Investigations
1st investigations to order
enzyme-linked immunosorbent assay (ELISA)
Test
Serological testing is the preferred method for diagnosis and is recommended in all patients with suspected infection.[1]
ELISA (especially IgG ELISA) has low specificity for eastern equine encephalitis virus (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.[1]
Serologies may be performed in paired acute and convalescent sera. A fourfold rise in EEEV-specific IgG is diagnostic.[47]
IgM and IgG become positive approximately after 5 days of onset of illness. IgM remains positive for at least 1 month, whereas IgG likely remains positive for decades.
Only available at some reference laboratories in endemic countries (e.g., US Centers for Disease Control and Prevention [CDC], state health departments).
Result
positive for IgG or IgM for EEEV
MRI brain
Test
While MRI is not necessary for the diagnosis, 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, and is the preferred imaging modality.[46][50]
Enhancement is often seen on T2 and fluid-attenuated inversion recovery (FLAIR), with early stages of infection revealing a preference for deep grey matter structures, especially the basal ganglia, bilateral thalami, mesial temporal lobes, and brainstem. Cerebral cortex involvement or meningeal enhancement may also be seen.[46][51]
Results between adults and children may differ. One study highlighted that children revealed 100% cortical involvement, while only 29% of adults exhibited cortical changes.[51]
Result
CNS lesions
plaque reduction neutralisation test (PRNT)
Test
If enzyme-linked immunosorbent assay (ELISA) is used for serology, further confirmation by PRNT is needed.[1]
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 in endemic countries (e.g., US Centers for Disease Control and Prevention [CDC], state health departments).
Result
reduction of plaques (commonly used measure is 80% reduction)
FBC
basic metabolic panel
Test
Order in patients presenting with signs and symptoms suggestive of infection.
Hyponatraemia is seen in approximately 60% of patients.[46]
Result
hyponatraemia
erythrocyte sedimentation rate (ESR)
Test
Order in patients presenting with signs and symptoms suggestive of infection.
ESR may be elevated in some patients.[14]
Result
may be elevated
C-reactive protein (CRP)
Test
Order in patients presenting with signs and symptoms suggestive of infection.
CRP may be elevated in some patients.[14]
Result
may be elevated
cerebrospinal fluid (CSF) studies
Test
Perform a lumbar puncture and CSF analysis for cell count and standard chemistries (e.g., glucose, protein) if central nervous system involvement is suspected.[1]
Results usually reveal initial neutrophilic pleocytosis (followed by lymphocyte predominance), elevated red blood cells (RBCs), normal glucose, and elevated protein.[1][33][46]
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). Eastern equine encephalitis virus (EEEV) IgM may also be detected in CSF.
Result
pleocytosis with initial neutrophilic predominance then lymphocyte predominance; normal glucose; elevated RBCs; elevated protein; positive for EEEV IgM
Investigations to consider
real-time polymerase chain reaction (RT-PCR)
Test
Molecular testing with RT-PCR may be required for immunocompromised patients.[1]
Immunocompromised patients present a particular diagnostic challenge, particularly individuals with solid organ transplant, who are unable to mount an appropriate, measurable immune response, and present a higher mortality risk.[48][49]
Serological testing can be challenging in these patients; therefore, they may require additional molecular testing for diagnosis.
Result
positive for eastern equine encephalitis virus RNA (EEEV RNA)
CT brain
Test
While CT is not necessary for the diagnosis, it can be used to assess for central nervous system (CNS) involvement (e.g., if MRI is not available).
Initial CT may be normal.[33] When lesions are seen, they tend to be present in the basal ganglia, thalamus, or cerebral cortex.[33][46]
Result
CNS lesions
electroencephalogram
Test
May be ordered to assess for central nervous system involvement.
Findings include generalised slowing, subclinical status epilepticus, and epileptiform activity.[33]
Can exhibit periodic 0.25 to 0.5 Hz transient epileptiform discharges.[52]
Voltage in eastern equine encephalitis virus infection is significantly lower compared with herpes encephalitis.[52]
Result
generalised slowing; subclinical status epilepticus; epileptiform activity
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