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Diagnosing Genital Herpes Simplex Virus Infections

Posted March 1, 2007

Zsolt Jobbagy, MD, PhD, FCAP
Past Member of CAP/ACMG Biochemical & Molecular Genetics Resource Committee

Genital infections caused by herpes simplex viruses (HSV-1 and HSV-2) have the highest prevalence and the third highest incidence rate among all sexually transmitted diseases in the USA.1 When symptomatic, primary genital herpes can present with grouped vesicles at the site of infection that are painful and associated with a regional lymphadenopathy. In most cases, however, both primary infection and recurrences are asymptomatic.2 In fact, 70% of transmission occurs during periods of asymptomatic HSV shedding.3 Because effective antiviral therapy is available, identifying individuals with genital herpes infections may help decrease HSV transmission. The Centers for Disease Control recommends the performance of laboratory tests to confirm all clinical diagnoses of genital herpes because routine history and physical examination are neither sensitive nor specific enough to reliably diagnose HSV infections.4

Viral identification tests are generally used to establish a diagnosis of genital herpes in patients presenting with lesions. These tests include viral culture, polymerase chain reaction (PCR) and immunofluorescent assays. The viral culture system is considered the gold standard for diagnosis, and is positive in 70% of patients with active lesions. This method documents the presence of HSV in one to 10 days, so it is not useful for rapid clinical diagnosis.7 Moreover, its sensitivity is not optimal, especially for recurrent HSV infections.3 The commercial enzyme linked viral inducible system (ELVIS) is a cell culture-based method that utilizes baby hamster kidney cells transfected with a LacZ reporter gene driven by an HSV promoter, allowing for the overnight detection of HSV.6 There are several method comparison studies reporting similar sensitivities and specificities for the ELVIS system when compared to traditional viral culture,6 shell vial culture methods5,9 and spin-amplified tube cell culture methodology.8 Traditional PCR-based diagnostic methods have been shown to surpass traditional viral culture and direct HSV enzyme immunoassay (EIA) in sensitivity, typing and turnaround time.10,11 Furthermore, real-time PCR-based assays can further improve turnaround time and decrease contamination risk while allowing viral titer determination and maintaining superior sensitivity.12

Serologic tests are generally recommended for patients with atypical symptoms and negative culture or for partners of patients with genital herpes.3,4 Both type-specific and non-type-specific antibodies to HSV develop during the first several weeks after infection and persist indefinitely. Type-specific HSV serologic assays detect the HSV-specific glycoprotein G2 (HSV-2) and glycoprotein G1 (HSV-1) and are more accurate than older non-type-specific serologic assays. The detection of HSV-2 antibodies suggests anogenital infection. In the majority of patients, the presence of HSV-1 antibodies alone would implicate oral HSV infection, but HSV-1 specific antibodies are also detected in an ever-increasing number of genital herpes cases. HSV screening of the general population is currently not justified.4


  1. Cohen J, Powderly WG. Infectious Diseases. 2nd ed. St. Louis, Missouri: Mosby. 2004;789.
  2. Steben M. Genital herpes simplex virus infection. Clin Obstet Gynecol. 2005;48(4):838–844.
  3. Mertz GJ. Epidemiology of genital herpes infections. Infect Dis Clin North Am. 1993;7(4):825–839.
  4. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2006. Accessed Feb. 21, 2007
  5. Crist GA, Langer JM, Woods GL, et al. Evaluation of the ELVIS plate method for the detection and typing of herpes simplex virus in clinical specimens. Diagn Microbiol Infect Dis. 2004;49(3):173–177.
  6. Stabell EC, O’Rourke SR, Storch GA, et al. Evaluation of a genetically engineered cell line and a histochemical beta-galactosidase assay to detect herpes simplex virus in clinical specimens. J Clin Microbiol. 1993;31(10): 2796–2798.
  7. Arvin AM, Prober CG. Herpes simplex viruses. In: Murray PR, Baron EJ, Pfaller MA, et al, eds. Manual of Clinical Microbiology. Washington, DC: American Society for Microbiology;1995;876–883.
  8. LaRocco MT. Evaluation of an enzyme-linked viral inducible system for the rapid detection of Herpes simplex virus. Eu. J Clin Microbiol Infect Dis. 2000;19(3):233–235.
  9. Turchek BM, Huang YT. Evaluation of ELVIS HSV ID Typing System for the detection and typing of herpes simplex virus from clinical specimens. J Clin Virol. 1999;12(1):65–69.
  10. Slomka MJ, Emery L, Munday PE, et al. A comparison of PCR with virus isolation and direct antigen detection for diagnosis and typing of genital herpes. J Med Virol. 1998;55(2):177–183.
  11. Marshall DS, Linfert DR, Draghi A, et al. Identification of herpes simplex virus genital infection: comparison of a multiplex PCR assay and traditional viral isolation techniques. Mod Pathol. 2001;14(3):152–156.
  12. Filen F, Strand A, Allard A, et al. Duplex real-time polymerase chain reaction assay for detection and quantification of herpes simplex virus type 1 and herpes simplex virus type 2 in genital and cutaneous lesions. Sex Transm Dis. 2004;31(6):331–336.

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NewsPath® Editor: Megan J. DiFurio, MD, FCAP
This newsletter is produced in cooperation with the College of American Pathologists Public Affairs Committee and may be reproduced in whole or in part as a service to the medical community. Copyright © 2006 by the College of American Pathologists.
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