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