In Mali, malaria exhibits strong seasonality, posing significant health risks to young children. To reduce this burden, Seasonal Malaria Chemoprevention (SMC) has been introduced, which entails providing monthly doses of antimalarial medication to children aged 3–59 months over a four-month period coinciding with peak malaria transmission. This study investigated changes in malaria incidence in the general population across the health districts of Kadiolo, Kati, Yorosso, Sikasso, and Tominian during the rollout of SMC. We conducted a cross-sectional analysis using routine malaria case data combined with meteorological records from Nasa Giovanni for 2016–2018. The relationship between malaria incidence and climate variables was assessed using Generalized Additive Models (GAMs). Over the three-year period, malaria incidence in all districts was positively linked to relative humidity, rainfall, and minimum temperatures. While relative humidity and monthly incidence varied between districts, average temperature and rainfall were relatively uniform. A reduction in malaria cases among children under five was observed in 2017 and 2018 compared to 2016. The SMC program coincided with a decline in malaria incidence among young children, highlighting its potential effectiveness. Strategic timing of SMC administration is crucial to achieve optimal protection during peak transmission periods.
