One of the reasons is the conditions required for the disease to originate.
Small pox, for example originated some is thought to have first appeared in human population around 10, 000 BC. It is also thought to be a variation of what was originally a disease that plagued rat populations.
The earliest medical evidence of the disease is thought to be found in India about 1500 BC although examination of the mummified remains of Ramses V indicates that Rameses V had been infected with the disease around 3000 BC. It is difficult to say where small pox originated, the most likely target is Egypt where it spread to India and then China. Increased trade with European countries would have allowed the contagion to be spread into Europe.
Nobody with the disease was in contact with the Americas where climate and population density made the mutations a likelihood.