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Various theories for the decline of the Native American populations emphasize epidemic diseases, conflicts with Europeans, and conflicts among warring tribes. Scholars now believe that, among the various contributing factors, epidemic disease was the overwhelming cause of the population decline of the American natives. Some believe that after first contacts with Europeans and Africans, Old World diseases caused the death of 90 to 95% of the native population of the New World in the following 150 years. Smallpox killed up to one third of the native population of Hispaniola in 1518. By killing the Incan ruler Huayna Capac, smallpox caused the Inca Civil War. Smallpox was only the first epidemic. Typhus (probably) in 1546, influenza and smallpox together in 1558, smallpox again in 1589, diphtheria in 1614, measles in 1618—all ravaged the remains of Inca culture.

What disease killed almost a third of the population of Hispaniola in 1518?
Smallpox