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Changing Trends in Global Burden of Mpox Infection from 1970 to 2025: A Systematic Review and Observational Study
68 Pages Posted: 26 Dec 2025
More...Abstract
Background: Mpox is a re-emerging zoonosis caused by an Orthopoxvirus. After the first human case in 1970, outbreaks remained confined to Central-/West-Africa until 2022, when clade IIb triggered sustained global transmission. Smallpox-vaccine cessation has left populations universally susceptible, and clade-specific differences in severity have been described but never quantified across five decades. We aimed to map the global burden of mpox from 1970 to 2025, to provide scientific basis for subsequent prevention and control efforts.
Methods: We firstly conducted a systematic review and meta-analysis to estimate the global burden of mpox infection from 1970 to 2025. Literature searches were performed in Scopus, Web of Science, Embase, and the WHO website from inception to October 11, 2025. Studies reporting incidence, hospitalization, or case fatality rates in confirmed mpox cases were included. Pooled estimates were calculated using random- or fixed-effects models based on heterogeneity (I² statistic). Subgroup analyses were performed by clade, region, gender, age, MSM proportion, HIV status, and vaccination rate and supplemented with mixed linear models to investigate influencing factors. Then, we conducted an observational study collecting data from WHO surveillance reports from May 2022 to November 2025 to analyze temporal and regional trends of 2022-2025 Mpox outbreak wave.
Findings: A total of 70 studies were included in the meta-analysis. Prior to 2022, the pooled hospitalization rate was 33.00% and the case fatality rate was 3.28%. After 2022, the pooled incidence rate was 7.52 per 1000 person-years, while hospitalization and case fatality rates decreased to 10.20% and 0.71. Subgroup analyses revealed that clade Ia was associated with the highest hospitalization (≈80%) and case fatality (≈9%) rates, whereas clade IIb outbreaks outside Africa were larger but clinically milder. The African Region (AFRO) consistently reported higher case fatality rates compared to the American (AMRO) and European (EURO) regions. Surveillance data indicated a shift in case burden to AFRO from 2024 onward, with Central Africa experiencing a sharp rise in cases.
Interpretation: For the first time we quantify a 55-year gradient of mpox burden: pre-2022 Central African clade-Ia outbreaks were >4-fold deadlier than the 2022-2025 global clade-IIb wave. Despite higher 2022-2023 case counts in high-income regions, Africa continues to bear the excess mortality. Strengthening clade-Ia surveillance, targeted vaccination and health-system capacity in Central-Africa is urgently needed to reduce the still-disproportionate global burden.
Keywords: Mpox, Disease burden, Incidence, Hospitalization, Case fatality, Meta-analysis, Cross-sectional
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