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Genital herpes is an important public health disease and is the leading cause of genital ulcer disease worldwide. We present the latest evidence based guidelines from the British Association for Sexual Health and HIV (BASHH), the Centers for Disease Control and Prevention (CDC), and other expert committees to provide an up to date account of genital infection with herpes simplex virus (HSV), its clinical features and diagnosis, and a practical approach to management of affected patients. Treatment regimens have largely been based on evidence obtained from randomised controlled trials, while certain new diagnostic tests are limited by lower levels of evidence obtained only from descriptive or case studies.
We searched PubMed (1966-2006) for relevant studies using keywords and text terms for genital herpes. We accessed the WHO and Health Protection Agency (United Kingdom) website to assess the disease burden of genital herpes and consulted guidelines on genital herpes from the British Association for Sexual Health and HIV (2001) and the Centers for Disease Control and Prevention (CDC, 2006). Additional data and references were obtained from International Union against Sexually Transmitted Infections (IUSTI) meetings, BASHH meetings, the International Herpes Management Forum (IHMF), the World STI/HIV congress, and a personal archive of references.
Genital herpes is caused by infection with herpes simplex virus (HSV), commonly by HSV type 2 and now increasingly by type 1. Both HSV-1 and HSV-2 infections are acquired from contact with infectious secretions on oral, genital, or anal mucosal surfaces. Genital herpes can also be acquired from contact with lesions from other anatomical sites such as the eyes and non-mucosal surfaces such as herpetic whitlow on fingers or from lesions on the buttocks and trunk.
In the UK, there was a 15% increase in the number of diagnoses of first attack of genital herpes from 16479 cases in 1995 to 19180 cases in 2004.1 In the United States, an estimated 40-60 million people are infected with HSV-2, with an incidence of 1-2 million infections and 600000-800000 clinical cases a year.2 The prevalence of genital herpes in developing countries varies from 2-74% according to the country. In some African countries that are experiencing HIV epidemics, HSV-2 is highly prevalent (≥70%), and there is evidence that genital HSV increases the risk of HIV infection and that people with both are more likely to transmit HIV infection.3
The initial episode is the first episode of genital infection with either HSV-1 or HSV-2 (box 1). Primary genital herpes is the first episode in an individual with no pre-existing antibodies to either HSV type. A non-primary first episode is the first infection in an individual with pre-existing antibodies to the other HSV type.4 5
Groups of vesicles or ulcers develop in a single anatomical site and heal within 10 days. For the first two years patients may experience an average of five clinical episodes a year, which may reduce in frequency thereafter. Genital HSV caused by type 1 infection recurs less often, and thus typing of infection may inform patient counselling.
Most people with HSV infection have mild unrecognised or subclinical disease and are unaware of their infection. They may shed the virus intermittently in the genital tract and thus transmit the infection to their sexual partners entirely unknowingly. Subclinical shedding occurs most commonly in the first year of infection in patients with genital HSV-2 infection and in individuals with frequent symptomatic recurrences. Perianal shedding is common in HIV negative, HSV-2 seropositive men who have sex with men and are asymptomatic.w1 Most infections of genital herpes are transmitted by people who are unaware that they are infected or who have no symptoms when transmission occurs.
The clinical diagnosis of genital HSV infection has a low sensitivity and specificity; laboratory confirmation of infection and typing of HSV is essential as it influences the management, prognosis, and counselling of patients.
Detection of HSV in clinical lesions—Table 1 compares the methods of detection.detection. Take swabs from the base of the lesion or fluid from a vesicle. For culture tests it is essential that the cold chain (4ºC) is maintained and appropriate media are used. Polymerase chain reaction (PCR) is the most useful test as less meticulous handling of specimens is required.
Serology—Commercial tests that use complement fixation are not type specific. Seroconversion from a zero baseline is usually diagnostic of a primary infection. In the case of recurrent infection, an immune response from a non-zero baseline may be detected. These tests cannot distinguish between initial and recurrent infections, however, and have been replaced by sensitive tests such as enzyme linked immunosorbent assay (ELISA) and radioimmunoassay (RIA). Type specific serology tests (TSSTs), which detect glycoprotein G2 specific to HSV-2 and glycoprotein G1 specific to HSV-1 infection, are the only commercially available diagnostic tools available to identify those with asymptomatic HSV infection and can effectively distinguish the two types with high sensitivity (80-98%) and specificity (≥ 96%).8 Case control studies have shown that there are certain clinical settings when these tests may help the diagnosis of HSV infection9w2-4 (boxes 2 and 3).
General measures (evidence level IV, grade C, table 2) for treating patients with a first episode include cleaning affected areas with normal saline, giving analgesia (systemic or local, such as lidocaine gel), and treating any secondary bacterial infection.infection.
Aciclovir has a good record of safety and efficacy and is available in generic formulations. Other drugs, such as valaciclovir and famciclovir, have less frequent dosing regimens compared with aciclovir (box 4) but are more expensive. Randomised control trials have shown that all three drugs reduce the severity and duration of clinical attacks.10w5 None of these drugs eradicate the infection or latent virus.
There is no evidence of benefit from courses of treatment longer than five days. BASHH guidelines, however, recommend that treatment should be continued beyond five days if new lesions continue to form, if symptoms and signs are severe, or if the patient also has HIV. The guidelines also state that combined oral and topical treatment is of no additional benefit. Numerous over the counter and internet based topical and oral “herbal cures” are available. There is no scientific evidence for the use of essential oils, plant extracts, zinc, and L-lysine, and they have no place in the management of genital herpes.
Our preferred treatment is aciclovir 400 mg orally three times a day for seven days because it is effective, low cost, and patients comply with treatment.
Treatment of recurrent attacks includes supportive therapy, episodic antiviral therapy, or suppressive antiviral therapy. Most recurrent attacks are mild and self limiting however, and can be managed with supportive therapy only. General measures for treating patients include cleaning the affected areas with normal saline, giving analgesia (systemic or local such as lidocaine gel), and treating secondary bacterial infection.
Supportive therapy—Supportive therapy includes saline bathing, the use of analgesia, and counselling of sexual behaviour and can be instituted when recurrences are mild and self limiting.
Episodic antiviral therapy (1a, A)—Initiate episodic antiviral therapy during the prodrome or early in an attack (box 5).w6 Oral aciclovir, valaciclovir,11 and famciclovirw7 reduce the severity and duration by a median of one to two days.w6 w8 w9 Topical antiviral therapy is less effective than systemic therapy.4w10 Randomised controlled trials have shown all these regimens to be effective. Our preferred treatment is aciclovir 400 mg orally three times a day for five days because it is effective and low cost.
Suppressive antiviral therapy (1a, A)—Meta-analyses of randomised controlled trials have shown that suppressive antiviral therapy can significantly reduce (by 70 to 80%) the number of recurrences in patients with frequently recurring (≥6 recurrences a year) genital herpes.12w11 Box 6 shows the recommended regimen. Patients should discontinue treatment after 12 months to assess the ongoing frequency of recurrences. The timing of this should be agreed with the patient, and recurrences should be treated.
A landmark study by Corey et al found that daily suppressive treatment with valaciclovir can reduce HSV-2 transmission among HSV-2 discordant heterosexual couples by 75% for clinical disease and reduce acquisition (measured by serology) by 48%.13 Other antiviral drugs may be effective but have not been investigated.14
Counselling infected people and their sexual partners is integral to the successful management of genital herpes.w12 Physicians should provide counselling to help patients cope with infection and prevent sexual and perinatal transmission.15
We have summarised the various points that physicians need to consider and discuss when counselling patients (box 7). This guide comes from personal practices and guidance from the British Association for Sexual Health and HIV (BASHH), the Centers for Disease Control and Prevention (CDC), and the International Herpes Management Forum. Educational reading material16 and access to web based literature on genital herpes should be provided as part of the counselling process.
Data from the aciclovir pregnancy registry on the use of aciclovir in pregnancy does not show any increase in the number of birth defects.w13
For women who acquire the infection in the first and second trimester treat with oral or intravenous aciclovir in standard doses and plan for vaginal delivery. For women in who vaginal delivery is planned, continuous aciclovir in the last four weeks of pregnancy will reduce the risk of clinical recurrence at term delivery by caesarean section (1b, A).17
All women presenting with the first episode of genital herpes after 34 weeks' gestation should be delivered by caesarean section. If vaginal delivery is unavoidable, treat the mother and baby with aciclovir.
In women with recurrent infection caesarean section should not be performed if there are no genital lesions at the time of delivery. Daily suppressive aciclovir in the last four weeks of pregnancy might prevent recurrences of genital herpes at term and might be cost effective.18w14 If genital lesions are present at the onset of labour, experts recommend delivery by caesarean section.19
Both HSV and HIV have reached epidemic proportions in certain developing countries. Genital herpes caused by HSV-2 infection has been shown to double the risk of becoming infected with HIV through sexual transmission.20 The ulcers and breaks in the genital mucosa and skin caused by HSV-2 infection facilitate entry of the HIV virus. These lesions contain large numbers of CD4 lymphocytes, which are target cells for HIV. Transmission of HIV is more likely from people who also have HSV-2,w15 possibly because of high titres of HIV in genital secretions during HSV-2 reactivation.w16
In patients with HIV or who are otherwise immunocompromised, episodes may be prolonged, more severe, and require a longer duration of antiviral treatment (box 8). A recent study found that treatment with valaciclovir at 1 g a day significantly reduced HIV RNA genital shedding as well as the plasma viral load.21 These data support the hypothesis that therapy for genital HSV infection in people with HIV reduces the risk of their transmitting HIV and may affect the natural progression of HIV infection. Further studies to investigate this are ongoing.
To date the development of effective vaccines has not been promising. Difficulties arise because of the complexity of the life cycle of the virus (latency) and the current lack of understanding of the human mechanism of control of primary and recurrent disease.22 A large scale study of a gD2-AS04 vaccine is being carried out to further evaluate the protective effects in women as initial studies have shown differential effects in men and women.
Genital herpes is an important public health disease that can cause substantial morbidity if it is undiagnosed and untreated. Clinicians should suspect HSV infection in all patients presenting with ulcers in the genital area. Genital HSV infection increases the risk of HIV infection and people with both infections are more likely to transmit HIV to their sexual partners.
Contributors: Both authors contributed equally to the manuscript.
Competing interests: None declared.
Provenance and peer review: Commissioned, peer reviewed.