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Smallpox is spread most commonly in droplets from the oropharynx of infected individuals,
although infrequent transmission from aerosol and direct contact with infected lesions, clothing,
or bedding has been reported. Patients are not infectious during the incubation period or febrile
prodrome but become infectious with the onset of mucosal lesions (enanthemas), which occur
within hours of the rash. The first week of rash illness is regarded as the most infectious period,
although patients remain infectious until all scabs have separated. Because most smallpox
patients are extremely ill and bedridden, spread generally is limited to household contacts,
hospital workers, and other health care professionals. Secondary household attack rates for
smallpox were considerably lower than for measles and similar to or lower than rates for
varicella. The incubation period is 7–17 days (mean 12 days).
Variola major in unimmunized people was associated with case fatality rates of approximately
30% during epidemics of smallpox. The mortality rate was highest in children younger than 1
year and adults older than 30. The potential for modern supportive therapy in improving outcome
is not known. Death was most likely to occur during the second week of illness and was
attributed to overwhelming viremia. Secondary bacterial infections occurred but were a less
significant cause of mortality.
For help in evaluating a rash illness suspicious of smallpox, see
http://www.bt.cdc.gov/agent/smallpox/diagnosis/riskalgorithm/index.asp.
Diagnosis. Variola virus can be detected in vesicular or pustular fluid by culture or by PCR
assay. Electron microscopy can detect orthopoxvirus infection but cannot distinguish between
viruses. Currently, variola diagnostic testing is conducted only at the CDC. Reports of patients
classified by the CDC as at high risk of having smallpox will trigger a rapid response, with a
team deployed to obtain specimens and advise on clinical management.
Treatment. There is no effective antiviral therapy available to treat smallpox. Infected patients
should receive supportive care. Cidofovir, currently licensed for cytomegalovirus retinitis, has
been suggested as having a role in smallpox therapy, but data to support its use in smallpox are
not available. The drug must be given IV and is associated with significant renal toxicity.
Vaccinia immune globulin (VIG) is reserved for certain complications of immunization and has
no role in treatment of smallpox.
Control measures. If a patient is suspected of having smallpox, standard, contact, and airborne
precautions should be implemented immediately, and the State and local health departments
should be alerted at once. Hospital infection control personnel should be notified when the
patient is admitted, and the patient should be placed in a private, airborne infection isolation
room equipped with negative-pressure ventilation with high-efficiency particulate air filtration.
Anyone entering the room must wear an N95 or higher-quality respirator, gloves, and gown,
even if there is a history of recent successful immunization. If the patient is moved from the
room, he or she should wear a mask and be covered with sheets or gowns to decrease the risk of
fomite transmission. Rooms vacated by patients should be decontaminated using standard
hospital disinfectants, such as sodium hypochlorite or quaternary ammonia solutions. Laundry
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