West Nile Virus Encephalitis

Aka: West Nile Virus Encephalitis, West Nile Encephalitis, West Nile Fever, West Nile Virus

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II. Epidemiology

  1. Most common vector-borne Arbovirus in United States (as of 2016)
    1. Reported cases: ~50,000 between 1999 and 2018
  2. Most severe illness occurs in older patients
    1. Over age 50: Twenty fold risk of severe illness
  3. Timing
    1. Temperate climate: Late summer and early fall
      1. Range of infections: Mid-July to early December
      2. Peaks in late August to early September
    2. Southern climate: Year round transmission
    3. Most favorable weather conditions
      1. Hot,dry summer with brief unseasonably cool weather
  4. Distribution
    1. Africa
      1. First identified in Uganda's West Nile Province (1937)
    2. West Asia
    3. Eastern Europe
    4. Middle East
    5. United States (as of 1999)
      1. Queens, New York outbreak (1999)
      2. Central States
      3. Great Plains States

III. Pathophysiology

  1. Arbovirus (Arthopod-borne)
    1. Mosquito-borne infection
    2. Transmitted by Culex, Ochlerotatus, Culiseta and Aedes Mosquitos
  2. Flaviviridae (Flavivirus) family
    1. Flaviviridae are transmitted by arthropods (Group B Arbovirus, ticks or Mosquitos)
    2. Flaviviridae are enveloped, Icosahedral single stranded RNA Viruses
    3. Flaviviridae are Message Sense RNA Viruses (Positive Stranded, +ssRNA)
      1. Message sense RNA (+ssRNA) are identical to Messenger RNA (mRNA)
      2. Like mRNA, +ssRNA may be immediately translated by host ribosomes into Protein
  3. Humans are incidental hosts
    1. Typically cycles between birds, Mosquitos and then back to birds
  4. Transmission
    1. Most commonly by Mosquito Bite
    2. Organ transplant or Blood Transfusion (screened in U.S. before transplant or transfusion)
    3. Transplacental transmission
  5. Incubation: 3-14 days
  6. Animals affected
    1. Wild birds are usual hosts
      1. Dead birds may suggest endemic area
      2. Corvids (Crows and Jays) are most often affected
    2. Horses are most affected domesticated animals
    3. Cats
    4. Bats
    5. Chipmunks
    6. Skunks
    7. Squirrels
    8. Rabbits

IV. Types

  1. Asymptomatic Infection (80%)
    1. Majority of children are asymptomatic or have mild symptoms
  2. West Nile Fever (WNF, 20%)
  3. West Nile Neuroinvasive Disease (WNND, 1%)
    1. Meningitis or Encephalitis
    2. More severe cases occur in older adults
    3. Risk Factors
      1. Age over 50 years old
      2. Diabetes Mellitus
      3. Alcohol Abuse
      4. Male gender
      5. Organ transplant or Immunosuppression
      6. Autoimmune Disease

V. Symptoms: West Nile Fever

  1. Spectrum of disease
    1. See Types above
  2. Symptoms (abrupt onset without prodrome): Flu-like illness
    1. Fever up to 40 Celsius
    2. Malaise
    3. Muscle Weakness to Flaccid Paralysis
    4. Profound Fatigue (may persist for weeks)
    5. Chills and myalgias (e.g. back pain)
    6. Drowsiness or lethargy
  3. Variable symptoms
    1. Severe frontal or retro-orbital Headache
    2. Nausea or Vomiting
    3. Eye Pain
    4. Cough
  4. Rare Symptoms
    1. Abdominal Pain (if hepatitis or Pancreatitis)
  5. Classic presentation
    1. Late summer, early fall onset of Prolonged Fever and neurologic symptoms

VI. Signs: West Nile Fever

  1. Non-tender Generalized Lymphadenopathy
    1. Occipital Lymphadenopathy
    2. Axillary Lymphadenopathy
    3. Inguinal Lymphadenopathy
    4. Lymphadenopathy may persist for months
  2. Facial Flushing
  3. Conjunctival injection
  4. Coating of Tongue
  5. Pale maculopapular rash (Roseola-like)
    1. Affects trunk and upper arms
    2. Onset on days 2 to 5 (typically as fever subsides)

VII. Signs: Neurologic signs (West Nile Neuroinvasive Disease or WNND)

  1. No sensory deficits
  2. Motor Findings (Polio-like syndrome or similar to Guillain-Barre Syndrome)
    1. Severe Muscle Weakness to Acute Flaccid Paralysis or Myelitis (related to anterior horn cell involvement)
    2. Polyradiculitis
    3. Myoclonus
    4. Decreased or absent Deep Tendon Reflexes
    5. Myelitis
  3. Cranial Nerve findings
    1. Cranial Nerve abnormalities
    2. Optic Neuritis
  4. MIscellaneous findings
    1. Ataxia
    2. Extrapyramidal signs
    3. Tremor
    4. Seizures

VIII. Differential Diagnosis

  1. See Viral Encephalitis
  2. St. Louis Encephalitis
  3. Dengue

IX. Labs: General

  1. Metabolic panel
    1. Hyponatremia may occur with Encephalitis
  2. Complete Blood Count (CBC)
    1. Leukopenia (Leukocytes <4000/mm3)
    2. Mild Leukocytosis may also occur
  3. Lumbar Puncture
    1. Initial Neutrophilia, then Lymphocytosis
    2. Normal CSF Glucose
    3. Mild increases in CSF Protein concentration

X. Labs: Diagnosis

  1. West Nile Virus serum or CSF IgM by MAC-ELISA (preferred)
    1. Best lab test for diagnosis (95% sensitive)
    2. Collect 8-21 days after onset of symptoms (False Negative in first 7 days)
    3. Positive CSF IgM confirms CNS Infection
    4. False Positives due to cross reactivity
      1. St. Louis Encephalitis virus
      2. FlavivirusVaccine (e.g. Yellow Fever, Dengue)
      3. Prior West Nile Virus (CSF IgM may persist for >1 years from prior infection)
  2. Other testing (not used routinely)
    1. Blood isolation of virus
      1. Sensitivity on Day 1: 75% of cases positive
      2. Sensitivity decreases over first 5 infection days
    2. CSF Testing
      1. CSF Viral culture
      2. CSF West Nile PCR
        1. Low Test Sensitivity as CSF (and blood) have often been cleared of Antigen by time of diagnostics
        2. May be associated with worse prognosis when present

XI. Imaging

  1. MRI Brain
    1. Abnormal in 25-35% of cases
    2. Nonspecific findings (esp. in Thalamus, Basal Ganglia)

XII. Complications

  1. Neurologic disease (one in 30-70 cases, some studies report 1 in 150 cases)
    1. Meningitis
    2. Encephalitis
    3. West Nile Poliomyelitis-like syndrome
      1. Asymmetric Flaccid Paralysis (may include respiratory Muscles)
    4. Guillain-Barre Syndrome
    5. Extrapyramidal symptoms
    6. Long-term neuropsychiatric sequelae
      1. Fatigue
      2. Memory Loss
      3. Difficulty walking
      4. Muscle Weakness
      5. Major Depression
  2. Other complications (rare)
    1. Myocarditis
    2. Chorioretinitis
    3. Cardiac Arrhythmias
    4. Pancreatitis
    5. Hepatitis
    6. Rhabdomyolysis

XIII. Management

  1. Supportive care in most cases
    1. Hydration
    2. Analgesia
  2. Investigational agents to consider in severe cases
    1. Ribavirin
    2. Interferon Alfa-2B

XIV. Prognosis

  1. Most Mosquitos in endemic areas are not infected
  2. If infection occurs, 99% of cases are self-limited
  3. Severe cases (meningoencephalitis) occur in less than 1-2% of infections
    1. Mortality in severe cases is 5-15% (up to 30% in some cohorts)
    2. Elderly account for majority of fatal cases
    3. Immunocompromised patients also have a worse prognosis

XV. Course

  1. Incubation up to 6 days
  2. Duration for 3 to 5 days in 80% of cases
  3. Prolonged recovery may take up to one year to return to full functional and cognitive capacity
    1. Fatigue may take weeks to months or longer for resolution
    2. Up to 50% of patients have persistent symptoms and functional Impairment at >1.5 years
    3. More prolonged course with West Nile Neuroinvasive Disease (WNND)

XVI. Prevention

  1. See Prevention of Vector-borne Infection (includes Insect Repellent, esp. DEET)
  2. Eliminate areas of standing water (and other Mosquito control)
  3. No available Vaccination
  4. Blood donor screening

XVII. Resources

  1. CDC West Nile Virus
    1. http://www.cdc.gov/ncidod/dvbid/westnile/

XVIII. References

  1. Della-Giustina, Fox and Siegel (2021) Crit Dec Emerg Med 35(4): 17-23
  2. Douglas in Goldman (2000) Cecil Medicine, p. 1851
  3. Huhn (2003) Am Fam Physician 68(4):653-72 [PubMed]
  4. Huntington (2016) Am Fam Physician 94(7): 551-7 [PubMed]
  5. Nash (2001) N Engl J Med 3441:1807-1814 [PubMed]
  6. Petersen (2002) Ann Intern Med 137:173-9 [PubMed]

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