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std curriculum for clinical educators genital herpes simplex virus (hsv) module target audience - faculty in clinical education programs, including those programs that train advanced practice nurses, physician assistants, and physicians contents - the following resources are provided in this module -faculty notes (microsoft word and adobe acrobat formats) - includes notes that correspond to the slide presentation, a case study with discussion points, and test questions with answers. -slide presentation (microsoft word and adobe acrobat formats) -student handouts --case study (microsoft word format) --test questions (microsoft word format) --slides handout (adobe acrobat format) --resources (microsoft word format) suggested time allowance - the approximate time needed to present this module is 60-90 minutes.

These materials were developed by the

Training and Health Communication Branch,

Division of STD Prevention, CDC. They are

Based on the curriculum developed by the

National Network of STD/HIV Prevention

Training Centers (NNPTC) which includes

recommendations from the 2010 CDC STD

Treatment Guidelines

Information on the NNPTC can be

Accessed at:
The 2010 CDC STD Treatment Guidelines

Can be accessed or ordered online at:

January 2014
hhs logo july 2008 centers for disease control and prevention division of std prevention program and training branch

[Slide 1]

Genital and Perirectal Herpes Simplex Virus (HSV) Infection
[Slide 2]

Learning Objectives

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

  • Describe the epidemiology of genital HSV infection in the U.S.,

  • Describe the pathogenesis of genital HSV,

  • Discuss the clinical manifestations of genital HSV infection,

  • Identify the common methods used in the diagnosis of genital HSV,

  • Describe patient management for genital HSV infection,

  • List public health measures for the prevention of genital HSV infection, and

  • Summarize appropriate prevention counseling messages for genital HSV infection.

[Slide 3]


  1. Epidemiology: Disease in the U.S.

  2. Pathogenesis

  3. Clinical manifestations

  4. Diagnosis

  5. Patient management

  6. Patient Counseling and Education

[Slide 4]

Lesson I: Epidemiology: Disease in the U.S.
[Slides 5–6]

Background and Burden of Disease

      • Genital herpes is a chronic viral infection.

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

      • Most cases of recurrent genital herpes in the U.S. are caused by HSV-2. However, an increasing proportion of anogenital herpetic infection in some populations has been attributed to HSV-1 infection.

      • At least one in six adolescents and adults in the U.S. are infected with HSV-2, with an estimated 776,000 new cases occurring each year.

      • In the general U.S. population, 16.2% of adults aged 14–49 years have HSV-2 antibodies.

      • HSV-2 antibodies are not routinely detected until puberty, and then HSV-2 seroprevalence increases with age. HSV-2 seroprevalence is higher in women than men in all age groups and varies by race/ethnicity.

      • Most persons infected with HSV-2 have not been diagnosed with HSV-2.

[Slide 7]

Seroprevalence According to the Lifetime Number of Six Partners, NHANES 1999–2004

Bar Graph

seroprevalence according to the lifetime number of six partners, nhanes 1999–2004
[Slide 8]

Genital Herpes — Initial Visits to Physicians’ Offices, United States, 1966 – 2012

Line Graph

genital herpes — initial visits to physicians’ offices, united states, 1966 – 2012
[Slides 9–10]


  • 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 nonsexual route; however, an increasing proportion of genital herpes is due to HSV-1.

  • The majority of genital herpes infections are transmitted by persons unaware that they have the infection, or who are asymptomatic when transmission occurs.

  • The risk of sexual transmission is difficult to quantify, but is estimated at >5% per year in studies of monogamous heterosexual couples with discordant, type-specific HSV.

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

  • The presence of serum antibody to HSV-1 is not thought to protect against acquisition of HSV-2 infection. However, HSV-1 seropositivity increases the likelihood that an acquired HSV-2 infection will be asymptomatic.

  • Frequency of recurrences and asymptomatic viral shedding, and thus likelihood of transmission to others, declines with increased duration of infection.

  • Incubation period after acquisition is 2–12 days (average is four days).

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

[Slide 11]

HSV-2 and HIV Infection

      • Genital HSV-2 infection facilitates acquisition of HIV infection.

        • Prevalent HSV-2 infection is associated with a 2–4-fold increased risk of acquiring HIV infection.

        • Incident (new) HSV-2 infection is associated with an even higher risk of acquiring HIV infection.

      • Genital HSV-2 infection is thought to facilitate transmission of HIV infection from persons who are coinfected with both viruses.

[Slide 12]

Lesson II: Pathogenesis
[Slide 13]


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

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

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

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

      • Infection persists, despite the host immune response, often resulting in recurrent disease. Reinfection can rarely occur despite immunity.

[Slide 14]

Transmission electron micrograph of Herpes Simplex Virus


transmission electron micrograph of herpes simplex virus
[Slide 15]


      • 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.

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

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

        • Virus remains latent indefinitely in the paraspinous ganglia.

        • Reactivation induces viral replication and is precipitated by multiple known factors (e.g., trauma, fever, ultraviolet light, stress, etc.), as well as unknown factors.

        • The reactivated virus migrates centrifugally to mucosal surfaces by way of the peripheral sensory nerves, where it may cause a cutaneous outbreak of herpetic lesions or subclinical viral shedding.

      • Histopathologic changes include focal necrosis, ballooning degeneration of cells, production of mononucleated giant epithelial cells, and eosinophilic intranuclear inclusions called Cowdry type A bodies.

      • Up to 90% of persons seropositive for HSV-2 antibody have not been diagnosed with genital herpes. However, many have mild or unrecognized disease and probably most, if not all, shed virus from the genital area intermittently.

[Slide 16]

Lesson III: Clinical Manifestations
[Slides 17–18]

Definitions of Infection Types

      • First clinical episode

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

          • No serum antibody present when symptoms appear.

          • Disease more severe than recurrent disease.

          • Serum antibody may take several weeks to a few months to appear.

        • Nonprimary infection

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

          • Manifestations tend to be milder than primary infection.

          • Type-specific antibody to the prior infection is present initially. Antibody to new infection may take several weeks to a few months to appear.

        • First episode, recurrence

        • Twenty-five percent of patients with first clinical episode of HSV-2 have had a prior unrecognized primary or nonprimary first infection.

        • Type-specific antibody will be present when the patient presents, and the severity of the episode is comparable to a recurrence.

      • Recurrent symptomatic infection

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

        • Disease is usually mild and short in duration.

      • Asymptomatic infection

        • Serum antibody is present.

        • No known history of clinical outbreaks.

        • Up to two-thirds of patients with identified “asymptomatic” HSV-2 infection may actually have unrecognized symptomatic infection.

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

[Slide 19]

Types of Infection


types of infection
[Slides 20–21]

First Episode Primary infection without Treatment

Clinical manifestations of primary (initial) infection without treatment are 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.

        • Typical lesion progression: papules  vesicles  pustules  ulcers  crusts  healed. Patients may present at any stage and lesions may be atypical (e.g., fissures).

        • Often associated with systemic symptoms, including fever, headache, malaise, myalgia; and may cause urinary retention in women.

        • Illness lasts 2–4 weeks. Painful, numerous, bilateral genital lesions last an average of 11–12 days. Full reepithelialization takes an average of 17–20 days.

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

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

        • Median duration of viral shedding detected by culture (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.

        • 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.

        • HSV cervicitis occurs in 70%–90% of primary HSV-2 infections and about 70% of primary HSV-1 infections. It may involve the exocervix or endocervix and may be symptomatic or asymptomatic. The cervix will appear abnormal in most cases, with ulcerative lesions, erythema, or friability. Clinical differentiation from gonococcal or chlamydial cervicitis may be difficult, although cervical ulceration suggests HSV.

        • Herpes proctitis may be characterized by pain, discharge, tenesmus, constipation with or without symptoms of autonomic dysfunction, and severe ulceration on anoscopy.

        • Urethral involvement

          • Men with first-episode HSV have a positive urethral culture in 33% of cases. Urethritis and/or meatitis may be part of the clinical syndrome and may cause a clear mucoid discharge.

          • Over 80% of women with primary HSV report dysuria, both external and internal. HSV has been isolated from approximately 5% of women with the dysuria-frequency syndrome.

[Slide 22]

Recurrent Infection Without Treatment

        • Prodromal symptoms (localized tingling, irritation) are common and begin 12–24 hours before lesions and sometimes occur without lesions ("false prodrome").

        • Duration of episodes is shorter than in a primary infection. Painful genital lesions last four to six days. Average duration of viral shedding is four days.

        • Lesions tend to be unilateral and much less extensive than with primary infection.

        • Symptoms tend to be less severe. Usually there are no systemic symptoms.

        • Atypical presentations can occur, such as small linear ulcerations, fissures, or abrasions.

        • Rate of cervical virus shedding during recurrences is 15%–20%.

        • Up to 90% of patients with symptomatic first episode HSV-2 infection will have a recurrence within the first 12 months of infection.

        • The median recurrence rate is 4.5 recurrences per year in the first year of HSV-2 infection, but is highly variable.

        • HSV-2 has been found to recur slightly more frequently in men than in women; median of five recurrences per year compared with four per year in the first year.

        • A prolonged primary episode of more than 30 days predicts more frequent recurrences.

        • HSV-1 primary infection is much less likely to recur than HSV-2 primary infection (median of 1.3 recurrences per year in the first year).

        • The frequency of symptomatic recurrences gradually decreases over time. The frequency of recurrences decreases more quickly for HSV-1 than for HSV-2 infections.

[Slide 23]

Genital Herpes: Primary Lesions


genital herpes: primary lesions
[Slide 24]

Genital Herpes: Multiple Ulcers


genital herpes: multiple ulcers
[Slide 25]

Genital Herpes: Recurrent Ulcer


genital herpes: recurrent ulcer
[Slide 26]

Genital Herpes: Periurethal Lesions


genital herpes: periurethal lesions
[Slide 27]

Genital Herpes: Cervicitis


genital herpes: cervicitis
[Slide 28]

Herpes on the Buttock


herpes on the buttock
[Slide 29]

Oral Herpes: Soft Palate


oral herpes: soft palate
[Slides 30–31]

Asymptomatic Viral Shedding

        • Asymptomatic viral shedding has been documented in the majority of HSV-2 seropositive persons studied.

        • The amount of virus shed has been shown to be similar in those with symptomatic and asymptomatic infection.

        • Most HSV-2 is transmitted during asymptomatic shedding.

        • Using more sensitive techniques (e.g., PCR) and more frequent sampling, shedding is found more frequently (up to 20%–25% of days).

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

        • Rates of asymptomatic shedding are highest with newly-acquired infections (less than two years) and gradually decrease over time.

        • Asymptomatic shedding episodes are of briefer duration than shedding during clinical recurrences.

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

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

        • Antiviral suppressive therapy dramatically reduces, but does not completely eliminate shedding.

[Slide 32]

Complications of Genital Infection

      • Aseptic meningitis

        • More common in primary than in recurrent infection

        • More common with HSV-2 than HSV-1

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

        • May be severe, requiring hospitalization or parenteral narcotics

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

      • Other complications (rare)

        • Stomatitis and pharyngitis

        • Radicular pain, sacral paresthesias

        • Transverse myelitis

        • Autonomic dysfunction — hyperesthesias, neurogenic bladder, constipation, and impotence

        • Disseminated (viremic) infection — occasional in patients with atopic eczema, pregnant women, impaired CMI (cell-mediated immunity), neonates. Can be a cause of fulminant hepatitis in immunosuppressed patients.

        • Ocular involvement (more common with HSV-1)

        • Herpetic whitlow (more common with HSV-1)

[Slide 33]

Lesson IV: Diagnosis
[Slide 34]

HSV Diagnosis

      • Clinical diagnosis is insensitive and nonspecific; therefore, the clinical diagnosis of genital herpes should be confirmed by laboratory testing.

      • The typical painful multiple vesicular or ulcerative lesions are absent in many infected persons. Up to 50% of symptomatic first-episode cases are caused by HSV-1 in some populations, but recurrences and subclinical shedding are much less frequent for genital HSV-1 infection than genital HSV-2 infection, therefore, HSV serotype influences prognosis and counseling.

      • There are two main types of lab tests used for confirmatory diagnosis:

        • Virologic tests

        • Type-specific serologic tests

      • Both virologic and type-specific serologic tests for HSV should be available in clinical settings that provide care for patients with STDs or those at risk for STDs.

[Slides 35–36]

Virologic Tests

      • Viral culture

        • Isolation of HSV in cell culture is the preferred test, if genital ulcers or other mucocutaneous lesions are present.

        • Highly specific (greater than 99%), but sensitivity depends on stage of lesion and proper collection technique (e.g., Dacron swab to obtain specimen from ulcer base) and declines rapidly as lesions begin to heal.

        • Viral recovery for early vesicles — 90%, ulcers — 70%, and crusted lesions —30%. Culture is more often positive in primary infection (80%–90%) as contrasted with recurrences (30%).

        • Time limitations: Most cultures will be positive between 24 and 72 hours, and are generally held for between five and seven days. The enzyme-linked virus-inducible system (ELVIS) for HSV is a 24-hour culture system, but it is less sensitive than traditional culture.

        • Stable in viral transport media for 48 to 72 hours at 4°C

        • Allows for easiest typing; all cultures should be typed to determine if HSV-1 or HSV-2 is the cause of infection.

      • Polymerase Chain Reaction (PCR) assays

        • PCR assays for HSV DNA are highly sensitive and specific.

        • PCR is more sensitive than viral culture and has been increasingly used instead of culture in many settings.

        • PCR may be a reasonable choice for diagnosing genital lesions since the assays are now FDA-cleared for use with anogenital specimens, and they are clinically available.

        • PCR is the test of choice for detecting HSV in spinal fluid for the diagnosis of HSV infection of the central nervous system (CNS).

      • Antigen detection (DFA or EIA)

        • Some HSV antigen tests, unlike other virologic tests, do not distinguish HSV-1 from HSV-2.

        • Moderately sensitive (greater than 85%) in symptomatic shedders.

        • Rapid (2–12 hours).

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

        • May be better than culture for healing lesions.

      • Cytology (Tzanck or Pap)

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

        • Cytologic detection of cellular changes of herpes virus infection is insensitive (50%) and nonspecific and should not be relied on for HSV diagnosis, either for genital lesions (i.e., Tzanck preparation) or for cervical Pap smears.

[Slide 37]

Type-Specific Serologic Tests

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

      • Presence of HSV-2 antibody indicates anogenital infection.

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

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

      • Serological tests based on HSV type-specific antigens glycoprotein G1 (HSV-1) and glycoprotein G2 (HSV-2) are commercially available for type-specific testing.

        • 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 equal to or greater than 96%; false-positive results can occur, especially in patients with low likelihood of HSV infection. Therefore, repeat or confirmatory testing may be indicated in some settings.

      • The Western blot assay has been used as the gold standard technique for HSV antibody detection and can differentiate between type 1 and type 2 antibodies. However, such tests have not been developed commercially due to high cost and labor intensity.

      • Serologic tests for HSV based on IgM are not reliable for diagnosis of genital lesions or neonatal herpes, and should not be used. A positive IgM test does not necessarily indicate new infection because the test might be positive during recurrent episodes of herpes and responses are nonspecific.

[Slide 38]

Uses of Type-Specific Serologic Tests

      • Type-specific serologic assays might be useful in the following scenarios:

        • Recurrent or atypical genital symptoms with negative HSV cultures

        • A clinical diagnosis of genital herpes without laboratory confirmation

        • A sex partner with genital herpes

        • As part of a comprehensive evaluation for STDs among persons with multiple sex partners, HIV infection, and among MSM at increased risk for HIV acquisition. Cost-benefit analyses have not been performed comparing the costs of the tests versus the savings resulting from preventing further cases.

      • 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 39]

Evaluation of a Genital, Anal, or Perianal Ulcer

      • A diagnosis based only on the patient’s medical history and physical examination is frequently inaccurate.

      • All patients with genital, anal or perianal ulcers should be evaluated with a serologic test for syphilis in addition to a diagnostic evaluation for genital herpes. In settings where chancroid is prevalent, a test for Haemophilus ducreyi should also be performed.

      • Specific tests for evaluation of genital, anal, or perianal ulcers

          • Includes syphilis serology and darkfield examination

          • HSV culture and PCR are preferred serologic testing for type-specific HSV antibody.

  • No FDA-cleared PCR test for syphilis or chancroid is available in the U.S.; however, such testing can be performed by clinical laboratories that have developed their own tests and conducted a Clinical Laboratory Improvement Amendment (CLIA) verification study.

      • Healthcare providers frequently must treat patients before test results are available, because early treatment decreases the possibility of ongoing transmission and because successful treatment of genital herpes depends on prompt initiation of therapy.

[Slide 40]

Lesson V: Patient Management
[Slide 41]

Principles of Management of Genital Herpes

      • Counseling about the natural history of genital herpes, sexual and perinatal transmission, and methods to reduce transmission is integral to clinical management.

      • Antiviral chemotherapy offers clinical benefits to most symptomatic patients and is the mainstay of management.

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

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

[Slide 42]

Antiviral Therapy for HSV

      • HSV systemic antiviral chemotherapy includes three oral medications:

        • Acyclovir (ACV)

        • Valacyclovir (Valine ester of acyclovir) — high oral bioavailability

        • Famciclovir (Penciclovir prodrug) — high oral bioavailability

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

[Slide 43]

Management of First Clinical Episode of Genital Herpes

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

      • Antiviral therapy has a dramatic effect in initial HSV infection, especially if the patient has had symptoms less than seven days and has no previous history of oral HSV.

[Slide 44]

CDC-Recommended Regimens for First Clinical Episode

  • Recommended regimens are

        • Acyclovir 400 mg orally three times a day for 7–10 days, or

        • Acyclovir 200 mg orally five times a day for 7–10 days, or

        • Famciclovir 250 mg orally three times a day for 7–10 days, or

        • Valacyclovir 1 g orally twice a day for 7–10 days.

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

      • Higher dosages of acyclovir (e.g., 400 mg orally five times a day) have been used in treatment studies of first-episode herpes proctitis. However, no comparative studies have been conducted, and whether HSV proctitis requires higher doses of antiviral drugs than those used for genital herpes is unknown.

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

[Slide 45]

Recurrent Episodes of Genital Herpes

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

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

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

      • Treatment options should be discussed with all patients.

[Slide 46]

Suppressive Therapy for Recurrent Genital Herpes

        • Suppressive therapy reduces the frequency of genital herpes recurrences by 70%–80% among patients who have frequent recurrences (six or more recurrences per year), and many patients report no symptomatic outbreaks.

        • Treatment is also effective in patients with less frequent recurrences.

        • Safety and efficacy have been documented among patients receiving daily therapy with acyclovir for as long as six years, and with valacyclovir or famciclovir for one year.

        • Suppressive therapy reduces, but does not eliminate, subclinical viral shedding.

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

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

        • Daily treatment with valacyclovir 500 mg decreases the rate of HSV-2 transmission in discordant, heterosexual couples in which the source partner has a history of genital HSV-2 infection. Such couples should be encouraged to consider suppressive antiviral therapy as part of a strategy to prevent transmission, in addition to consistent condom use and avoidance of sexual activity during recurrences.

        • Suppressive antiviral therapy probably reduces transmission when used by persons who have multiple partners (including MSM) and by those who are HSV-2 seropositive without a history of genital herpes.

[Slide 46–47]

CDC-Recommended Regimens for Suppressive Therapy

  • Recommended regimens are

        • Acyclovir 400 mg orally twice a day, or

        • Famciclovir 250 mg orally twice a day, or

        • Valacyclovir 500 mg orally once a day, or

        • Valacyclovir 1 g orally once a day.

      • Acyclovir, famciclovir, and valacyclovir appear equally effective for episodic treatment for genital herpes, but famciclovir appears somewhat less effective for suppression of viral shedding.

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

[Slide 48]

Episodic Treatment for Recurrent Genital Herpes

        • Successful episodic treatment requires initiation of therapy within one day of lesion onset.

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

[Slide 49]

CDC-Recommended Regimens for Episodic Therapy

Recommended regimens are

        • Acyclovir 400 mg orally three times a day for five days, or

        • Acyclovir 800 mg orally twice a day for five days, or

        • Acyclovir 800 mg orally three times a day for two days, or

        • Famciclovir 125 mg orally twice a day for five days, or

        • Famciclovir 1,000 mg orally twice a day for one day, or

        • Famciclovir 500 mg orally once, followed by 250 mg orally twice daily for two days, or

        • Valacyclovir 500 mg orally twice a day for three days, or

        • Valacyclovir 1 g orally once a day for five days.

[Slide 50]

Severe Disease

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

      • CDC-recommended regimen

        • Acyclovir 5–10 mg/kg intravenously every eight hours for two to seven days, or until clinical improvement, followed by oral antiviral therapy to complete at least ten days of total therapy.

        • Acyclovir dose adjustment is recommended for impaired renal function.

[Slide 51]

Allergy, Intolerance, and Adverse Reactions

Allergic and other adverse reactions to acyclovir, valacyclovir, and famciclovir are rare. Desensitization to acyclovir is described in Henry RE, et al. Successful oral acyclovir desensitization. Ann Allergy 1993; 70:386-8.

[Slide 52]

Herpes in HIV-Infected Persons

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

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

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

      • AIDS case definition applies if lesions persist more than one month in recurrent disease.

      • HSV shedding is increased in HIV-infected persons. While antiretroviral therapy reduces the severity and frequency of symptomatic genital herpes, frequent subclinical shedding still occurs.

      • Suppressive or episodic therapy with oral antiviral agents is effective in decreasing the clinical manifestations of HSV among HIV-positive persons.

      • HSV type-specific serologies can be offered to HIV-positive persons during their initial evaluation, if infection status is unknown, and suppressive antiviral therapy can be considered in those who have HSV-2 infections.

      • Suppressive antiviral therapy with acyclovir and valacyclovir has been shown to decrease plasma HIV viral load and genital and rectal HIV shedding; it is currently unknown whether suppressive antiviral therapy can affect acquisition or transmission of HIV.

[Slide 53]

CDC-Recommended Regimens for Daily Suppressive Therapy in HIV-Infected Persons

Recommended regimens are

        • Acyclovir 400–800 mg orally two to three times a day, or

        • Famciclovir 500 mg orally twice a day, or

        • Valacyclovir 500 mg orally twice a day.

[Slide 54]

CDC-Recommended Regimens for Episodic Infection in HIV-Infected Persons

  • Recommended regimens are

        • Acyclovir 400 mg orally three times a day for five to ten days, or

        • Famciclovir 500 mg orally twice a day for five to ten days, or

        • Valacyclovir 1 g orally twice a day for five to ten days.

      • Acyclovir, valacyclovir, and famciclovir are safe for use in immunocompromised patients in doses recommended for treatment of genital herpes. For severe cases, initiating therapy with acyclovir 5–10 mg/kg intravenously every eight hours may be necessary.

      • 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 2010 STD Treatment Guidelines for treatment alternatives

[Slides 55–58]

Genital Herpes in Pregnancy

  • General

      • The majority of mothers of infants who acquire neonatal herpes lack histories of clinically-evident genital herpes.

      • Risk for transmission to neonate from infected mother is high (30%–50%) in women who acquire genital herpes near time of delivery and low (less than 1%) in women with histories of recurrent herpes, or who acquire genital HSV during the first half of pregnancy. However, because recurrent genital herpes is much more common than initial HSV infection during pregnancy, the proportion of neonatal HSV infections acquired from mothers with recurrent herpes is substantial.

      • Prevention of neonatal herpes depends on avoiding acquisition of HSV during late pregnancy and avoiding exposure of infant to herpetic lesions during delivery.

      • Women without known genital herpes should be counseled to avoid intercourse during the third trimester with partners known or suspected of having genital herpes.

      • Women without known orolabial herpes should be counseled to avoid receptive oral sex during the third trimester with partners known or suspected of having orolabial herpes.

      • Type-specific serologic tests may be useful to identify pregnant women at risk for HSV infection and to guide counseling regarding the risk for acquiring genital herpes during pregnancy. Such testing should be offered to women without genital herpes whose sex partner has HSV infection.

      • 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.

      • The effectiveness of antiviral therapy to decrease the risk for HSV transmission to pregnant women has not been studied.

      • All pregnant women should be asked whether they have a history of genital herpes.

      • At onset of labor

        • All women should be questioned carefully about symptoms of genital herpes, including prodromal symptoms; and

        • All women should be examined carefully for herpetic lesions.

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

      • Although cesarean section does not completely eliminate the risk for HSV transmission to the infant, women with recurrent genital herpetic lesions at onset of labor should deliver by cesarean section to prevent neonatal herpes.

      • Risk factors for HSV transmission to the infant include the following:

      • New infection

      • Primary infection

      • Lack of type-specific antibodies

      • Use of scalp electrodes

      • Safety of systemic acyclovir, valacyclovir, and famciclovir therapy in pregnant women has not been definitively established. 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. These findings provide some assurance to women who have had prenatal exposure to acyclovir. The experience with prenatal exposure to valacyclovir and famciclovir is too limited to provide useful information on pregnancy outcomes.

      • Acyclovir may be administered orally to pregnant women with first episode genital herpes or severe recurrent herpes and should be administered intravenously to pregnant women with severe HSV infection. Acyclovir treatment late in pregnancy reduces the frequency of cesarean sections among women who have recurrent genital herpes by diminishing the frequency of recurrences at term. The effect of antiviral therapy late in pregnancy on the incidence of neonatal herpes is not known.

      • No data support the use of antiviral therapy among HSV seropositive women without a history of clinical genital herpes.

    • Neonatal Herpes

      • Infants exposed to HSV during birth, as documented by maternal virologic testing or presumed by observation of maternal lesions, should be followed carefully in consultation with a specialist.

      • Surveillance cultures of mucosal surfaces to detect HSV infection might be considered before development of clinical signs of neonatal herpes.

      • Acyclovir might be considered for infants born to women who acquired HSV near term because the risk of neonatal herpes is high for these infants.

      • All infants who have neonatal herpes should be promptly evaluated and treated with systemic acyclovir.

      • The recommended regimen for infants treated for known or suspected neonatal herpes is acyclovir 20 mg/kg body weight intravenously every eight hours for 21 days for disseminated and central nervous system (CNS) disease, or for 14 days for disease limited to the skin and mucous membranes.

    • Therapy of acyclovir-resistant HSV infections

      • All acyclovir-resistant strains are resistant to valacyclovir and most are resistant to famciclovir.

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

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

      • Topical cidofovir gel 1% applied to lesions might be effective. This preparation is not commercially available and must be compounded by a pharmacy.

    • Adjunctive therapy

      • Pain relief — usually necessary only in primary disease. Painful urination can be alleviated by urinating in warm bath.

      • Topical measures — drying or analgesia is of unproven benefit, but some patients report relief.

      • Sitz baths

[Slide 59]

Lesson VI: Patient Counseling and Education
[Slide 60–61]

Patient Counseling and Education

      • Counseling has two main goals:

        • To help patients cope with the infection

        • To prevent sexual and perinatal transmission

      • 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.

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

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

      • 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.

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

      • The psychological effect of a serologic diagnosis of HSV-2 infection in a person with asymptomatic or unrecognized genital herpes appears small and transient.

    • Patient education should include

      • Natural history of the infection,

      • Treatment options,

      • Transmission and prevention issues,

      • Neonatal HSV prevention issues, and

      • Emphasize the potentials for recurrent episodes, asymptomatic viral shedding, and sexual transmission.

[Slide 62]

Counseling: Natural History of the Infection

      • Recurrent episodes will likely follow a symptomatic first episode.

        • HSV-2 infections have more frequent recurrences than HSV-1 infections.

        • The frequency of outbreaks generally decreases over time.

      • Asymptomatic viral shedding occurs, and HSV can be transmitted to a sex partner during asymptomatic periods.

        • Asymptomatic shedding is more frequent in genital HSV-2 infection than genital HSV-1 infection.

        • Asymptomatic shedding is most frequent during the first 12 months after acquiring HSV-2.

      • Stressful events may trigger recurrences.

      • Prodromal symptoms may precede outbreaks.

[Slide 63]

Counseling: Treatment Options

      • Suppressive therapy is available and is effective in preventing symptomatic recurrent episodes.

      • Episodic therapy is sometimes useful in shortening the duration of recurrent episodes, if started within one day of lesion onset.

      • Counseling on when and how to take antiviral medications

      • Recognition of prodromal symptoms to know when to begin episodic therapy

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

[Slide 64]

Counseling: Transmission and Prevention

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

      • Encourage all persons with genital herpes infection to

        • Inform current sex partners about diagnosis of genital herpes,

        • Inform future partners before initiating a sexual relationship, and

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

  • Correct and consistent use of latex condoms might reduce the risk of genital herpes transmission.

  • Daily treatment with valacyclovir 500 mg decreases the rate of HSV-2 transmission in discordant, heterosexual couples in which the source partner has a history of genital HSV-2 infection. Such couples should be encouraged to consider suppressive antiviral therapy as part of a strategy to prevent transmission, in addition to consistent condom use and avoidance of sexual activity during recurrences. Episodic therapy does not reduce the risk for transmission and its use should be discouraged for this purpose among persons whose partners might be at risk for HSV-2 acquisition.

  • Suppressive antiviral therapy probably reduces transmission when used by persons who have multiple partners (including MSM) and by those who are HSV-2 seropositive without a history of genital herpes.

[Slide 65]

Counseling: Neonatal Herpes Prevention

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

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

      • Advise pregnant women who are not infected with HSV-2 to avoid intercourse during the third trimester with men who have genital herpes.

      • Advise pregnant women who are not infected with HSV-1 to avoid genital exposure to HSV-1 during the third trimester (e.g., oral sex with a partner with oral herpes and vaginal intercourse with a partner with genital HSV-1 infection).

[Slide 66]

Counseling for Asymptomatic Persons

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

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

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

[Slide 67]

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