Laboratory Studies
The Centers for Disease Control and Prevention (CDC) has made available an algorithm that has worked well to guide clinical and public health responses to suspected smallpox cases. The poster is available from the CDC, and the CDC's Web site contains an interactive version of the algorithm and laboratory protocol (see Evaluate a Rash Illness Suspicious for Smallpox).
Perform a viral swab of the pharynx in patients in whom smallpox is suspected, or swab a freshly opened pustule, if available. Otherwise, open a lesion with a scalpel and obtain a culture.
The following are recommended rapid tests (all providing test results within hours) for assessing smallpox infection, in increasing order of reliability:
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Electron microscopy - May be useful to differentiate herpes viruses and poxviruses
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Tzanck smear - Not specific for varicella because it detects all alphaherpesviruses
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Varicella-zoster virus (VZV) direct fluorescent antibody (DFA) assay - Agent specific, simple, and commercially available (however, reliability requires careful collection and prompt processing of specimens)
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Real-time polymerase chain reaction (PCR) testing - Most sensitive and specific rapid assay for detection of VZV (now available to all state health departments and Laboratory Response Network [LRN] laboratories)
Send the swab samples in a Vacutainer tube with the rubber stopper taped. Double seal the tube, and inform the receiving laboratory and courier of the potential biohazard. Prior to collection of samples or shipment, the CDC or the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) should be consulted directly, as should local public health authorities. In addition to individual state laws concerning highly infectious agents, specific federal laws apply to the shipping of such pathogens across state lines.
Serologic testing is not useful for rapid diagnostic purposes.
Imaging Studies
No imaging studies assist in making the diagnosis of variola infection.
Procedures
Include a lumbar puncture in the workup for hemorrhagic variola to exclude meningococcemia.
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Characteristic skin lesion of variola on the arms and legs of an adolescent. Photo used with permission from the World Health Organization (WHO).
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Small child with pustular lesions of variola. Photo used with permission of the World Health Organization (WHO).
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Infant with advanced lesions of variola. Photo used with permission of the World Health Organization (WHO).
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Unvaccinated infant with centrifugally distributed umbilicated pustules on day 3 of ordinary form of variola major strains of smallpox. Reprinted with permission from Fenner F, Henderson DA, Arita I, et al: Smallpox and its eradication. Geneva, Switzerland: World Health Organization; 1988: 10-14, 35-36; photographs by Arita.
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Unvaccinated infant with centrifugally distributed umbilicated pustules on day 5 of ordinary form of variola major strains of smallpox. Reprinted with permission from Fenner F, Henderson DA, Arita I, et al: Smallpox and its eradication. Geneva, Switzerland: World Health Organization; 1988: 10-14, 35-36; photographs by Arita.
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Unvaccinated infant with centrifugally distributed umbilicated pustules on day 7 of ordinary form of variola major strains of smallpox. Reprinted with permission from Fenner F, Henderson DA, Arita I, et al: Smallpox and its eradication. Geneva, Switzerland: World Health Organization; 1988: 10-14, 35-36; photographs by Arita.
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Ordinary form of variola minor strain of smallpox (alastrim) in an unvaccinated woman 12 days after onset of skin lesions. The facial lesions are sparser and evolved more rapidly than the extremity lesions. Reprinted with permission from Fenner F, Henderson DA, Arita I, et al: Smallpox and its eradication. Geneva, Switzerland: World Health Organization; 1988: 10-14, 35-36; photographs by Arita.
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Ordinary form of variola minor strain of smallpox (alastrim) in an unvaccinated woman 12 days after onset of skin lesions. The facial lesions are sparser and evolved more rapidly than the extremity lesions. Reprinted with permission from Fenner F, Henderson DA, Arita I, et al: Smallpox and its eradication. Geneva, Switzerland: World Health Organization; 1988: 10-14, 35-36; photographs by Arita.
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Ordinary form of variola minor strain of smallpox (alastrim) in an unvaccinated woman 12 days after onset of skin lesions. The facial lesions are sparser and evolved more rapidly than the extremity lesions. Reprinted with permission from Fenner F, Henderson DA, Arita I, et al: Smallpox and its eradication. Geneva, Switzerland: World Health Organization; 1988: 10-14, 35-36; photographs by Arita.
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Adult with variola major with hundreds of pustular lesions distributed centrifugally. Fitzsimmons Army Medical Center slide file.
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Hemorrhagic-type variola major lesions. Death usually ensued before typical pustules developed. Reprinted with permission from Herrlich A, Mayr A, Munz E, et al: Die pocken; Erreger, Epidemiologic und klinisches Bild. 2nd ed. Stuttgart, Germany: Thieme; 1967. In: Fenner F, Henderson DA, Arita I, et al: Smallpox and its eradication. Geneva, Switzerland: World Health Organization; 1988: 10-14, 35-36.
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Boy with monkeypox in Democratic Republic of the Congo in 1996. Note the centrifugal distribution as was typical of smallpox. Courtesy of William Clemm.
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Boy with monkeypox in Democratic Republic of the Congo in 1996. Note synchronicity of lesions as was typical of smallpox. Courtesy of William Clemm.
