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Herpes Simplex Virus 2 Serology

Genital herpes is a sexually transmitted disease caused by two related viruses, HSV-1 and HSV-2. In the United States, most cases of genital herpes historically have been caused by infection with HSV-2, but the incidence of genital herpes due to HSV-1 infection may be increasing.  In adolescents and adults, genital herpes infection produces vesicles in and around the genitals and rectum. These vesicles rupture, resulting in painful ulcers. Patients may also develop flu-like symptoms.

Currently, there is no cure for genital HSV infection. Patients remain infected for life. For this reason, the prevalence of infection increases with age. The prevalence of HSV-2 infection ranges from 1.4% among teens ages 14 to 19 years to 26.1% among adults ages 40 to 49 years. Women are almost twice as likely to be infected with HSV-2 as men (20.9% vs. 11.5%).  Rates are higher among men who have sex with men. Seventy to 90% of persons who have a symptomatic first outbreak will have at least one recurrence within the first year and average four outbreaks per year.

Although the risk of transmission is higher during a symptomatic outbreak, persons with genital herpes can spread the infection to sexual partners when they are asymptomatic.

HSV infection may be transmitted from mother to infant during vaginal delivery. Vertical transmission and subsequent severe neonatal HSV infection are most likely in pregnant women who develop the initial genital HSV infection during pregnancy. Among women who have a prior history of symptomatic genital herpes, nearly 75% will have at least one recurrence during pregnancy and about 14% will have symptoms or clinical recurrence at delivery. The most recent estimate of neonatal herpes incidence is 13 cases per 100,000 live births. Approximately 45% of infants with neonatal HSV infection develop relatively mild skin, eye, or mucous membrane infections; 30% develop a central nervous system infection; and 25% develop disseminated disease.

HerpeSelect® (Focus Diagnostics, Cypress, CA) is the most widely used FDA approved enzyme immunoassay for the qualitative detection of type specific HSV-2 IgG. In this immunoassay, HSV-2 antibodies bind to HSV-2 specific glycoprotein G2.  Medical literature indicates that sensitivity is 97 to 100% and specificity is 72 to 91%. Based on an HSV-2 infection prevalence of 15%, the positive predictive value of HerpeSelect may be as low as 50%.

The American Academy of Family Physicians, the American College of Obstetricians and Gynecologists (ACOG), and the CDC do not recommend routine serologic screening for genital HSV infection in asymptomatic adolescents or adults because of the large number of false positive results and the lack of a widely available confirmatory test. False positive results are associated with social and emotional harms as well as the risks associated with unnecessary treatment with antiviral medications.

Diagnostic testing of persons with recurrent atypical genital symptoms may be helpful. CDC recommends consideration of serologic testing for HSV-2 in persons presenting with symptoms suggestive of sexually transmitted infection and for persons living with HIV infection. CDC also recommends consideration of screening for HSV infection in men who have sex with men and are at high risk for HIV infection.

During primary infection with HSV-2, the first antibodies produced belong to the IgM class. The presence of IgM antibodies may indicate a primary infection, a super-infection with the other serotype, or reactivation of a latent HSV infection, (HSV-1 or HSV-2). For this reason, IgM testing is not recommended for diagnosis.

  1. Centers for Disease Control and Prevention. Genital herpes: CDC fact sheet. link goes offsite. Click to read the external link disclaimer. Accessed July 12, 2016.
  2. Feltner C, Grodensky CA, Middleton JC, et al. Serologic Screening for Genital Herpes Infection: An Evidence Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 149. AHRQ Publication No. 15-05223-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2016.
  3. American Academy of Family Physicians. Clinical preventive service recommendation: genital herpes simplex virus infection. link goes offsite. Click to read the external link disclaimer.
  4. American College of Obstetricians and Gynecologists. ACOG-endorsed documents. link goes offsite. Click to read the external link disclaimer..
  5. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015: genital HSV infections. link goes offsite. Click to read the external link disclaimer. Accessed July 12, 2016.
  6. ACOG Committee on Practice Bulletins. ACOG practice bulletin. Clinical management guidelines for obstetrician-gynecologists. No. 82 June 2007. Management of herpes in pregnancy. Obstet Gynecol. 2007;109(6):1489-98.
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