Project Details

Measuring the impact of newly deployed malaria vaccine on malaria infection in Uganda

Anne Martin, PhD, MPH

Summary

BACKGROUND: Malaria is a leading cause of death in children worldwide, resulting in 597,000 deaths per year. In 2025, Uganda began rollout of the R21/Matrix-M malaria vaccine. GAP: In multi-site phase-3 vaccine trials, efficacy in preventing infection varied by site transmission intensity; one proposed explanation is that efficacy is proportional to the amount of exposure (via mosquito bite) children experience. To capture the full vaccine effect, effectiveness should be measured against each exposure and not just against infection. Multiplicity of infection (MOI), the number of genetically distinct strains in an individual infection, is considered representative of biting frequency of infected mosquitoes, and can act as a proxy measure of exposure. HYPOTHESIS: We hypothesize that even when vaccination-conferred protection is not complete (i.e. prevents any infection from all exposures), vaccination-conferred protection prevents some infections from some exposures, such that the MOI will be higher in unvaccinated children compared to vaccinated children METHODS: We will estimate the impact of R21 vaccine via multiplicity of infection in vaccine-eligible febrile children in an established test-negative case-control study at two clinics in Uganda (2026, PI Martin, enrollment ongoing). The study is an observational study enrolling, sampling, and ascertaining vaccination status in children who present with malaria symptoms. We will measure vaccine effectiveness per exposure by performing amplicon sequencing on malaria cases, to measure MOI in collected samples and we will compare vaccination status across levels of MOI. RESULTS: Pending. IMPACT: Understanding effectiveness of the vaccine in high transmission settings will inform WHO-recommendations for vaccine scheduling in the more than 20 countries that are rolling out R21/Matrix-M.