UC Irvine

The scaling up of vector interventions, improved diagnostics, and effective treatments of malaria collectively contributed to significant reductions in global malaria mortality and morbidity at the turn of the 21st century. Despite the strides made in malaria control, global malaria elimination remains a distant prospect. As transmission declines, the proportion of asymptomatic malaria infections increases. Asymptomatic infections are often missed by conventional detection methods, thus constituting an obscure parasite reservoir that sustains transmission and impedes malaria control efforts. Countries that have achieved success in controlling malaria face an “out of sight, out of mind” paradox, whereby the more “invisible” a disease becomes to policymakers, the greater the risk that funding for control measures will be withdrawn.This dissertation addresses the pressing need for enhanced malaria surveillance systems capable of identifying transmission reservoirs as malaria transmission declines in Eastern Africa. The overarching goal was to evaluate surveillance strategies and tools for monitoring changes in malaria epidemiology following the implementation of intensive malaria control programs. I leveraged field sites in western Kenya and Ethiopia that were established through the NIH-funded sub-Saharan Africa International Center of Excellence for Malaria Research program to generate high-resolution human serological and parasite genetic data. In Chapter 1, I analyzed a panel of 10 serological markers to identify risk factors associated with recent and cumulative exposure to Plasmodium falciparum (Pf) and Plasmodium vivax infection in two sites of contrasting transmission intensity in southwestern Ethiopia. In Chapter 2, I assessed the prevalence of PfKelch 13 artemisinin drug resistance mutations at sites of varying transmission intensities in western Kenya and across Ethiopia between 2018-2022. In Chapter 3, I utilized a suite of molecular methods to assess changes in malaria parasite prevalence and parasite genetic diversity in the context of environmental modifications and changes in malaria control interventions over a three-year period in a western Kenya. In Chapter 4, I pilot tested a cross-sectional, reactive case detection strategy in western Kenya and identified groups at higher risk of P. falciparum infection who can be targeted to optimize case detection. The findings of this dissertation underscore the need for considering both current and historic transmission intensities when tailoring malaria surveillance and control strategies to further reduce malaria burden in declining malaria transmission settings of Kenya and Ethiopia.