What is the difference between mpox and smallpox?

Mpox and smallpox are both caused by orthopoxviruses, but they are distinct diseases. Smallpox (Variola virus) was eradicated in 1980 and no longer occurs naturally. Mpox (Monkeypox virus) is an ongoing zoonotic disease, with outbreaks in 2022-2024 (clade IIb, global) and 2024-2025 (clade I, primarily Democratic Republic of Congo). Key clinical difference: mpox causes prominent lymphadenopathy (swollen lymph nodes), which does NOT occur in smallpox. Mpox is significantly less severe: clade II fatality rate is under 1%, while smallpox killed approximately 30% of those infected.