Johns Hopkins Division of Infectious Diseases
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Author: Anne Marie Rompalo Last modified: December 19, 2001


  • Herpes is a member of the human herpes viruses which include: herpes simplex virus type 1 (HSV-1) which commonly causes fever blisters or cold sores, herpes simplex virus type 2 (HSV-2), varicella zos
  • All members of this family of virus establish latent infection and can cause recurrent disease.
  • HSV-1 and HSV-2 cause sores that look and act the same. HSV-1, however, recurs more frequently in the oral area, wherease HSV-2 recurrs more often in the genital area.
  • The majority of herpes outbreaks in the U.S. are caused by HSV-2, but 10-50% of first episodes are due to HIV-1.
  • An estimated 1 million new cases occur each year. More than 50% of these new cases are asymptomatic or unrecognized
  • In the general U.S. population, 22% of adults over age 12 have HSV-2 antibodies. Among whites, 15% of men and 20% of women are HSV-2 seropositive, and among blacks, 35% of men and 55% of women are se


  • Seropositivity increases with age and number of lifetime sexual partners.
  • Most sexual transmission occurs when the person with herpes is shedding the virus and is asymptomatic.
  • The risk of sexual transmission is difficult to quantify, but is estimated at 10% per year in monogamous heterosexual couples where on is infected and the other one isn’t.
  • Transmission efficiency is greater from men to women than from women to men (17% vs. 4%).
  • HSV-1 seropositivity partially protects against having a symptomatic infection.
  • Likelihood of transmission (frequency of occurrences and asymptomatic viral shedding) to others declines with increased duration of infection.
  • Incubation period after acquisition is 2-12 days (average is 4 days).
  • HSV is readily inactivated by drying and soap and water, so that fomite transmission is unlikely.
  • There is mounting evidence that genital HSV-2 infection facilitates both acquisition and transmission of HIV infection.


  • Primary Infection:
  • First infection EVER with either HSV-1 or HSV-2
  • Blood tests show no antibody to HSV-1 or HSV-2 when symptoms appear
  • Disease is more severe
  • Blood tests show antibody appears 2 to 3 months after symptoms
  • Symptoms of Primary Infection
  • 40% of men and 70% of women may have low grade fever, headache, malaise, muscle aches and urinary retention (10% women)
  • Generally, symptoms peak within 3 to 4 days of lesions appearing and recede over the next 3 to 4 days
  • Lesions tend to be numerous, on both sides of the genitals, painful, itch with healing; these sores can last 11 to 12 days and may take 17 to 21 days to completely heal
  • Urethral discharge can occur in 30% of men
  • Inguinal lymph nodes are swollen and tender on both sides in 80% of patients; they may be swollen for 2 to 3 weeks and are often the last symptom to resolve
  • The average duration of viral shedding is about 12 days, and declines as the sores crust.
  • Non-Primary Infection
  • A new infection with either HSV-1 or HSV-2 in a person who already is infected with the other type of HSV. For example, a person who has cold sores or a blood test showing antibodies to HSV-1 and now
  • Clinical symptoms tend to be milder than in primary infection
  • Symptoms of non-primary infection
  • Similar to those of primary infection but tend to be milder
  • Recurrent symptomatic infection:
  • Blood tests show antibody is present when symptoms appear, although the patient may not be aware of previous episodes
  • Symptoms of recurrent infection
  • About half of infected people will begin to have localized tingling or irritation at the site of the lesions 12 to 24 hours before they appear. This is called a prodrome
  • Symptoms tend to be localized to painful genital lesions that last 4 to 6 days. There is usually no headache, or fever.
  • The average duration of viral shedding is 4 days
  • Sores tend to be at one site
  • Genital HSV-2 tend to recur more frequently than genital HSV-1
  • After primary infection with HSV-2, HSV-2 will recur slightly more frequently and after a shorter period of time in men than in women with about 5 recurrence per year.
  • If the primary genital infection was severe and prolonged, recurrences will be more frequent
  • Asymptomatic viral shedding
  • Blood test show present of antibody BUT the patient has no known history of clinical outbreaks
  • Up to two-thirds of patients who think they are asymptomatic can be taught to recognize the signs and symptoms of their genital herpes.
  • Most HSV-2 is transmitted during asymptomatic shedding
  • Penile skin and perianal area in men are the most common sites of asymptomatic shedding
  • Asymptomatic shedding is of briefer duration than during clinical recurrences
  • Shedding is dramatically reduced, although not eradicated by suppressive antiherpes medication


  • Syphilis, chancroid infections, trauma, molluscum contagiosum, rarely veneral warts and cancer can cause genital lesions.
  • A culture of the lesion will grow HSV which can be typed. The earlier the culture is taken when the lesions first appear (such as during the ulcer stage and not the crusted stage), the better the cha
  • New blood tests that can reliably detect HSV-1 and HSV-2 are now available. These are called gG-based type-specific assays. False positive blood tests, however, can occur, especially in patients wit
  • The best results occur when the drug is taken within 24 to 48 hours of lesion appearance or within 12 to 24 hours of prodromal symptoms. None eradicate latent infection.
  • Acyclovir
  • Famciclovir
  • Valacyclovir
  • Acyclovir 400 mg t.i.d. for 7-10 days until complete crusting has occurred.
  • Acyclovir 200 mg 5 time’s daily also effective, but compliance is difficult.
  • Acyclovir 400 mg 5 time’s daily in HIV-infected patients or for herpes proctitis or oral stomatitis.
  • Valacyclovir 1 gm b.i.d. for 7-10 days.
  • Famciclovir 250 mg t.i.d. for 7-10 days.
  • Treatment may be extended if healing is incomplete after 10 days of therapy.
  • Acyclovir 400 mg orally 3 times a day for 5 days, or 200 mg 5 times a day for 5 days, or 800 mg twice a day for 5 days
  • Famciclovir 125 mg orally twice a day for 5 days
  • Valacyclovir 500 mg twice a day for 5 days or valacyclovir 500 mg twice a day for 3 days.
  • 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.
  • In recurrent HSV, therapy shortens virus shedding and lesion and symptom duration.
  • Therapy appears to have no effect on interval until recurrence or frequency of recurrences.
  • Patient should self-start the medication.
  • Acyclovir 400 mg b.i.d.
  • Valacyclovir 500 mg once daily or 1,000 mg once daily
  • Famciclovir 250 mg b.i.d.
  • Valacyclovir 500 mg once a day appears less effective than other valacyclovir dosing regimens in patients who have very frequent recurrences (i.e. >10 episodes per year).
  • Acyclovir has been used safely for up to 10 years and with valacyclovir and famciclovir for 1 year.
  • Use continuously for 1 year, and then discuss discontinuation in order to reassess rate of recurrent episodes.
  • Patients should be warned that they may have rebound outbreaks when suppression is discontinued, suppression does not eliminate latency
  • Abstain from sex when lesion present.
  • Use condoms with all new sexual partners; however, they may not be completely effective at preventing HSV transmission.
  • Transmission can occur without lesions and most cases are transmitted during asymptomatic periods. Asymptomatic shedding is more common with HSV-2 and those with recently acquired HSV.
  • Frequency of outbreaks generally decreases with increasing duration of infection.
  • Become familiar with your prodromal symptoms and when/how to take medication.
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