Before the European arrival, the Americas had been largely isolated from the Eurasian–African landmass.
First large-scale contacts between Europeans and native people of the American continents brought overwhelming pandemics of measles and smallpox, as well as other Eurasian diseases. These diseases spread rapidly among native peoples, often ahead of actual contact with Europeans, and led to a drastic drop in population and the collapse of native American cultures. Smallpox and other diseases invaded and crippled the Aztec and Inca civilizations in Central and South America in the 16th century.
This disease, with loss of population and death of military and social leaders, contributed to the downfall of both American empires and the subjugation of American peoples to Europeans. Diseases, however, passed in both directions; syphilis was carried back from the Americas and swept through the European population, decimating large numbers.