Smallpox is a serious, highly contagious, and sometimes fatal infectious disease. There is no specific treatment for smallpox disease, and the only prevention is vaccination. The name is derived from the Latin word for "spotted" and refers to the raised bumps that appear on the face and body of an infected person. Two clinical forms of smallpox have been described. Variola major is the severe form of smallpox, with a more extensive rash and higher fever. It is also the most common form of smallpox. There are four types of variola major smallpox: ordinary (the most frequent); modified (mild and occurring in previously vaccinated persons); flat; and hemorrhagic. Historically, variola major has a case-fatality rate of about 30%. However, flat and hemorrhagic smallpox, which are uncommon types of smallpox, are usually fatal. Hemorrhagic smallpox has a much shorter incubation period and is likely not to be initially recognized as smallpox when presenting to medical care. Smallpox vaccination also does not provide much protection, if any, against hemorrhagic smallpox. Variola minor is a less common clinical presentation, and much less severe disease (for example, historically, death rates from variola minor are 1% or less).
Variola virus is the etiological agent of smallpox. During the smallpox era, the only known reservoir for the virus was humans; no known animal or insect reservoirs or vectors existed. The most frequent mode of transmission was person-to-person, spread through direct deposit of infective droplets onto the nasal, oral, or pharyngeal mucosal membranes, or the alveoli of the lungs from close, face-to-face contact with an infectious person. Indirect spread (i.e., not requiring face-to-face contact with an infectious person) through fine-particle aerosols or a fomite containing the virus was less common.
Symptoms of smallpox begin 12--14 days (range: 7--17) after exposure, starting with a 2--3 day prodrome of high fever, malaise, and prostration with severe headache and backache. This preeruptive stage is followed by the appearance of a maculopapular rash (i.e., eruptive stage) that progresses to papules 1--2 days after the rash appears; vesicles appear on the fourth or fifth day; pustules appear by the seventh day; and scab lesions appear on the fourteenth day. The rash appears first on the oral mucosa, face, and forearms, then spreads to the trunk and legs. Lesions might erupt on the palms and soles as well. Smallpox skin lesions are deeply embedded in the dermis and feel like firm round objects embedded in the skin. As the skin lesions heal, the scabs separate and pitted scarring gradually develops. Smallpox patients are most infectious during the first week of the rash when the oral mucosa lesions ulcerate and release substantial amounts of virus into the saliva. A patient is no longer infectious after all scabs have separated (i.e., 3--4 weeks after the onset of the rash).
Dryvax, a smallpox vaccine, originally licensed in 1944 to Wyeth Laboratories, Inc. of Madison, N.J., was manufactured until the mid 1980s when the World Health Organization declared that smallpox had been eradicated. Currently there is one licensed smallpox vaccine; ACAM2000, licensed on August 31, 2007, which is manufactured by Sanofi Pasteur Biologics Co. of Cambridge, MA and is based on the same strain of virus as Dryvax. ACAM2000 is indicated for active immunization against smallpox disease for persons determined to be at high risk for smallpox infection. ACAM2000 is administered by scarification to the deltoid muscle or the posterior aspect of the arm over the triceps muscle.
On May 2, 2005, CBER licensed Vaccinia Immune Globulin, Intravenous (VIGIV) manufactured by Cangene Corporation of Winnepeg, Manitoba, Canada. VIGIV, is used to treat rare serious complications of smallpox vaccination.