From forest to frontline: A comprehensive review of Mpox's global leap and viral evolution (2022-2024).

Background: Since 2022, the global epidemiology of Mpox (MPXV) has transformed, with Clade IIb driving widespread transmission in non-endemic regions and Clade I resurging across Central Africa. Genomic adaptations, such as APOBEC3 mutations, and increasing human-to-human transmission have raised public health alarms. This review synthesizes the latest evidence on Clade I and Clade II MPXV outbreaks from 2022 to 2024, with an emphasis on geographic expansion, demographic disparities, and systemic response gaps. Methods: A comprehensive literature search was conducted between September and December 2024 using PubMed, CDC, WHO, and ECDC databases. Studies were included if they reported primary data on Clade I or Clade II MPXV epidemiology. Gray literature, including public health reports and situation summaries, was also analyzed. Data extraction focused on demographic trends, transmission modes, genomic mutations, and public health responses. Results: Fifty-one sources were reviewed, including 14 peer-reviewed articles and 37 Gy literature reports. Clade IIb accounted for 117,000+ cases across 123 countries, primarily affecting men who have sex with men (MSM). Clade I resurged in the Democratic Republic of the Congo (DRC) with over 19,000 confirmed cases and 975 deaths, disproportionately affecting children under five. APOBEC3-type mutations were linked to increased Clade I transmissibility. International spread of Clade I was reported in the U.S., Europe, and Asia. Diagnostic limitations, especially in the DRC, and gaps in pediatric vaccine access remain major challenges. Conclusion: MPXV's global trajectory now includes sustained transmission of both Clades I and II. Expanded genomic surveillance, pediatric-focused outbreak response, and equitable diagnostic and vaccine access are urgently needed. A One Health approach is essential to address evolving viral behavior and health disparities in endemic and non-endemic regions.