Mathematical modeling of the impact of malaria vaccines on the clinical epidemiology and natural history of Plasmodium falciparum malaria: Overview.

We report a major project to develop integrated mathematical models for predicting the epidemiologic and economic effects of malaria vaccines both at the individual and population level. The project has developed models of the within-host dynamics of Plasmodium falciparum that have been fitted to parasite density profiles from malaria therapy patients, and simulations of P. falciparum epidemiology fitted to field malariologic datasets from a large ensemble of settings across Africa. The models provide a unique platform for predicting both the short- and long-term effects of malaria vaccines on the burden of disease, allowing for the temporal dynamics of effects on immunity and transmission. We discuss how the models can be used to obtain robust cost-effectiveness estimates for a wide range of malaria vaccines and vaccination delivery strategies in different eco-epidemiologic settings. This paper outlines for a non-mathematical audience the approach we have taken and its underlying rationale.