Approach Considerations
Encephalitis is clinically diagnosed in 2-4% of adults and in 3-5% of children infected with the virus.
In patients presenting to the emergency department (ED) with a febrile illness, perform standard laboratory tests, including a complete blood count (CBC), electrolyte assessment, liver function tests, urinalysis, and other tests as indicated by the history and physical examination. The results of most laboratory studies in patients infected with Venezuelan equine encephalitis are nonspecific for febrile illnesses.
Electrolytes, blood glucose, renal function
Routine laboratory studies for the evaluation of an acutely ill patient with fever and headache is likely to include evaluation of electrolytes, blood glucose, and renal function.
Transaminases
Levels of transaminases, particularly serum aspartate transaminase and lactate dehydrogenase, may be elevated in Venezuelan equine encephalitis.
Liver function testing
In patients who are severely ill with Venezuelan equine encephalitis, hepatic compromise may produce abnormalities in liver synthetic function testing.
Liver function testing may reveal elevated lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) levels.
CBC count
A CBC count for analysis of the white blood cell count, hemoglobin, and platelet count is usually included in the evaluation. A decreased lymphocyte or a lymphocyte and granulocyte count 1-3 days after onset of symptoms is common.
Eosinopenia and vacuolated monocytes have been described. Lymphopenia and thrombocytopenia may also be observed.
Urinalysis and cultures
Urinalysis as part of the evaluation of other sources of infection is common. Urine culture and blood culture studies are case dependent.
Viral isolation
A specific diagnosis of Venezuelan equine encephalitis may be made with isolation of virus in the blood or from a throat swab within 1-3 days after onset of symptoms.
Lumbar puncture
Lumbar puncture with analysis of the obtained cerebrospinal fluid (CSF) is essential in reaching a diagnosis and determining the severity of illness. In patients with Venezuelan equine encephalitis, CSF analysis typically reveals a mononuclear pleocytosis of several hundred cells with a glucose concentration within the reference range.
Serologic Studies
Sera from patients with full-blown Venezuelan equine encephalitis are usually negative for the virus, but the diagnosis can be made using serologic studies.
Enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and neutralization tests can be used to identify the virus. Immunoglobulin M (IgM) and IgG ELISA, using attenuated Venezuelan equine encephalitis as the antigen, are most sensitive but need to be followed by plaque reduction neutralization to provide diagnostic specificity. Demonstration of a 4-fold rise in serum antibody titer is also useful diagnostically.
Serum can also be sent to a laboratory with the ability to test for Venezuelan equine encephalitis and other, similar diseases using ultrasensitive qualitative detection by reverse transcription coupled real-time polymerase chain reaction (PCR) assay. Diagnostic methods also include microsphere-based immunoassay (MIA).
Imaging Studies
Chest radiography and head computed tomography (CT) scanning may be helpful adjuncts in assessing the complications of Venezuelan equine encephalitis or in helping to eliminate other diagnostic possibilities.
Interstitial infiltrates on chest radiography indicate acute pneumonitis, which is occasionally observed in patients with Venezuelan equine encephalitis. A CT scan of the head that reveals edema or hemorrhage necessitates emergency intervention. Magnetic resonance imaging (MRI) may also be useful in establishing the diagnosis of encephalitis.
Histologic Findings
Death due to Venezuelan equine encephalitis follows diffuse congestion and edema with hemorrhage in the brain, gastrointestinal tract, and lungs. Pathologic changes in the brain include congestion, perivascular cuffing and hemorrhage, glial nodule formation, and focal necrosis. The pathology is most prominent in the basal ganglia and substantia nigra but is also found in the cerebral cortices and deep white matter. Meningoencephalitis with necrotizing vasculitis and cerebritis has been observed in some patients. Hepatocellular degeneration and interstitial pneumonitis have been noted in fatal human infections.
Equine infections are characterized by a striking depletion of lymphocytes in the lymph nodes, spleen, and gastrointestinal tract.
