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
    • 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

   
Meningoencephalitis Panel with Reflex to Herpes Simplex Virus Types 1 and 2 Glycoprotein G-Specific Antibodies, IgG, Serum 2008918
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Chemiluminescent Immunoassay

Evaluate patients presenting with possible meningitis/encephalitis

Panel includes CE, EEE, St. Louis encephalitis, WEE, WNV, measles, mumps, VZV, and HSV-1 and HSV-2 antibodies

May be cross-reactive positivity in tests for related viruses (eg, flaviviruses)

 
Meningoencephalitis Panel with Reflex to Herpes Simplex Virus Types 1 and 2 Glycoprotein G-Specific Antibodies, IgG, CSF 2008917
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Chemiluminescent Immunoassay

Evaluate patients presenting with possible meningitis/encephalitis

Panel includes CE, EEE, St. Louis encephalitis, WEE, WNV, measles, mumps, VZV, HSV-1 and HSV-2 antibodies

May be cross-reactive positivity in tests for related viruses (eg, flaviviruses)

 
Arbovirus Antibodies, IgG and IgM, Serum 2001594
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Panel includes St. Louis encephalitis, WNV, EEE, and WEE antibodies

May be cross-reactive positivity in tests for related viruses (eg, flaviviruses)

 
Arbovirus Antibodies, IgG and IgM, CSF 2001597
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Panel includes St. Louis encephalitis, WNV, EEE, and WEE antibodies

May be cross-reactive positivity in tests for related viruses (eg, flaviviruses)

 
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
Arbovirus Antibodies, IgM, Serum 2001592
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Arbovirus Antibodies, IgG, Serum 2001593
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Arbovirus Antibodies, IgM, CSF 2001595
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Arbovirus Antibodies, IgG, CSF 2001596
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Enzyme-Linked Immunosorbent Assay
California Encephalitis Antibody, IgM by IFA, Serum 0098731
Method: Semi-Quantitative Indirect Fluorescent Antibody
California Encephalitis Antibody, IgG by IFA, Serum 0050508
Method: Semi-Quantitative Indirect Fluorescent Antibody
California Encephalitis Antibody, IgM by IFA, CSF 0098898
Method: Semi-Quantitative Indirect Fluorescent Antibody
California Encephalitis Antibody, IgG by IFA, CSF 0098893
Method: Semi-Quantitative Indirect Fluorescent Antibody
Eastern Equine Encephalitis Antibody, IgM by IFA, Serum 0098733
Method: Semi-Quantitative Indirect Fluorescent Antibody
Eastern Equine Encephalitis Antibody, IgG by IFA, Serum 0050509
Method: Semi-Quantitative Indirect Fluorescent Antibody
Eastern Equine Encephalitis Antibody, IgM by IFA, CSF 0098729
Method: Semi-Quantitative Indirect Fluorescent Antibody
Eastern Equine Encephalitis Antibody, IgG by IFA, CSF 0098896
Method: Semi-Quantitative Indirect Fluorescent Antibody
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
St. Louis Encephalitis Antibody, IgG by IFA, CSF 0098895
Method: Semi-Quantitative Indirect Fluorescent Antibody
St. Louis Encephalitis Antibody, IgG by IFA, Serum 0050507
Method: Semi-Quantitative Indirect Fluorescent Antibody
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
Western Equine Encephalitis Antibody, IgM by IFA, Serum 0098734
Method: Semi-Quantitative Indirect Fluorescent Antibody
Western Equine Encephalitis, Antibody, IgM by IFA, CSF 0098730
Method: Semi-Quantitative Indirect Fluorescent Antibody
Western Equine Encephalitis Antibody, IgG by IFA, CSF 0098897
Method: Semi-Quantitative Indirect Fluorescent Antibody
Western Equine Encephalitis Antibody, IgG by IFA, Serum 0050514
Method: Semi-Quantitative Indirect Fluorescent Antibody