<p>Scenarios and coverage levels for modelling.</p>

Malaria constitutes a major public health burden in sub-Saharan Africa. It remains a key health concern and the leading cause of death in children under five in Benin. Since October 2021, the World Health Organization has recommended the use of malaria vaccines for the prevention of Plasmodium falciparum malaria in children living in malaria endemic areas, prioritizing areas of moderate and high transmission in sub-Saharan Africa. However, with the exception of Ghana, there is a scarcity of studies modelling the potential impact of the RTS,S/AS01 vaccine in the context of West Africa. A compartmental mathematical model was developed to estimate clinical and severe malaria cases averted in children under five with the primary series of the RTS,S/AS01 malaria vaccine in Benin. Over a period of 10 years, scenarios involving vaccine introduction at different coverage levels alongside the use of long-lasting insecticidal nets were modelled to assess the impact of the RTS,S/AS01 vaccine on malaria transmission. The combination of childhood malaria vaccination at a coverage similar to that of the third dose of diphtheria, tetanus, and pertussis (DTP3) vaccine, along with the current use of nets, is projected to result in a 40% reduction in malaria clinical cases and deaths among children under five years old, compared to using nets alone, from 2025 to 2034. However, if the introduction of a malaria vaccine has the unintended consequence of decreased net use, cumulative benefits may be offset. A 1.5-fold decrease in the use of nets is projected to result in an increase in malaria burden. This modelling exercise concludes that childhood vaccination is expected to avert clinical and severe cases of malaria and is an additional tool to advance malaria control efforts in Benin but potential unintended consequences of a reduction in net usage may reduce these gains.