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Herpes Simplex Virus 2 Serology

Humans are the only natural reservoir of herpes simplex virus (HSV) type 1 (HSV-1) and type 2 (HSV-2).  HSV is one of the most prevalent viral infections in the world. Genital herpes is a sexually transmitted disease caused by either HSV-1 or HSV-2. HSV-1 causes both genital and orolabial disease, while HSV-2 infections are limited to the genitalia. 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 2015-2016 National Health and Nutrition Examination Survey (NHANES) of persons aged 14 to 49 years estimated seroprevalence of HSV-1 to be highest in Mexican American (72%) and non-Hispanic Black (59%) persons compared with the general US population (48%). Estimated seroprevalence of HSV-2 in US non-Hispanic Black adolescents and adults (35%) is nearly 3 times that in the general US population (12%). 

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 while they are asymptomatic.

An estimated 22% of pregnant persons in the United States US are seropositive for HSV-2. 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. HSV infection may be transmitted from mother to infant during vaginal delivery. 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 HSV-2 ELISA (Focus Diagnostics, Cypress, CA) and Biokit HSV-2 Rapid Test (American Screening LLC) are the two most widely used FDA approved enzyme immunoassays for the qualitative detection of type specific HSV-2 IgG.  HerpeSelect test has a pooled sensitivity estimate of 99% (95% CI, 97%-100%) and a pooled specificity estimate of 81% (95% CI, 68%-90%) compared with Western blot.Biokit test has a pooled sensitivity estimate of 84% (95% CI, 73%-91%) and pooled specificity estimate of 95% (95% CI, 93%-97%), compared with Western blot. The estimated positive predictive value for HerpeSelect may be as low as 50% and as low as 75% for Biokit. 

In 2016, the United States Preventive Services Task Force (USPSTF) recommended against routine serologic screening for genital HSV infection in asymptomatic adolescents and adults, including pregnant persons. In 2023, USPSTF reaffirmed its 2016 recommendation. 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.

HSV screening may be helpful for pregnant persons with a clinical history suggestive of HSV without laboratory confirmation. Antiviral therapy may be indicated for symptomatic pregnant persons. Cesarean delivery is recommended for pregnant persons with active genital lesions or prodromal symptoms.

Diagnostic testing of persons with recurrent atypical genital symptoms may be helpful. CDC recommends consideration of serologic testing for HSV-2 in persons presenting 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.

References

1. Centers for Disease Control and Prevention. Genital herpes: CDC fact sheet. http://www.cdc.gov/std/herpes/stdfact-herpes.htmThis 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. http://www.aafp.org/patient-care/clinical-recommendations/all/genital-herpes.htmlThis link goes offsite. Click to read the external link disclaimer. 
4. American College of Obstetricians and Gynecologists. ACOG-endorsed documents. http://www.acog.org/Resources-And-Publications/Endorsed-DocumentsThis 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. http://www.cdc.gov/std/tg2015/herpes.htmThis 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. 
7. US Preventive Services Task Force. Serologic Screening for Genital Herpes Infection: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. 2023;329(6):502–507. doi:10.1001/jama.2023.0057