National case definition: West Nile virus

Date of last revision: January 2024

On this page

• National notification
• Type of surveillance
• Case classification
  • West Nile virus neuroinvasive disease (West Nile virus neurological syndrome)
  • West Nile virus non-neuroinvasive disease (West Nile virus non-neurological syndrome)
  • West Nile virus asymptomatic infection
• Clinical comments
• ICD code(s)
• Type of international reporting
• Laboratory comments

National notification

Probable and confirmed cases of disease should be notified.

Type of surveillance

Routine case-by-case notification to the federal level

Case classification

West Nile virus neuroinvasive disease (West Nile virus neurological syndrome)

Confirmed case

Clinical criteria for West Nile virus neuroinvasive disease (West Nile virus neurological syndrome) and at least one of the confirmed case diagnostic test criteria:

• a significant (i.e., fourfold or greater) change in West Nile virus (WNV) neutralizing antibody titres (i.e., plaque reduction neutralization tests (PRNT)) in paired acute and convalescent sera, or cerebrospinal fluid (CSF) sample, or
• isolation of WNV from, or demonstration of WNV antigen in tissue or WNV-specific genomic sequences in tissue, blood, CSF or other body fluids, or
• demonstration of WNV antibodies in a single serum using a WNV immunoglobulin M (IgM) enzyme-linked immunoassay (ELISA), confirmed by the detection of WNV neutralizing antibodies using a PRNT (acute or convalescent serum), or
• demonstration of WNV antibodies in a CSF sample using a WNV IgM ELISA, confirmed by the detection of WNV neutralizing antibodies using a PRNT (CSF or acute or convalescent serum).

See Clinical criteria for West Nile virus neuroinvasive disease (West Nile virus neurological syndrome) 

See Laboratory comments for confirmatory PRNT for endemic areas in season and low/non-endemic areas, or out of season; and cross-reactivity among flaviviruses.

Probable case

Clinical criteria for West Nile virus neuroinvasive disease (West Nile virus neurological syndrome) and at least one of the probable case diagnostic test criteria:

• detection of flavivirus antibodies in a single serum or CSF sample using a WNV IgM ELISA without confirmatory neutralization serology (i.e., PRNT), or
• a significant (i.e., fourfold or greater) change in flavivirus antibodies in paired acute and convalescent sera or demonstration of a seroconversion using a WNV immunoglobulin G (IgG) ELISA without confirmatory neutralization serology (i.e., PRNT).

See Clinical criteria for West Nile virus neuroinvasive disease (West Nile virus neurological syndrome) 

See Laboratory comments for confirmatory PRNT for endemic areas in season and low/non-endemic areas, or out of season; and cross-reactivity among flaviviruses.

Suspect case

Clinical criteria for West Nile virus neuroinvasive disease (West Nile virus neurological syndrome) in the absence of diagnostic test criteria or pending diagnostic test criteria and in the absence of any other obvious cause.

See Clinical criteria for West Nile virus neuroinvasive disease (West Nile virus neurological syndrome) 

See Laboratory comments.

Clinical criteria for West Nile virus neuroinvasive disease (West Nile virus neurological syndrome)

History of exposure when and where WNV transmission is present historically, or could be present, or history of travel to an area with confirmed WNV activity in birds, horses, other mammals, mosquitoes, or humans

or

History of exposure to an alternate mode of transmission (laboratory-acquired, in utero, receipt of blood components, organ/tissue transplant, and possibly via breast milk)

and

Onset of fever^{Footnote 1}

and

recent onset of at least one of the following:

• encephalitis
• viral meningitis
• acute flaccid paralysis^{Footnote 2}
• other neurological syndromes^{Footnote 3}

See Clinical comments

West Nile virus non-neuroinvasive disease (West Nile virus non-neurological syndrome)

Confirmed case

Clinical criteria for West Nile virus non-neuroinvasive disease (West Nile virus non-neurological syndrome) and at least one of the confirmed case diagnostic test criteria:

• a significant (i.e., fourfold or greater) change in WNV neutralizing antibody titres (i.e., PRNT) in paired acute and convalescent sera, or
• isolation of WNV from, or demonstration of WNV antigen in tissue or WNV-specific genomic sequences in tissue, blood, or other relevant body fluids, or
• demonstration of WNV antibodies in a single serum using a WNV IgM ELISA, confirmed by the detection of WNV neutralizing antibodies using a PRNT (acute or convalescent serum).

See Clinical criteria for West Nile virus non-neuroinvasive disease (West Nile virus non-neurological syndrome)

See Laboratory comments for confirmatory PRNT for endemic areas in season and low/non-endemic areas, or out of season; and cross-reactivity among flaviviruses.

Probable case

Clinical criteria for West Nile virus non-neuroinvasive disease (West Nile virus non-neurological syndrome) and at least one of the probable case diagnostic test criteria:

• detection of flavivirus antibodies in a single serum using a WNV IgM ELISA without confirmatory neutralization serology (i.e., PRNT) or
• a significant (i.e., fourfold or greater) change in flavivirus antibodies in paired acute and convalescent sera or demonstration of a seroconversion using a WNV IgG ELISA without confirmatory neutralization serology (i.e., PRNT)

See Clinical criteria for West Nile virus non-neuroinvasive disease (West Nile virus non-neurological syndrome)

See Laboratory comments for confirmatory PRNT for endemic areas in season and low/non-endemic areas, or out of season; and cross-reactivity among flaviviruses.

Suspect case

Clinical criteria for West Nile virus non-neuroinvasive disease (West Nile virus non-neurological syndrome)) in the absence of or pending diagnostic test criteria and in the absence of any other obvious cause

See Clinical criteria for West Nile virus neuroinvasive disease (West Nile virus neurological syndrome) 

See Laboratory comments.

Clinical criteria for West Nile virus non-neuroinvasive disease (West Nile virus non-neurological syndrome)

History of exposure when and where WNV transmission is present historically, or could be present, or history of travel to an area with confirmed WNV activity in birds, horses, other mammals, mosquitoes, or humans.

or

History of exposure to an alternate mode of transmission (e.g., laboratory-acquired, in utero, receipt of blood components, organ/tissue transplant, and possibly via breast milk)

and

at least two of the following:

• fever
• myalgia^{Footnote 4}
• anthralgia
• headache
• fatigue
• rash (maculopapular or morbilliform)
• gastrointestinal manifestations (e.g., vomiting, nausea, diarrhea, abdominal pain)
• other (e.g., eye pain, chills, back pain)

See Clinical comments.

West Nile virus asymptomatic infection

Asymptomatic testing should be limited to blood and organ donors as part of blood and organ donor screening programs.

Confirmed case

At least one of the following confirmed case diagnostic test criteria in the absence of clinical criteria:

• a significant (i.e., fourfold or greater) change in WNV neutralizing antibody titres (i.e., PRNT) in paired sera, or
• isolation of WNV from, or demonstration of WNV antigen in tissue or WNV-specific genomic sequences in tissue, blood or other relevant body fluids, or
• demonstration of WNV antibodies in a single serum using a WNV IgM ELISA, confirmed by the detection of WNV neutralizing antibodies using a PRNT (acute or convalescent serum), or
• demonstration of Japanese encephalitis serocomplex-specific genomic sequences in blood by nucleic acid amplification test (NAAT) confirmed by WNV-specific NAAT or sequencing, or demonstration of WNV-specific genomic sequences in blood by NAAT by blood operators (e.g., Canadian Blood Services or Héma-Québec) in Canada.

Probable case

At least one of the following probable case diagnostic criteria in the absence of clinical criteria:

• a significant (i.e., fourfold or greater) change in flavivirus antibodies in paired sera or demonstration of a seroconversion using a WNV IgG ELISA without confirmatory neutralization serology (i.e., PRNT)
• demonstration of Japanese encephalitis serocomplex-specific genomic sequences in blood by NAAT by blood operators in Canada when WNV-specific NAAT was not performed

Suspect case

The following suspect case diagnostic criteria in the absence of clinical criteria:

• detection of flavivirus antibodies in a single serum using a WNV IgM ELISA pending further investigation

See Laboratory comments.

Clinical comments

The clinical information presented below is not intended to describe the complete range of signs and symptoms that may be used in a clinical diagnosis of WNV disease.

West Nile virus neuroinvasive disease occurs in less than 1% of cases.

• Encephalitis commonly manifests as extrapyramidal disorders.
  • Common movement disorder manifestations include: coarse tremor (particularly in upper extremities), myoclonus (in upper extremities and facial muscles), features of Parkinsonism and cerebellar ataxia.
• Meningitis associated with WNV has clinical manifestations that are similar to other viral meningitides.
  • "Aseptic" meningitis without encephalitis or acute flaccid paralysis occurring in summer and fall when WNV is circulating may be due to non-polio enteroviruses circulating at the same time. This should be considered in the differential diagnosis.
• Acute flaccid paralysis typically manifests as rapid-onset, marked muscle weakness that is more frequently asymmetric, usually affecting one or more limbs.
  • The majority of cases of acute flaccid paralysis occur in conjunction with encephalitis or meningitis.
  • The most common form of acute flaccid paralysis is poliomyelitis-like syndrome
  • Other forms of acute flaccid paralysis associated with WNV include radiculopathy and Guillain-Barré syndrome.
  • Electromyography, lumbar puncture and nerve conduction studies should be performed to differentiate between poliomyelitis and other forms of acute flaccid paralysis.
  • WNV should be considered in the differential diagnosis of all suspected cases of acute flaccid paralysis with or without sensory deficit.
  • Respiratory muscle innervation may be involved and lead to respiratory failure.

West Nile virus non-neuroinvasive disease occurs in about 20 to 25% of cases.

• Also commonly referred to as "West Nile fever," although fever is not universally present among those with West Nile non-neuroinvasive disease.
• Younger individuals are more likely to present with WNV non-neuroinvasive disease than WNV neuroinvasive disease.

West Nile virus asymptomatic infection occurs in about 70 to 80% of cases.

Other manifestations described in association with WNV infection include:

• Ocular manifestations:
  • Frequently reported sequelae of WNV infection following neuroinvasive disease
  • Chorioretinitis is the most common manifestation, with lesions that are described as "multifocal" and "target-like," located primarily in the temporal and nasal regions of the periphery of the fundus. The distribution and appearance of these lesions are thought to be distinctive of WNV infection.
  • Other ocular manifestations include: vitritis, choroiditis, retinal haemorrhages, occlusive vasculitis, uveitis.
• Less commonly described clinical manifestations and complications associated with West Nile virus infection include: rhabdomyolysis, hepatitis, pancreatitis, myocarditis, cardiac arrhythmias.

ICD code(s)

ICD 11 code(s)

• XN4E1 West Nile virus
• 1D46 West Nile virus infection
• 1C80 Viral encephalitis not elsewhere classified

ICD 10 code(s)

A92.3 West Nile virus infection

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 5}, 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 IHR^{Footnote 6}), 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).

Laboratory comments

• Confirmatory plaque reduction neutralization test (PRNT) for:

  • Endemic areas in season: It is currently recommended that health jurisdictions/authorities use the Confirmed Case Diagnostic Test Criteria (i.e., PRNT on serum or immunoglobulin M (IgM) detection in cerebrospinal fluid (CSF)) to confirm the first few index cases (locally acquired) in an endemic area during the WNV transmission season each year; for subsequent cases, health jurisdictions/authorities in endemic areas could use the Probable Case Diagnostic Test Criteria to classify cases in their area as "confirmed", for the purposes of surveillance.

    It is recommended that a follow-up serum sample be submitted in addition to the initial CSF sample so a PRNT may be done on the serum.

  • Low or non-endemic areas, or out of season: For cases where the epidemiology does not support the IgM result in CSF, such as in low endemic areas or results received outside the WNV transmission season, confirmatory antibody testing should be performed on serum, with acute or convalescent PRNT.

    It is recommended that a follow-up serum sample be submitted in addition to a CSF sample so a PRNT may be done on the serum.

  • Due to high serological cross reactivity among flaviviruses, travel and vaccination history should be obtained to determine if other flaviviruses should be tested for (e.g., Dengue virus, St. Louis encephalitis and Japanese encephalitis). False-positive WNV serologic tests may occur because antibodies to other arthropod-borne flaviviruses cross-react with WNV virus. A false-positive result can be due to recent immunization with flavivirus vaccines (namely, yellow fever or Japanese encephalitis) or due to infections with other related flaviviruses (e.g., St. Louis encephalitis, dengue, or Zika). In this situation, a PRNT should only be performed to help confirm the diagnosis if there is concern that the positive serological test results are due to cross-reactivity from a different flavivirus infection (e.g., dengue, yellow fever, St. Louis encephalitis, Zika, Japanese encephalitis viruses) or after recent vaccination for Japanese encephalitis.
• Throughout the remainder of the transmission season, health jurisdictions/authorities may wish to document PRNT antibody titres to WNV 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.
• If a CSF sample appears to contain blood, non-specific reactivity may be observed; therefore, it is recommended that the IgM result be interpreted with caution.
• Demonstration of WNV IgM antibodies in a single serum sample with no clinical history should not be used as a diagnostic approach. WNV IgM antibodies may persist for more than a year, and the demonstration of IgM antibodies in a patient's serum, particularly in residents of areas with a history of exposure may not be diagnostic of an acute WNV infection. IgM antibodies usually remain detectable in serum for at least one to two months following clinical resolution, but may persist for 12 months or more. Thus, patients from endemic areas may have detectable IgM antibody from a previous WNV infection that is unrelated to their current clinical illness.
• Seroconversion demonstrates a current WNV infection. IgM seroconversion usually develops between 4 and 10 days after infection. Therefore, the collection of acute and convalescent sera for serologic analysis is particularly important to rule out diagnostic misinterpretation 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.
• Immunocompromised individuals may not be able to mount an immune response necessary for a serologic diagnosis. For immunocompromised patients, viremia may be prolonged and antibody development may be delayed or absent. Viral detection methods may be helpful for confirming diagnosis. West Nile virus diagnostic test criteria for these individuals should be discussed with a medical microbiologist.
• For asymptomatic blood donors, blood is screened using a nucleic acid amplification test (NAAT) by blood operators and is subsequently brought to the attention of public health officials. Blood operators may use a WNV-specific NAAT or a NAAT designed to detect viruses in the Japanese encephalitis serocomplex, including West Nile virus. Supplementary tests (WNV-specific NAAT) following a positive screening from blood donor screening may be performed by provincial/territorial lab or National Microbiology Laboratory.

References

• Abroug N, Khairallah M, Zina S et al. Ocular manifestations of emerging arthropod-borne infectious diseases. J Curr Opthalmol 2021;33:227-35.
• Petersen LR, Brault AC, Nasci RS. West Nile virus: review of the literature. JAMA 2013;310(3):308-15.
• Sejvar JJ. Clinical manifestations and outcomes of West Nile virus infection. Viruses. 2014; 6(2):606-23.
• Sejvar JJ. West Nile virus infection. Microbiol Spectrum 2016;4(3):EI10-0021-2016.
• 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.
• World Health Organization. International Health Regulations (2005). 3rd ed. Geneva, 2016
  http://www.who.int/ihr/publications/9789241580496/en/