Gale R. Burstein
Kimberly A. Workowski
Genital herpes is a chronic lifelong viral disease. Herpes genitalis lesions are caused by a large DNA virus, herpes simplex virus (HSV), with two serotypes, herpes simplex type 1 (HSV-1) and herpes simplex type 2 (HSV-2). Although HSV-1 is becoming more prominent as a cause of first-episode genital herpes, most cases of recurrent genital herpes are caused by HSV-2. These viruses have the ability to become latent and recur. Although the herpes genitalis prevalence has increased dramatically over the last 30 years, over the last decade the HSV-2 infection has declined. On the basis of serological studies, genital HSV-2 infection has affected at least 50 million persons in the United States. Most persons infected with HSV-2 have not been diagnosed. Many such persons have mild or unrecognized infections but shed virus intermittently in the genital tract. Most genital herpes infections are transmitted by persons unaware that they have the infection or who are asymptomatic when transmission occurs.
Incidence and Prevalence
in HSV-2 infected females (2% of days) compared to HSV-1 infected females (0.7% of days).
Health care providers have an obligation to inform their patients about the natural history of disease with potential recurrent episodes and the risk of transmitting HSV during asymptomatic periods. Persons with genital HSV infection should be encouraged to inform their current or prospective sexual partners that they have genital herpes.
Infections by Serological Type
Virus particles can be shed in salivary, cervical, and seminal secretions of infected individuals. The virus gains entry into the body through mucosal surfaces or abraded skin and replicates in the epidermal and dermal cells of a susceptible host. After replication, the virus spreads through contiguous cells to mucocutaneous projections of sensory nerves.
In oral herpes, the virus lodges in the trigeminal ganglion; in genital herpes, the sacral dorsal root (S2 to S4) ganglion is the target site. Centrifugal spread can then occur through peripheral sensory nerves back to the skin surface, so that large areas may be involved.
After resolution of the primary disease, the virus becomes latent. Latency appears to be life long but is interrupted by periods of viral reactivation, leading to silent viral shedding or clinically apparent recurrence. Reactivation of latent virus leads to transport of viral genomes to the skin surface, where replication occurs in the dermis and epidermis. Reactivation can be triggered by a variety of stimuli, such as ultraviolet light, immunosuppression, fever, pneumococcal pneumonia, stress, and local trauma. Frequency and clinical severity of reactivation depend on factors such as the host immunological status and the severity and viral type of the primary infection.
Definition of Terms
Classic Primary Infection
over the second week. Crusting and reepithelization occurs in the penile and mons area, but crusting does not occur on mucosal surfaces. Scarring is uncommon. New crops of lesions can form in more than 75% of primary infections. Lesions typically heal by the end of the third week of disease.
First Clinical Episode
Herpes genitalis lesions must be differentiated from early syphilis, chancroid, lymphogranuloma venereum, granuloma inguinale, excoriations, allergic and irritant contact dermatitis, and genital lesions of Behçet syndrome.
Genital herpes is the most prevalent cause of genital ulcers in the United States. Patients with genital ulcer disease can also be infected with syphilis and/or chancroid. The clinical diagnosis of genital herpes is both insensitive and nonspecific. The classical painful multiple vesicular or ulcerative lesions are absent in many infected persons. Up to 50% of first-episode cases of genital herpes are caused by HSV-1, but recurrences and subclinical shedding are much less frequent for genital HSV-1 infection than genital HSV-2 infection. As the distinction between HSV-1 and HSV-2 influences prognosis and counseling, the clinical diagnosis of genital herpes should be confirmed by laboratory testing.
If viral transport medium is not available, substitute sterile distilled water. Leave the swab in the transport medium if transport time is <8 hours. If transport time is longer, swirl the swab vigorously in the medium and remove. If a laboratory courier is used, refrigerate the specimen before pickup.
Some experts believe that HSV serological testing should be included in a comprehensive evaluation for STDs in persons with multiple sexual partners, in persons with HIV infection, and in men who have sex with men (who have a higher risk of HIV acquisition). Screening for HSV-1 or HSV-2 in the general population is not indicated.
Principles of Genital Herpes Management
Antiviral chemotherapy offers clinical benefits to most symptomatic patients and is the mainstay of management. In addition, counseling regarding the natural history of genital herpes, sexual and perinatal transmission, and methods to reduce transmission is integral to clinical management.
Systemic antiviral drugs partially control the symptoms and signs of herpes episodes when used to treat first clinical episodes and recurrent episodes or when used as daily suppressive therapy. However, these drugs neither eradicate latent virus nor affect the risk, frequency, or severity of recurrences after the drug is discontinued. Randomized trials indicate that three antiviral medications provide clinical benefit for genital herpes—acyclovir, valacyclovir, and famciclovir. Valacyclovir is the valine ester of acyclovir and has enhanced absorption on oral administration. Famciclovir, a prodrug of penciclovir, also has high oral bioavailability. Topical therapy with antiviral drugs for genital HSV offers minimal clinical benefit, and is not recommended (Centers for Disease Control and Prevention, 2006).
First Clinical Episode of Genital Herpes
Many patients with first-episode herpes present with mild clinical manifestations but later develop severe or prolonged symptoms. The Centers for Disease Control and Prevention (CDC) (Centers for Disease Control and Prevention, 2006) recommend that patients with initial genital herpes should receive antiviral therapy.
CDC recommended regimens:
Established Herpes Simplex Virus -2 Infection
Most patients with symptomatic, first-episode genital HSV-2 infection subsequently experience recurrent episodes of genital lesions; recurrences are much less frequent following initial genital HSV-1 infection. Intermittent asymptomatic shedding occurs in all patients with genital HSV-2 infection, even in those with long-standing or clinically silent infection. Treatment options should be discussed with all patients, regardless of severity or frequency of recurrent outbreaks. Antiviral therapy for recurrent genital herpes can be administered either episodically to diminish or shorten the duration of lesions, or continuously as suppressive therapy to reduce the frequency of recurrences and possibly decrease the risk of transmission to susceptible partners.
Suppressive Therapy for Recurrent Genital Herpes
Suppressive therapy reduces the frequency of genital herpes recurrences by 70% to 80% among patients who have frequent recurrences (i.e., ≥6 recurrences/year), and many patients report no symptomatic outbreaks. Treatment is also effective in patients with less frequent recurrences. Safety and efficacy have been documented among patients receiving daily therapy with acyclovir for as long as 6 years, and with valacyclovir or famciclovir for 1 year. Quality of life is often improved in patients with frequent recurrences who receive suppressive compared with episodic treatment. The frequency of recurrent outbreaks diminishes over time in many patients, and the patient's psychological adjustment to the disease may change. Therefore, the need to continue therapy should be discussed periodically during suppressive treatment (e.g., once a year).
CDC recommended regimens:
Overall, valacyclovir and famciclovir are most likely comparable to acyclovir in clinical outcome. Ease of administration and cost also are important considerations for prolonged treatment.
Episodic Therapy for Recurrent Genital Herpes
Effective episodic treatment of recurrent herpes requires initiation of therapy within 1 day of lesion onset, or during the prodrome that precedes some outbreaks. In those with known genital infection, a supply of drug or a prescription can be provided with instructions to self-initiate treatment immediately when symptoms begin.
CDC recommended regimens:
Intravenous acyclovir therapy should be provided for patients who have severe disease or complications that necessitate hospitalization, such as disseminated infection, pneumonitis, hepatitis, or complications of the central nervous system (e.g., meningitis or encephalitis). The recommended regimen is acyclovir 5 to 10 mg/kg body weight IV every 8 hours for 2 to 7 days or until clinical improvement is observed, followed by oral antiviral therapy to complete at least 10 days of total therapy (Centers for Disease Control and Prevention, 2006).
Human Immunodeficiency Virus Infection
Immunocompromised patients may have prolonged or severe episodes of genital, perianal, or oral herpes. Lesions caused by HSV are common among HIV-infected patients and may be severe, painful, and atypical. HSV shedding is increased in HIV-infected persons. Although antiretroviral therapy reduces the severity and frequency of symptomatic genital herpes, frequent subclinical shedding still occurs. Subclinical mucosal HSV is associated with higher loads of mucosal HIV. Suppressive or episodic therapy with oral antiviral agents is effective in decreasing the clinical manifestations of HSV among HIV-seropositive persons. HIV-infected persons are likely to be more contagious for HSV; the extent to which suppressive antiviral therapy will decrease HSV transmission from this population is unknown. As HIV-infected persons are evaluated for a variety of chronic infections that may become problematic with increasing immunosuppression, some experts suggest that type-specific serologies should be offered to HIV-infected persons during their initial evaluation, and suppressive antiviral therapy considered.
CDC recommended regimens for daily suppressive therapy in persons infected with HIV:
Recommended regimens for episodic infection in persons infected with HIV:
In the doses recommended for treatment of genital herpes, acyclovir, valacyclovir, and famciclovir are safe for use in immunocompromised patients. For severe cases, initiating therapy with acyclovir 5 to 10 mg/kg body weight IV every 8 hours may be necessary.
If lesions persist or recur in a patient receiving antiviral treatment, HSV resistance should be suspected and a viral isolate obtained for sensitivity testing. Such patients should be managed in consultation with a specialist, and alternate therapy, such as foscarnet or topical cidofovir gel 1%, should be considered.
Management of Sex Partners
The sex partners of patients who have genital herpes likely benefit from evaluation and counseling. Symptomatic sex partners should be evaluated and treated in the same manner as patients who have genital lesions. Asymptomatic sex partners of patients who have genital herpes should be questioned concerning histories of genital lesions, and offered type-specific serological testing for HSV infection.
For Teenagers and Parents
http://www.ashastd.org". The Herpes Resource Center (HRC, supported by the American Social Health Association [ASHA]) focuses on increasing education, public awareness, and support to anyone concerned about herpes. The HRC provides accurate information about herpes with informational Web sites, brochures and books, a hotline, a chat room, e-mail responses to questions, and referrals to local Support Groups. Accessed May 7, 2007.
National Herpes Hotline (supported by ASHA).Provides accurate information and appropriate referrals to anyone concerned about herpes. Telephone:1-800-277-8922.
http://www.cdc.gov/std/Herpes/default.htm. Centers for Disease Control and Prevention. Provides patient HSV information. Accessed May 7, 2007.
http://www.herpeshelp.com/(Supported by Glaxo Wellcome). Herpes help informational Web site. Accessed May 7, 2007.
http://www.iwannaknow.org/(Supported by ASHA). Provides information to teens and parents about teen sexual health and STDs. Accessed May 7, 2007.
http://www.plannedparenthood.org/. Planned Parenthood HSV informational Web site. Accessed May 7, 2007.
For Health Professionals
http://www.cdc.gov/STD/treatment. Sexually Transmitted Diseases Treatment Guidelines, 2006. Accessed May 7, 2007.
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