What are the symptoms and diagnostic workup for West Nile virus (WNV) infection?

West Nile Virus: Symptoms and Diagnostic Workup

West Nile virus (WNV) infection should be diagnosed primarily through serologic testing of serum and/or cerebrospinal fluid (CSF) for WNV-specific IgM antibodies, followed by confirmatory neutralizing antibody testing in cases with potential cross-reactivity with other flaviviruses. 1

Clinical Presentation

Spectrum of Disease

• Asymptomatic infection: Approximately 80% of WNV infections 2
• West Nile fever: 20% of infected individuals 2
• Neuroinvasive disease: Less than 1% of infected individuals 2
  • Meningitis
  • Encephalitis
  • Acute flaccid myelitis/paralysis

Symptoms by Clinical Presentation

West Nile Fever

• Fever
• Headache
• Fatigue
• Body aches
• Nausea/vomiting
• Occasionally rash
• Lymphadenopathy

Neuroinvasive Disease

• All symptoms of West Nile fever plus:
• Neck stiffness
• Disorientation/confusion
• Tremors/seizures
• Paralysis/weakness
• Vision loss
• Numbness
• Coma (in severe cases)

Risk Factors for Severe Disease

• Age ≥70 years (20% mortality) 2
• Immunocompromised status:
  • Hematologic malignancies
  • Solid organ transplants
  • B-cell-depleting monoclonal antibody therapy (30-40% mortality) 2

Diagnostic Workup

Timing Considerations

• IgM antibodies to WNV are detectable 3-8 days after symptom onset 1
• IgM antibodies typically decline after 2-3 months but may persist for up to 12 months 1

Recommended Laboratory Testing

1. First-line testing:

   • Serum WNV-specific IgM antibodies
   • CSF WNV-specific IgM antibodies (for suspected neuroinvasive disease)

2. Confirmatory testing:

   • Plaque reduction neutralization test (PRNT) when:
     • Cross-reactivity with other flaviviruses is suspected
     • Patient has received yellow fever vaccination
     • Patient has history of dengue or St. Louis encephalitis 1
     • Atypical presentation or death
     • Unusual transmission mode is suspected 2

3. Nucleic acid amplification testing (NAAT):

   • More sensitive in immunocompromised patients due to prolonged viremia 1
   • Specimens for NAAT:
     • CSF (sterile tube)
     • Plasma (EDTA or PPT)
     • Serum (SST) 1

4. Seroconversion documentation:

   • Paired acute and convalescent sera (collected 7-10 days apart) showing seroconversion to anti-WNV IgM and/or IgG 1

Special Considerations

• Presence of anti-WNV IgG alone at presentation suggests prior infection, not acute disease 1
• CSF IgM indicates neuroinvasive disease, as IgM antibodies do not naturally cross the blood-brain barrier 1
• False-positive CSF IgM may occur with traumatic lumbar puncture or compromised blood-brain barrier 1

Additional Testing for Neuroinvasive Disease

• Brain MRI
• EEG (for seizure activity)
• Complete blood count
• Comprehensive metabolic panel
• Consider testing for other causes of viral encephalitis/meningitis

Special Populations

Pregnant Women

• No routine screening of asymptomatic pregnant women is recommended 1
• For symptomatic pregnant women in endemic areas:
  • Test serum and CSF (if clinically indicated) for WNV antibodies 1
  • Consider detailed fetal ultrasound 2-4 weeks after maternal illness onset 1

Infants Born to WNV-Infected Mothers

• Physical examination with attention to neurological findings
• Consider ophthalmologic examination
• Consider cranial imaging
• Laboratory testing for congenital WNV infection 1

Immunocompromised Patients

• Lower threshold for testing
• Consider NAAT testing even if serology is negative
• Higher risk of severe disease and death (30-40% mortality) 2

Common Pitfalls and Caveats

1. Relying solely on PCR testing in immunocompetent patients: Viremia is often short-lived; serology is more reliable in most cases.
2. Failing to consider WNV during mosquito season: Include WNV in differential diagnosis for unexplained fever or neurological symptoms during summer and fall.
3. Not accounting for cross-reactivity: False positives can occur with other flavivirus infections or yellow fever vaccination.
4. Misinterpreting persistent IgM: IgM antibodies can persist for up to 12 months, potentially leading to misdiagnosis of acute infection.
5. Overlooking WNV in children: Although less common and typically milder than in adults, children can develop neuroinvasive disease.

Remember that WNV has no specific treatment, so early diagnosis is important for supportive care and monitoring for complications.