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**Genital Herpes Simplex Virus (HSV)**

\[Slide 2\]

**Learning Objectives**

Upon completion of this content, the learner will be able to:

1.  Describe the epidemiology of genital HSV infection in the U.S.

2.  Describe the pathogenesis of genital HSV.

3.  Discuss the clinical manifestations of genital HSV infection.

4.  Identify the common laboratory tests used in the diagnosis of
    genital HSV infection.

5.  Describe patient management for genital HSV infection.

6.  List public health measures for the prevention of genital HSV
    infection.

7.  Summarize appropriate prevention counseling messages for genital HSV
    infection.

\[Slide 3\]

**Course Outline**

I.  Epidemiology: Disease in the U.S.

II. Pathogenesis

III. Clinical manifestations

IV. Diagnosis

V.  Patient management

VI. Prevention

\[Slide 4\]

I.  **Epidemiology**

\[Slides 5-7\]

A.  Incidence and prevalence

    1.  Genital herpes is a recurrent, life-long viral infection.

    2.  Two serotypes of herpes simplex virus (HSV) have been
        identified: HSV-1 and HSV-2.

    3.  The majority of genital and perirectal herpetic outbreaks in the
        U.S. are caused by HSV-2, although up to 30% of first episodes
        are due to HSV-1.

    4.  It is estimated that at least 1 million new cases occur each
        year.

    5.  50% or more of new cases are asymptomatic or unrecognized.

    6.  In the general U.S. population, 22% of adults over age 12 have
        HSV-2 antibodies.

    7.  HSV-2 antibodies are not routinely detected until puberty, and
        HSV-2 seroprevalence rates increase with age up to 40 years then
        level off.

\[Slides 8-9\]

B.  Transmission

    1.  HSV-2 is transmitted sexually (genital to genital, oral to
        genital, or genital to oral) and perinatally (mother to child).
        HSV-1 is usually transmitted via a non-sexual route.

    2.  Most sexual transmission occurs while the source contact case is
        asymptomatic.

    3.  The risk of sexual transmission is difficult to quantify, but is
        estimated at 10% per year in recent studies of monogamous
        heterosexual couples with discordant HSV serum antibody status.

    4.  Efficiency of sexual transmission is greater from men to women
        than from women to men.

    5.  The presence of serum antibody to HSV-1 may be partially
        protective against acquisition of infection. HSV-1
        seropositivity partially protects against having a symptomatic
        infection.

    6.  Likelihood of transmission (frequency of occurrences and
        asymptomatic viral shedding) to others declines with increased
        duration of infection.

    7.  Incubation period after acquisition is 2-12 days (average is 4
        days).

    8.  Drying and soap and water readily inactivate HSV; therefore,
        fomite transmission is unlikely.

    9.  Genital HSV-2 infection facilitates both acquisition and
        transmission of HIV infection.

\[Slide 10\]

II. **Pathogenesis**

\[Slides 11-12\]

A.  Virology

    1.  Members of the human herpes viruses (herpetoviridae), which
        include: HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8.

    2.  HSV-1 and HSV-2 are double-stranded DNA viruses surrounded by an
        envelope of lipid glycoprotein.

    3.  50% DNA homology exists between HSV-1 and HSV-2.

    4.  All members of this species establish latent infection in
        specific target cells.

    5.  Infection persists despite the host immune response, often
        resulting in recurrent disease. Re-infection can occasionally
        occur despite immunity.

\[Slide 13\]

B.  Pathogenesis

    1.  Transmission of HSV usually occurs through close contact with a
        person who is shedding virus at a peripheral site, mucosal
        surface, or in genital or oral secretions.

        a.  HSV penetrates susceptible mucosal surfaces or abraded
            cracks in the skin.

        b.  After mucosal inoculation (in genital infection), the virus
            is transported along peripheral nerve axons to the nerve
            cell bodies' sacral ganglia.

        c.  Virus remains latent indefinitely in the paraspinous
            ganglia.

        d.  Reactivation, precipitated by multiple known (e.g., trauma,
            fever, UVL, stress, etc.) and unknown factors, induces viral
            replication.

        e.  The re-activated virus migrates centrifugally to mucosal
            surfaces by way of the peripheral sensory nerves, where it
            may cause a cutaneous outbreak of herpetic lesions.

    2.  Histopathologic changes include focal necrosis, ballooning
        degeneration of cells, production of mononucleated giant
        epithelial cells, and eosinophilic intra-nuclear inclusions
        called Cowdry type A bodies.

    3.  Up to 90% of persons seropositive for HSV-2 antibody have no
        clinical history of anogenital herpes outbreaks. However, most
        have mild unrecognized disease and probably all shed virus from
        the genital area intermittently.

\[Slide 14\]

III. **Clinical Manifestations**

\[Slides 15-17\]

A.  Definitions of types of infection

    1.  First clinical episode

        a.  Primary infection

            1.  First infection ever with either HSV-1 or HSV-2

            2.  No serum antibody present when symptoms appear

            3.  Disease more severe than recurrent disease

            4.  Serum antibody appears in convalescence

        b.  Non-primary infection

            1.  Newly acquired infection with HSV-1 or HSV-2 in an
                individual previously seropositive to the other virus

            2.  Manifestations tend to be milder than primary infection.

            3.  Cross-reacting antibody is present initially and may
                rise in convalescence. Type-specific antibody appears
                and rises in convalescence.

            4.  25% of patients with first clinical episode of HSV-2
                have had a prior asymptomatic primary infection.
                Type-specific antibody will be present when the patient
                presents and the severity of the episode is comparable
                to a recurrence (first episode, recurrence).

    2.  Recurrent symptomatic infection

        a.  Antibody is present when symptoms appear, although the
            patient may not be aware of previous episodes.

        b.  Generally, there is no or little change in antibody titer in
            convalescence.

        c.  Disease is usually mild and short in duration.

    3.  Asymptomatic infection

        a.  Serum antibody is present

        b.  No known history of clinical outbreaks

        c.  Up to two-thirds of patients with identified asymptomatic
            HSV-2 infection actually have unrecognized symptomatic
            infection.

        d.  Patients should be informed about clinical signs and
            symptoms of genital herpes, as this may help them recognize
            symptomatic infection.

+------------------+--------------------+--------------+--------------+
| Infection Type   | Lesions/ Symptoms  | T            |              |
|                  |                    | ype-specific |              |
|                  |                    | antibody     |              |
|                  |                    |              |              |
|                  |                    | at time of   |              |
|                  |                    | presentation |              |
+------------------+--------------------+--------------+--------------+
|                  |                    | HSV-1        | HSV-2        |
+------------------+--------------------+--------------+--------------+
| First episode    | +/Severe,          | \-           | \-           |
|                  | bilateral          |              |              |
| Primary          |                    |              |              |
|                  |                    |              |              |
| (Type 1 or 2)    |                    |              |              |
+------------------+--------------------+--------------+--------------+
| First episode    | +/Moderate         | \+           | \-           |
|                  |                    |              |              |
| Non-primary      |                    |              |              |
|                  |                    |              |              |
| Type 2           |                    |              |              |
+------------------+--------------------+--------------+--------------+
| First episode    | +/Mild             | +/-          | \+           |
|                  |                    |              |              |
| Recurrence       |                    |              |              |
|                  |                    |              |              |
| Type 2           |                    |              |              |
+------------------+--------------------+--------------+--------------+
| Symptomatic      | +/Mild, unilateral | +/-          | \+           |
|                  |                    |              |              |
| Recurrence       |                    |              |              |
|                  |                    |              |              |
| Type 2           |                    |              |              |
+------------------+--------------------+--------------+--------------+
| Asymptomatic     | \-                 | +/-          | \+           |
|                  |                    |              |              |
| Infection        |                    |              |              |
|                  |                    |              |              |
| Type 2           |                    |              |              |
+------------------+--------------------+--------------+--------------+

\[Slides 18-19\]

B.  Clinical manifestations

    1.  Primary (initial) infection without treatment: characterized by
        the occurrence of numerous bilateral painful genital lesions.
        These lesions are more severe, last longer, and have higher
        titers of virus than recurrent infections.

        a.  Lesion progression: papules vesicles pustules ulcers crusts
            healed

        b.  Illness lasts 2-4 weeks.

        c.  Often associated with systemic symptoms, including fever,
            headache, malaise, myalgia; urinary retention in women.

        d.  Systemic symptoms peak within 3-4 days of onset of lesions
            and gradually recede over the next 3-4 days.

        e.  Local symptoms are predominantly pain, itching, dysuria,
            vaginal or urethral discharge, and tender inguinal
            adenopathy (80%).

        f.  Painful genital lesions that are numerous and bilateral;
            last an average of 11-12 days; full re-epithelialization
            takes an average of 17-20 days.

        g.  Median duration of viral shedding (from the onset of lesions
            to the last positive culture) is approximately 12 days, and
            correlates well with the mean time from the onset of
            vesicles to crusting.

        h.  Inguinal adenopathy peaks in week 2-3 and is often the last
            finding to resolve. Nodes are firm, nonfluctuant, and tender
            to palpation. Suppuration is rare.

        i.  Primary HSV cervicitis occurs in approximately 90% of
            primary HSV-2 infection and about 70% of primary HSV-1
            infections. It may manifest as a mucopurulent cervicitis, or
            it may be asymptomatic. The cervix will appear abnormal to
            inspection in the majority of cases, with ulcerative
            lesions, erythema, or friability. Clinical differentiation
            from gonorrheal or chlamydial cervicitis may be difficult,
            although cervical ulceration may suggest HSV. The exo-or
            endocervix may be involved. Herpes proctitis may be
            characterized by pain, discharge, tenesmus, constipation
            with or without symptoms of autonomic dysfunction and severe
            ulceration on anoscopy.

        j.  Urinary involvement

            1.  Men with first-episode HSV have a positive urethral
                culture in 33% of cases. In first episode of primary
                genital herpes, urethritis may be part of the clinical
                syndrome and may cause a clear mucoid discharge.

            2.  HSV has been isolated from approximately 5% of women
                with the dysuria-frequency syndrome.

\[Slide 20\]

Image: Herpes: Primary complex

\[Slide 21\]

Image: Herpes: Genitalis multiple ulcer

\[Slide 22\]

Image: Herpes: Genitalis external-labia minor

\[Slide 23\]

Image; Herpes: Genitalis clinical periurethal lesions on vestibule

\[Slide 24\]

Image: Herpes: Cervicitis

\[Slide 25\]

Image: Herpes on the buttock

\[Slide 26\]

Image: Herpes: Possible oralis soft palate

\[Slide 27\]

2.  Recurrent infection without treatment

    a.  Illness lasts 5-10 days

    b.  Prodromal symptoms (localized tingling, irritation) in
        approximately 50% begin 12-24 hours before lesions and sometimes
        without lesions (\"false prodrome\").

    c.  Duration is shorter than in primary infection: painful genital
        lesions last 4-6 days; average duration of viral shedding is 4
        days.

    d.  Lesions tend to be unilateral.

    e.  Symptoms tend to be milder and less severe. Usually there are no
        systemic symptoms.

    f.  Rate of cervical virus shedding in women is 12%-20%.

    g.  Average of 2-6 recurrences/year, but highly variable.

    h.  HSV-2 primary infection is much more prone to recur than HSV-1
        primary infection.

    i.  HSV-2 will recur slightly more frequently and after a shorter
        period of time in men than in women; median 5 recurrences per
        year compared with 4 in the first year of infection.

    j.  Recurrences are more frequent if the primary episode is
        prolonged \> 30 days.

\[Slides 28-29\]

3.  Asymptomatic viral shedding

    a.  Asymptomatic shedding as detected by PCR is present on 28% of
        days (range 0 to 77%).

    b.  Rates of asymptomatic shedding are greater with HSV-2 than with
        HSV-1.

    c.  Asymptomatic shedding has been documented in almost all HSV-2
        seropositive persons studied.

    d.  Most HSV-2 is transmitted during asymptomatic shedding.

    e.  Shedding rates are greatest in the first 3 months after
        infection.

    f.  Asymptomatic shedding occurs less frequently in women with
        established HSV-2 infection (mean\--4% of days). In those with
        newly acquired infections (\<2 years), asymptomatic shedding
        occurs in up to 5%-10% of days.

    g.  Asymptomatic shedding is of briefer duration than during
        clinical recurrences.

    h.  Presence of serum antibody of HSV-1 seems to decrease rates of
        asymptomatic shedding with HSV-2.

    i.  Acyclovir chemosuppression dramatically reduces, but does not
        eradicate shedding.

    j.  In a recent study, the rate of subclinical shedding in patients
        with no reported history of genital herpes was similar to that
        in patients with such a history (3.0% vs. 2.7%).

    k.  Most common sites of asymptomatic shedding are the vulva and
        perianal areas in women and penile skin and perianal area in
        men.

\[Slide 30\]

C.  Complications of genital infection

    1.  Aseptic meningitis

        a.  More common in primary than in recurrent infection

        b.  More common with HSV-2 than HSV-1

        c.  More common in women than in men (36% of women versus 11% of
            men with primary HSV-2 infection)

        d.  May be severe, requiring hospitalization or parenteral
            narcotics

        e.  There are generally no neurologic sequelae, however recent
            data suggest that benign recurrent meningitis (Mollaret's
            meningitis) is usually caused by HSV-2.

    2.  Other complications (rare)

        a.  Stomatitis and pharyngitis

        b.  Radicular pain, sacral paresthesias

        c.  Transverse myelitis

        d.  Autonomic dysfunction: hyperesthesias, neurogenic bladder,
            constipation, and impotence

        e.  Disseminated (viremic) infection\--occasional in patients
            with atopic eczema, pregnant women, impaired CMI, neonates.
            Can be a cause of fulminant hepatitis in immunosuppressed
            patients.

        f.  Ocular involvement (more common with HSV-1)

        g.  Herpetic whitlow (more common with HSV-1)

\[Slide 31\]

IV. **Diagnosis**

\[Slide 32\]

A.  Diagnosis

    1.  Clinical diagnosis is insensitive and nonspecific.

    2.  The typical painful multiple vesicular or ulcerative lesions are
        absent in many infected persons. Up to 30% of first-episode
        cases are caused by HSV-1, but recurrences are much less
        frequent for genital HSV-1 infection than genital HSV-2
        infection, therefore HSV serotype influences prognosis and
        counseling.

    3.  Clinical diagnosis should be confirmed by lab testing; there are
        2 main types of lab tests used for confirmatory diagnosis:

        a.  Virologic tests

        b.  Type-specific serologic tests

\[Slides 33-34\]

B.  Virologic tests

    1.  Viral culture (gold standard)

        a.  Isolation of HSV in cell culture is the preferred test for
            patients with genital ulcers or other mucocutaneous lesions.

        b.  Sensitivity of culture declines rapidly as lesions begin to
            heal, usually within a few days of onset.

        c.  Highly specific (\>99%) and sensitive but not as sensitive
            as PCR.

        d.  Viral recovery depends on stage of lesion and proper
            collection technique, vesicles\--90%, ulcers\--70%, and
            crusted lesions\--30%. Culture is more commonly positive in
            primary infection (80%--90%) as contrasted with recurrences
            (30%).

        e.  Time limitations: most cultures will be positive within
            24-72 hours, but are generally held for 5-7 days.

        f.  Stable in viral transport media for 48-72 hours at 4°C.

        g.  Allows for easiest typing (HSV-1 vs. HSV-2).

    2.  Antigen detection (DFA or EIA)

        a.  Some HSV antigen tests, unlike culture and the direct
            fluorescent antibody test, do not distinguish HSV-1 from
            HSV-2.

        b.  Fairly sensitive (\>85%) in symptomatic shedders

        c.  Rapid (2-12 hours)

        d.  Highly specific; can differentiate HSV-1 from HSV-2 or VZV
            using monoclonal antibodies, but false positives can occur.

        e.  May be better than culture for healing lesions

    3.  Cytology (Tzanck or Pap)

        a.  Cytologic detection of cellular changes of herpes virus
            infection is insensitive (50%) and nonspecific (cannot
            differentiate HSV from VZV) and should not be relied on for
            HSV diagnosis.

        b.  Identifies typical HSV-infected cells (multi-nucleated giant
            cells and eosinophilic inclusion bodies) in exfoliated cells
            or biopsies.

        c.  Cytologic tests include Tzanck preparation for genital
            lesions and cervical Pap smears.

    4.  PCR assay is the preferred test for detecting HSV in spinal
        fluid. PCR is highly sensitive and specific, but its role in
        diagnosis of genital ulcer disease has not been well-defined.

    5.  Comparison of virologic tests:

  ------------- -------------- -------------- -------------- --------------
                Viral culture  Antigen        Cytology       PCR
                               detection (DFA (Tzanck or     
                               or EIA)        Pap)           

  Sensitivity   80%-90%        \>85% (in      50%            
                (primary       symptomatic                   
                episode)       shedders)                     

  Specificity   99%                           Non-specific   

  Test notes    Positive in    May be better  Identifies     Clinical
                80%-90% of     than culture   typical        significance
                primary        for healing    HSV-infected   of positive
                infections and lesions; rapid cells in       result being
                30% of         (2-12 hours)   exfoliated     established
                recurrent                     cells or       
                infections;                   biopsies       
                allows for                                   
                easiest                                      
                typing; most                                 
                are positive                                 
                in 1-3 days,                                 
                but held 5-7                                 
                days                                         
  ------------- -------------- -------------- -------------- --------------

\[Slides 35-36\]

C.  Serologic tests

    1.  Type-specific and nonspecific antibodies to HSV develop during
        the first several weeks following infection and persist
        indefinitely.

    2.  Presence of HSV-2 antibody indicates anogenital infection.

    3.  Presence of HSV-1 does not distinguish anogenital from orolabial
        infection.

    4.  The older serological tests (CF, IFA, EIA) did not distinguish
        between HSV-1 and HSV-2 antibody.

    5.  New serological tests using HSV type-specific antigens
        glycoprotein G1 (HSV-1) and glycoprotein G2 (HSV-2) and EIA and
        Western blotting (WB) methods have been developed and are now
        commercially available for type-specific testing. Currently the
        FDA-approved glycoprotein G (gG)-based type-specific assays
        include laboratory-based assays manufactured by Focus
        Technology, Inc: HerpeSelect™ ELISA IgG and HerpeSelect™
        Immunoblot. The sensitivities of these tests for detection of
        HSV-2 antibody vary from 80% to 98% and false-negative results
        may occur, especially early after infection. The specificities
        of these assays are \> 96%; false-positive results can occur,
        especially in patients with low likelihood of HSV infection.
        Therefore, repeat testing or a confirmatory test may be
        indicated in some settings.

    6.  Uses of type-specific serologic tests:

        a.  To confirm clinical diagnosis in cases of recurrent or
            healing lesions or atypical genitourinary symptoms where
            false-negative HSV cultures are more common

        b.  To diagnose unrecognized infection

        c.  To manage sex partners of persons with genital herpes and to
            counsel couples in which one of the pair has genital herpes
            and the other does not know or is unsure (may be valuable in
            planning pregnancy or for expectant couples)

        d.  To screen in selected high-risk populations such as STD
            clinic patients. Cost-benefit analyses have not been
            performed comparing the costs of the tests vs. the savings
            resulting from preventing further cases.

    7.  While serologic assays from HSV-2 should be available for
        persons who request them, screening for HSV-1 or HSV-2 infection
        in the general population is not indicated.

\[Slide 37\]

D.  Special diagnostic considerations

    1.  Establish the etiology of atypical genital ulcer(s) to include
        mixed infections (e.g., syphilis and chancroid), unusual
        infections (e.g., LGV, HIV, CMV), and other causes (e.g.,
        cancer).

    2.  Evaluate for acyclovir resistance in patients with persistent
        genital herpes despite antiviral suppressive therapy.

\[Slide 38\]

V.  **Patient Management**

\[Slide 39\]

A.  Principles of management of genital herpes

    1.  Systemic antiviral chemotherapy offers clinical benefits to most
        symptomatic patients and is the mainstay of management.

        a.  Partially controls symptoms and signs of herpes episodes
            when used to treat first clinical episodes and recurrent
            episodes or when used as daily suppressive therapy.

        b.  Does not eradicate latent virus and does not affect risk,
            frequency, or severity of recurrences after drug is
            discontinued.

    2.  Counseling is integral to clinical management and should include
        natural history, sexual and perinatal transmission, and methods
        to reduce transmission.

\[Slide 40\]

B.  Antiviral therapy for HSV

    1.  HSV systemic antiviral chemotherapy includes three oral
        medications:

        a.  Acyclovir (ACV)

        b.  Valacyclovir (Valine ester of acyclovir)\--high oral
            bioavailability

        c.  Famciclovir (Penciclovir prodrug)\--high oral
            bioavailability

    2.  Topical antiviral treatment is of minimal clinical benefit and
        is not recommended.

\[Slide 41\]

C.  Management of first clinical episode of genital herpes

    1.  Many patients with first episode herpes present with mild
        clinical manifestations but later develop severe or prolonged
        symptoms. Therefore, most patients with initial genital herpes
        should receive antiviral therapy.

    2.  Antiviral therapy has dramatic effect in initial HSV infection,
        especially if symptoms \<7 days and no history of oral HSV.

\[Slide 42\]

3.  CDC-recommended regimens for the treatment of first clinical episode

    a.  Acyclovir 400 mg orally 3 times a day for 7-10 days until
        complete crusting has occurred, or

    b.  Acyclovir 200 mg orally 5 times a day for 7-10 days, or

    c.  Famciclovir 250 mg orally 3 times a day for 7-10 days, or

    d.  Valacyclovir 1 g orally twice a day for 7-10 days.

4.  Higher dosages of acyclovir (e.g., 400 mg orally 5 times a day) were
    used in treatment studies of first-episode herpes proctitis and
    first-episode oral infection. However, no comparative studies have
    been conducted, and whether these forms of HSV infection require
    higher doses of antiviral drugs than used for genital herpes is
    unknown. Valacyclocvir and famciclovir probably are also effective
    for acute HSV proctitis or oral infection, but clinical experience
    is lacking.

5.  Treatment may be extended if healing is incomplete after 10 days of
    therapy.

6.  Factors to weigh when considering treatment: severity of symptoms,
    immune status, pregnancy, history of complications, and cost.

\[Slide 43\]

D.  Recurrent episodes of genital herpes

    1.  Most patients with symptomatic primary genital HSV-2 infection
        experience recurrent outbreaks.

    2.  Recurrences are less frequent after initial HSV-1 infection.

    3.  Antiviral therapy for recurrent genital herpes can be
        administered either episodically, to ameliorate or shorten the
        duration of lesions, or continuously as suppressive therapy, to
        reduce the frequency of occurrences.

    4.  Treatment options should be discussed with ALL patients.

\[Slide 44\]

5.  Episodic therapy

    a.  Successful episodic treatment requires initiation of therapy
        within 1 day of lesion onset.

    b.  Clinicians should provide the patient with a supply of drug or a
        prescription and instructions to self-initiate treatment
        immediately when symptoms begin.

\[Slide 45\]

6.  CDC-recommended regimens for episodic therapy for recurrent
    infection

    a.  Acyclovir 400 mg orally 3 times a day for 5 days, or

    b.  Acyclovir 200 mg orally 5 times a day for 5 days, or

    c.  Acyclovir 800 mg orally twice a day for 5 days; or

    d.  Famciclovir 125 mg orally twice a day for 5 days, or

    e.  Valacyclovir 500 mg orally twice a day for 3-5 days, or

    f.  Valacyclovir 1 g orally once a day for 5 days.

7.  A 3-day course of valacyclovir 500 mg twice daily has been shown to
    be as effective as a 5-day course. Similar studies have not been
    done with acyclovir and famciclovir.

\[Slide 46\]

8.  Suppressive therapy

    a.  Suppressive therapy reduces the frequency of genital herpes
        recurrences by 70%-80% among patients who have frequent
        recurrences (\> 6 recurrences per year), and many patients
        report no symptomatic outbreaks.

    b.  Treatment probably is also effective in patients with less
        frequent recurrences, although definitive data are lacking.

    c.  Quality of life often is improved in patients with frequent
        recurrences who receive suppressive therapy compared with
        episodic therapy.

    d.  Suppressive antiviral therapy reduces but does not eliminate
        subclinical viral shedding and decreases transmission 48%-75% in
        the susceptible partner in discordant couple studies.

\[Slide 47\]

9.  CDC-recommended regimens for suppressive therapy for recurrent
    infection

    a.  Acyclovir 400 mg orally twice a day, or

    b.  Famciclovir 250 mg orally twice a day, or

    c.  Valacyclovir 500 mg orally once a day, or

    d.  Valacyclovir 1 g orally once a day.

10. Valacyclovir 500 mg once a day might be less effective than other
    valacyclovir or acyclovir dosing regimens in patients who have very
    frequent recurrences (i.e., \>10 episodes per year).

11. Ease of administration and cost are important considerations for
    prolonged treatment.

12. The frequency of recurrent outbreaks diminishes over time in many
    patients, and the patient's psychological adjustment to the disease
    may change.

    a.  Periodically during suppressive treatment (e.g., once a year),
        discontinuation of therapy should be discussed with the patient
        to reassess the need for continued suppressive therapy.

    b.  Patients should be warned that they might have rebound outbreaks
        when suppression is discontinued; suppression does not eliminate
        ganglionic latency.

\[Slides 48-49\]

E.  Severe disease

    1.  IV acyclovir should be provided for patients with severe disease
        or complications requiring hospitalization such as disseminated
        infection, pneumonitis, hepatitis, or complications of the
        central nervous system (e.g., meningitis or encephalitis).

    2.  CDC-recommended regimen

        a.  Acyclovir 5-10 mg/kg IV every 8 hours for 2-7 days or until
            clinical improvement, followed by oral antiviral therapy to
            complete at least 10 days total therapy.

    3.  Allergic and other adverse reactions to acyclovir, valacyclovir,
        and famciclovir are rare.

    4.  Desensitization to acyclovir is described in Henry RE, et al.
        Successful oral acyclovir desensitization. Ann Allergy 1993;
        70:386-8.

\[Slide 50\]

F.  Herpes and HIV

    1.  Immunocompromised patients may have prolonged or severe episodes
        of genital, perianal, or oral herpes.

    2.  Herpes lesions are common in HIV-infected patients and may be
        persistent, severe, painful, and atypical.

    3.  Genital ulcers increase the risk of HIV transmission and
        acquisition.

    4.  AIDS case definition applies if lesions persist \>1 month in
        recurrent disease.

\[Slide 51\]

5.  CDC-recommended regimens for episodic therapy for HIV-infected
    persons

    a.  Acyclovir 400 mg orally 3 times a day for 5-10 days, or

    b.  Acyclovir 200 mg orally 5 times a day for 5-10 days, or

    c.  Famiciclovir 500 mg orally twice a day for 5-10 days, or

    d.  Valacyclovir 1 g twice a day for 5-10 days.

\[Slide 52\]

6.  CDC-recommended regimens for suppressive therapy for HIV-infected
    persons

    a.  Acyclovir 400-800 mg orally twice to 3 times a day, or

    b.  Famciclovir 500 mg orally twice a day, or

    c.  Valacyclovir 500 mg orally twice a day.

7.  In 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 5-10
    mg/kg IV every 8 hours may be necessary.

8.  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 alternative therapy should be
    administered. All acyclovir-resistant strains are resistant to
    valacyclovir and most are resistant to famciclovir. (Refer to the
    CDC 2002 STD Treatment Guidelines for treatment alternatives
    <http://www.cdc.gov/STD/treatment/>).

\[Slides 53-56\]

G.  Herpes in pregnancy

    1.  Risk for transmission to neonate from infected mother is high
        (30%-50%) in women who acquire genital herpes near time of
        deliver and low (\<1%) in women with histories of recurrent
        herpes at term or who acquire genital HSV during the first half
        of pregnancy.

    2.  Prevention of neonatal herpes depends on avoiding acquisition of
        HSV during late pregnancy and avoiding exposure of infant to
        herpetic lesions during delivery. Type-specific serologic tests
        may be useful in determining risk status and management of HSV
        in pregnancy.

    3.  Counsel all women without known genital herpes to avoid
        intercourse during 3rd trimester with partners known or
        suspected of having genital herpes.

    4.  Counsel all women without known orolabial herpes to avoid
        cunnilingus during 3rd trimester with partners known or
        suspected of having orolabial herpes.

    5.  Ask all pregnant women whether they have a history of genital
        herpes.

    6.  At onset of labor:

        a.  Question all women about symptoms of genital herpes,
            including prodrome.

        b.  Examine all women for herpetic lesions.

    7.  Women without symptoms or signs of genital herpes or its
        prodrome can deliver vaginally.

    8.  Most specialists recommend that women with recurrent genital
        herpetic lesions at onset of labor deliver by cesarean section
        to prevent neonatal herpes. However, abdominal delivery does not
        completely eliminate the risk for HSV transmission to the
        infant.

    9.  Risk factors for HSV transmission to the infant include: new
        infection, primary infection, lack of type-specific antibodies,
        and use of scalp electrodes.

    10. The results of viral cultures during pregnancy in women with or
        without visible herpetic lesions do not predict viral shedding
        at the time of delivery, and therefore routine viral cultures of
        pregnant women with recurrent genital herpes are not
        recommended.

    11. The risk of neonatal herpes is high in women who acquire genital
        HSV in late pregnancy, and such women should be managed in
        consultation with an expert. Some experts recommend acyclovir
        therapy in this setting, and some recommend routine cesarean
        section to reduce the risk of neonatal herpes or both. Acyclovir
        near term for women with recurrent herpes may decrease the need
        for abdominal deliveries.

    12. 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.

    13. Safety of systemic acyclovir, valacyclovir, and famciclovir
        therapy in pregnant women has not been established, although
        available data do not indicate increased risk for major birth
        defects compared with the general population in women treated
        with acyclovir during the first trimester. There are ongoing
        studies assessing the efficacy and safety of acyclovir given
        around the time of delivery for mother and child.

H.  Therapy of complicated HSV infection

    1.  The therapy of choice in acyclovir resistant HSV infections is
        intravenous sodium phosphonoformate (Foscarnet).

    2.  Foscarnet injections once or twice weekly may be necessary to
        suppress recurrent episodes of Acyclovir resistant HSV in
        immunosuppressed patients.

    3.  Cidofovir gel is currently under investigation and is not
        available for use at this time.

I.  Adjunctive therapy

    1.  Pain relief\--usually necessary only in primary disease. Painful
        urination can be alleviated by urinating in warm bath.

    2.  Topical measures: drying or analgesia\--of unproven benefit, but
        some patients report relief.

    3.  Sitz baths

\[Slide 57\]

VI. **Patient Counseling and Education**

\[Slide 58\]

A.  Counseling

    1.  Counseling has two main goals:

        a.  To help patients cope with the infection, and

        b.  To prevent sexual and perinatal transmission.

    2.  Psychological impact of infection is often substantial.

    3.  HSV-infected persons may express anxiety about genital herpes
        that does not reflect the actual clinical severity of their
        disease.

    4.  The misconception that HSV causes cancer should be dispelled,
        because HSV-2 is not a primary etiologic agent in cervical
        cancer.

    5.  Common concerns about genital herpes include the severity of
        initial clinical manifestations, recurrent episodes, sexual
        relationships and transmission to sex partners, and ability to
        bear healthy children.

    6.  Although initial counseling can be provided at first visit, many
        patients benefit from learning about the chronic aspects of the
        disease after the acute illness subsides.

    7.  Numerous resources are available to assist patients and
        clinicians in counseling (see the Resources list at the end of
        this module for more information).

\[Slide 59\]

B.  Patient counseling and education should include:

    1.  Nature of the infection

    2.  Transmission

    3.  Treatment issues

    4.  Risk reduction strategies

    5.  An emphasis on the potential for recurrent episodes,
        asymptomatic viral shedding, and sexual transmission

\[Slide 60\]

C.  Nature of the infection

    1.  Sexual transmission of HSV can occur during asymptomatic periods

    2.  The frequency of outbreaks generally decreases with increasing
        duration of infection

    3.  Stressful events may trigger recurrences

    4.  Prodromal symptoms may precede outbreaks

\[Slide 61\]

D.  Transmission

    1.  HSV can be transmitted when lesions are not present and most
        cases are transmitted during asymptomatic periods.

    2.  Abstain from sexual activity with uninfected partners when
        lesions or prodromal symptoms are present.

    3.  Inform current sex partners about diagnosis of genital herpes.

    4.  Inform future partners before initiating a sexual relationship.

\[Slide 62\]

E.  Treatment options

    1.  Effectiveness of suppressive and episodic therapy in preventing
        or shortening the duration of recurrent episodes

    2.  When and how to take antiretroviral medications

    3.  Recognition of prodromal symptoms

    4.  Strategies for relief of painful urination such as urinating in
        a tub and the use of topical analgesics

\[Slide 63\]

F.  Risk reduction strategies

    1.  Assess client\'s behavior-change potential.

    2.  Discuss prevention strategies (abstinence, mutual monogamy with
        an uninfected partner, condoms, limiting the number of sex
        partners, etc.).

    3.  Inform the patient that genital ulcer diseases can occur in male
        or female genital areas that are covered or protected by a latex
        condom, as well as in areas that are not covered.

    4.  Correct and consistent use of latex condoms can reduce the risk
        of genital herpes only when the infected area or site of
        potential exposure is protected.

    5.  Work with the patient to develop individualized risk-reduction
        plans.

    6.  Risk of neonatal infection should be explained to all patients,
        including men.

    7.  Advise pregnant women and women of child-bearing age to inform
        their prenatal and neonatal care providers that they have
        genital herpes.

\[Slide 64\]

G.  Counseling for asymptomatic persons

    1.  Give asymptomatic persons diagnosed with HSV-2 infection by
        type-specific serologic testing the same counseling messages as
        persons with symptomatic infection.

    2.  Teach about the common manifestations of genital herpes, as many
        will become aware of them with time.

    3.  Antiviral therapy is not recommended for persons without
        clinical manifestations of infection.

    4.  Type-specific serological testing of asymptomatic partners can
        determine whether risk of HSV acquisition exists.

\[Slide 65\]

VII. **Partner Management**

     A.  Counseling of infected persons and their sex partners is
         critical to management of genital herpes. Sex partners are
         likely to benefit from evaluation and counseling.

     B.  Symptomatic sex partners should be evaluated and treated in the
         same manner as patients who have genital lesions.

     C.  Asymptomatic sex partners of patients who have genital herpes
         should be asked about any history of genital lesions, counseled
         to recognize symptoms of herpes, and offered type-specific
         serologic testing for HSV infection.

         1.  Sex partners of infected persons should be advised that
             they might be infected even if they have no symptoms.

         2.  Type-specific serologic testing of asymptomatic partners of
             persons with genital herpes can determine whether risk of
             HSV acquisition exists.

**CASE STUDY**

\[Slide 67\]

Roberta Patterson is a 26-year-old woman who presents for her first
prenatal visit. She is concerned for her baby because of her husband
Franklin's history of genital herpes. She states that she is 6 weeks
pregnant.

**History**

-   Roberta has never had symptoms of vaginal or oral herpes.

-   She was diagnosed and treated for chlamydia seven years ago (age
    19); no other STD diagnoses reported.

-   Her 26-year-old husband had his first episode of genital herpes
    during his last year of high school; no other STD diagnoses
    reported.

-   Her husband (and sex partner for the last 16 months) has not had HSV
    lesions visible since she's been sexually active with him, and
    reports having had no prodromal symptoms or symptoms of active
    disease.

-   She has had no sex partners, other than her husband, for the last 16
    months.

\[Slide 68\]

**Physical Exam**

-   Vital signs: blood pressure 112/68, pulse 58, respiration 13,
    temperature 38.5° C

-   Cooperative, good historian

-   Chest, heart, musculoskeletal, and abdominal exams within normal
    limits

-   Uterus consistent with a 6-week pregnancy

-   Normal vaginal exam without signs of lesions or discharge

-   No lymphadenopathy

\[Slide 69\]

1\. Which HSV general education messages should be discussed with
Roberta?

Correct responses include the following:

-   Genital herpes is a recurrent, life-long viral infection.

-   HSV-2 causes the majority of genital herpes cases in the U.S.

-   At least 50 million people in the U.S. have genital HSV infection.

-   Most persons infected with HSV-2 are undiagnosed.

-   50% or more of new cases are asymptomatic or unrecognized.

-   Most sexual transmission occurs while the source case is
    asymptomatic.

-   Up to 90% of persons seropositive for HSV-2 antibody have no
    clinical history of anogenital herpes outbreaks.

2\. Given that Roberta's husband Franklin has a history of genital
herpes, would it be appropriate to test Roberta for genital herpes using
a type-specific serologic test?

Yes, it would be appropriate to use a type-specific serologic test to
test Roberta for genital herpes, given that she is pregnant and her
husband has a history of genital herpes. Some specialists believe
type-specific serologic tests are useful to identify pregnant women at
risk for HSV infection and to guide counseling with regard to the risk
of acquiring genital herpes during pregnancy. Such testing and
counseling may be especially important when a woman's sex partner has
HSV infection.

3\. What other STD screening should be considered for Roberta?

Because of the potential for neonatal infection, CDC recommends
screening all pregnant women for syphilis, chlamydia, gonorrhea, and
HIV.

\[Slide 70\]

**Roberta's Laboratory Results**

-   HSV gG-based type-specific serologies: HSV-1 negative; HSV-2
    positive

-   DNA probe for *Chlamydia trachomatis*: negative

-   Culture for *Neisseria gonorrhoeae*: negative

-   RPR: nonreactive

-   HIV antibody test: negative

-   Pregnancy test: positive

4\. What would you tell Roberta about her HSV infection, based on
clinical manifestations and test results?

Roberta most likely has an asymptomatic infection. Asymptomatic
infection is defined as infection in which serum antibody is present,
but there is no known history of clinical outbreaks.

Up to two-thirds of patients with identified asymptomatic HSV-2
infection actually have unrecognized symptomatic infection. Patients
should be taught to recognize signs and symptoms of genital herpes.
Roberta does have HSV-2 antibodies, but she has no symptoms and reports
no previous episodes.

5\. Would routine viral cultures during Roberta\'s pregnancy be
recommended?

No. The results of viral cultures during pregnancy of women with or
without visible herpetic lesions do NOT predict viral shedding at the
time of delivery, and therefore routine viral cultures of pregnant women
with recurrent genital herpes are NOT recommended.

\[Slide 71\]

**Partner Management**

Sex partner and exposure information:

Franklin Patterson

First sexual exposure: 16 months ago

Last sexual exposure: 1 month ago

History of genital herpes infection; first episode 8 years ago. No HSV
testing or treatment at time of first episode or with subsequent
episodes.

No history of other STDs.

6\. Franklin reports genital lesions during Roberta\'s sixth month of
pregnancy. Which laboratory tests should be performed on him?

Correct responses include the following:

HSV viral culture of the lesions. Viral cultures are the preferred HSV
test for patients with genital ulcers or other mucocutaneous lesions.
Tzanck stain of the lesions is insensitive and nonspecific, and should
not be relied on for HSV diagnosis. Viral culture is preferred over DFA
or EIA antigen detection tests when a patient has a genital lesion.

Darkfield microscopy or DFA-TP on genital lesions and RPR to test for
syphilis. Syphilis testing should be considered for any patient
presenting with genital lesions since genital lesions are a symptom of
primary syphilis.

Testing for *C. trachomatis*, *N. gonorrhoeae*, and HIV. Because
patients who have contracted an STD may be at greater risk for exposure
to other STDs, it is useful to screen for other STDs, such as chlamydia,
gonorrhea, and HIV.

\[Slide 72\]

**Laboratory Results for Franklin**

Franklin\'s laboratory test results are as follows:

HSV cultures: HSV-1 negative; HSV-2 positive

DNA probe for *Chlamydia trachomatis*: negative

Culture for *Neisseria gonorrhoeae*: negative

RPR: nonreactive

DFA: negative for *Treponema pallidum*

HIV antibody test: negative

7\. What is an appropriate episodic treatment for Franklin?

Correct responses include the following:

Acyclovir 400 mg orally 3 times a day for 5 days

Acyclovir 200 mg orally 5 times a day for 5 days

Famciclovir 125 mg orally twice a day for 5 days

Valacyclovir 500 mg orally twice a day for 5 days

Valacyclovir 1 g orally once a day for 5 days

\[Slide 73\]

**Follow-Up**

Roberta had no HSV symptoms during her pregnancy.

Roberta opted to take the acyclovir treatment in late pregnancy after a
discussion with her certified nurse-midwife that included the following
points:

-   The safety of systemic acyclovir therapy in pregnant women has not
    been established.

-   Preliminary data suggest that acyclovir treatment late in pregnancy
    might diminish the frequency of HSV occurrence at term that would
    necessitate an abdominal delivery.

At onset of labor, she reported no prodromal or other HSV symptoms and
no lesions were found on examination.

After a 14-hour labor, she vaginally delivered a healthy 7.2 lb baby
girl.

\[Slide 74\]

8\. What questions should ALL women beginning labor (regardless of their
history of genital HPV infection) be asked?

All women beginning labor should be questioned about prodromal and other
HSV symptoms and should be examined for lesions.

9\. If Roberta had genital herpetic lesions at the onset of labor,
should she deliver vaginally or abdominally? What is the risk to the
infant?

Most specialists recommend that women with genital herpetic lesions at
the onset of labor deliver abdominally to reduce the risk of neonatal
herpes. However, abdominal delivery does not completely eliminate the
risk for HSV transmission to the infant.

\[Slide 75\]

10\. Roberta is asymptomatic at the time of delivery. Is it medically
appropriate for her to deliver vaginally?

Yes, women without symptoms of genital herpes or its prodrome can
deliver vaginally.

11\. If Roberta had acquired genital herpes around the time of delivery,
would she be more or less likely to transmit genital herpes to her baby
during a vaginal delivery than if she had a history of recurrent genital
herpes?

If she had acquired genital herpes around the time of delivery, she
would be more likely to transmit it to her baby than if she had a
history of recurrent genital herpes. In vaginal delivery, transmission
from an infected mother to the neonate occurs in up to 30%-50% of
genital herpes infections acquired around the time of delivery and in
\<1% of recurrent infections.

**TEST QUESTIONS**

1.  Genital herpes is:

    a.  A recurrent, life-long bacterial infection

    b.  **A recurrent, life-long viral infection**

    c.  A transient infection caused by a protozoal organism

    d.  A transient viral infection

2.  The majority of genital and perirectal herpetic outbreaks in the
    U.S. are caused by HSV-1.

    a.  True

    b.  **False**

3.  Which of the following statements is true about the prevalence and
    incidence of HSV-2?

    a.  There are over 1.6 million new cases of HSV-2 each year in the
        U.S.

    b.  Most people with HSV-2 have not been diagnosed.

    c.  Fifty percent or more of new cases are asymptomatic or
        unrecognized.

    d.  **All of the above**

4.  Which of the following statements is true about the transmission of
    HSV?

    a.  The average incubation period is 10 days.

    b.  Likelihood of transmission does not change with increased
        duration of infection.

    c.  **HSV is readily inactivated by drying and soap and water.**

    d.  Most sexual transmission occurs while the source contact case is
        symptomatic.

5.  In most cases of sexual transmission of genital HSV, the source case
    is asymptomatic.

    a.  **True**

    b.  False

6.  Sexual transmission of genital herpes is **less efficient** from

    a.  **Women to men**

    b.  Men to women

    c.  Transmission efficiency is the same from men to women and from
        women to men.

7.  Up to \_\_% of persons seropositive for HSV-2 antibody have no
    clinical history of anogenital herpes outbreaks.

    a.  75

    b.  80

    c.  **90**

    d.  95

8.  Which of the following statements is true about the pathogenesis of
    HSV?

    a.  Up to 90% of persons seropositive for HSV-2 antibody have a
        clinical history of anogenital herpes outbreaks.

    b.  **Most persons who are seropositive for HSV-2 with no symptoms
        still shed virus from the genital area intermittently.**

    c.  Reactivation and viral replication never occur.

    d.  All herpes viruses establish active infection in specific target
        cells.

9.  Which clinical presentation is typical of the first episode with
    primary HSV-2 infection?

    a.  No lesions or symptoms, HSV-1 antibodies may or may not be
        present, HSV-2 antibodies are present

    b.  Lesions present, symptoms usually mild, HSV-1 antibodies may or
        may not be present, HSV-2 antibodies are present

    c.  **Lesions present, symptoms usually severe, HSV-1, HSV-2
        antibodies are not present**

    d.  Lesions present, symptoms usually moderate, HSV-1 antibodies are
        present, HSV-2 antibodies are not present

10. The median duration of viral shedding in primary infection without
    treatment is:

    a.  Approximately 4 days

    b.  **Approximately 12 days**

    c.  5-10 days

    d.  2-4 weeks

11. All of the following are true of asymptomatic viral shedding,
    EXCEPT:

    a.  Asymptomatic shedding occurs in almost all HSV-2 seropositive
        persons.

    b.  **Rates of asymptomatic shedding are greater with HSV-1 than
        HSV-2.**

    c.  Rates of asymptomatic shedding with HSV-2 appear to be decreased
        by the presence of HSV-1 serum antibody.

    d.  The most common sites of asymptomatic shedding are the vulva and
        the perianal area in women and penile skin and the perianal area
        in men.

12. Which of the following is true about aseptic meningitis, a
    complication of genital herpes infection?

    a.  **It is more common in women than men.**

    b.  It is more common in HSV-1 than HSV-2.

    c.  It is more common in recurrent than primary infection.

    d.  It generally has severe neurologic sequelae.

13. Which of the following factors can affect the severity and frequency
    of clinical manifestations and recurrence rates of genital herpes
    infection?

    a.  Viral type

    b.  Immune status of the host

    c.  Gender

    d.  **All of the above**

14. Which of the following statements describes non-primary HSV
    infection?

    a.  First infection ever with either HSV-1 or HSV-2

    b.  Disease is more severe than recurrent disease'

    c.  No serum antibody present when symptoms appear

    d.  **Newly acquired infection with HSV-1or HSV-2 in an individual
        previously seropositive to the other virus**

15. Primary infection without treatment lasts:

    a.  3-4 days

    b.  5-7 days

    c.  10-12 days

    d.  **2-4 weeks**

16. Which of the following statements is true about recurrent infection
    without treatment?

    a.  **Duration is shorter than primary infection.**

    b.  HSV-1 infection is much more likely to recur than HSV-2.

    c.  There are usually systemic symptoms associated with the
        recurrent infection.

    d.  HSV-2 will recur slightly more frequently and after a shorter
        period of time in women than in men.

17. Which of the following statements is true about asymptomatic viral
    shedding?

    a.  Most HSV-2 is not transmitted during asymptomatic shedding.

    b.  Rates of asymptomatic shedding in HSV-2 seropositive persons are
        greatest in the first 6 months.

    c.  **Presence of serum antibody of HSV-1 seems to decrease rates of
        asymptomatic shedding with HSV-2.**

    d.  Asymptomatic shedding occurs less frequently in men with
        established HSV-2 infection.

18. Which type of lab test is considered the gold standard for HSV
    diagnosis?

    a.  Cytology

    b.  PCR assay

    c.  Antigen detection

    d.  **Viral culture**

19. Which of the following tests is considered better than culture for
    diagnosing HSV if the lesions are healing?

    a.  Type-specific serology

    b.  **Antigen detection**

    c.  Tzanck smear

    d.  PCR assay

20. Type-specific serologic tests are recommended for all of the
    following reasons EXCEPT:

    a.  To confirm clinical diagnosis

    b.  To diagnose unrecognized infection

    c.  **To screen for HSV-1 or HSV-2 infection in the general
        population**

    d.  To manage sex partners of persons with genital herpes

21. Which of the following best describes antigen detection (DFA or EIA)
    testing?

    a.  Preferred test for detecting HSV in spinal fluid; highly
        sensitive and specific; role in diagnosis of genital ulcer
        disease not well-defined

    b.  **Rapid and highly specific; fairly sensitive for symptomatic
        shedders; may be better than culture for healing lesions**

    c.  Considered the gold standard; preferred test for patients with
        genital ulcers or other mucocutaneous lesions

    d.  Insensitive and nonspecific; should not be relied on for HSV
        diagnosis

22. Which of the following is true regarding systemic antiviral therapy?

    a.  **It partially controls symptoms and signs of herpes episodes
        when used to treat first clinical and recurrent episodes or when
        used as daily suppressive therapy.**

    b.  It reduces the frequency of genital herpes recurrences by
        40%-50% when used as suppressive therapy for patients who have
        frequent recurrences.

    c.  It should never be provided to patients to self-initiate
        treatment when symptoms begin.

    d.  It is less effective than topical antiviral treatment for
        management of severe disease.

23. HSV systemic antiviral chemotherapy includes which of the following
    oral medications?

    a.  Acyclovir

    b.  Valacyclovir

    c.  Famciclovir

    d.  **All of the above**

24. Which of the following is true about episodic treatment of recurrent
    episodes of HSV disease?

    a.  It can ameliorate or shorten the duration of lesions

    b.  Patient should self-initiate the medication

    c.  Successful treatment requires initiation of therapy within 1 day
        of lesion onset

    d.  **All of the above**

25. All of the following are true of herpes in pregnancy, EXCEPT:

    a.  The risk for transmission from infected mother to neonate is
        30%-50% in women who acquire genital herpes near the time of
        delivery.

    b.  The risk for transmission from infected mother to neonate is
        \<1% in women with histories of recurrent genital herpes or who
        acquire genital HSV during the first half of pregnancy.

    c.  Most specialists recommend that women with recurrent genital
        herpetic lesions at the onset of labor be delivered abdominally.

    d.  **Most specialists recommend that women with histories of
        recurrent genital herpes who have no symptoms or signs of
        genital herpes or its prodrome at the onset of labor be
        delivered abdominally.**

26. Asymptomatic sex partners of persons diagnosed with genital herpes
    should be:

    a.  Counseled about the risk of asymptomatic transmission

    b.  Taught to recognize symptoms of genital herpes

    c.  Offered type-specific serologic testing for HSV infection

    d.  **All of the above**

27. Patients with genital herpes should be informed that:

    a.  Sexual transmission of HSV can occur during asymptomatic
        periods.

    b.  Stressful events may trigger recurrences.

    c.  The frequency of outbreaks generally decreases with increasing
        duration of the infection.

    d.  **All of the above**

28. Which of the following is true of the relationship between HSV and
    HIV infection?

    a.  Genital ulcers have no effect on the risk of HIV transmission
        and acquisition.

    b.  Lesions caused by HSV are uncommon in HIV-infected persons.

    c.  **Increased doses of antiviral drugs have been demonstrated to
        be beneficial in HIV-infected persons with genital herpes.**

    d.  All of the above

29. Patient education should include all of the following, EXCEPT:

    a.  HSV can be transmitted sexually during asymptomatic periods.

    b.  The frequency of outbreaks generally decreases with increasing
        duration of infection.

    c.  **Condom use can protect against HSV transmission regardless of
        whether the infected area or site of infection is covered by the
        condom.**

    d.  Risks of neonatal infection should be explained to women and
        men.

30. Patients with genital herpes should be advised to:

    a.  Abstain from sexual activity with uninfected partners when
        prodromal symptoms are present.

    b.  Inform their providers of their HSV status, if they are women of
        child-bearing age.

    c.  Inform future sex partners that they have genital herpes before
        initiating a sexual relationship.

    d.  **All of the above**

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**Websites and Other Resources**

1.  CDC, Division of STD Prevention:
    [www.cdc.gov/std](http://www.cdc.gov/std)

2.  National Network of STD/HIV Prevention Training Centers:
    <http://depts.washington.edu/nnptc/>

3.  2002 CDC STD Treatment Guidelines (including downloadable version
    for Palm devices): <http://www.cdc.gov/STD/treatment/>

4.  CDC National STD Hotline: 800-227-8922 or 800-342-2437; En Español:
    800-344-7432; TTY for the Deaf and Hard of Hearing: 800-243-7889

5.  CDC National Prevention Information Network (NPIN):
    [www.cdcnpin.org](http://www.cdcnpin.org/)

6.  American Social Health Association (ASHA):
    [www.ashastd.org](http://www.ashastd.org/)