Accelerating Malaria Elimination: Funding for Quality and Safety Surveillance of Medicines and Vaccines, Evaluating Deployment Strategies and Cost-Effectiveness of Interventions, and Therapeutic Trials

Abstract

Malaria remains a major cause of morbidity and mortality in sub-Saharan Africa, where the burden continues to fall disproportionately on young children. Although the global malaria strategy calls for at least a 90% reduction in malaria incidence and mortality by 2030 relative to 2015, progress in many high-burden settings has slowed, highlighting the need for stronger systems to monitor the safety and quality of antimalarial medicines and vaccines, more effective deployment of malaria control interventions, and expanded treatment options for vulnerable populations. This dissertation addresses three critical gaps that limit progress toward malaria control and prevention in sub-Saharan Africa. First, it examines donor support for strengthening pharmacovigilance systems for antimalarial medicines and vaccines. Second, it evaluates potential intervention deployment strategies and their associated costs for accelerating malaria reduction in Siaya County, western Kenya, a perennial high-transmission setting. Third, it reviews therapeutic trials in the first trimester of pregnancy and identifies barriers to conducting these studies. These three studies aim to generate data-driven evidence to inform funding priorities, optimize intervention deployment strategies, and support the expansion of safe and effective malaria treatment and prevention options.The first study examined donor funding for pharmacovigilance and quality-assured malaria medicines and vaccines in sub-Saharan Africa between 2021 and 2024 from grant and award data from major international donors and development agencies. Grant data were extracted from publicly accessible sources, cross-validated using the International Aid Transparency Initiative, and supplemented through expert consultation. A keyword-in-context search was conducted across available grant documents, including budgets, audited financial statements, funding applications, project briefs, and procurement plans, to identify support for pharmacovigilance-related activities and procurement of quality-assured commodities. Of the 545 malaria grants and awards identified, 264 included detailed documentation, and 105 of these referenced pharmacovigilance-related activities. Across all grants, total malaria disbursements exceeded US$10.4 billion, of which US$43.0 million, or 0.4%, was allocated to pharmacovigilance activities. These findings indicate that pharmacovigilance remains substantially underfunded in sub-Saharan Africa despite expanding malaria vaccine rollout and the introduction of new antimalarial therapies. In the second study, an agent-based malaria transmission model was developed and calibrated for Siaya County, western Kenya, to evaluate the epidemiologic impact and cost-effectiveness of alternative malaria intervention packages for achieving the 2030 Global Technical Strategy targets. The model incorporated site-specific seasonality, parasite prevalence, clinical incidence, vector dynamics, and climate, and was validated against independent outpatient malaria case and mortality data. Six intervention scenarios were simulated from 2016 to 2030, including business as usual, moderate scale-up of core interventions, introduction of perennial malaria chemoprevention, supplementary indoor residual spraying, and an expanded 80% target package combining strengthened case management, insecticide-treated nets, malaria vaccination, perennial malaria chemoprevention, and indoor residual spraying. Under business as usual, malaria burden was projected to remain substantially above 2015 levels by 2030. The expanded 80% target package produced the greatest impact, reducing all-age incidence by 91.0% and mortality by 93.6% relative to 2015 levels by 2030. It was also dominant relative to business as usual, averting 16,291 disability-adjusted life years, 417 deaths, and 3.82 million cases while remaining cost saving by reducing costs by US$15.28 million over the 2016–2030 period. These findings suggest that achieving malaria reduction targets in perennial high-transmission settings such as Siaya County will likely require high-coverage, integrated intervention packages and that such strategies may also be cost-saving. In the third study, a systematic review and key informant survey were conducted to assess the landscape of clinical trials prospectively including women in the first trimester of pregnancy and to identify barriers to conducting such research. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, five databases and trial registries were searched for studies published or registered between 2000 and 2025, and data were extracted on therapeutic areas, endpoints, sample sizes, study locations, and pre-trial evidence, including developmental and reproductive toxicology studies and prior pregnancy exposures. Twelve key informants also provided perspectives on implementation barriers to conducting trials during the first trimester. Of 124 records screened, 22 studies met inclusion criteria, including 14 completed trials and eight trial protocols. Most trials focused on pregnancy-related complications, while only four addressed infectious diseases, including two malaria trials and two HIV trials. Trials rarely reported pre-clinical safety evidence, and key informants identified major barriers including safety concerns, limited regulatory and clinical guidance, insufficient pre-clinical data, ethical challenges, and logistical difficulties in identifying and enrolling women early in pregnancy. These findings highlight the persistent evidence gap surrounding therapeutic research in early pregnancy and the need for more intentional inclusion of first-trimester pregnant women in clinical trials. Together, these three studies provide evidence to inform malaria financing, intervention planning, and therapeutic research needed to accelerate progress toward control and prevention in sub-Saharan Africa. By examining gaps in pharmacovigilance financing, intervention planning, and therapeutic research, this dissertation provides evidence to inform malaria policy, strengthen program implementation, and support progress toward malaria control and prevention in sub-Saharan Africa.