Assessing the impact of routine malaria vaccination on total disease burden in Cameroon: a nationwide difference‑in‑differences analysis using health district surveillance data (2023–2025)

Cameroon introduced the RTS, S/AS01 malaria vaccine into routine expanded immunisation (EPI) in 2024, targeting 42 priority health districts. We assessed changes in total malaria burden between intervention and non-intervention districts over 2023–2025. We conducted a retrospective, quasi-experimental, ecological longitudinal study using a difference-in-differences (DiD) approach on routine district-level surveillance data from 206 districts (42 intervention, 164 non-intervention) for 2023–2025. Outcomes included severe malaria rate (per 1,000 children < 5), uncomplicated malaria rate, all malaria-related hospitalisations, and malaria mortality rate (per 100,000). Crude pre-post changes and DiD were calculated. Adjusted linear DiD models with district and year fixed effects and cluster-robust standard errors were also fitted. Subgroup analyses examined interactions with seasonal malaria chemoprevention (SMC), intermittent preventive treatment in infants (IPTi), insecticide-treated nets (ITNs), and ecological region. Baseline characteristics differed significantly: intervention districts had higher ITN coverage (60.2% vs. 45.5%, p = 0.006), higher IPT coverage (35.1% vs. 24.4%, p = 0.001), and larger populations (median 121,284 vs. 89,592, p = 0.029). From 2023 to 2025, intervention districts experienced larger declines in all outcomes. Crude DiD showed a 2.6 per 1000 (15%) reduction in severe malaria, 8.1 per 1000 (22%) reduction in uncomplicated malaria, 5.3 per 1000 (28%) reduction in hospitalisations, and 4.1 per 100,000 (26%) reduction in malaria deaths. Adjusted linear DiD estimates were not statistically significant (e.g., severe malaria coefficient − 0.54, 95% CI − 11.07 to 9.99, p = 0.920). Subgroup analyses indicated the largest effects in the Sahel (crude rate ratio 0.78) and added benefit when the vaccine was combined with SMC (additional − 5.6 per 1000 reduction). In 2025 alone, vaccination averted an estimated 7,200 severe cases, 12,800 uncomplicated cases, 5,300 hospitalisations, and 77 deaths. Crude trends show favourable declines in malaria burden in intervention districts, but adjusted estimates were null, likely due to selection bias and low power. These findings support continued vaccine scale-up and use of routine data for monitoring, while acknowledging the limitations of non-randomised evaluations.