Public health impact and cost-effectiveness of the RTS,S/AS01 malaria vaccine: A systematic comparison of predictions from four mathematical models

Abstract

A phase 3 trial of the RTS,S/AS01 malaria vaccine demonstrated modest efficacy against Plasmodium falciparum malaria but did not assess mortality. To evaluate the public health impact and cost-effectiveness of routine vaccine use, we modeled four malaria transmission scenarios across various African settings. Using trial data, we simulated the vaccine’s effectiveness over 15 years for different Plasmodium falciparum parasite prevalence rates in children aged 2-10 years. Our model predicted that in regions with high prevalence (10-65%), RTS,S/AS01 could avert thousands of clinical cases and hundreds of deaths per 100,000 vaccinated children. The vaccine’s effectiveness decreased with lower prevalence levels. Cost-effectiveness analysis indicated that, for a vaccine price of $5 per dose, the vaccine was highly cost-effective in areas with high prevalence, with incremental cost-effectiveness ratios of $30-$80 per clinical case averted or DALY averted. These findings suggest that RTS,S/AS01 holds significant public health potential in various settings, but implementation decisions should consider factors like malaria burden, existing interventions, and health system capacity.