Detection of Herpes Simplex Virus and Varicella-Zoster Virus by Traditional and Multiplex Molecular Methods

Dejan Nikolic, MD, PhD; Debra Kohn; Belinda Yen-Lieberman, PhD; Gary W Procop, MD, MS


Am J Clin Pathol. 2018;151(1):122-126. 

In This Article

Abstract and Introduction


Objectives: To compare multiplex nucleic acid amplification tests (NAATs) that detect and differentiate herpes simplex virus (HSV) and varicella-zoster virus (VZV) with traditional virologic assays.

Methods: The HSV ELVIS Test System (Quidel, San Diego, CA) and/or Light Diagnostics VZV direct fluorescent antibody (DFA) kit (Millipore Sigma, Billerica, MA), as well as an ARIES HSV 1&2/VZV assay (Luminex, Austin, TX) and the Solana HSV1 + 2/VZV Assay (Quidel), were performed on non–cerebrospinal fluid specimens.

Results: The sensitivities/specificities for the ELVIS, Aries, and Solana assays for HSV were 71.1%/93.2%, 94.9%/93.2%, and 94.7%/100%, respectively. The sensitivities/specificities for the DFA, Aries, and Solana assays for VZV were 71.4%/100%, 100%/96.0%, and 95.3%/100%, respectively. HSV and VZV were detected but clinically unsuspected in 5.4% and 4.2% of the specimens, respectively.

Conclusions: Both NAAT assays were comparable and more sensitive than traditional methods. The recovery of unsuspected HSV and VZV from clinical specimens supports the implementation of a combined HSV/VZV assay.


Herpes simplex virus (HSV) type 1 (HSV-1) and type 2 (HSV-2) and the varicella-zoster virus (VZV) are closely related members of the Herpesviridae family.[1] After primary infection, these viruses remain latent state in sensory ganglia. The reactivation of latent viruses may result in asymptomatic shedding, vesicular lesions, or aseptic meningitis.[1] Although the clinical presentation of reactivation disease is often distinct, overlapping presentations may occur.[2] The vesiculo-ulcerative lesions produced by the reactivation of HSV are most commonly associated with mucocutaneous locations (ie, cold sores or genital herpes), whereas those produced by the reactivation of VZV (ie, shingles) typically present in clusters in a dermatomal distribution.[1,3,4] Early eruptions that involve the sacral dermatomes, particularly S2 to S5, may be mistaken for genital herpes, and early vesicular lesions in an immunocompromised patient could represent disease caused by either HSV or VZV.[5–9] The reactivation of both HSV and VZV is a cause of aseptic meningitis.[10,11]

Previous studies have demonstrated that the sensitivity of traditional methods for the detection of HSV and VZV is inferior to that of nucleic acid amplification methods.[12–15] We sought to compare the traditional methods offered in our laboratory for detection of HSV and VZV with two nucleic acid amplification methods that simultaneously detect and differentiate HSV-1, HSV-2, and VZV. Furthermore, we investigated instances wherein the specimen submitted for HSV actually contained VZV and vice versa.