Investigations
1st investigations to order
enzyme-linked immunosorbent assay (ELISA)
Test
ELISA (especially IgG ELISA) has low specificity for EEEV as it tends to cross-react with other alphaviruses (e.g., Venezuelan equine encephalitis virus, Mayaro virus, chikungunya virus); therefore, further confirmation by plaque reduction neutralisation test is warranted if ELISA is used for serology.
Serologies may be performed in paired acute and convalescent sera. A 4-fold rise in EEEV-specific IgG is diagnostic.
IgM and IgG become positive approximately after 5 days of onset of illness. IgM remains positive for at least a month, whereas IgG likely remains positive for decades.
Only available at some reference laboratories (e.g., the Centers for Disease Control and Prevention [CDC] in the US).
Result
positive for IgG or IgM for EEEV
MRI brain
Test
While MRI is not necessary for the diagnosis of EEEV infection, it can be used to assess for central nervous system (CNS) involvement.
MRI is a more sensitive diagnostic modality than CT for the detection of encephalitis due to its ability to discern early signs of oedema and infection.[37]
Enhancement is often seen on T2 and fluid-attenuated inversion recovery (FLAIR) images of the basal ganglia, thalamus, and cerebral cortex. Meningeal enhancement may also be seen.
Result
CNS lesions
plaque reduction neutralisation test (PRNT)
Test
Most specific serological test. Allows differentiation between cross-reactive alphaviruses.
Does not differentiate between IgM and IgG.
Requires skill and is time consuming.
Only available at some reference laboratories (e.g., the Centers for Disease Control and Prevention [CDC] in the US).
Result
reduction of plaques (commonly used measure is 80% reduction)
FBC
basic metabolic panel
Test
Ordered in patients presenting with signs and symptoms suggestive of EEEV infection.
Hyponatraemia is seen in approximately 60% of patients with EEEV infection.[36]
Result
hyponatraemia
Investigations to consider
cerebrospinal fluid (CSF) studies
Test
Lumbar puncture should be performed and CSF analysed for cell count and standard chemistries (e.g., glucose, protein) if CNS involvement is suspected.
If facilities and expertise for viral detection are available, virus may be detected from CSF during the early phase of infection (i.e., using reverse transcription-polymerase chain reaction [RT-PCR] or viral isolation). EEEV IgM may also be detected in CSF.
Result
pleocytosis with neutrophilic predominance; elevated RBCs; elevated protein; positive for EEEV IgM in CSF
CT brain
Test
While CT is not necessary for the diagnosis of EEEV infection, it can be used to assess for CNS involvement.
Initial CT may be normal.[2]
Hypointense lesions may be seen in the basal ganglia, thalamus, and cerebral cortex.
Result
CNS lesions
electroencephalogram
Test
Findings include generalised slowing, subclinical status epilepticus, and epileptiform activity.[2]
Result
generalised slowing; subclinical status epilepticus; epileptiform activity
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