Emergence of mpox in Guinea: sporadic clade IIa cases and a clade IIb upsurge

Abstract Background Mpox virus (MPXV) has caused recurrent outbreaks in West Africa. However, Guinea had not previously reported laboratory-confirmed cases or MPXV genomic data. Methods Suspected cases were identified in the N’Zérékoré region as well as in the Conakry (Sept 2024– Dec 2025) and confirmed by real-time PCR in regional and central laboratories, respectively. Whole-genome sequencing using nanopore technology was performed in-country, followed by phylogenetic and time-scaled evolutionary analyses. Findings The first mpox case was clinically diagnosed in September 2024 in the N’Zérékoré region and laboratory-confirmed by the prefectural laboratory in Guéckédou. In total, seven cases were confirmed in Forest Guinea, of which five complete or almost complete MPXV genomes were recovered. All belonged to MPXV clade IIa. Genomic divergence, ancestral dating, and low APOBEC3-associated mutation frequencies were consistent with multiple independent zoonotic spillover events. In June 2025, one of the first mpox cases of an unfolding outbreak was confirmed in Conakry. Whole genome sequencing revealed MPXV clade IIb lineage G.1. By December 2025, the number of laboratory-confirmed mpox cases nationwide increased to 2,151. A total of nine outbreak strains were sequenced, all belonging to Clade IIb. The genomes clustered with contemporaneous genomes from Sierra Leone and showed high APOBEC3-associated mutation frequencies, suggesting sustained human-to-human transmission in the region. Interpretation These data demonstrate simultaneous circulation of MPXV clade IIa and IIb strains in Guinea, likely resulting from zoonotic spillover and human-to-human transmission, respectively. Decentralised diagnostics and in-country sequencing facilitated rapid case confirmation and genomic surveillance, highlighting the importance of these critical capacities for outbreak preparedness and response. Funding German Federal Ministry of Health and the German Center for Infection Research (DZIF).