Mini review
New developments in the epidemiology, natural history and management of genital herpes

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Abstract

The prevalence of genital herpes is increasing in several populations worldwide. Factors that may be contributing to this increase include greater numbers of sexual partners, the high frequency of asymptomatic infections, poor use of safe sexual practices, and possibly the decreased incidence of childhood oral herpes simplex virus infection. Transmission occurs via skin-to-skin or mucous membrane contact during periods of viral shedding when lesions are present but may also occur when the patient is unaware of the lesions or when lesions are not clinically apparent. This has important implications for strategies to prevent transmission of the disease. The introduction of the antiherpes agent, acyclovir, and more recently famciclovir and valacyclovir, facilitates the management of genital herpes. Treatment of first-episode genital herpes reduces the severity and duration of symptoms, time to lesion healing, and cessation of viral shedding. Episodic treatment of recurrences as they occur may be of benefit to some patients. Daily suppressive therapy significantly reduces the frequency of recurrences and asymptomatic viral shedding. Accordingly, patients who experience frequent or severe recurrences, those particularly troubled by their disease, and those who wish to reduce the frequency of asymptomatic infection generally prefer suppressive therapy. The possibility that suppressive therapy may have an impact on transmission of the disease is currently under investigation. Antiviral treatments have important implications for public health and may help reduce the psychological and psychosocial impact of genital herpes on individual patients.

Introduction

Genital herpes is one of the most widespread sexually transmitted diseases in the developed world. It most commonly results from infection with the herpes simplex virus (HSV) type 2 (HSV-2), or sometimes with HSV type 1 (HSV-1). Genital herpes may be associated with symptoms ranging from mild irritation to severe pain. In the majority of cases, the symptoms of genital herpes are mild or absent and the infected individual may not seek medical help. Most people are intermittently infectious (irrespective of the severity of symptoms, frequency of recurrences, or whether medical help is sought). Therefore, all patients require advice on how to prevent transmission. This risk of transmitting the disease to sexual partners makes genital herpes an important public health issue as well as a medical condition that may cause significant pain and social and psychological distress to individuals.

Over recent years, we have seen important changes in our understanding of the epidemiology, transmission dynamics and clinical manifestations of genital herpes. In addition, our diagnostic and treatment options have improved. This article reviews these changes and how this improved understanding of the disease and its treatment should be used to improve patient care. The review is the outcome of a meeting that was held in Avon, Colorado between 6 and 8 April 1997, to examine new information and developments concerning genital herpes.

Section snippets

Epidemiology

The past 10–20 years have seen a significant increase in the prevalence of genital herpes in several different communities worldwide. For example, there has been a 30% increase in HSV-2 seropositivity in the USA between 1978 and 1992 with a marked shift toward younger ages of acquisition (Johnson et al., 1989, Fleming et al., 1997). Similar trends have been reported in other countries (Cowan et al., 1994, Forsgren et al., 1994). The factors responsible for the increase in prevalence are not

Transmission

Advances in our understanding of the transmission of HSV-1 and HSV-2 may help in the development of better strategies. It has long been recognized that transmission occurs via direct skin-to-skin or mucous membrane contact and occurs when lesions are clinically apparent (Mertz et al., 1985). Transmission may also occur when the patient is unaware of lesions (atypical/unrecognized lesions) or when lesions are not clinically apparent (asymptomatic shedding) (Mertz et al., 1985, Mertz et al., 1992

Impact of genital herpes on the patient

The psychological and psychosocial effects of genital herpes have been under-appreciated. For many persons these effects may well be more troublesome than the physical manifestations.

The diagnosis of genital herpes is usually unexpected, especially for those in monogamous relationships. This can lead to feelings of shock, embarrassment, depression, anger, diminished self-esteem and isolation (Catotti et al., 1993, Longo and Koehn, 1993, Carney et al., 1994). Depression is thought to result from

Diagnosis of genital herpes

The diagnosis of genital herpes is often established on clinical grounds alone, without laboratory confirmation. While the presence of bilateral vesicles or shallow ulcerations with an erythematous base in the genital area of a sexually active person is characteristic of primary genital herpes, the most common presentations are atypical and easily missed. Even when the presentation is considered typical, laboratory studies are important not only for confirming the diagnosis (often an aid in

Management of genital herpes—antiviral therapy

Antiviral agents assist in the management of genital herpes in patients who seek medical intervention for their symptoms, and may also offer the potential to reduce the risk of transmission. There are now three antiviral agents available for the treatment of genital herpes: acyclovir, valacyclovir and famciclovir. Acyclovir was the first oral antiherpes agent to be developed. Although acyclovir is very effective, it is poorly bioavailable following oral administration (10–20%) (O’Brien and

Impact on recurrences

The impact of daily antiviral therapy on the frequency of recurrences has been studied extensively for both acyclovir and the new antiviral agents. Mindel (Mindel et al., 1988) showed that the efficacy of acyclovir in suppressing recurrences is markedly influenced by the frequency of administration (Fig. 1). Of the patients receiving acyclovir twice a day or more frequently, at least 80% remained recurrence-free at 3 months. This decreased to 40% recurrence-free when acyclovir was administered

Impact on asymptomatic viral shedding

In addition to reducing the frequency of recurrences, antiviral therapy can also reduce asymptomatic shedding. Wald (Wald et al., 1996) has shown that twice-daily therapy with acyclovir 400 mg can significantly suppress viral shedding in women with recurrent genital herpes. In this study involving 34 patients, viral shedding on days without lesions was observed in 15 of the 17 patients receiving placebo, compared with only 3 of the 17 patients receiving acyclovir over the 10-week study period.

Impact on psychological well-being

Chronic suppressive therapy may also improve psychological well-being. Evidence supporting this comes from a study of the impact of acyclovir on 102 patients with frequently recurring genital herpes (Carney et al., 1993). A questionnaire was completed before therapy and every 3 months for 1 year to assess psychological morbidity. A significant improvement in all three measures of psychological morbidity used in the study was noted during acyclovir therapy. Further studies are required to

Recommended therapy

The results of these studies of suppressive antiviral therapy suggest that both once- and twice-daily regimens are effective in the suppression of recurrences, depending on the agent administered. Regardless of the drug chosen, it is crucial that treatment adequately controls the patients’ disease. Several concerns exist about once-daily regimens for suppressive therapy. Firstly, based on the pharmacokinetic profiles of antiherpes agents, once-daily regimens may be more likely to allow

Patient perspective

It is important to communicate information about options in antiviral therapy to the patient. Clinicians can make clear recommendations to their patients regarding the optimum management of their disease, the advantages and disadvantages of the various options, and the issues that patients should consider. However, each patient should be considered individually and the management programme should be tailored to his or her specific situation and needs. The patient’s views of the disease and how

Summary

Increases in the incidence and prevalence of HSV genital infections in many countries and populations are being accompanied by a greater recognition of the psychological impact of the disease and the need for counselling and support, as well as a better understanding of its transmission.

The new antiviral agents, famciclovir and valacyclovir, offer more convenient treatment schedules thus facilitating the management of patients. Of particular importance is the recognition of the value of

Acknowledgements

This review is based on discussions that took place at a meeting held in Avon, Colorado in April, 1997 that was sponsored by SmithKline Beecham Pharmaceuticals, Inc. Several of the authors have received grants for their work on herpes simplex virus from the National Institutes of Health, SmithKline Beecham, Glaxo Wellcome or other companies. The contents of this review, however, reflect the independent views of the authors.

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