Modelling the Cost-Effectiveness of a Placental Malaria Vaccine in Sub-Saharan Africa

Introduction: Placental malaria increases the risk of adverse birth outcomes. Current preventive measures are undermined by poor coverage, growing resistance to chemo-preventive and therapeutic drugs, and vector eliminating insecticides. Candidate placental malaria (PM) vaccines (PAMVAC and PRIMVAC) have shown safety and immunogenicity in Phase I trials, but empirical evidence on their potential population-level value is lacking. This study modelled the expected cost-effectiveness of a PM vaccine administered before pregnancy. Methods: A decision-analytic model compared two strategies from the provider's perspective: vaccinating women of childbearing age versus no vaccination. The model incorporated gravidity-specific risks of PM, neonatal mortality and the malaria attributable fractions from the literature. Since the efficacy of a PM vaccine for malaria prevention is unknown, we assumed a 40% efficacy and varied this estimate widely in sensitivity analyses. Primary outcomes were incremental cost-effectiveness ratios (ICERs) per perinatal disability adjusted life years (DALYs) averted. Baseline, best-case, and worst-case scenarios were analysed. One-way and probabilistic sensitivity analyses were used to assess parameter uncertainty. Cost-effectiveness was defined as an ICER below half of sub- Saharan Africa's 2025 GDP per capita ($1556). Results: The vaccine was most cost-effective among primigravidae. Under baseline assumptions (40% efficacy; 30% uptake; $5 dose price), the ICER was $321 per perinatal DALY averted for primigravidae versus $4444 for multigravidae. Best-case assumptions further improved cost-effectiveness ($225 vs. $3148). Sensitivity analyses showed robust cost-effectiveness for primigravidae across all plausible parameter ranges, while ICERs in multigravidae were highly sensitive to programme costs and vaccine efficacy. Cost-effectiveness acceptability curves demonstrated that vaccination becomes favourable for primigravidae at relatively low willingness-to-pay thresholds. Conclusions: A placental malaria vaccine delivered before pregnancy has high potential to be cost-effective in endemic areas when targeted to protect primigravidae. These findings support prioritised deployment strategies and highlight the value of early economic modelling to inform vaccine development and policy planning.