Monkeypox: A Viral Zoonotic Disease of Rising Global Concern

Abstract Monkeypox (mpox) is a rare viral zoonotic disease, endemic to Central and West Africa, caused by the monkeypox virus, an orthopoxvirus similar to the variola virus (smallpox). Although sporadic travel-associated cases have historically occurred outside Africa, in May 2022, mpox began spreading globally in multiple nonendemic countries across several continents. In 2024, there has been an increase in globally reported confirmed cases of mpox and deaths from mpox, making it a public health emergency of international concern. The reasons for the unusual global spread are under investigation but likely relate to increased travel and waning population immunity to orthopoxviruses. Transmission now appears to be mainly through close, intimate contact, especially among men who have sex with men. Mpox is usually a self-limited disease. Although limited approved antiviral treatments are available, such as tecovirimat, which the European Medicines Agency approved in January 2022 for the treatment of mpox, their widespread availability and effectiveness in the current outbreak remain to be investigated. Public health control measures include surveillance, case identification/isolation, contact tracing, and targeted vaccination of contacts at high risk of exposure. However, challenges remain in curtailing the current unprecedented outbreak. Critical knowledge gaps include animal reservoir(s) responsible for initial spillover events, viral mutations that may enhance transmissibility, optimal diagnostics for noninvasive specimens, effective antiviral therapies, next-generation vaccines providing longer-term immunity, and building global capacity for outbreak response. This review summarizes the current literature on mpox virology, epidemiology, pathogenesis, clinical manifestations, diagnostics, treatment, prevention, and public health control measures. Ongoing investigation and research are needed to better understand mpox’s evolving epidemiology, pathogenicity, transmissibility, and ecology to guide strategies for containing the outbreak and preventing future global emergence.