The resurgence of monkeypox virus: a critical global health challenge and the need for vigilant intervention.

The resurgence of the monkeypox virus (MPXV), a zoonotic Orthopoxvirus historically regarded as endemic to the tropical rainforests of Central and West Africa, represents a significant and evolving global health challenge. Waning Orthopoxvirus immunity following the cessation of smallpox vaccination and inequitable vaccine access have increased susceptibility, especially in resource-limited settings. Combined with urbanization, environmental degradation, global travel, and human-wildlife interactions, these factors have driven MPXV beyond its traditional regions. Notably, recent outbreaks in non-endemic countries have exhibited a distinct epidemiological shift, with a higher incidence among men who have sex with men, often in the absence of travel history to endemic areas, underscoring evolving transmission dynamics. This review provides a comprehensive examination of MPXV's epidemiology, clinical features, and transmission mechanisms, highlighting the complexities of its containment. Key challenges-including surveillance gaps, vaccine inequities, and limited access to diagnostics and therapeutics-are compounded by unresolved controversies over MPXV's natural reservoirs and respiratory transmissibility, as well as critical research gaps in zoonotic spillover mechanisms and long-term immunity. Addressing these issues demands global collaboration to leverage next-generation vaccines and antivirals, paired with an integrated public health response: enhanced surveillance, targeted education, and equitable resource allocation. Sustaining these efforts is vital to curbing MPXV's resurgence and preventing its entrenchment as a global health threat.