Diagnosis Synopsis
Smallpox is a contagious and often fatal infection caused by the variola virus. It presents in two clinical forms: variola major smallpox (historic mortality rate: 30%) and variola minor, which produces a milder smallpox-like illness (historic mortality rate: less than 1%). There are 4 clinical subtypes of smallpox: ordinary, modified, flat and hemorrhagic. 90% 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 to 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 to 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.
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 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 to 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. Although routine vaccination of children in the United States against smallpox was discontinued in 1972, beginning in 2002 military personnel and some clinicians, law enforcement personnel, public health officials and other first responders have participated in a vaccination effort. Currently the vaccination is not available to the general public.
The only people at risk for smallpox outside of a bioterrorist attack are those maintaining authorized stocks in laboratories at the CDC in Atlanta and in Moscow. Terrorist groups may be exposed if they are growing stocks of the virus for illicit purposes.
A case of smallpox must be reported immediately to local and state health authorities and would be considered an international emergency.
Precautions: Immediately institute isolation (negative pressure room) and airborne/respiratory precautions. Cohort and quarantine all suspected exposures.
Look For
After an incubation period of 1 to 2 weeks, erythematous macules and papules quickly spread centrifugally and uniformly from the face and extremities to the rest of the body. Red macules are transient. There is quick evolution to the characteristic vesicles and pustules. Lesions appear to progress uniformly. Umbilication is characteristically seen (there is a central dent in many of the vesicles and pustules).
The palms and soles are affected. In the hemorrhagic form of smallpox, petechiae and hemorrhage are associated with intense abdominal pain, headache, backache and high fever.
In the flat form, constitutional symptoms are also severe, but the skin lesions are confluent, soft, red-orange papules that do not evolve into pustules and crusts.
Variola minor has much less severe constitutional symptoms and fewer skin lesions.
Diagnostic Pearls
At any given time, lesions are in one uniform stage of development wherever they are located on the body.
Differential Diagnosis & Pitfalls
In disseminated varicella (chickenpox), lesions are in multiple stages of development. In the Congo, monkeypox has identical lesions, however, in a 2003 outbreak in the United States, this was not the case, as lesions were present at various stages simultaneously. Generalized vaccinia was previously mistaken for smallpox during eradication efforts in the 1960s and 70s. If smallpox vaccination is occurring, generalized vaccinia should be considered within the differential diagnosis. Herpes simplex, disseminated.
Best Tests
Harvest blister or pustular fluid on a cotton swab and place in a Vacutainer, use stopper and adhesive tape to seal. Enclose this tube in a second watertight container. Contact local public health officials for handling and evaluation. Laboratory examination should only occur in high containment (BL-4) facilities. Electron microscopy of blister fluid.
PCR
Management Pearls
Assign those who have been previously vaccinated to caring for patients. Use gowns, masks and gloves. In a very small outbreak (few cases), admit to hospital or separate designated facility, and use negative pressure rooms. In large outbreaks, home isolation is imperative. Vaccination of individuals exposed to an aerosol attack and health care workers may prevent severe disease if administered within 4 days of exposure. Contacts are defined as those in the same household or persons having face-to-face exposure with the patient. Patients are not infectious until about 1 day before the rash stage develops. ISOLATION in the home and contact public health authorities immediately. Patients are infectious from the onset of the rash until the last scab falls off. Smallpox is easily spread person-to-person by respiratory droplets and contact with bodily fluids or contaminated clothing or bedding.
Therapy
Supportive therapy.
Fluids.
Cidofovir is untested in smallpox but has proven effective against other poxviruses.
Medical Disclaimer:
The information contained in this web page is intended to be an adjunct to traditional medical information sources. It is not intended to be a substitute for professional medical judgment.
Authors and Editors:
Tener Goodwin Veenema PhD, MPH, MS, CPNP
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