Varicella-Zoster Virus - VZV

Varicella-zoster virus (VZV) is the etiologic agent of chickenpox in children and herpes zoster (shingles) in adults. According to the CDC, clinical diagnosis is challenging because fewer people get varicella and varicella in vaccinated people is often mild and atypical in presentation. Therefore, laboratory confirmation of varicella is becoming increasingly important in routine clinical practice. Antibody testing can be used to assess immunity to VZV, and DFA and PCR can both be used on fluid from lesions for rapid identification of the virus.

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

Indications for Testing 

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

Laboratory Testing

  • Varicella/chickenpox case definition and classification (CDC, 2010)
  • 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
    • Assessing immunity to VZV (CDC, 2016)
  • Congenital
    • Presence of IgM antibodies
    • PCR of skin lesions

Differential Diagnosis


  • Incidence – 1 million 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


  • 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, hepatitis
    • 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
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.

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


Not recommended for CSF samples

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


~20% of specimens 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/Cell Culture


Not recommended for CSF specimens

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

Varicella-Zoster Virus Antibodies, IgG and IgM 0050162
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Chemiluminescent Immunoassay


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


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, Non-Gynecologic 2000623
Method: Microscopy


U.S. Department of Health and Human Services, Centers for Disease Control and Prevention (CDC). Adult Immunization Schedule. Center for Disease Control and Prevention. [Last updated: Feb 2017; Accessed: Sep 2017]

U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Manual for the Surveillance of Vaccine-Preventable Diseases. Centers for Disease Control and Prevention. Atlanta, GA [Last updated: Apr 2016; Accessed: Aug 2017]

U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Recommended Immunization Schedules for Children and Adolescents Aged 18 Years or Younger. United States, 2016. Centers for Disease Control and Prevention. Atlanta, GA [Last Updated: Jan 2017; Accessed: Sep 2017]

General References

Gershon AA. Varicella-zoster virus infections. Pediatr Rev. 2008; 29(1): 5-10; quiz 11. PubMed

Leung J, Harpaz R, Baughman AL, Heath K, Loparev V, Vázquez M, Watson BM, Schmid S. Evaluation of laboratory methods for diagnosis of varicella. Clin Infect Dis. 2010; 51(1): 23-32. PubMed

Mandelbrot L. Fetal varicella - diagnosis, management, and outcome. Prenat Diagn. 2012; 32(6): 511-8. PubMed

Nagel MA, Gilden DH. The protean neurologic manifestations of varicella-zoster virus infection. Cleve Clin J Med. 2007; 74(7): 489-94, 496, 498-9 passim. PubMed

Neu N, Duchon J, Zachariah P. TORCH infections. Clin Perinatol. 2015 Mar;42(1):77-103, viii. PubMed

Sampathkumar P, Drage LA, Martin DP. Herpes zoster (shingles) and postherpetic neuralgia. Mayo Clin Proc. 2009; 84(3): 274-80. PubMed

Weinberg JM. Herpes zoster: epidemiology, natural history, and common complications. J Am Acad Dermatol. 2007; 57(6 Suppl): S130-5. PubMed

Medical Reviewers

Last Update: November 2017