The biggest negative effect of the Columbian Exchange was the introduction of European diseases to the Americas. Diseases like typhus, measles, plague, and especially smallpox devastated Native Americans who had no immunity to them. The death toll, which some historians estimate at close to 90% of the indigenous population before contact, makes this aspect of the Columbian Exchange one of the worst demographic disasters in the history of the world. Native peoples who were lucky enough to be spared by these diseases, which hit in waves of so-called "virgin soil epidemics," saw their lives change dramatically. Villages and entire tribes of people were forced to seek shelter with other native groups, and many were adopted into tribes like the Catawba, which emerged in the seventeenth and eighteenth centuries in response to the disaster. Disease also facilitated the conquest of many Native peoples, perhaps most famously the Inca, who faced a terrible smallpox epidemic that paved the way for Pizarro and his conquistadores. So the spread of epidemic diseases was by far the worst impact of the Columbian Exchange.
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