Monkeypox Emergence and the Eradication of Smallpox: An Historical Review

Background: Human monkeypox infection was first identified in 1970 in African. Small rodents were the natural reservoir of this orthopoxvirus, with humans and primates as incidental hosts. Smallpox vaccination induces cross protection against monkeypox. In Africa monkeypox overlapped with the Global Smallpox Eradication Program (GSEP) six decades ago. The 2022 human monkeypox epidemic prompted literature review re potential impact of monkeypox upon GSEP efforts.
Methods: Literature review from 1960 to present related to GSEP launched in 1969 with particular focus on monkeypox epidemiology during planning of GSEP in the 1960’s through 1989 including surveillance years later.
Results: Establishing the lack of a non-human reservoir of smallpox was essential to assessing the GSEP because of the similarity of the two orthopoxviruses. It was found that a non-human smallpox reservoir was highly remote. Human monkeypox did not occur in smallpox-vaccinated humans and was limited to non-vaccinees. Surveillance in Democratic Republic of the Congo (DRC) until 1989 found monkeypox was very unlikely to persist in humans and unlikely to become a major public health problem. From 2005-2007, decades after cessation of smallpox vaccination, monkeypox surveillance in DRC revealed 20-fold higher incidence of human monkeypox correlated with much lower rates of prior smallpox vaccination.
Conclusions: Human monkeypox rates in DRC were 20-fold higher decades after cessation of smallpox vaccination compared to when smallpox vaccination was still used. The resultant decreased cross-protection against monkeypox contributed to the 2022 multinational outbreak of human monkeypox.