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Orthopoxviruses are a genus of DNA viruses of which four species are known to cause disease in humans: vaccinia virus (VACV), cowpox virus (CPXV), variola virus (VARV), and monkeypox virus (MPXV).<br /><br />Monkeypox virus is a zoonotic virus, endemic to central and Western Africa that can cause smallpox-like symptoms in humans.The virus was initially identified in non-human primate rash lesions in 1958 and first identified in humans in 1970 during the smallpox eradication efforts. Incidence of MPXV infections in the Democratic Republic of the Congo (DRC), where the majority of cases occur, has increased as much as 20-fold since the end of smallpox vaccination in 1980. The first case of human MPXV in the USA occurred in 2003 and was linked to the handling of prairie dogs that had been housed with imported African rodents.Similar to VARV or smallpox, MPXV disease presents with fever 10–12 days after exposure, followed by rash 2–3 days later. This rash progresses from macular to papular, vesicular, and finally pustular phases, similar to smallpox. This makes differentiation between these diseases based on clinical presentation difficult. While smallpox was declared eradicated by the World Health Organization in 1979, it is still a concern as a potential biological weapon or potential accidental release.