View source for Medicine:Herpes

{{Short description|Viral disease caused by herpes simplex viruses}}
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{{Pp-semi-indef}}
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{{Infobox medical condition (new)
| synonyms        = Herpes simplex
| name            =
| image           = Herpes(PHIL 1573 lores).jpg
| alt             =
| caption         = [[Medicine:Cold sore|Oral herpes]] of the lower lip. Note the blisters in a group marked by an arrow.
| pronounce       = {{IPAc-en|ˈ|h|ɜɹ|p|iː|z}}
| field           = [[Medicine:Infectious disease (medical specialty)|Infectious disease]]
| symptoms        = Blisters that break open and form small [[Medicine:Ulcer|ulcer]]s, fever, swollen [[Biology:Lymph node|lymph node]]s<ref name=CDC2014F/>
| complications   =
| onset           =
| duration        = 2–4 weeks<ref name=CDC2014F/>
| causes          = Herpes simplex virus spread by direct contact<ref name=CDC2014F/>
| risks           = [[Biology:Immunosuppression|Decreased immune function]], stress, sunlight<ref name=Bal2014/><ref name="Cancer"/>
| diagnosis       = Based on symptoms, [[Biology:Polymerase chain reaction|PCR]],  [[Biology:Viral culture|viral culture]]<ref name=CDC2014F/><ref name=Bal2014/>
| differential    =
| prevention      =
| treatment       =
| medication      = [[Chemistry:Aciclovir|Aciclovir]], [[Chemistry:Valaciclovir|valaciclovir]], [[Chemistry:Paracetamol|paracetamol]] (acetaminophen), topical lidocaine<ref name=CDC2014F/><ref name=Bal2014/>
| prognosis       =
| frequency       = 60–95% (adults)<ref name=Peds09/>
| deaths          =
}}

'''Herpes simplex''', often known simply as '''herpes''', is a [[Medicine:Viral disease|viral infection]] caused by the herpes simplex virus.<ref name="WHO2022">{{cite web |title=Herpes simplex virus |url=https://www.who.int/news-room/fact-sheets/detail/herpes-simplex-virus |website=World Health Organization |access-date=21 November 2022}}</ref> Herpes infections are categorized by the area of the body that is infected. The two major types of herpes are [[Medicine:Cold sore|oral herpes]] and [[Medicine:Genital herpes|genital herpes]], though [[Medicine:Herpes simplex#Types of herpes|other forms]] also exist. 

Oral herpes involves the face or mouth. It may result in small [[Medicine:Blister|blister]]s in groups, often called cold sores or fever blisters, or may just cause a sore throat.<ref name=Bal2014/><ref>{{cite book|last1=Mosby|title=Mosby's Medical Dictionary|date=2013|publisher=Elsevier Health Sciences|isbn=9780323112581|pages=836–37|edition=9|url=https://books.google.com/books?id=aW0zkZl0JgQC&pg=PA836|url-status=live|archive-url=https://web.archive.org/web/20170906210724/https://books.google.com/books?id=aW0zkZl0JgQC&pg=PA836|archive-date=2017-09-06}}</ref> Genital herpes involves the genitalia. It may have minimal symptoms or form blisters that break open and result in small [[Medicine:Ulcer|ulcer]]s.<ref name=CDC2014F/> These typically heal over two to four weeks.<ref name=CDC2014F/> Tingling or shooting pains may occur before the blisters appear.<ref name=CDC2014F/> 

Herpes cycles between periods of active disease followed by periods without symptoms.<ref name=CDC2014F/> The first episode is often more severe and may be associated with fever, muscle pains, swollen [[Biology:Lymph node|lymph node]]s and headaches.<ref name=CDC2014F/> Over time, episodes of active disease decrease in frequency and severity.<ref name=CDC2014F/>

[[Medicine:Herpetic whitlow|Herpetic whitlow]] typically involves the fingers or thumb,<ref>{{cite journal|last1=Wu|first1=IB|last2=Schwartz|first2=RA|title=Herpetic whitlow.|journal=Cutis|date=March 2007|volume=79|issue=3|pages=193–06|pmid=17674583}}</ref> [[Medicine:Herpes simplex keratitis|herpes simplex keratitis]] involves the eye,<ref>{{cite journal|last1=Rowe|first1=AM|last2=St Leger|first2=AJ|last3=Jeon|first3=S|last4=Dhaliwal|first4=DK|last5=Knickelbein|first5=JE|last6=Hendricks|first6=RL|title=Herpes keratitis.|journal=Progress in Retinal and Eye Research|date=January 2013|volume=32|pages=88–101|pmid=22944008|doi=10.1016/j.preteyeres.2012.08.002|pmc=3529813}}</ref> [[Medicine:Herpesviral encephalitis|herpesviral encephalitis]] involves the brain,<ref>{{cite journal|last1=Steiner|first1=I|last2=Benninger|first2=F|title=Update on herpes virus infections of the nervous system.|journal=Current Neurology and Neuroscience Reports|date=December 2013|volume=13|issue=12|pages=414|pmid=24142852|doi=10.1007/s11910-013-0414-8|s2cid=22139709}}</ref> and neonatal herpes involves any part of the body of a newborn, among others.<ref>{{cite journal|last1=Stephenson-Famy|first1=A|last2=Gardella|first2=C|title=Herpes Simplex Virus Infection During Pregnancy.|journal=Obstetrics and Gynecology Clinics of North America|date=December 2014|volume=41|issue=4|pages=601–14|pmid=25454993|doi=10.1016/j.ogc.2014.08.006}}</ref>

There are two types of herpes simplex virus, type 1 (HSV-1) and type 2 (HSV-2).<ref name=CDC2014F/> HSV-1 more commonly causes infections around the mouth while HSV-2 more commonly causes genital infections.<ref name=Bal2014/> They are transmitted by direct contact with body fluids or lesions of an infected individual.<ref name=CDC2014F/> Transmission may still occur when symptoms are not present.<ref name=CDC2014F/> Genital herpes is classified as a [[Medicine:Sexually transmitted infection|sexually transmitted infection]].<ref name=CDC2014F/> It may be spread to an infant during childbirth.<ref name=CDC2014F/> After infection, the viruses are transported along [[Biology:Sensory neuron|sensory nerves]] to the nerve cell bodies, where they [[Biology:Virus latency|reside lifelong]].<ref name=Bal2014>{{cite journal|last1=Balasubramaniam|first1=R|last2=Kuperstein|first2=AS|last3=Stoopler|first3=ET|title=Update on oral herpes virus infections.|journal=Dental Clinics of North America|date=April 2014|volume=58|issue=2|pages=265–80|pmid=24655522|doi=10.1016/j.cden.2013.12.001}}</ref> Causes of recurrence may include: [[Biology:Immunosuppression|decreased immune function]], stress, and sunlight exposure.<ref name=Bal2014/><ref name="Cancer">{{cite journal |author=Elad S |title=A systematic review of viral infections associated with oral involvement in cancer patients: a spotlight on Herpesviridea |journal=Support Care Cancer |volume=18 |issue=8 |pages=993–1006 |date=August 2010 |pmid=20544224 |doi=10.1007/s00520-010-0900-3 |name-list-style=vanc|author2=Zadik Y |author3=Hewson I |display-authors=3 |last4=Hovan |first4=Allan |last5=Correa |first5=M. Elvira P. |last6=Logan |first6=Richard |last7=Elting |first7=Linda S. |last8=Spijkervet |first8=Fred K. L. |last9=Brennan |first9=Michael T.|s2cid=2969472 }}</ref> Oral and genital herpes is usually diagnosed based on the presenting symptoms.<ref name=Bal2014/> The diagnosis may be confirmed by [[Biology:Viral culture|viral culture]] or detecting herpes DNA in fluid from blisters.<ref name=CDC2014F/> Testing the blood for [[Biology:Antibodies|antibodies]] against the virus can confirm a previous infection but will be negative in new infections.<ref name=CDC2014F/>

The most effective method of avoiding genital infections is by avoiding vaginal, oral, manual, and anal sex.<ref name=CDC2014F/><ref>{{cite book| last1 = Hoyle | first1 = Alice | last2 = McGeeney | first2 = Ester |title=Great Relationships and Sex Education|publisher=Taylor and Francis|year=2019|access-date=July 11, 2023|isbn=978-1-35118-825-8|url=https://books.google.com/books?id=KE7ADwAAQBAJ&pg=PT261}}</ref> [[Medicine:Condom|Condom]] use decreases the risk.<ref name=CDC2014F/> Daily [[Biology:Antiviral drug|antiviral medication]] taken by someone who has the infection can also reduce spread.<ref name=CDC2014F/> There is no available [[Biology:Vaccine|vaccine]]<ref name=CDC2014F/> and once infected, there is no cure.<ref name=CDC2014F/> [[Chemistry:Paracetamol|Paracetamol]] (acetaminophen) and topical lidocaine may be used to help with the symptoms.<ref name=Bal2014/> Treatments with antiviral medication such as [[Chemistry:Aciclovir|aciclovir]] or [[Chemistry:Valaciclovir|valaciclovir]] can lessen the severity of symptomatic episodes.<ref name=CDC2014F/><ref name=Bal2014/>

Worldwide rates of either HSV-1 or HSV-2 are between 60% and 95% in adults.<ref name=Peds09/> HSV-1 is usually acquired during childhood.<ref name=CDC2014F>{{cite web |title=Genital Herpes – CDC Fact Sheet |url=https://www.cdc.gov/std/herpes/STDFact-Herpes-detailed.htm |website=cdc.gov |access-date=31 December 2014 |date=December 8, 2014 |url-status=live |archive-url=https://web.archive.org/web/20141231122747/http://www.cdc.gov/std/herpes/STDFact-Herpes-detailed.htm |archive-date=31 December 2014}}</ref> Since there is no cure for either HSV-1 or HSV-2, rates of both inherently increase as people age.<ref name=Peds09/> Rates of HSV-1 are between 70% and 80% in populations of low socioeconomic status and 40% to 60% in populations of improved socioeconomic status.<ref name=Peds09>{{cite journal |vauthors=Chayavichitsilp P, Buckwalter JV, Krakowski AC, Friedlander SF |title=Herpes simplex |journal=Pediatr Rev |volume=30 |issue=4 |pages=119–29; quiz 130 |date=April 2009 |pmid=19339385 |doi=10.1542/pir.30-4-119 |s2cid=34735917 }}</ref> An estimated 536 million people worldwide (16% of the population) were infected with HSV-2 as of 2003 with greater rates among women and those in the developing world.<ref name=Looker2008>{{cite journal|last=Looker|first=KJ|author2=Garnett, GP |author3=Schmid, GP |title=An estimate of the global prevalence and incidence of herpes simplex virus type 2 infection.|journal=Bulletin of the World Health Organization|date=October 2008|volume=86|issue=10|pages=805–12, A|pmid=18949218|pmc=2649511|doi=10.2471/blt.07.046128}}</ref> Most people with HSV-2 do not realize that they are infected.<ref name=CDC2014F/>


==Etymology==
The name is from {{lang-grc-gre|ἕρπης}} ''herpēs'', which is related to the meaning "to creep", referring to spreading blisters.<ref>{{cite journal |last1=Beswick |first1=TSL |title=The Origin and the Use of the Word Herpes |journal=Med Hist |volume=6 |date=1962 |issue=3 |pages=214–232|doi=10.1017/S002572730002737X |pmid=13868599 |pmc=1034725 }}</ref> The name does not refer to latency.<ref>{{cite web |last1=Reese |first1=Vail |title=Countering Creeping Confusion: A Proposal to Re-Name Herpes Virus TAXONOMY |url=http://ojcpcd.com/reese-v/countering-creeping-confusion-a-proposal-to-re-name-herpes-virus-taxonomy/ |website=Online Journal of Community and Person-Centered Dermatology |publisher=Dr. David Elpern |access-date=22 September 2018}}</ref>

== Signs and symptoms == 

[[File:Herpes Infection.png|thumb|Herpes infection]]
 
HSV infection causes several distinct medical disorders.  Common infection of the skin or mucosa may affect the face and mouth (orofacial herpes), genitalia (genital herpes), or hands ([[Medicine:Herpetic whitlow|herpetic whitlow]]).  More serious disorders occur when the virus infects and damages the eye (herpes keratitis), or invades the central nervous system, damaging the brain (herpes encephalitis).  People with immature or suppressed immune systems, such as newborns, transplant recipients, or people with AIDS,  are prone to severe complications from HSV infections. HSV infection has also been associated with cognitive deficits of [[Medicine:Bipolar disorder|bipolar disorder]],<ref name="Dickerson2004 Mar 15">{{cite journal|author=Dickerson FB |title=Infection with herpes simplex virus type 1 is associated with cognitive deficits in bipolar disorder |journal=Biol. Psychiatry |volume=55 |issue=6 |pages=588–93 |date=March 2004|pmid=15013827|doi=10.1016/j.biopsych.2003.10.008|name-list-style=vanc|author2=Boronow JJ|author3=Stallings C|display-authors=3|last4=Origoni|first4=Andrea E|last5=Cole|first5=Sara|last6=Krivogorsky|first6=Bogdana|last7=Yolken|first7=Robert H|s2cid=25338399 }}</ref> and [[Medicine:Alzheimer's disease|Alzheimer's disease]], although this is often dependent on the [[Biology:Genetics|genetics]] of the infected person.

In all cases, HSV is never removed from the body by the [[Biology:Immune system|immune system]].  Following a primary infection, the virus enters the nerves at the site of primary infection, migrates to the cell body of the neuron, and becomes latent in the [[Biology:Ganglion|ganglion]].<ref name="pmid18156035">{{cite journal |vauthors=Gupta R, Warren T, Wald A |title=Genital herpes |journal=Lancet |volume=370 |issue=9605 |pages=2127–37 |date=December 2007 |pmid=18156035 |doi=10.1016/S0140-6736(07)61908-4 |s2cid=40916450 }}</ref> As a result of primary infection, the body produces antibodies to the particular type of HSV involved, which can help reduce the odds of subsequent infection of that type at a different site. In HSV-1-infected individuals, [[Biology:Seroconversion|seroconversion]] after an oral infection helps prevent additional HSV-1 infections such as whitlow, genital herpes, and herpes of the eye. Prior HSV-1 seroconversion seems to reduce the symptoms of a later HSV-2 infection, although HSV-2 can still be contracted.

Many people infected with HSV-2 display no physical symptoms—individuals with no symptoms are described as asymptomatic or as having [[Medicine:Subclinical infection|subclinical]] herpes.<ref name="pmid11095834">{{cite journal |author=Handsfield HH |title=Public Health Strategies to Prevent Genital Herpes: Where Do We Stand? |journal=Curr Infect Dis Rep |volume=2 |issue=1 |pages=25–30 |year=2000 |pmid=11095834 |doi=10.1007/s11908-000-0084-y|s2cid=41426466 }}</ref> However, infection with herpes can be fatal.<ref>{{Cite news |title=Inquests to be held into deaths of new mothers who died from herpes |last=Marsh |first=Sarah |newspaper=The Guardian |date=30 December 2021 |url= https://www.theguardian.com/global-development/2021/dec/30/inquests-to-be-held-into-deaths-of-new-mothers-who-died-from-herpes}}</ref>

===Types of herpes===

{| class="wikitable"
|-
! Condition
! Description
! Illustration
|-
|[[Medicine:Herpetic gingivostomatitis|Herpetic gingivostomatitis]]
| Herpetic gingivostomatitis is often the initial presentation during the first herpes infection.  It is of greater severity than herpes labialis, which is often the subsequent presentation.
|[[File:Herpesgingiva.JPG|center|150px]]
|-
| [[Medicine:Herpes labialis|Herpes labialis]]
| Commonly referred to as cold sores or fever blisters, herpes labialis is the most common presentation of recurrent HSV-1 infection following the re-emergence of the virus from the trigeminal nerve.
| [[File:Cold sore.jpg|center|150px]]
|-
| [[Medicine:Genital herpes|Herpes genitalis]]
| When symptomatic, the typical manifestation of a primary HSV-1 or HSV-2 genital infection is clusters of inflamed papules and vesicles on the outer surface of the genitals resembling cold sores.
| [[File:SOA-Herpes-genitalis-female.jpg|center|150px]]
|-
| [[Medicine:Herpetic whitlow|Herpetic whitlow]] and herpes gladiatorum
| Herpes whitlow is a painful infection that typically affects the fingers or thumbs.  On occasion, infection occurs on the toes or the nail cuticle.  Individuals who participate in contact sports such as wrestling, rugby, and football (soccer), sometimes acquire a condition caused by HSV-1 known as herpes gladiatorum, scrumpox, wrestler's herpes, or mat herpes, which presents as skin ulceration on the face, ears, and neck. Symptoms include fever, headache, sore throat, and swollen glands.  It occasionally affects the eyes or eyelids.
|  [[File:Herpetic whitlow in young child.jpg|center|150px]]
|-
| [[Medicine:Herpesviral encephalitis|Herpesviral encephalitis]] and herpesviral meningitis
| Herpes simplex encephalitis (HSE) is a rare life-threatening condition that is thought to be caused by the transmission of HSV-1 either from the nasal cavity to the brain's [[Biology:Temporal lobe|temporal lobe]] or from a peripheral site on the face, along the [[Biology:Trigeminal nerve|trigeminal nerve]] [[Biology:Axon|axon]], to the [[Biology:Brainstem|brainstem]].<ref>{{EMedicine|article|341142|Herpes Encephalitis}}</ref><ref>{{Cite journal|last1=van Riel|first1=Debby|last2=Verdijk|first2=Rob|last3=Kuiken|first3=Thijs|date=January 2015|title=The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system|journal=The Journal of Pathology|volume=235|issue=2|pages=277–287|doi=10.1002/path.4461|issn=1096-9896|pmid=25294743|s2cid=22929529|doi-access=free}}</ref><ref>{{Cite journal|last=Esiri|first=M. M.|date=May 1982|title=Herpes simplex encephalitis. An immunohistological study of the distribution of viral antigen within the brain|journal=Journal of the Neurological Sciences|volume=54|issue=2|pages=209–226|issn=0022-510X|pmid=6284882|doi=10.1016/0022-510X(82)90183-6|s2cid=20325355}}</ref><ref>{{Cite journal|last1=Whitley|first1=R. J.|last2=Soong|first2=S. J.|last3=Linneman|first3=C.|last4=Liu|first4=C.|last5=Pazin|first5=G.|last6=Alford|first6=C. A.|date=1982-01-15|title=Herpes simplex encephalitis. Clinical Assessment|journal=JAMA|volume=247|issue=3|pages=317–320|issn=0098-7484|pmid=6275134|doi=10.1001/jama.1982.03320280037026}}</ref> Despite its low incidence, HSE is the most common sporadic fatal encephalitis worldwide. HSV-2 is the most common cause of Mollaret's meningitis, a type of recurrent viral meningitis.
| [[File:Hsv encephalitis.jpg|center|150px]]
|-
| Herpes esophagitis
| Symptoms may include painful swallowing (odynophagia) and difficulty swallowing (dysphagia).  It is often associated with impaired immune function (e.g. HIV/AIDS, [[Biology:Immunosuppression|immunosuppression]] in solid organ transplants).
| [[File:Herpes esophagitis.JPG|center|150px]]
|}

=== Other === 

Neonatal herpes simplex is an HSV infection in an infant. It is a rare but serious condition, usually caused by [[Biology:Vertical transmission|vertical transmission]] of HSV-1 or -2 from mother to newborn. During immunodeficiency, herpes simplex can cause unusual lesions in the skin.  One of the most striking is the appearance of clean linear erosions in skin creases, with the appearance of a knife cut.<ref>{{cite journal|title=Linear erosive Herpes Simplex Virus infection in immunocompromised patients: the "Knife-Cut Sign"|journal=Clin Infect Dis|year=2008|volume=47|pages=1440–41|doi=10.1086/592976|author1=Jocelyn A. Lieb |author2=Stacey Brisman |author3=Sara Herman |author4=Jennifer MacGregor |author5=Marc E. Grossman |pmid=18937574|issue=11|doi-access=}}</ref> Herpetic sycosis is a recurrent or initial herpes simplex infection affecting primarily the hair follicles.<ref name="Andrews">{{cite book|author=James, William D. |title=Andrews' Diseases of the Skin: clinical Dermatology |publisher=Saunders Elsevier |year=2006 |isbn=978-0-7216-2921-6 |last2=Berger |first2=Timothy G. }}</ref>{{rp|369}} Eczema herpeticum is an infection with herpesvirus in patients with chronic [[Medicine:Atopic dermatitis|atopic dermatitis]] may result in spread of herpes simplex throughout the eczematous areas.<ref name="Andrews" />{{rp|373}}

Herpetic keratoconjunctivitis, a primary infection, typically presents as swelling of the [[Medicine:Conjunctiva|conjunctiva]] and eyelids (blepharoconjunctivitis), accompanied by small white itchy lesions on the surface of the [[Medicine:Cornea|cornea]].

Herpetic sycosis is a recurrent or initial herpes simplex infection affecting primarily the hair follicle.<ref name="Andrews"/>{{rp|369}}<ref name="Bolognia">{{cite book |author1=Rapini, Ronald P. |author2=Bolognia, Jean L. |author3=Jorizzo, Joseph L. |title=Dermatology: 2-Volume Set |publisher=Mosby |location=St. Louis |year=2007 |isbn=978-1-4160-2999-1 }}</ref>

=== Bell's palsy ===

Although the exact cause of [[Medicine:Bell's palsy|Bell's palsy]]{{mdash}}a type of facial [[Engineering:Paralysis|paralysis]]{{mdash}}is unknown, it may be related to the reactivation of HSV-1.<ref>{{cite journal |vauthors=Tankéré F, Bernat I |title=[Bell's palsy: from viral aetiology to diagnostic reality] |language=fr |journal=Rev Méd Interne |volume=30 |issue=9 |pages=769–75 |date=September 2009 |pmid=19195745 |doi=10.1016/j.revmed.2008.12.006 }}</ref> This theory has been contested, however, since HSV is detected in large numbers of individuals having never experienced facial paralysis, and higher levels of antibodies for HSV are not found in HSV-infected individuals with Bell's palsy compared to those without.<ref name="pmid15699730">{{cite journal |vauthors=Linder T, Bossart W, Bodmer D |title=Bell's palsy and Herpes simplex virus: fact or mystery? |journal=Otol. Neurotol. |volume=26 |issue=1 |pages=109–13 |date=January 2005 |pmid=15699730 |doi= 10.1097/00129492-200501000-00020|s2cid=33873521 }}</ref> Antivirals may improve the condition slightly when used together with corticosteroids in those with severe disease.<ref>{{Cite journal|last1=Gagyor|first1=Ildiko|last2=Madhok|first2=Vishnu B.|last3=Daly|first3=Fergus|last4=Somasundara|first4=Dhruvashree|last5=Sullivan|first5=Michael|last6=Gammie|first6=Fiona|last7=Sullivan|first7=Frank|date=2015-11-09|title=Antiviral treatment for Bell's palsy (idiopathic facial paralysis)|url=http://discovery.dundee.ac.uk/ws/files/743606/Lockhart_2010.pdf|journal=The Cochrane Database of Systematic Reviews|issue=11|pages=CD001869|doi=10.1002/14651858.CD001869.pub8|issn=1469-493X|pmid=26559436}}</ref>

=== Alzheimer's disease === 

HSV-1 has been proposed as a possible cause of [[Medicine:Alzheimer's disease|Alzheimer's disease]].<ref>{{cite journal |vauthors=Itzhaki RF, Wozniak MA |title=Herpes simplex virus type 1 in Alzheimer's disease: the enemy within |journal=J. Alzheimers Dis. |volume=13 |issue=4 |pages=393–405 |date=May 2008 |pmid=18487848 |doi=10.3233/JAD-2008-13405 }}</ref><ref>{{cite journal |vauthors=Holmes C, Cotterell D |title=Role of infection in the pathogenesis of Alzheimer's disease: implications for treatment |journal=CNS Drugs |volume=23 |issue=12 |pages=993–1002 |date=December 2009 |pmid=19958038 |doi=10.2165/11310910-000000000-00000 |s2cid=25248989 }}</ref> In the presence of a certain gene variation (APOE-epsilon4 allele carriers), HSV-1 appears to be particularly damaging to the nervous system and increases one's risk of developing Alzheimer's disease.  The virus interacts with the components and receptors of lipoproteins, which may lead to its development.<ref name="Dobson1999">{{cite journal|vauthors=Dobson CB, Itzhaki RF |title=Herpes simplex virus type 1 and Alzheimer's disease |journal=Neurobiol. Aging |volume=20 |issue=4 |pages=457–65 |year=1999 |pmid=10604441 |doi=10.1016/S0197-4580(99)00055-X|s2cid=23633290 }}</ref><ref>{{cite journal|author=Pyles RB |title=The association of herpes simplex virus and Alzheimer's disease: a potential synthesis of genetic and environmental factors |journal=Herpes |volume=8 |issue=3 |pages=64–68 |year=2001 |pmid=11867022}}</ref>

==Pathophysiology==
{| class="wikitable" style="float:right"
|+ Herpes shedding<ref>{{cite book|last=Warren|first=Terri|title=The Good News about the Bad News: Herpes: Everything You Need to Know|year=2009|publisher=New Harbinger Publications|isbn=978-1-57224-618-8|page=28|url=https://books.google.com/books?id=PoRB5qQXW70C&pg=PA28|url-status=live|archive-url=https://web.archive.org/web/20160527071727/https://books.google.com/books?id=PoRB5qQXW70C&pg=PA28|archive-date=2016-05-27}}</ref>
|-
| HSV-2 genital
| 15–25% of days
|-
| HSV-1 oral
| 6–33% of days
|-
| HSV-1 genital
| 5% of days
|-
| HSV-2 oral
| 1% of days
|}
Herpes is contracted through direct contact with an active lesion or body fluid of an infected person.<ref name="titleAHMF: Preventing Sexual Transmission of Genital Herpes">{{cite web |url=http://www.ahmf.com.au/health_professionals/guidelines/preventing_gh_transmission.htm |title=AHMF: Preventing Sexual Transmission of Genital herpes |access-date=2008-02-24 |archive-url = https://web.archive.org/web/20080121164311/http://www.ahmf.com.au/health_professionals/guidelines/preventing_gh_transmission.htm |archive-date = January 21, 2008}}</ref> Herpes transmission occurs between discordant partners; a person with a history of infection (HSV seropositive) can pass the virus to an HSV seronegative person. Herpes simplex virus 2 is  typically contracted through direct skin-to-skin contact with an infected individual, but can also be contracted by exposure to infected saliva, semen, vaginal fluid, or the fluid from herpetic blisters.<ref>{{cite book|author1=Anita L. Nelson|author2=Jo Ann Woodward|title=Sexually Transmitted Diseases: A Practical Guide for Primary Care|url=https://books.google.com/books?id=7U9ZE_8y0kwC&pg=PA50|date=2007-12-14|publisher=Springer Science & Business Media|isbn=978-1-59745-040-9|pages=50–}}</ref> 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.

HSV asymptomatic [[Biology:Viral shedding|shedding]] occurs at some time in most individuals infected with herpes.  It can occur more than a week before or after a symptomatic recurrence in 50% of cases.<ref name="pmid16238897"/>  Virus enters into susceptible cells by entry receptors<ref>
{{cite journal| title = Viral entry mechanisms: cellular and viral mediators of herpes simplex virus entry| last1 = Akhtar| first1 = Jihan| last2 = Shukla| first2 = Deepak| journal = FEBS Journal|volume=276 |issue=24 |pages=7228–36 |date=December 2009 |pmid=19878306 |pmc=2801626 |doi=10.1111/j.1742-4658.2009.07402.x }}</ref>
such as nectin-1, HVEM and 3-O sulfated heparan sulfate.<ref>
{{cite journal| title = A Novel Role for 3-O-Sulfated Heparan Sulfate in Herpes Simplex Virus 1 Entry| journal = Cell| volume = 99| issue = 1| pages = 13–22| last1 = Shukla| first1 = Deepak| last2 = Liu| first2 = Jian| last3 = Blaiklock| first3 = Peter| last4 = Shworak| first4 = Nicholas W.| last5 = Bai| first5 = Xiaomei| last6 = Esko| first6 = Jeffrey D.| last7 = Cohen| first7 = Gary H.| last8 = Eisenberg| first8 = Roselyn| last9 = Rosenberg| first9 = Robert D.| display-authors = 8| doi = 10.1016/S0092-8674(00)80058-6| pmid = 10520990| year = 1999| s2cid = 14139940| doi-access = free}}</ref> Infected people who show no visible symptoms may still shed and transmit viruses through their skin; asymptomatic shedding may represent the most common form of HSV-2 transmission.<ref name="pmid16238897">{{cite journal |author=Leone P |title=Reducing the risk of transmitting genital herpes: advances in understanding and therapy |journal=Curr Med Res Opin |volume=21 |issue=10 |pages=1577–82 |year=2005 |pmid=16238897 |doi=10.1185/030079905X61901|s2cid=26738979 }}</ref> Asymptomatic shedding is more frequent within the first 12 months of acquiring HSV. Concurrent infection with HIV increases the frequency and duration of asymptomatic shedding.<ref>{{cite journal |vauthors=Kim H, Meier A, Huang M, Kuntz S, Selke S, Celum C, Corey L, Wald A | title = Oral herpes simplex virus type 2 reactivation in HIV-positive and -negative men | journal = J Infect Dis | volume = 194 | issue = 4 | pages = 420–27 | year = 2006 | pmid = 16845624 | doi = 10.1086/505879| doi-access = free }}</ref>  Some individuals may have much lower patterns of shedding, but evidence supporting this is not fully verified; no significant differences are seen in the frequency of asymptomatic shedding when comparing persons with one to 12 annual recurrences to those with no recurrences.<ref name="pmid16238897"/>

Antibodies that develop following an initial infection with a type of HSV can reduce the odds of reinfection with the same virus type.<ref name="wikidoc_simplex">{{cite web |title=Herpes simplex pathophysiology |url=https://www.wikidoc.org/index.php/Herpes_simplex_pathophysiology |website=WikiDoc |access-date=2021-03-06}}</ref> In a [[Social:Monogamy|monogamous]] couple, a seronegative female runs a greater than 30% per year risk of contracting an HSV infection from a seropositive male partner.<ref name=Mertz1993>{{cite journal |author = Mertz, G.J. | year = 1993 |title = Epidemiology of genital herpes infections |journal = Infect Dis Clin North Am |volume = 7 |issue = 4 |pages = 825–39 |doi = 10.1016/S0891-5520(20)30561-4 | pmid = 8106731}}</ref> 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.<ref name="wikidoc_simplex"/> Herpes simplex is a double-stranded [[Biology:DNA virus|DNA virus]].<ref>{{cite journal |pmc = 164775 |pmid=12805441 |volume=77 |issue=13 |title=The herpes simplex virus type 1 alkaline nuclease and single-stranded DNA binding protein mediate strand exchange in vitro |year=2003 |journal=J. Virol. |pages=7425–33 |vauthors=Reuven NB, Staire AE, Myers RS, Weller SK |doi=10.1128/jvi.77.13.7425-7433.2003}}</ref>

==Diagnosis==
===Classification===
Herpes simplex virus is divided into two types.<ref name=Peds09/> However, each may cause infections in all areas.<ref name=Peds09/> 
# HSV-1 causes primarily mouth, throat, face, eye, and [[Biology:Central nervous system|central nervous system]] infections.<ref name=Peds09/> 
# HSV-2 causes primarily anogenital infections.<ref name=Peds09/>

===Examination===
Primary orofacial herpes is readily identified by examination of persons with no previous history of lesions and contact with an individual with known HSV infection. The appearance and distribution of sores is typically presents as multiple, round, superficial oral ulcers, accompanied by acute [[Medicine:Gingivitis|gingivitis]].<ref name="pmid17939933">{{cite journal |vauthors=Fatahzadeh M, Schwartz RA |title=Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management |journal=J. Am. Acad. Dermatol. |volume=57 |issue=5 |pages=737–63; quiz 764–6 |year=2007 |pmid=17939933 |doi=10.1016/j.jaad.2007.06.027}}</ref> Adults with atypical presentation are more difficult to diagnose. Prodromal symptoms that occur before the appearance of herpetic lesions help differentiate HSV symptoms from the similar symptoms of other disorders, such as [[Medicine:Allergy|allergic]] [[Medicine:Stomatitis|stomatitis]]. When lesions do not appear inside the mouth, primary orofacial herpes is sometimes mistaken for [[Medicine:Impetigo|impetigo]], a bacterial [[Medicine:Infection|infection]]. Common mouth ulcers (aphthous ulcer) also resemble intraoral herpes, but do not present a vesicular stage.<ref name="pmid17939933"/>

Genital herpes can be more difficult to diagnose than oral herpes, since most people have none of the classical symptoms.<ref name="pmid17939933"/> Further confusing diagnosis, several other conditions resemble genital herpes, including fungal infection, [[Medicine:Lichen planus|lichen planus]], [[Medicine:Atopic dermatitis|atopic dermatitis]], and [[Medicine:Urethritis|urethritis]].<ref name="pmid17939933"/>

===Laboratory testing===
Laboratory testing is often used to confirm a diagnosis of genital herpes. Laboratory tests include culture of the virus, [[Direct fluorescent antibody|direct fluorescent antibody]] (DFA) studies to detect virus, skin biopsy, and [[Biology:Polymerase chain reaction|polymerase chain reaction]] to test for presence of viral DNA. Although these procedures produce highly sensitive and specific diagnoses, their high costs and time constraints discourage their regular use in clinical practice.<ref name="pmid17939933"/>

Until the 1980s [[Biology:Serology|serological]] tests for antibodies to HSV were rarely useful to diagnosis and not routinely used in clinical practice.<ref name="pmid17939933"/> The older IgM serologic assay could not differentiate between antibodies generated in response to HSV-1 or HSV-2 infection.  However, a glycoprotein G-specific (IgG) HSV test introduced in the 1980s is more than 98% specific at discriminating HSV-1 from HSV-2.<ref name="ClinMicro1988;26:662-667">{{cite journal |vauthors=Ashley RL, etal |title=Comparison of Western blot (immunoblot) and glycoprotein G-specific immunodot enzyme assay for detecting antibodies to herpes simplex virus types 1 and 2 in human sera |journal=J. Clin. Microbiol. |volume=26 |issue=4 |pages=662–67 |year=1988 |pmid=2835389 |pmc=266403 |doi=10.1128/JCM.26.4.662-667.1988 }}</ref>

===Differential diagnosis===
It should not be confused with conditions caused by other viruses in the ''[[Biology:Herpesviridae|herpesviridae]]'' family such as herpes zoster (also known as shingles), which is caused by varicella zoster virus. The [[Medicine:Differential diagnosis|differential diagnosis]] includes hand, foot and mouth disease due to similar lesions on the skin. Lymphangioma circumscriptum and dermatitis herpetiformis may also have a similar appearance.

==Prevention==
[[File:Kondom.jpg|thumb|Barrier protection, such as a [[Medicine:Condom|condom]], can reduce the risk of herpes transmission.]]
As with almost all sexually transmitted infections, women are more susceptible to acquiring genital HSV-2 than men.<ref>{{cite news |author=Carla K. Johnson |title=Percentage of people with herpes drops |url=http://www.aegis.com/news/ap/2006/ap060840.html |access-date=2011-04-12 |agency=Associated Press |date= August 23, 2006 |archive-url=https://web.archive.org/web/20120318125331/http://www.aegis.com/news/ap/2006/ap060840.html |archive-date=2012-03-18 |url-status=dead}}</ref> On an annual basis, without the use of antivirals or condoms, the transmission risk of HSV-2 from infected male to female is about 8–11%.<ref name=Mertz1993/><ref name=Kulhanjian1992>{{cite journal |doi=10.1056/NEJM199204023261403 |author=Kulhanjian J A |title=Identification of women at unsuspected risk of primary infection with herpes simplex virus type 2 during pregnancy |journal=N. Engl. J. Med. |volume=326 |issue=14 |pages=916–20 |pmid=1311799 |date=April 2, 1992 |name-list-style=vanc |author2=Soroush V |author3=Au DS |display-authors=3 |last4=Bronzan |first4=Rachel N. |last5=Yasukawa |first5=Linda L. |last6=Weylman |first6=Laura E. |last7=Arvin |first7=Ann M. |last8=Prober |first8=Charles G. |doi-access=free}}</ref> 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 around 4–5% annually.<ref name=Kulhanjian1992/> Suppressive antiviral therapy reduces these risks by 50%.<ref name=Corey2004>{{cite journal|author=Corey L|title=Once-daily valacyclovir to reduce the risk of transmission of genital herpes|journal=N Engl J Med|volume=350|issue=1|pages=11–20|date=January 2004|pmid=14702423|doi=10.1056/NEJMoa035144|name-list-style=vanc|author2=Wald A|author3=Patel R|display-authors=3|last4=Sacks|first4=Stephen L.|last5=Tyring|first5=Stephen K.|last6=Warren|first6=Terri|last7=Douglas|first7=John M.|last8=Paavonen|first8=Jorma|last9=Morrow|first9=R. Ashley|s2cid=21573428|doi-access=free}}</ref> Antivirals also help prevent the development of symptomatic HSV in infection scenarios, meaning the infected partner will be seropositive but symptom-free by about 50%. Condom use also reduces the transmission risk significantly.<ref name=Wald>{{cite journal | vauthors=Wald A, Langenberg AG, Link K, Izu AE, Ashley R, Warren T, Tyring S, ((Douglas JM Jr)), Corey L | title=Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women | journal=JAMA | year=2001 | pages=3100–06 | volume=285 | issue=24 | pmid=11427138 | doi=10.1001/jama.285.24.3100 | doi-access= }}</ref><ref name=Wald2005>{{cite journal|author=Wald A|title=The relationship between condom use and herpes simplex virus acquisition|journal=Annals of Internal Medicine|volume=143|issue=10|pages=707–13|date=November 2005|pmid=16287791|name-list-style=vanc|author2=Langenberg AG|author3=Krantz E|display-authors=3|last4=Douglas Jr|first4=JM|last5=Handsfield|first5=HH|last6=Dicarlo|first6=RP|last7=Adimora|first7=AA|last8=Izu|first8=AE|last9=Morrow|first9=RA|doi=10.7326/0003-4819-143-10-200511150-00007|s2cid=37342783}}</ref> Condom use is much more effective at preventing male-to-female transmission than ''vice versa''.<ref name=Wald/> Previous HSV-1 infection may reduce the risk for acquisition of HSV-2 infection among women by a factor of three, although the one study that states this has a small sample size of 14 transmissions out of 214 couples.<ref>{{cite journal |last=Mertz |first=GJ |author2=Benedetti J |author3=Ashley R |author4=Selke SA |author5=Corey L. |title=Risk factors for the sexual transmission of genital herpes |journal=Annals of Internal Medicine |date=1 February 1992 |volume=116 |issue=3 |pages=197–202 |pmid=1309413 |doi=10.7326/0003-4819-116-3-197|s2cid=40143915 }}</ref>

However, asymptomatic carriers of the HSV-2 virus are still contagious.  In many infections, the first symptom people will have of their own infections is the horizontal transmission to a sexual partner or the vertical transmission of neonatal herpes to a newborn at term. Since most asymptomatic individuals are unaware of their infection, they are considered at high risk for spreading HSV.<ref>{{cite web |url=https://www.cdc.gov/std/herpes/STDFact-herpes-detailed.htm#ref21 |title=Genital Herpes – CDC Fact Sheet |publisher=Center for Disease Control and Prevention |access-date=2014-01-30 |url-status=live |archive-url=https://web.archive.org/web/20140130165350/http://www.cdc.gov/std/Herpes/STDFact-herpes-detailed.htm#ref21 |archive-date=2014-01-30 }}</ref>

In October 2011,  the anti-HIV drug tenofovir, when used topically in a microbicidal vaginal gel, was reported to reduce herpes virus sexual transmission by 51%.<ref>McNeil DG. [https://www.nytimes.com/2011/10/21/health/research/21herpes.html Topical Tenofovir, a Microbicide Effective against HIV, Inhibits Herpes Simplex Virus-2 Replication] {{webarchive|url=https://web.archive.org/web/20170409082250/http://www.nytimes.com/2011/10/21/health/research/21herpes.html |date=2017-04-09 }}. ''NY Times''. Research article: {{cite journal|date=October 2011|title=Topical Tenofovir, a Microbicide Effective against HIV, Inhibits Herpes Simplex Virus-2 Replication|journal= Cell Host & Microbe|volume=10|issue=4|pages=379–89|doi=10.1016/j.chom.2011.08.015|pmc=3201796|pmid=22018238|author1=Andrei G|author2=Lisco A|author3=Vanpouille C|display-authors=0}}</ref>

===Barrier methods===
Condoms offer moderate protection against HSV-2 in both men and women, with consistent condom users having a 30%-lower risk of HSV-2 acquisition compared with those who never use condoms.<ref name=Martin>{{cite journal | vauthors = Martin ET, Krantz E, Gottlieb SL, Magaret AS, Langenberg A, Stanberry L, Kamb M, Wald A | title = A pooled analysis of the effect of condoms in preventing HSV-2 acquisition | journal = Archives of Internal Medicine | volume = 169 | issue = 13 | pages = 1233–40 | date = July 2009 | pmid = 19597073 | pmc = 2860381 | doi = 10.1001/archinternmed.2009.177 }}</ref> A female condom can provide greater protection than the male condom, as it covers the labia.<ref>
{{cite web | publisher = UBM Medica | url=http://www.obgyn.net/femalepatient/femalepatient.asp?page=herpes_tfp | title=Putting Herpes in Perspective  | access-date=20 July 2011}}</ref> The virus cannot pass through a synthetic condom, but a male condom's effectiveness is limited<ref>{{cite web|url=https://www.cdc.gov/condomeffectiveness/latex.htm|title=Condom Effectiveness – Male Latex Condoms and Sexually Transmitted Diseases|publisher=Center for Disease Control and Prevention|archive-url=https://web.archive.org/web/20111002073943/http://www.cdc.gov/condomeffectiveness/latex.htm|archive-date=2011-10-02|url-status=live|access-date=2011-10-01}}</ref>  because herpes ulcers may appear on areas not covered by it. Neither type of condom prevents contact with the scrotum, anus, buttocks, or upper thighs, areas that may come in contact with ulcers or genital secretions during sexual activity. Protection against herpes simplex depends on the site of the ulcer; therefore, if ulcers appear on areas not covered by condoms, abstaining from sexual activity until the ulcers are fully healed is one way to limit risk of transmission.<ref>{{cite web|url=https://www.cdc.gov/std/herpes/stdfact-herpes.htm|title=STD Facts – Genital Herpes|publisher=Center for Disease Control and Prevention|archive-url=https://web.archive.org/web/20111001182509/http://www.cdc.gov/std/herpes/stdfact-herpes.htm|archive-date=2011-10-01|url-status=live|access-date=2011-10-01}}</ref> The risk is not eliminated, however, as viral shedding capable of transmitting infection may still occur while the infected partner is asymptomatic.<ref>{{cite journal |last=Koelle |first=D.M. |author2=Wald, A. |title=Herpes simplex virus: The importance of asymptomatic shedding |date=April 2000 |journal=J. Antimicrob. Chemother. |volume=45 |issue=Suppl T3 |pages=1–8  |pmid=10855766 |doi=10.1093/jac/45.suppl_4.1|doi-access=free }}</ref> The use of condoms or 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. When one partner has a herpes simplex infection and the other does not, the use of antiviral medication, such as [[Chemistry:Valaciclovir|valaciclovir]], in conjunction with a condom, further decreases the chances of transmission to the uninfected partner.<ref name="pmid18156035"/> Topical [[Biology:Microbicide|microbicide]]s that contain chemicals that directly inactivate the virus and block viral entry are being investigated.<ref name="pmid18156035"/>

===Antivirals===
Antivirals may reduce asymptomatic shedding; asymptomatic genital HSV-2 viral shedding is believed to occur on 20% of days per year in patients not undergoing antiviral treatment, versus 10% of days while on antiviral therapy.<ref name="pmid16238897"/>

===Pregnancy===
The risk of transmission from mother to baby is highest if the mother becomes infected around the time of delivery (30% to 60%),<ref>{{cite journal|author=Brown ZA|title=The acquisition of herpes simplex virus during pregnancy|journal=N Engl J Med|volume=337|pages=509–15|year=1997|doi=10.1056/NEJM199708213370801|pmid=9262493|name-list-style=vanc|author2=Selke S|author3=Zeh J|display-authors=3|last4=Kopelman|first4=Jerome|last5=Maslow|first5=Arthur|last6=Ashley|first6=Rhoda L.|last7=Watts|first7=D. Heather|last8=Berry|first8=Sylvia|last9=Herd|first9=Millie|issue=8|doi-access=free}}</ref><ref>{{cite journal|vauthors=Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L |title=Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant|journal=JAMA|volume=289|pages=203–09|year=2003|doi=10.1001/jama.289.2.203|pmid=12517231|issue=2|doi-access=free}}</ref> since insufficient time will have occurred for the generation and transfer of protective maternal antibodies before the birth of the child. In contrast, the risk falls to 3% if the  infection is recurrent,<ref name=pmid1849612/> and is 1–3% if the woman is seropositive for both HSV-1 and HSV-2,<ref name=pmid1849612>{{cite journal |author=Brown ZA |title=Neonatal herpes simplex virus infection in relation to asymptomatic maternal infection at the time of labor |journal=N. Engl. J. Med. |volume=324 |issue=18 |pages=1247–52 |date=May 1991 |pmid=1849612 |doi= 10.1056/NEJM199105023241804 |name-list-style=vanc|author2=Benedetti J |author3=Ashley R |display-authors=3 |last4=Burchett |first4=Sandra |last5=Selke |first5=Stacy |last6=Berry |first6=Sylvia |last7=Vontver |first7=Louis A. |last8=Corey |first8=Lawrence|doi-access=free }}</ref><ref name=Whitley_RJ>{{cite journal|vauthors=Whitley RJ, Kimberlin DW, Roizman B | title=Herpes simplex viruses| journal=Clin Infect Dis| year=1998| pages=541–53| volume=26| issue=3| pmid=9524821|doi=10.1086/514600| doi-access=free}}</ref> and is less than 1% if no lesions are visible.<ref name=pmid1849612/> Women seropositive for only one type of HSV are only half as likely to transmit HSV as infected seronegative mothers. 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 [[Medicine:Caesarean section|caesarean section]] to reduce exposure of the child to infected secretions in the birth canal.<ref name="pmid18156035"/> 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.<ref name="pmid18156035"/>

Aciclovir is the recommended antiviral for herpes suppressive therapy during the last months of pregnancy.  The use of valaciclovir and famciclovir, while potentially improving compliance, have less-well-determined safety in pregnancy.

==Management==
No method  eradicates herpes virus from the body, but antiviral medications can reduce the frequency, duration, and severity of outbreaks.  [[Biology:Analgesic|Analgesic]]s such as [[Chemistry:Ibuprofen|ibuprofen]] and [[Chemistry:Paracetamol|paracetamol]] (acetaminophen) can reduce pain and fever.  Topical anesthetic treatments such as [[Chemistry:Prilocaine|prilocaine]], [[Chemistry:Lidocaine|lidocaine]], [[Chemistry:Benzocaine|benzocaine]], or [[Chemistry:Tetracaine|tetracaine]] can also relieve itching and pain.<ref name="pmid3147021">{{cite journal |vauthors=O'Mahony C, Timms MS, Ramsden RT |title=Local anesthetic creams |journal=BMJ |volume=297 |issue=6661 |page=1468 |date=December 1988 |pmid=3147021 |pmc=1835116 |doi=10.1136/bmj.297.6661.1468-a}}</ref><ref name="pmid10570387">{{cite journal |author=Kaminester LH |title=A double-blind, placebo-controlled study of topical tetracaine in the treatment of herpes labialis |journal=J. Am. Acad. Dermatol. |volume=41 |issue=6 |pages=996–1001 |date=December 1999 |pmid=10570387 |doi= 10.1016/S0190-9622(99)70260-4 |name-list-style=vanc|author2=Pariser RJ |author3=Pariser DM |display-authors=3 |last4=Weiss |first4=Jonathan S. |last5=Shavin |first5=Joel S. |last6=Landsman |first6=Larry |last7=Haines |first7=Harold G. |last8=Osborne |first8=David W.}}</ref><ref name="Leung">{{cite journal |vauthors=Leung DT, Sacks SL |title=Current treatment options to prevent perinatal transmission of herpes simplex virus |journal=Expert Opin Pharmacother |volume=4 |issue=10 |pages=1809–19 |date=October 2003 |pmid=14521490 |doi=10.1517/14656566.4.10.1809 |s2cid=33261337 }}</ref>

===Antiviral===
[[File:Acyclovir pills.jpg|thumb|The antiviral medication aciclovir]]
Several [[Biology:Antiviral drug|antiviral drug]]s are effective for treating herpes, including [[Chemistry:Aciclovir|aciclovir]] (acyclovir), [[Chemistry:Valaciclovir|valaciclovir]], [[Chemistry:Famciclovir|famciclovir]], and [[Chemistry:Penciclovir|penciclovir]]. Aciclovir was the first discovered and is now available in generic.<ref>{{cite book|author = Robert L. LaFemina|title=Antiviral research : strategies in antiviral drug discovery|year=2009|publisher=ASM Press|location=Washington, DC|isbn=978-1-55581-439-7|pages=1|url=https://books.google.com/books?id=kyXjngXgU5YC&pg=PA1|url-status=live|archive-url=https://web.archive.org/web/20160502123637/https://books.google.com/books?id=kyXjngXgU5YC&pg=PA1|archive-date=2016-05-02}}</ref> Valaciclovir is also available as a generic<ref>{{cite book|last=Agrawal|first=Caroline A. Hastings, Joseph Torkildson, Anurag Kishor|title=Handbook of pediatric hematology and oncology : Children's Hospital & Research Center Oakland|publisher=Wiley-Blackwell|location=Chichester, West Sussex|isbn=978-0-470-67088-0|pages=360|url=https://books.google.com/books?id=H4t4PjtC730C&pg=PA360|edition=2nd|url-status=live|archive-url=https://web.archive.org/web/20160430224839/https://books.google.com/books?id=H4t4PjtC730C&pg=PA360|archive-date=2016-04-30|date=2012-04-30}}</ref> and is slightly more effective than aciclovir for reducing lesion healing time.<ref name="ChenXu2017">{{cite journal|last1=Chen|first1=Fangman|last2=Xu|first2=Hao|last3=Liu|first3=Jinli|last4=Cui|first4=Yuan|last5=Luo|first5=Xiaobo|last6=Zhou|first6=Yu|last7=Chen|first7=Qianming|last8=Jiang|first8=Lu|title=Efficacy and safety of nucleoside antiviral drugs for treatment of recurrent herpes labialis: a systematic review and meta-analysis|journal=Journal of Oral Pathology & Medicine|volume=46|issue=8|pages=561–568|year=2017|issn=0904-2512|doi=10.1111/jop.12534|pmid=27935123|s2cid=10391761}}</ref>

Evidence supports the use of aciclovir and valaciclovir in the treatment of herpes labialis<ref name=Best07>{{cite journal |vauthors=Chon T, Nguyen L, Elliott TC |title=Clinical inquiries. What are the best treatments for herpes labialis? |journal=J Fam Pract |volume=56 |issue=7 |pages=576–78 |date=July 2007 |pmid=17605952 }}</ref> as well as herpes infections in people with [[Medicine:Cancer|cancer]].<ref name="pmid19160295">{{cite journal | vauthors = Glenny AM, Fernandez Mauleffinch LM, Pavitt S, Walsh T | title = Interventions for the prevention and treatment of herpes simplex virus in patients being treated for cancer | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD006706 | date = January 2009 | pmid = 19160295 | doi = 10.1002/14651858.CD006706.pub2}}</ref> The evidence to support the use of aciclovir in primary herpetic gingivostomatitis is weaker.<ref name="pmid18843726">{{cite journal | vauthors = Nasser M, Fedorowicz Z, Khoshnevisan MH, Shahiri Tabarestani M | title = Acyclovir for treating primary herpetic gingivostomatitis | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD006700 | date = October 2008 | pmid = 18843726 | doi = 10.1002/14651858.CD006700.pub2| editor1-last = Nasser | editor1-first = Mona }} {{Retracted |doi=10.1002/14651858.cd006700.pub3}}</ref>

===Topical===
A number of topical antivirals are effective for herpes labialis, including aciclovir, penciclovir, and [[Chemistry:Docosanol|docosanol]].<ref name=Best07/><ref>{{cite journal |vauthors = Treister NS, Woo SB |title=Topical n-docosanol for management of recurrent herpes labialis |journal=Expert Opin Pharmacother |volume=11 |issue=5 |pages=853–60 |date=April 2010 |pmid=20210688 |doi=10.1517/14656561003691847 |s2cid=26237384 }}</ref>

===Alternative medicine===
Evidence is insufficient to support use of many of these compounds, including [[Biology:Echinacea|echinacea]], eleuthero, L-lysine, [[Chemistry:Zinc|zinc]], [[Chemistry:Monolaurin|monolaurin]] bee products, and [[Biology:Aloe vera|aloe vera]].<ref name="pmid16209859">{{cite journal |vauthors=Perfect MM, Bourne N, Ebel C, Rosenthal SL |title=Use of complementary and alternative medicine for the treatment of genital herpes |journal=Herpes |volume=12 |issue=2 |pages=38–41 |date=October 2005 |pmid=16209859 }}</ref> While a number of small studies show possible benefit from monolaurin, L-lysine, [[Chemistry:Aspirin|aspirin]], lemon balm, topical zinc, or licorice root cream in treatment, these preliminary studies have not been confirmed by higher-quality randomized controlled studies.<ref>{{cite journal |last=Beauman |first=JG |title=Genital herpes: a review. |journal=American Family Physician |date=Oct 15, 2005 |volume=72 |issue=8 |pages=1527–34 |pmid=16273819}}</ref>

==Prognosis==
Following active infection, herpes viruses establish a [[Biology:Virus latency|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 [[Biology:Cell nucleus|nucleus]] of a nerve's [[Biology:Soma|cell body]].  HSV latency is static; no virus is produced; and is controlled by a number of viral genes, including latency-associated transcript.<ref name="pmid12409612">{{cite journal |vauthors=Stumpf MP, Laidlaw Z, Jansen VA |title=Herpes viruses hedge their bets |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue=23 |pages=15234–37 |year=2002 |pmid=12409612 |doi=10.1073/pnas.232546899 |pmc=137573 |bibcode=2002PNAS...9915234S |doi-access=free }}</ref>

Many HSV-infected people experience recurrence within the first year of infection.<ref name="pmid18156035"/>  Prodrome precedes development of lesions.  Prodromal symptoms include tingling ([[Unsolved:Paresthesia|paresthesia]]), itching, and pain where lumbosacral nerves innervate the skin. Prodrome may occur as long as several days or as short as a few hours before lesions develop.  Beginning antiviral treatment when prodrome is experienced can reduce the appearance and duration of lesions in some individuals. During recurrence, fewer lesions are likely to develop and  are less painful and heal faster (within 5–10 days without antiviral treatment) than those occurring during the primary infection.<ref name="pmid18156035"/>  Subsequent outbreaks tend to be periodic or episodic, occurring on average four or five times a year when not using antiviral therapy.

The causes of reactivation are uncertain, but several potential triggers have been documented. A 2009 study showed the protein VP16 plays a key role in reactivation of the dormant virus.<ref>{{Cite journal|last1=Thompson|first1=Richard L.|last2=Preston|first2=Chris M.|last3=Sawtell|first3=Nancy M.|date=2009-03-01|title=De novo synthesis of VP16 coordinates the exit from HSV latency in vivo|journal=PLOS Pathogens|volume=5|issue=3|pages=e1000352|doi=10.1371/journal.ppat.1000352|issn=1553-7374|pmc=2654966|pmid=19325890 |doi-access=free }}</ref> Changes in the immune system during [[Medicine:Menstruation|menstruation]] may play a role in HSV-1 reactivation.<ref name="pmid11022124">{{cite journal |vauthors=Myśliwska J, Trzonkowski P, Bryl E, Lukaszuk K, Myśliwski A |title=Lower interleukin-2 and higher serum tumor necrosis factor-a levels are associated with perimenstrual, recurrent, facial herpes simplex infection in young women |journal=Eur. Cytokine Netw. |volume=11 |issue=3 |pages=397–406 |year=2000 |pmid=11022124 }}</ref><ref name="pmid4526372">{{cite journal |vauthors=Segal AL, Katcher AH, Brightman VJ, Miller MF |title=Recurrent herpes labialis, recurrent aphthous ulcers, and the menstrual cycle |journal=J. Dent. Res. |volume=53 |issue=4 |pages=797–803 |year=1974 |pmid=4526372 |doi=10.1177/00220345740530040501|s2cid=43134857 }}</ref> Concurrent infections, such as viral [[Medicine:Upper respiratory tract infection|upper respiratory tract infection]] or other febrile diseases, can cause outbreaks.  Reactivation due to other infections is the likely source of the historic terms 'cold sore' and 'fever blister'.

Other identified triggers include local injury to the face, lips, eyes, or mouth; trauma; surgery; radiotherapy; and exposure to wind, ultraviolet light, or sunlight.<ref name="pmid18083428">{{cite journal |vauthors=Chambers A, Perry M |title=Salivary mediated autoinoculation of herpes simplex virus on the face in the absence of "cold sores," after trauma |journal=J. Oral Maxillofac. Surg. |volume=66 |issue=1 |pages=136–38 |year=2008 |pmid=18083428 |doi=10.1016/j.joms.2006.07.019}}</ref><ref name="pmid2821086">{{cite journal |vauthors=Perna JJ, Mannix ML, Rooney JF, Notkins AL, Straus SE |title=Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model |journal=J. Am. Acad. Dermatol. |volume=17 |issue=3 |pages=473–78 |year=1987 |pmid=2821086 |doi=10.1016/S0190-9622(87)70232-1|url=  https://zenodo.org/record/1259937}}</ref><ref name="pmid1323616">{{cite journal |author=Rooney JF |title=UV light-induced reactivation of herpes simplex virus type 2 and prevention by acyclovir |journal=J. Infect. Dis. |volume=166 |issue=3 |pages=500–06 |year=1992 |pmid=1323616 |doi=10.1093/infdis/166.3.500 |name-list-style=vanc|author2=Straus SE |author3=Mannix ML |display-authors=3 |last4=Wohlenberg |first4=CR |last5=Banks |first5=S |last6=Jagannath |first6=S |last7=Brauer |first7=JE |last8=Notkins |first8=AL}}</ref><ref name="pmid9377190">{{cite journal |vauthors=Oakley C, Epstein JB, Sherlock CH |title=Reactivation of oral herpes simplex virus: implications for clinical management of herpes simplex virus recurrence during radiotherapy |journal=Oral Surg Oral Med Oral Pathol Oral Radiol Endod |volume=84 |issue=3 |pages=272–78 |year=1997 |pmid=9377190 |doi=10.1016/S1079-2104(97)90342-5}}</ref><ref name="pmid15603217">{{cite journal |vauthors=Ichihashi M, Nagai H, Matsunaga K |title=Sunlight is an important causative factor of recurrent herpes simplex |journal=Cutis |volume=74 |issue=5 Suppl |pages=14–18 |year=2004 |pmid=15603217 }}</ref>

The frequency and severity of recurrent outbreaks vary greatly between people. Some individuals' outbreaks can be quite debilitating, with large, painful lesions persisting for several weeks, while others experience only minor itching or burning for a few days. Some evidence indicates genetics play a role in the frequency of cold sore outbreaks.  An area of human chromosome 21 that includes six genes has been linked to frequent oral herpes outbreaks. An immunity to the virus is built over time. Most infected individuals experience fewer outbreaks and outbreak symptoms often become less severe. After several years, some people become perpetually [[Medicine:Asymptomatic|asymptomatic]] and no longer experience outbreaks, though they may still be contagious to others. Immunocompromised individuals may experience longer, more frequent, and more severe episodes. Antiviral medication has been proven to shorten the frequency and duration of outbreaks.<ref name="pmid18192785">{{cite journal |vauthors=Martinez V, Caumes E, Chosidow O |title=Treatment to prevent recurrent genital herpes |journal=Current Opinion in Infectious Diseases |volume=21 |issue=1 |pages=42–48 |year=2008 |pmid=18192785 |doi=10.1097/QCO.0b013e3282f3d9d3|s2cid=25681412 }}</ref>  Outbreaks may occur at the original site of the infection or in proximity to nerve endings that reach out from the infected ganglia. In the case of a genital infection, sores can appear at the original site of infection or near the base of the spine, the buttocks, or the back of the thighs. HSV-2-infected individuals are at higher risk for acquiring HIV when practicing unprotected sex with HIV-positive persons, in particular during an outbreak with active lesions.<ref name="pmid18186706">{{cite journal |vauthors=Koelle DM, Corey L |title=Herpes Simplex: Insights on Pathogenesis and Possible Vaccines |journal=Annu Rev Med |volume=59 |pages=381–95|year=2008 |pmid=18186706 |doi=10.1146/annurev.med.59.061606.095540}}</ref>

==Epidemiology==
{{Main|Medicine:Epidemiology of herpes simplex}}
Worldwide rates of either HSV-1 and/or HSV-2 are between 60 and 95% in adults.<ref name=Peds09/> HSV-1 is more common than HSV-2, with rates of both increasing as people age.<ref name=Peds09/> HSV-1 rates are between 70% and 80% in populations of low socioeconomic status and 40% to 60% in populations of improved socioeconomic status.<ref name=Peds09/> An estimated 536 million people or 16% of the population worldwide were infected with HSV-2 as of 2003 with greater rates among women and in those in the developing world.<ref name="Looker2008"/> Rates of infection are determined by the presence of [[Biology:Antibodies|antibodies]] against either viral species.<ref name="pmid12353183">{{cite journal |vauthors=Smith JS, Robinson NJ |title=Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review |journal=J. Infect. Dis. |volume=186 |issue=Suppl 1 |pages=S3–28 |year=2002 |pmid=12353183 |doi=10.1086/343739|doi-access=free }}</ref>

In the {{wipe|United States}}, 58% of the population is infected with HSV-1<ref name="JAMA. 2006;296:964-973.">{{cite journal|last=Xu|first=Fujie|author2=Fujie Xu|author3=Maya R. Sternberg|author4=Benny J. Kottiri|author5=Geraldine M. McQuillan|author6=Francis K. Lee|author7=Andre J. Nahmias|author8=Stuart M. Berman|author9=Lauri E. Markowitz|date=2006-10-23|title=Trends in Herpes Simplex Virus Type 1 and Type 2 Seroprevalence in the United States|journal=JAMA|volume=296|issue=8|pmid=16926356|doi=10.1001/jama.296.8.964|pages=964–73|doi-access=}}</ref> and 16% are infected with HSV-2. Among those HSV-2-seropositive, only 19% were aware they were infected.<ref>{{cite journal|last=Xu|first=F|author2=MR Sternberg|author3=SL Gottlieb|author4=SM Berman|author5=LE Markowitz|display-authors=0|title=Seroprevalence of Herpes Simplex Virus Type 2 Among Persons Aged 14–49 Years – United States, 2005–2008|journal=Morbidity and Mortality Weekly Report|date=23 April 2010|volume=59|issue=15|pages=456–59|pmid=20414188|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5915a3.htm|access-date=12 April 2011|url-status=live|archive-url=https://web.archive.org/web/20110625091920/http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5915a3.htm|archive-date=25 June 2011}}</ref> During 2005–2008, the prevalence of HSV-2 was 39% in black people and 21% in women.<ref>{{cite web |url=https://www.cdc.gov/stdconference/2010/hsv2pressrelease.pdf |title=CDC Study Finds U.S. Herpes Rates Remain High |publisher=Center for Disease Control and Prevention |date=2010-03-09 |access-date=2012-02-19 |url-status=live |archive-url=https://web.archive.org/web/20160306090032/http://www.cdc.gov/stdconference/2010/hsv2pressrelease.pdf |archive-date=2016-03-06 }}</ref>

The annual incidence in Canada of genital herpes due to HSV-1 and HSV-2 infection is not known (for a review of HSV-1/HSV-2 prevalence and incidence studies worldwide, see Smith and Robinson 2002). As many as one in seven Canadians aged 14 to 59 may be infected with herpes simplex type 2 virus<ref>{{Cite journal |last1=Rotermann |first1=Michelle |last2=Langlois |first2=Kellie A. |last3=Severini |first3=Alberto |last4=Totten |first4=Stephanie |date=2013-04-01 |title=Prevalence of Chlamydia trachomatis and herpes simplex virus type 2: Results from the 2009 to 2011 Canadian Health Measures Survey |journal=Health Reports |volume=24 |issue=4 |pages=10–15 |issn=1209-1367 |pmid=24258059}}</ref> and more than 90 per cent of them may be unaware of their status, a new study suggests.<ref>{{Cite news |url=http://news.nationalpost.com/health/herpes-virus-has-infected-nearly-one-in-five-canadians-over-age-35-most-unaware-they-have-it-study |title=Herpes virus has infected nearly one in five Canadians over age 35, most unaware they have it: study |newspaper=National Post |access-date=2017-02-20}}</ref> In the United States, it is estimated that about 1,640,000 HSV-2 seroconversions occur yearly (730,000 men and 910,000 women, or 8.4 per 1,000 persons).<ref>{{cite journal |author = Smith JS, Robinson NJ |year = 2002 |title = Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review |journal = J Infect Dis |volume = 186 |issue = suppl 1 |pages = S3–28 |doi=10.1086/343739 |pmid = 12353183 |doi-access = free }}</ref>

In British Columbia in 1999, the seroprevalence of HSV-2 antibody in leftover serum submitted for antenatal testing revealed a prevalence of 17%, ranging from 7% in women 15–19 years old to 28% in those 40–44 years.<ref name="pmid11323323">{{cite journal | vauthors = Armstrong GL, Schillinger J, Markowitz L, Nahmias AJ, Johnson RE, McQuillan GM, St Louis ME | title = Incidence of herpes simplex virus type 2 infection in the United States | journal = American Journal of Epidemiology | volume = 153 | issue = 9 | pages = 912–20 | date = May 2001 | pmid = 11323323 | doi = 10.1093/aje/153.9.912| doi-access = free }}</ref>

In Norway, a study published in 2000 found that up to 70–90% of genital initial infections were due to HSV-1.<ref>{{cite journal |author = Nilsen A, Myrmel H |year = 2000 |title = Changing trends in genital herpes simplex virus infection in Bergen, Norway |journal = Acta Obstet Gynecol Scand |volume = 79 |issue = 8|pages = 693–96 |doi=10.1080/j.1600-0412.2000.079008693.x |pmid=10949236}}</ref>

In Nova Scotia, 58% of 1,790 HSV isolates from genital lesion cultures in women were HSV-1; in men, 37% of 468 isolates were HSV-1.<ref>{{cite journal |author = Forward KR, Lee SHS |year = 2003 |title = Predominance of herpes simplex virus type 1 from patients with genital herpes in Nova Scotia |journal = Can J Infect Dis |volume = 14 |issue = 2 |pages = 94–96 |doi=10.1155/2003/168673 |pmid = 18159431 |pmc = 2094909 |doi-access = free }}</ref>

== History == 
Herpes has been known for at least 2,000 years. Emperor Tiberius is said to have banned kissing in Rome for a time due to so many people having cold sores. In the 16th century ''Romeo and Juliet'',  blisters "o'er ladies' lips" are mentioned. In the 18th century, it was so common among prostitutes that it was called "a vocational disease of women".<ref name="scarlet">{{cite news |url=http://www.time.com/time/magazine/article/0,9171,1715020,00.html |title=The New Scarlet Letter |author=John Leo |date=1982-08-02 |magazine={{wipe|Time (magazine)}} |archive-url=https://web.archive.org/web/20100202153257/http://www.time.com/time/magazine/article/0%2C9171%2C1715020%2C00.html |archive-date=2010-02-02 |url-status=dead}}</ref> The term 'herpes simplex' appeared in Richard Boulton's ''A System of Rational and Practical Chirurgery'' in 1713, where the terms 'herpes miliaris' and 'herpes exedens' also appeared. Herpes was not found to be a virus until the 1940s.<ref name=scarlet />

Herpes antiviral therapy began in the early 1960s with the experimental use of medications that interfered with viral replication called deoxyribonucleic acid (DNA) inhibitors. The original use was against normally fatal or debilitating illnesses such as adult encephalitis,<ref name="pmid4790599">{{cite journal|author=Chow AW|title=Cytosine Arabinoside Therapy for Herpes Simplex Encephalitis – Clinical Experience with Six Patients|journal=Antimicrob. Agents Chemother.|volume=3|issue=3|pages=412–17|date=March 1973|pmid=4790599|pmc=444424|doi=10.1128/aac.3.3.412|name-list-style=vanc|author2=Roland A|author3=Fiala M|display-authors=3|last4=Hryniuk|first4=W|last5=Weil|first5=ML|last6=Geme Jr|first6=JS|last7=Guze|first7=LB}}</ref> keratitis,<ref name="pmid14454441">{{cite journal | vauthors = Kaufman HE, Howard GM| title = Therapy of experimental herpes simplex keratitis | journal = Investigative Ophthalmology | volume = 1 | pages = 561–4 | date = August 1962 | pmid = 14454441 }}</ref> in immunocompromised (transplant) patients,<ref name="pmid180198">{{cite journal|vauthors=Ch'ien LT, Whitley RJ, Alford CA, Galasso GJ |title=Adenine arabinoside for therapy of herpes zoster in immunosuppressed patients: preliminary results of a collaborative study|journal=J. Infect. Dis.|volume=133|issue=Suppl|pages=A184–91|date=June 1976|pmid=180198|doi=10.1093/infdis/133.supplement_2.a184}}</ref> or disseminated herpes zoster (also known as disseminated shingles).<ref name="pmid5352659">{{cite journal|vauthors=McKelvey EM, Kwaan HC|title=Cytosine arabinoside therapy for disseminated herpes zoster in a patient with IgG pyroglobulinemia|journal=Blood|volume=34|issue=5|pages=706–11|date=November 1969|pmid=5352659|doi=10.1182/blood.V34.5.706.706|doi-access=free}}</ref> The original compounds used were 5-iodo-2'-deoxyuridine, AKA idoxuridine, IUdR, or(IDU) and 1-β-D-arabinofuranosylcytosine or ara-C,<ref name="pmid4364937">{{cite journal|vauthors=Fiala M, Chow A, Guze LB |title=Susceptibility of Herpesviruses to Cytosine Arabinoside: Standardization of Susceptibility Test Procedure and Relative Resistance of Herpes Simplex Type 2 Strains|journal=Antimicrob. Agents Chemother.|volume=1|issue=4|pages=354–57|date=April 1972|pmid=4364937|pmc=444221|doi=10.1128/aac.1.4.354}}</ref> later marketed under the name cytosar or cytarabine. The usage expanded to include topical treatment of herpes simplex,<ref name="pmid6598">{{cite journal|author=Allen LB|title=Effect of 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate on genital lesions and encephalitis induced by Herpesvirus hominis type 2 in female mice|journal=J. Infect. Dis.|volume=133|issue= Suppl|pages=A178–83|date=June 1976|pmid=6598|name-list-style=vanc|author2=Hintz OJ|author3=Wolf SM|display-authors=3|last4=Huffman|first4=JH|last5=Simon|first5=LN|last6=Robins|first6=RK|last7=Sidwell|first7=RW|doi=10.1093/infdis/133.supplement_2.a178}}</ref> zoster, and varicella.<ref name="pmid4190397">{{cite journal|author=Juel-Jensen BE|title=Varicella and cytosine arabinoside|journal=Lancet|volume=1|issue=7646|page=572|date=March 1970|pmid=4190397|doi=10.1016/S0140-6736(70)90815-9}}</ref> Some trials combined different antivirals with differing results.<ref name="pmid4790599"/> The introduction of 9-β-D-arabinofuranosyladenine, (ara-A or vidarabine), considerably less toxic than ara-C, in the mid-1970s, heralded the way for the beginning of regular neonatal antiviral treatment. Vidarabine was the first systemically administered antiviral medication with activity against HSV for which therapeutic efficacy outweighed toxicity for the management of life-threatening HSV disease. Intravenous vidarabine was licensed for use by the U.S. Food and Drug Administration in 1977. Other experimental antivirals of that period included: heparin,<ref name="pmid4289440">{{cite journal|vauthors=Nahmias AJ, Kibrick S |title=Inhibitory Effect of Heparin on Herpes Simplex Virus|journal=J. Bacteriol.|volume=87|issue=5|pages=1060–66|date=May 1964|pmid=4289440|pmc=277146|doi=10.1128/JB.87.5.1060-1066.1964}}</ref> trifluorothymidine (TFT),<ref name="pmid4790562">{{cite journal|vauthors=Allen LB, Sidwell RW |title=Target-Organ Treatment of Neurotropic Virus Diseases: Efficacy as a Chemotherapy Tool and Comparison of Activity of Adenine Arabinoside, Cytosine Arabinoside, Idoxuridine, and Trifluorothymidine|journal=Antimicrob. Agents Chemother.|volume=2|issue=3|pages=229–33|date=September 1972|pmid=4790562|pmc=444296|doi=10.1128/aac.2.3.229}}</ref> Ribivarin,<ref name="pmid212976">{{cite journal|vauthors=Allen LB, Wolf SM, Hintz CJ, Huffman JH, Sidwell RW |title=Effect of ribavirin on Type 2 Herpesvirus hominis (HVH/2) ''in vitro'' and ''in vivo''|journal=Annals of the New York Academy of Sciences|volume=284|issue=1|pages=247–53|date=March 1977|pmid=212976|doi=10.1111/j.1749-6632.1977.tb21957.x|bibcode=1977NYASA.284..247A|s2cid=12159958}}</ref> interferon,<ref name="pmid4404669">{{cite journal|vauthors=Allen LB, Cochran KW |title=Target-Organ Treatment of Neurotropic Virus Disease with Interferon Inducers|journal=Infection and Immunity|volume=6|issue=5|pages=819–23|date=November 1972|pmid=4404669|pmc=422616|doi=10.1128/IAI.6.5.819-823.1972}}</ref> Virazole,<ref name="pmid4340949">{{cite journal|vauthors=Sidwell RW, Huffman JH, Khare GP, Allen LB, Witkowski JT, Robins RK |title=Broad-spectrum antiviral activity of Virazole: 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide|journal=Science|volume=177|issue=4050|pages=705–06|date=August 1972|pmid=4340949|doi=10.1126/science.177.4050.705|bibcode=1972Sci...177..705S|s2cid=43106875}}</ref> and 5-methoxymethyl-2'-deoxyuridine (MMUdR).<ref name="pmid1239978">{{cite journal|vauthors=Babiuk LA, Meldrum B, Gupta VS, Rouse BT |title=Comparison of the Antiviral Effects of 5-Methoxymethyl-deoxyuridine with 5-Iododeoxyuridine, Cytosine Arabinoside, and Adenine Arabinoside|journal=Antimicrob. Agents Chemother.|volume=8|issue=6|pages=643–50|date=December 1975|pmid=1239978|pmc=429441|doi=10.1128/aac.8.6.643}}</ref> The introduction of 9-(2-hydroxyethoxymethyl)guanine, AKA aciclovir, in the late 1970s<ref name="pmid91931">{{cite journal|vauthors=O'Meara A, Deasy PF, Hillary IB, Bridgen WD |title=Acyclovir for treatment of mucocutaneous herpes infection in a child with leukaemia|journal=Lancet|volume=2|issue=8153|page=1196|date=December 1979|pmid=91931|doi=10.1016/S0140-6736(79)92428-0|s2cid=40775996}}</ref> raised antiviral treatment another notch and led to vidarabine vs. aciclovir trials in the late 1980s.<ref name="pmid1988829">{{cite journal|author=Whitley R|title=A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group|journal=N. Engl. J. Med.|volume=324|issue=7|pages=444–49|date=February 1991|pmid=1988829|doi=10.1056/NEJM199102143240703|name-list-style=vanc|author2=Arvin A|author3=Prober C|display-authors=3|last4=Burchett|first4=Sandra|last5=Corey|first5=Lawrence|last6=Powell|first6=Dwight|last7=Plotkin|first7=Stanley|last8=Starr|first8=Stuart|last9=Alford|first9=Charles|doi-access=free}}</ref> The lower toxicity and ease of administration over vidarabine has led to aciclovir becoming the drug of choice for herpes treatment after it was licensed by the FDA in 1998.<ref name="pmid11483782">{{cite journal|author=Kimberlin DW|title=Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections|journal=Pediatrics|volume=108|issue=2|pages=230–38|date=August 2001|pmid=11483782|doi=10.1542/peds.108.2.230|url=http://pediatrics.aappublications.org/cgi/pmidlookup?view=long&pmid=11483782|name-list-style=vanc|author2=Lin CY|author3=Jacobs RF|display-authors=3|last4=Powell|first4=D. A.|last5=Corey|first5=L.|last6=Gruber|first6=W. C.|last7=Rathore|first7=M.|last8=Bradley|first8=J. S.|last9=Diaz|first9=P. S.}}</ref> Another advantage in the treatment of neonatal herpes included greater reductions in mortality and morbidity with increased dosages, which did not occur when compared with increased dosages of vidarabine.<ref name="pmid11483782"/> However, aciclovir seems to inhibit antibody response, and newborns on aciclovir antiviral treatment experienced a slower rise in antibody titer than those on vidarabine.<ref name="pmid11483782"/>

== Society and culture == 

Some people experience negative feelings related to the condition following diagnosis, in particular, if they have acquired the genital form of the disease. Feelings can include [[Medicine:Depression (mood)|depression]], fear of rejection, feelings of isolation, fear of being found out, and self-destructive feelings.<ref name="Vezina">{{cite journal| vauthors=Vezina C, Steben M| title=Genital Herpes: Psychosexual Impacts and Counselling| journal=The Canadian Journal of CME| year=2001| pages=125–34| issue=June| url=http://www.stacommunications.com/journals/cme/images/cmepdf/june01/hsv.pdf| url-status=dead| archive-url=https://web.archive.org/web/20081216222217/http://www.stacommunications.com/journals/cme/images/cmepdf/june01/hsv.pdf| archive-date=2008-12-16| access-date=2008-09-10}}</ref> Herpes support groups have been formed in the United States and the United Kingdom, providing information about herpes and running message forums and dating websites for affected people. 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 whom they consider casual.<ref name="Green">{{cite journal|last=Green|first=J|author2=Ferrier, S |author3=Kocsis, A |author4=Shadrick, J |author5=Ukoumunne, OC |author6=Murphy, S |author7= Hetherton, J |title=Determinants of disclosure of genital herpes to partners.|journal=Sexually Transmitted Infections|date=February 2003|volume=79|issue=1|pages=42–44|pmid=12576613|pmc=1744583|doi=10.1136/sti.79.1.42}}</ref>

In a 2007 study, 1,900 people (25% of which had herpes) ranked genital herpes second for social stigma, out of all sexually transmitted diseases ([[Biology:HIV|HIV]] took the top spot for STD stigma).<ref>{{cite web|url=http://www.webmd.com/genital-herpes/news/20070824/genital-herpes-stigma-still-strong/|archive-url=https://web.archive.org/web/20131116185722/http://www.webmd.com/genital-herpes/news/20070824/genital-herpes-stigma-still-strong|title=Stigma Still Strong|author=Miranda Hitti|publisher=WebMD|date=24 August 2007|archive-date=16 November 2013}}</ref><ref>{{Cite web |url=http://www.herpesdatesites.com/meetup-groups.html |title=Herpes groups on Meetup {{!}} HerpesDateSites |website=www.herpesdatesites.com|access-date=2017-02-20|url-status=live|archive-url=https://web.archive.org/web/20170406073606/http://www.herpesdatesites.com/meetup-groups.html |archive-date=2017-04-06}}</ref><ref>{{Cite web |url=http://genitalherpesdatingsites.org/ |title=Genital Herpes Dating Sites Review {{!}} Best Herpes Dating Sites for Genital HSV Singles in 2016 |website=genitalherpesdatingsites.org |access-date=2017-02-20 |url-status=live |archive-url=https://web.archive.org/web/20170522182714/http://genitalherpesdatingsites.org/ |archive-date=2017-05-22}}</ref>

=== Support groups ===
==== United States ==== 
A source of support is the ''National Herpes Resource Center'' which arose from the work of the American Sexual Health Association (ASHA).<ref>{{cite web |title=Herpes Support Forum |url=http://www.HerpesSupportForum.com |access-date=15 May 2016 |url-status=live |archive-url=https://web.archive.org/web/20160504160451/http://herpessupportforum.com/  |archive-date=4 May 2016}}</ref> The ASHA  was created in 1914 in response to the increase in sexually transmitted diseases that had spread during [[Social:World War I|World War I]].<ref>{{cite web|title=Our History|url=http://www.ashasexualhealth.org/who-we-are/312-2/|access-date=19 October 2014 |quote=ASHA was founded in 1914 in New York City, formed out of early 20th-century social reform movements focused on fighting sexually transmitted infections (known then as venereal disease, or VD) and prostitution. |url-status=live |archive-url=https://web.archive.org/web/20141021144339/http://www.ashasexualhealth.org/who-we-are/312-2/|archive-date=21 October 2014}}</ref> During the 1970s, there was an increase in sexually transmitted diseases.  One of the diseases that increased dramatically was genital herpes. In response, ASHA created the National Herpes Resource Center in 1979. The Herpes Resource Center (HRC) was designed to meet the growing need for education and awareness about the virus. One of the projects of the HRC was to create a network of local support (HELP) groups.  The goal of these HELP groups was to provide a safe, confidential environment where participants can get accurate information and share experiences, fears, and feelings with others who are concerned about herpes.<ref>{{cite web |url=http://www.ashastd.org./about/about_history.cfm |archive-url=https://web.archive.org/web/20080820110233/http://www.ashastd.org./about/about_history.cfm |archive-date=2008-08-20 |title=American Social Health Association }}</ref><ref>{{cite web |url=http://www.arbor.edu/Transcript-Evaluation-Incoming-Transfers/International-Students/Index.aspx |archive-url=https://web.archive.org/web/20111003200251/http://www.arbor.edu/Transcript-Evaluation-Incoming-Transfers/International-Students/Index.aspx |archive-date=2011-10-03 |title=The Herpes Resource Center}}</ref>

==== UK ==== 
In the UK, the Herpes Association (now the Herpes Viruses Association) was started in 1982, becoming a registered charity with a Department of Health grant in 1985. The charity started as a string of local group meetings before acquiring an office and a national spread.<ref>{{Cite web |url=http://www.hva.org.uk |title=Helping You With Herpes |publisher=Herpes Viruses Association |access-date=2017-02-20 |url-status=live |archive-url=https://web.archive.org/web/20150726180701/http://www.hva.org.uk/|archive-date=2015-07-26}}</ref>

==Research==
Research has gone into vaccines for both prevention and treatment of herpes infections. 

As of October 2022, the U.S. [[Organization:Food and Drug Administration|FDA]] have not approved a vaccine for herpes.<ref>{{Cite web |title=mRNA-1608 Herpes Vaccine |url=https://www.precisionvaccinations.com/vaccines/mrna-1608-herpes-vaccine |access-date=2022-12-11 |website=www.precisionvaccinations.com |language=en-US}}</ref> However, there are herpes vaccines currently in clinical trials, such as [[Company:Moderna|Moderna]] mRNA-1608.<ref>{{Cite web |date=2022-09-27 |title=Can herpes kill you? - Technology Org |url=https://www.technology.org/2022/09/27/can-herpes-kill-you/ |access-date=2022-12-11 |website=www.technology.org |language=en-US}}</ref> Unsuccessful clinical trials have been conducted for some glycoprotein subunit vaccines.{{citation needed|date=May 2019}} As of 2017, the future pipeline includes several promising replication-incompetent vaccine proposals while two replication-competent (live-attenuated) HSV vaccine are undergoing human testing.{{citation needed|date=May 2019}}

A genomic study of the herpes simplex type 1 virus confirmed the human migration pattern theory known as the out-of-Africa hypothesis.<ref>{{cite web|last=Foley|first=James A.|title=Hitchhiking Herpes Virus Aligns with Spread of Human Civilization|url=http://www.natureworldnews.com/articles/4548/20131021/hitchhiking-herpes-virus-aligns-spread-human-civilization.htm|publisher=NatureWorldNews.com|access-date=22 October 2013|date=21 Oct 2013|url-status=live|archive-url=https://web.archive.org/web/20131022012824/http://www.natureworldnews.com/articles/4548/20131021/hitchhiking-herpes-virus-aligns-spread-human-civilization.htm|archive-date=22 October 2013}}</ref>

==References==
{{Reflist}}

==External links==
<!-- BEFORE inserting new links here you should first post it to the talk page, otherwise your edit is likely to be reverted. -->
* {{curlie|Health/Conditions_and_Diseases/Infectious_Diseases/Viral/Herpes/}}

{{Medical condition classification and resources
 | DiseasesDB      = 5841
 | DiseasesDB_mult = {{DiseasesDB2|33021}}
 | ICD10           = {{ICD10|A|60||a|50}}, {{ICD10|B|00||b|00}}, {{ICD10|G|05|1|g|00}}, {{ICD10|P|35|2|p|35}}
 | ICD9            = {{ICD9|054.0}}, {{ICD9|054.1}}, {{ICD9|054.2}}, {{ICD9|054.3}}, {{ICD9|771.2}}
 | ICDO            =
 | OMIM            =
 | MedlinePlus     =
 | eMedicineSubj   = med
 | eMedicineTopic  = 1006
 | MeshID         = D006561
}}
{{STD/STI}}
{{Viral cutaneous conditions}}

{{DEFAULTSORT:Herpes Simplex}}
[[Category:Conditions of the mucous membranes]]
[[Category:Viral diseases]]
[[Category:Wikipedia medicine articles ready to translate]]

{{Sourceattribution|Herpes}}