Background: Monkeypox virus (MPXV) attracted global attention in 2022 during a widespread outbreak linked primarily to sexual contact. Clade I MPXV is prevalent in Central Africa and characterized by severe disease and high mortality, while Clade II is confined to West Africa and associated with milder illness. A Clade IIb MPXV emerged in Nigeria in 2017, with protracted human-to-human transmission a forerunner of the global Clade II B.1 lineage outbreak in 2022. In October 2023, a large mpox outbreak emerged in the Kamituga mining region of the Democratic Republic of the Congo (DRC), of which we conducted an outbreak investigation. Methods: Surveillance data and hospital records were collected between October 2023 and January 2024. Blood samples and skin/oropharyngeal swabs were obtained for molecular diagnosis at the National Institute of Biomedical Research, Kinshasa. MPXV genomes were sequenced and analyzed using Illumina NextSeq 2000 and bioinformatic tools. Results: The Kamituga mpox outbreak spread rapidly, with 241 suspected cases reported within 5 months of the first reported case. Of 108 confirmed cases, 29% were sex workers, highlighting sexual contact as a key mode of infection. Genomic analysis revealed a distinct MPXV Clade Ib lineage, divergent from previously sequenced Clade I strains in DRC. Predominance of APOBEC3-type mutations and estimated time of emergence around mid-September 2023 suggest recent human-to-human transmission. Conclusions: Urgent measures, including reinforced, expanded surveillance, contact tracing, case management support, and targeted vaccination are needed to contain this new pandemic-potential Clade Ib outbreak.

The authors have declared no competing interest.

This work was funded by the Belgian Directorate-general Development Cooperation and Humanitarian Aid and the Research Foundation - Flanders (FWO, grant number G096222 N to L.L.); the International Mpox Research Consortium (IMReC) through funding from the Canadian Institutes of Health Research and International Development Research Centre (grant no. MRR-184813); Department of Defense, Defense Threat Reduction Agency, Monkeypox Threat Reduction Network; and USDA Non-Assistance Cooperative Agreement #20230048; Africa Pathogen Genomics Initiative helped acquiring and maintaining the sequencer; Agence Francaise de Developement through the AFROSCREEN project (grant agreement CZZ3209, coordinated by ANRS-MIE Maladies infectieuses emergentes in partnership with Institut de Recherche pour le Developpement (IRD) and Pasteur Institute) for laboratory support and PANAFPOX project funded by ANRS-MIE. E.L. received a PhD grant from the French Foreign Office. A.O.T. and A.R. acknowledge the support of the Wellcome Trust (Collaborators Award 206298/Z/17/Z, ARTIC network).

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