Test ID: HSVG    
Herpes Simplex Virus (HSV) Type 1- and Type 2-Specific Antibodies, IgG, Serum

Determining whether a patient has been previously exposed to herpes simplex virus (HSV) types 1 and 2

Distinguishing between infection caused by HSV types 1 and 2, especially in patients with subclinical or unrecognized HSV infection

Herpes simplex virus (HSV) types 1 and 2 are members of the Herpesviridae family, and produce infections that may range from mild stomatitis to disseminated and fatal disease. Clinical conditions associated with HSV infection include gingivostomatitis, keratitis, encephalitis, vesicular skin eruptions, aseptic meningitis, neonatal herpes, genital tract infections, and disseminated primary infection.

Infections with HSV types 1 and 2 can differ significantly in their clinical manifestations and severity. HSV type 2 primarily causes urogenital infections and is found almost exclusively in adults. HSV type 1 is closely associated with orolabial infection, although genital infection with this virus can be common in certain populations.

The diagnosis HSV infections is routinely made based on clinical findings and supported by laboratory testing using PCR or viral culture. However, in instances of subclinical or unrecognized HSV infection, serologic testing for IgG-class antibodies to type-specific HSV glycoprotein G (gG) may be useful. There are several circumstances in which it may be important to distinguish between infection caused by HSV types 1 and 2.(1) For example, the likelihood of reactivation of the infection (type 2 -> type 1) and the method of antiviral therapy may be different depending on the specific type of HSV causing disease. In addition, the results of HSV type-specific IgG testing is sometimes used during pregnancy to identify risks of congential HSV disease and allow for focused counseling prior to delivery.(2-3)

Negative (reported as positive, negative, or equivocal)

This assay detects IgG-class antibodies to type-specific herpes simplex virus (HSV) glycoprotein G (gG), and may allow for the differentiation of infection caused by HSV types 1 and 2. The presence of IgG-class antibodies to HSV types 1 or 2 indicates previous exposure, and does not necessarily indicate that HSV is the causative agent of an acute illness.

Detection of IgG-class antibodies to herpes simplex virus (HSV) should not be used routinely as the primary means of diagnosing HSV infection. For patients presenting with presumed acute infection with HSV, a clinical specimen (eg, oral, dermal, or genital lesion) should be sampled and submitted for detection of HSV types 1 and 2 by rapid PCR (LHSV/80575 Herpes Simplex Virus [HSV], Molecular Detection, PCR).

Serum specimens collected too early in the course of infection may not have detectable levels of HSV IgG. In cases of suspected early disease, a repeat serum specimen should be collected 14 to 21 days later and submitted for testing.

The presence of IgG-class antibodies to either HSV type 1 or 2 does not differentiate between remote infection or acute disease.

HSV serology cannot distinguish genital from nongenital infections.

The predictive value of positive or negative results depends on the prevalence of disease and the pretest likelihood of HSV-1 and HSV-2.

False-positive results may occur. Repeat testing, or testing by a different method, may be indicated in some settings (eg, patients with low likelihood of HSV infection.)

Accuracy:

To evaluate the accuracy of the BioPlex HSV assay, 505 prospective serum samples were tested by EIA (HerpeSelect, Focus Diagnostics, Cypress, CA) and the BioPlex HSV-1/2 IgG assay. Samples that had discordant results after initial testing were repeated by both assays during the same freeze/thaw cycle.

Further discrepancies were evaluated by glycoprotein G (gG) type-specific Western blot (WB) at the University of Washington Virology laboratory (Seattle, WA).

The results are summarized in Tables 1 and 2 below:

Table 1. Comparison of the Bio-Rad BioPlex HSV-1 IgG assay to the HerpeSelect HSV-1 EIA using prospective serum specimens (n=505).

a. All 5 of these specimens were positive by WB

b. Both of these specimens were positive by WB

Sensitivity=99.2% (254/256); 95% Confidence Intervals (CI) (97.0, 99.9)

Specificity=96.8% (240/248); 95% CI (93.7, 98.5)

Overall percent agreement=97.8% (494/505); 95% CI (96.1, 98.8)

Table 2. Comparison of the Bio-Rad BioPlex HSV-2 IgG assay to the HerpeSelect HSV-2 EIA using prospective serum specimens (n=505).

a. Two of these 9 specimens were positive by WB; 2 of these 9 specimens were equivocal by WB.

b. This specimen was negative by WB.

Sensitivity=98.3% (115/117); 95% CI (93.6, 99.9)

Specificity=97.4% (376/386); 95% CI (95.2, 98.7)

Overall percent agreement=97.2% (493/505); 95% CI (95.4, 98.4)

1. Ashley RL, Wald A: Genital herpes: review of the epidemic and potential use of type-specific serology. Clin Microbiol Rev 1999;12:1-8

2. Ashley RL, Wu L, Pickering JW, et al: Premarket evaluation of a commercial glycoprotein G-based enzyme immunoassay for herpes simplex virus type-specific antibodies. J Clin Microbiol 1998;36:294-295

3. Brown ZA, Selke S, Zeh J, et al: The acquisition of herpes simplex virus during pregnancy. N Engl J Med 1997;337:509-515

4. Lafferty WE, Coombs RW, Benedetti J, et al: Recurrences after oral and genital herpes simplex infection. N Engl J Med 1987;316:1444-1449

5. Binnicker MJ, Jespersen DJ, Harring JA: Evaluation of three multiplex flow immunoassays to enzyme immunoassay for the detection and differentiation of IgG-class antibodies to herpes simplex virus types 1 and 2. Clin Vac Immunol 2010 Feb;17(2):253-257