Case Definition

Clinical Description
Most WNV infections are asymptomatic. Mild infections are also common and symptoms include fever, headache, and body aches, often with a skin rash and swollen lymph glands. More severe infections involve the central nervous system and result in meningitis (inflammation of the lining of the brain and spinal cord), encephalitis (inflammation of the brain), or acute flaccid paralysis.

WNV encephalitis cannot be distinguished clinically from many other causes of encephalitis. Manifestations can include headache, confusion, lethargy, nausea, altered consciousness, vomiting, fever, cranial nerve palsies, paresis (muscular weakness) or paralysis, sensory deficits, altered reflexes, tremors, convulsions, abnormal movements, coma of varying degree, and, in some cases, death. Case-fatality rates for WNV encephalitis range from 3% to 15%.

Cases of arboviral disease, including WNV, are classified as either neuroinvasive or not neuroinvasive based on clinical criteria, and classified as confirmed or probable based on laboratory criteria.

Neuroinvasive disease requires the presence of fever and at least one of the following, as documented by a physician and in the absence of a more likely clinical explanation:
  • Acutely altered mental status (e.g., disorientation, obtundation, stupor, or coma)
  • Other acute signs of central or peripheral neurologic dysfunction (e.g., paresis or paralysis, nerve palsies, sensory deficits, abnormal reflexes, generalized convulsions, or abnormal movements)
  • Pleocytosis (increased white blood cell concentration in the CSF) associated with illness clinically compatible with meningitis (e.g., headache or stiff neck)
not neuroinvasive disease requires, at minimum:
  • The presence of documented fever, as measured by the patient or clinician
  • The absence of neuroinvasive disease (above)
  • The absence of a more likely clinical explanation for the illness
Laboratory Diagnosis
Laboratory diagnosis is based on isolation of virus or identification of viral antigen or nucleic acids in clinical specimens, demonstration of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies in cerebrospinal fluid (CSF) or serum by enzyme-linked immunoassay (enzyme-linked immunosorbent assay ELISA, enzyme immunoassay EIA, and immunofluorescence assay IFA), hemagglutination inhibition, polymerase chain reaction (PCR), and plaque-reduction neutralizing test.

Case Classification
Confirmed
A clinically compatible neuroinvasive or not neuroinvasive case and at least one of the following:
  • Four-fold or greater change in virus-specific serum antibody titer
  • Isolation of virus from or demonstration of specific viral antigen or genomic sequences in tissue, blood, CSF, or other body fluid
  • Virus-specific IgM antibodies demonstrated in CSF by antibody-capture EIA
  • Virus-specific IgM antibodies demonstrated in serum by antibody-capture EIA and confirmed by demonstration of virus-specific serum IgG antibodies in the same or a later specimen by another serologic assay (e.g., neutralization or hemagglutination inhibition)
Probable
A clinically compatible neuroinvasive or not neuroinvasive case and at least one of the following:
  • Stable (less than or equal to a 2-fold change) but elevated titer of virus-specific serum antibodies
  • Virus-specific serum IgM antibodies detected by antibody-capture EIA but with no available results of a confirmatory test for virus-specific serum IgG antibodies in the same or a later specimen