Yeah, syphilis
Not confirmed. Lacking dense urban populations, as Loud Whispers said, pandemic disease couldn't really get a foothold. Once full-fledged sickness
arrived, however, it could be spread effectively enough.
I figured that the steelmaking Algonquinesque tribe forced other tribes to innovate or die, spreading steel west. There were urban societies at the time, the image of the native North American as a nomadic bison-hunter is entirely a result of Europeans uprooting and burning out Indian settlements everywhere they outlasted the plague. Granted, the populations were far less dense, but they still had stratified societies with craftsmen and specialists.
Speaking of reversing the disease flow, though, let's move the divergence point back a few million years: The horse never dies out in NA. As a result, they domesticate the horse, and with the horse they can domesticate the buffalo. Animal domestication leads to denser urban societies, and the two together result in a diverse plague portfolio.
When Columbus buys a few tame bison and a shipful of slaves in Cuba, he sails home with Buffalo Pox and Llama Fever, resulting in western, (and then middle eastern, and then far eastern) civilization eventually losing 90% of it's population. At the same time, the native cities burn under introduced smallpox and plauge and see similar population declines. Some children do inherit both sets of resistances, so there's that...