• Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

Laboratory Testing

  • CDC testing
  • Initial testing
    • CBC with differential – lacks sensitivity/specificity but may aid in ruling out bacterial etiology
    • Cerebrospinal fluid (CSF)
  • Antibody testing
    • Majority of arbovirus-induced illnesses are diagnosed by serology
    • Best evidence for infection is a significant change (fourfold increase) in titer on two appropriately timed specimens done at the same laboratory
      • Appropriate timing – acute and convalescent samples ≥2 weeks apart
      • IgG usually negative in first 2 weeks of infection
      • Positive IgG without increase in convalescent sample and/or with negative IgM may indicate past exposure
      • CSF testing for WNV and JE

Imaging Studies

  • MRI more sensitive than CT
    • MRI may be normal
    • Findings vary but include increased T2 signal in basal ganglia, thalamus, and brainstem
    • If patient has focal neurologic signs and symptoms, MRI or CT should be performed prior to lumbar tap

Other Tests

  • EEG – if patient has seizures or is comatose
    • May show diffuse slow waves, focal sharp waves, seizures
    • No specific findings for viral encephalitis

Differential Diagnosis

Arthropod-borne viruses are transmitted to humans by arthropod bites and cause a spectrum of disease, from a mild viral syndrome to encephalitis.


  • Prevalence
    • >300 cases reported annually in U.S.
    • Seasonal – April to October
  • Age – young children and elderly more likely to have severe disease
  • Transmission – mosquito bite


  • More than 500 species of arbovirus

Risk Factors

  • Older age
  • Outdoor activity during peak mosquito activity (morning and evening)

Clinical Presentation

  • Commonly asymptomatic
  • Nonspecific flu-like symptoms/illness
    • Fever
    • Headache
    • Myalgias
    • Nausea, anorexia
    • Cough
    • Sore throat
  • Acute encephalitis (neuro-invasive disease)
    • Lasts a few days to months with slow and sometimes incomplete recovery
    • EEE has more abrupt onset and shorter, more severe course than arbovirus encephalitides
    • Presentation begins as nonspecific illness but progresses to any of the following
      • Cognitive dysfunction
      • Memory impairment
      • Muscle weakness
      • Paralysis
      • Seizures
      • Coma
  • WNV
    • Acute flaccid paralysis can occur
      • Causes poliomyelitis-like syndrome with involvement of anterior horn cells in spinal cord
      • Meningoencephalitis occasionally complicates disease
      • Mortality – 5-20% in affected patients
        • Up to 70% in affected patients >75 years
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

West Nile Virus Antibodies, IgG and IgM by ELISA, Serum 0050226
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay


Repeat in 10-14 days if results equivocal

West Nile Virus RNA by RT-PCR 0050229
Method: Qualitative Reverse Transcription Polymerase Chain Reaction

Japanese Encephalitis Virus Antibodies, IgG and IgM by ELISA 2005689
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay


Repeat testing in 10-14 days if results are equivocal


Tunkel AR, Glaser CA, Bloch KC, Sejvar JJ, Marra CM, Roos KL, Hartman BJ, Kaplan SL, Scheld M, Whitley RJ, Infectious Diseases Society of America. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008; 47(3): 303-27. PubMed

General References

Davis LE, Beckham D, Tyler KL. North American encephalitic arboviruses. Neurol Clin. 2008; 26(3): 727-57, ix. PubMed

McVey DS, Wilson WC, Gay CG. West Nile virus. Rev Sci Tech. 2015; 34(2): 431-9. PubMed

Petersen LR, Brault AC, Nasci RS. West Nile virus: review of the literature. JAMA. 2013; 310(3): 308-15. PubMed

Sejvar JJ. The evolving epidemiology of viral encephalitis. Curr Opin Neurol. 2006; 19(4): 350-7. PubMed

Zacks MA, Paessler S. Encephalitic alphaviruses. Vet Microbiol. 2010; 140(3-4): 281-6. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Baillie GJ, Kolokotronis S, Waltari E, Maffei JG, Kramer LD, Perkins SL. Phylogenetic and evolutionary analyses of St. Louis encephalitis virus genomes. Mol Phylogenet Evol. 2008; 47(2): 717-28. PubMed

Malan AK, Martins TB, Hill HR, Litwin CM. Evaluations of commercial West Nile virus immunoglobulin G (IgG) and IgM enzyme immunoassays show the value of continuous validation. J Clin Microbiol. 2004; 42(2): 727-33. PubMed

Malan AK, Stipanovich PJ, Martins TB, Hill HR, Litwin CM. Detection of IgG and IgM to West Nile virus. Development of an immunofluorescence assay. Am J Clin Pathol. 2003; 119(4): 508-15. PubMed

Rawlins ML, Swenson EM, Hill HR, Litwin CM. Evaluation of an enzyme immunoassay for detection of immunoglobulin M antibodies to West Nile virus and the importance of background subtraction in detecting nonspecific reactivity. Clin Vaccine Immunol. 2007; 14(6): 665-8. PubMed

Welch RJ, Anderson BL, Litwin CM. Evaluation of a new commercial enzyme immunoassay for the detection of IgM antibodies to West Nile virus using a ratio method to eliminate nonspecific reactivity. J Clin Lab Anal. 2008; 22(5): 362-6. PubMed

Medical Reviewers

Last Update: July 2017