Sexually Transmitted Diseases  >  Publications  >  Report of the Genital Herpes Prevention Consultants Meeting May 5-6, 1998

Report of the Genital Herpes Prevention Consultants Meeting May 5-6, 1998

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1. Performance and Uses of Type-Specific HSV Serological Tests

Clinical recognition and diagnosis of genital herpes are insensitive due to the frequency of subclinical infection and the insensitivity of virologic testing, especially for healing lesions, and the inability of heretofore widely available serological tests for HSV to differentiate the serological responses to HSV-1 and HSV-2. Several truly type-specific serological tests have been developed, most based on antibody to HSV glycoproteins G1 and G2, which have antigenic specificities to HSV-1 and HSV-2, respectively. Type-specific assays have been available in research settings for about 15 years, but only recently have tests been developed for the commercial market.

A. Availability and Cost

Selected tests currently available in research and commercial settings are listed in Appendix 3. The Western blot has been offered commercially and is widely accepted as the most accurate overall assay but is too cumbersome and expensive for routine use ($95 at the University of Washington), although it is likely to retain a role as a confirmatory assay. The HSV gG type-specific ELISA (Gull Laboratories) and the POCkit-HSV-2 test (Diagnology) are in late stages of clinical testing and are likely to be commercially available in the near future. Their costs are uncertain, but the cost of materials and labor to perform them are likely to be in the range of $8.00 to $40.00 per assay. A few other tests are in various stages of commercial development, whereas others are likely to be available only on a limited basis as research tools.

B. Performance

The Western blot detects antibodies to a large number of HSV antigens and has been shown to have both sensitivity and specificity >99% for symptomatic infections established >6 months.* Most other assays detect antibody to single antigens and compared to Western blot are at present less sensitive and/or less specific (Appendix 3). All assays have variable and relatively low sensitivities for infection <6 months’ duration.

Substantial discussion addressed the newer tests’ specificity, approximating 97-99% compared with Western blot, which has important implications for the use and interpretation of test results in individual patients. For example, in a population with 10% prevalence (as might be expected in some screening settings, such as teen clinics) a test with 95% sensitivity and 98% specificity has a positive predictive value (PPV) of 84%, corresponding to an unacceptable 16% rate of false positive results. Thus, serious concerns were raised about the utility of the newer assays as single tests for screening. A possible approach would be to use a sequential testing scheme, with re-testing all positives with a second assay, a strategy that probably would substantially increase for the cost of screening programs. However, in a population with a 50% prevalence rate the PPV rises to 98%, which may be acceptable for some uses, such as diagnosis of genital ulcer disease or evaluating the sex partners of persons with genital herpes.

Although concerns have been raised that some infected persons may lose antibody to HSV-2 over time ("seroreversion"), there was consensus that this phenomenon is due not to loss of antibody but to a lower sensitivity of antibody detection for some assays, which are operating at or near their limits of detection. However, no studies have determined the natural course of seroreactivity in persons with longstanding subclinical infection or in never-symptomatic infected persons.

There was broad consensus that type-specific serological tests for HSV are useful in the diagnosis of genital ulcer disease (e.g., for patients with recurrent genital lesions in whom viral isolation is impractical or unsuccessful) and for counseling, and that all clinicians who manage patients with STD or at risk should have access to such assays when they become generally available at reasonable cost. Nevertheless, several unknowns must be resolved before the full scope of serological testing is known and its role in genital herpes prevention fully defined. These include the "real world" performance of the newer assays, outside research settings; performance of all assays in chronic, subclinical infection, including the natural history of seroreactivity in subclinically infected persons; and the psychological and behavioral responses to being informed of a reactive test, especially in persons with neither clinical nor epidemiologic histories to suggest genital herpes. It was recognized that many patients seeking STD clinical services assume that evaluation routinely includes assessment for all common STDs, including herpes, but that almost no STD clinics and few other providers of STD clinical services routinely offer this service. However, quantitative data are lacking.

C. Recommendations

1. Test performance
   • DC should more assertively publicize the fact that most HSV serological tests now on the market are not truly type-specific, despite frequent claims to the contrary, and are not useful in diagnosing or screening for genital herpes infection; and that if serological testing is to be used in managing patients with or at risk for genital herpes, type-specific tests should be used (consensus high, priority high).
   • CDC should undertake or support studies of "real world" performance of the newer type-specific assays, including studies of the need for confirmatory tests in various settings and the appropriate confirmatory tests to use (consensus high, priority high)
2. Use of HSV type-specific serological tests
   • DC should conduct or support formative research in a variety of populations and among health care providers to explore the acceptability of serologic testing, responses to test results, content of counseling messages based on the test results, and how to deliver those messages (consensus high, priority high)
3. Serological diagnosis of genital ulcer disease
   • Studies of type-specific serological tests should include assessment of test performance in the diagnosis of genital ulcer disease (consensus high, priority high)
4. Pregnant women
   • DC should conduct or support demonstration projects that involve serological screening of pregnant women, and perhaps their sex partners, to assess strategies to prevent both neonatal herpes and unnecessary cesarean sections attributable to maternal genital herpes (Section 3, below).
5. Genital herpes-discordant couples
   • DC should undertake or support demonstration projects to assess the willingness of partners to know their infection status, the psychological impact of testing, effects on behavior change, effects on relationships, and comparative utility of serological vs clinical/virologic diagnosis of index patients and their partners (high consensus, high priority).
6. STD clinic populations and patients seeking STD clinical services
   • DC should promote standards of care in STD clinics and other facilities where STD services are routinely provided which stipulate that patients should be informed if genital herpes assessment is not included in the clinical evaluation (consensus high, priority not stated).
   • CDC should promote standards of care in STD clinics and other facilities where STD services are routinely provided which stipulate that, at a minimum, type-specific serological tests should be available to patients on request (consensus high, priority not stated).
   • CDC should promote standards of care in STD clinics and other facilities where STD services are routine provided which stipulate that tests to detect HSV (virus, antigens, or DNA) should be available and used routinely in the diagnosis of genital ulcer disease (consensus high, priority not stated) .
   • CDC should undertake or support demonstration projects to assess the willingness of STD clinic attendees, as well as patients in other settings where STD clinical services are routinely offered (e.g., reproductive health clinics) to know the results of HSV serological tests, psychological impact, behavior change, effects on relationships, and the comparative impacts of serological vs clinical/virologic diagnosis on these variables (consensus high, priority medium to low) .
   • CDC should assess HSV diagnostic tests offered and approaches to HSV screening and clinical assessment in public STD clinics and other settings where STD clinical services are routinely offered, and should develop guidelines to define the minimal standards for such care (consensus high, priority not stated) .
7. General public
   • Mass screening of the general public is not warranted (high consensus).
   • DC should conduct or support systematic surveys or opinion polls of the public to assess interest and willingness to know HSV serological status (high consensus, high priority).

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