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These days, smallpox exists only in a few dedicated research laboratories in the United States and Russia, and a couple of other places. "In the wild", smallpox is extinct, the first major worldwide disease to be eliminated.

Before about 1900, smallpox could be easily transmitted by casual contact; breathing the same air, sharing the same blankets, or by touch. It was wildly virulent and quite deadly to its victims. In pre-1400s Europe, smallpox was a serious disease, but most people had developed at least a little resistance because of repeated contact.

When Europeans began to travel the world, smallpox traveled with them. Smallpox had never existed in the Americas or in much of Asia, and the arrival of smallpox was deadly to large numbers of people, who had no resistance to it.

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