West Nile virus infection – 6 Interesting Facts


Key Points

  1. West Nile virus is a mosquito-borne viral infection in humans that is asymptomatic in the majority of cases, but may present as a generalized febrile illness (West Nile virus fever) or as neurologic disease (ie, meningitis, encephalitis, flaccid paralysis)
  2. In the United States, its peak occurrence is July through September
  3. No effective antiviral therapy has been identified; treatment is supportive
  4. Environmental and personal protection measures are important for prevention
  5. Blood and organ donations are screened to prevent transmission to recipients
  6. West Nile virus infection is a notifiable disease in the United States, and should be reported to public health authorities


  • Antibodies may not be detectable early in the course (up to 8 days from symptom onset); a negative test result in early illness does not rule out the disease
  • Diagnostic antibody testing may be confounded by cross-reacting antibodies to other flaviviruses (eg, dengue, yellow fever, Zika, St. Louis encephalitis)


Clinical Clarification

  • West Nile virus is a mosquito-borne viral infection in humans that is asymptomatic in the majority of cases, but may present as a generalized febrile illness (West Nile virus fever) or as neurologic disease (ie, meningitis, encephalitis, flaccid paralysis)


Clinical Presentation


  • West Nile virus fever occurs in about 20% to 25% 1 2 3 of infected persons, lasting several days to several weeks 2
    • Nonspecific presentation
      • Onset is abrupt
      • Fever, headache, generalized weakness, myalgias, and rash are reported by more than 50% 3
      • Chills, eye pain, arthralgias, and gastrointestinal symptoms are less frequent 3
  • West Nile virus neuroinvasive disease occurs in fewer than 1% of infected persons 4
    • May take 1 of 3 forms:
      • Encephalitis (about 63%) 4
      • Meningitis (about 33%) 4
      • Flaccid paralysis (about 3%) 4
    • May occur in the setting of nonspecific systemic symptoms (eg, chills, myalgias, nausea)
    • Onset of neurologic symptoms is abrupt
      • Encephalitis
        • Altered level of consciousness
        • Confusion
        • Personality change
        • Lethargy
      • Meningitis
        • Fever
        • Severe headache and neck stiffness
        • Photophobia
      • Flaccid paralysis
        • Asymmetric weakness of the extremities, with progression over a 48-hour period
        • May be associated with facial weakness
        • Sensory symptoms are usually absent, although pain in the extremities can occur
        • Most patients with flaccid paralysis also have encephalitis

Physical examination

  • West Nile virus fever
    • Fever is noted in a majority of symptomatic cases, but is not universal
    • Macular or maculopapular rash over trunk and extremities, excluding palms and soles, occurs in some patients
    • Lymphadenopathy is present in a small number of cases
  • West Nile virus neuroinvasive disease
    • Encephalitis
      • Confusion and lethargy are common; may progress to severe encephalopathy or coma
      • Tremors and myoclonus may be seen, especially in the upper extremities
      • Seizures are uncommon
    • Meningitis
      • Nuchal rigidity
      • Kernig sign
      • Brudzinski sign
    • Flaccid paralysis
      • Asymmetric weakness; may include facial asymmetry
      • Hypo- or areflexia of the involved extremities
      • Respiratory muscles may be involved
    • Occasional findings in neuroinvasive presentations include: 5
      • Fever
      • Lymphadenopathy
      • Rash is less common in neuroinvasive disease than in West Nile fever
      • Optic neuritis
      • Cranial neuropathies
      • Ataxia

Causes and Risk Factors


  • West Nile virus; belongs to the Flaviviridae genus
  • Transmission by mosquito is the cause in nearly all cases; many mosquito species have been implicated
  • Rarely, transmission occurs through transfusion of blood products or through organ transplantation 2
  • Transplacental transmission or infection through ingestion of breast milk may rarely occur 2

Risk factors and/or associations

  • Cases reported in all age groups (1 month to 99 years)
  • Median age for West Nile virus fever is 47 years; about one-half of cases occur in the fifth and sixth decades 4
  • Median age for West Nile virus neuroinvasive disease is 57 years; about one-half of cases occur in the seventh decade or later 4
    • Risk increases with age
  • West Nile virus neuroinvasive disease is more common in males (58%) 4
  • Defect in the OAS1 gene (HGNC 8086), which regulates degradation of foreign RNA, may predispose to infection 2 6
  • Non-white race has been associated with a higher risk for neuroinvasive disease 7
Other risk factors/associations
  • In the United States, over 90% of cases occur July through September 4
  • In addition to advanced age and male sex, underlying cancer, diabetes, hypertension, alcoholism, and/or renal disease increase the risk of West Nile virus neuroinvasive disease 2
  • Acquisition of infection through transplantation carries a high risk for neuroinvasive disease 2

Diagnostic Procedures

Primary diagnostic tools

  • Demonstration of West Nile virus IgM antibodies in serum or cerebrospinal fluid; detection of viral RNA may be helpful in some cases 8
    • Combination testing detects more cases than either test alone 9
  • Imaging and electrodiagnostic testing for neuroinvasive disease


  • IgM antibody-capture ELISA
    • Viral antibodies are usually detectable within 3 to 8 days of symptom onset; in West Nile virus neuroinvasive disease, antibodies are usually detectable in cerebrospinal fluid before the onset of neurologic symptoms 8 10
    • Presence in cerebrospinal fluid is diagnostic of West Nile virus neuroinvasive disease 2
    • West Nile virus IgM antibodies may be present for 90 days or more 8
    • West Nile antibodies may cross react with antibodies to other flaviviruses (eg, dengue, yellow fever, Zika, St. Louis encephalitis); plaque reduction neutralization assay can be performed to identify the antibodies with more certainty if clinically indicated 10
  • Polymerase chain reaction 2 8 9
    • May be performed on serum, cerebrospinal fluid, or tissue
    • Detects viral RNA early in the course of illness, before IgM antibodies are detectable
      • Most useful in first 8 days 9
    • In neuroinvasive disease, result may be negative by the time of symptom onset 10
    • Useful for immunocompromised patients who may not mount an antibody response
  • Cerebrospinal fluid analysis 11
    • Indicated for patients with signs of meningitis or encephalitis
    • Cerebrospinal fluid pleocytosis is usually lymphocytic, but neutrophils predominate in a some cases
    • Mildly elevated protein level and glucose level within reference range are typical of viral meningitis


  • In patients with encephalitis or meningitis, CT or MRI may show focal lesions in the pons, basal ganglia, or thalamus; leptomeningeal enhancement may be seen 2 5
  • In patients with flaccid paralysis, imaging may show abnormalities in the anterior horn regions of the spinal cord 5


Lumbar puncture
General explanation
  • Collection of cerebrospinal fluid by inserting a needle into the spinal canal
  • Suspicion of meningitis
  • Bleeding disorder
  • Elevated intracranial pressure (may be suspected with papilledema and/or decorticate or decerebrate posture)
Interpretation of results
  • Mild pleocytosis, protein elevation, and normal or mildly decreased glucose levels are consistent with viral infection
    • In West Nile virus neuroinvasive disease, pleocytosis is usually measured as less than 500 cells/mm³ and more often lymphocytic than neutrophilic; protein levels greater than 100 mg/dL are more common in patients with encephalitis than those with meningitis 11

Differential Diagnosis

Most common

  • Influenza
    • Fever and myalgias are prominent
    • Presents with rhinitis, sore throat; pronounced dry cough
    • Seasonal pattern differs from that of West Nile virus, although influenza can be seen during late summer and early fall in travelers who have returned from the southern hemisphere, or from Alaska or Asia, where influenza season begins in the northern hemisphere
    • Diagnosis of influenza usually can be confirmed with a rapid antigen test or polymerase chain reaction on respiratory secretions
  • Viral meningitis
    • Similar clinical picture to that of West Nile virus meningitis, including fever, headache, photophobia, and stiff neck
    • Similar cerebrospinal profile (eg, lymphocytic pleocytosis, mild elevation of protein, normal or mildly decreased glucose levels)
    • Seasonal pattern overlaps that of West Nile virus (ie, late summer, fall)
    • Polymerase chain reaction for potential pathogens may identify etiologic virus
  • Bacterial meningitis (Related: )Bacterial meningitis in adults
    • Similar clinical picture to that of West Nile virus meningitis, including fever, headache, photophobia, and stiff neck; degree of systemic illness (toxicity) may be more severe, with confusion and hypotension
    • Petechial rash may be evident in meningococcal infection
    • Cerebrospinal fluid may show:
      • Neutrophilic pleocytosis exceeding 500 cells/mm³
      • Protein level exceeding 200 mg/dL
      • Low glucose level (less than 50% of a concurrent serum value)
    • Gram stain or polymerase chain reaction for specific pathogens might provide early diagnosis; culture of cerebrospinal fluid or blood may reveal diagnosis in 24 to 48 hours
  • Herpes encephalitis
    • Similar clinical picture to that of West Nile virus encephalitis, including fever, headache, lethargy, and confusion
    • Temporal lobe involvement is a characteristic finding on CT, MRI, and EEG
    • Occurs most often in the winter
    • Diagnosis can be confirmed through polymerase chain reaction on cerebrospinal fluid
  • Guillain-Barre syndrome
    • Characterized by progressive ascending paralysis, with demonstrable muscle weakness, hypo- or areflexia
    • Associated autonomic abnormalities (tachycardia or bradycardia, labile blood pressure) may be observed
    • Can follow viral illness, but trigger may be unidentified; has been reported after West Nile virus infection
    • Distinct from West Nile virus flaccid paralysis, which shows anterior horn cell involvement
    • Cerebrospinal fluid usually shows elevated protein but no (or minimal) pleocytosis
    • Diagnosis is made by typical clinical picture and electromyogram findings



  • Support patient through the acute infection
  • Provide rehabilitative care as needed to regain fullest function possible


Admission criteria

Patients with West Nile virus neuroinvasive disease

Patients with West Nile virus nonneuroinvasive disease and profound generalized weakness or debility who cannot be cared for at home

Criteria for ICU admission
  • Coma and/or seizures
  • Flaccid paralysis
  • Need for mechanical ventilation

Recommendations for specialist referral

  • Refer to an infectious diseases specialist to aid in diagnostic work-up and coordination with public health authorities
  • Refer to a neurologist for West Nile virus neuroinvasive disease
  • Refer to a critical care specialist for patients admitted to ICU
  • Refer to a rehabilitation medicine specialist for patients with significant residual weakness or paralysis

Treatment Options

Treatment is primarily supportive; no effective antiviral therapy has been identified 12

Nondrug and supportive care

  • Fluid replacement to maintain adequate hydration
  • Ventilatory support for patients with respiratory muscle involvement or need for airway protection
  • Nutrition supplementation to maintain adequate caloric intake
  • Rehabilitative therapy for patients with significant residual weakness or paralysis


  • Some comorbidities increase the risk of West Nile virus neuroinvasive disease: 2
    • Cancer
    • Diabetes
    • Alcoholism
    • Renal disease
    • Hypertension
    • Immunosuppression, including HIV infection

Special populations

  • Elderly patients are at increased risk for West Nile virus neuroinvasive disease, and risk increases progressively at a rate of 1.5 times per decade 13 14
  • Pregnant women do not appear to experience more severe disease or negative outcomes of pregnancy 15 16
  • Patients who acquire infection through organ donation have the highest risk and highest mortality for West Nile virus neuroinvasive disease 14

Complications and Prognosis


  • Prolonged muscle weakness is the most common sequela, especially after neuroinvasive disease; persistent myalgias also is common 17
  • Patients may experience prolonged fatigue, lasting months to years, especially after neuroinvasive disease
    • Nearly one-third of all West Nile virus patients have persistent fatigue 6 months after the acute illness 18
  • Some patients experience cognitive impairment, with memory deficits and decreased concentration 17
  • Movement disorders (eg, tremors, myoclonus, parkinsonism) have been described 17


  • Prognosis of West Nile fever and West Nile meningitis is generally favorable 7
  • Patients with flaccid paralysis may experience irreversible loss of function; about one-third recover fully, one-third recover partially, and one-third recover little 5
  • Mortality is highest in patients with encephalitis or flaccid paralysis, and may reach 20% in that population 5

Screening and Prevention


At-risk populations

  • Blood and organ donors
  • The FDA recommends West Nile virus screening for oocyte and semen donors in the United States from June 1 through October 31 every year 19

Screening tests

  • West Nile virus polymerase chain reaction of serum sample


  • No human vaccine is available at present, but a number of candidate vaccines are in development 20
  • It is recommended that practitioners defer gamete donors who have confirmed or suspected West Nile virus infections in the preceding 120 days 19
  • Prevention revolves around controlling mosquito populations and avoiding exposure to mosquitos 10
    • Mosquito control measures
      • Source reduction to inhibit breeding and hatching of mosquitos
        • Eliminate standing water when feasible
        • Treat standing water that cannot be removed (eg, ponds, swamps) with larvacidal agents
      • Control of adult mosquitos
        • Apply pesticide to affected areas
    • Measures to avoid exposure and prevent bites
      • Ensure that door and window screens are in good repair
      • Avoid outdoor activities between dusk and dawn, or wear long pants and long-sleeved shirts
      • Apply mosquito repellent to skin and clothing 21
        • Repellents approved by the US Environmental Protection Agency include:
          • N,N-diethyl-m-toluamide (DEET)
            • Can be applied to skin or clothing
          • Picaridin (also known as KBR 3023 or icaridin outside the United States)
          • IR3535
          • Oil of lemon eucalyptus
            • Not for use in children younger than 3 years
          • Para-menthane-diol
            • Not for use in children younger than 3 years
          • 2-undecanone
        • Permethrin can be applied to clothing and camping equipment
          • Extensive use has resulted in resistance in some areas (eg, Puerto Rico)
        • Repellents should not be used on infants younger than 2 months; mosquito netting can be used over strollers
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