CBRNE - Smallpox Workup

Updated: Jul 21, 2021
  • Author: Christopher J Hogan, MD; Chief Editor: Duane C Caneva, MD, MSc  more...
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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:

  • Electron microscopy - May be useful to differentiate herpes viruses and poxviruses

  • Tzanck smear - Not specific for varicella because it detects all alphaherpesviruses

  • 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)

  • 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) [8]

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.



Include a lumbar puncture in the workup for hemorrhagic variola to exclude meningococcemia.