LA JOLLA, CA—Historically, most human mpox infections have resulted from zoonotic transmission—meaning from animals to humans—and these spillovers have rarely led to human-to-human transmission. But during the 2022 global outbreak, mpox began spreading readily between people. A new study now shows the virus was circulating long before then.
Published in Nature on May 19, 2025, the study notes that mpox transmitted among humans in Nigeria for eight years before sparking the international outbreak in 2022. Using genomic tracing, the researchers estimate that the virus' ancestor first emerged in southern Nigeria in August 2014 and spread to 11 states before human infections were detected in 2017. The findings highlight the need for improved global surveillance and medicines, given the threat of impending pandemics.
"We could have very easily prevented the 2022 multi-country outbreak if countries in Africa were given better access to therapeutics, vaccines and surveillance technologies," says Edyth Parker, a professional collaborator in the Kristian Andersen Lab at Scripps Research and one of the paper's first authors. "In a vulnerably connected world, we cannot neglect epidemics until they get exported to the Global North."
Because the virus involved in the 2022 outbreak had an unexpected number of genetic mutations, scientists thought that mpox might have been circulating in Nigeria for much longer than expected. However, due to a lack of genomic data, it was unclear when and where the virus had first emerged, and what had driven its emergence.
To solve this problem, the study's senior author, Christian Happi, director of the Institute of Genomics and Global Health at Redeemer's University in Nigeria, organized a Pan-African consortium to share and generate mpox genomic data. The consortium involved researchers and public health agencies in West and Central Africa, with support from international collaborators including Scripps Research. By pooling samples and laboratory methods, the group generated a genomic dataset that is around three times larger than any previous mpox dataset.
Altogether, the team analyzed 118 viral genomes from human mpox cases that occurred in Nigeria and Cameroon between 2018 and 2023. All of the sequences were identified as Clade IIb—the mpox strain endemic to West Africa. By comparing the genomes' sequences, the researchers created something called a phylogenetic tree, which estimates how related the different viruses are, and how recently they evolved.
They found that most of the viral samples from Nigeria were the result of human-to-human transmission (105/109), while the remaining four were caused by zoonotic spillover. In contrast, all nine mpox samples from Cameroon were derived from isolated zoonotic spillover events.
"Mpox is no longer just a zoonotic virus in Nigeria; this is very much a human virus," says Parker. "But the fact that there's ongoing zoonotic transmission means there's also a continual risk of re-emergence."
Using the phylogenetic tree, the team estimated that the ancestor of the human-transmitting mpox virus emerged in animals in November 2013 and first entered the human population in southern Nigeria in August 2014. They also showed that southern Nigeria was the main source of subsequent cases of human mpox: though the virus spread throughout Nigeria, continual human-to-human transmission only occurred in the country's south.
The team also showed that two of the zoonotically transmitted viral samples from southern Nigeria were related to the Cameroonian viruses, suggesting that viruses are traveling across the border.
"There's likely a lot more bi-directional viral movement happening between these countries, but we just don't have the wildlife sampling to detect it," says Parker. "Our study highlights the need for better wildlife surveillance, as well as better surveillance in the human populations that interface with animals in that forested border region."
Overall, the study shows the importance of better access to diagnostics, vaccines and therapeutics in Africa, the researchers say.
"Global health inequities really impede our ability to control both zoonotic and sustained human transmission," says Parker. "We cannot continue to neglect either the human epidemics in Africa or the risk of re-emergence—not only does it perpetuate suffering in these regions, it means that inevitably there will be another pandemic."
The article, "Genomics reveals zoonotic and sustained human Mpox spread in West Africa ," was authored by several dozen researchers from multiple organizations. Authors from Scripps Research include Mark Zeller, Karthik Gangavarapu, and Kristian G. Andersen. (For a full author list, view the journal article.)
The Pan-African consortium was supported by the Africa CDC, the Nigerian CDC, the Institute of Genomics and Global Health at Redeemer's University, Centre Pasteur du Cameroun, Institut Pasteur de Bangui, Institut National de la Recherche Biomédicale, the Republic of Congo public laboratory service, Scripps Research, The University of Edinburgh, and the Broad Institute.
This work was supported by grants from the National Institute of Allergy and Infectious Diseases grants U01HG007480, U54HG007480, U01AI151812, U19AI135995, U19AI110818, R01AI153044, and R01AI162611; 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); the Science for Africa Foundation; and a cohort of generous donors through TED's Audacious Project, including the ELMA Foundation, MacKenzie Scott, the Skoll Foundation, and Open Philanthropy.
About Scripps Research
Scripps Research is an independent, nonprofit biomedical research institute ranked one of the most influential in the world for its impact on innovation by Nature Index. We are advancing human health through profound discoveries that address pressing medical concerns around the globe. Our drug discovery and development division, Calibr-Skaggs, works hand-in-hand with scientists across disciplines to bring new medicines to patients as quickly and efficiently as possible, while teams at Scripps Research Translational Institute harness genomics, digital medicine and cutting-edge informatics to understand individual health and render more effective healthcare. Scripps Research also trains the next generation of leading scientists at our Skaggs Graduate School, consistently named among the top 10 US programs for chemistry and biological sciences. Learn more at www.scripps.edu .
