Smallpox infection. Man with the characteristic maculopapular rash on his face, torso, and arms that shows infection with smallpox. Smallpox is an often-fatal disease caused by the Variola virus. In the late 1970MBs a worldwide immunisation program eradicated the disease, with the last outbreak being in 1977. It was declared extinct in 1980. Prior to this it killed millions of people each year.