Impact of vaccination coverage and timing on recent yellow fever outbreaks in Africa: a modeling study

Background: Multiple recent yellow fever (YF) outbreaks have occurred despite a highly effective vaccine. Increasing vaccination coverage and decreasing response times have been key components of the Eliminate Yellow Fever Epidemics (EYE) strategy. However, the combined impacts of these factors on YF outbreaks, especially since implementation of the EYE strategy in 2017, remain uncertain. Methods: We developed mathematical models to simulate the effects of vaccination coverage and timing, calibrating them to recent YF outbreaks in Ghana (2021-2022) and South Sudan (2023-2024). We then projected YF morbidity and mortality under different EYE strategy thresholds for vaccination coverage and timing. Results: In Ghana, where reactive vaccination was observed at 22 days with an estimated 70% baseline coverage, modeled delays of 60 and 120 days yielded 62 (95% uncertainty interval [UI] 30-119) and 281 (95% UI 59-927) additional severe cases, respectively. Increasing baseline vaccination coverage to 80% averted an estimated 20 severe cases (95% UI 14-25). In South Sudan, where reactive vaccination occurred at 61 days with estimated 50% baseline coverage, shortening the response time to 20 days and increasing baseline coverage to 80% averted an estimated 80 (95% UI 68-91) and 95 severe cases (95% UI 80-112) independently or 103 severe cases (95% UI 85-120) if combined. Conclusion: Increasing baseline YF vaccination coverage to at least 80% can avert substantial morbidity from YF outbreaks. Decreasing vaccination response time for reactive vaccination can provide additional benefit.