Mpox Exposes the Cost of Waiting Until a Regional Disease Becomes a Global Emergency

The global mpox emergency of 2022 looked sudden. A new review of more than five decades of evidence argues that it was anything but. Long before cases spread across more than 100 non-endemic countries, West Africa had already experienced years of weak surveillance, declining population immunity, changing transmission patterns and viral evolution that remained only partially visible to public-health systems.

The review, "Five Decades of Mpox in West Africa: History, Epidemiology, Viral Evolution, and Reservoir Ecology (1970–2025)," was published in Zoonotic Diseases by Adeyinka Jeremy Adedeji and 18 co-authors from Nigeria's National Veterinary Research Institute and the University of Jos. Using a PRISMA-guided review of 110 studies, the authors reconstruct how mpox moved from a neglected zoonosis to a disease capable of sustained human transmission and international spread.

The deeper warning is that health systems failed to detect, investigate and respond to those changes early enough. Mpox therefore offers a broader lesson for pandemic preparedness: pathogens regarded as geographically peripheral can become global threats when ecological surveillance, laboratory capacity and sustained investment remain weak.

The 2022 Outbreak Had Roots in Decades of Neglect

Human mpox was first identified in 1970, yet for much of the following four decades West Africa reported few or no cases. The review calls this period an "Era of Silence," but the silence was largely epidemiological rather than biological. Evidence suggests the virus continued circulating in wildlife even when human surveillance systems detected little or nothing.

A striking warning came in 2003, when an outbreak in the United States was traced to small mammals imported from Ghana. At the time, Ghana had not reported human mpox cases, yet the virus was found in species including rope squirrels, dormice and Gambian pouched rats. The episode demonstrated how animal circulation could remain largely invisible to routine human disease reporting.

At the same time, population immunity was eroding. Routine smallpox vaccination ended around 1980, and the review notes historical evidence that smallpox vaccination provided about 85% cross-protection against mpox. As vaccinated generations aged and younger populations grew up without that protection, the number of people susceptible to infection increased.

This combination, silent animal circulation, weakening immunity and limited surveillance, created an environment in which mpox could change without attracting sustained global attention. The policy failure was thus cumulative. What appeared in 2022 as an emerging crisis had been developing within an under-monitored disease ecosystem for years.

Nigeria's 2017 Resurgence Revealed That Mpox Had Changed

The most important epidemiological turning point came in Nigeria in 2017. Earlier West African infections had largely been described as sporadic rural cases, often involving children and animal-to-human transmission. The 2017 outbreak instead disproportionately affected young adult males and increasingly appeared in urban and peri-urban settings. The clinical profile was also different. The review reports that approximately 68% of patients had anogenital ulcers, contributing to growing recognition that close physical and sexual contact was becoming an important pathway of transmission. The disease was no longer behaving simply as an occasional zoonotic spillover from wildlife into isolated communities.

Between 2018 and 2021, cases linked to Nigeria appeared in the United Kingdom, Israel, Singapore and the United States. These were effectively early-warning events. Then, in 2022, clade IIb spread internationally, reaching more than 110 non-endemic countries and prompting WHO to declare a Public Health Emergency of International Concern.

The significance is difficult to overstate. Public-health systems were dealing with a pathogen whose transmission environment had shifted from predominantly zoonotic and rural toward increasingly sustained person-to-person spread. Yet surveillance and research had not evolved at the same speed.

Genomics Shows a Virus Adapting While Surveillance Lagged

Genomic evidence strengthens the case that mpox was changing before the world recognized the scale of the problem. Molecular-clock analyses reviewed by the authors suggest that the ancestor of the human-transmitting clade IIb lineage emerged in southern Nigeria around late 2014 and may have circulated undetected among people between 2014 and 2016.

The review also highlights an unusual pattern of accelerated microevolution. Viral genomes collected between 2017 and 2022 accumulated mutations dominated by TC→TT substitutions, a signature associated with APOBEC3, part of the human antiviral defence system. The authors argue that this pattern provides molecular evidence of prolonged viral exposure to human immune pressure.

In practical terms, genomic surveillance was revealing transmission history that ordinary case surveillance had missed. Instead of a virus suddenly acquiring global potential in 2022, the evidence is more consistent with sustained, partly hidden circulation during which the virus accumulated changes within human transmission chains.

The ecological picture remains even less certain. No definitive animal reservoir has been identified despite evidence involving dormice, pouched rats, rope squirrels and other small mammals. More recent surveys have also found orthopoxvirus antibodies in shrews and feral cats, raising questions about whether peri-urban animals could increasingly bridge wildlife and human environments.

The Bigger Lesson Is About One Health and the Cost of Looking Away

The review ultimately makes a strong case for One Health surveillance, integrating human medicine, veterinary science, wildlife ecology and environmental monitoring. Conventional surveillance that begins only after human cases increase is inadequate for pathogens sustained within complex animal reservoirs and capable of adapting during prolonged transmission.

For African governments, the immediate priorities are stronger diagnostic capacity, continuous genomic sequencing and systematic wildlife surveillance. International organizations and development partners should treat these investments as long-term public goods rather than temporary emergency expenditures. The authors argue that sustained, equity-focused surveillance is essential to detect viral evolution early and stop localized threats before they become global emergencies.

The review also exposes important gaps in the evidence. Historical surveillance during the "Era of Silence" was extremely limited, genomic sampling is heavily weighted toward human cases, and the definitive wildlife reservoir remains unknown. The authors also acknowledge that restricting their review to English-language studies may have excluded relevant Francophone research from West Africa.

There is an additional methodological question worth noting. The authors state that their formal database search covered publications through August 2025, yet the reference list includes studies published in 2026. This may reflect updates made during manuscript revision, but the review does not clearly explain how those later studies were incorporated into the original systematic search process.

That said, the broader conclusion is persuasive. Mpox demonstrates how a neglected regional disease can become a global public-health problem when declining immunity, changing human behaviour, animal reservoirs and weak surveillance interact over time.