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Smallpox is a highly contagious disease caused by the smallpox virus, an orthopoxvirus. It causes death in up to 30%. Indigenous infection has been eradicated. The main concern for outbreaks is from bioterrorism. Severe constitutional symptoms and a characteristic pustular rash develop. Treatment is supportive. Prevention involves vaccination, which, because of its risks, is done selectively.
No cases of smallpox have occurred in the world since 1977 because of worldwide vaccination. In 1980, the World Health Organization (WHO) recommended discontinuation of routine smallpox vaccination. Routine vaccination in the US ended in 1972. Because humans are the only natural host of the smallpox virus and because the virus cannot survive > 2 days in the environment, WHO has declared natural infection eradicated. Recent concerns about terrorist access to existing stockpiles of smallpox virus raise the possibility of a recurrence (see Biology of Infectious Disease: Biological Warfare and Terrorism).
Because immunity declines over time, nearly all people—even those previously vaccinated—are now thought to be susceptible to smallpox.
Pathophysiology
There are at least 2 strains of smallpox virus. The more virulent strain causes variola major (classic smallpox); the less virulent strain causes variola minor (alastrim).
Smallpox is transmitted from person to person by direct contact or inhalation of droplet nuclei. Contaminated clothing or bed linens can also transmit infection. The infection is most communicable for the first 7 to 10 days after the rash appears. Once crusts form on the skin lesions, infectivity declines.
The attack rate is as high as 85% in unvaccinated people, and infection may lead to as many as 4 to 10 secondary cases from each primary case. However, infection tends to spread slowly and mainly among close contacts.
The virus invades the oropharyngeal or respiratory mucosa and multiplies in regional lymph nodes, causing subsequent viremia. It eventually localizes in small blood vessels of the dermis and the oropharyngeal mucosa. Other organs are seldom clinically involved, except for occasionally the CNS, with encephalitis. Secondary bacterial infection may develop in skin lesions.
Symptoms and Signs
Variola major has a 10- to 12-day incubation period (range 7 to 17 days), followed by a 2- to 3-day prodrome of fever, headache, backache, and extreme malaise. Sometimes severe abdominal pain and vomiting occur. After the prodrome, a maculopapular rash develops on the oropharyngeal mucosa, face, and arms, spreading shortly thereafter to the trunk and legs. The oropharyngeal lesions quickly ulcerate. After 1 or 2 days, the cutaneous lesions become vesicular, then pustular. Pustules are denser on the face and extremities than on the trunk, and they may appear on the palms. The pustules are round and tense and appear deeply embedded. Skin lesions of smallpox, unlike those of chickenpox, are all at the same stage of development on a given body part. After 8 or 9 days, the pustules become crusted. Severe residual scarring is typical. Mortality rate is about 30%, due to a massive inflammatory response causing shock and multiple organ failure; death usually occurs in the 2nd wk of illness.
Variola minor results in symptoms that are similar but much less severe, with a less extensive rash. Mortality rate is < 1%.
About 5 to 10% of people with smallpox develop either a hemorrhagic or a malignant variant. The hemorrhagic form is rarer and has a shorter, more intense prodrome, followed by generalized erythema and cutaneous and mucosal hemorrhage. It is uniformly fatal within 5 or 6 days. The malignant form has a similar, severe prodrome, followed by development of confluent, flat, nonpustular skin lesions. In the rare survivors, the epidermis frequently peels.
Diagnosis
Diagnosis is confirmed by documenting the presence of variola DNA by PCR of vesicular or pustular samples. Or the virus can be confirmed by electron microscopy or viral culture of material scraped from skin lesions (ideally, with subsequent confirmation by PCR). Suspected smallpox must be reported immediately to local public health agencies or the Centers for Disease Control and Prevention (CDC) at 770-488-7100. These agencies then arrange for testing in a laboratory with high-level containment capability (biosafety level 4).
Treatment
Treatment is generally supportive, with antibiotics for the occasional secondary bacterial infection. Antiviral drugs have never been used clinically, but cidofovir may be considered for use under an investigational new drug protocol sponsored by the CDC.
Isolation of people with smallpox is essential. In limited outbreaks, patients may be isolated in a hospital in a negative-pressure room equipped with high-efficiency particulate (HEPA) filters. In mass outbreaks, home isolation may be required. Contacts should be placed under surveillance, typically with daily temperature measurement, and isolated at home if they develop a temperature of > 38° C or other sign of illness.
Prevention
Smallpox vaccine consists of live vaccinia virus, which is related to smallpox and provides cross-immunity. Vaccine is administered with a bifurcated needle dipped in reconstituted vaccine. The needle is rapidly jabbed 15 times in an area about 5 mm in diameter and with sufficient force to draw a trace of blood. The vaccine site is covered with a dressing to prevent spread of the vaccine virus to other body sites. Fever, malaise, and myalgias are common the week after vaccination. Successful vaccination is indicated by development of a pustule by about the 7th day. Revaccination may cause only a papule surrounded by erythema, which peaks between 3 and 7 days. People without such signs of successful vaccination should be given another dose of vaccine.
Until an outbreak in the population occurs, preexposure vaccination remains recommended only for people at high risk of exposure to the virus (eg, laboratory technicians).
Vaccine complications:
Risk factors for complications include extensive skin disorders (particularly eczema), immunosuppressive diseases or therapies, ocular inflammation, and pregnancy. Widespread vaccination is not recommended because of the risk. Serious complications occur in about 100 per million primary vaccines and include
Postvaccinial encephalitis occurs in about 1 of 300,000 recipients of primary vaccination, typically 8 to 15 days postvaccination.
Progressive vaccinia results in a nonhealing vaccinial (vesicular) skin lesion that spreads to adjacent skin and ultimately other skin areas, bones, and viscera. Progressive vaccinia may occur after primary vaccination or revaccination but occurs almost exclusively in patients with an underlying defect in cell-mediated immunity; it can be fatal.
Eczema vaccinatum results in vaccinial skin lesions appearing on areas of active or even healed eczema.
Generalized vaccinia results from hematogenous dissemination of the vaccinia virus and causes vaccinia lesions at multiple body locations; it is usually benign. If there is inadvertent ocular viral implantation, vaccinia keratitis occurs rarely.
Some serious vaccine complications are treated with vaccinia immune globulin (VIG). In the past, high-risk patients who required vaccination because of viral exposure were simultaneously given VIG to try to prevent complications. The efficacy of this practice is unknown, and it is not recommended by the CDC. VIG is available only from the CDC.
Postexposure prophylaxis:
Postexposure vaccination can prevent or significantly limit the severity of illness and is indicated for family members and close personal contacts of smallpox patients. Early administration is most effective, but some benefit is realized up to 4 days postexposure.
Last full review/revision November 2009 by Mary T. Caserta, MD
Content last modified November 2009
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