Diagnosis

Due to the risk of using smallpox virus as potential bio warfare agent or terrorist weapon, there is a need to be able to identify smallpox unambiguously, rapidly and reliably (1).

The Health Protection Agency (HPA) has released the following cardinal signs for case detection:

• an abrupt onset moderate fever (up to 39ºC), with extreme prostration.
• characteristic vesicular rash most dense on the extremities and face beginning on the third to fourth day of illness (click here).
• skin lesions over one area of body generally at the same stage of development. New and enlarging vesicles coalesce to form soft, flaccid bullae covered by skin, which easily rubs off.
• less commonly, an erythematous or purpuric rash may appear earlier in illness (associated with a poorer prognosis) (1)

For the initial cases during an outbreak,

• confirmation of cases is carried out by identification of
  • orthopox particles by electron microscopy (EM) -
  • smallpox DNA by polymerase chain reaction (PCR)
• clinical samples from suspected cases must be handled with due regard to the likelihood that smallpox is present, and the appropriate procedures observed (1)
• diagnostic samples which can be used include: vesicular/ pustular fluid, scab biopsy, pharyngeal swab, clotted blood (2)

Full blood count shows a lymphocytosis or, at least, a predominance of lymphocytes, with many atypical and activated mononuclear cells. Haemorrhagic disease would be preceded by a fall in the platelet count (3)

In a case with strongly suspicious clinical features and no other diagnosis, failure to detect any organism with EM or PCR does not exclude smallpox, and such cases may be regarded as probable (1)

Note:

• in the event of a deliberate release in the UK population (mostly non-immune), it is extremely unlikely that single, mild cases of feverish, pox-like illness will occur - it is much more likely that clusters of cases of moderate to severe disease would be seen
• if a patient presents with any of the above, expert clinical opinion should be sought urgently. In addition in England, Wales and Northern Ireland the local HPU Consultant in Communicable Disease Control (or their counterpart in Scotland) and the HPA Duty Doctor should also be contacted urgently and given details. In Scotland the Health Protection Scotland should be contacted

Reference:

• (1) Department of health (DH) 2010. Guidelines for Smallpox Response and Management in the Post-Eradication Era
• (2) Health Protection Agency (HPA) 2011. Unusual Illness, including Deliberate or Accidental Releases: Cardinal Signs and Tips for Key Biological Agents
• (3) Health Protection Agency (HPA) 2010 Smallpox (Deliberate Releases). Guidance. Clinical Features of Disease.