Diagnosis of Herpes

Your health care provider can diagnose typical genital herpes by looking at the sores. Some cases, however, are more difficult to diagnose. The virus sometimes, but not always, can be detected by a laboratory test called a culture. A culture is done when your health care provider uses a swab to get and study material from a suspected herpes sore. You may still have genital herpes, however, even if your culture is negative (which means it does not show HSV).

A blood test cannot show whether you are having a herpes outbreak, but it can show if you are infected with HSV. Newer blood tests, called type-specific tests, can tell whether you are infected with HSV-1 or HSV-2. Blood tests cannot tell between genital and other herpes infections. Health experts assume, however, that if you are positive for HSV-2, you have had genital infection.

There are two main types of lab tests used for confirmatory diagnosis:

• Virologic Tests
• Type-specific Serologic Tests

Virologic Tests

Viral culture is considered the gold standard for herpes diagnosis. It is the preferred test for patients with genital ulcers or other mucocutaneous lesions. Viral culture is highly specific (>99%) and sensitive, but not as sensitive as PCR. Sensitivity declines rapidly as lesions begin to heal, usually within a few days of onset. Viral recovery depends on stage of lesion and proper collection technique. Virus is recovered from vesicles about 90% of the time, from ulcers about 70% of the time, and from crusted lesions about 30% of the time. Culture is more commonly positive in primary infection (80%–90%) than with recurrences (30%). Most cultures will be positive within 24-72 hours.

Antigen detection is fairly sensitive (>85%) in symptomatic shedders and may be better than culture for detecting HSV in healing lesions. Antigen detection is rapid (2-12 hours) and highly specific, but false positives can occur. The direct fluorescent antibody (DFA) test distinguishes between HSV-1 and HSV-2, while the enzyme immunoassay (EIA) test does not.

Cytologic detection (Tzanck or Pap) of cellular changes resulting from HSV infection is insensitive (50%) and nonspecific. It should not be relied upon for HSV diagnosis.

PCR assay is highly sensitive and specific, but its role in diagnosis of genital ulcer disease has not been well defined. PCR is the preferred test for detecting HSV in spinal fluid.

Type-Specific Serologic Tests

Serologic tests detect type-specific and nonspecific antibodies to HSV that develop during the first several weeks following infection and persist indefinitely.
Type-specific serological tests using antigens specific for HSV-1 (gG1) and HSV-2 (gG2)

have been developed and are now commercially available. Serologic type-specific gG-based assays should be specifically requested when serology is performed, because older assays do not accurately distinguish HSV-1 from HSV-2 antibody.

Currently, the FDA-approved gG-based type-specific assays include: HerpeSelect™-1 and HerpeSelect™-2 ELISA IgG (manufactured by Focus Technology, Inc.); and HerpeSelect™ 1 and 2 Immunoblot IgG (manufactured by Focus Technology, Inc.).

The sensitivities of these tests for detection of HSV-2 antibody vary from 80% to 98%, and false-negative results may occur, especially early after infection. The specificities of these assays are > 96%; false-positive results can occur, especially in patients with low likelihood of HSV infection. Therefore, repeat testing or a confirmatory test (e.g., an immunoblot assay if the initial test was an ELISA) may be indicated in some settings.

Because almost all HSV-2 infections are sexually acquired, type-specific HSV-2 antibody indicates anogenital infection. However, the presence of HSV-1 antibody does not distinguish anogenital from orolabial infection.

The standard testing procedure for herpes is to obtain a viral culture of a sore within the first 48 hours after symptoms appear. Beyond 48 hours, there is a risk of the culture yielding a "false negative" result because the sore may have begun healing and there may not be live virus present. Blood tests can be used to confirm a negative viral culture result or to help determine herpes infection in a person with no visible symptoms.

The two most accurate FDA-cleared type-specific blood tests are shown below.

* Accuracy is in comparison to Western Blot testing

Uses of type-specific serologic tests include:

• Confirming a clinical diagnosis of genital herpes in cases of recurrent or healing lesions or atypical genitourinary symptoms where false-negative cultures are more likely.
• Managing sex partners of persons with genital herpes and counseling couples in which one of the pair has genital herpes and the other does not know or is unsure (may be valuable in planning pregnancy or for expectant couples).
• Diagnosing persons with unrecognized infections.

While serologic assays for HSV-2 should be available for persons who request them, screening for HSV-1 or HSV-2 infection in the general population is not indicated.

Sources: CDC, DHHS