The earliest credible clinical evidence of smallpox is found in the Egyptian mummy of Ramses V who died over 3000 years ago (1145 BC). Historical records from Asia describe evidence of smallpox-like disease in medical writings from ancient India (as early as 1500 BC) and China (1122 BC). It has been speculated that Egyptian traders brought smallpox to India during the 1st millennium BC, where it remained as an endemic human disease for at least 2000 years. Smallpox was probably introduced in China during the 1st century AD from the southwest, and in the 6th century was carried from China to Japan. In Japan, the epidemic of 735–737 is believed to have killed up to one-third of the population. At least seven religious deities have been specifically dedicated to smallpox, such as the god Sopona in the Yoruba religion. In India, the Hindu goddess of smallpox, Sitala Mata, was worshiped in temples throughout the country.
The arrival of smallpox in Europe and south-western Asia is less clear. Smallpox is not clearly described in either the Old or New Testaments of the Bible or in literature of the Greeks and Romans. While some have identified the Plague of Athens – which was said to have originated in "Ethiopia" and Egypt – or the plague that lifted Carthage's 396 BC siege of Syracuse with smallpox, many scholars agree it is very unlikely such a serious disease as variola major would have escaped a description by Hippocrates if it existed in the Mediterranean region during his time. While the Antonine Plague that swept through the Roman Empire in AD 165–180 may have been caused by smallpox, Saint Nicasius of Rheims became the patron saint of smallpox victims for having supposedly survived a bout in 450, and Saint Gregory of Tours recorded a similar outbreak in France and Italy in 580, the first use of the term variola; other historians speculate that Arab armies first carried smallpox out of Africa to Southwestern Europe during the 7th and 8th centuries. In the 9th century the Persian physician, Rhazes, provided one of the most definitive observations of smallpox and was the first to differentiate smallpox from measles and chickenpox in his Kitab fi al-jadari wa-al-hasbah (The Book of Smallpox and Measles). During the Middle Ages, smallpox made periodic incursions into Europe but did not become established there until the population increased and population movement became more active during the time of the Crusades. By the 16th century smallpox was well established over most of Europe. With its introduction in populated areas in India, China and Europe, smallpox affected mainly children, with periodic epidemics that killed up to 30% of those infected. The appearance of smallpox in Europe is of particular importance, as successive waves of European exploration and colonization served to spread the disease to other parts of the world. By the 16th century it had become an important cause of morbidity and mortality in the known world.
There are no credible descriptions of smallpox-like disease in the Americas before the westward exploration by Europeans in the 15th century AD. In 1507 smallpox was introduced into the Caribbean island of Hispaniola and to the mainland in 1520, when Spanish settlers from Hispaniola arriving in Mexico brought smallpox with them. Smallpox devastated the native Amerindian population and was an important factor in the conquest of the Aztecs and the Incas by the Spaniards. Settlement of the east coast of North America in 1633 in Plymouth, Massachusetts was also accompanied by devastating outbreaks of smallpox among Native American populations, and subsequently among the native-born colonists. Some estimates indicate case fatality rates of 80–90% in Native American populations during smallpox epidemics. Smallpox was introduced into Australia in 1789 and again in 1829. Although the disease was never endemic on the continent, it was the principal cause of death in Aboriginal populations between 1780 and 1870.
By the mid-18th century smallpox was a major endemic disease everywhere in the world except in Australia and in several small islands. In Europe smallpox was a leading cause of death in the 18th century, killing an estimated 400,000 Europeans each year. Through the century smallpox resulted in the deaths of perhaps 10% of all the infants of Sweden every year, and the death rate of infants in Russia may have been even higher. The widespread use of variolation in a few countries, notably Great Britain, its North American colonies, and China, somewhat reduced the impact of smallpox among the wealthy classes during the latter part of the 18th century, but a real reduction in its incidence did not occur until vaccination became a common practice toward the end of the 19th century. Improved vaccines and the practice of re-vaccination led to a substantial reduction in cases in Europe and North America, but smallpox remained almost unchecked everywhere else in the world. In the United States and South Africa a much milder form of smallpox, variola minor, was recognized just before the close of the 19th century. By the mid-20th century variola minor occurred along with variola major, in varying proportions, in many parts of Africa. Patients with variola minor experience only a mild systemic illness, are often ambulant throughout the course of the disease, and are therefore able to more easily spread disease. Infection with v. minor induces immunity against the more deadly variola major form. Thus as v. minor spread all over the USA, into Canada, the South American countries and Great Britain it became the dominant form of smallpox, further reducing mortality rates.
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