Read this excerpt from "Edward Jenner and the History of Smallpox and Vaccination.” Smallpox was introduced to Europe sometime between the fifth and seventh centuries and was frequently epidemic during the Middle Ages. The disease greatly affected the development of Western civilization. The first stages of the decline of the Roman Empire (AD 108) coincided with a large-scale epidemic: the plague of Antonine, which accounted for the deaths of almost 7 million people. The Arab expansion, the Crusades, and the discovery of the West Indies all contributed to the spread of the disease.
Unknown in the New World, smallpox was introduced by the Spanish and Portuguese conquistadors. The disease decimated the local population and was instrumental in the fall of the empires of the Aztecs and the Incas. Similarly, on the eastern coast of North America, the disease was introduced by the early settlers and led to a decline in the native population.

Before it reached the New World, smallpox played a role in

the fall of the Aztecs and Incas.
the battle plan of the French-Indian War.
the decline of the Roman Empire.
the decline of North American native population.