Important features that contributed to the unique success of this vaccine program included (1) universal interest in eliminating this costly disease with high morbidity and mortality, (2) the infection's long incubation period and low level of communicability, (3) the ease of diagnosis of skin lesions by characteristic histology or antigen detection, (4) the fact that humans were the sole reservoir of the infection, (5) the absence of a carrier state, and (6) the availability of an effective live-virus vaccine that could readily be delivered to less developed countries because of its resistance to chemicals, temperature changes, and drying. The only known remaining repositories of smallpox virus reside in two research laboratories (located in the United States and Russia), and the issue of whether these last samples should be maintained or destroyed remains controversial.
Before the eradication of smallpox, variola virus existed as two related strains: variola major (smallpox), with a case-mortality rate of 20 to 50%, and variola minor (alastrim), which caused a clinically milder form of smallpox with a mortality of <1%. The clinical presentation of smallpox is now primarily of historic note. However, the threat of biologic terrorism means that smallpox remains a remote possibility in the differential diagnosis of a vesicular exanthem. Fever and macular rash appear after an average incubation period of 12 days, with a progression to typical vesicular and pustular lesions over 1 to 2 weeks. Rash generally appears first on the face, oral mucosa, and arms, with relative sparing of the trunk. Smallpox lesions may be confused with common chickenpox (varicella-zoster) infection but tend to be more diffuse, peripheral, and uniform in their stage of development. When the lesions heal they leave a scar.
Polymerase chain reaction promises to be more useful than traditional electron microscopy or virus isolation for confirming variola or other poxvirus infections.
The origin of vaccinia virus -- the virus used for vaccination against smallpox -- is uncertain, but it was probably derived from cowpox virus, variola virus, or a hybrid of the two. It is now a laboratory virus with no natural host. Experience has proven the effectiveness of live vaccinia virus vaccine, although its efficacy and safety were not established in controlled studies. Percutaneous administration of vaccinia virus vaccine results in protective cellular and humoral immune responses in >95% of primary vaccinees. Formation of a pustule and scab at the site of inoculation is indicative of immunity; because immunity wanes after 10 to 20 years, revaccination every 10 years is recommended for continued protection. Routine smallpox vaccination was discontinued in 1971 and has not been required for international travel since 1982.