Background In September 2023, an mpox outbreak was reported in the eastern part, South Kivu Province, of Democratic Republic of the Congo. This outbreak is still ongoing and expanding to other regions and countries. Here, we describe the epidemiological and genomic evolution of the outbreak from September 2023 to June 2024. Methods Consenting patients with mpox-like symptoms admitted to the Kamituga and the Kamanyola hospitals were recruited to the study. Samples from throat, lesions, breast milk and placenta were collected for PCR testing and sequencing. For the patients from Kamituga hospital, data on place of residence and possible exposures were collected by interviews. The location and numbers of employees were collected for all bars with sex workers. Where possible, exposures were linked to the genomic sequencing data for cluster analysis. Findings In total, 670 (suspected) mpox cases were admitted to the Kamituga hospital. There were slightly more female than male cases (351/670 [52,4%] versus 319/670, [47,6%], and cases were reported from 17 different health areas. The majority of cases were reported in Mero (205/670 [30,6%]), followed by Kimbangu (115/670 [17,2%]), Kabukungu (105/670 [16,7%]), and Asuku (73/670 [10.9%]). During this period, 7 deaths occurred and 8 out of 14 women who were pregnant had fetal loss. Three healthcare workers acquired mpox infection when caring for patients. In depth case ascertainment showed that 83,4% of patients reported recent visits to bars for (professional) sexual interactions as a likely source of infection. Whole genome sequencing resulted in the generation of 58 genome sequences. Three main clusters characterized by specific mutations were identified and several miniclusters of 2 or more sequences with over two shared mutations. No clear link between sequence cluster, bar or health area was observed. The more recent sequences from Kamanyola were related to the sequences in Kamituga and confirmed to be Clade Ib. However, relatively long branches were observed and one of the sequences clustered with publicly released sequences from travelers in Kenya, Uganda, Sweden and Thailand, indicating more undocumented ongoing spread for cluster A than for the other clusters. Most observed mutations were APOBEC-3 related mutations indicative of ongoing human-to-human transmission. Interpretation These data suggests that the rapid transmission of monkeypox virus until June 2024 was mostly related to interactions with professional sex workers (PSW) within densely populated health areas. The expanding number of cases and the recent expansion to 29 other nearby health zones of South -Kivu as well as Rwanda, Burundi, Uganda and Kenya stresses the need for cross border surveillance and collaboration. Urgent enhanced response action is needed, including case finding, diagnostic capacity building, health education programmes focussing on sex workers, and possibly vaccination to limit further escalation and stop this outbreak.

The authors have declared no competing interest.

The work received support from the Global Health EDCTP3 Joint Undertaking (Global Health EDCTP3) program under grant agreement No. 101103059 (GREATLIFE) to build local capacity in terms of sequencing, the EU Horizon 2020 grant VEO (874735) for bioinformatic analysis. The Clade Ib specific PCR assay was developed with support from DURABLE (HERA funded network), LMM was supported by a scholarship from the Wildlife Conservation Network (WCN) and Conservation Action Research Network (CARN).

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The ethical clearance to conduct these studies was obtained from the Ethical Review Committee of the Catholic University of Bukavu (Number UCB/CIES/NC/022/2023.

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