Plasmodium falciparum malaria is a preventable but deadly parasitic disease, leading to an estimated 409,000 deaths per year, 95% of which occur in the African region. Despite overall reductions in the risk of malaria mortality in the past two decades, progress in further improvements has stagnated since 2016. Timely access to effective first-line artemisinin combination therapies (ACT) remains one of the most important components of case management and successful malaria control interventions. The effect of delay to treatment is difficult to study but important to quantify and include in estimates of malaria morbidity and mortality. This thesis aims to explore the coverage and effectiveness of antimalarials in the community, quantify the impact of delay to treatment on severe malaria and mortality, and evaluate current interventions that reduce treatment delays.
Using nationally representative household surveys conducted in Sub-Saharan African communities, I estimate the coverage of different types of antimalarials and rates of potential parasite clearance following self-reported antimalarial treatment. I also develop and calibrate an individual-based model to the household survey data to explore antimalarial effectiveness in the community. Factors affecting antimalarial effectiveness, such as duration of treatment and type of provider are also explored. Further, I conduct a systematic review and individual participant meta-analysis to quantify the impact of prompt treatment on reducing severe malaria and different severe malaria phenotypes. Using these, I model the relationship between age and presentation with severe malaria symptoms and subsequently estimate the burden of severe malaria phenotypes and malaria mortality across sub-Saharan Africa using a model of malaria transmission, developed by Imperial College London. Finally, I estimate the impact of prompt treatment in terms of severe malaria cases and deaths averted using baseline and endline data from the Rapid Access Expansion (RAcE) programme, following implementation of integrated Community Case Management (iCCM) interventions in high-burden countries of Sub-Saharan Africa.
This thesis explores several key aspects relevant to progression to different severe malaria phenotypes and mortality and demonstrates the importance of prompt and effective first-line ACT treatment, good treatment adherence, adequate provision of community health care services, as well as regulation and provision of high-quality antimalarials. It also highlights differences in both the fatality and the impact of delay to treatment for different severe malaria phenotypes. Understanding the distribution of these phenotypes and their contribution to malaria mortality is important in informing malaria control interventions.