EPIDEMIOLOGY, DIVERSITY, AND RECURRENCE PATTERNS OF PLASMODIUM OVALE SPECIES IN COASTAL TANZANIA

While the prevalence of P. ovale (Po) species appears to be rising in regions where control of P. falciparum (Pf) is improving, their characteristics in endemic regions remain poorly understood. Specifically, the population genomics of P. ovale curtisi (Poc) and wallikeri (Pow) across sub-Saharan Africa, their distributions in endemic populations, and patterns of longitudinal carriage have not been thoroughly investigated.In our first dissertation aim, we employed whole-genome hybrid capture amplification of 21 Poc and 24 Pow isolates collected across Africa, revealing lower nucleotide diversity in Pow and geographic population structure in both species. We also found signatures of directional selection near the dhfr-ts gene, an antimalarial resistance marker, and of balancing selection at msp1, an immunogenic antigen on the surface of blood-stage parasites.We then used cross-sectional screening of 7,174 asymptomatic individuals in coastal Tanzania to characterize the patterns of Po (including both species) and Pf carriage in this endemic community with overall Po prevalence of 11.5%. Po appeared most prevalent in the seasons of the year in which Pf was least common, and the two were less likely to infect the same hosts than expected by random chance. Conversely, we found frequent co-infection of Poc and Pow within the same hosts, indicating that efforts to control P. ovale may be able to address the two species in tandem.Finally, we followed a longitudinal cohort of 74 participants who were positive for Po at baseline, screening them by PCR every two weeks, in order to determine the Po incidence rate and risk of recurrence within 6 months. We found over half (55%) of the participants to experience an additional Po infection during the follow-up interval, with an incidence rate of 1.9 new infections per person-year at risk.Overall, this dissertation reveals high prevalence and incidence of Po spp. in an endemic community (distinct from Pf) and the potential for parasite selection by antimalarial exposure. Improved surveillance of P. ovale infection, characterization of the vector species driving transmission, and consideration of relapse prophylaxis, will be needed to ensure that malaria control efforts do not neglect non-falciparum species.