Smallpox was an infectious disease caused by one of two virus variants, Variola major and Variola minor. The agent of variola virus (VARV) belongs to the genus Orthopoxvirus. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) certified the global eradication of the disease in 1980.The initial symptoms of the disease included fever and vomiting. This was followed by formation of ulcers in the mouth and a skin rash. Over a number of days the skin rash turned into characteristic fluid-filled blisters with a dent in the center. The bumps then scabbed over and fell off, leaving scars. The disease was spread between people or via contaminated objects. Prevention was achieved mainly through the smallpox vaccine. Once the disease had developed, certain antiviral medication may have helped. The risk of death was about 30%, with higher rates among babies. Often those who survived had extensive scarring of their skin, and some were left blind.The origin of smallpox is unknown; however, the earliest evidence of the disease dates to the 3rd century BCE in Egyptian mummies. The disease historically occurred in outbreaks. In 18th-century Europe, it is estimated that 400,000 people died from the disease per year, and that one-third of all cases of blindness were due to smallpox. Smallpox is estimated to have killed up to 300 million people in the 20th century and around 500 million people in the last 100 years of its existence. Earlier deaths included six European monarchs. As recently as 1967, 15 million cases occurred a year.Inoculation for smallpox appears to have started in China around the 1500s. Europe adopted this practice from Asia in the first half of the 18th century. In 1796, Edward Jenner introduced the modern smallpox vaccine. In 1967, the WHO intensified efforts to eliminate the disease. Smallpox is one of two infectious diseases to have been eradicated, the other being rinderpest in 2011. The term "smallpox" was first used in Britain in the early 16th century to distinguish the disease from syphilis, which was then known as the "great pox". Other historical names for the disease include pox, speckled monster, and red plague.