National case definition: West Nile virus
Date of last revision/review: September 2008
Probable and confirmed cases of disease should be notified.
Type of surveillance
Routine case-by-case notification to the federal level
West Nile Virus Neurological Syndrome (WNNS)
Clinical criteria AND at least one of the confirmed case diagnostic test criteria
Clinical criteria AND at least one of the probable case diagnostic test criteria
Clinical criteria in the absence of or pending diagnostic test criteria AND in the absence of any other obvious cause
History of exposure in an area where West Nile virus (WNV) activity is occurring (see Comments section)
history of exposure to an alternative mode of transmission (see Comments section)
onset of fever
recent onset of at least one of the following:
- encephalitis (acute signs of central or peripheral neurologic dysfunction) or
- viral meningitis (pleocytosis and signs of infection, e.g. headache, nuchal rigidity) or
- acute flaccid paralysis (e.g. poliomyelitis-like syndrome or Guillain-Barré-like syndrome), or
- movement disorders (e.g. tremor, myoclonus) or
- Parkinsonism or Parkinsonian-like conditions (e.g. cogwheel rigidity, bradykinesia, postural instability) or
- other neurological syndromes
West Nile Virus Non-Neurological Syndrome (WN Non-NS)
Clinical criteria and at least one of the confirmed case diagnostic test criteria
Clinical criteria and at least one of the probable case diagnostic test criteria
Clinical criteria in the absence of or pending diagnostic test criteria and in the absence of any other obvious cause
History of exposure in an area where WN virus (WNV) activity is occurring
history of exposure to an alternative mode of transmission
at least two of the following:
- maculopapular rash
West Nile Virus Asymptomatic Infection (WNAI)
Confirmed case diagnostic test criteria in the absence of clinical criteria
Probable case diagnostic test criteria in the absence of clinical criteria
Confirmed case diagnostic test criteria
It is currently recommended that health jurisdictions/authorities use the Confirmed Case Diagnostic Test Criteria to confirm index cases (locally acquired) in their area each year; for subsequent cases, health jurisdictions/authorities could use the Probable Case Diagnostic Test Criteria to classify cases in their area as “confirmed”, for the purposes of surveillance. Throughout the remainder of the transmission season health jurisdictions/authorities may wish to document PRN antibody titres to West Nile virus in a proportion of cases, to be determined by that health jurisdiction/authority, in order to rule out the possibility of concurrent activity by other flaviviruses. (For further information on diagnostic testing algorithms for West Nile virus, see the section entitled Laboratory Specimen Diagnostic Testing Algorithm in Appendix 4 of the National Guidelines for Response to West Nile virus.)
At least one of the following:
- a significant (e.g. fourfold or greater) change in WN virus neutralizing antibody titres (using a PRN or other kind of neutralization assay) in paired acute and convalescent sera, or CSF (see Comments section for testing of immunocompromised individuals)
- isolation of WN virus from, or demonstration of WN virus-specific genomic sequences in, tissue, blood, CSF or other body fluids
- demonstration of WN virus antigen in tissue
- demonstration of flavivirus antibodies in a single serum or CSF sample using a WN virus IgM EIA (see Comments section), confirmed by the detection of WN virus specific antibodies using a PRN (acute or convalescent specimen)
- a significant (e.g. fourfold or greater) change in flavivirus haemagglutination inhibition (HI) titres in paired acute and convalescent sera or demonstration of a seroconversion using a WN virus IgG EIA AND the detection of WN specific antibodies using a PRN (acute or convalescent serum sample)
Probable case diagnostic test criteria (see “Comments” section)
At least one of the following:
- detection of flavivirus antibodies in a single serum or CSF sample using a WN virus IgM EIA without confirmatory neutralization serology (e.g. PRN)
- a significant (e.g. fourfold or greater) change in flavivirus HI titres in paired acute and convalescent sera or demonstration of a seroconversion using a WN virus IgG EIA
- a titre of > 1:320 in a single WN virus HI test or an elevated titre in a WN virus IgG EIA, with a confirmatory PRN result (Note: a confirmatory PRN or other kind of neutralization assay is not required in a health jurisdiction/authority where cases have already been confirmed in the current year.)
- demonstration of Japanese encephalitis (JE) serocomplex-specific genomic sequences in blood by NAT screening on donor blood, by Blood Operators in Canada
Sensitivity of NAT testing is approximately 50% when used on plasma/serum samples collected less than eight days after symptoms have been detected. Individuals infected with WN virus display a low level of viremia (on average several thousand genome copies) for approximately one week after symptom onset. The use of NAT testing on acute serum/plasma samples can complement IgM testing when used together to assay "early" acute specimens(1).
West Nile Neurological Syndrome (WNNS)
- A significant feature of West Nile viral neurologic illness may be marked muscle weakness that is more frequently unilateral but can be bilateral. WNV should be considered in the differential diagnosis of all suspected cases of acute flaccid paralysis with or without sensory deficit. WNV- associated weakness typically affects one or more limbs (sometimes affecting one limb only). Muscle weakness may be the sole presenting feature of WNV illness (in the absence of other neurologic features) or may develop in the setting of fever, altered reflexes, meningitis or encephalitis. Weakness typically develops early in the course of clinical infection. Patients should be carefully monitored for evolving weakness and in particular for acute neuromuscular respiratory failure, which is a severe manifestation associated with high morbidity and mortality. For the purpose of WNV Neurologic Syndrome Classification, muscle weakness is characterized by severe (polio-like), non-transient and prolonged symptoms. Electromyography (EMG) and lumbar puncture should be performed to differentiate WNV-associated paralysis from acute demyelinating polyneuropathy (e.g. Guillain-Barré syndrome). Lymphocytic pleocytosis (an increase in white blood cells with a predominance of lymphocytes in the CSF) is commonly seen in acute flaccid paralysis because of WNV, whereas pleocytosis is not a feature of Guillain-Barré syndrome. Other emerging clinical syndromes, identified during 2002, included, but were not limited to, the following: myelopathy, rhabdomyolysis (acute destruction of skeletal muscle cells), peripheral neuropathy; polyradiculoneuropathy; optic neuritis; and acute demyelinating encephalomyelitis (ADEM). Ophthalmologic conditions, including chorioretinitis and vitritis, were also reported. As well, facial weakness was reported. Myocarditis, pancreatitis and fulminant hepatitis have not been identified in North America but were reported in outbreaks of WNV in South Africa. “Aseptic” meningitis without encephalitis or acute flaccid paralysis occurring in August and September when WNV is circulating may be due to non-polio enteroviruses circulating at the same time. This should be considered in the differential diagnosis(2-4).
- A person with WNV-associated acute flaccid paralysis may present with or without fever or mental status changes. Altered mental status could range from confusion to coma with or without additional signs of brain dysfunction (e.g. paralysis, cranial nerve palsies, sensory deficits, abnormal reflexes, generalized convulsions and abnormal movements). Acute flaccid paralysis with respiratory failure is also a problem.
West Nile Virus Non-Neurological Syndrome (WN Non-NS)
- It is possible that other clinical signs and symptoms could be identified that have not been listed and may accompany probable case or confirmed case diagnostic test criteria. For example, gastrointestinal symptoms were seen in many WNV patients in Canada and the USA in 2003 and 2004.
- Muscle weakness may be a presenting feature of WNV illness. For the purpose of WNV Non-Neurological Syndrome classification, muscle weakness or myalgia (muscle aches and pains) is characterized by mild, transient, unlikely prolonged symptoms that are not associated with motor neuropathy.
West Nile Virus Asymptomatic Infection (WNAI)
- This category could include asymptomatic blood donors whose blood is screened using a nucleic acid amplification test (NAT) by Blood Operators (i.e. Canadian Blood Services or Héma-Québec) and is subsequently brought to the attention of public health officials. The NAT that will be used by Blood Operators in Canada is designed to detect all viruses in the Japanese encephalitis (JE) serocomplex. The JE serocomplex includes WN virus and nine other viruses, although from this group only WN virus and St Louis encephalitis virus are currently endemic to parts of North America. Blood Operators in Canada perform a supplementary WN virus-specific NAT following any positive result from donor screening.
ICD 10 code(s)
ICD 9 code(s)
066.40, 066.41, 066.42, 066.49
Type of international reporting
Under Article 6 of the International Health Regulations (IHR) (2005), each State Party shall notify the World Health Organization (WHO) by way of the IHR National Focal Point,Footnote 1 and within 24 hours of assessment of public health information, of all events which may constitute a public health emergency of international concern within its territory in accordance with the decision instrument (Annex 2 of the IHRFootnote 2), as well as any health measure implemented in response to those events.
- An event involving West Nile fever shall always lead to the utilization of the algorithm in Annex 2 of the IHR, because it has demonstrated the ability to cause serious public health impact and to spread rapidly internationally. The need to notify such events to the WHO will depend upon the outcome of the assessment using the Annex 2 decision instrument.
Note: If event does not meet the criteria for notification under Article 6 of the IHR, then other IHR-related reporting requirements may still apply with WHO and/or other States Parties, including those under Art. 7 (information-sharing during unexpected or unusual public health events), Art. 8 (consultation with WHO on public health events), Art. 9 (any public health risk that may cause international disease spread), Art. 10 (requests for verification from WHO), and Art. 44 (collaboration and assistance).
- History of exposure when and where West Nile virus transmission is present, or could be present, or history of travel to an area with confirmed WNV activity in birds, horses, other mammals, sentinel chickens, mosquitoes or humans.
- Alternative modes of transmission, identified to date, include laboratory acquired; in utero; receipt of blood components; organ/tissue transplant; and, possibly, through breast milk.
- Both CDC and commercial IgM/IgG EIAs are now available for front-line serologic testing. Refer to appropriate assay procedures and kit inserts for the interpretation of test results.
- Early in infection the immune system generates antibodies that bind relatively weakly to viral antigen (low avidity). As the infection proceeds, an increasing percentage of newly generated IgG antibody displays higher binding affinity to virus antigen and thus avidity also rises (note: avidity is usually measured according to the ability of IgG to dissociate from antigen preparations after incubation with a solution of urea). As long as high avidity IgG is not yet detected in the serum it can be assumed that the individual was exposed to the viral agent during a recent exposure. With respect to WNV infection it has not been precisely determined when (i.e. after exposure) high avidity antibodies reach levels in serum that can be accurately detected by serologic assays (there may be significant variation depending on the individual). However, it has been shown that greater than 95% of sera collected from individuals exposed to WNV six to eight months previously will have IgG antibodies that bind strongly to viral antigen and will give high avidity scores using both IFA and EIA testing formats. Note: Avidity testing will not replace confirmatory neutralization testing; non-WNV flavivirus IgG antibody (e.g. dengue, St. Louis encephalitis) may bind to the antigen preparations used in avidity assays.
- Note: WNV IgM antibody may persist for more than a year, and the demonstration of IgM antibodies in a patient’s serum, particularly in residents of endemic areas, may not be diagnostic of an acute WN viral infection. Seroconversion (by HI, IgG EIA or PRN titre assays) demonstrates a current WNV infection. Therefore, the collection of acute and convalescent sera for serologic analysis is particularly important to rule out diagnostic misinterpretation early in the WNV season (e.g. May, June) and to identify initial cases in a specific jurisdiction. However, it should be noted that seroconversions may not always be documented because of the timing of acute sample collection (i.e. titres in acute sera may have already peaked). If static titres are observed in acute and convalescent paired sera, it is still possible the case may represent a recent infection. To help resolve this, the use of IgG avidity testing may be considered to distinguish between current and past infection. The presence of both IgM antibody and low avidity IgG in a patient’s convalescent serum sample is consistent with current cases of viral-associated illness. However, test results that show the presence of IgM and high avidity IgG are indicative of exposures that have occurred in the previous season.
- Immunocompromised individuals may not be able to mount an immune response necessary for a serologic diagnosis. West Nile virus diagnostic test criteria for these individuals should be discussed with a medical microbiologist.
Tilley P, Fox JD, Jayaraman GC, Preiksaitis JK. Nucleic acid test for West Nile virus RNA in plasma enhances rapid diagnosis of acute infection in symptomatic patients. J Infect Dis 2006;193:1361-1.
Sejvar J, Haddad MB, Tierney BC et al. Neurologic manifestations and outcome of West Nile virus infection. JAMA 2003;290:511-5.
Sejvar J. Bode AV, Marfin AA et al. West Nile virus-associated flaccid paralysis. Emerg Infect Dis 2003;9:788-93.
Burton JM, Kern RJ, Halliday W et al. Neurological manifestations of West Nile virus infection. Can J Neurol Sci 2004;31:185-93.
World Health Organization. International Health Regulations (2005). 3rd ed. Geneva, 2016
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