Mathematical assessment of the impact of the R21/Matrix-M vaccine on the control of malaria in children in Burkina Faso

This study is based on the design and analysis of a novel age- and dose-structured model for assessing the population-level impact of the recently-approved R21/Matrix-M malaria vaccine (which is administered in three doses followed by a booster dose) on controlling the spread of malaria in children under five in Burkina Faso. While the current malaria vaccination program in Burkina Faso prioritizes children 0-3 years of age (Group 1 in our model), we also assessed a hypothetical scenario where children 3-5 years of age (Group 2 in our model) are also vaccinated (since children under five years of age suffer the brunt of malaria morbidity and mortality). The vaccination-free version of the model was calibrated using yearly cumulative malaria mortality data for children in Burkina Faso. In addition to establishing well-posedness, we showed that the disease-free equilibrium of the model is locally-asymptotically stable whenever the control reproduction number ([R]v) is below one. Conditions for achieving vaccine-induced herd immunity (needed for disease elimination) under varying age-group structures and dosage schedules were derived, and a global sensitivity analysis was conducted to identify the parameters of the model that most strongly influence [R]v. Simulations of a homogeneous model including only Group 1 indicate that administering only the first dose of the vaccine with baseline bednet usage requires an impractically high herd immunity threshold of 97%. However, with all four doses, herd immunity is achievable without bednet when the required coverage ratios receiving doses 2, 3, and the booster dose are 73% to 90%. With baseline bednets, these ratios drop to just 10%-30%, dramatically improving elimination prospects. In a heterogeneous setting incorporating both Groups 1 and 2, herd immunity can be achieved (with bednet at baseline) by vaccinating either 46% of the total population of Groups 1 and 2 or 75% of individuals in Group 1 alone. Simulations of the full two-group model (with bednet at baseline) show that vaccinating only children in Group 1 with the first dose reduces the cumulative number of new malaria cases and malaria-induced deaths in Group 1 by about 19%-20%, and produces spillover reductions of about 11%-12% in the unvaccinated Group 2, indicating a moderate indirect benefit across groups. If children in Group 1 receive all four doses, the reductions in Group 1 increase to about 36%-38%, with larger spillover reductions of about 25%-26% in Group 2. When both groups receive only the first dose, the malaria burden decreases by about 24%-26% in each group. The greatest reductions occur when both groups receive all four doses, yielding decreases of about 43%-46%. These results show that extending Burkina Fasos current vaccination program to include children in the 3-5-year age group can substantially improve malaria elimination prospects, particularly when combined with bednet usage at baseline levels or higher.