Europeans already had to face ecological barriers of many kinds and overcame them insofar as military and political matters went, like malaria, yellow fever, high altitude in the Andes or even Mexico, dense tropical rainforests and so on.Diseases change over time as well, so what strain the populace has become used to will not necessarily guarantee a immune Native American population. However, with the introduction of isolated domesticated animals, the Europeans could deal with devastating outbreaks of New World strains of illness that they haven't come in contact with before. Just a thought
So I don't think that any zoonic disease could singlehandedly change the picture, if it was so easy to create diseases with comparable mortalities we humans would be extinct by this point.
I agree with Gwyain that a scenario like this has to start before, maybe Norse travelers can indeed bring some animals and iron goods but 5 centuries is frankly very little to change the picture outside Eastern North America, having agriculture spread around earlier, maybe have more Siberian contacts which can reliably happen way earlier than Polynesian/North Sea contacts.
It's not an easy thing to achieve.