Herpes simplex pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2], Lakshmi Gopalakrishnan, M.B.B.S.


HSV-1 and HSV-2 can be found in and released from the sores that the viruses cause, but they also may be released between outbreaks from skin that does not appear to have a sore. Generally, a person can only acquire HSV-2 infection during sexual contact with someone who has a genital HSV-2 infection. Transmission can occur from an infected partner who does not have a visible sore and may not know that he or she is infected. HSV-1 can cause genital herpes, but it more commonly causes infections of the mouth and lips, so-called fever blisters. HSV-1 infection of the genitals can be caused by oral-genital or genital-genital contact with a person who has HSV-1 infection. Genital HSV-1 outbreaks recur less regularly than genital HSV-2 outbreaks.

The surest way to avoid transmission of genital herpes, is to abstain from sexual contact, or to be in a long-term mutually monogamous relationship with a partner who has been tested and is known to be uninfected. Genital ulcer diseases can occur in both male and female genital areas that are covered or protected by a latex condom, as well as in areas that are not covered. Correct and consistent use of latex condoms can reduce the risk of genital herpes. Persons with herpes should abstain from sexual activity with uninfected partners when lesions or other symptoms of herpes are present. It is important to know that even if a person is asymptomatic, he or she can still infect sex partners. A positive HSV-2 blood test most likely indicates a genital herpes infection.


Mode of Transmission

  • Herpes can be contracted through direct contact with an active lesion or body fluid of an infected person.[1] Infected people that show no visible symptoms may still shed and transmit virus through their skin, and this asymptomatic shedding may represent the most common form of HSV-2 transmission.[2]
  • There are no documented cases of infection via an inanimate object (e.g. a towel, toilet seat, drinking vessels).
  • To infect a new individual, HSV travels through tiny breaks in the skin or mucous membranes in the mouth or genital areas. Even microscopic abrasions on mucous membranes are sufficient to allow viral entry.

Population At Risk

  • Herpes transmission occurs between discordant partners and a person with a history of infection (HSV seropositive) can pass the virus to an HSV seronegative person.[3] Antibodies that develop following an initial infection with that type of HSV help prevent reinfection with the same herpes type. In a monogamous couple, a seronegative female runs greater than 30% per year risk of contracting an HSV-1 infection from a seropositive male partner. If an oral HSV-1 infection is contracted first, seroconversion will have occurred after 6 weeks to provide protective antibodies against a future genital HSV-1 infection.
  • As with almost all sexually transmited infections, women are more susceptible to acquiring genital HSV-2 than men.[4] On an annual basis, without the use of antivirals or condoms, the transmission risk of HSV-2 from infected male to female is approximately 8-10%. This is believed to be due to the increased exposure of mucosal tissue to potential infection sites. Transmission risk from infected female to male is approximately 4-5% annually.
  • HSV seropositive individuals practicing unprotected sex with HIV positive persons pose a high risk of HIV transmission, and are even more susceptible to HIV during an outbreak with active sores.[5]

Prevention of Transmission

  • For genital herpes, condoms are a highly effective in limiting transmission of herpes simplex infection.[6][7] Condom use reduce the risk of transmission by 50%. The use of condom is much more effective in the prevention of male to female transmission than vice-versa. However, condoms are by no means completely effective. The virus cannot get through latex, but their effectiveness is somewhat limited on a public health scale by the limited use of condoms in the community,[8] and on an individual scale because the condom may not completely cover blisters on the penis of an infected male, or base of the penis or testicles not covered by the condom may come into contact with free virus in vaginal fluid of an infected female.
  • In cases where condom use is ineffective, abstinence from sexual activity, or washing of the genitals after sex, is recommended.
  • The use of dental dams also limits the transmission of herpes from the genitals of one partner to the mouth of the other (or vice versa) during oral sex.
  • Topical microbicides contain chemicals that directly inactivate the virus and block viral entry are currently being investigated.[3]
  • When one partner has herpes simplex infection and the other does not, the use of antiviral medication, such as valaciclovir, in conjunction with a condom, further decreases the chances of transmission to the uninfected partner.[3]
  • Antivirals also help to prevent the development of symptomatic HSV infection in approximately 50%, indicating that the infected partner may be seropositive but symptom-free. The effects of combining antiviral and condom use is roughly additive, thus resulting in approximately a 75% combined reduction in annual transmission risk. These figures reflect experiences with subjects having frequently recurring genital herpes (greater than 6 recurrences per year). Subjects with low recurrence rates and those with no clinical manifestations were excluded from these studies.
  • Suppressive antiviral therapy reduces the risk of transmission by 50%. Suppressive antiviral therapy with valaciclovir 500 mg once daily reduces the rate of acquisition of HSV-2 infection and clinically symptomatic genital herpes in serodiscordant couples. In a randomised trial involving 1,484 patients treated for 8 months, 0.5% valaciclovir recipients developed symptomatic infection compared with 2.2% of placebo recipients, and 1.6% compared with 3.2% acquired HSV-2 infection. Although valaciclovir reduced the risk of acquiring symptomatic infection by 75%, approximately 60 people needed to be treated to prevent one transmission.
  • Vaccines for HSV are currently undergoing trials. Once developed, they may be used to help with prevention or minimize initial infections as well as treatment for existing infections. [9]
  • To prevent neonatal infections, seronegative women are advised to avoid unprotected oral-genital contact with an HSV-1 seropositive partner and conventional sex with a partner having a genital infection during the last trimester of pregnancy. Mothers infected with HSV are advised to avoid procedures that would cause trauma to the infant during birth (e.g. fetal scalp electrodes, forceps and vacuum extractors) and, should lesions be present, to elect caesarean section to reduce exposure of the child to infected secretions in the birth canal.[3] The use of antiviral treatments, such as aciclovir, given from the 36th week of pregnancy limits HSV recurrence and shedding during childbirth, thereby reducing the need for caesarean section.[3]


  1. "AHMF: Preventing Sexual Transmission of Genital Herpes". Retrieved 2008-02-24.
  2. Leone P (2005) Reducing the risk of transmitting genital herpes: advances in understanding and therapy. Curr Med Res Opin 21 (10):1577-82. DOI:10.1185/030079905X61901 PMID: 16238897
  3. 3.0 3.1 3.2 3.3 3.4 Gupta R, Warren T, Wald A (2007) Genital herpes. Lancet 370 (9605):2127-37. DOI:10.1016/S0140-6736(07)61908-4 PMID: 18156035
  4. Carla K. Johnson (August 23, 2006). "Percentage of people with herpes drops". Associated Press.
  5. Koelle DM, Corey L (2008). "Herpes Simplex: Insights on Pathogenesis and Possible Vaccines". Annu Rev Med. 59: 381–395. doi:10.1146/annurev.med.59.061606.095540. PMID 18186706.
  6. Wald A, Langenberg AG, Link K, Izu AE, Ashley R, Warren T, Tyring S, Douglas JM Jr, Corey L. (2001). "Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women". JAMA. 285 (24): 3100–3106. PMID 11427138.
  7. Casper C, Wald A. (2002). "Condom use and the prevention of genital herpes acquisition". Herpes. 9 (1): 10–14. PMID 11916494.
  8. de Visser RO, Smith AM, Rissel CE, Richters J, Grulich AE. (2003). "Sex in Australia: safer sex and condom use among a representative sample of adults". Aust. N. Z. J. Public Health. 27 (2): 223–229. PMID 14696715.
  9. Seppa, Nathan (2005-01-05). "One-Two Punch: Vaccine fights herpes with antibodies, T cells". Science News. p. 5. Retrieved 2007-03-29.

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