The causes can be traced to the isolation of North American plant and animal life, to a large indigenous population, and to geographical barriers to population exchanges. These factors for thousands of years prevented indigenous peoples from building up resistance to viral diseases and left them exceedingly vulnerable to them.
推究原因，北美洲的動植物物種單純、地形的阻隔又使得各民族間少有交流，千年來缺乏疫病的鍛鍊，才會被病菌輕易征服。