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West Nile Virus

Information for Clinicians

Clinical Features

Mild Infection

Most West Nile Virus infections are mild and often clinically unapparent.

  • Approximately 20% of those infected develop a generally mild illness (West Nile fever).
  • The incubation period is thought to range from 3 to 14 days.
  • Symptoms generally last 3 to 6 days.

Reports from earlier outbreaks describe the mild form of WNV infection as a febrile illness of sudden onset often accompanied by

malaise
headache
anorexia
myalgia
nausea
rash
vomiting
lymphadenopathy
eye pain

The full clinical spectrum of West Nile fever has not been determined in the United States.

Severe Infection

Approximately 1 in 150 infections will result in severe neurological disease.

  • The most significant risk factor for developing severe neurological disease is advanced age.
  • Encephalitis is more commonly reported than meningitis.
  • In recent outbreaks, symptoms occurring among patients hospitalized with severe disease include

fever
gastrointestinal symptoms
weakness
change in mental status

  • A minority of patients with severe disease developed a maculopapular or morbilliform rash involving the neck, trunk, arms, or legs.
  • Several patients experienced severe muscle weakness and flaccid paralysis.
  • Neurological presentations included

ataxia and extrapyramidal signs
optic neuritis
cranial nerve abnormalities
polyradiculitis
myelitis
seizures

Although not observed in recent outbreaks, myocarditis, pancreatitis, and fulminant hepatitis have been described.

Clinical Suspicion

Diagnosis of WNV infection is based on a high index of clinical suspicion and obtaining specific laboratory tests.

  • WNV, or other arboviral diseases such as St. Louis encephalitis, should be strongly considered in adults >50 years who develop unexplained encephalitis or meningitis in summer or early fall.
  • The local presence of WNV enzootic activity or other human cases should further raise suspicion.
  • Obtaining a recent travel history is also important.

Note: Severe neurological disease due to WNV infection has occurred in patients of all ages. Year-round transmission is possible in some areas. Therefore, WNV should be considered in all persons with unexplained encephalitis and meningitis.

Diagnosis and Reporting

Procedures for submitting diagnostic samples and reporting persons with suspected WNV infection vary among states and jurisdictions. Links to state and local websites are available here.

Diagnostic Testing

West Nile virus (WNV) testing for patients with encephalitis, meningitis, or other serious central nervous system infections can be obtained through local or state health departments. For WNV diagnosis, public health laboratories usually perform an IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA). Using this assay, virus-specific IgM can be detected in nearly all cerebrospinal fluid (CSF) and serum specimens received from WNV-infected patients at the time of their clinical presentation. Because serum IgM antibody may persist for more than a year, physicians must determine whether the antibody is the result of a WNV infection in the previous year and unrelated to the current clinical presentation. The following procedures are recommended:

  • The most conclusive diagnostic method to identify persons with WNV infection of the central nervous system (CNS) is detecting WNV-specific IgM antibody in CSF using MAC-ELISA. This can be done with a CSF specimen obtained during initial clinical presentation. Because IgM antibody does not readily cross the blood-brain barrier, IgM antibody in CSF strongly suggests acute CNS infection
  • If CSF is not obtained and serum samples are used to make the diagnosis, paired acute- and convalescent-phase serum samples should be acquired. The acute-phase specimen should be obtained during initial clinical presentation and the convalescent-phase specimen should be obtained 7-14 days later. Both samples should be tested with MAC-ELISA.
  • If a convalescent-phase specimen cannot be obtained, the acute-phase specimen should be tested with MAC-ELISA. If the specimen is IgM-negative, then the illness is very unlikely to be an acute WNV infection. If the specimen is IgM-positive and the illness is clinically compatible, then it may be a recent WNV infection (presuming the test results for IgM antibody to St. Louis encephalitis (SLE) virus are significantly lower or negative; see below).

Ideally, MAC-ELISA testing should be performed, using both WNV and SLE virus. If the MAC-ELISA results for WNV and SLE are similar, it is necessary to use the plaque-reduction neutralization test (PRNT) to confirm either a WNV or SLE virus infection. Note: Patients who have been recently vaccinated against or recently infected with related flaviviruses (e.g., yellow fever, Japanese encephalitis, dengue) may have positive WNV MAC-ELISA results.

Reporting Suspected WNV Infection

Refer to local and state health department reporting requirements

  • WNV encephalitis is on the list of designated nationally notifiable arboviral encephalitides.
  • Aseptic meningitis is reportable in some jurisdictions.

The timely identification of persons with acute WNV or other arboviral infection may have significant public health implications and will likely augment the public health response to reduce the risk of additional human infections.

Laboratory Findings

Among patients in recent outbreaks

  • Total leukocyte counts in peripheral blood were mostly normal or elevated, with lymphocytopenia and anemia also occurring
  • Hyponatremia was sometimes present, particularly among patients with encephalitis.
  • Examination of the cerebrospinal fluid (CSF) showed pleocytosis, usually with a predominance of lymphocytes.
  • Protein was universally elevated.
  • Glucose was normal.
  • Computed tomographic scans of the brain mostly did not show evidence of acute disease, but in about one-third of patients, magnetic resonance imaging showed enhancement of the leptomeninges, the periventricular areas, or both.

Treatment

Treatment is supportive, often involving hospitalization, intravenous fluids, respiratory support, and prevention of secondary infections for patients with severe disease.

  • Ribavirin in high doses and interferon alpha-2b were found to have some activity against WNV in vitro, but no controlled studies have been completed on the use of these or other medications, including steroids, antiseizure drugs, or osmotic agents, in the management of WNV encephalitis.

For additional clinical information, please refer to Petersen LR and Marfin AA, "West Nile Virus: A Primer for the Clinician [Review]" Annals of Internal Medicine (August 6) 2002:137:173-9.
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For clinical and laboratory case definitions, see "Epidemic/Epizootic West Nile Virus in the United States: Revised Guidelines for Surveillance, Prevention, and Control, 2001,"