The Peculiar Emergence of Mpox (Monkeypox): Directions for the Search for the Natural Reservoir and Vaccination Strategies

Background/Objectives: Mpox (monkeypox) is a zoonosis with origins in a currently unknown African reservoir. The first epidemiological accounts of mpox date back to the early 1980s, yet mpox only emerged as a pandemic threat in 2022–2023, more than 40 years later. This scenario is very different from those of other emerging diseases such as HIV and SARS, which immediately spread globally, in fully susceptible populations, starting from patients zero. Methods: We use mathematical modeling to illustrate the dynamics of mpox herd immunity in small communities in touch with the mpox natural reservoir. In particular, we employ an stochastic model. Results: The peculiar emergence of mpox can be explained by its relationship with smallpox, which was eradicated through universal mass vaccination in 1980. Mpox first emerged in small rural communities in touch with mpox’s animal reservoir and then spread globally. The relative isolation of these communities and their herd-immunity dynamics against mpox worked to delay the introduction of mpox in large urban centers. Conclusions: Mathematical modeling suggests that the search for the mpox animal reservoir would be most fruitful in communities with high mpox seroprevalence and small outbreaks. These are communities is tight contact with the mpox natural reservoir. We propose vaccinating individuals in communities in these communities to severely reduce the importation of cases elsewhere.