Biology and Epidemiology of Genital HSV Acquisition

Anna Wald, MD, MPH

This research is concerned with the epidemiologic, virologic and immunologic events associated with the transmission and acquisition of HSV. Recent large seroepidemiologic studies have shown that the age-adjusted prevalence of HSV-2 infection is around 21% representing a 30% increase over the last 15 years. To date, no effective control strategy has been developed for the prevention of genital herpes. This research program is working to define the events surrounding transmission and acquisition of genital herpes to allow the design of active preventative tools for the reduction of HSV-2 transmission.

In this research study the investigators are testing the hypotheses that:

• most genital HSV infections are acquired soon after initiation of a sexual relationship with source partners who are unaware of their genital HSV infection, and
• high subclinical shedding rates, recent acquisition of HSV-2 in the source partner, and inconsistent condom use predict HSV transmission early in the relationship.

This study is combining molecular epidemiology with application of a proportional hazards model to analyze the risk factors for transmission of HSV in sex partnerships. The specific aims are of this study are to:

1. Determine (based on the duration of sex partnerships prior to transmission) the behavioral, virologic and immunologic risk factors and sexual practices that confer increased risk of HSV transmission. Persons with newly acquired genital HSV infections and their sex partners are identified through the UW Virology Research Clinic and the Seattle/King County STD Clinic. The acquisition of HSV in the index case is verified by virus isolation and HSV type-specific serology. Potential source partners are identified by standard means. Index cases and potential source partners are interviewed in detail and a battery of virologic, immunologic and serologic tests are performed. Restriction enzyme analyses are used to define the source partner of index cases. Shedding rates in source partners is evaluated prospectively with daily viral cultures.
2. Further define the biologic and behavioral risk factors for HSV transmission by comparing sex partnerships in which laboratory -confirmed HSV transmission has occurred to sex partnerships, with serologically discordant partners, where HSV-2 transmission has not occurred despite potential exposure.

This investigation is focused on characterizing the sex partnerships that do not result in HSV-2 transmission, despite repeated exposures, and determine the factors responsible for this lack of transmission. Partnerships discordant for HSV-2 infection are being analyzed with the same methods as for partnerships where HSV transmission has occurred. These studies will determine if increasing duration of a relationship reduces the risk of HSV transmission and if so, if the reduction of risk is due to:

• changes in sexual behavior,
• changes in subclinical shedding rates in the source partner, or
• acquisition of acquired resistance to infection.

These studies are also evaluating the role of local and systemic immune responses to HSV-2 among source partners who do and do not transmit HSV.

Laboratory tests used to characterize the study populations include HIV antibody tests, HSV Western blot analyses, HSV isolation in cell culture, HSV DNA polymerase chain reaction (PCR), restriction enzyme analyses, cellular immunology studies and mucosal immunity studies. In addition, the Cox proportional hazards regression model is being used as an analytic tool in this investigation to assess the relative risk of characteristics associated with HSV-2 transmission.

The investigators have found that individuals who are HSV-2 seropositive shed HSV-2 in the absence of detectable genital herpes and that the subclinical shedding rate of individuals with asymptomatic HSV-2 infection is as high as that in persons with symptomatic HSV-2 infection. It appears that most subclinical infections are unrecognized but virologically active and that these individuals can serve as sources of new infections. Continued findings from this study will characterize those persons at risk for transmitting HSV-2 infection and those at high risk for acquiring HSV-2 infection so that prevention strategies can focus on these groups.

Report courtesy of Anna Marie Beckmann

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Recent Publications

Wald A, Zeh J, Selke S, Ashley RL, Corey L. Virologic characteristics of subclinical and symptomatic genital herpes infection. N Engl J Med 1995; 333:770-5.

Wald A, Corey L, Cone R, Hobson A, Davis G, Zeh J. Frequent genital herpes simplex virus 2 shedding in immunocompetent women. Effect of acyclovir treatment. J Clin Infect 1997; 99:1092-7.

Wald A, Koutsky L, Ashley RL, Corey L. Genital herpes in a primary care clinic. Demographic and sexual correlates of herpes simplex type 2 infections. Sex Transm Dis 1997; 24:149-55.