The smallpox virus appears to have been with humanity for millennia before a global vaccination drive wiped it out. Current genome research suggests how smallpox spread and where it came from.
What happened to make plague able to cause devastating epidemics, as in this depiction from 1349?
Pierart dou Tielt/Wikimedia
People caught and died from plague long before it caused major epidemics like the Black Death in the middle ages. Could what scientists call cultural resistance be what kept the disease under control?