Mpox severity and mortality in Africa: a systematic review and meta-analysis

Mpox presents a significant public health threat with variable severity driven by viral clades and host factors. After over 50 years of outbreaks, this study aimed at providing a comprehensive continent-wide assessment of its severity and mortality for evidence-based public health planning and clinical management.

This systematic review and meta-analysis, conducted per PRISMA guidelines and registered with PROSPERO (CRD420251133745), aggregated data from studies on mpox severity and mortality in Africa from 1970 to 2025. A systematic search of multiple databases was performed. The primary outcomes were the mpox severity rate (proportion of severe cases among confirmed cases) and the case fatality rate (CFR). Random-effects models were used due to high heterogeneity.

The pooled severity rate among confirmed mpox cases in Africa was 43.8% (95% CI: 36.3-51.6; n = 5,417; 37 reports). The pooled CFR was 3.8% (95% CI: 1.9-7.6; n = 6,877; 43 reports) for confirmed cases and 2.5% (95% CI: 1.3-4.6; n = 3,815; 47 reports) for suspected cases. A significant temporal decline was observed; after the 2022 global outbreak, the CFR for confirmed cases dropped to 1.04% from 6.50% beforehand. Substantial geographical disparities existed, with the Central African region bearing the highest burden (severity: 45.51%; CFR: 5.44%), compared to West Africa (severity: 25.43%; CFR: 0.97%). Infections with Clades Ia and Ib were associated with higher severity, whereas Clade II was linked to milder disease. Key risk factors for severe outcomes and death included young age (< 10 years), HIV coinfection, lack of prior smallpox vaccination, and pregnancy. Community-based studies reported higher CFRs than hospital-based studies. No significant publication bias was detected, and sensitivity analyses confirmed the robustness of the pooled estimates.

This study confirms a high but declining burden of severe and fatal mpox in Africa, characterized by significant temporal, geographic, and clade-specific variations. While a global shift towards milder disease is evident, Central Africa remains disproportionately at risk due to the persistent circulation of more virulent clades and underlying health inequities. Sustained investment in surveillance, vaccination, and strengthened healthcare capacity in endemic regions is crucial to reduce future morbidity and mortality.