The Sea Wasp (Ryk E. Spoor)

Thirded. We domesticated cattle, which allowed cowpox to jump to humans and become smallpox. Smallpox has a mortality rate of about 30-35%, and the survivors have a resistance to the disease. So by the time the Western explorers hit the Americas, they could carry quite a viral load without getting sick. The natives, on the other hand...

There's a theory, based on the sudden collapse of the Mississippian Culture circa 1400CE, that smallpox actually traveled to the Americas with the Norse, who passed it on to the tribes they interacted with during their brief stay. This would explain why much of the culture had already vanished before "solid" European contact, and why some tribes were better at surviving the pox than others. We may have stumbled into a situation where "Rome" had fallen and all that was left were the barbarians.