Disease dies out if population is under a half million because everybody has been exposed and is either dead or resistant. Disease only survives with travel between populations or between uninfected pockets within a population. Then disease died out. Don't get transmitted human to human. Transfers human to human but not yet long-established.
Diseases evolve to effectively work in new host.
Hispaniola had 8 million inhabitants in 1492, zero by 1535. There were estimated 20 million Indians in USA before European diseases. 19 million died Also 20 million in Mexico, reduced by disease to 1.6 million. No large domestic animals. Writing Writing marched together with weapons, microbes and centralized political organization as a modern agent of conquest.