If its pre-Black Death, would anyone try to flee the plagues to America?
Or, conversely, would the American Indians be even more ravaged by the plague brought along with refugees?
Well as Measles, Small Pox, and others killed off enough as is, The Black Death might have added to more woe. But seeing as North America did not have the trade routes to as conveyers of the Black Death, I do not think it would have been the cause of decimation that it was in Europe and Asia.
If there had been enough ships, then you might have seen cultures and creeds flee to NA to get away from purges from Europe.