From my readings, syphilis was brought to Europe by the explorers returning from America. I believe some called it the French disease. I suspect that the more common diseases like smallpox, measles and others did the most killing. I don’t know how quickly Orellana and crew arrived on the Amazon. Once there and exchanging germs, river traffic by the residents would have spread infections quickly up and down the Amazon and into tributaries.
In California, smallpox was less devastating to tribal peoples, primarily because trade was irregular due to grizzly bears, the total lack of pack animals, and relatively uniform resources. Together, these conditions suppressed inter-tribelet contact which is why California had such tremendous variation in languages. Spanish "soldiers" brought in the syphilis.
I am guessing that, although the river would facilitate trade, again, the region has a relatively uniform distribution of resources. Smallpox, by respiratory transmission, is highly contagious, and has a very short incubation period but was devastating once contracted. One would get sick and not wish to travel, wiping out a village very quickly. So in that respect what is unknown is how settled people in the Amazon were. I've seen estimates of 125 million. So in a sense, the larger numbers would favor smallpox as the cause of their demise.
My problem with that attribution is the term of travel of a Spanish expeditionary force. It would take long enough to get there that the soldiers would get so sick they'd have a hard time surviving the trip long enough to transmit the virus to the Amazonian people.
There’s still a bias toward syphilis *not* having originated in the Americas, but I don’t think there’s any credibility to it. Earlier traces in ancient autopsies have all been shown to be known “old world” STIs like Yaws.