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Test ID: VHSV    
Herpes Simplex Virus (HSV), Culture From Neonates, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

An aid in the diagnosis of congenital herpes simplex virus (HSV) infection in patients younger than 35 days old through the recovery of HSV using viral culture (shell-vial)

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Herpes simplex virus (HSV) types 1 (HSV-1) and 2 (HSV-2) are DNA viruses that cause localized infections of the skin, oral mucosa, oral cavity, eyes, genital tract, and central nervous system (CNS).(1,2) Systemic disease may occur. Primary infection typically results in no symptoms or localized pain and lesions at the site of infection (usually the oral or genital areas). After a primary infection, the virus enters a latent state. Latent virus may or may not reactivate in the future. Typically, the primary infection is more severe than subsequent reactivations. However, not all individuals have symptoms during the primary infection and the first recognized symptoms may be in the setting of a reactivation.

 

HSV infections are common. Seroprevalence of HSV-1 and HSV-2 in the United States (2005-2010) is 53.9% and 15.7%, respectively.(3) HSV-1 has historically been associated with oral lesions, but increasingly it is also a cause of genital herpes. Both HSV-1 and HSV-2 can cause severe CNS disease. In particular, HSV encephalitis in neonates is considered a medical emergency. Even with antiviral medication, there is significant morbidity and mortality associated with HSV encephalitis, especially in neonates.

 

Fetal and neonatal HSV infections can be acquired in utero or at the time of delivery. The greatest risk for transmitting HSV is when the mother experiences a primary HSV infection, but there is also increased risk of transmission during periods of reactivation. Primary infection and reactivation may not be symptomatic, but nevertheless result in viral transmission to the fetus or newborn.

 

Diagnostic methods for HSV include routine viral culture, molecular testing by PCR, and serology. It is difficult to recover HSV from spinal fluid (CSF) specimens using viral culture, and a serologic response to HSV is not detectable immediately after infection.

 

Detection of HSV by real-time PCR is now recognized as the most sensitive approach to diagnose HSV infection, especially CNS-associated HSV disease. However, it is still recommended to test neonates by viral culture when testing for potential congenital herpes by peripheral (eg, skin) swab, since PCR may detect low levels of HSV DNA or inactive virus in the absence of infectious viral particles. Infants younger than 4 weeks of age may have detectable HSV DNA on them that was shed by an infected mother, even in the absence of active HSV infection in the infant. On the other hand, a positive result by viral culture indicates the presence of live virus, suggesting active infection in the newborn.(4)

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.

No virus isolated

Interpretation Provides information to assist in interpretation of the test results

Recovery of herpes simplex virus (HSV) from clinical specimens supports the diagnosis of congenital HSV infection. A negative result by shell vial assay should be interpreted in the context of the patient's clinical presentation and exposure history. Furthermore, testing by real-time PCR for this virus should be considered prior to ruling out HSV disease.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test should not be performed on patients older than 4 weeks of age. It is intended for the recovery of herpes simplex virus (HSV) in suspected cases of congenital herpes. For patients older than 4 weeks of age, detection of HSV by real-time PCR is recommended.

 

A negative result does not rule out the possibility of congenital HSV infection.

 

Real-time PCR for HSV is the recommended test for all cases of central nervous system disease caused by this virus. Viral culture is an insensitive approach for detection of HSV in spinal fluid.

Supportive Data

Herpes simplex virus (HSV) shell-vial is a standard method that has been compared to real-time PCR in several published studies. Data from these studies suggest that real-time PCR increased the detection rate for HSV-1 and HSV-2 by up to 62.5%.(5,6)

 

Despite the increased sensitivity of real-time PCR compared to routine viral culture, detection of live virus may be useful in cases of suspected congenital herpes infection when the ability to distinguish between the presence of active, replicating virus and inactive virus or viral nucleic acid is important.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Schiffer JT, Corye L: New concepts in understanding genital herpes. Curr Infect Dis Rep Nov 2009;11(6):457-464

2. Sauerbrei A, Eichhorn U, Hottenrott G, Wutzler P: Virological diagnosis of herpes simplex encephalitis. J Clin Virol 2000;17(1):31-36

3. American Academy of Pediatrics. Red Book: 2012 Report of the Committee on Infectious Diseases. Herpes Simplex. Edited by LK Pickering. 29th edition. Elk Grove Village, IL: American Academy of Pediatrics, 2012

4. Bradley H, Markowitz LE, Gibson T, McQuillan GM: Seroprevalence of Herpes Simplex Virus types 1 and 2-United States, 1999-2010. J Infect Dis 2014 Feb 1;209(3):325-333

5. Stranska R, Schuurman R, de Vos M, van Loon AM: Routine use of a highly automated and internally controlled real-time PCR assay for the diagnosis of herpes simplex and varicella-zoster virus infections. J Clin Virol 2004 May;30(1):39-44

6. Espy MJ, Uhl JR, Mitchell PS, et al: Diagnosis of herpes simplex virus infections in the clinical laboratory by LightCycler PCR. J Clin Microbiol 2000;38(2):795-799