Spatiotemporal Transmission Characteristics of Global Monkeypox - Worldwide, January 2022-September 2025.

Introduction: Since 2022, the global monkeypox (mpox) epidemic has undergone clade replacement from clade IIb to clade Ib, accompanied by a geographic shift in the epidemic's epicenter. However, systematic analyses spanning the entire epidemic cycle from 2022 to 2025 remain limited. Integrating global epidemiological and genomic data is essential for determining spatiotemporal transmission dynamics. Methods: Global mpox surveillance data, mpox virus whole-genome sequences, and demographic data were collected. Retrospective spatiotemporal scan statistics were used to identify significant transmission clusters. Phylogenetic trees were used to characterize evolutionary relationships among clades, and haplotype network analysis was used to infer transmission pathways. Results: A total of 165,244 mpox cases were reported globally, showing a two-phase pattern. From January 2022 to August 2023, clade IIb predominated, accounting for 96.18% of cases in Europe and the Americas. From September 2023 to September 2025, the epicenter shifted to Africa, where clade Ib became dominant; during this phase, Africa accounted for 71.48% of global cases. Spatiotemporal scan analysis identified 10 significant clusters, with the highest relative risk observed in the West African cluster in 2025. Phylogenetic analyses linked clade IIb to the European and American phases, whereas clade Ib was associated with the African phase. The haplotype network suggested that Africa is the core transmission region of clade Ib, with Europe serving as a dissemination hub. Conclusion: Mpox evolved from IIb-driven global dissemination to Ib-dominated regional clustering in Africa, with clade replacement driving the geographic shifts. The current risk is concentrated in Africa, underscoring the need for strengthened surveillance, genomic tracing, equitable access to resources, and targeted interventions.