Genomic epidemiology of the 2025 mpox epidemic in Sierra Leone

Mpox is a re-emerging zoonotic disease caused by MPXV, which has led to outbreaks across multiple countries in recent years. Sierra Leone reported its first mpox case in 8 years in January 2025, rapidly becoming the epicenter of a continental outbreak with more than 5,000 confirmed cases by August, a surge with unknown origins, timings and drivers. Phylodynamic analyses using 338 genomes generated from 14 districts suggests that the outbreak was caused by lineage G.1 (A.2.2.1) which descended from lineages circulating in Nigeria. Here we observed a strong APOBEC3 mutational enrichment, consistent with sustained human transmission that circulated undetected for ~3 months before the first confirmed case in January 2025. The Western Area Urban district served as the primary hub for nationwide spread and persistence, as well as multiple international export events. We further estimated that the true epidemic size was nearly double official case counts, highlighting substantial surveillance gaps. These findings underscore the urgent need for strengthened genomic and diagnostic surveillance systems across West Africa to pre-empt epidemics.

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Journal
Nature Medicine
Published
2026-05-12
DOI
https://doi.org/10.1038/s41591-026-04385-8
Primary Topic
Poxvirus research and outbreaks
Type
article
Field-Weighted Citation Impact
0.00

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article

Genomic epidemiology of the 2025 mpox epidemic in Sierra Leone

Paul Cronan, Alie Tia, Dolo Nosamiefan, Anise Happi et al.
Nature Medicine
Poxvirus research and outbreaks
article

Genomic epidemiology of the 2025 mpox epidemic in Sierra Leone

Paul Cronan, Alie Tia, Dolo Nosamiefan, Anise Happi, John Demby Sandi, Oludayo O. Ope-ewe, Alexandra Tuttle, Francis Baimba, Tiangay Kallon, Isatta Wurie, Aboubacry Gaye, Ifeanyi F. Omah, Mignane Ndiaye, Ian Baudi, Ben Fry, Monique A. Foster, Joshua I. Levy, Edyth Parker, Zein Souma, J. M. Campbell, Doris Harding, Andy Mahine Diouf, Colby Wilkason, Jolly Amoche Adole, Ayotunde E. Sijuwola, Patrick Varilly, Anu Jegede Williams, Mouhamed Kane, Zikan Koroma, Abebaw Kebede, K Sesay, Ibrahim Umaru Fofanah, Danny Park, Yenew Kebede, Al Ozonoff, Crystal M. Gigante, Ellory Laning, George Ameh, Walter O. Oguta, Ebenezer Kehinde Ogundana, Naomi Daniel Sesay, Roberta Lansana, Vidalyn Folorunso, Komba Koninga, Foday Thoronka, Alusine Fofanah, Imonikhe Kennedy Kio, Folefac Agnes Njeandoh, Choe Miller, Sofonias Tessema, Mohamed Saio Kamara, Harouna Soumare, Pardis Sabeti, Christopher Tomkins‐Tinch, Aminata Koroma, Donald S. Grant, Allan K. O. Campbell, Jone Ngobeh, Amanda Kargbo, Foday Sahr, Ruth Oluwaseun Obaado, Mohamed Boie Jalloh, Alhaji N’jai, Joseph Kanu, Sia Mani, Christopher Shin, Amadou Alpha Sall, Kristian G. Andersen, Karlie Zhao, Simon Ruhweza, Mohamed Alex Vandi, Ibrahima Socé Fall, Christian Happi, Femi Saibu, Brendan Blumenstiel, Marietou F. Paye, Ivan Specht, Mamadou Aliou Barry, James Squire, Taylor Brock-Fisher, Christine Hughes, John Klena, Boubacar Diallo, Moussa Moise Diagne, Collins Tanui, Martin Faye, Andrew Rambaut, Abdourahmane Sow, Jonathan Greene
article en

Abstract

Mpox is a re-emerging zoonotic disease caused by MPXV, which has led to outbreaks across multiple countries in recent years. Sierra Leone reported its first mpox case in 8 years in January 2025, rapidly becoming the epicenter of a continental outbreak with more than 5,000 confirmed cases by August, a surge with unknown origins, timings and drivers. Phylodynamic analyses using 338 genomes generated from 14 districts suggests that the outbreak was caused by lineage G.1 (A.2.2.1) which descended from lineages circulating in Nigeria. Here we observed a strong APOBEC3 mutational enrichment, consistent with sustained human transmission that circulated undetected for ~3 months before the first confirmed case in January 2025. The Western Area Urban district served as the primary hub for nationwide spread and persistence, as well as multiple international export events. We further estimated that the true epidemic size was nearly double official case counts, highlighting substantial surveillance gaps. These findings underscore the urgent need for strengthened genomic and diagnostic surveillance systems across West Africa to pre-empt epidemics.

Nature Medicine
Broad Institute (US), Scripps Research Institute (US), Centers for Disease Control and Prevention (US), Harvard University (US), University of Sierra Leone (SL), Liverpool School of Tropical Medicine (GB), Njala University (SL), Nnamdi Azikiwe University (NG), Redeemer's University (NG), Africa Centres for Disease Control and Prevention (ET), Public Health Agency (GB), Institut Pasteur de Dakar (SN), World Health Organization Regional Office for Africa (CG), Sierra Leone Urban Research Centre (SL), St John of God Hospital Sierra Leone (SL), Stanford University (US), University of Edinburgh (GB)
U.S. Department of Health and Human Services, U.S. Department of State, World Health Organization, Wellcome, Pennsylvania Department of Health, Minnesota Department of Health, Virginia Department of Health, Wellcome Trust, Open Philanthropy Project, Texas Department of State Health Services, Skoll Foundation, ELMA Foundation, Centers for Disease Control and Prevention
Good health and well-being
Openalex Percentile: Top 6%
Poxvirus research and outbreaks
DOIOpen Access PDFOpenAlex
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