Provincial stratification and equity-weighted cost-effectiveness of malaria vaccines in Zambia under climate variability

Introduction Malaria remains a major public health burden in Zambia, with 5–6 million cases annually. Heterogeneous transmission complicates vaccine deployment. While RTS, S/AS01 has been piloted, the impact and cost-effectiveness of RTS, S and next-generation R21 require rigorous provincial-level evaluation. Methods We developed a province-stratified susceptible, exposed, infectious and recovered (SEIR) –mosquito transmission model incorporating entomological inoculation rates, calibrated to routine surveillance data. The model generated expressions for the basic reproduction number (R₀) and herd immunity thresholds. Cost-effectiveness was assessed from the Zambia Ministry of Health perspective over a 5-year analytic horizon (2024–2028), with 3% annual discounting, using disability-adjusted life-years (DALYs) averted. Costs included procurement, delivery, cold-chain investment and treatment savings. Incremental cost-effectiveness ratios (ICERs) and probabilistic sensitivity analyses (10 000 simulations) were benchmarked against Zambia’s US500/DALY willingness-to-pay threshold. Equity was assessed via ICER distributions and concentration indices. Results Over the 5-year analytic horizon, malaria vaccination substantially reduced transmission intensity and disease burden relative to a no-vaccination baseline, with marked heterogeneity across provinces. Nationally, deployment of the RTS, S vaccine was estimated to avert a median of 9. 80 × 10 5 malaria cases (95% uncertainty interval (UI): 8. 88×10 5 −1. 08×10 6), while the higher-efficacy R21 vaccine averted 1. 09×10 6 cases (95% UI: 9. 91×10 5 −1. 21×10 6). These reductions corresponded to approximately 1960 deaths averted under RTS, S and 2188 deaths averted under R21 over 5 years. Vaccine impact varied across provinces in line with baseline transmission intensity and climate-driven differences in malaria risk, influencing both health outcomes and cost-effectiveness. Conclusions Provincial stratification highlights the need for targeted vaccine roll-out and infrastructure strengthening. RTS, S is borderline cost-effective at current prices, while R21 is highly cost-effective and potentially dominant. Findings support phased provincial deployment with equity weighting, budget integration and climate-adaptive investment to maximise health gains.