The age-specific impact of seasonal malaria chemoprevention on malaria incidence, antibody responses, and parasite reservoirs in Malian children

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PROJECT SUMMARY According to the World Health Organization (WHO), in 2018, there were an estimated 405 000 deaths from malaria. Children aged under 5 years are the most vulnerable group affected by malaria and accounted for 67% (272 000) of all malaria deaths worldwide. The WHO African Region was home to the highest number of malaria deaths in with 94% of all malaria deaths in 2018. In regions with highly seasonal malaria transmission, several studies have shown a sharp decline in malaria infections through the use of intermittent preventive treatment pregnant women and young children between the ages of three and fifty-nine months. Seasonal malaria chemoprevention (SMC) in these young children consists of treatment courses of sulfadoxine– pyrimethamine plus amodiaquine given at monthly intervals during the malaria season to maintain therapeutic anti-malarial drug concentrations in the blood throughout the period of greatest malaria risk. Despite the substantial benefits provided by SMC, one concern is that SMC will impair the acquisition of protective immune responses, thereby increasing the risk of disease in later years. Studies have shown changes in the ages of peak susceptibility to malaria, with older children more vulnerable to disease following the implementation of control strategies. In 2016, SMC was implemented nationwide in Mali. This project will measure the age- specific incidence of malaria in children in Bandiagara, a rural town in central Mali that has been a malaria field research site for two decades. This will include three age groups: 0-4 years (representing the targeted group for SMC), 5-10 years (a “mixed” group of children who received SMC and older ones who did not) and 11-18 years (no history of SMC). We will compare the incidence of asymptomatic and symptomatic malaria to that measured in similar strata before the implementation of seasonal malaria chemoprevention in the community. Using custom protein microarrays, we will compare the antibody responses to malaria antigens by age group before and with SMC implementation. We will identify and map the spatial distribution of parasite reservoirs (including both symptomatic and asymptomatic parasite carriage) using ultra-sensitive molecular testing and define asymptomatic parasite carrier hotspots, particularly in the dry season (January to May). The dry season is of particular interest because during this period, parasite carriage (symptomatic or asymptomatic carriage) and transmission (gametocyte carriage) are very low, and the human reservoir of parasites is significantly reduced. The dry season is thus a critical temporal window of opportunity to eliminate malaria. The results of this study will define the consequences of SMC in pediatric populations in Mali and identify parasite reservoirs, helping to shape new approaches for future malaria control strategies, including treating populations with high asymptomatic carriage and targeting mosquito populations in defined hotspots.