Five Decades of Mpox in West Africa: History, Epidemiology, Viral Evolution, and Reservoir Ecology (1970–2025)

Historically, mpox was thought to be a geographically constrained ‘disease of poverty,’ leading to decades of neglect by global health actors. Waning population immunity from the cessation of smallpox vaccination and prolonged scientific neglect created conditions that enabled the monkeypox virus (MPXV) to adapt cryptically. This ultimately contributed to the emergence of unprecedented global public health crises. This review aims to systematically trace the history, epidemiology, genomic evolution, and reservoir ecology of mpox in West Africa from 1970 to 2025. Following PRISMA guidelines, 110 articles met the inclusion criteria and were synthesized to map the virus’s trajectory. For nearly four decades, an “Era of Silence” (1970–2016) masked the silent enzootic circulation of MPXV within West African wildlife, primarily rodents and small mammals. This epidemiological quiescence ended with the 2017 re-emergence in Nigeria, which signaled a fundamental paradigm shift. The disease profile transitioned from sporadic, rural paediatric infections to sustained, urban and secondary transmission among young adult males. This shift was often associated with sexual networks, especially among men who have sex with men, and was characterized by novel clinical presentations, including genital and perianal lesions. Genomic analyses revealed that clade II diverged from clade I approximately 3500 years ago and is uniquely defined by the deletion of virulence factors, such as the complement-binding protein. Importantly, the clade IIb lineage, which triggered the 2022 global outbreak, exhibits accelerated microevolution consistent with APOBEC3-mediated hypermutation. This host-driven mutational signature provides genomic evidence supporting the hypothesis that clade IIb circulated cryptically within human-to-human transmission chains in West Africa as early as 2014. Ecologically, while no definitive reservoir has yet been identified, evidence suggests diverse rodents and an expanding host range. The transformation of mpox from a rare zoonosis to a global threat underscores the severe consequences of delayed intervention, demanding robust, integrated “One Health” surveillance.