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.
Recurrences and triggers
Following active infection, herpes viruses become quiescent to establish a latent infection in sensory and autonomic ganglia of the nervous system. The double-stranded DNA of the virus is incorporated into the cell physiology by infection of the cell nucleus of a nerve's cell body. HSV latency is static - no virus is produced - and is controlled by a number of viral genes including Latency Associated Transcript (LAT).[1]
The causes of reactivation from latency are uncertain but several potential triggers have been documented. Physical or psychological stress can trigger an outbreak of herpes.[2] Local injury to the face, lips, eyes or mouth, trauma, surgery, wind, radiotherapy, ultraviolet light or sunlight are well established triggers.[3][4][5][6][7] Some studies suggest changes in the immune system during menstruation may play a role in HSV-1 reactivation.[8][9] In addition, concurrent infections, such as viral upper respiratory tract infection or other febrile diseases, can cause outbreaks, hence the historic terms "cold sore" and "fever blister".
The frequency and severity of recurrent outbreaks may vary greatly depending upon the individual. Outbreaks may occur at the original site of the infection or in close proximity to nerve endings that reach out from the infected ganglia. In the case of a genital infection, sores can appear near the base of the spine, the buttocks, back of the thighs, or they may appear at the original site of infection. Immunocompromised individuals may experience episodes that are longer, more frequent and more severe. The human body is able to build up an immunity to the virus over time and antiviral medication has been proven to shorten the duration and/or frequency of the outbreaks.[10]
Transmission and prevention
Mode of Transmission
- Herpes can be contracted through direct contact with an active lesion or body fluid of an infected person.[11] 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.[12]
- 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.[13] Antibodies that develop following an initial infection with that type of HSV prevents reinfection with the same herpes type - a person with a history of a cold sore caused by HSV-1 cannot contract a herpes whitlow or genital infection caused by HSV-1. 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.[14] 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 practising 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.[15]
Prevention of Transmission
- For genital herpes, condoms are a highly effective in limiting transmission of herpes simplex infection.[16][17] 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,[18] 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.[13]
- 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.[13]
- 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. [19]
- To prevent neonatal infections, seronegative women are recommended 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.[13] 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.[13]
References
- ↑ Stumpf MP, Laidlaw Z, Jansen VA (2002). "Herpes viruses hedge their bets". Proc. Natl. Acad. Sci. U.S.A. 99 (23): 15234–7. doi:10.1073/pnas.232546899. PMID 12409612.
- ↑ Sainz B, Loutsch JM, Marquart ME, Hill JM (2001). "Stress-associated immunomodulation and herpes simplex virus infections". Med. Hypotheses. 56 (3): 348–56. doi:10.1054/mehy.2000.1219. PMID 11359358.
- ↑ Chambers A, Perry M (2008). "Salivary mediated autoinoculation of herpes simplex virus on the face in the absence of "cold sores," after trauma". J. Oral Maxillofac. Surg. 66 (1): 136–8. doi:10.1016/j.joms.2006.07.019. PMID 18083428.
- ↑ Perna JJ, Mannix ML, Rooney JF, Notkins AL, Straus SE (1987). "Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model". J. Am. Acad. Dermatol. 17 (3): 473–8. PMID 2821086.
- ↑ Rooney JF, Straus SE, Mannix ML; et al. (1992). "UV light-induced reactivation of herpes simplex virus type 2 and prevention by acyclovir". J. Infect. Dis. 166 (3): 500–6. PMID 1323616.
- ↑ Oakley C, Epstein JB, Sherlock CH (1997). "Reactivation of oral herpes simplex virus: implications for clinical management of herpes simplex virus recurrence during radiotherapy". Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 84 (3): 272–8. PMID 9377190.
- ↑ Ichihashi M, Nagai H, Matsunaga K (2004). "Sunlight is an important causative factor of recurrent herpes simplex". Cutis. 74 (5 Suppl): 14–8. PMID 15603217.
- ↑ Myśliwska J, Trzonkowski P, Bryl E, Lukaszuk K, Myśliwski A (2000). "Lower interleukin-2 and higher serum tumor necrosis factor-a levels are associated with perimenstrual, recurrent, facial Herpes simplex infection in young women". Eur. Cytokine Netw. 11 (3): 397–406. PMID 11022124.
- ↑ Segal AL, Katcher AH, Brightman VJ, Miller MF (1974). "Recurrent herpes labialis, recurrent aphthous ulcers, and the menstrual cycle". J. Dent. Res. 53 (4): 797–803. PMID 4526372.
- ↑ Martinez V, Caumes E, Chosidow O (2008). "Treatment to prevent recurrent genital herpes". Curr Opin Infect Dis. 21 (1): 42–48. doi:10.1097/QCO.0b013e3282f3d9d3. PMID 18192785.
- ↑ "AHMF: Preventing Sexual Transmission of Genital Herpes". Retrieved 2008-02-24.
- ↑ 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
- ↑ 13.0 13.1 13.2 13.3 13.4 Gupta R, Warren T, Wald A (2007) Genital herpes. Lancet 370 (9605):2127-37. DOI:10.1016/S0140-6736(07)61908-4 PMID: 18156035
- ↑ Carla K. Johnson (August 23, 2006). "Percentage of people with herpes drops". Associated Press.
- ↑ 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.
- ↑ 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.
- ↑ Casper C, Wald A. (2002). "Condom use and the prevention of genital herpes acquisition". Herpes. 9 (1): 10–14. PMID 11916494.
- ↑ 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.
- ↑ Seppa, Nathan (2005-01-05). "One-Two Punch: Vaccine fights herpes with antibodies, T cells". Science News. p. 5. Retrieved 2007-03-29.