Clinical Evidence Concise
A Publication of BMJ Publishing Group
Am Fam Physician. 2004 Sep 1;70(5):912-914.
This clinical content conforms to AAFP criteria for evidence-based continuing medical education (EB CME). EB CME is clinical content presented with practice recommendations supported by evidence that has been systematically reviewed by an AAFP-approved source. The practice recommendations in this activity are available at http://www.clinicalevidence.com/ceweb/conditions/seh/1603/1603.jsp.
What are the effects of interventions to prevent transmission?
LIKELY TO BE BENEFICIAL
Male Condom Use to Prevent Sexual Transmission from Infected Men to Noninfected Sex Partners. Limited evidence from a prospective cohort study suggests that condom use by men infected with genital herpes may reduce transmission of herpes simplex virus type 2 (HSV-2) to their noninfected sex partners. (Categorization based on observational evidence)
Antiviral Treatment to Prevent Transmission. We found no systematic reviews or randomized controlled trials (RCTs) on the effects of antiviral treatments to prevent sexual transmission.
Cesarean Delivery in Women with Genital Lesions at Term. We found no systematic review or RCTs on the effects of cesarean delivery on mother-to-infant transmission of genital herpes in patients with genital lesions at term. The procedure carries the risk of increased maternal morbidity and mortality.
Daily Oral Antiviral Treatment in Late Pregnancy (36 or More Weeks of Gestation) in Women with a History of Genital Herpes. One systematic review and two subsequent RCTs found that acyclovir reduced the rate of genital lesions at term in women with first or recurrent episodes of genital HSV during pregnancy. The review and the RCTs provided insufficient evidence to assess the effect of oral antiviral treatment during pregnancy on neonatal infection.
Female Condoms. We found no systematic review or RCTs on the effects of female condoms to prevent sexual transmission.
HSV-2 Glycoprotein-D-adjuvant Vaccine in HSV-1 and HSV-2-seronegative Women. Limited evidence from one RCT comparing recombinant HSV-2 glycoprotein-D-adjuvant vaccine versus placebo showed protection of the vaccine against new genital herpes infection in women who had been seronegative for HSV-1 and HSV-2 at baseline.
HSV-2 Glycoprotein-D-adjuvant Vaccine in Men and HSV-1-seropositive Women. Limited evidence from one RCT comparing recombinant HSV-2 glycoprotein-D-adjuvant vaccine versus placebo showed no protection of the vaccine against new genital herpes infection in women who had been seropositive for HSV-1 at baseline or in men.
Male Condom Use to Prevent Transmission from Infected Women to Noninfected Men. Limited evidence from one prospective cohort study suggests that male condom use may provide no protection from transmission of HSV-2 to noninfected men from their infected female partners.
Other Forms of Vaccination. We found no good evidence on other forms of vaccination.
Serologic Screening and Counseling in Late Pregnancy. We found no systematic review or RCTs on the effects of interventions to prevent maternal infection in late pregnancy (such as serologic screening and counseling).
UNLIKELY TO BE BENEFICIAL
Recombinant Glycoprotein Vaccine (gB2 and gD2). One RCT found no significant difference between recombinant glycoprotein vaccine (gB2 plus gD2) and placebo in the prevention of HSV-2 infection.
What are the effects of treatments in people with a first episode of genital herpes?
Oral Antiviral Treatment Versus Placebo in First Episodes. RCTs found that oral antiviral treatment versus placebo decreases the duration of lesions, symptoms, and viral shedding, and reduces neurologic complications in people with a first episode of genital herpes. Two small RCTs provided insufficient evidence to assess time to recurrence and frequency of recurrence compared with placebo.
Different Routes of Antiviral Administration in First Episodes. We found no systematic reviews or RCTs comparing different routes of administration in antiviral treatment. A nonrandomized comparison of results of different trials from one institution suggests that systemic (oral or intravenous) antiviral treatment may be more effective and associated with fewer reported side effects than topical medication. (Categorization based on observational or nonrandomized evidence in the context of practical and ethical problems of performing RCTs.)
Different Types of Oral Treatment in First Episodes. RCTs found no difference in clinical outcomes among oral acyclovir, valacyclovir, and famciclovir in people with a first episode of genital herpes. (Categorization based on observational or nonrandomized evidence in the context of practical and ethical problems of performing RCTs.)
What interventions reduce the impact of recurrence?
Daily Oral Antiviral Treatment in People with High Rates of Recurrence. RCTs have found that daily maintenance treatment with oral antiviral agents reduces the frequency of recurrences and improves psychosocial morbidity in people with frequent recurrence compared with placebo.
Oral Antiviral Treatment Taken at the Start of a Recurrence. One systematic review and one subsequent RCT found that oral antiviral treatment taken at the start of recurrence reduced the duration of lesions, episode duration, and viral shedding and increased the rate of aborted recurrences compared with placebo in people with recurrent genital herpes. RCTs found no significant differences among different antiviral agents. All agents were found to be similarly effective in reducing the duration of symptoms and viral shedding compared with placebo. One RCT found no difference between valacyclovir taken for three versus five days.
Psychotherapy to Reduce Recurrence. One systematic review found insufficient evidence on the effects of psychotherapy on genital herpes recurrence.
What are the effects of treatments in people with genital herpes and HIV infection?
Oral Antiviral Treatment in People Immunocompromised with Human Immunodeficiency Virus (HIV) Infection. We found no systematic review or RCTs evaluating antiviral treatment for genital herpes in people immunocompromised with HIV infection. However, evidence from other settings suggests that antiviral agents may be effective treatments of genital herpes in immunocompromised people. (Categorization based on observational or nonrandomized evidence in the context of practical and ethical problems of performing RCTs.)
Genital herpes is an infection with HSV-1 or HSV-2, causing ulceration in the genital area. HSV infections can be confirmed on the basis of virologic and serologic findings. Types of infection include first episode primary infection, which is defined as HSV confirmed in a person without prior findings of HSV-1 or HSV-2 antibodies; first episode nonprimary infection, which is HSV-2 in a person with prior HSV-1 antibodies or vice versa; first recognized recurrence, which is HSV-1 or HSV-2 confirmed in a person with prior findings of HSV-1 or HSV-2 antibodies; and recurrent genital herpes, which is caused by reactivation of latent HSV. HSV-1 also can cause gingivostomatitis and orolabial ulcers; HSV-2 also can cause other types of herpes infections, such as ocular herpes; and both can cause infection of the central nervous system (e.g., encephalitis).
Genital herpes infections are among the most common sexually transmitted diseases. Seroprevalence studies show that 22 percent of adults in the United States have HSV-2 antibodies.1 A United Kingdom study found that 23 percent of adults attending sexual medicine clinics and 7.6 percent of blood donors in London had antibodies to HSV-2.2 Seroprevalence of HSV-2 increased by 30 percent (95 percent confidence interval [CI], 15.8 to 45.8 percent) between the periods 1976 to 1980 and 1988 to 1994.1 However, it should be noted that although antibody levels prove the existence of present or past infections, they do not differentiate between possible manifestations of HSV-2 infections (e.g., genital, ocular). Thus, the figures have to be treated with caution when applied to genital herpes only.
HSV-1 and HSV-2 can cause a first episode of genital infection, but HSV-2 is more likely to cause recurrent disease.3 Most people with HSV-2 infection have only mild symptoms and remain unaware that they have genital herpes. However, these people can pass on the infection to sexual partners and newborns.4,5
Sequelae of HSV infection include neonatal HSV infection, opportunistic infections in immunocompromised people, recurrent genital ulceration, and psychosocial morbidity. HSV-2 infection is associated with an increased risk of HIV transmission and acquisition.6 The most common neurologic complications are aseptic meningitis (reported in about 25 percent of women during primary infection) and urinary retention (reported in up to 15 percent of women during primary infection).5 The absolute risk of neonatal infection is high (41 percent, 95 percent CI, 26 to 56 percent) in infants born to women who acquire infection near the time of labor7,8 and low (less than 3 percent) in women with established infection, even in those who have a recurrence at term.7,8 About 15 percent of neonatal infections result from postnatal transmission from oral lesions of relatives or hospital personnel.5
SEARCH DATE: July 2003
editor’s note: Recombinant glycoprotein vaccine is not available in the United States.
Adapted with permission from Jungmann EM. Genital herpes. Clin Evid Concise 2004;11:390–3.
1. Fleming DT, McQuillan GM, Johnson RE, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med. 1997;337:1105–11.
2. Cowan FM, Johnson AM, Ashley R, et al. Antibody to herpes simplex virus type 2 as serological marker of sexual lifestyle in populations. BMJ. 1994;309:1325–9.
3. Benedetti J, Corey L, Ashley R. Recurrence rates in genital herpes after symptomatic first-episode infection. Ann Intern Med. 1994;121:847–54.
4. Mertz GJ, Schmidt O, Jourden JL, et al. Frequency of acquisition of first-episode genital infection with herpes simplex virus from symptomatic and asymptomatic source contacts. Sex Transm Dis. 1985;12:33–9.
5. Whitley RJ, Kimberlin DW, Roizman B. Herpes simplex viruses. Clin Infect Dis. 1998;26:541–53.
6. Wald A, Link K. Risk of HIV infection in HSV-2 sero-positive persons: a meta-analysis. J Infect Dis. 2002;185:45–52.
7. Brown ZA, Selke SA, Zeh J, et al. Acquisition of herpes simplex virus during pregnancy. N Engl J Med. 1997;337:509–15.
8. Smith J, Cowan FM, Munday P. The management of herpes simplex virus infection in pregnancy. Br J Obstet Gynaecol. 1998;105:255–68.
This is one in a series of chapters excerpted from Clinical Evidence Concise, published by the BMJ Publishing Group, Tavistock Square, London, United Kingdom. Clinical Evidence Concise is published in print twice a year and is updated monthly online. Each topic is revised every eight months, and subscribers should view the most up-to-date version at http://www.clinicalevidence.com. If you are interested in contributing to Clinical Evidence, please contact Claire Folkes (firstname.lastname@example.org). This series is part of the AFP’s CME. See “Clinical Quiz” on page 813.
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