Prevention of smallpox with cowpox vaccine. Smallpox is an acute infectious disease caused by infection with the smallpox virus, which has a very high lethality rate and is regarded as one of the most devastating diseases in human history. With the widespread use of vaccines, smallpox has been eradicated. Although smallpox has been eradicated, smallpox virus is still of worldwide concern as a potential biological weapon due to its very high transmissibility and pathogenicity. After vaccination with cowpox vaccine (smallpox vaccine), smallpox is usually no longer present. The main clinical manifestations of smallpox are symptoms such as high fever, chills, malaise and skin lesions. Because smallpox has now been eradicated and because of the risks associated with smallpox vaccination, smallpox vaccination is no longer routinely administered.