Molecular epidemiology of recurrent zoonotic transmission of mpox virus in West Africa

Nigeria and Cameroon reported their first mpox cases in over three decades in 2017 and 2018 respectively. The outbreak in Nigeria is recognised as an ongoing human epidemic. However, owing to sparse surveillance and genomic data, it is not known whether the increase in cases in Cameroon is driven by zoonotic or sustained human transmission. Notably, the frequency of zoonotic transmission remains unknown in both Cameroon and Nigeria. To address these uncertainties, we investigated the zoonotic transmission dynamics of the mpox virus (MPXV) in Cameroon and Nigeria, with a particular focus on the border regions. We show that in these regions mpox cases are still driven by zoonotic transmission of a newly identified Clade IIb.1. We identify two distinct zoonotic lineages that circulate across the Nigeria-Cameroon border, with evidence of recent and historic cross border dissemination. Our findings support that the complex cross-border forest ecosystems likely hosts shared animal populations that drive cross-border viral spread, which is likely where extant Clade IIb originated. We identify that the closest zoonotic outgroup to the human epidemic circulated in southern Nigeria in October 2013. We also show that the zoonotic precursor lineage circulated in an animal population in southern Nigeria for more than 45 years. This supports findings that southern Nigeria was the origin of the human epidemic. Our study highlights the ongoing MPXV zoonotic transmission in Cameroon and Nigeria, underscoring the continuous risk of MPXV (re)emergence.Competing Interest StatementThe authors have declared no competing interest.Funding StatementFlu Lab TEDs Audacious Project including the ELMA Foundation MacKenzie Scott the Skoll Foundation and Open Philanthropy This work was supported by grants from the National Institute of Allergy and Infectious Diseases grants: U01HG007480 U54HG007480 U01AI151812 U19AI135995 U19AI110818 R01AI153044 R01AI162611 This work was also supported by the World Bank grants projects ACE-019 and ACE-IMPACT The Rockefeller Foundation Grant $#$2021 HTH The Africa CDC through the African Society of Laboratory Medicine Grant $#$INV018978 Science for Africa Foundation Ifeanyi Omah is supported by the Wellcome Trust Hosts Pathogens & Global Health program Grant number 218471/Z/19/Z in partnership with Tackling infectious Disease to Benefit Africa TIBA PL is supported by the European Unions Horizon 2020 project MOOD grant agreement no 874850 and by the Research Foundation - Flanders Fonds voor Wetenschappelijk Onderzoek - Vlaanderen G0D5117N G005323N and G051322N We thank Advanced Micro Devices Inc for the donation of massively parallel computing hardwareAuthor DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Nigerian CDC Centre Pasteur du Cameroun National Reference LaboratoryI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll sequences are available on Genbank under Accession numbers PP860025-PP860033. All other data are available at https://github.com/andersen-lab/MPXV_zoonotic_transmission_West_Africa https://github.com/andersen-lab/MPXV_zoonotic_transmission_West_Africa

2