Mpox Resurgence: A Global Wake-Up Call for Zoonotic Disease Preparedness
September 4, 2025
The resurgence of mpox highlights the fragility of global health security. Once primarily linked to zoonotic spillovers in Central and West Africa, the virus is now sustained through human-to-human transmission across more than 100 countries. A recent review underscores how waning smallpox immunity, ecological disruption, and inequitable vaccine access fuel its spread. Vulnerable groups—immunocompromised individuals, pregnant people, and children—remain at highest risk of severe outcomes. While tools like MVA-BN vaccines and antivirals exist, their uneven distribution threatens to entrench mpox. The lesson is clear: without equity, sustained investment, and One Health approaches, regional outbreaks will continue to spark global crises.
Mpox’s re-emergence as a global threat illustrates both the adaptability of viruses and the shortcomings of international preparedness. Historically tied to zoonotic spillovers in Central and West Africa, mpox is now largely driven by human-to-human transmission, particularly in urban environments and through close-contact networks. The recent review in Frontiers in Public Health identifies several forces behind this shift: waning population immunity following the end of smallpox vaccination, genomic adaptations favoring sustained transmission, and ecological disruptions that heighten spillover risk.
Clinically, mpox no longer follows a predictable pattern. While classic cases involved fever, widespread rash, and lymphadenopathy, recent outbreaks have revealed localized lesions, mild or absent systemic symptoms, and even asymptomatic transmission. For most, the disease is self-limiting, yet severe outcomes—including encephalitis, ocular involvement, sepsis, and fetal loss—remain significant risks. Immunocompromised individuals, especially those with advanced HIV, pregnant people, and young children in areas where virulent clades circulate face mortality rates exceeding 20% in hospital settings.
Despite available tools, gaps persist. The MVA-BN vaccine offers high levels of protection, and antivirals such as tecovirimat provide therapeutic options, but access is profoundly unequal. While wealthier nations have secured stockpiles, endemic regions in Africa struggle with shortages, high costs, and insufficient diagnostic infrastructure. These inequities amplify the burden in populations already most at risk.
The resurgence of mpox is not only a clinical issue but also a warning of systemic failures. Climate change, ecological disruption, and underfunded public health systems create fertile ground for pathogens to expand beyond traditional boundaries. To prevent mpox from becoming entrenched globally, the response must go beyond outbreak control. Investments in One Health systems, decentralized diagnostics, regional vaccine manufacturing, and stigma reduction are essential. Mpox has changed, and so too must the world’s strategy—toward equity, preparedness, and global solidarity.