West Nile Virus (WNV) Infection and Encephalitis (WNE) Workup

Updated: Apr 05, 2021
  • Author: David J Cennimo, MD, FAAP, FACP, FIDSA, AAHIVS; Chief Editor: Michael Stuart Bronze, MD  more...
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Laboratory Studies

A laboratory diagnosis of WNV infection is based on isolation of the virus antigen or RNA in tissue, blood, CSF, or other body fluid. Diagnosis can also be made based on four-fold antibody titer increase or detection of viral-specific IgM antibody in CSF or serum. [6] The presence of WNV IgM almost always indicates recent WNV infection; however, because of cross-reactivity with IgM, this sometimes indicates recent infection with another flavivirus. The IgM antibodies are usually short-lived, lasting weeks to months; however, in cases of reinfection, it is important to measure titers approximately 2-3 weeks apart to establish a diagnosis. [22] Detection of IgM in CSF is presumptive of recent neuroinvasive disease.

Nucleic acid testing, if positive, is also diagnostic of active disease; however, negative results may reflect viremia that is inadequate for detection, especially in immunocompetent patients. [22] Therefore, RNA PCR is not recommended for diagnosis in immunocompetent patients. [22]


West Nile encephalitis (WNE), as with many viral illnesses, may feature mild leukopenia. Leukocytosis usually suggests another diagnosis.


Although relative lymphopenia is not specific for WNE, it is a helpful diagnostic finding if present in a patient with aseptic meningitis, meningoencephalitis, or, particularly, encephalitis of unknown cause.

Although patients with HIV infection or Venezuelan equine encephalitis often present with relative lymphopenia, the relative lymphopenia of WNE is usually more profound and may be prolonged, which should be suggestive.

ESR/CRP ratio

An ESR/CRP ratio of less than 1 suggests WNE in adults with encephalitis.

Serum transaminases

Mild elevations of serum glutamic-pyruvic transaminase (SGPT) levels are not a feature of most arboviral encephalitides.

In addition to WNE, mild elevations of serum glutamic-oxaloacetic transaminase (SGOT)/SGPT levels in a patient with encephalitis should suggest Epstein-Barr virus, Rocky Mountain spotted fever, ehrlichiosis, HHV-6 infection, or Legionnaires disease.

Serum ferritin levels

Serum ferritin levels are usually elevated in WNE and not in other causes of encephalitis. The magnitude/duration of serum ferritin elevations also has prognostic importance.


Imaging Studies

Imaging studies may be helpful, especially during the early phases of an evaluation. It may facilitate exclusion of other causes of encephalopathy.

Imaging findings in patients with WNE vary wildly and, when present, are nonspecific. Imaging results may be normal even in severe WNE. [28, 29] No particular MRI or CT findings are specific for WNE. [28, 29]

Patients with MRI abnormalities of the nerve roots or spinal cord were found to be more likely to have residual neurological deficits upon resolution of acute illness, and those with normal findings were found to be more likely to have a favorable prognosis. [29]

EEG may be used as an adjunctive study but is not likely sufficient for confirmation. EEG may show generalized continuous slowing, particularly in the anterior (frontal, temporal) regions, consistent with a nonspecific encephalopathy28; however, not all patients with WNE have generalized slowing, and generalized slowing is not specific to WNE.



Lumbar puncture

CSF reveals mild to moderate pleocytosis with a lymphocytic predominance in WNE. [19, 30] CSF protein levels are variably elevated, and the CSF glucose level is not decreased.

The CSF lactic acid level is not elevated, and RBCs, excluding traumatic taps, are not present in WNE. CSF Gram stain and bacterial culture findings are negative.

CSF testing for immunoglobulin M (IgM) antibodies against West Nile virus (WNV) should be performed (in addition to testing of the patient’s serum).


Histologic Findings

Brain biopsy findings exhibit diffuse encephalitis, which is nonspecific and nondiagnostic for WNE.