Smallpox (Variola major) Technical Description: Smallpox Close Window The classic disease of smallpox, caused by variola major virus, was globally eradicated in 1980. The orthopox virus, variola major, causes the more severe form of disease (up to 30% mortality), while variola minor is relatively mild. The smallpox virus is easily transmitted by aerosol and was weaponized by the former Soviet Union from approximately the 1960s through the 1980s. Currently, per mandate of the United Nations’ World Health Organization (WHO), only two laboratories in the world (located in the United States and Russia) are official repositories for smallpox virus, although there are suspicions that countries such as North Korea and Iraq may continue to keep the virus. Symptoms from smallpox generally begin 12 days following exposure, including fever, vomiting, headache, and sometimes (15%) delirium. After initial infection with smallpox virus, such as that of the upper respiratory tissue, virus is brought to regional lymph nodes. Replication then takes place, followed by dramatic increase in virus in the blood. The initial stages of smallpox disease involve a rash that develops into raised papules on the skin, all occurring at roughly the same time (unlike chicken pox, caused by the varicella zoster virus). Lesions are also formed along the lining of the respiratory tract, where virus can be shed and then transmitted by contaminated droplets and aerosolized particles (such as through coughing). Survivors of smallpox are permanently scarred by pock marks and hyperpigmentation, especially on the face. The only known protection against smallpox is the use of a live vaccine, vaccinia, which carries the immunizing principle against smallpox, but does not cause disease in most healthy people. There is also passive protection available through the use of a vaccinia immunoglobulin (VIG) serum. Anti-viral therapy against smallpox is currently being investigated, although the lack of a suitable animal model has hindered advances in this regard. In the United States, the last routinely administered vaccine against smallpox occurred in 1972, while US military personnel were vaccinated up until about 1989. While some (limited) cell-mediated immunity may exist in individuals who were vaccinated many years ago, the conventional wisdom is that nearly all individuals are immunologically naïve against smallpox.