Mpox Epidemics: A Call to Restore Humanity’s Lost Herd Immunity to Orthopoxviruses

Global efforts to eradicate smallpox—an Orthopoxvirus infection—began in the mid-20th century, with the last naturally occurring case reported in 1977. This was achieved through global solidarity efforts that expanded the smallpox eradication vaccination program. Approximately 50 years following the cessation of mass smallpox vaccination and in the absence of access to a sustainable boosting program, the population immunologically naïve to Orthopoxviruses has increased significantly. With increasing global movements and travels, we argue that the emergence of two back-to-back yet distinct mpox epidemics in the 21st century is a sign of humanity’s lost herd immunity to Orthopoxviruses. This needs concerted efforts to restore.