Epidemiology and phylogenomic characterisation of two distinct mpox outbreaks in Kinshasa, DR Congo, involving a new subclade Ia lineage: a retrospective observational study

Authors: Hensley, Lisa; MERRITT, SYDNEY - University Of California (UCLA); KINGANDA-LUSAMAKI, EDDY - Institute National Research Biomedical; JANSEN, DAAN - Institute Of Tropical Medicine; HALBROOK, MEGAN - University Of California (UCLA); O'TOOLE, AINE - University Of Edinburgh; PUKUTA-SIMBU, ELISABETH - Institute National Research Biomedical; HASIVIRWE VAKANIAKI, EMMANUEL - Institute National Research Biomedical; OLA-MPUMBE, RILIA - Institute National Research Biomedical; KWETE-MBOKAMBA, PAPY - Institute National Research Biomedical; WAWINA-BOKALANGA, TONY - Institute National Research Biomedical; AKIL-BANDALI, PRINCE - Institute National Research Biomedical; KACITA, CRIS - Ministry Of Public Health; PONGA-MUSEME, ANGE - Institute National Research Biomedical; MAPENZI-MAPENZI, NELSON - Institute National Research Biomedical; AMURI-AZIZA, ADRIENNE - Institute National Research Biomedical; TSHIANI-MBAYA, OLIVER - Institute National Research Biomedical; PAKU-TSHAMBU, PRINCESSE - Institute National Research Biomedical; DANTAS, PEDRO - Institute Of Tropical Medicine; DE BLOCK, TESSA - Institute Of Tropical Medicine; LOKILO, EMMANUEL - Institute National Research Biomedical; MUSWAMBA, CHLOE - Institute National Research Biomedical; MAKANGARA-CIGOLO, JEAN CLAUDE - Institute National Research Biomedical; LUAKANDA, GRADI - Institute National Research Biomedical; KELVIN, DAVID - Dalhousie University; PRATT, CATHERINE - Biosurv International; AYOUBA, AHIDJO - University Of Montpellier; TESSEMA, SOFONIAS - Africa Center For Disease Control And Prevention (CDC); MAURO REZENDE, ANTONIO - Fiocruz-Instituto Rene Rachou; DELAPORTE, ERIC - University Of Montpellier; MWAMBA, DIEUDONNEE - National Institute Of Public Health; SUBISSI, LORENZO - World Health Organization (WHO); LIESENBORGHS, LAURENS - Institute Of Tropical Medicine; HOFF, NICOLE - University Of California (UCLA); PEETERS, MARTINE - University Of Montpellier; LOW, NICOLA - University Of Bern; AHUKA-MUNDEKE, STEVE - Institute National Research Biomedical; MUYEMBE-TAMFUM, JEAN-JACQUES - Institute National Research Biomedical; RIMOIN, ANNE - University Of California (UCLA); KINDRACHUK, J - University Of Manitoba; VERCAUTEREN, KOEN - Institute Of Tropical Medicine; RAMBAUT, ANDREW - University Of Edinburgh; MBALA-KINGEBENI, PLACIDE - Institute National Research Biomedical

Submitted to: Lancet
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/16/2025
Publication Date: 7/5/2025
Citation: Hensley, L.E., Merritt, S., Kinganda-Lusamaki, E., Jansen, D., Halbrook, M., O'Toole, A., Pukuta-Simbu, E., Hasivirwe Vakaniaki, E., Ola-Mpumbe, R., Kwete-Mbokamba, P., Wawina-Bokalanga, T., Akil-Bandali, P., Kacita, C., Ponga-Museme, A., Mapenzi-Mapenzi, N., Amuri-Aziza, A., Tshiani-Mbaya, O., Paku-Tshambu, P., Dantas, P.H., De Block, T., Lokilo, E., Muswamba, C., Makangara-Cigolo, J., Luakanda, G., Kelvin, D.J., Pratt, C., Ayouba, A., Tessema, S., Mauro Rezende, A., Delaporte, E., Mwamba, D., Subissi, L., Liesenborghs, L., Hoff, N.A., Peeters, M., Low, N., Ahuka-Mundeke, S., Muyembe-Tamfum, J., Rimoin, A.W., Kindrachuk, J., Vercauteren, K., Rambaut, A., Mbala-Kingebeni, P. 2025. Epidemiology and phylogenomic characterisation of two distinct mpox outbreaks in Kinshasa, DR Congo, involving a new subclade Ia lineage: a retrospective observational study. Lancet. 406:63-75. https://doi.org/10.1016/S0140-6736(25)00294-6.
DOI: https://doi.org/10.1016/S0140-6736(25)00294-6

Interpretive Summary: Mpox, the disease caused by the mpox virus (MPXV), is endemic and widespread in the Democratic Republic of the Congo (DRC). Historically, mpox infections have been isolated to rural, self-limiting clusters driven by animal-to-human transmission of clade I MPXV. However, recently, Clade I MPXV has been subdivided into two distinct subclades, Ia and Ib. These two subclades are different in their genetic signature, and also primary transmission mode: subclade Ib has been shown to transmit between humans. Given the expanding outbreaks of mpox in the DRC, we sought to analyze the epidemiologic and phylogenomic dynamics of the outbreak in the capital city of Kinshasa. We show two distinct periods of mpox transmission (before and after the introduction of Clade Ib in July 2024), as well as present evidence of supposed human-to-human transmission of subclade Ia, and high rates of APOBEC-3 mutation. Ultimately, these findings have major implications for mpox control and surveillance in the city. As a major metropolitan hub of the African continent, sustained mpox transmission in Kinshasa (as evident in this study) is a major public health concern.

Technical Abstract: Background: Clade I mpox virus (MPXV) is endemic in the Democratic Republic of the Congo (DRC). We aimed to describe the epidemiologic and genomic characteristics of PCR-confirmed mpox cases in Kinshasa, DRC, in 2024. Methods: In this retrospective observational study, we analysed diagnostic, epidemiological, and clinical data from suspected mpox cases in Kinshasa from January 2023 to October 2024. MPXV infection and subclade were confirmed by polymerase chain reaction (PCR). Whole genome sequencing was conducted for phylogenomic analysis and assessment of APOBEC3 mutational signature. Findings: Among PCR-confirmed cases (n=440) we defined two distinct periods of MPXV introduction and circulation. From August 2023, self-limiting transmission chains resulted from different introductions of subclade Ia.; Subclade Ib cases were detected from July 2024. Case investigation data was available from 127 confirmed cases (95 subclade Ia and 32 subclade Ib). . Fever and rash were the reported most frequently for both subclades; (ano)-genital lesions were also commonly reported. Genomic analysis of 93 samples indicated that most mutations were consistent with APOBEC3-driven mutations, 68% for subclade Ia and 72% for subclade Ib. Interpretation: Sustained human transmission of MPXV subclades Ia and Ib occurred in Kinshasa, as of July 2024. Increased proportions of APOBEC3-driven changes in the new subclade Ia lineage support a shift towards increased human-to-human transmission. This highlights important changes in mpox transmission dynamics and suggests the potential for MPXV to cause sustained human outbreaks if favourable transmission conditions are met. Funding: Belgian Directorate-General for Development Cooperation and Humanitarian Aid; The Research Foundation - Flanders; ITM SOFI programme supported by the Department of Economy, Science, and Innovation of the Flemish government; Global Health EDCTP3; Canadian Institutes of Health Research and International Development Research Centre; Department of Defense Threat Reduction Agency; United States Department for Agriculture Agriculture Research Service; Agence Française de Développement through the AFROSCREEN project.