Herpes simplex antibody testing

, Associate Editor-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S.

Overview
Both type-specific and nontype-specific antibodies to HSV develop during the first several weeks after infection and persist indefinitely. Accurate type-specific HSV serologic assays are based on the HSV-specific glycoprotein G2 (HSV-2) and glycoprotein G1 (HSV-1). Both laboratory-based assays and point-of-care tests that provide results for HSV-2 antibodies from capillary blood or serum during a clinic visit are available. The sensitivities of these glycoprotein G type-specific tests for the detection of HSV-2 antibody vary from 80%–98%, and false-negative results might be more frequent at early stages of infection. The specificities of these assays are greater than 96%. False-positive results can occur, especially in patients with a low likelihood of HSV infection. Repeat or confirmatory testing might be indicated in some settings, especially if recent acquisition of genital herpes is suspected. IgM testing for HSV is not useful, because the IgM tests are not type-specific and might be positive during recurrent episodes of herpes.

Nearly all HSV-2 infections are sexually acquired and the presence of type-specific HSV-2 antibody implies anogenital infection. Hence, education and counseling appropriate for persons with genital herpes should be provided. The presence of HSV-1 antibody alone is however more difficult to interpret. Most persons with HSV-1 antibody have oral HSV infection acquired during childhood, which might be asymptomatic. However, acquisition of genital HSV-1 appears to be increasing, and genital HSV-1 also can be asymptomatic. Lack of symptoms in an HSV-1 seropositive person does not distinguish anogenital from orolabial or cutaneous infection, and regardless of site of infection, these persons remain at risk for acquiring HSV-2. HSV serologic testing should be considered for persons presenting for an STD evaluation, in particular for patients with multiple sex partners, patients with HIV infection, and patients at increased risk for HIV acquisition. However, screening for HSV-1 and HSV-2 in the general population is not indicated.

Indications for Type-specific HSV Serologic Assay

 * Recurrent genital symptoms or atypical symptoms with negative HSV cultures
 * Clinical diagnosis of genital herpes without laboratory confirmation
 * Partner with genital herpes

British Association for Sexual Health and HIV (BASHH) Recommendations

 * Testing for HSV type-specific antibodies can be used to diagnose HSV infection in asymptomatic persons.


 * HSV-2 antibodies are indicative of genital herpes. HSV-1 antibodies do not differentiate between genital and oropharyngeal infection.


 * Arguments in favour of serological screening include:
 * HSV-2 infection rates are as high as or higher than those of other sexually transmitted infections for which screening is in place.
 * Persons with asymptomatic or undiagnosed infection may transmit HSV to sexual partners or neonates.
 * Behavioural changes, condom use and suppressive antiviral therapy reduce the risk of HSV transmission.
 * Vaccines may soon become available to protect HSV seronegative persons from infection and disease.
 * HSV-2 seropositive persons who engage in high-risk sexual behaviour can be counselled about the increased risk of HIV acquisition


 * Arguments against screening include:
 * The specificity and sensitivity of current antibody assays are less than 100%.
 * False-positive results generate unnecessary psychological morbidity.
 * False-positive and false-negative results lead to inappropriate counselling.
 * Counselling of HSV-2 seronegative HSV-1 seropositive persons is problematic, given the large proportion of GH due to HSV-1.


 * Assays should be used that detect antibodies against the antigenically unique glycoproteins gG1 and gG2.


 * Western blot (WB) is the diagnostic gold-standard. It is >97% sensitive and >98% specific, but is labour-intensive and not commercially available.


 * Several commercial assays have become available. Among commercial assays, the HerpeSelect-1 and HerpeSelect-2 enzyme-linked immunosorbent assay (ELISA) immunoglobulin G (IgG). HerpeSelect 1 and 2 Immunoblot IgG have been approved by the American Food and Drug Administration.
 * In sexually active adults, sensitivity and specificity of ELISA relative to WB are 91% and 92% for HSV-1 and 96% and 97% for HSV-2. Immunoblot sensitivity and specificity are 99% and 95% for HSV-1 and 97% and 98% for HSV-2.


 * HSV seroprevalence rates in the local population and the presence or absence of risk factors for genital herpes influence the positive predictive value of HSV type-specific antibody assays. Local epidemiological data and patient demographic characteristics should guide testing and result interpretation.


 * In patients with a low likelihood of genital herpes, a positive HSV-2 result should be confirmed in a repeat sample or by using a different assay.


 * Type-specific antibody can take months to develop and false-negative results may occur early after infection. In first episode disease the diagnostic use of type-specific antibody testing will require follow-up samples after 3 months to demonstrate seroconversion.

Source
BASHH guidelines mentioned in National Guideline Clearinghouse