Smallpox is a contagious and often fatal infection caused by the variola virus. It presents in 2 clinical forms: variola major smallpox (historic mortality rate is 30%) and variola minor, which produces a milder smallpox-like illness (historic mortality rate is less than 1%).

There are 4 clinical subtypes of smallpox: ordinary, modified, flat, and hemorrhagic. Ninety percent of all smallpox cases were ordinary. Modified smallpox occurs in persons that have already been vaccinated against smallpox. Flat and hemorrhagic smallpox are very severe and rare.

Smallpox, in all its forms, was declared eradicated in 1980, and there has not been a case since, but the virus still exists in some laboratories and may be in the hands of terrorists.

Smallpox is classified as a Category A bioterrorism agent because of its ease of dissemination, contagiousness, and high mortality rate. The most likely method of dispersal would be as an aerosol, but simply having an infected individual walk around infecting others is also a likely mode of dissemination. One case of smallpox most certainly represents a terrorist attack.

The initial symptoms of smallpox occur after a 3-17 day incubation period and include a prodrome of high fever, chills, headache, backache, malaise, and vomiting. Severe abdominal pain and delirium can also be present. After 2-4 days, a rash of macules and papules appears in the mouth and on the face and extremities and spreads to the rest of the body, including the palms and soles. The lesions of the rash evolve uniformly to vesicles and pustules, which usually umbilicate, crust over, scab, and fall off, leaving pitted scars. Pregnant individuals may be at increased risk for severe illness from smallpox.

After 2 weeks of infection, death can occur from a toxemia secondary to circulating immune complexes or from secondary infection. Encephalitis is a possible complication. Hemorrhagic and flat forms are fulminant with mortality rates approaching 100%, and these do not display the typical umbilicated papules.

Humans are the only known hosts of the variola virus. Smallpox is one of the most contagious diseases known, with only 5-10 virions sufficient to produce infection. Smallpox is easily spread person to person by respiratory droplets and/or contact with bodily fluids, lesions or scabs, and contaminated clothing or bedding. On rare occasions, in enclosed spaces, it has been transmitted by virus carried in the air. Patients are most contagious from about 24 hours before the time the typical rash first appears until the scabs heal and fall off. During the incubation period, it is not contagious.

The only people at risk for smallpox outside of a bioterrorist attack are those maintaining authorized stocks in laboratories at the Centers for Disease Control and Prevention (CDC) in Atlanta and in Moscow. Terrorist groups might be exposed if they are growing stocks of the virus for illicit purposes.