You can find the answer to that question in Jared Diamond's book Guns, Germs and Steel. He states that people get infected by their pets and that all great epidemics (variola, tuberculosis, malaria, plague, influenza ...) evolved from animals. Microbes needs a mass of people to spread around so big societies, living in cities and connected with good trading roads, were is the best place for them. They can't survive in small societies because they kill anyone who isn't resistant and therefore fails to spread. Those who survive develop antibodies. Microbes can't survive in small communities of farmers and hunters.
Because american Indians didn't have antibodies to European diseases so many died - sometimes the whole villages. In this diseases it is also success in Pizarro's and Cortes' success. Some scientist believe that there were 95 % decrease in population in 200 years after Columbus.
The only infectious disease coming from America to Europe was syphilis.
In America there were great civilizations living in big cities: Aztecs, Incas and Indians who lived in Mississippi. But this cities were never connected with trading paths so microbes couldn't spread as they did in Europe and Asia. The main reason for lack of infectious diseases is that there were no animals, living in herds. There were only five domestic animals: a turkey, a lama, a cavy, some bird and a dog - and they were no source of microbes as cows, sheep.
It doesn't mean that there are no infectious diseases, but there are not so many. But epidemics, diseases of masses, can appear only in dense crowd. This started with agriculture 10.000 years ago and increased with building cities. People live close to each other, they also have pets ...
If I sum it up: according to Jared Diamond there were no epidemics in Americas before 1492.