Herpes simplex overview

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Herpes simplex Microchapters


Patient Information

Genital Herpes
Congenital Herpes



Orofacial Infection
Anogenital Infection
Ocular Infection
Herpes Encephalitis
Neonatal Herpes
Herpetic Whitlow
Herpes Gladiatorum
Mollaret's Meningitis


Epidemiology and Demographics

Asymptomatic Shedding

Recurrences and Triggers

Natural History, Complications and Prognosis


History and Symptoms

Physical Examination

Laboratory Findings

Direct detection of Genital Lesions


Antiviral Therapy

Antivirals for First Episode of Genital Herpes
Antivirals for Recurrent Genital Herpes

Primary Prevention


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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.


Herpes simplex is a viral disease caused by Herpes simplex viruses. Infection of the genitals is commonly known as herpes and predominantly occurs following sexual transmission of the type 2 strain of the virus (HSV-2).[1] Oral herpes, colloquially called cold sores, is usually caused by the type 1 strain of herpes simplex virus (HSV-1).[2] Both viruses cause periods of active disease—presenting as painful blisters containing infectious virus particles—that lasts 2-21 days and is followed by remission when the sores disappear. Most cases of genital herpes are asymptomatic, although viral shedding may still occur.[3] HSV-1 and HSV-2 are transmitted by direct contact with a sore or body fluid of an infected individual. After initial infection, these viruses move to sensory nerves, where they reside as life-long, latent viruses. The viruses lie dormant in trigeminal ganglia that provide sensation to the lips, lower mouth, and neck, or in lumbrosacral, which supply sensation to the genitals, perineum, and upper legs.[4] Occasionally, these viruses reactivate and return to the area of skin infected during the primary infection. Triggers for recurrences are uncertain but may include sunburn, ultraviolet light, wind, trauma, surgery, and stress. Over time, episodes of active disease reduce and the frequency of recurrences is regulated by specific immunity developed against the virus.[5]


Anogenital Infection

HSV-2 is widespread, affecting an estimated 1 in 4 females and 1 in 5 males in the United States. Most young, sexually active patients who have genital, anal, or perianal ulcers have either genital herpes or syphilis. The frequency of each condition differs by geographic area and population. Genital herpes is the most prevalent of these diseases.

Ocular Infection

Ocular herpes is generally caused by HSV-1 and is a special case of facial herpes infection known as herpes keratitis. It begins with infection of epithelial cells on the surface of the eye and retrograde infection of nerves serving the cornea.[6]

Herpes Encephalitis

Herpes simplex encephalitis (HSE) is a very serious disorder and one of the most severe viral infections of the human central nervous system.

Herpes Simplex Neonatorum

Neonatal HSV disease is a rare but serious condition, usually as a consequence of vertical transmission of the virus from the mother to the newborn child, although an estimated 10% of cases may be acquired postnatally from a parent, caretaker, or sibling. From 1/3,000 to 1/20,000 of live births are infected with neonatal herpes. Approximately 22% of pregnant women have had a previous exposure HSV-2, and a further 2% or more women acquire the virus during pregnancy.[7] Particularly among young adults, genital herpes infections are increasing caused by HSV-1.[8]

Herpetic Whitlow

A herpetic whitlow is a lesion on a finger or thumb caused by the herpes simplex virus. In children the primary source of infection is the orofacial area, and it is commonly inferred that the virus (in this case commonly HSV-1) is transferred by the chewing or sucking of fingers or thumbs. In adults it is more common for the primary source to be the genital region, with a corresponding preponderance of HSV-2. It is also seen in adult health care workers such as dentists because increased exposure to the herpes virus.

Herpes Gladiotorum

Individuals that participate in contact sports such as wrestling, rugby, and soccer sometimes acquire a condition caused by HSV-1 known as herpes gladiatorum, scrumpox, wrestler’s herpes or mat herpes. Abraded skin caused by contacts sports provides an area of entry for HSV-1. Symptoms present within 2 weeks of direct skin-to-skin contact with an infected person, and include skin ulceration on the face, ears, and neck. This disorder may cause fever, headache, sore throat and swollen glands, and occasionally affects the eyes. Physical symptoms sometimes recur in the skin.[4]

Mollaret's Meningitis

Mollaret's meningitis is a recurrent inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. Mollaret's meningitis is caused by herpes simplex virus. It is a recurrent, benign, aseptic meningitis.


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 the skin that does not appear to have a sore. Generally, a person can only get 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.

Epidemiology and Demographics

Prevalence of HSV-1 and HSV-2 infections varies throughout the world.[4] Socioeconomic status appears to be an important factor associated with HSV-1 infection levels with developing countries, such as those in Sub-Saharan Africa, showing higher levels of HSV-1 and younger acquisition rates than industrialized countries like the United States and countries in Northern Europe. The risk of infection for HSV-1 is associated with lower income and a more crowded living environment. Levels of HSV-2 infections are much lower in the U.S. (20-30%), Australia (12%), the United Kingdom (4%) and Germany (14%).[9] Risk factors for acquiring HSV-2 include being female, being Black, becoming sexually active at a young age, having a high number of sexual partners, and lower socioeconomic status.

Asymptomatic Shedding

HSV asymptomatic shedding occurs at some time in most individuals infected with herpes.


Genital herpes can cause recurrent painful genital sores in many adults, and herpes infection can be severe in patients with suppressed immune systems. It is important that women avoid contracting herpes during pregnancy because a newly acquired infection during late pregnancy poses an increased risk of transmission to the baby. If a woman has active genital herpes at delivery, a cesarean delivery is usually indicated. Patients infected with herpes are more susceptible to HIV infection; hence, herpes may indirectly play a role in the spread of HIV.

Natural History, Complications and Prognosis

If left untreated herpes simplex can become recurrent. Neonatal herpes infection is a rapidly progressive disease resulting in CNS disease and disseminated disease. Clinical presentation of herpes initially include vesicular skin rash. Early diagnosis and treatment with acyclovir prevents the progression of disease. If left untreated the infection can rarely progress to involve the CNS and other organ systems. Involvement of CNS presents with irritability, confusion and respiratory difficulty. Disseminated disease may result in rare cases. CNS disease can have residual neurological deficits. Other complications include pneumonia, esophagitis, encephalitis, premature birth, spontaneous abortion and death of the infant. Babies can have developmental delay and death.[10]The prognosis is good for herpes skin infections in immunocompetent individuals. The use of acyclovir has reduced mortality in CNS and disseminated disease but the overall prognosis is poor in immunocompromized and infants.[11]


History and Symptoms

Primary orofacial herpes / Herpes simplex type 1 presents itself as multiple, round, superficial oral ulcers [4] Adults with non-typical presentation are more difficult to diagnose. However, prodromal symptoms that occur before the appearance of herpetic lesions helps to differentiate HSV from other conditions with similar symptoms like allergic stomatitis. Genital herpes can be more difficult to diagnose than oral herpes since most genital herpes/HSV-2-infected persons have no classical signs and symptoms.[4] They present with blisters and ulcers in genital area that are similar to orofacial herpes. Herpes infection can recur even after successful initial treatment. The first episode is usually longer (two to four weeks), more painful, and more severe than the subsequent/recurrent episodes.

Physical Examination

On physical examination multiple, round, superficial oral ulcers accompanied by acute gingivitis can be seen. Also lymphadenopathy, gingivitis and tonsillitis may accompany the primary lesions [4].

Direct Detection of Lesions

The confirmation and characterization of the infection and its type, by direct detection of herpes simplex virus in genital lesions, is essential for the diagnosis, prognosis, counseling, and management. Cell culture and PCR are the preferred HSV tests for persons who seek medical treatment for genital ulcers or other mucocutaneous lesions. The sensitivity of viral culture is low, especially for recurrent lesions, and declines rapidly as lesions begin to heal. PCR assays for HSV DNA are more sensitive and are increasingly used in many settings.[12][13] PCR is the test of choice for detecting HSV in spinal fluid for diagnosis of HSV infection of the central nervous system. Viral culture isolates should be typed to determine which type of HSV is causing the infection. Failure to detect HSV by culture or PCR does not indicate an absence of HSV infection, because viral shedding is intermittent. The use of cytologic detection of cellular changes of HSV infection is an insensitive and nonspecific method of diagnosis, both for genital lesions (i.e., Tzanck preparation) and for cervical Pap smears and therefore should not be relied upon.


Medical Therapy

Treatments are available to reduce the symptoms and speed up the healing process of herpes infections, but there is currently no cure.[5] Antiviral medications can shorten and prevent outbreaks, but only for the period of time during which the person is taking the medication. In addition, daily suppressive therapy for symptomatic herpes can reduce transmission to partners. Antiviral drugs, such as aciclovir and valaciclovir, taken orally, reduce viral reproduction and shedding, and some topical creams, such as Docosanol and Tromantadine, prevent the virus from entering the skin. Some other drugs reduce herpetic symptoms by functioning in conjunction with with oral antiviral medication; Cimetidine and probenecid can reduce aciclovir clearance and aspirin can reduce inflammation associated with viral infection. Some natural remedies may have potential benefits in reducing herpes outbreaks or their symptoms. No vaccine is currently available to prevent or treat herpes.[5]

Primary Prevention

The National Institutes of Health (NIH) in the United States is currently in the midst of phase III trials of a vaccine against HSV-2, called Herpevac.[14] The vaccine has only been shown to be effective for women who have never been exposed to HSV-1. Overall, the vaccine is approximately 48% effective in preventing HSV-2 seropositivity and about 78% effective in preventing symptomatic HSV-2.[14] Assuming FDA approval, a commercial version of the vaccine is estimated to become available around 2008. During initial trials, the vaccine did not exhibit any evidence in preventing HSV-2 in males.[14] Additionally, the vaccine only reduced the acquisition of HSV-2 and symptoms due to newly acquired HSV-2 among women who did not have HSV-2 infection at the time they got the vaccine.[14] Because about 20% of persons in the United States have HSV-2 infection, this further reduces the population for whom this vaccine might be appropriate.[14]


Since there is currently no cure for herpes, some people experience negative feelings related to the condition following diagnosis, particularly if they have acquired the genital form of the disease. Though these feelings lessen over time, they can include depression, fear of rejection, feelings of isolation, fear of being "found out," self-destructive feelings, and fear of masturbation.[15] In order to improve the well-being of people with herpes, support groups have been formed in the United States and the UK which provide supportive communities, as well as information about herpes via message forums and dating websites.[16][17][18][19][20]

People with the herpes virus are often hesitant to divulge to other people, including friends and family, that they are infected. This is especially true of new or potential sexual partners that they consider "casual."[21] A perceived reaction is sometimes taken into account before making a decision about whether to inform new partners and at what point in the relationship. Many people choose not to disclose their herpes status when they first begin dating someone, and rather wait until it later becomes clear that they are moving towards a sexual relationship. Other people disclose their herpes status upfront. Still others choose only to date other people who already have herpes.


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  2. Bruce AJ, Rogers RS (2004). "Oral manifestations of sexually transmitted diseases". Clin. Dermatol. 22 (6): 520–7. doi:10.1016/j.clindermatol.2004.07.005. PMID 15596324.
  3. 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.
  4. 4.0 4.1 4.2 4.3 4.4 4.5 Fatahzadeh M, Schwartz RA (2007). "Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management". J. Am. Acad. Dermatol. 57 (5): 737–63, quiz 764–6. doi:10.1016/j.jaad.2007.06.027. PMID 17939933.
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  6. Carr DJ, Härle P, Gebhardt BM (2001). "The immune response to ocular herpes simplex virus type 1 infection". Exp. Biol. Med. (Maywood). 226 (5): 353–66. PMID 11393165.
  7. Brown ZA, Gardella C, Wald A, Morrow RA, Corey L (2005). "Genital herpes complicating pregnancy". Obstet Gynecol. 106 (4): 845–56. doi:10.1097/01.AOG.0000180779.35572.3a. PMID 16199646.
  8. Baker DA (2007). "Consequences of herpes simplex virus in pregnancy and their prevention". Curr. Opin. Infect. Dis. 20 (1): 73–6. doi:10.1097/QCO.0b013e328013cb19. PMID 17197885.
  9. Xu F, Sternberg MR, Kottiri BJ; et al. (2006). "Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States". JAMA. 296 (8): 964–73. doi:10.1001/jama.296.8.964. PMID 16926356.
  10. Kimberlin DW, Lin CY, Jacobs RF, Powell DA, Frenkel LM, Gruber WC, Rathore M, Bradley JS, Diaz PS, Kumar M, Arvin AM, Gutierrez K, Shelton M, Weiner LB, Sleasman JW, de Sierra TM, Soong SJ, Kiell J, Lakeman FD, Whitley RJ (2001). "Natural history of neonatal herpes simplex virus infections in the acyclovir era". Pediatrics. 108 (2): 223–9. PMID 11483781.
  11. Whitley RJ, Corey L, Arvin A, Lakeman FD, Sumaya CV, Wright PF, Dunkle LM, Steele RW, Soong SJ, Nahmias AJ (1988). "Changing presentation of herpes simplex virus infection in neonates". J. Infect. Dis. 158 (1): 109–16. PMID 3392410.
  12. Scoular A, Gillespie G, Carman WF (2002) Polymerase chain reaction for diagnosis of genital herpes in a genitourinary medicine clinic. Sex Transm Infect 78 (1):21-5. PMID: 11872854
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  15. Vezina C, Steben M. (2001). "Genital Herpes: Psychosexual Impacts and Counselling". The Canadian Journal of CME (June): 125–134.
  16. Herpes Support Groups & Clinics
  17. Herpes Viruses Association - a patient run group
  18. Herpes message forum with over 4000 members
  19. H-Date, a dating site for persons with either or both of HSV-1 or HSV-2
  20. MPwH - Meeting People with Herpes, a dating site with over 65000 members
  21. Green J, Ferrier S, Kocsis A, Shadrick J, Ukoumunne OC, Murphy S, Hetherton J. (2003). "Determinants of disclosure of genital herpes to partners". Sex. Transm. Infect. 79 (1): 42–44. PMID 12576613.

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