Sexually Transmitted Infections: Herpes

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Chapter 50 Sexually Transmitted Infections: Herpes

INTRODUCTION

Description: Infection by the herpes simplex virus (HSV) results in recurrent symptoms that range from uncomfortable to disabling, and there is a special risk to the neonate when herpes infection occurs during pregnancy.
Prevalence: Forty-five to 50 million recurrent cases; 1 million new cases per year; one in four women have been infected.
Predominant Age: 15 to 30 years (85%).
Genetics: No genetic pattern.

ETIOLOGY AND PATHOGENESIS

Causes: Roughly 80% of genital herpes infections are caused by HSV type 2, with the remaining 20% caused by the HSV type 1 virus. (Up to 50% of first-episode cases of genital herpes are caused by HSV-1.) Exposure to type 1 virus often happens in childhood and causes oral “cold sores.” Previous infection with type 1 virus appears to provide some immunity to type 2 infections. The incubation period from infection to symptoms is generally approximately 6 days (range 3 to 9), with first episodes lasting from 10 to 12 days. The majority of patients with symptomatic, first-episode genital HSV-2 infection subsequently have recurrent episodes; recurrences are less frequent after initial genital HSV-1 infection.
Risk Factors: Roughly 75% of sexual partners of infected individuals contract the disease if intercourse occurs during viral shedding. Patients are infectious during the period from first prodrome through crusting of the lesions. Viral shedding may also occur asymptomatically. (Persons unaware that they have the infection or who are asymptomatic when transmission occurs transmit the majority of genital herpes infections.) Nonsexual transmission has not been documented.

CLINICAL CHARACTERISTICS

Signs and Symptoms

• Prodromal phase—mild paresthesia and burning (beginning approximately 2 to 5 days after infection)
• Progresses to very painful vesicular and ulcerated lesions, 3 to 7 days after exposure (may prompt hospitalization in up to 10% of patients)
• Dysuria caused by vulvar lesions, urethral and bladder involvement, or autonomic dysfunction (may lead to urinary retention)
• Malaise, low-grade fever, and inguinal adenopathy (40%)
• Systemic symptoms, including aseptic meningitis, fever, headache, and meningismus, can be found in 70% of patients 5 to 7 days after the appearance of the genital lesions in primary infections

DIAGNOSTIC APPROACH

Differential Diagnosis

• Chancroid
• Syphilis
• Granuloma inguinale
• Folliculitis

Associated Conditions: Other sexually transmitted diseases, cervicitis.

Workup and Evaluation

Laboratory: Viral cultures (including type-specific serologic tests) of material taken by swab from the lesions (95% sensitivity). Smears of vesicular material may also be stained with Wright’s stain to visualize giant multinucleated cells with characteristic eosinophilic intranuclear inclusions.
Imaging: No imaging indicated.
Special Tests: Scrapings from the base of vesicles may be stained using immunofluorescence techniques to detect the presence of viral particles.
Diagnostic Procedures: History, physical examination, viral culture, and serologic testing.

Pathologic Findings

The virus replicates in the parabasal and intermediate cells of the skin. It passes from cell to cell until it encounters nerve cell endings, providing access to local ganglia. Typical lesions consist of clear vesicles that lyse, progressing to shallow, painful ulcers with a red border. These may coalesce, becoming secondarily infected and necrotic.

MANAGEMENT AND THERAPY

Nonpharmacologic

General Measures: Topical cleansing, sitz baths followed by drying with a heat lamp or hair dryer, analgesics.
Specific Measures: Topical analgesics (lidocaine [Xylocaine] 2% jelly, nonprescription throat spray with phenol), antiviral agents. If secondary infections occur, therapy with a local antibacterial cream, such as Neosporin, is appropriate.
Diet: No specific dietary changes indicated.
Activity: Pelvic rest until lesions have healed.
Patient Education: American College of Obstetricians and Gynecologists Patient Education Pamphlet AP009 (How to Prevent Sexually Transmitted Diseases). Patients should be advised to have all sexual partners seen for diagnosis and treatment. (Counseling regarding the natural history of genital herpes, sexual and perinatal transmission, and methods to reduce transmission is integral to clinical management.)

Drug(s) of Choice

Acute (begun within 48 hours of onset)—acyclovir ointment (Zovirax or generic 5% applied locally every 3 hours) or acyclovir (400 mg PO three times a day or 200 mg PO five times a day while lesions are present) or famciclovir (Famvir 250 mg PO three times a day for 7 to 10 days) or valacyclovir (Valtrex, 1 g PO twice a day for 5 days) will decrease the duration of symptoms and viral shedding. However, these later therapies have not been shown to decrease the likelihood of recurrence and the shortening of symptom duration is often minimal.
For frequent recurrences or suppression—acyclovir (200 mg PO three times a day or 400 mg PO twice a day, increased to five times per day with lesions) or famciclovir (Famvir, 125 mg PO twice a day for 5 days during outbreaks) or valacyclovir (Valtrex 500 mg to 1 gm PO daily) is effective in decreasing frequency and severity of flare-ups, but use is limited to less than 6 months.
Contraindications: Known or suspected hypersensitivity. Acyclovir is pregnancy category C; famciclovir and valacyclovir are pregnancy category B. Suppressive therapy should not be used for pregnant patients.
Precautions: Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome has been reported in some patients with human immunodeficiency virus (HIV) taking valacyclovir. It has not been encountered in patients who are immunocompetent. Antiviral agents should be used with caution in patients with compromised renal function.

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Interactions: Antiviral agents may interact with or enhance the effects of nephrotoxic agents.

Alternative Drugs

In severe infections, acyclovir 5 to 10 mg/kg IV every 8 hours for 5 to 7 days may be required.

FOLLOW-UP

Patient Monitoring: Normal health maintenance. Watch for possible recurrence.
Prevention/Avoidance: Sexual continence during prodrome to full healing, use of condoms to reduce risk, sexual monogamy.
Possible Complications: Between 60% and 90% of patients have recurrences of the herpetic lesions in the first 6 months after initial infection. Although generally shorter and milder, these recurrent attacks are no less virulent.
Expected Outcome: Healing of the lesions is generally complete. Inguinal adenopathy may persist for several weeks after the resolution of the vulvar lesions. Suppuration is uncommon. Complete resolution of all symptoms occurs in 2 to 4 weeks.

MISCELLANEOUS

Pregnancy Considerations: Significant risk to neonate if acute infection or viral shedding is occurring at the time of delivery or rupture of the membranes. Infection is also associated with an increased risk of early fetal loss. The risk for transmission to the neonate from an infected mother is high (30% to 50%) among women who acquire genital herpes near the time of delivery and is low (<1%) among women with histories of recurrent herpes at term or who acquire genital HSV during the first half of pregnancy. Women with recurrent genital herpetic lesions at the onset of labor should give birth by cesarean delivery to prevent neonatal herpes; however, this does not completely eliminate the risk. Acyclovir may be administered orally to pregnant women with first-episode genital herpes or severe recurrent herpes and should be administered IV to pregnant women with severe HSV infection. Acyclovir treatment late in pregnancy reduces the frequency of cesarean deliveries among women who have recurrent genital herpes by diminishing the frequency of recurrences at term.
ICD-9-CM Codes: 054.11 (Vulvovaginal).

REFERENCES

Level I

Aoki FY, Tyring S, Diaz-Mitoma F, et al. Single-day patient initiated famciclovir therapy for recurrent genital herpes: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2006;42:8.

Sheffield JS, Hill JB, Hollier LM, et al. Valacyclovir prophylaxis to prevent recurrent herpes at delivery: a randomized clinical trial. Obstet Gynecol. 2006;108:141.

Watts DH, Brown ZA, Money D, et al. A double-blind, randomized, placebo-controlled trial of acyclovir in late pregnancy for the reduction of herpes simplex virus shedding and cesarean delivery. Am J Obstet Gynecol. 2003;188:836.

Level II

Andrews WW, Kimberlin DF, Whitley R, et al. Valacyclovir therapy to reduce recurrent genital herpes in pregnant women. Am J Obstet Gynecol. 2006;194:774.

Benedetti JK, Corey L, Ashley R. Recurrence rates in genital herpes after symptomatic first-episode infection. Ann Intern Med. 1994;121:847.

Bryson Y, Dillon M, Bernstein DI, et al. Risk of acquisition of genital herpes simplex virus type 2 in sex partners of persons with genital herpes: a prospective couple study. J Infect Dis. 1993;167:942.

Cone RW, Swenson PD, Hobson AC, et al. Herpes simplex virus detection from genital lesions: a comparative study using antigen detection (HerpChek) and culture. J Clin Microbiol. 1993;31:1774.

Corey L, Wald A, Patel R, et al. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med. 2004;350:11.

Eckert LO, Lentz GM. Infections of the lower genital tract. In: Katz VL, Lentz GM, Lobo RA, Gershenson DM, editors. Comprehensive Gynecology. 5th ed. Philadelphia: Mosby/Elsevier; 2007:578.

Gottlieb SL, Douglas JMJr, Foster M, et al. Incidence of herpes simplex virus type 2 infection in 5 sexually transmitted disease (STD) clinics and the effect of HIV/STD risk-reduction counseling. J Infect Dis. 2004;190:1059.

Gupta R, Wald A, Krantz E, et al. Valacyclovir and acyclovir for suppression of shedding of herpes simplex virus in the genital tract. J Infect Dis. 2004;190:1374. Epub 2004 Sep 20

Nagot N, Ouedraogo A, Foulongne V, et alANRS 1285 Study Group. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med. 2007;356:790.

Oxman MN, Levin MJ, Johnson GR, et alShingles Prevention Study Group. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352:2271.

Roberts CM, Pfister JR, Spear SJ. Increasing proportion of herpes simplex virus type 1 as a cause of genital herpes infection in college students. Sex Transmit Dis. 2003;30:801.

Scott LL, Hollier LM, McIntire D, et al. Acyclovir suppression to prevent recurrent genital herpes at delivery. Infect Dis Obstet Gynecol. 2002;10:71.

Sheffield JS, Hollier LM, Hill JB, et al. Acyclovir prophylaxis to prevent herpes simplex virus recurrence at delivery: a systematic review. Obstet Gynecol. 2003;102:1396.

Stone KM, Reiff-Eldridge R, White AD, et al. Pregnancy outcomes following systemic prenatal acyclovir exposure: conclusions from the International Acyclovir Pregnancy Registry, 1984–1999. Birth Defects Research (Part A). 2004;70:201.

Level III

American College of Obstetricians and Gynecologists. Gynecologic herpes simplex virus infections. ACOG Practice Bulletin 57. Washington, DC: ACOG, 2004.

American College of Obstetricians and Gynecologists. Sexually transmitted diseases in adolescents. ACOG Committee Opinion 301. Washington, DC: ACOG, 2004.

Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2006. MMWR. 2006;55:16.

Engelberg R, Carrell D, Krantz E, et al. Natural history of genital herpes simplex virus type 1 infection. Sex Transmit Dis. 2003;30:174.

Sen P, Barton SE. Genital herpes and its management. BMJ. 2007;334:1048.

Tita AT, Grobman WA, Rouse DJ. Antenatal herpes serologic screening: an appraisal of the evidence. Obstet Gynecol. 2006;108:1247.

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