Tests
1st tests to order
polymerase chain reaction
Test
Order in all patients with suspected smallpox. Definitive diagnosis requires laboratory confirmation. Polymerase chain reaction (PCR) is the preferred laboratory test given its accuracy and sensitivity. Testing is available at regional public health laboratories.
Recommended specimen type is skin lesion material, including swabs of lesion exudate, roofs from more than one lesion, or lesion crusts. Collect other diagnostic material as dictated by the reference laboratory protocol, such as oropharyngeal swabs, ethylenediamine tetra-acetic acid (EDTA) blood, clotted blood for serum separation, or urine.
Collect, label, package, and send specimens according to local or national protocols. Notify the laboratory of the possibility of smallpox prior to sending specimens. There are local protocols in place for the safe handling of these specimens in the laboratory and onward transport of virologic materials to the reference laboratory. Package samples for testing for other infections separately.
Testing the sample for varicella zoster virus should automatically be performed by the reference laboratory when undertaking PCR for poxviral DNA. It may be positive for varicella zoster virus DNA if coinfection is present.
Result
positive for smallpox DNA
CBC
Test
Order in all patients with suspected smallpox.
Result
may show lymphocytosis, relative neutropenia early in eruptive phase, thrombocythemia after vesicular phase, marked thrombocytopenia in rare hemorrhagic variant
BUN and electrolytes
Test
Order in all patients with suspected smallpox.
There is very little information on BUN and electrolytes in patients with smallpox; however, acute kidney injury in toxemic patients with hypotension may occur.
Result
may show elevated serum creatinine, high serum potassium, metabolic acidosis
LFTs
Test
Order in all patients with suspected smallpox.
There is very little information on LFTs in smallpox; however, liver injury from direct cytopathic effect and visceral involvement by the smallpox virus may occur.
In nonfatal smallpox, liver enzymes were reportedly unremarkable during a clinical trial in Ethiopia.[26] In a study of hemorrhagic smallpox in Madras, transaminases were raised.[27]
Result
may be elevated or normal
venous lactate
Test
Order in all patients with suspected smallpox.
Venous lactate is a marker for tissue perfusion and the need for intravenous fluids in sepsis syndrome. It has not been studied in relation to smallpox, but, given the high rates of "prostration" and death, it is likely to be useful as part of modern supportive care.
Result
elevated in severe disease
clotting screen
Test
Order in all patients with suspected hemorrhagic smallpox.
Hemorrhagic smallpox has poor outcomes and is associated with prolonged clotting times that may benefit from support with clotting factors and platelet infusions.[27]
Result
prolonged clotting times (hemorrhagic smallpox)
Tests to consider
blood culture
Test
Order in all patients with suspected smallpox.
Blood cultures were not routinely performed historically, but empiric antibiotics were given especially when bacterial superinfection of cutaneous lesions was suspected, or if bacterial infection was thought possible in a very sick patient.
It is good practice to take blood cultures prior to antibiotic administration, although the evidence for bacteremia in smallpox is missing.
Result
may show bacteremia
malaria antigen test
Test
Order in all patients with suspected smallpox if there is a recent history of travel to a malaria-endemic area.
Always rule out coinfection with malaria in any febrile patient who has been to a malaria-endemic area, especially in the 3 weeks prior to the onset of fever.
An antigen detection test poses less of an infection hazard to laboratory staff than preparation of thick and thin films. The laboratory must first be notified of the risk of smallpox and secure transportation of specimens organized as per local policies.
Result
negative; may be positive if coinfection
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