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Why did introduced diseases cause major losses among Indigenous peoples after European contact?

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Map of Mesoamerica showing the geographic distribution of various Indigenous peoples, with regions labeled for groups such as the Maya, Nahua, Zapotec, Mixtec, Otomi, Mazahua, Huastec, Tarasco, and others across present-day Mexico and parts of Central America. Boundaries indicate the approximate areas inhabited by each group. — Mesoamerican Indian Distribution of Meso-American Indians.

Indigenous peoples in the Americas suffered catastrophic population losses following European contact primarily because they lacked immunity to the suite of acute infectious diseases introduced from Eurasia and Africa.1

Before 1492, Native American populations had not been exposed to pathogens such as smallpox, measles, influenza, mumps, typhus, and whooping cough. This lack of exposure was largely due to the region's ecological history; because Indigenous peoples had not domesticated herd animals like cattle or pigs, they had not developed the diseases that typically evolve from close human-animal contact.1

When these diseases were introduced, they spread as devastating epidemics among populations with no prior resistance. The impact was further exacerbated by secondary factors, including famine, pneumonia, mass violence, and the social disruption caused by conquest. For example, during the Spanish conquest of the Aztecs, smallpox significantly reduced the population of Tenochtitl\u00e1n, severely impairing the city's ability to resist the siege.1234