s life cycle between humans and female Anopheles mosquitoes. At any point in the cycle, a bottleneck could occur, limiting malaria’s variability. Using 973 human samples, 123 Anopheles mosquito heads, and 185 Anopheles mosquito abdomens collected in a 14-month longitudinal study in Webuye, Kenya, we will investigate population bottlenecks of P. falciparum malaria throughout its life cycle in humans, mosquito abdomens, and mosquito heads. Using sequencing data, we will use two methods to determine if a population level bottleneck exists. The first method will use the empirical sequencing results to compare the malaria infections found at each part of the cycle. The second method will adapt David Rasmussen’s viral evolution model to estimate how mutations that arise during different stages could increase and decrease malaria diversity and form a bottleneck. These results will inform where in the P. falciparum life cycle diversity is limited, forming a bottleneck, that we could target for malaria interventions to reduce the population’s malaria variability and, consequently, increase success of interventions like the new vaccine.
Sumner KM, Freedman E, Mangeni JN, et al. (2021). Exposure to diverse Plasmodium falciparum genotypes shapes the risk of symptomatic malaria in incident and persistent infections: A longitudinal molecular epidemiologic study in Kenya. Clinical Infectious Diseases.