Smallpox was a severe infectious disease caused by a virus, and often fatal. Symptoms included fever, headache, and general malaise, followed by a rash. The rash characteristically affected face and limbs more than trunk and lesions start simultaneously. From a maculo-papular appearance, the rash passed into a pustular or vesicular stage and ended with scab formation; the lesions were deep and caused scarring. Major and minor forms of smallpox existed, with high fatality rate in major, often with extensive skin hemorrhage. Transmission was from infected cases by secretions and skin lesions; these were infectious for the duration of the rash. Immunization against smallpox was the earliest form practiced, initially through self-inoculation with the minor form. Later Jenner introduced vaccination with the related cowpox virus (later vaccinia were used). In 1980, the World Health Organization declared that the disease had been eliminated. Quarantine and vaccination were crucial to this. Today, smallpox viruses are found only in a few laboratories for research purposes.