"Investigating the rebound effects of seasonal malaria chemoprevention (SMC) in Mali"

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Summary Seasonal Malaria Chemoprevention (SMC) has been recommended by WHO for malaria endemic countries in sub-Saharan Africa with strong seasonal malaria transmission since 2012. The intervention consists of the administration of full treatment doses of Sulfadoxine-Pyrimethamine (SP) plus Amodiaquine to children less than 5 years of age every 4 weeks during the malaria transmission season for 3 to 4 rounds per year. Since 2016, Mali has implemented the strategy countrywide. While significant decreases in malaria cases among the target age group was observed, increasing trends in malaria among children 5 years and above is also reported in the many settings where SMC is being implemented. The proposed study considers previous studies and pilot data showing that approximately out of every eight children (12.5%) have historically received either no doses or a single dose out of a the required four doses for the treatment regimen. This study seeks to enroll a large cohort of children to permit a large-scale comparison between children previously compliant to SMC with a valid control group (children not previously compliant to SMC) to elucidate the effects of phasing out of the SMC program due to age ineligibility. The primary objective of this R01 proposal is to investigate the withdrawal effects of SMC due to age eligibility requirements through the following three specific aims: 1) Determine malaria rebound occurrence following SMC enrollment including its association with severe malaria and anemia; 2) Assess changes in the age-specific P. falciparum prevalence, sexual and asexual parasites, and multiplicity of infection following SMC deployment; and 3) Assess the change in immune response to malaria antigens during and following SMC eligibility and the relationship with disease. The study will provide valuable information on the impact of SMC stoppage at five years of age which can significant contribute improving monitoring malaria outcomes in other low- and middle-income countries overall.