Genomic epidemiology uncovers the origin of the mpox epidemic in Sierra Leone

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Abstract
In January 2025, Sierra Leone reported its first mpox case in eight years, followed by a rapid nationwide surge that made it the epicenter of the continental mpox virus (MPXV) Clade IIb A.2.2 outbreak, with more than 5,000 confirmed cases reported by August. To investigate the origin, timing, and spread of this epidemic, we generated 338 high-quality MPXV genomes from cases across 14 districts and conducted Bayesian phylogeographic analyses. We found that transmission was driven by a newly emerging Clade IIb lineage, G.1, descended from lineages circulating in the ongoing Nigerian epidemic. Phylogeographic reconstructions indicate that G.1 arose in late September 2024 and circulated undetected for approximately three months before establishing sustained transmission in the densely populated Western Area Urban and Rural districts, which became the principal source of repeated viral introductions that drove epidemics in other regions. Together, these findings reveal the origins and dispersal dynamics of the 2025 mpox outbreak in Sierra Leone and underscore that effective control remains achievable through targeted vaccination, strengthened early warning systems, and improved access to genomic and diagnostic surveillance.

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