Prevention Agenda for Genital Herpes

ALTHOUGH GENITAL HERPES is one of the three most prevalent sexually transmitted diseases (STDs) in the United States, the Centers for Disease Control and Prevention (CDC) has no established programs or guidelines specifically for its prevention. Several recent developments have enhanced the perceived need and prospects for genital herpes prevention strategies. The national prevalence of infection with type 2 herpes simplex virus (HSV-2) rose 30% between 1978 and 1991, with 22% of the population aged ≥12 years infected by the early 1990s.1 Understanding of the importance of genital herpes in facilitating sexual transmission of human immunodeficiency virus (HIV) has increased,2 and recent data suggest that HSV infection increases HIV transcription and plasma viral load, which may adversely affect the clinical course of HIV disease.3 Type-specific HSV serologic tests, which are likely to be useful for case detection and counseling, will be widely available in the near future.4 Antiviral therapy has been shown to reduce subclinical shedding of HSV,5 raising the possibility that chemotherapy may prevent transmission. Research on prophylactic vaccines appears promising, despite failure of one recent vaccine candidate to prevent HSV-2 infection.6 Lessons from HIV prevention have expanded the arsenal for prevention of incurable viral STDs to include individual and community-level behavioral interventions.7 Finally, progress in control of the bacterial STDs may create opportunities to address the viral STDs. Indeed, it is likely that aside from HIV infection, the dominant STDs of concern in the United States by 2010 will be genital herpes, human papillomavirus (HPV) infection, and perhaps other viral STDs. The desirability of preventing genital and neonatal herpes is self-evident, and some authorities recommend prompt initiation of a national control program,8 but others are skeptical about the need for public health prevention efforts or their potential efficacy.9 CDC's Division of STD Prevention (DSTDP), National Center for HIV, STD, and TB Prevention, recently initiated activities that will lead to linked programmatic and research agendas to address prevention of genital herpes. On May 5 and 6, 1998, DSTDP sponsored a meeting of 25 consultants and 20 CDC participants with expertise in genital herpes, STD epidemiology, behavioral sciences, mathematical modeling, health education, and STD program development and implementation. The intent was not to recommend definitive national prevention and control strategies, but to assess the prospects for a national prevention program and identify initial steps to determine the need and feasibility of such an effort. The consultants addressed six primary issues: 1) the performance and uses of type-specific HSV serologic tests, 2) the magnitude and burden of genital herpes morbidity in the United States, 3) prevention of neonatal herpes and herpes-related cesarean sections, 4) strategies to prevent sexual transmission of HSV, 5) interactions between genital herpes and HIV infection, and 6) knowledge about genital herpes among health care providers and the public. Recommended Program Development and Research Objectives The meeting participants recommended that CDC pursue several program development and research objectives. Recognizing that the performance characteristics of new diagnostic tests, as determined in preclinical testing, may differ when such tests are employed in diverse populations outside research settings, an overriding priority expressed by the consultants is for CDC to support studies to determine the “real world” performance of newer type-specific HSV serologic tests in varied populations. Substantial attention was given to the newer tests' specificity, estimated at 96% to 98% compared with an estimated specificity of ≥99% for the Western blot assay.4 Specificities ≤98% may result in low positive predictive values-i.e., high rates of false-positive results-in populations with low or moderate prevalences of HSV-2 infection. This raises the possibility that confirmatory testing of seropositive specimens may be required in some clinical settings. Few data are available on the psychologic and behavioral impact of HSV serologic testing on asymptomatic persons and their responses to the complex counseling and behavioral messages implied by uncovering serologic evidence of HSV-2 infection. The consultants advised that studies of these issues are necessary before comprehensive guidelines for serologic screening can be developed. Studies of partner management strategies and the related behavioral issues were recommended. Although it was recognized that partner services were implemented for bacterial STDs and HIV infection without the benefit of such research, the lifelong nature of HSV infection and uncertainties about both the short-term and long-term efficacy of interventions to prevent further transmission are inherent difficulties that must be addressed. The meeting participants cited an ongoing industry-supported study to determine the efficacy of antiviral chemotherapy to prevent sexual transmission of genital herpes, and expressed optimism that such therapy is likely to be at least partially effective. Accordingly, further studies to determine the use-effectiveness of this approach were considered to be a high priority. National data on the prevalence of HSV-2 infection are more complete than for most other STDs. Nevertheless, the incidence of genital herpes, the rate of complications, and other clinical correlates are poorly understood in comparison with the bacterial STDs and HIV infection. Such data are important for devising effective prevention strategies. Therefore, the consultants recommended that CDC support surveillance demonstration projects for genital and neonatal herpes in a variety of populations and geographic areas. In addition to better defining the incidence and morbidity of genital and neonatal herpes, another goal of such demonstration projects would be to explore the efficacy and feasibility of various approaches to surveillance and their abilities to assess trends and the efficacy of prevention efforts. Studies of potential strategies to prevent neonatal herpes were recommended, with emphasis on the roles of serologic screening of pregnant women and their sex partners, sexual abstinence near term, and antiviral therapy. Mathematical modeling of sexual transmission of HSV and of trends in incidence and prevalence were endorsed as potentially effective tools to understand the course of the genital herpes epidemic and the effects of intervention strategies. Research suggests that the direct medical costs attributable to genital and neonatal herpes are modest in comparison with those of many other STDs. However, the available studies were unable to account for the indirect and intangible costs of HSV infection, such as psychologic morbidity and adverse effects on sexuality and lifestyle, which are believed to be substantial. Studies that quantitate or otherwise account for these effects were considered a high priority. Studies of the effect of antiherpetic chemotherapy on HIV viral load and the natural course of HIV-related immunodeficiency and on the efficacy of such therapy in preventing sexual transmission of HIV were considered high priorities. Conversely, studies of the effect of highly active antiretroviral therapy on clinically evident herpes, subclinical shedding, and HSV transmission in HIV-infected persons also were considered important. Recommended Prevention Activities Although the emphasis of the meeting was on program development and research to inform future efforts, the consultants also recommended that selected direct prevention activities be initiated immediately. Knowledge about genital herpes is generally acknowledged to be poor among both health care providers and persons at risk. Therefore, the consultants cited education programs for health care providers and the public about the epidemiology, clinical manifestations, natural course, therapy, and transmission of genital herpes as a high priority. Recognizing that serologic assays that are not type-specific for HSV infection are widely used inappropriately and the results commonly are misinterpreted, CDC was encouraged to recommend that only type-specific serologic tests should be used for the purpose of diagnosis or case-finding of genital HSV infection, or for counseling of persons with or at risk for genital herpes. However, it was considered premature to make recommendations for specific populations or patients to whom serologic screening should be routinely offered. The 1998 STD Treatment Guidelines10 recommend that serologic tests that are not type-specific not be employed in the evaluation of the sex partners of persons with genital herpes, but this advice is not prominently displayed and deserves greater emphasis. The consultants expressed the consensus that many persons who undergo screening or diagnostic evaluation for STD desire to know whether or not they are infected with HSV-2, may expect that testing for genital herpes is routine, and may be dismayed to learn that a negative evaluation does not exclude HSV infection. However, few public STD clinics or other health care providers routinely offer such testing. Accordingly, the consultants urged CDC to promote standards of care that persons who undergo comprehensive STD evaluation (e.g., persons who request STD screening, most patients attending STD clinics, and patients with symptoms suggesting an STD) should be specifically informed whenever evaluation does not include diagnostic testing for HSV infection. Recognizing that genital herpes is the most common cause of genital ulcer disease in the United States, including most settings where syphilis or chancroid are prevalent, the consultants advised CDC to recommend to all health care providers that virologic tests for HSV be routinely employed in the evaluation of genital ulcer disease in sexually active young persons. Although such advice is included in the 1998 STD Treatment Guidelines,10 it should also be incorporated into specific herpes-prevention recommendations. There was consensus among the meeting participants that sufficient data are available to develop and promulgate recommendations to prevent unnecessary herpes-related cesarean sections. Some consultants advised that CDC recommend that all HIV-infected persons be evaluated for genital herpes, to include type-specific serologic tests when available, in the belief that appropriate counseling and judicious use of antiherpetic chemotherapy may reduce the risk of transmission of both HSV and HIV and perhaps delay the progression of immunodeficiency. However, other consultants disagreed with this recommendation, preferring to await additional data on the efficacy of such interventions. Summary Few meeting participants envisioned a prevention and control program on the scale or scope of CDC's programs to prevent HIV infection, syphilis, gonorrhea, and chlamydial infection, but all agreed that the virtual absence of public health interventions to prevent genital herpes is no longer appropriate in light of evolving epidemiologic knowledge and other research advances. The ultimate scope of a national genital herpes prevention effort will depend in part on the results of the recommended research agenda, which probably will evolve over the better part of a decade. Numerous other STD prevention partners will also need to contribute to this effort and help to determine the makeup of future programs. Substantial new fiscal resources will be required both to implement the proposed research agenda and, depending on the results, to undertake the prevention efforts indicated by those studies. Competing STD prevention priorities and other national health needs will influence the availability of those resources. The consultants' meeting and the research and program activities summarized above are described in more detail in the full meeting report, which is posted on the Division's web site (www.cdc.gov/nchstp/dstd/dstdp.html) or may be requested directly from the Division. DSTDP is interested in receiving comments and suggestions about herpes prevention.