Smallpox: A Brief Overview

The last naturally occurring case of smallpox was reported in Somalia in October 1977. Despite the eradication of smallpox, the causative agent, variola virus, remains in existence.^1,2 As a result of waning or nonexistent human immunity to this organism, claims of clandestine viral stockpiles, and purported efforts by the former Soviet Union to create a weapon from the agent, variola virus is considered a possible biowarfare and bioterrorism agent. This virus is extremely infectious by aerosol route, is readily transmissible from person to person, is stable, and produces relatively high mortality. Moreover, the impact of its use would be compounded by the inadequacy of current vaccine stockpiles in the United States.^3,4 In addition, there is concern that the closely related monkeypox virus, which is not under strict surveillance, might be employed as a weapon. EPIDEMIOLOGY The most recent outbreaks of variola major carried mortality rates of 30% in nonimmunized persons and 3% in immunized persons. In 10% of cases, smallpox assumes either of 2 highly fatal and less specific pictures: hemorrhagic disease accompanied by a diffuse erythematous rash that evolves into petechiae and hemorrhages, and a malignant form accompanied by papules that coalesce and never become pustular. Both of these variant pictures would be much less easily recognized by most practitioners. Fewer skin lesions develop in persons with variola minor or with preexisting partial immunity. CLINICAL COURSE After an incubation period of 12 to 14 days (range, 7 to 17 days), clinical manifestations of smallpox begin abruptly with fever, malaise, rigors, vomiting, headache, and backache. Delirium and abdominal pain occur in a minority of patients. Some patients exhibit an erythematous rash at this stage.^4-6 After 2 to 3 days, a maculopapular eruption appears on the face, hands, forearms, and oropharyngeal mucosa; it later spreads centripetally. Lesions progress within a few days from macules to papules to vesicles and then to pustular vesicles; 8 to 14 days after onset of the illness, scabs form, with subsequent formation of pigmented depressed scars. Unlike varicella lesions—with which smallpox lesions might easily be confused (see Photo Essay, page 176h)—smallpox lesions remain synchronized during the course of the illness and are more deeply seated in the dermis; in addition, there is a greater abundance of lesions on the face and extremities than on the trunk. PREVENTIVE MEASURES Persons with suspected smallpox and their close contacts must be placed in strict quarantine with respiratory isolation for 17 days. The virus is shed in oropharyngeal secretions primarily after the onset of the exanthem.^4-6 While mucous membrane secretion of the virus diminishes after the first few days of the eruptive lesions, the virus can be recovered from scabs throughout the illness period. All exposed persons and their contacts should receive the vaccinia viral vaccine as soon as possible. Some protection against disease may be achieved if the vaccine is given within a few days of exposure. The current supply of vaccinia vaccine and vaccinia immune globulin, which would be needed for those with postvaccination complications and those at risk, is potentially inadequate; however, this problem is currently being addressed. The duration of protective immunity following primary vaccination is probably less than 15 years; following revaccination, it may last 30 years. Current efforts are focused on the evaluation of possible antiviral agents, such as cidofovir( and its derivatives, in the treatment of variola infections. DIAGNOSTIC ISSUES Confirmation of the diagnosis of smallpox is crucial; PCR and ELISA are the most useful assays. Virions and Guarnieri bodies may be seen with electron and light microscopy, respectively, but these findings do not distinguish between variola and the other orthopoxviruses. Monkeypox, which is still endemic in areas in Africa, can produce a clinically indistinguishable disease, although person-to-person spread is less common than with smallpox.^3,7,8 Monkeypox may also be an attractive and tractable weapon.⁵ Any suspicion of smallpox should prompt immediate notification of public health authorities.