For one thing, the deaths of Aztec and Incan rulers touched off wars, which in turn made it easier to spread disease, because, you know, the number one way to catch smallpox is via hand-to-hand combat. Plus, leaders kept dying. Huayna Capac, the leader of the Inca Empire, succumbed to smallpox before Pizarro even arrived. His death led to a violent succession struggle between his sons, which was won by Atahualpa, who in turn was captured and killed by Pizarro. And without that war, the Inca would have had a much better chance against the Spaniards, whose numbers were comparatively tiny. A similar thing happened to the Aztecs. The Moctezuma who eventually lost to Cortes was the nephew of a much more powerful king who died of smallpox.