Arboviruses

Diagnosis

Indications for Testing

Laboratory Testing

  • Initial testing 
    • CBC with differential – lacks sensitivity/specificity but may aid in ruling out bacterial etiology
    • Cerebrospinal fluid (CSF) 
      • Cell count
      • Gram stain with culture
      • Culture – limited use because of low sensitivity
      • CNS disease – consider ordering multiple panel tests on CSF and serum to rule out other viral illnesses (eg, varicella-zoster virus [VZV], herpes simplex virus [HSV])
      • Protein
      • Glucose
      • Cellular profiles
        • WNV
          • Lymphocytic pleocytosis <1,000 cells/mm3
          • Neutrophils may predominate in early infections
          • Protein – moderately increased
          • Glucose – normal
        • St. Louis encephalitis
          • Lymphocytic pleocytosis <200 cells/mm3
          • Protein – >200 mg/dL in majority
          • Glucose – normal
        • Bunyavirus
          • Lymphocytic pleocytosis <200 cells/mm3
          • Protein – mildly increased
        • Togavirus
          • Lymphocytic pleocytosis 1,200-2,000 cells/mm3
          • Protein – elevated
          • May have increased CSF opening pressure
  • Serum or CSF antibody testing – currently only West Nile virus and Japanese encephalitis serology testing available in the U.S.
    • Majority of cases 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

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

Clinical Background

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

Epidemiology

  • 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

Organisms

  • More than 500 species of arbovirus
  • RNA viruses of importance in the U.S. include the following
    • Bunyavirus – California encephalitis (CE) serogroup
      • La Crosse virus
        • Primarily in upper Mississippi River valley
      • Jamestown Canyon virus
        • Upper midwestern states and New York
      • Snowshoe hare virus
        • Southern Canada
      • Mosquito species
        • Aedes triseriatus
    • Flavivirus
      • St. Louis encephalitis
        • Present in nearly all of the U.S.
        • Mosquito species
          • Culex pipiens and C. quinquefasciatus
            • Gulf Coast; Ohio and Mississippi River valleys
          • C. nigripalpus
            • Florida
          • C. tarsalis
            • Western states
      • Japanese encephalitis (JE) virus
        • Leading cause of viral encephalitis in Asia
        • Rare in U.S.
        • Mosquito-borne Culex tritaeniorhynchus group
      • West Nile virus encephalitis (WNV)
        • Endemic in U.S.
        • Mosquito species
          • C. tarsalis
        • Refer to Dengue fever virus for more information
    • Togaviruses
      • Eastern equine encephalitis (EEE)
        • Present in the eastern half of the U.S.
        • Mosquito species
          • Aedes vexans, Coquillettidia perturbans, Ochlerotatus sollicitans and canadensis
      • Western equine encephalitis (WEE)
        • Present in western and midwestern U.S.
        • Mosquito species
          • C. tarsalis

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

Treatment

  • Supportive care
  • Recovery may be prolonged

Indications for Laboratory Testing

  • 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
Test Name and Number Recommended Use Limitations Follow Up
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Initial evaluation of white blood cell count and differential in infectious diseases

Findings not specific for arbovirus infections

 
Cell Count, CSF 0095018
Method: Cell Count/Differential

Evaluation of white blood cell count and differential in suspected infectious meningitis/encephalitis

Findings not specific for arbovirus infections

 
Protein, Total, CSF 0020514
Method: Reflectance Spectrophotometry

Evaluation of protein level in suspected infectious meningitis/encephalitis

Findings not specific for arbovirus infections

 
Cerebrospinal Fluid (CSF) Culture and Gram Stain 0060106
Method: Stain/Culture/Identification

Identify agent of presumed meningitis

   
Glucose, CSF 0020515
Method: Enzymatic

Help differentiate viral from bacterial source

   
Encephalitis Panel with Reflex to Herpes Simplex Virus Types 1 and 2 Glycoprotein G-Specific Antibodies, IgG, Serum 2008915
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Chemiluminescent Immunoassay

Evaluate patients presenting with possible meningitis/encephalitis

Panel includes WNV, measles, mumps, VZV, and HSV-1 and HSV-2 antibodies

   
Encephalitis Panel with Reflex to Herpes Simplex Virus Types 1 and 2 Glycoprotein G-Specific Antibodies, IgG, CSF 2008916
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Chemiluminescent Immunoassay

Evaluate patients presenting with possible meningitis/encephalitis

Panel includes WNV, measles, mumps, VZV, HSV-1 and HSV-2 antibodies

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

Detect WNV-specific IgG and IgM, with a clinical suspicion of WNV

Because other members of the Flaviviridae family (St. Louis encephalitis virus or Dengue fever virus) show extensive cross-reactivity with WNV, serologic testing specific for these species should also be performed

Results must be correlated with clinical history and other data

Repeat in 10-14 days if results equivocal

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

Confirm positive antibodies test or clarify equivocal serologic test results

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

Detection of antibodies indicates current or past infection

 

Repeat testing in 10-14 days if results are equivocal

Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Japanese Encephalitis Virus Antibody, IgG by ELISA 2005687
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Japanese Encephalitis Virus Antibody, IgM by ELISA 2005685
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay
West Nile Virus Antibody, IgM by ELISA, Serum 0050236
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay
West Nile Virus Antibody, IgG by ELISA, Serum 0050234
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay
West Nile Virus Antibodies, IgG and IgM by ELISA, CSF 0050228
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay
West Nile Virus Antibody, IgG by ELISA, CSF 0050238
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay
West Nile Virus Antibody, IgM by ELISA, CSF 0050239
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay