Mpox: emergence following smallpox eradication, ongoing outbreaks and strategies for prevention.

Purpose Of Review: This review focuses on the temporal relationship between the discontinuation of the global smallpox eradication effort with the rise of mpox in Africa and worldwide. It also discusses the global 2022 clade II mpox epidemic and the current 2024 clade I mpox outbreak. Newer findings on viral evolution and pathogenesis, plus current and future strategies for disease prevention, are reviewed.

Recent Findings: The temporal association between the incidence of mpox and the World Health Organization's Global Smallpox Eradication Program (GSEP) is presented. The 2022 global mpox epidemic is discussed. Recent data show that clade IIb monkeypox virus (MPXV)-2022 has novel genetic features supporting a greater propensity for mutations that may be responsible for enhanced human-to-human transmissibility, increased disease severity and accelerated viral evolution. In 2023, another outbreak of mpox began in Africa, this time due to the potentially more virulent MPXV clade Ib strains. This outbreak remains ongoing in Africa, and clade Ib mpox cases have recently been reported elsewhere including the United States and Great Britain. The World Health Organization has deemed mpox to be a global public health emergency. Two smallpox vaccines are approved for mpox prevention in the United States; a third smallpox vaccine and an improved diagnostic test have recently received WHO Emergency Use authorization. Newer mRNA-based vaccines for evolving orthopoxvirus infections are discussed.

Summary: Vaccination to prevent smallpox provides immunologic cross-protection against infection with other members of genus Orthopoxvirus, including mpox. Discontinuation of the global smallpox eradication program in the 1980s and the subsequent waning of herd immunity contributed to the 2022 multinational epidemic of human clade IIb mpox infections. A second multinational outbreak with clade Ib MPXV is ongoing. Vaccination against smallpox remains the gold standard for mpox prevention, however newer multiepitope mRNA-based vaccines are in development and hold promise for prevention of mpox and other orthopoxvirus outbreaks.