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Determination of immune status of individuals to the varicella-zoster virus (VZV)
Documentation of previous infection with VZV in an individual without a previous record of immunization to VZV
Varicella-zoster virus (VZV), a herpes virus, causes 2 distinct exanthematous (rash-associated) diseases: chickenpox (varicella) and herpes zoster (shingles). Chickenpox is a highly contagious, though typically benign disease, usually contracted during childhood. Chickenpox is characterized by a dermal vesiculopustular rash that develops in successive crops approximately 10 to 21 days following exposure.(1) Although primary infection with VZV results in immunity and protection from subsequent infection, VZV remains latent within sensory dorsal root ganglia and upon reactivation, manifests as herpes zoster or shingles. During reactivation, the virus migrates along neural pathways to the skin, producing a unilateral rash, usually limited to a single dermatome. Shingles is an extremely painful condition typically occurring in older nonimmune adults or those with waning immunity to VZV and in patients with impaired cellular immunity.(2)
Individuals at risk for severe complications following primary VZV infection include pregnant women, in whom the virus may spread through the placenta to the fetus, causing congenital disease in the infant. Additionally, immunosuppressed patients are at risk for developing severe VZV-related complications, which include cutaneous disseminated disease and visceral organ involvement.(2,3)
Serologic screening for IgG-class antibodies to VZV aids in identifying nonimmune individuals.
Vaccinated: Positive (> or =1.1 AI)
Unvaccinated: Negative (< or =0.8 AI)
Reference values apply to all ages.
Positive: Antibody index (AI) value of 1.1 or higher:
The reported AI value is for reference only. This is a qualitative test and the numeric value of the AI is not indicative of the amount of antibody present. AI values above the manufacturer recommended cutoff for this assay indicate that specific antibodies were detected, suggesting prior exposure or vaccination. The presence of detectable IgG-class antibodies indicates prior exposure to the varicella-zoster virus (VZV) through infection or immunization. Individuals testing positive are considered immune to varicella-zoster.
Equivocal: AI 0.9-1.0
Submit an additional specimen for testing in 10 to 14 days to demonstrate IgG seroconversion if recently vaccinated or if otherwise clinically indicated.
Negative: AI of 0.8 or lower
The absence of detectable IgG-class antibodies suggests no prior exposure to the VZV or the lack of a specific immune response to immunization.
IgG-class antibodies to varicella-zoster virus may be present in serum specimens from individuals who have received blood products within the past several months but have not been immunized or experienced past infection with this virus.
Serum specimens drawn early during acute phase of infection may be negative for IgG-class antibodies to this virus.
To evaluate the accuracy of the BioPlex Varicella-Zoster Virus (VZV) IgG multiplex flow immunoassay (MFI), 500 prospective serum specimens were analyzed in a blinded fashion by the Diamedix VZV IgG EIA (Diamedix) and the BioPlex VZV IgG assay. Specimens with discordant results after initial testing were repeated by both assays during the same freeze/thaw cycle. Further discrepancies were evaluated by the SeraQuest VZV IgG EIA.(Quest International) The results are summarized below:
| Diamedix VZV IgG EIA | |||
BioPlex VZV IgG |
| Positive | Negative | Equivocal |
Positive | 436 | 0 | 0 | |
Negative | 18(a) | 22 | 4 | |
Equivocal | 19 | 0 | 1 |
a. All 18 specimens tested positive by the SeraQuest VZV IgG EIA.
Sensitivity: 92.2% (436/473); 95% CI: 89.4%-94.3%
Specificity: 100.0 (22/22); 95% CI: 82.5%-100.0%
Overall percent agreement: 91.8% (459/500); 95% CI: 89.0%-93.9%
1. Yankowitz J, Grose C: Congenital infections. In: Storch GA, ed. Essentials of Diagnostic Virology. Churchill Livingstone. 2000, pp 187-201
2. Gnann JW, Whitley RJ: Herpes zoster. N Engl J Med. 2002;347:340-346
3. Cvjetkovic D, Jovanovic J, Hrnjakovic-Cvjetkovic I, et al: Reactivation of herpes zoster infection by varicella-zoster virus. Med Pregl. 1999;52(3):125-128
4. Whitely RJ: Chickenpox and Herpes Zoster (Varicella-Zoster virus). In Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 9th ed. Elsevier; 2020: 1849-1856