Varicella-Zoster Virus, Molecular Detection, PCR
Rapid (qualitative) detection of varicella-zoster virus DNA in clinical specimens for laboratory diagnosis of disease due to this virus
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Varicella-zoster virus (VZV) causes both varicella (chickenpox) and herpes zoster (shingles). VZV produces a generalized vesicular rash on the dermis (chickenpox) in normal children, usually before 10 years of age. After primary infection with VZV, the virus persists in latent form and may emerge (usually in adults 50 years of age and older) clinically to cause a unilateral vesicular eruption, generally in a dermatomal distribution (shingles).
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Detection of varicella-zoster virus (VZV) DNA in clinical specimens supports the clinical diagnosis of infection due to this virus.
VZV DNA is not detected in cerebrospinal fluid from patients without central nervous system disease caused by this virus.
This LightCycler PCR assay does not yield positive results with other herpesvirus gene targets (herpes simplex virus, cytomegalovirus, Epstein-Barr virus).
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
A negative result does not exclude the possibility of varicella-zoster virus (VZV) infection.
The reference range is typically "negative" for this assay. This assay is only to be used for patients with a clinical history and symptoms consistent with VZV infection, and must be interpreted in the context of the clinical picture. This test is not used to screen asymptomatic patients.
The following validation data supports the use of this assay for clinical testing.
Accuracy/Diagnostic Sensitivity and Specificity:
LightCycler PCR (primers, directed to varicella-zoster virus [VZV], gene 28) was compared with shell vial cell cultures for the detection of VZV from 253 dermal specimens. Twenty-three specimens (9.1%) were positive for VZV by LightCycler PCR and by the shell vial cell culture assay. An additional 21 specimens exclusively yielded VZV DNA. These discrepant specimens were resolved as true-positive results by confirmation of results by PCR using primers directed to another gene of VZV. Importantly, there were no instances in which VZV was recovered by the shell vial assay and not detected by LightCycler PCR (specificity, 100%). Of 100 cerebrospinal fluid specimens tested by both conventional PCR and LightCycler PCR VZV DNA was detected in 49 specimens by both methods; 1 specimen was positive only by the conventional PCR assay. Fifty specimens were found to be negative for VZV DNA by both techniques.
Supplemental Data (Spiking Studies):
To supplement the above data, 30 negative specimens each of various types were spiked with VZV plasmid at the limit of detection (10-20 targets/microliter). The spiked specimens were run in a blinded fashion along with approximately 30 negative (nonspiked) specimens each of various specimen types; 90% to 100% of the spiked specimens were positive and 100% of the nonspiked specimens were negative
Analytical Sensitivity/Limit of Detection (LoD):
The LoD of this assay is 10 to 20 DNA target copies per microliter in specimen matrix.
No PCR signal was obtained from extracts of 27 bacterial, viral, and fungal isolates that could be found as normal flora in sites normally tested for this organism or that could cause similar symptoms.
Interassay precision was 100% and intraassay precision was 97%.
This test is a qualitative assay and results are reported as negative or positive for targeted VZV DNA.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Cinque P, Bossolasco S, Vago L, et al: Varicella-zoster virus (VZV) DNA in cerebrospinal fluid of patients infected with human immunodeficiency virus: VZV disease of the central nervous system or subclinical reactivation of VZV infection? Clin Infect Dis 1997;25(3):634-639
2. Brown M, Scarborough M, Brink N, et al: Varicella zoster virus-associated neurological disease in HIV-infected patients. Int J STD AIDS 2001;12(2):79-83
3. Studahl M, Hagberg L, Rekabdar E, Bergstrom T: Herpesvirus DNA detection in cerebrospinal fluid: differences in clinical presentation between alpha-, beta-, and gamma-herpesviruses. Scand J Infect Dis 2000;32(3):237-248
4. Iten A, Chatelard P, Vuadens P, et al: Impact of cerebrospinal fluid PCR on the management of HIV-infected patients with varicella-zoster virus infection of the central nervous system. J Neurovirol 1999;5(2):172-180