Impact of early childhood malaria prevention on malaria risk at school entry (ERASE)

Project Summary The World Health Organization (WHO) recommends two key interventions to protect young children in sub-Saharan Africa from Plasmodium falciparum (Pf) malaria morbidity and mortality. Seasonal malaria chemoprevention (SMC) provides a full course of antimalarial drugs every month of the high transmission period in seasonal transmission areas. More recently, RTS,S vaccination to prevent malaria in young children in areas of moderate to high transmission has also been recommended following the promising results of large-scale pilot study. Ghana is one of three countries in this pilot study and is the only country in the world where both SMC and RTS,S have been implemented in a broad population. SMC has been implemented at the regional level and RTS,S vaccine administration has been randomized by district through the implementation pilot program. This means that in a small geographic area, we can evaluate children who have received SMC and/or RTS,S or neither of these interventions. In our on-going surveillance of malaria in sub-Saharan Africa, we identified school-age children (ages five to fifteen years) as the population with the highest prevalence of malaria infection. These infections typically do not cause severe disease. However, because immunity to malaria is acquired through repeated exposures, children who receive SMC and/or RTS,S vaccine may have delayed immune development and experience increased malaria disease burden and more frequent severe disease after the interventions end at five years of age. Alternatively, decreasing exposure to malaria in early life may allow children to develop a more robust immune response to Pf and thus lead to a reduced risk of infection and disease as they reach school- age. Finally, vaccine antibodies, especially in children who completed the primary series plus the recommended booster, may continue to protect children beyond five years of age. Thus, the opportunity to study children who received various combinations of RTS,S and/or SMC is unique in Ghana and timely for all high malaria burden countries. We propose a longitudinal cohort study of four groups of children ages five to seven years with a history of different combinations of exposures to early childhood interventions: SMC alone, RTS,S alone, SMC plus RTS,S, or none of these interventions. We designed the study to understand the epidemiological impact of vaccination and SMC on the burden of malaria infection and disease at five to seven years of age through a longitudinal study assessing Pf prevalence and the incidence of clinical disease. We have also proposed innovative serological profiling, fine epitope mapping, and genomic approaches to understanding the immunological and parasitological basis of our observations to inform the next generation of interventions.