Varicella-Zoster Virus - VZV

Diagnosis

Indications for Testing 

  • VZV disease is usually a clinical diagnosis
  • Most common indication is to confirm severe or atypical disease

Laboratory Testing

  • CDC interpretion of laboratory tests for VZV
  • DFA or PCR – rapid identification of the virus
    • Best performed on fluid from lesions
    • Sensitivity and specificity >90%
    • PCR is recommended in VZV-CNS syndromes – viral recovery of organisms from CSF is poor
  • Tzanck smear – rapid; not specific for VZV; performed on swabs from lesions
  • Viral culture
    • Takes >1 week
    • Poor sensitivity
    • Difficult to cultivate
  • Antibody testing
    • Significant change in titer from paired sera or a single high titer IgM is indicative of acute infection
    • IgG titer is useful in assessing immunity to VZV

Differential Diagnosis

Clinical Background

Varicella-zoster virus (VZV) is the etiologic agent of chickenpox in children and herpes zoster (shingles) in adults.

Epidemiology

  • Incidence – 1,000,000 new cases annually in U.S.
  • Age
    • Varicella zoster – children (usually 1-9 years)
    • Herpes zoster – >60 years
  • Sex – M:F, equal
  • Climate variation
    • Temperate climates – 90% have infection before adolescence
    • Tropical climates – adults more susceptible than in temperate climates

Organism

  • DNA virus
  • Member of Herpesviridae family
  • Establishes latency in sensory ganglia

Risk Factors

  • Varicella
    • Direct contact with large-particle droplets (for non-immune individuals)
  • Herpes zoster
    • Immune deficiency, psychological stress, and localized physical trauma

Clinical Presentation

  • Varicella (chickenpox)
    • Fever and generalized vesicular exanthem
      • Rash begins as macules and rapidly progresses to papules and vesicles
      • Successive crops of lesions common
  • Complications
    • Secondary bacterial skin infections
    • Invasive disease – pneumonia, osteomyelitis
    • Central nervous system – strokes (vasculopathy), cerebellar ataxia, meningitis, transverse myelitis
  • Herpes zoster (reactivation of VZV)
    • Skin eruption (shingles)
      • Unilateral, painful maculopapular lesions followed by vesicular eruptions with dermatomal distribution (1-3 dermatomes is usual) that do not cross the midline
    • Facial nerve involvement (seventh cranial nerve) – Ramsey-Hunt syndrome
  • Congenital VZV 
    • Transmission (0.4-2% of children when mother has VZV during first 20 weeks of pregnancy) may cause severe disseminated neonatal infection with the following
      • Skin lesions 
      • Pneumonia
      • Hemorrhages
      • Developmental problems, including hypoplastic limbs, cataracts, chorioretinitis, microphthalmos
      • Death

Treatment

  • Early treatment of zoster with antivirals accelerates resolution and may lessen post-herpetic pain

Prevention

  • Childhood vaccination preventive for serious VZV in most cases
  • Universal vaccination has decreased outbreaks and severity of secondary complications
  • New vaccine recently approved for adults >60 years to prevent herpes zoster
    • Vaccine shown to reduce incidence of PHN by >65%
  • Passive immunization with varicella-zoster immune globulin can prevent severe disease in certain susceptible pediatric populations after exposure

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
Varicella-Zoster Virus DFA with Reflex to Varicella-Zoster Virus Culture 0060282
Method: Direct Fluorescent Antibody Stain

Confirm VZV, especially in active skin lesions

Sensitivity of DFA is highest when performed on scraping from the base of lesions; culture sensitivity is highest  when samples are collected early after symptom onset

Culture considered gold standard

Not recommended for CSF samples

  
Varicella-Zoster Virus DFA 0060290
Method: Direct Fluorescent Antibody Stain

Rapid confirmation of VZV

Sensitivity of DFA is highest when performed on scraping from the base of lesions

~20% of samples submitted for VZV are positive for HSV; HSV testing is NOT included in this test

  
Varicella-Zoster Virus and Herpes Simplex Virus DFA with Reflex to Varicella-Zoster Virus Culture and Herpes Simplex Virus Culture 0060283
Method: Direct Fluorescent Antibody Stain

Confirm VZV or HSV, especially in lesions with fluid

Not recommended for CSF samples

  
Varicella-Zoster Virus by PCR 0060042
Method: Qualitative Polymerase Chain Reaction

PCR most sensitive and rapid test, but because of assay expense, some laboratories may limit testing to

  • CNS syndromes
  • Body fluids or tissues from unusual varicella or herpes zoster infections
  • Vesicle fluid specimens negative for VZV by culture and/or DFA negative for HSV by culture where definitive etiologic determination clinically important
    
Varicella-Zoster Virus Antibodies, IgG and IgM 0050162
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Chemiluminescent Immunoassay

Diagnose clinical infections with varicella or herpes zoster

Identify hospitalized children with varicella

Assess immune status of individuals exposed to varicella, especially pregnant women

   Repeat testing in 10-14 days if results equivocal
Varicella-Zoster Virus Antibody, IgM by ELISA (CSF) 0054445
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Confirm VZV in acute infections

Antibody detection in CSF may reflect contamination by blood or antibody transfer across blood-brain barrier rather than VZV infection

Repeat in 10-14 days if results equivocal
Cytology, Tzanck Smear 8209714
Method: Microscopy

Nonspecific but rapid test for VZV

    
Additional Tests Available
 
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Varicella-Zoster Virus Antibody, IgM 0099314
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Varicella-Zoster Virus Antibody, IgG 0050167
Method: Semi-Quantitative Chemiluminescent Immunoassay
Varicella-Zoster Virus Antibody, IgG, CSF 0054444
Method: Semi-Quantitative Chemiluminescent Immunoassay
Encephalitis Panel, CSF with Reflex to HSV Type 1 and 2 Glycoprotein G-Specific Ab, IgG 2001741
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody Semi-Quantitative Chemiluminescent Immunoassay
Encephalitis Panel, Serum with Reflex to HSV Type 1 and Type 2 Glycoprotein G-Specific Ab, IgG 2001742
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Chemiluminescent Immunoassay
Meningoencephalitis Panel, CSF with Reflex to HSV Type 1 and Type 2 Glycoprotein G-Specific Ab, IgG 2001765
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Chemiluminescent Immunoassay
Meningoencephalitis Panel, Serum with Reflex to HSV Type 1 and Type 2 Glycoprotein G-Specific Ab, IgG 2001764
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Chemiluminescent Immunoassay
Viral Culture, Non-Respiratory, and Cytomegalovirus Rapid Culture 2006496
Method: Cell Culture/Immunofluorescence
Viral Culture, Non-Respiratory 2006498
Method: Cell Culture
Viral Culture, Respiratory 2006499
Method: Cell Culture
Viral Culture, Respiratory, and Cytomegalovirus Rapid Culture 2006497
Method: Cell Culture/Immunofluorescence