Genomic and Evolutionary Dynamic Surveillance of Mpox Diagnosed at the National Laboratory of Clinical Biology of Public Health in the Central African Republic

The recent MPXV epidemic in Africa revealed significant viral diversity and complex transmission dynamics, warranting a sub-regional genomic study. We analysed 1,630 high-quality MPXV clade Ia genomes from seven Central African countries, revealing the complex and concurrent circulation of subclades Ia and Ib. Sub clade Ia showed high viral diversity in reservoir hosts, detected through zoonotic transmission and associated with a recently observed persistent human epidemic. In contrast, clade Ib showed evidence of sustained human-to-human transmission in East and Southern Africa. Similar to clade Ia, clade IIb exhibits ongoing zoonotic transmission and a persistent human epidemic linked to the circulation of G1 and G2 lineages. Phylogeographic analyses revealed frequent cross-border transmission and significant interconnectedness, consistent with human mobility corridors and international borders. For example, the Democratic Republic of Congo and Sierra Leone appear to be sources of regional exports, while the Cameroon-Nigeria, Central African Republic-Cameroon, and Central African Republic-DRC interfaces reflect ongoing cross-border zoonotic spillovers. These findings underscore the need for harmonised genomic surveillance, APOBEC3-based triage, and integrated One Health strategies to prevent the escalation of local outbreaks into regional epidemics and to guide vaccine deployment and public health preparedness.