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Am Fam Physician. 2005;72(8):1557-1561

A more recent USPSTF on genital herpes is available.

This statement summarizes the U.S. Preventive Services Task Force (USPSTF) recommendations on screening for genital herpes simplex virus (HSV) infection and the supporting scientific evidence and updates the 1996 recommendations contained in the Guide to Clinical Preventive Services, 2d ed.1 Explanations of the ratings and of the strength of overall evidence are given in Table 1and Table 2, respectively. The complete information on which this statement is based, including evidence tables and references, is included in the brief update2 on this topic, available through the USPSTF Web site athttp://www.uspreventiveservicestaskforce.org. The recommendation also is posted on the Web site of the National Guideline Clearinghouse athttp://www.guideline.gov.

The USPSTF grades its recommendations according to one of five classifications (A, B, C, D, or I) reflecting the strength of evidence and magnitude of net benefit (benefits minus harms).
A.The USPSTF strongly recommends that clinicians provide [the service] to eligible patients. The USPSTF found good evidence that [the service] improves important health outcomes and concludes that benefits substantially outweigh harms.
B.The USPSTF recommends that clinicians provide [the service] to eligible patients. The USPSTF found at least fair evidence that [the service] improves important health outcomes and concludes that benefits outweigh harms.
C.The USPSTF makes no recommendation for or against routine provision of [the service]. The USPSTF found at least fair evidence that [the service] can improve health outcomes but concludes that the balance of benefits and harms is too close to justify a general recommendation.
D.The USPSTF recommends against routinely providing [the service] to asymptomatic patients. The USPSTF found at least fair evidence that [the service] is ineffective or that harms outweigh benefits.
I.The USPSTF concludes that the evidence is insufficient to recommend for or against routinely providing [the service]. Evidence that [the service] is effective is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.
The USPSTF grades the quality of the overall evidence for a service on a three-point scale (good, fair, or poor).
Good:Evidence includes consistent results from well-designed, well-conducted studies in representative populations that directly assess effects on health outcomes.
Fair:Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies; generalizability to routine practice; or indirect nature of the evidence on health outcomes.
Poor:Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information on important health outcomes.

Summary of Recommendations

The USPSTF recommends against routine serologic screening for HSV infection in asymptomatic pregnant women at any time during pregnancy to prevent neonatal HSV infection. D recommendation.

The USPSTF found fair evidence that screening asymptomatic pregnant women using serologic screening tests for HSV antibody does not reduce transmission of HSV to newborn infants. Women who develop primary HSV infection during pregnancy have the highest risk for transmitting HSV infection to their infants. Because these women initially are seronegative, serologic screening tests for HSV (e.g., enzyme-linked immunosorbent assay [ELISA], immunoblot, and western blot assay [WBA]) do not accurately detect those at highest risk. There is no evidence that treating seronegative women decreases risk for neonatal infection. There is limited evidence that the use of antiviral therapy in women with a history of recurrent HSV infection, or performance of cesarean section in women with active HSV lesions at the time of delivery, decreases neonatal herpes infection. There also is limited evidence of the safety of antiviral therapy in pregnant women and neonates.

The potential harms of screening include false-positive test results, labeling, and anxiety, as well as false-negative tests and false reassurance, although these potential harms are not well studied. The USPSTF determined that there are no benefits associated with screening, and therefore the potential harms outweigh the benefits.

The USPSTF recommends against routine serologic screening for HSV infection in asymptomatic adolescents and adults. D recommendation.

The USPSTF found no evidence that screening asymptomatic adolescents and adults with serologic tests for HSV antibody improves health outcomes or symptoms, or reduces transmission of the disease. There is good evidence that serologic screening tests can accurately identify those persons who have been exposed to HSV. There is good evidence that antiviral therapy improves health outcomes in symptomatic persons (e.g., those with multiple recurrences); however, there is no evidence that the use of antiviral therapy improves health outcomes in those with asymptomatic infection. The potential harms of screening include false-positive test results, labeling, and anxiety, although there is limited evidence of any potential harms of screening or treatment. The USPSTF determined that the benefits of screening are minimal, at best, and that the potential harms outweigh the potential benefits.

Clinical Considerations

• Serologic screening tests for genital HSV infection can detect prior infection with HSV in asymptomatic persons, and new type-specific serologic tests can differentiate between HSV-1 and HSV-2 exposure (these tests cannot differentiate between oral versus genital HSV exposure). However, given the natural history of genital HSV infection, there is limited evidence to guide clinical intervention in those asymptomatic persons who have positive serologic test results. False-positive test results may lead to labeling and psychologic stress without any potential benefit to patients. Negative test results (i.e., both false-negative and true-negative results) may provide false reassurance to continue high-risk sexual behaviors.

• There is new, good-quality evidence demonstrating that systemic antiviral therapy effectively reduces viral shedding and recurrences of genital HSV outbreaks in adolescents and adults with a history of recurrent genital herpes. There are multiple effective regimens that may be used to prevent the recurrence of clinical genital HSV infection.

• The USPSTF did not examine the evidence for the effectiveness of counseling to avoid high-risk sexual behavior in persons with a history of genital herpes to prevent transmission to discordant partners, or for the primary prevention of genital HSV infection in persons not infected with HSV. There are known health benefits of avoiding high-risk sexual behavior, including prevention of sexually transmitted infections and human immunodeficiency virus infection.

• Primary HSV infection during pregnancy presents the greatest risk for transmitting infection to the newborn. The fact that women with primary HSV infection are initially seronegative limits the usefulness of screening with antibody tests. The USPSTF did not find any studies testing the usefulness of antibody screening to find and prophylactically treat seronegative pregnant women (i.e., those at risk for primary HSV infection). However, the number of seronegative pregnant women who would need to be treated to theoretically avoid one primary infection would be very high, making the potential benefit small. At the same time, the potential harm to many low-risk women and fetuses from the side effects of antiviral therapy may be great.

• There is fair evidence that antiviral therapy in late pregnancy can reduce HSV recurrence and viral shedding at delivery in women with recurrent HSV infection. However, there is no evidence that the use of antiviral agents in women with a history of HSV infection leads to reduced neonatal infection. Likewise, there is limited information on the benefits of screening women in labor for signs of active genital HSV lesions, and for the performance of cesarean delivery on women with lesions.

Discussion

Genital herpes simplex infection (commonly caused by HSV-2, occasionally by HSV-1) is the most prevalent sexually transmitted disease in the United States.3 Seroprevalence surveys show that one out of five persons 12 years of age and older in the United States has been infected with HSV-2, and the rate is even higher among adults and women.3 An estimated 1.6 million new HSV-2 infections occur in the United States annually.4 Symptoms vary based on phase of infection: primary infection manifests as tender vesicular lesions, dysuria, itching, lymphadenopathy, fever, malaise, and myalgia; recurrent infections manifest as localized lesions; and viral shedding usually is asymptomatic. HSV in pregnant women can be transmitted vertically to the infant, primarily at the time of delivery. Primary infection during pregnancy, although less prevalent than recurrent infection, is associated with a much higher transmission rate (33 versus 3 percent transmission rates in primary and recurrent infection, respectively).5 Neonatal HSV disease is diagnosed in approximately one of every 3,000 deliveries in the United States, resulting in an estimated 1,500 cases annually.6 Infants infected with HSV may be born prematurely and with low birth weight; symptoms vary from mild localized disease to severe disseminated infection. Encephalitis and disseminated disease secondary to neonatal HSV infection are associated with long-term morbidity and mortality.7 Intrauterine infections (i.e., congenital herpes) are very rare (one out of 100,000 births), although they result in serious sequelae including hydrocephalus, microcephaly, and chorioretinitis.

The USPSTF reviewed the evidence from 1996 to 2002 and found no direct evidence that screening asymptomatic adolescents and adults, including pregnant women, for genital HSV infection reduces symptomatic recurrences or transmission of disease.

Methods for HSV detection include viral culture, polymerase chain reaction (PCR) testing, and antibody-based tests including WBA and type-specific glycoprotein G serologic tests. Viral culture has a sensitivity of 50 percent and a specificity of nearly 100 percent. PCR testing has a sensitivity of 80 to 90 percent for specimens obtained from lesions. Serologic tests are used to detect previous HSV infection in asymptomatic patients or to diagnose infection in a symptomatic patient when culture is not feasible or the clinical syndrome is unclear. WBA is considered the gold standard, with a sensitivity and specificity of greater than 99 percent.8,9 Currently, two type-specific glycoprotein G serologic tests, the ELISA and immunoblot tests, are available commercially in the United States; they have a sensitivity and specificity comparable to WBA.10

The USPSTF examined the evidence for the effectiveness of antiviral therapy in reducing symptomatic recurrences and transmission in adolescents and adults. Three good-quality randomized controlled trials (RCTs) and one fair-quality RCT examined the effectiveness of antiviral agents in the suppression of HSV recurrences.1114 These studies showed that in persons with six or more recurrences annually, those taking antiviral therapy had a significantly longer delay in the time to first recurrence compared with the placebo group. One good-quality RCT15 of women with a history of recurrent HSV showed that the relative risk for subclinical viral shedding was lower in women who took acyclovir (Zovirax) compared with women in the placebo group.

The USPSTF examined the evidence for the effectiveness of antiviral therapy and condom use in reducing HSV-2 transmission in adolescents and adults. A good-quality, randomized, multicenter, placebo-controlled trial16 showed that once-daily valacyclovir (Valtrex) reduced sexual transmission of genital HSV-2 in monogamous heterosexual couples who were discordant for HSV-2 infection. In this study,16 fewer of the susceptible partners developed clinical symptoms, and fewer of the source partners had evidence of viral shedding in the treatment group compared with the placebo group. One prospective cohort study17 suggested that male condom use in 25 percent of episodes of sexual intercourse was associated with a lower risk for HSV-2 acquisition among women but not among men. However, condom use was low throughout the study, with only 61 percent of couples reporting ever using condoms and only 8 percent reporting condom use for each sexual act, despite counseling at each clinic follow-up visit. In a second prospective cohort study,18 the use of condoms for more than 65 percent of episodes of sexual intercourse offered significant and comparable protection against HSV-2 acquisition for men and women.

The USPSTF examined the evidence for interventions in pregnant women to reduce HSV recurrence at the time of delivery, including antiviral use in late pregnancy and cesarean section delivery. One fair-quality RCT19 of women with recurrent genital HSV infection evaluated the use of suppressive acyclovir after 36 weeks’ gestation and found that 6 percent of patients treated with acyclovir had clinical HSV infection at delivery compared with 14 percent of patients in the placebo group. No patients in the acyclovir group had positive HSV cultures, compared with 6 percent of the placebo group. Three poor-quality studies2022 examined the reduction of neonatal infection as an outcome of antiviral therapy in pregnant women with a history of HSV infection. One poor-quality study23 examined the use of cesarean section to reduce neonatal infection.

Potential harms of screening for HSV-2 include labeling, anxiety, and disrupting partner relationships. A qualitative assessment of the psychosocial impact of a serologic diagnosis of HSV-2 concluded that patients may experience strong psychologic responses to their diagnoses.24 False-positive test results may lead to needless work-up and anxiety. Negative test results may provide false reassurance to continue high-risk sexual behavior. Potential harms of antiviral treatment may include drug hypersensitivity and renal impairment; however, antiviral treatments are generally well tolerated with mild harms.1113 There is limited evidence on the safety of antiviral treatments during pregnancy.25,26

A cost analysis of oral acyclovir prophylaxis in late pregnancy was compared with the current standard of cesarean delivery for women with genital HSV lesions. This analysis demonstrated that prophylactic acyclovir and monitoring of infants exposed to HSV during a noncesarean delivery was least expensive ($400,000 per neonatal infection prevented), whereas the use of cesarean section alone for women with active lesions at the time of delivery was most expensive ($1.3 million per neonatal infection prevented).27 Another study28 found that screening at-risk pregnant women and suppressive therapy in their seropositive partners were more costeffective interventions (at a cost of $363,000 per neonatal infection prevented) compared with no management or cesarean section delivery for women with lesions.

Further research is needed to define the clinical significance and natural history of asymptomatic persons who have seropositive test results, to identify effective strategies to decrease HSV transmission, and to examine the benefits of antiviral suppression and cesarean section delivery for pregnant women in reducing neonatal infection. Previous literature examining various study vaccines have reported poor effictiveness,29,30 and vaccine research is ongoing.

Recommendations of Others

The American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics guidelines are available in print.31 ACOG recommends that all women and their partners be asked about a history of HSV infection, and that women with a history of genital HSV infection be questioned about recent symptoms and undergo careful examination of the perineum before delivery. ACOG recommends cesarean delivery for all women with active primary and recurrent lesions at the time of delivery. ACOG does not recommend screening nonpregnant women for HSV; ACOG makes treatment recommendations, including methods to reduce the risk of transmission among discordant couples. The Centers for Disease Control and Prevention’s HSV treatment recommendations can be accessed online athttp://www.cdc.gov.32

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