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Why did smallpox cause especially severe losses among Indigenous peoples?

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A group of Native American men in colorful traditional regalia with feathered headdresses dance outdoors at a powwow ceremony on a grassy field. — Indigenous peoples of the Americas Performers at a Canadian powwow, c. 2008.

Smallpox caused devastating losses among Indigenous peoples in the Americas primarily because they had no prior exposure to the disease. Before 1492, Indigenous populations did not host the acute infectious diseases common in Eurasia and Africa, such as smallpox, measles, and influenza. Consequently, they lacked the immunity that had developed in populations elsewhere through centuries of endemic exposure.1

The absence of these diseases in the Americas was largely due to the region's ecological history; unlike in the Old World, where many human diseases originated from domesticated herd animals like cattle and pigs, the species domesticated by Indigenous peoples—such as llamas and turkeys—did not harbor infections that became human diseases.1

When smallpox was introduced by European conquerors and settlers, it acted as a virgin-soil epidemic. The impact was further exacerbated by secondary factors, including famine, pneumonia, mass violence, and the physical and psychological stress of conquest, which collectively led to mortality rates as high as 95 percent in some areas.123