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Hot Topics in Sexually Transmitted Infections and Associated Conditions

(Published November 2013)

Genital Herpes

  • Key facts about infection
    • HSV causes mucocutaneous infection, retrograde infection along sensory nerves, latent infection in cranial nerve or dorsal spinal ganglia, and mucocutaneous recurrences.9
    • Herpes simplex virus type 1 (HSV-1)
      • HSV-1 causes mostly orolabial infection with recurrences ("cold sores","fever blisters").
      • Owing to rising frequencies of oral-genital sexual exposures, HSV-1 has grown to account for 50 to 70 percent of initial genital herpes infections in the United States.18
      • The frequency of overt recurrent outbreaks and asymptomatic viral shedding, and therefore the risk of sexual transmission, is substantially lower for HSV-1 than for herpes simplex virus type 2 (HSV-2).19,20,21 Suppressive therapy is less likely to be necessary or helpful in the management of genital herpes due to HSV-1 compared with HSV-2.
    • HSV-2
      • Infections are almost always in the genital area; oral HSV-2 is relatively uncommon.
      • In the United States, more than 24 million individuals have HSV-2 infection.2
      • The prevalence of HSV-2 infection varies by race/ethnicity. A national survey found an HSV-2 sero­prevalence rate for non-Hispanic Blacks that was approximately three times the rate for non-Hispanic Whites and nearly four times that for Mexican Americans.22
      • Most people with HSV-2 are unaware that they are infected, owing to asymptomatic infection and failure to recognize or understand mild symptoms.9
      • Asymptomatic viral shedding, the potential for sexual transmission, and recurrences are more common with HSV-2.20,21
    • Timeline for genital herpes infection

Figure 1: Timeline of Primary HSV-2 Infection19,23,24

        • If lesions develop, they appear 2 to 14 days after exposure and last about 3 weeks if antiviral therapy is not used.19
        • Viral shedding lasts an average of 12 days (but duration varies widely), stopping a few days before lesions heal, if they are present.19
        • Seroconversion (i.e., the development of measurable HSV antibodies) usually will occur within 2 to 12 weeks after the infection.19
        • Research suggests that by six weeks, more than 60 percent of patients with new HSV-2 infections will have developed antibodies and by 12 weeks more than 70 percent will have seroconverted.23,24
        • Although the antibody response is lifelong, it does not protect against local recurrence.19
      • Most cases of genital herpes are due to transmission from a partner who is asymptomatic at the time of transmission or is unaware he or she is infected.
      • The classic presentation of primary infection begins with papules, which transform into vesicles, pustules, and ulcers over the course of 1 to 2 weeks.
      • Most individuals do not have the classic presentation but may have pain at the location of lesions and adenopathy.
      • Women may have cervicitis or urethritis; pharyngitis can occur with oral infection.
    • Diagnosis
      • Test all patients with genital ulcers, including those that seem atypical for herpes, unless there is another definitive diagnosis.
      • Because of the important differences between HSV-1 and HSV-2 in clinical course, transmission risk, and management, virus type should be determined in all patients with genital herpes.*
      • Two basic types of tests are available for genital herpes diagnosis:
          • Virologic (direct) tests of mucocutaneous lesions
          • NAAT (usually polymerase chain reaction) to detect HSV DNA: the test of choice, substantially more sensitive than culture; readily distinguishes HSV-1 from HSV-2, often routinely (without specific request); now widely available
          • Viral culture: less sensitive than NAAT (more false negative results), longer turnaround time, may require specific request and higher cost to determine virus type

    * Your laboratory may require a specific request to distinguish HSV-1 from HSV-2, sometimes at increased cost.

Table 7: Virologic Tests for Genital Herpes9,25,26

Viral culture NAAT
Reference standard for diagnosis of genital herpes-can be used if NAAT is unavailable Preferable due to higher sensitivity
High specificity but poor sensitivity Sensitivity is 98-100% and specificity is 8-97% (sensitivity and specificity vary depending on the clinical setting, specimen type, and other factors)
More stringent requirements for specimen management, i.e. transport medium, refrigeration Polymerase chain reaction¡ªbased tests are most commonly used
Yield is best early in course: requires swab from base of vesicular lesion Results in 2 hours compared with 1-5 days for culture
        • Serologic tests
          • Detect the presence of antibodies to HSV and can indicate past exposure
          • Are useful in symptomatic individuals to determine whether lesions represent initial infection or recurrence, to assess past infection with both virus types, and to diagnose in the presence of a false negative culture (e.g., in patients with recurrent genital herpes or healing lesions in whom culture is less sensitive)
          • Are useful for selective screening of an asymptomatic individual at high risk or the partner of a person with HSV infection (although specific criteria for screening are controversial)
          • Are useful if neither NAAT nor culture is performed or if one is performed but is negative
          • Include three types
            • Enzyme-linked immunosorbent assay (ELISA)-based serologic assays
            • Point-of-care tests (POCTs) or rapid serologic assays
            • Western blot

Table 8: Serologic Tests for Genital Herpes9,25,26,27,28

ELISA-based assays POCTs or Rapid Serologic Assays Western Blot
Sensitivity of 94-100% and specificity of 94-98% Provide rapid results with sensitivity of at least 91% and specificity of at least 94% Useful for confirmation in selected cases (only available in research applications)
Cross-reactivity between types can be an issue and may result in incorrect typing (HSV-1 vs. HSV-2) Detect viral antigen  
  More expensive than ELISA tests  
          • Older serologic tests (e.g., enzyme immunoassay) could not differentiate between types 1 and 2 and should not be used.
          • Useful serologic tests measure immunoglobulin G (IgG) antibody to HSV-1 and HSV-2.
          • Immunoglobulin M (IgM) antibody tests are discouraged, even when routinely offered by laboratories:
            • There is a high rate of false positive results.
            • Theoretically IgM antibody develops before IgG and indicates recently acquired infection, but in fact it performs poorly in distinguishing early from late HSV infection.
            • Currently available tests do not distinguish the HSV-1 from HSV-2 antibody.
  • Treatment and management
    • Initial genital herpes
        • Antiviral therapy speeds resolution of initial genital herpes.
        • It is recommended for all patients with an initial genital herpes unless healing is well under way at presentation.
        • Intravenous therapy can be used for severe infection requiring hospitalization.

Table 9: Recommended Treatment for Primary Genital Herpes*9

Medication Dosage Duration
Acyclovir 400 mg orally three times a day 7 to 10 days or longer as needed until healing of lesions
Famciclovir 250 mg orally three times a day
Valacyclovir 1 g orally twice a day

For guidance on therapy for patients with HIV infection or women who are pregnant, see CDC treatment guidelines.

    • Recurrent genital herpes
        • Ongoing suppressive therapy reduces the frequency of recurrences and of asymptomatic viral shedding and decreases the risk of transmission to partners.
        • Self-initiated episodic therapy of recurrent episodes, if started early, modestly speeds resolution. Episodic therapy should be initiated as soon as symptoms begin or during the prodrome that some patients experience before lesion outbreaks.
        • Topical antivirals are minimally effective and not recommended.
        • See CDC guidelines for information about treatment in pregnancy and for individuals with coexisting HIV infection.

Table 10: Suppression Therapy for Recurrent Genital Herpes*9

Medication Dosage Comments
Acyclovir 400 mg orally twice daily  
Valacyclovir 1 g orally twice a day  
Valacyclovir 500 mg orally once daily The higher dose is recommended for patients with frequent outbreaks (¡Ý 9 per year) and is preferred by some experts for all patients.

* Examples of suggested regimens are shown. For additional options, see CDC treatment guidelines.

Table 11: Self-Initiated Episodic Therapy for Recurrent Genital Herpes*9

Medication Dosage Duration
Acyclovir 400 mg orally twice daily 3 days
Valacyclovir 400 mg orally three times a day 5 days

* Examples of suggested regimens are shown. For additional options, see CDC treatment guidelines.

Note: All regimens shown are for HSV-2 infection. HSV-1 is less susceptible to these drugs than HSV-2 and may require higher doses, although no specific studies or recommendations are available.