BackgroundMonkeypox 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.MethodsSurveillance 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.ResultsThe 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.ConclusionsUrgent measures, including reinforced, expanded surveillance, contact tracing, case management support, and targeted vaccination are needed to contain this new pandemic-potential Clade Ib outbreak.