Objective: To synthesize updated epidemiological, genomic, clinical, and policy evidence on mpox, with emphasis on the emergence of Clade I sub-lineage "Clade Ib" and its implications for One Health-based preparedness.
Methods: This narrative, non-systematic state-of-the-art review draws on literature indexed in PubMed/MEDLINE, Scopus, Web of Science, and Embase, alongside official reports from WHO, Africa CDC, CDC, ECDC, and FAO. Searches covered January 2000 to May 2025, with epidemiological data included through 31 May 2025. Human observational studies, outbreak reports, genomic analyses, clinical trials, and guidance documents were included. Evidence was synthesized in alignment with SANRA principles.
Key findings: Since the 2022 global outbreak driven by Clade IIb, mpox epidemiology has shifted with sustained transmission of Clade I variants in Central Africa and the emergence of a proposed Clade Ib lineage characterized by APOBEC3-associated mutational signatures. Pediatric predominance and household transmission patterns distinguish recent outbreaks from earlier sexual-network-associated spread. Vaccine effectiveness of JYNNEOS varies by population and dosing regimen, while randomized trials (PALM007, STOMP) have not demonstrated statistically significant clinical benefit of tecovirimat on primary endpoints. Environmental surveillance and genomic sequencing remain critical to tracking transmission dynamics.
Implications: Even amid sustained human-to-human transmission, integrated One Health strategies-linking human, animal, and environmental surveillance are essential for outbreak containment, equitable vaccine deployment, and long-term prevention.
Keywords: APOBEC3; Clade I; Clade Ib; Genomic surveillance; Mpox; One Health; Vaccine effectiveness.
© 2026 Published by Elsevier Inc.