Herpes_simplex

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07-SEPTEMBER-2008 03:17:44 - simplex Herpes simplex Classification and external resources Electron micrograph of Herpes simplex virus. ICD-10 A60., B00., G05.1, P35.2 ICD-9 054.0, 054.1, 054.2, 054.3, 771.2 DiseasesDB 5841 33021 eMedicine med/1006 MeSH D006561 This article is about the disease. For information about the specific virus, see Herpes simplex virus. herpes redirects here. For all types of herpes viruses, see Herpesviridae. Herpes simplex is a viral disease caused by Herpes simplex viruses; both herpes simplex virus 1 HSV-1 and herpes simplex virus 2 HSV-2 cause herpes simplex. Infection with the herpes virus is categorized into one of several distinct disorders based on the site of infection. Oral herpes, the visible symptoms of which are colloquially called cold sores, infects the face and mouth. Oral herpes is the most common form of infection. Infection of the genitals, commonly known as herpes, is the second most common form of herpes. Other disorders such as herpetic whitlow, herpes gladiatorum, ocular herpes keratitis, cerebral herpes infection encephalitis, Mollaret's meningitis, neonatal herpes, and possibly Bell's palsy are all caused by herpes simplex viruses. Herpes viruses cycle between periods of active disease-presenting as blisters containing infectious virus particles-that last 2-21 days, followed by a remission period, during which the sores disappear. Genital herpes, however, is often asymptomatic, though viral shedding may still occur. After initial infection, the viruses move to sensory nerves, where they reside as life-long, latent viruses. Causes of recurrence are uncertain, though some potential triggers have been identified. Over time episodes of active disease reduce in frequency. Herpes simplex is most easily transmitted by direct contact with a lesion or the body fluid of an infected individual. Transmission may also occur through skin-to-skin contact during periods of asymptomatic shedding. Barrier protection methods are the most reliable, but not failsafe, method of preventing transmission of herpes. Oral herpes is easily diagnosed if the patient presents with visible sores or ulcers. Early stages of orofacial herpes and genital herpes are harder to diagnose; laboratory testing is usually required. Prevalence of HSV infections varies throughout the world. Poor hygiene, overcrowding, lower socioeconomic status, and birth in an undeveloped country have been identified as risk factors associated with increased HSV-1 childhood infection. Additional studies have identified other risk factors for both types of HSV. There is currently no cure for herpes; no vaccine is currently available to prevent or eliminate herpes. However, treatments are available to reduce viral reproduction and shedding, prevent the virus from entering the skin, and alleviate the severity of symptomatic episodes. Contents 1 Disorders 1.1 Orofacial infection 1.2 Genital infection 1.3 Herpes whitlow 1.4 Herpes Gladiatorium 1.5 Ocular Herpes 1.6 Neonatal herpes simplex 1.7 Viral meningitis 1.8 Bell's palsy 1.9 Alzheimer's disease 2 Recurrence 3 Transmission and Prevention 4 Diagnosis 5 Epidemiology 5.1 Europe 5.2 North America 5.2.1 United States 5.2.2 Canada 5.3 Africa 5.3.1 Sub-Saharan Africa 5.3.2 Northern Africa 5.4 Central and South America 5.5 Asia 5.5.1 Eastern and South East Asia 5.5.2 Southern Asia 5.5.3 Middle East 5.6 Oceania 6 Treatment 6.1 History 6.2 Antiviral medication 6.3 Topical treatments 6.4 Other drugs 6.5 Vaccines 6.6 Natural compounds 7 Psychological and social effects 8 References 9 External links Disorders 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 herpes 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. Patients with immature or suppressed immune systems, such as newborns, transplant recipients, or AIDS patients are prone to severe complications from HSV infections. In all cases HSV is never removed from the body by the 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 ganglion.1 As a result of primary infection, the body produces antibodies to the particular type of HSV involved, preventing a subsequent infection of that type at a different site. In HSV-1 infected individuals, seroconversion after an oral infection will prevent additional HSV-1 infections such as whitlow, genital herpes, and keratitis. Prior HSV-1 seroconversion seems to ameliorate the symptoms of a later HSV-2 infection, however HSV-2 can still be contracted. Most indications are that an HSV-2 infection contracted prior to HSV-1 seroconversion will immunize that person against HSV-1 infection. 2 This not neccessarily good, as prior HSV-1 infection has the tendency to ameliorate the effects of symptomatic HSV-2 reoccurences. Orofacial infection Herpesviral vesicular dermatitis Classification and external resources Herpes lesion on upper lip and face ICD-10 B00.1 Orofacial herpes affects the face and mouth. Infection occurs when the virus comes into contact with oral mucosa or abraded skin. Infection by the type 1 strain of herpes simplex virus HSV-1 is the most common cause of orofacial herpes, though cases of oral infection by the type 2 strain are increasing.3 Herpes infections are largely asymptomatic; when symptoms appear they will typically resolve within two weeks.3 The main symptom of oral infection is acute herpetic gingivostomatitis inflammation of the mucosa of the cheek and gums, which occurs within 5-10 days of infection. Other symptoms may also develop, including painful ulcers-sometimes confused with canker sores-fever, and sore throat.3 Primary HSV infection in adolescents frequently manifests as severe pharyngitis with lesions developing on the cheek and gums. Some individuals develop difficulty in swallowing dysphagia and swollen lymph nodes lymphadenopathy.3 Primary HSV infections in adults often results in pharyngitis similar to that observed in glandular fever infectious mononucleosis, but gingivostomatitis is less likely. Recurrent oral infection is more common with HSV-1 infections than with HSV-2. Prodromal symptoms often precede a recurrence. Symptoms typically begin with tingling itching and reddening of the skin around the infected site. Eventually, fluid-filled blisters form on the lip labial tissue and the area between the lip and skin vermilion border. The recurrent infection is thus often called herpes simplex labialis. Rare reinfections occur inside the mouth intraoral HSV stomatitis affecting the gums, alveolar ridge, hard palate, and the back of the tongue, possibly accompanied by herpes labialis.3 Genital infection Anogenital herpesviral infection Classification and external resources Genital herpes in a female ICD-10 A60. MeSH D006558 Genital herpes in a male Genital herpes in a male Following the classification HSV into two distinct categories of HSV-1 and HSV-2 in the 60s, 45It was established that HSV-2 was below the waist, HSV-1 was above the waist. Although genital herpes is largely believed to be caused by HSV-2, genital HSV-1 infections are increasing and now exceed 50% in certain populations, 678 and that rule of thumb no longer applies. Although HSV is believed to be asymptomatic in the majority of cases, thus aiding contagion and hindering containment, 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.9 These usually appear 4-7 days after sexual exposure to HSV for the first time.1 Genital HSV-1 infection recurs at rate of about one sixth of that of genital HSV-2. 10In males, the lesions occur on the shaft of the penis or other parts of the genital region, on the inner thigh, buttocks, or anus. In females, lesions appear on or near the pubis, labia, clitoris, vulva, buttocks or anus.9 Other common symptoms include pain, itching, and burning. Less frequent, yet still common, symptoms include discharge from the penis or vagina, fever, headache, muscle pain myalgia, swollen and enlarged lymph nodes and malaise.1 Women often experience additional symptoms that include painful urination dysuria and cervicitis. Herpetic proctitis inflammation of the anus and rectum is common for individuals participating in anal intercourse.1 After 2-3 weeks, existing lesions progress into ulcers and then crust and heal, although lesions on mucosal surfaces may never form crusts.1 Herpes whitlow Herpes whitlow herpetic whitlow is a painful infection that typically affects the fingers or thumbs. Occasionally infection occurs on the toes or on the nail cuticle. Herpes whitlow can be caused by infection by HSV-1 or HSV-2.11 HSV-1 whitlow is often contracted by health care workers that come in contact with the virus; it is most commonly contracted by dental workers and medical workers exposed to oral secretions.1213 It is also often observed in thumb-sucking children with primary HSV-1 oral infection autoinoculation prior to seroconversion,11 and in adults aged 20 to 30 following contact with HSV-2-infected genitals.14 Symptoms of herpetic whitlow include swelling, reddening and tenderness of the skin of infected finger. This may be accompanied by fever and swollen lymph nodes. Small, clear vesicles initially form individually, then merge and become cloudy. Associated pain often seems large relative to the physical symptoms. The herpes whitlow lesion usually heals in two to three weeks.15 Herpes Gladiatorium 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 provides an area of entry for HSV-1. Symptoms present within 2 weeks of direct skin-to-skin contact with an infected person. They include skin ulceration on the face, ears, and neck, fever, headache, sore throat and swollen glands. It occasionally affects the eyes or eyelids. In one of the largest outbreaks ever among high-school wrestlers at a four week intensive training camp, HSV was identified in 60 of 175 wrestler. Lesions were on the head in 73 percent of the wrestlers, the extremities in 42%, and the trunk in 28%.16 Physical symptoms sometimes recur in the skin.17 Previous adolescent HSV-1 seroconversion would preclude most herpes gladiatorum, but being that stress and trauma are recognized triggers, such a person would be likely to infect others. Ocular Herpes Herpesviral ocular disease Classification and external resources Herpes infection of the cornea ICD-10 B00.5 MeSH D016849 Ocular herpes is a special case of facial herpes infection, known as herpes keratitis. Occular herpes is generally caused by HSV-1. It begins with infection of epithelial cells on the surface of the eye and retrograde infection of nerves serving the cornea.18 Primary infection typically presents as swelling of the conjunctiva and eye-lids blepharoconjunctivitis, accompanied by small white itchy lesions on the surface of the cornea. The effect of the lesions varies, from minor damage to the epithelium superficial punctate keratitis, to formation of dendritic ulcers.19 Infection is unilateral, affecting one eye at a time. Additional symptoms include dull pain deep inside the eye, mild to acute dryness, and sinusitis. Most primary infections resolve spontaneously in a few weeks. Healing can be aided by the use of oral and topical antivirals. Subsequent recurrences may be more severe, with infected epithelial cells showing larger dendritic ulceration, and lesions forming white plaques.19 The epithelial layer is sloughed off as the dendritic ulcer grows, and mild inflammation iritis may occur in the underlying stroma of iris. Sensation loss occurs in lesional areas, producing generalised corneal anaesthesia with repeated recurrences.19 Recurrence can be accompanied by chronic dry eye, low grade intermittent conjunctivitis, or chronic unexplained sinusitis. Following persistent infection the concentration of viral DNA reaches a critical limit. Antibody responses against the viral antigen expression in the stroma can trigger a massive autoimmune response in the eye. The response may result in the destruction of the corneal stroma,19 resulting in loss of vision due to opacification of the cornea. This is known as immune-mediated stromal keratitis. Herpes simplex encephalitis HSE is one of the most severe viral infections of the human central nervous system. It is estimated to affect at least 1 in 500,000 individuals per year.20 About 1 in 3 cases of HSE result from primary HSV-1 infection, predominantly occurring in individuals under the age of 18; 2 in 3 cases occur in seropositive persons, few of whom have history of recurrent orofacial herpes. Approximately 50% of individuals that develop HSE are over 50 years of age.21 HSE is thought to be caused by the retrograde transmission of virus from a peripheral site on the face following HSV-1 reactivation, along a nerve axon, to the brain.20 The virus lies dormant in the ganglion of the trigeminal cranial nerve, but the reason for reactivation, and its pathway to gain access to the brain, remains unclear. The olfactory nerve may also be involved in HSE.22 For unknown reasons the virus seems to target the temporal lobes of the brain. Most individuals with HSE show a decrease in their level of consciousness and an altered mental state presenting as confusion, and changes in personality. Increased numbers of white blood cells can be found in patient's cerebrospinal fluid, without the presence of pathogenic bacteria and fungi. Patients typically have a fever.20 and may have seizures. The electrical activity of the brain changes as the disease progresses, first showing abnormalities in one temporal lobe of the brain, which spread to the other temporal lobe 7-10 days later.20 Without treatment, HSE results in rapid death in approximately 70% of cases.20 HSE is fatal in around 20% of cases treated, and causes serious long-term neurological damage in over half of survivors. Only a small population of survivors 2.5% regain completely normal brain function.21 Neonatal herpes simplex Congenital herpesviral herpes simplex infection Classification and external resources HSV disease in a newborn child ICD-10 P35.2 ICD-9 771.2 Neonatal HSV infection is a rare but serious condition, usually caused by vertical transmission of HSV from mother to newborn. The majority of cases 85%occur during birth when the baby comes in contact with infected genital secretions in the birth canal, an estimated 5% are infected in utero, and approximately 10% of cases are acquired postnatally. Detection and prevention is difficult because transmission is asymptomatic in 60% - 98%23 of cases. Neonatal HSV rates in the U.S. are estimated to be between 1 in 3,000 and 1 in 20,000 live births. Approximately 22% of pregnant women in the U.S. have had previous exposure to HSV-2, and an additional 2% acquire the virus during pregnancy, mirroring the HSV-2 infection rate in the general population.24 The risk of transmission to the newborn is 30-57% in cases where the mother acquired a primary infection in the third trimester of pregnancy. Risk of transmission by a mother with existing antibodies for both HSV-1 and HSV-2 has a much lower 1-3% transmission rate. This in part is due to the transfer of significant titer of protective maternal antibodies to the fetus from about the seventh month of pregnancy.2526However, shedding of HSV-1 from both primary genital infection and reactivations is associated with higher transmission from mother to infant.25 HSV-1 neonatal herpes is extremely rare in developing countries because development of HSV-1 specific antibodies usually occurs in childhood or adolescence, precluding a later genital HSV-1 infection. HSV-2 infections are much more common in these countries. In industrialized nations, the adolescent HSV-1 seroprevalance has been dropping steadily for the last 5 decades. The resulting increase in the number of young women becoming sexually active while HSV-1 seronegative has contributed to increased HSV-1 genital herpes rates, and as a result, increased HSV-1 neonatal herpes in developed nations. A recent three year study in Canada 2000-2003 revealed a neonatal HSV incidence of 5.9 per 100,000 live births. HSV-1 was the cause of 62.5% of cases of neonatal herpes of known type, and 98.3% of transmission was asymptomatic.23 Asymptomatic genital HSV-1 has been shown to be more infectious to the neonate, and is more likely to produce neonatal herpes, than HSV-2,2527. However, with prompt application of antiviral therapy, the prognosis of neonatal HSV-1 infection is better than that for HSV-2. Neonatal herpes manifests itself in three forms: skin, eyes, and mouth herpes SEM sometimes referred to as localized, disseminated herpes DIS, and central nervous system herpesCNS.28 SEM herpes is characterized by external lesions but no internal organ involvement. Lesions are likely to appear on trauma sites such as the attachment site of fetal scalp electrodes, forceps or vacuum extractors that are used during delivery, in the margin of the eyes, the nasopharynx, and in areas associated with trauma or surgery including circumcision.29DIS herpes affects internal organs, particularly the liver. CNS herpes is an infection of the nervous system and the brain that can lead to encephalitis. Infants with CNS herpes present with seizures, tremors, lethargy, and irritability, they feed poorly, have unstable temperatures, and their fontanelle soft spot of the skull may bulge.25 CNS herpes is associated with highest morbidity, and DIS herpes has a higher mortality rate. These categories are not mutually exclusive and there is often overlap of two or more types. SEM herpes has the best prognosis of the three, however, if left untreated it may progress to disseminated or CNS herpes with its attendant increases in mortality and morbidity. Death from neonatal HSV disease in the U.S. is currently decreasing; The current death rate is about 25%, down from as high as 85% in untreated cases just a few decades ago. Other complications from neonatal herpes include prematurity with approximately 50% of cases having a gestation of 38 weeks or less, and a concurrent sepsis in approximately one quarter of cases that further clouds speedy diagnosis. Reductions in morbidity and mortality are due to the use of antiviral treatments such as vidarabine and acyclovir.28303132 However, morbidity and mortality still remain high due to diagnosis of DIS and CNS herpes coming too late for effective antiviral administration; early diagnosis is difficult in the 20-40% of infected neonates that have no visible lesions.33 Harrison's Principles of Internal Medicine, recommends that pregnant women with active genital herpes lesions at the time of labor be delivered by caesarean section. Women whose herpes is not active can be managed with acyclovir.34 The current practice is to deliver women with primary or first episode non primary infection via caesarean section, and those with recurrrent infection vaginally, even in the presence of lesions because of the low risk 1-3% of vertical transmission associated with recurrent herpes. Viral meningitis HSV-2 is the most common cause of Mollaret's meningitis, a type of recurrent viral meningitis.3536 This condition was first described in 1944 by French neurologist Pierre Mollaret. Recurrences usually last a few days or a few weeks, and resolve without treatment. They may recur weekly or monthly for approximately 5 years following primary infection.37 Bell's palsy In a mouse model a type of facial paralysis called Bell's palsy has been linked to the presence and reactivation of latent HSV-1 inside the sensory nerves of the face geniculate ganglia.3839 This is supported by findings that show the presence of HSV-1 DNA in saliva at a higher frequency in patients with Bell's palsy relative to those without the condition.40 However, since HSV can also be detected in these ganglia in large numbers of individuals that have never experienced facial paralysis, and high titers of antibodies for HSV are not found in HSV-infected individuals with Bell's palsy relative to those without, this theory has been contested.41 In other studies HSV-1 DNA was not detected in the cerebrospinal fluid of Bell's palsy sufferers, raising questions whether HSV-1 is the causative agent in this type of facial paralysis.4243 The potential effect of HSV-1 in the etiology of Bell's palsy has prompted the use of antiviral medication to treat the condition. The benefits of acyclovir and valacyclovir have been studied.44 Alzheimer's disease Scientists discovered a link between HSV-1 and Alzheimer's disease in 1979.45 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 the development of Alzheimer's disease.46 This research identifies HSVs as the pathogen most clearly linked to the establishment of Alzheimer's.47 Without the presence of the gene allele, HSV type 1 does not appear to cause any neurological damage and thus increase the risk of Alzheimer's.48 Recurrence Following active infection herpes viruses establish a latent infection in sensory and autonomic ganglia of the nervous system. The double-stranded DNA of the virus is incorporated into the cell physiology by infection of the nucleus of a nerve's cell body. HSV latency is static-no virus is produced-and is controlled by a number of viral genes, including Latency Associated Transcript LAT.49 Many HSV infected people experience recurrence within the first year of infection.1 Prodrome precedes development of lesions. Prodromal symptoms include tingling 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, lesions are less painful, and lesions heal faster within 5-10 days without antiviral treatment, than those occurring during the primary infection.1 Subsequent outbreaks tend to be periodic or episodic, occurring on average four to five times a year when not using antiviral therapy. The causes of reactivation are uncertain, but several potential triggers have been documented. Physical or psychological stress can trigger an outbreak of herpes.50 Changes in the immune system during menstruation may play a role in HSV-1 reactivation.5152 Concurrent infections, such as viral upper respiratory tract infection or other febrile diseases, can cause outbreaks. Reactivation due to infection 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.5354555657 The frequency and severity of recurrent outbreaks may vary greatly between patients. An immunity to the virus is built over time; immunocompromised individuals may experience episodes that are longer, more frequent and more severe. Antiviral medication has been proven to shorten the frequency and duration of outbreaks.58 Outbreaks may occur at the original site of the infection or in close proximity to nerve endings that reach out from the infected ganglia. In the case of a genital infection, sores can appear at the original site of infection or near the base of the spine, the buttocks, back of the thighs. Transmission and Prevention Herpes is contracted through direct contact with an active lesion or body fluid of an infected person.59 Herpes transmission occurs between discordant partners; a person with a history of infection HSV seropositive can pass the virus to an HSV seronegative person.1 There are no documented cases of infection via an inanimate object e.g. a towel, toilet seat, drinking vessels.citations needed 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 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.60 Infected people that show no visible symptoms may still shed and transmit virus through their skin; asymptomatic shedding may represent the most common form of HSV-2 transmission.60 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.61 There are indications that 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 1 to 12 annual recurrences to those that have no recurrences.60 Antibodies that develop following an initial infection with a type of HSV prevents reinfection with the same virus type-a person with a history of orofacial infection caused by HSV-1 cannot contract herpes whitlow or a genital infection caused by HSV-1. In a monogamous couple, a seronegative female runs a greater than 30% per year risk of contracting an HSV infection from a seropositive male partner.62 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. Barrier protection, such as a condom, can reduce the risk of herpes transmission in some cases. Barrier protection, such as a condom, can reduce the risk of herpes transmission in some cases. For genital herpes, condoms are highly effective in limiting transmission of herpes simplex infection.6364 The virus cannot pass through latex, but a condom's effectiveness is somewhat limited on a public health scale by their limited use in the community,65 and on an individual scale because the condom may not completely cover blisters on the penis of an infected male, or the base of the penis or testicles not covered by the condom may come into contact with free virus in vaginal fluid of an infected female. In such cases, abstinence from sexual activity or washing of the genitals after sex is recommended. 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 valaciclovir, in conjunction with a condom, further decreases the chances of transmission to the uninfected partner.1 Topical microbicides which contain chemicals that directly inactivate the virus and block viral entry are currently being investigated.1 Vaccines for HSV are currently undergoing trials. Once developed, they may be used to help with prevention or minimize initial infections as well as treatment for existing infections.66 As with almost all sexually transmitted infections, women are more susceptible to acquiring genital HSV-2 than men.67 On an annual basis, without the use of antivirals or condoms, the transmission risk of HSV-2 from infected male to female is approximately 8-10%. 6862 This is believed to be due to the increased exposure of mucosal tissue to potential infection sites. Transmission risk from infected female to male is approximately 4-5% annually.68 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 by 50%.636469 Condom use is much more effective at preventing male to female transmission than vice-versa.63 The effects of combining antiviral and condom use is roughly additive, thus resulting in approximately a 75% combined reduction in annual transmission risk.citation needed These figures reflect experiences with subjects having frequently-recurring genital herpes 6 recurrences per year. Subjects with low recurrence rates and those with no clinical manifestations were excluded from these studies.citation needed 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. A seronegative mother that contracts HSV at this time has up to a 57% chance of conveying the infection to her baby during childbirth, since insufficient time will have occurred for the generation and transfer of protective maternal antibodies before the birth of the child, whereas a woman seropositive for both HSV-1 and HSV-2 has around a 1-3% chance of transmitting infection to her infant.7026 Women that are seropositive for only one type of HSV are only half as likely to transmit HSV as infected seronegative mothers. Mothers infected with HSV are advised to avoid procedures that would cause trauma to the infant during birth e.g., fetal scalp electrodes, forceps, and vacuum extractors and, should lesions be present, to elect caesarean section to reduce exposure of the child to infected secretions in the birth canal.1 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.1 HSV-2 infected individuals are at higher risk for acquiring HIV when practicing unprotected sex with HIV positive persons, particularly during an outbreak with active lesions.71 Diagnosis Primary orofacial herpes is readily identified by clinical examination of persons with no previous history of lesions and contact with an individual with known HSV-1 infection. The appearance and distribution of sores in these individuals typically presents as multiple, round, superficial oral ulcers, accompanied by acute gingivitis.17 Adults with non-typical 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 allergic stomatitis. When lesions do not appear inside the mouth primary orofacial herpes is sometimes mistaken for impetigo, a bacterial infection. Common mouth ulcers aphthous ulcer also resemble intraoral herpes, but do not present a vesicular stage.17 Genital herpes can be more difficult to diagnose than oral herpes since most HSV-2-infected persons have no classical symptoms.17 Further confusing diagnosis, several other conditions resemble genital herpes, including lichen planus, atopic dermatitis, and urethritis.17 Laboratory testing is often used to confirm a diagnosis of genital herpes. Laboratory tests include: culture of the virus, direct fluorescent antibody DFA studies to detect virus, skin biopsy, and polymerase chain reaction PCR 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.17 Serological tests for antibodies to HSV are rarely useful to diagnosis and not routinely used in clinical practice17, but are important in epidemiological studies. Serologic assays cannot differentiate between antibodies generated in response to a genital versus an oral HSV infection, and as such cannot confirm the site of infection. Absence of antibody to HSV-2 does not exclude gential infection because of the increasing incidence of genital infections caused by HSV-1. Epidemiology Although many people infected with HSV develop labial or genital lesions, the majority are either undiagnosed or display no physical symptoms-individuals with no symptoms are described as asymptomatic or as having subclinical herpes.72 In many infections, the first symptom a person will have of their own infection 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. Many studies have been performed around the world to estimate the numbers of individuals infected with HSV-1 and HSV-2 by determining if they have developed antibodies against either viral species.73 This information provides population prevalence of HSV viral infections in individuals with or without active disease. Seroprevalence estimates for HSV-1 and HSV-273 Location Years Prevalence % HSV-1 HSV-2 Total Female Male Africa Benin 1997-8 - 30 12 Cameroon 1997-8 - 46-51 24-27 Central African Republic 1998-9 99 82 - Eritrea 1995 84-97 23 24-27 The Gambia 1998-9 - 29-32 5 Kenya 1997-8 - 68 35 Mali74 1991-7 93 43 - Morocco74 1991-7 99 26 - South Africa 1999 - 53 17 Tanzania 1992 - 42 19 Uganda 1989-93 91 71 36 Zambia 1997-8 - 55 36 Zimbabwe 1993-8 - 67 36-53 Asia Bangladesh 1996-8 46# 8-14 - China 1987-95 - 18-29 17 Israel 1998-9 70 5 4 Japan 1985-93 50-60 1-17 2 Jordan 2000 - 41 53 South Korea75 2004 - 28 22 Philippines 1991-3 - 9 - Syria 1995-8 80-100 0 0-1 Thailand7473 1991-7 51 35 15 Turkey 1991-2 97 42 - Australasia Australia 1992-8 79-80 11-15 - New Zealand 1993-8 - 4-15 3-7 Central/South America Brazil 1990-7 - 23-42 - Colombia74 1985-97 89 57 - Costa Rica 1984-5 - 39 - Haiti 1992 - 54 - Mexico 1992-7 - 30 - Peru74 1991-7 92 36 - Europe Bulgaria76 1999 84 15-40 15-30 Denmark 1986 76 31 - Finland 1966-89 - 26-31 - Germany 1996-7 87 15 11 Greenland 1986 98 68 - Italy 1981-8 81-93 1-5 0-5 Norway 1992-4 79 27 - Spain 1992-3 79 4 4 Sweden 1989-93 41# 21-33 - Switzerland 1997 65-87 22 11 UK 1984-95 69-78 5 3 North America Canada 1999 57 13 - USA 1988-94 68 26 18 # in children Europe Large differences in HSV-1 seroprevalence are seen in different European countries. HSV-1 seroprevalence is high in Bulgaria 83.9% and The Czech Republic 80.6%, and lower in Belgium 67.4%, The Netherlands 56.7%, and Finland 52.4%.76 The typical age at which HSV-1 infection is acquired ranges from 5 to 9 years in Eastern European countries like Bulgaria and the Czech Republic, to over 25 years of age in Northern European countries such as Finland, The Netherlands, Germany, and England and Wales. Young adults in Northern European countries are less likely to be infected with HSV-1. European women are more likely to be HSV-1 seropositive than men.76 HSV-2 seropositivity is widely distributed in Europeans older than 12, although there are large differences in the percentage of the population exposed to HSV-2. Bulgaria has a high 23.9% HSV-2 seroprevalence relative to other European countries: Germany 13.9%, Finland 13.4%, Belgium 11.1%, The Netherlands 8.8%, the Czech Republic 6.0%, and England and Wales 4.2%.76 Women are more likely to be seropositive than men, and likely acquire the virus at an earlier age. In each country of Europe, HSV-2 seropositivity becomes more common from adolescence onwards and increases in the population with age, with a decline in the older age groups in some countries.76 North America United States African Americans and immigrants from developing countries typically have an HSV-1 seroprevalance in their adolescent population that is two or three times higher than that of Caucasian Americans, possibly reflecting differences in their socioeconomic backgrounds.17 Many white Americans become sexually active while seronegative for HSV-1. The absence of antibodies from a prior oral HSV-1 infection leaves these individuals susceptible to herpes whitlow, herpes gladiatorium, and HSV-1 genital infection. Primary genital infection brings with it the risk of vertical transmission to the neonate, and is highest if the mother contracts a primary infection during the third trimester of pregnancy. In the U.S. the number of genital infections caused by HSV-1 is now thought to be about 50% of first episodes of genital infection.777 In healthy adults, HSV-2 infection occurs more frequently in the USA than in Europe, and infection rates appear to be increasing. In individuals over 12 years old, HSV-2 seroprevalence has increased from 16.4% in 1976 to 21.8% in 1994 and is still rising.78 The current incidence of genital herpes caused by HSV-2 in the U.S. is roughly one in four or five adults, with approximately 50 million people infected with genital herpes and an estimated 0.5 million new genital herpes infections occurring each year.17 African Americans appear more susceptible to HSV-2, although the presence of active genital symptoms is more likely in Caucasian Americans. The largest increase in HSV-2 acquisition during the past few years is in white adolescents. People with many lifetime sexual partners and those who are sexually active from a young age are also at higher-risk for the transmission of HSV-2 in the U.S.79808182 Women are at higher risk than men for acquiring HSV-2 infection, and the chance of being infected increases with age.17 Canada According to a study in Ontario, up to 55% of Canadians age of 15 to 16, and 89% of individuals in their early forties have antibodies to HSV-1.83 Teenagers are less likely to be seropositive for HSV-2-antibodies against this virus are only found in 0-3.8% of 15-16 year olds. However, 21% of individuals in their early forties have antibodies against HSV-2, reflecting the sexually transmitted nature of this virus. When standardising for age, HSV-2 seroprevalence in Ontario for individuals between the ages of 15 to 44 was 9.1%. This is much lower than estimated levels of HSV-2 seroprevalence in people of a similar age range in the United States.83 HSV-2 seroprevalence in pregnant women between the ages of 15-44 in British Columbia is similar, with 57% having antibodies for HSV-1 and 13% having antibodies for HSV-2.73 In British Columbia in 1999, the seroprevalence of HSV-2 antibody in leftover serum submitted for antenatal testing revealed a prevalence of 17.3%, ranging from 7.1% in women 15-19 years old to 28.2% in those 40-44 years.84 In attendees at an Alberta sexually transmitted infection STI clinic in 1994 and 1995, the seroprevalence of HSV-1 and -2 in leftover sera was 56% and 19%, respectively.85 In Nova Scotia, 58.1% of 1,790 HSV isolates from genital lesion cultures in women were HSV-1; in men, 36.7% of 468 isolates were HSV-186 Africa Sub-Saharan Africa HSV-2 is more common in Sub-Saharan Africa than in Europe or the North America. Up to 82% of women and 53% of men in Sub-Saharan Africa are seropositive for HSV-2. These are the highest levels of HSV-2 infection in the world, although exact levels vary from country to country in this continent.87 In most African countries, HSV-2 prevalence increases with age. However, age-associated decreases in HSV-2 seroprevalence has been observed for women in Uganda and Zambia, and in men in Ethiopia, Benin, and Uganda.73 Northern Africa Genital herpes appears less common in Northern Africa compared to Sub-Saharan Africa. For example, only 26% of middle-aged women have antibodies for HSV-2 in Morocco.74 Women are more likely to be infected with HSV-2 once they are over the age of 40.74 Children in Egypt are often infected with HSV from a young age-HSV-1 or HSV-2 antibodies are present in an estimated 54% of children under the age of 5, and 77% in children over 10 years of age.88 Algerian children are also likely to acquire HSV-1 infection at a young age under 6 and 81.25% of the population has antibodies to HSV-1 by the age of 15.89 Central and South America Relative to rates in Europe and North America, HSV-2 seroprevalency is high in Central and South America. Infection levels are estimated at 20% to 60%.7387 During the mid 1980s, HSV-2 prevalence was 33% in 25-29 year old women and 45% in those aged 40 and over in Costa Rica. In the early 1990s HSV-2 prevalence was approximately 45% among women over 60 in Mexico.73 The highest HSV-2 prevalence in Central or South America-60%-has been found in Colombian middle-aged women, although similar HSV-2 prevalence has been observed in younger women in Haiti 54%.73 HSV-2 infects about 30% of women over 30 years old in Colombia, Costa Rica, Mexico, and Panama. HSV-2 antibodies were found in more than 41% of women of childbearing age in Brazil.73 However, no increase in seroprevalence was associated with age in women over 40 years old in Brazil-HSV-2 prevalence was estimated at 50% among women aged 40-49, 33% among women 50-59, and 42% among women over 60. Women in Brazil are more likely to acquire an HSV-2 infection if their male partners had history of anal sex and had many sexual partners in his lifetime.74 In Peru, HSV-2 prevalence is also high among women in their 30s but is lower in men.73 Asia Eastern and South East Asia HSV-1 seroprevalence in some Asian countries is low, relative to other countries worldwide, with only 51% women in Thailand, and between 50-60% in Japan possessing antibodies.7473 HSV-2 seroprevalence in developing Asian countries is comparable 10-30% to that observed in North America and Northern Europe.87 However, estimates of HSV-2 infectivity in Thailand are higher than observed in other Eastern Asian countries; total HSV-2 seroprevalence is approximately 37% in this country.74 HSV-2 seroprevalence is low in women in the Philippines 9%, although commencing activity while young is associated with an increase risk of acquiring HSV-2 infection; woman starting sexual activity by the time they reach 17 are seven times more likely to be HSV-2 seropositive that those starting sexual activity when over 21.90 In South Korea, incidence of HSV-2 infection in those under the age of 20 is low, only 2.7% in men and 3.0% in women.75 Seroprevalence levels increase in older South Koreans however, such that the population over 20 that has antibodies against HSV-2 is 21.7% of men and 28% of women.75 Southern Asia In India 33.3% of individuals are seropositive for HSV-1 and 16.6% are seropositive for HSV-2. Those with both HSV-1 and HSV-2 antibodies are estimated at 13.3% of the population. Indian men are more likely to be infected with HSV-2 than women, and increasing seroprevalence of this virus is associated with an increasing age.91 Middle East Turkey- High levels of HSV-1 97% and HSV-2 42% were found amongst pregnant women in the city of Erzurum in Eastern Anatolia Region, Turkey.73 In Istanbul however, lower HSV-2 seroprevalence was observed; HSV-2 antibodies were found in 4.8% of sexually active adults, while HSV-1 antibodies were found in 85.3%.92 Only 5% of pregnant women were infected with HSV-2, and 98% were infected with HSV-1. Prevalence of these viruses was higher in sex workers of Istanbul, reaching levels of 99% and 60% for HSV-1 and HSV-2 prevalence respectively.92 Jordan- The prevalence of HSV-2 in Jordan is 52.8% for men and 41.5% for women.93 Israel- HSV-1 seroprevalence is 59.8% in the population of Israel and increases with age in both genders and but the adolescent seroprevalence has been declining as in most industrialized nations. 94An estimated 9.2% of Israeli adults are infected with HSV-2. Infection of either HSV-1 or HSV-2 is higher in females; HSV-2 seroprevalence reaches 20.5% in females in their 40s. These values are similar to levels in HSV infection in Europe.95 Antibodies for HSV-1 or HSV-2 are also more likely to be found individuals born outside of Israel, and individuals residing in Jerusalem and Southern Israel; people of Jewish origin living in Israel are less likely to possess antibodies against herpes.95 Among pregnant women in Israel a small scale cross sectional study found the prevalence of HSV-2 infection was 13.3% and that of HSV-1 was 94.9%. The HSV-2 infection rate was 3-fold higher among immigrants from the former Soviet Union 27.5% than among Israeli-born Jewish and Arab women 9%. 96 Approximately 78% of HSV-2 infections in Israel are asymptomatic.97HSV-1 causes 66.3% of genital herpes in the Tel Aviv area.98 Syria- Genital herpes infection from HSV-2 is predicted to be low in Syria although HSV-1 levels are high. HSV-1 infections is common 95% among healthy Syrians over the age of 30, while HSV-2 prevalence is low in healthy individuals 0.15%, and persons infected with other sexually transmitted diseases 9.5%. High risk groups for acquiring HSV-2 in Syria, include prostitutes and bar girls; they have 34% and 20% seroprevalence respectively.99 Oceania In Australia the seroprevalence of HSV-1 is 76%, with differences associated with age, gender and Indigenous status.100 An estimated 12% of Australian adults are seropositive for HSV-2, with higher prevalence in women 16% than in men 8%.100 Larger cities have higher HSV-2 seroprevalence 13% than rural populations 9%. Higher prevalence is found in Indigenous Australians 18% than non-Indigenous Australians 12% but is lower than HSV-2 prevalence observed in the United States.100 As in the U.S., HSV-1 is increasingly identified as the cause of genital herpes in Australians; HSV-1 was identified in the anogenital area of only 3% of the population in 1980, but had risen to 41% in 2001.101 This was most common in females and persons under 25.101 The number of genital herpes infections appears to be rising in New Zealand with three times more cases in 1993 compared to 1977.102 In this country, HSV-2 affects 60% more women than men of similar age.73 Treatment There is currently no cure that can eradicate herpes virus from the body, but antiviral medications can reduce the frequency, duration, and severity of outbreaks. Antiviral drugs also reduce asymptomatic shedding; it is believed asymptomatic shedding occurs on 10.8% of days in patients not undergoing antiviral treatment, versus 2.9% of days while on antiviral therapy.60 Non-prescription analgesics can reduce pain and fever during initial outbreaks. Topical anesthetic treatments such as prilocaine, lidocaine or tetracaine can also relieve itching and pain.103104 History Herpes antiviral therapy began in the early 1960s with the experimental use of medication that interfered with viral replication called deoxyribonucleic acid inhibitors. The original use was against normally fatal or disabilitating illness such as adult encephalitis,105 keratitis,106 in immunocompromised transplant patients,107 or disseminated herpes zoster.108 The original compounds used were 5-iodo-2'-deoxyuridine, AKA idoxuridine, IUdR, orIDU and 1-β-D-arabinofuranosylcytosine or ara-C,109 later marketed under the name cytosar or cytorabine. The usage expanded to include topical treatment of herpes simplex,110 zoster, and varicella.111 Some trials combined different antivirals with differing results.105 The introduction of 9-β-D-arabinofuranosyladenine, AKA 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 FDA in 1977. Other experimental antivirals of that period included: trifluorothymidine TFT112, Ribivarin,113 interferon,114 Virazole,115 and 5-methoxymethyl-2'-deoxyuridine MMUdR.116 The introduction of 9-2-hydroxyethoxymethylguanine, AKA acyclovir, in the late 1970s117 raised antiviral treatment another notch and led to vidarabine vs. acyclovir trials in the late 1980s.118 The lower toxicity and ease of administration over vidarabine has led to acyclovir becoming the drug of choice for herpes treatment after it was licensed By the FDA in 1998.119 Another advantage in the treatment of neonatal herpes included greater reductions in mortality and morbidity with increased dosages, something that did not occur when compared with increased dosages of vidarabine.119 On the other side of the equation, acyclovir seems to inhibit antibody response and newborns on acyclovir antiviral treatment experienced a slower rise in antibody titer than those on vidarabine.119 Antiviral medication Antiviral medications used against herpes viruses work by interfering with viral replication, effectively slowing the replication rate of the virus and providing a greater opportunity for the immune response to intervene. All drugs in this class depend on the activity of the viral enzyme thymidine kinase to convert the drug sequentially from its prodrug form to monophosphate with one phosphate group, diphosphate with two phosphate groups, and finally to the triphosphate with three phosphate groups form which interferes with viral DNA replication.120 The antiviral medication acyclovir The antiviral medication acyclovir There are several prescription antiviral medications for controlling herpes simplex outbreaks, including aciclovir Zovirax, valaciclovir Valtrex, famciclovir Famvir, and penciclovir. Aciclovir was the original, and prototypical, member of this drug class; it is now available in generic brands at a greatly reduced cost. Valaciclovir and famciclovir-prodrugs of aciclovir and penciclovir, respectively-have improved solubility in water and better bioavailability when taken orally.120 Aciclovir is the recommended antiviral for suppressive therapy for use during the last months of pregnancy to prevent transmission of herpes simplex to the neonate in cases of maternal recurrent herpes.121 The use of valaciclovir and famciclovir, while potentially improving treatment compliance and efficacy, are still undergoing safety evaluation in this context. Several studies with mice provide evidence that treatment with famciclovir soon after initial infection can help lower the incidence of future outbreaks, by reducing the amount of latent virus in the neural ganglia.122123124 A review of human subjects treated with famciclovir during their first herpes episode supports these findings, with only 4.2 percent of famciclovir-treated patients experiencing a recurrence within one to six months after the first outbreak, compared to 19 percent of acyclovir-treated patients.125 Despite these promising results, early famciclovir treatment for herpes has yet to find mainstream adoption. However, the potential effect on latency drops to zero a few months post-infection.126 Antiviral medications are also available as topical creams for treating recurrent outbreaks on the lips, although their effectiveness is disputed.127 Penciclovir cream has a 7-17 hour longer cellular half-life than aciclovir cream, increasing its effectiveness relative to aciclovir when topically applied.128 Topical treatments Docosanol is available as a cream for direct application to the affected area of skin. It prevents HSV from fusing to cell membranes, thus barring the entry of the virus into the skin. Docosanol was approved for use after clinical trials by the FDA in July 2000.129 Docosanol is marketed by Avanir Pharmaceuticals under the name Abreva. It was the first over-the-counter antiviral drug approved for sale in the United States and Canada. Avanir Pharmaceuticals and GlaxoSmithKiline Consumer Healthcare were the subject of a U.S. nationwide class-action suit in March, 2007 due to the misleading claim that it cut recovery times in half.130 Tromantadine is available as a gel that inhibits the entry and spread of the virus by altering the surface composition of skin cells and inhibiting release of viral genetic material. Zilactin is a topical analgesic barrier treatment, which forms a shield at the area of application to prevent a sore from increasing in size, and decrease viral spreading during the healing process. There is some limited research that has shown that tea tree oil may have topical anti-viral activity, especially with the Herpes virus131 Other drugs Cimetidine, a common component of heartburn medication, has been shown to lessen the severity of herpes zoster outbreaks in several different instances.132133134 This is an off-label use of the drug. It and probenecid have been shown to reduce the renal clearance of aciclovir.135 These compounds also reduce the rate, but not the extent, at which valaciclovir is converted into aciclovir. Limited evidence suggests that low dose aspirin 125 mg daily might be beneficial in patients with recurrent HSV infections. Aspirin acetylsalicylic acid is an non-steroidal anti-inflammatory drug which reduces the level of prostaglandins-naturally occurring lipid compounds-that are essential in creating inflammation.136 A recent study in animals showed inhibition of thermal heat stress induced viral shedding of HSV-1 in the eye by aspirin, and a possible benefit in reducing the frequency of recurrences.137 Another treatment is the use of petroleum jelly. Healing of cold sores is sped by barring water or saliva from reaching the sore. Vaccines The National Institutes of Health NIH in the United States is currently conducting phase III trials of Herpevac, a vaccine against HSV-2.138 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-2.138 Assuming FDA approval, a commercial version of the vaccine is estimated to become available in 2008.citation needed During initial trials, the vaccine did not exhibit any evidence of preventing HSV-2 in males.138 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.138 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.138 Researchers at the University of Florida have made a hammerhead ribozyme that targets and cleaves the mRNA of essential genes in HSV-1. The hammerhead which targets the mRNA of the UL20 gene greatly reduced the level of HSV-1 ocular infection in rabbits and reduced the viral yield in vivo.139 Natural compounds Many people seek benefits in natural products and dietary supplements for treatment of herpes Certain dietary adjustments, dietary supplements, and alternative remedies are believed to be beneficial in the treatment of herpes, either alone, or in conjunction with prescribed antiviral therapy. There is currently insufficient scientific and clinical evidence to support the effective use of many of these compounds to treat herpes in humans.140 Lysine supplementation has been used for the prophylaxis and treatment of herpes simplex although doses smaller than 1 gram per day appear to be ineffective.141142143 Aloe vera, available as a cream or gel, makes an affected area heal faster and may prevent recurrences.144 Lemon balm Melissa officinalis has antiviral activity against HSV-2 in cell culture and may reduce HSV symptoms in herpes infected people.145146146 Carrageenans-linear sulphated polysaccharides extracted from red seaweeds-have been shown to have antiviral effects in HSV-infected cells and in mice.147 148 There is conflicting evidence on a possible benefit from extracts from the plant echinacea in treating oral149, but not genital, herpes.150 Resveratrol, a compound naturally produced by plants and a component of red wine, prevents HSV replication in cultured cells and reduces cutaneous HSV lesion formation in mice. It is not considered potent enough to be an effective treatment on its own.151152 Extracts from garlic have shown antiviral activity against HSV in cell culture experiments, although the extremely high concentrations of the extracts required to produce an antiviral effect was also toxic to the cells.153 The plant Prunella vulgaris, commonly known as selfheal, also prevents expression of both type 1 and type 2 herpes in cultured cells.154 Lactoferrin, a component of whey protein, has been shown to have a synergistic effect with aciclovir against HSV in vitro.155 Some dietary supplements have been suggested to positively treat herpes. These include vitamin C, vitamin A, vitamin E, and zinc.156157 Butylated hydroxytoluene BHT, commonly available as a food preservative, has been shown in cell culture and animal studies to inactivate herpes virus.158159 However, BHT has not been clinically tested and approved to treat herpes infections in humans. Psychological and social effects Some people experience negative feelings related to the condition following diagnosis, particularly if they have acquired the genital form of the disease. Feelings can include depression, fear of rejection, feelings of isolation, fear of being found out, self-destructive feelings, and fear of masturbation.160 These feelings usually lessen over time. Herpes support groups have been formed in the United States and the UK, providing information about herpes and running message forums and dating websites for sufferers.161162163164165166 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.167 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, but 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. References ^ a b c d e f g h i j k l Gupta R, Warren T, Wald A 2007. Genital herpes. Lancet 370 9605: 2127-37. doi:10.1016/S0140-67360761908-4. PMID 18156035. ^ Brown Za, Selke S., Zeh J, Kopelman J, Maslow A, Asley RL, Watts DH, Berry S, Herd M, Corey L 1997 Aug 21. The acquisition of herpes simplex virus during pregnancy. N Engl J Med 3378: 509-15. ^ a b c d e 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. ^ Dowdle Wr, Nahmias AJ, Harwell RW, Pauls FP. 1967. Association of antigenic type of Herpesvirus hominis with site of viral recovery. J Immunol 995: 974-80. ^ Nahmias Aj, Dowdle W.R. 1968. Antigenic and biologic differences in herpesvirus hominis.. Prog Med Virol 10: 110-59. ^ Ribes Ja, Steele AD, Seabolt JP, Baker DJ 2001 Sep. Six-year study of the incidence of herpes in genital and nongenital cultures in a central Kentucky medical center patient population. J Clin Microbiol 399: 3321-5. ^ a b Mertz Gj, Rosenthal SL, Stanberry LR 2003 Oct. Is Herpes Simplex Virus Type 1 HSV-1 Now More Common than HSV-2 in First Episodes of Genital Herpes?. Sex Trans Dis 3010: 801-802. ^ Coyle Pv, O'neill HJ, Wyatt DE, McCaughey C, Quah S, McBride MO 2003 May. Emergence of herpes simplex type 1 as the main cause of recurrent genital ulcerative disease in women in Northern Ireland. J Clin Virol 271: 22-9. ^ a b STD Facts - Genital Herpes. Retrieved on 2008-02-22. ^ Lafferty We, Coombs RW, Benedetti J, Critchlow C, Corey L 1987 Jun 4. Recurrences after oral and genital herpes simplex virus infection. Influence of site of infection and viral type. N Engl J Med 31623: 1444-9. ^ a b Clark DC 2003. Common acute hand infections. Am Fam Physician 68 11: 2167-76. PMID 14677662. ^ Lewis MA 2004. Herpes simplex virus: an occupational hazard in dentistry. Int Dent J 54 2: 103-11. PMID 15119801. ^ Avitzur Y, Amir J 2002. Herpetic whitlow infection in a general pediatrician--an occupational hazard. Infection 30 4: 234-6. PMID 12236568. ^ Wu IB, Schwartz RA 2007. Herpetic whitlow. Cutis 79 3: 193-6. PMID 17674583. ^ Anonymous 1971. Herpetic whitlow: a medical risk. Br Med J 4 5785: 444. PMID 5125276. ^ Belongia EA, Goodman JL, Holland EJ, et al September 1991. An outbreak of herpes gladiatorum at a high-school wrestling camp. N. Engl. J. Med. 325 13: 906-10. PMID 1652687. ^ a b c d e f g h i j 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. ^ 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. ^ a b c d Suresh PS, Tullo AB 1999. Herpes simplex keratitis. Indian J Ophthalmol 47 3: 155-65. PMID 10858770. ^ a b c d e Whitley RJ 2006. Herpes simplex encephalitis: adolescents and adults. Antiviral Res. 71 2-3: 141-8. doi:10.1016/j.antiviral.2006.04.002. PMID 16675036. ^ a b Whitley RJ, Gnann JW 2002. Viral encephalitis: familiar infections and emerging pathogens. Lancet 359 9305: 507-13. PMID 11853816. ^ Dinn J 1980. Transolfactory spread of virus in herpes simplex encephalitis.. Br Med J 281 6252: 1392. PMID 7437807. ^ a b Kropp RY., Wong T, et al 2006. Neonatal Herpes Simplex Virus Infections in Canada: Results of a 3-Year National Prospective Study. Pediatrics 117 61: 1955-1962. PMID 16740836. ^ 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 inactive 2008-06-25. PMID 16199646. ^ a b c d Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L 2003. Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. JAMA 289 2: 203-9. PMID 12517231. ^ a b Brown ZA, Benedetti J, Ashley R, Burchett S, Selke S, Berry S, Vontver LA, Corey L 1991. Neonatal herpes simplex virus infection in relation to asymptomatic maternal infection at the time of labor. N Engl J Med 325 13: 965-6. PMID 1849612. ^ Brown ZA, Gardella C, Malm G, Prober CG, Forsgren M, Krantz EM, Arvin AM, Yasukawa LL, Mohan K, Brown Z, Corey L, Wald A 2007. Effect of maternal herpes simplex virus HSV serostatus and HSV type on risk of neonatal herpes. Acta Obstet et Gynecol Scand 86 5: 523-529. PMID 17564578. ^ a b Kimberlin DW, Whitley RJ 2005. Neonatal herpes: what have we learned. Semin Pediatr Infect Dis 16 1: 7-16. doi:10.1053/j.spid.2004.09.006. PMID 15685144. ^ Prober CG. Herpes simplex virus, 1138. ^ Kesson AM 2001. Management of neonatal herpes simplex virus infection. Paediatr Drugs 3 2: 81-90. PMID 11269641. ^ cite web |url=http://www.merck.com/mmpe/sec19/ch279/ch279h.html |title=The Merck Manual, Neonatal Herpes Simplex Virus HSV Infection ^ Brocklehurst P, Kinghorn GA et al. 1998. randomised placebo controlled trial of suppressive acyclovir in late pregnancy in women with recurrent genital herpes infection. Br J Obstet Gynaecol 105 3: 275-80. ^ Jacobs RF 1998. Neonatal herpes simplex virus infections. Semin. Perinatol. 22 1: 64-71. PMID 9523400. ^ Ch. 6, Medical Disorders during Pregnancy, in Harrison's Principles of Internal Medicine, 16th ed., 2005 ^ Tyler KL 2004. Herpes simplex virus infections of the central nervous system: encephalitis and meningitis, including Mollaret's. Herpes 11 Suppl 2: 57A-64A. PMID 15319091. ^ Recurring viral meningitis herpes II. Med Help International. Retrieved on 2006-11-21. ^ Sendi P, Graber P 2006. Mollaret's meningitis. CMAJ 174 12: 1710. doi:10.1503/cmaj.051688. PMID 16754896. ^ Takasu T, Furuta Y, Sato KC, Fukuda S, Inuyama Y, Nagashima K 1992. Detection of latent herpes simplex virus DNA and RNA in human geniculate ganglia by the polymerase chain reaction. Acta Otolaryngol. 112 6: 1004-11. PMID 1336296. ^ Sugita T, Murakami S, Yanagihara N, Fujiwara Y, Hirata Y, Kurata T 1995. Facial nerve paralysis induced by herpes simplex virus in mice: an animal model of acute and transient facial paralysis. Ann. Otol. Rhinol. Laryngol. 104 7: 574-81. PMID 7598372. ^ Lazarini PR, Vianna MF, Alcantara MP, Scalia RA, Caiaffa Filho HH 2006. Herpes simplex virus in the saliva of peripheral Bell's palsy patients in Portuguese. Rev Bras Otorrinolaringol Engl Ed 72 1: 7-11. PMID 16917546. ^ Linder T, Bossart W, Bodmer D 2005. Bell's palsy and Herpes simplex virus: fact or mystery?. Otol. Neurotol. 26 1: 109-13. PMID 15699730. ^ Kanerva M, Mannonen L, Piiparinen H, Peltomaa M, Vaheri A, Pitkäranta A 2007. Search for Herpesviruses in cerebrospinal fluid of facial palsy patients by PCR. Acta Otolaryngol. 127 7: 775-9. doi:10.1080/00016480601011444. PMID 17573575. ^ Stjernquist-Desatnik A, Skoog E, Aurelius E 2006. Detection of herpes simplex and varicella-zoster viruses in patients with Bell's palsy by the polymerase chain reaction technique. Ann. Otol. Rhinol. Laryngol. 115 4: 306-11. PMID 16676828. ^ Tiemstra JD, Khatkhate N 2007. Bell's palsy: diagnosis and management. Am Fam Physician 76 7: 997-1002. PMID 17956069. ^ Middleton PJ, Peteric M, Kozak M, Rewcastle NB, McLachlan DR. 1980. Herpes simplex viral genome and senile and presenile dementias of Alzheimer and Pick.. Lancet 315: 1038. doi:10.1016/S0140-67368091490-7. ^ Dobson, C.B.; Itzhaki, R.F. 1999. Herpes simplex virus type 1 and Alzheimer's disease.. Neurobiol Aging 20 4: 457-65. doi:10.1016/S0197-45809900055-X. Retrieved on 2008-03-15. ^ Pyles, R.B. 2001. The association of herpes simplex virus and Alzheimer's disease: a potential synthesis of genetic and environmental factors. Herpes 8 3: 64-68. Retrieved on 2008-03-15. ^ Itzhaki, R.F.; Lin, W.R.; Shang, D.; Wilcock, G.K.; Faragher, B.; Jamieson, G.A. 1997. Herpes simplex virus type 1 in brain and risk of Alzheimer's disease.. Lancet 349 9047: 241-4. doi:10.1016/S0140-67369610149-5. Retrieved on 2008-03-15. ^ Stumpf MP, Laidlaw Z, Jansen VA 2002. Herpes viruses hedge their bets. Proc. Natl. Acad. Sci. U.S.A. 99 23: 15234-7. doi:10.1073/pnas.232546899. PMID 12409612. ^ Sainz B, Loutsch JM, Marquart ME, Hill JM 2001. Stress-associated immunomodulation and herpes simplex virus infections. Med. Hypotheses 56 3: 348-56. doi:10.1054/mehy.2000.1219. PMID 11359358. ^ Myśliwska J, Trzonkowski P, Bryl E, Lukaszuk K, Myśliwski A 2000. Lower interleukin-2 and higher serum tumor necrosis factor-a levels are associated with perimenstrual, recurrent, facial Herpes simplex infection in young women. Eur. Cytokine Netw. 11 3: 397-406. PMID 11022124. ^ Segal AL, Katcher AH, Brightman VJ, Miller MF 1974. Recurrent herpes labialis, recurrent aphthous ulcers, and the menstrual cycle. J. Dent. Res. 53 4: 797-803. PMID 4526372. ^ Chambers A, Perry M 2008. Salivary mediated autoinoculation of herpes simplex virus on the face in the absence of cold sores, after trauma. J. Oral Maxillofac. Surg. 66 1: 136-8. doi:10.1016/j.joms.2006.07.019. PMID 18083428. ^ Perna JJ, Mannix ML, Rooney JF, Notkins AL, Straus SE 1987. Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model. J. Am. Acad. Dermatol. 17 3: 473-8. PMID 2821086. ^ Rooney JF, Straus SE, Mannix ML, et al 1992. UV light-induced reactivation of herpes simplex virus type 2 and prevention by acyclovir. J. Infect. Dis. 166 3: 500-6. PMID 1323616. ^ Oakley C, Epstein JB, Sherlock CH 1997. Reactivation of oral herpes simplex virus: implications for clinical management of herpes simplex virus recurrence during radiotherapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 84 3: 272-8. PMID 9377190. ^ Ichihashi M, Nagai H, Matsunaga K 2004. Sunlight is an important causative factor of recurrent herpes simplex. Cutis 74 5 Suppl: 14-8. PMID 15603217. ^ Martinez V, Caumes E, Chosidow O 2008. Treatment to prevent recurrent genital herpes. Curr Opin Infect Dis 21 1: 42-48. doi:10.1097/QCO.0b013e3282f3d9d3 inactive 2008-06-25. PMID 18192785. ^ AHMF: Preventing Sexual Transmission of Genital herpes. Retrieved on 2008-02-24. ^ a b c d 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. ^ Kim H, Meier A, Huang M, Kuntz S, Selke S, Celum C, Corey L, Wald A 2006. Oral herpes simplex virus type 2 reactivation in HIV-positive and -negative men.. J Infect Dis 194 4: 420-7. doi:10.1086/505879. PMID 16845624. ^ a b Mertz, G.J. 1993. Epidemiology of genital herpes infections.. Infect Dis Clin North Am 7 4: 825-39. PMID 8106731. ^ a b c Wald A, Langenberg AG, Link K, Izu AE, Ashley R, Warren T, Tyring S, Douglas JM Jr, Corey L. 2001. Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women. JAMA 285 24: 3100-3106. doi:10.1001/jama.285.24.3100. PMID 11427138. ^ a b Casper C, Wald A. 2002. Condom use and the prevention of genital herpes acquisition,. Herpes 9 1: 10-14. PMID 11916494. ^ de Visser RO, Smith AM, Rissel CE, Richters J, Grulich AE. 2003. Sex in Australia: safer sex and condom use among a representative sample of adults. Aust. N. Z. J. Public Health. 27 2: 223-229. doi:10.1111/j.1467-842X.2003.tb00812.x. PMID 14696715. ^ Seppa, Nathan 2005-01-05. One-Two Punch: Vaccine fights herpes with antibodies, T cells in English, Science News, pp. 5. Retrieved on 2007-03-29. ^ Carla K. Johnson August 23, 2006. Percentage of people with herpes drops, Associated Press. ^ a b Kulhanjian Ja, Soroush V., Au DS 1992. Identification of women at unsuspected risk of primary infection with herpes simplex virus type 2 during pregnancy. N Engl J Med 32614: 916-20. ^ Wald A, Langenberg A.G., Krantz E, Douglas JM jr, Handsfield HH, DiCarlo RP, Adimora AA, Izu AE, Morrow RA, Corey L 2005. The relationship between condomn use and herpes simplex virus acquisition. Ann Intern Med 14310: 707-13. ^ Whitley RJ, Kimberlin DW, Roizman B 1998. Herpes simplex viruses. Clin Infect Dis 26 3: 541-53. PMID 9524821. ^ Koelle DM, Corey L 2008. Herpes Simplex: Insights on Pathogenesis and Possible Vaccines. Annu Rev Med 59: 381-395. doi:10.1146/annurev.med.59.061606.095540. PMID 18186706. ^ Handsfield HH 2000. Public Health Strategies to Prevent Genital Herpes: Where Do We Stand?. Curr Infect Dis Rep 2 1: 25-30. PMID 11095834. ^ a b c d e f g h i j k l m Smith JS, Robinson NJ 2002. Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review. J. Infect. Dis. 186 Suppl 1: S3-28. PMID 12353183. ^ a b c d e f g h i j Patnaik P, Herrero R, Morrow RA, et al 2007. Type-specific seroprevalence of herpes simplex virus type 2 and associated risk factors in middle-aged women from 6 countries: the IARC multicentric study. Sex Transm Dis 34 12: 1019-24. PMID 18080353. ^ a b c Shin HS, Park JJ, Chu C, et al 2007. Herpes simplex virus type 2 seroprevalence in Korea: rapid increase of HSV-2 seroprevalence in the 30s in the southern part. J. Korean Med. Sci. 22 6: 957-62. PMID 18162706. ^ a b c d e Pebody RG, Andrews N, Brown D, et al 2004. The seroepidemiology of herpes simplex virus type 1 and 2 in Europe. Sex Transm Infect 80 3: 185-91. PMID 15170000. ^ Roberts CM, Pfister JR, Spear SJ 2003. Increasing proportion of herpes simplex virus type 1 as a cause of genital herpes infection in college students. Sex Transm Dis 30 10: 797-800. PMID 14520181. ^ Malkin JE 2004. Epidemiology of genital herpes simplex virus infection in developed countries. Herpes 11 Suppl 1: 2A-23A. PMID 15115626. ^ Herpes simplex HTML in English. University of Maryland Medical Center. Retrieved on 2007-09-03. ^ LEARN ABOUT HERPES Fast Facts HTML in English. ASHA Herpes Resource Center. Retrieved on 2007-09-03. ^ STD Facts - Genital Herpes HTML in English. Centers for Disease Control and Prevention. Retrieved on 2007-09-03. ^ Herpes HTML in English. Stanford University Sexual Health Peer Resource Center. Retrieved on 2007-09-03. ^ a b Howard M, Sellors J.W., Jang D, Robinson NJ, Fearon M, Kaczorowski J, Chernesky M 2003. Regional Distribution of Antibodies to Herpes Simplex Virus Type 1 HSV-1 and HSV-2 in Men and Women in Ontario, Canada. J Clin Microbiol 411: 84-89. PMID 12517830. ^ Patrick DM, Dawar M, Cook DA, Krajden M, Ng HC, Rekart ML July 2001. Antenatal seroprevalence of herpes simplex virus type 2 HSV-2 in Canadian women: HSV-2 prevalence increases throughout the reproductive years. Sex Transm Dis 28 7: 424-8. PMID 11460028. ^ Singh AE, Romanowski B, Wong T, et al February 2005. Herpes simplex virus seroprevalence and risk factors in 2 Canadian sexually transmitted disease clinics. Sex Transm Dis 32 2: 95-100. PMID 15668615. ^ Forward KR, Lee SH March 2003. Predominance of herpes simplex virus type 1 from patients with genital herpes in Nova Scotia. Can J Infect Dis 14 2: 94-6. PMID 18159431. PMC:2094909. ^ a b c Weiss H 2004. Epidemiology of herpes simplex virus type 2 infection in the developing world. Herpes 11 Suppl 1: 24A-35A. PMID 15115627. ^ Loutfy SA, Alam El-Din HM, Ibrahim MF, Hafez MM 2006. Seroprevalence of herpes simplex virus types 1 and 2, Epstein-Barr virus, and cytomegalovirus in children with acute lymphoblastic leukemia in Egypt. Saudi Med J 27 8: 1139-45. PMID 16883441. ^ Meguenni S, Djenaoui T, Bendib A, et al 1989. Herpes simplex virus infections in Algiers in French. Arch Inst Pasteur Alger 57: 61-72. PMID 2562258. ^ Smith JS, Herrero R, Muñoz N, et al 2001. Prevalence and risk factors for herpes simplex virus type 2 infection among middle-age women in Brazil and the Philippines. Sex Transm Dis 28 4: 187-94. PMID 11318248. ^ Kaur R, Gupta N, Baveja UK 2005. Seroprevalence of HSV1 and HSV2 infections in family planning clinic attenders. J Commun Dis 37 4: 307-9. PMID 17278662. ^ a b Dolar N, Serdaroglu S, Yilmaz G, Ergin S 2006. Seroprevalence of herpes simplex virus type 1 and type 2 in Turkey. J Eur Acad Dermatol Venereol 20 10: 1232-6. doi:10.1111/j.1468-3083.2006.01766.x. PMID 17062037. ^ Abuharfeil N, Meqdam MM 2000. Seroepidemiologic study of herpes simplex virus type 2 and cytomegalovirus among young adults in northern Jordan. New Microbiol. 23 3: 235-9. PMID 10939038. ^ Davidovici Bb, Grotto I., Balicer RD, Robinson NJ, Cohen D 2006-Nov. Decline in the prevalence of antibodies to herpes simplex virus types 1 and 2 among Israeli young adults between 1984 and 2002. Sex Transm Dis 3311: 641-5.. ^ a b Davidovici BB, Green M, Marouni MJ, Bassal R, Pimenta JM, Cohen D 2006. Seroprevalence of herpes simplex virus 1 and 2 and correlates of infection in Israel. J. Infect. 52 5: 367-73. doi:10.1016/j.jinf.2005.08.005. PMID 16213591. ^ Dan M, Sadan O., Glezerman M, Raveh D, Samra Z 2003. Prevalence and risk factors for herpes simplex virus type 2 infection among pregnant women in Israel. Sex Transm Dis 3011: 835-8. PMID 14603091. ^ Feldman Pa, Steinberg J., Madeb R, Bar G, Nativ O, Tal J, Srugo I 2003. Herpes simplex virus type 2 seropositivity in a sexually transmitted disease clinic in Israel. Isr Med Assoc J 59: 626-8. ^ Samra Z, Scherf E, Dan M 2003. Herpes simplex virus type 1 is the prevailing cause of genital herpes in the Tel Aviv area, Israel. Sex Transm Dis 30 10: 794-6. PMID 14520180. ^ Ibrahim AI, Kouwatli KM, Obeid MT 2000. Frequency of herpes simplex virus in Syria based on type-specific serological assay. Saudi Med J 21 4: 355-60. PMID 11533818. ^ a b c Cunningham AL, Taylor R, Taylor J, Marks C, Shaw J, Mindel A 2006. Prevalence of infection with herpes simplex virus types 1 and 2 in Australia: a nationwide population based survey. Sex Transm Infect 82 2: 164-8. doi:10.1136/sti.2005.016899. PMID 16581748. ^ a b Haddow LJ, Dave B, Mindel A, et al 2006. Increase in rates of herpes simplex virus type 1 as a cause of anogenital herpes in western Sydney, Australia, between 1979 and 2003. Sex Transm Infect 82 3: 255-9. doi:10.1136/sti.2005.018176. PMID 16731681. ^ Lyttle PH 1994. Surveillance report: disease trends at New Zealand sexually transmitted disease clinics 1977-1993. Genitourin Med 70 5: 329-35. PMID 8001945. ^ Local anesthetic creams 1988. BMJ 297 6661: 1468. PMID 3147021. ^ Kaminester LH, Pariser RJ, Pariser DM, et al 1999. A double-blind, placebo-controlled study of topical tetracaine in the treatment of herpes labialis. J. Am. Acad. Dermatol. 41 6: 996-1001. PMID 10570387. ^ a b Chow AW, Roland A, Fiala M, et al March 1973. Cytosine arabinoside therapy for herpes simplex encephalitis--clinical experience with six patients. Antimicrob. Agents Chemother. 3 3: 412-7. PMID 4790599. PMC:444424. ^ Kaufman HE, Howard GM August 1962. Therapy of experimental herpes simplex keratitis. Invest Ophthalmol 1: 561-4. PMID 14454441. ^ Ch'ien LT, Whitley RJ, Alford CA, Galasso GJ June 1976. Adenine arabinoside for therapy of herpes zoster in immunosuppressed patients: preliminary results of a collaborative study. J. Infect. Dis. 133 Suppl: A184-91. PMID 180198. ^ McKelvey EM, Kwaan HC November 1969. Cytosine arabinoside therapy for disseminated herpes zoster in a patient with IgG pyroglobulinemia. Blood 34 5: 706-11. PMID 5352659. ^ Fiala M, Chow A, Guze LB April 1972. Susceptibility of herpesviruses to cytosine arabinoside: standardization of susceptibility test procedure and relative resistance of herpes simplex type 2 strains. Antimicrob. Agents Chemother. 1 4: 354-7. PMID 4364937. PMC:444221. ^ Allen LB, Hintz OJ, Wolf SM, et al June 1976. Effect of 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate on genital lesions and encephalitis induced by Herpesvirus hominis type 2 in female mice. J. Infect. Dis. 133 Suppl: A178-83. PMID 6598. ^ Juel-Jensen BE March 1970. Varicella and cytosine arabinoside. Lancet 1 7646: 572. PMID 4190397. ^ Allen LB, Sidwell RW September 1972. Target-organ treatment of neurotropic virus diseases: efficacy as a chemotherapy tool and comparison of activity of adenine arabinoside, cytosine arabinoside, idoxuridine, and trifluorothymidine. Antimicrob. Agents Chemother. 2 3: 229-33. PMID 4790562. PMC:444296. ^ Allen LB, Wolf SM, Hintz CJ, Huffman JH, Sidwell RW March 1977. Effect of ribavirin on Type 2 Herpesvirus hominis HVH/2 in vitro and in vivo. Ann. N. Y. Acad. Sci. 284: 247-53. PMID 212976. ^ Allen LB, Cochran KW November 1972. Target-organ treatment of neurotropic virus disease with interferon inducers. Infect. Immun. 6 5: 819-23. PMID 4404669. PMC:422616. ^ Sidwell RW, Huffman JH, Khare GP, Allen LB, Witkowski JT, Robins RK August 1972. Broad-spectrum antiviral activity of Virazole: 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide. Science journal 177 50: 705-6. PMID 4340949. ^ Babiuk LA, Meldrum B, Gupta VS, Rouse BT December 1975. Comparison of the antiviral effects of 5-methoxymethyl-deoxyuridine with 5-iododeoxyuridine, cytosine arabinoside, and adenine arabinoside. Antimicrob. Agents Chemother. 8 6: 643-50. PMID 1239978. PMC:429441. ^ O'Meara A, Deasy PF, Hillary IB, Bridgen WD December 1979. Acyclovir for treatment of mucocutaneous herpes infection in a child with leukaemia. Lancet 2 8153: 1196. PMID 91931. ^ Whitley R, Arvin A, Prober C, et al February 1991. A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group. N. Engl. J. Med. 324 7: 444-9. PMID 1988829. ^ a b c Kimberlin DW, Lin CY, Jacobs RF, et al August 2001. Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections. Pediatrics 108 2: 230-8. PMID 11483782. ^ a b De Clercq E, Field HJ 2006. Antiviral prodrugs - the development of successful prodrug strategies for antiviral chemotherapy. Br. J. Pharmacol. 147 1: 1-11. doi:10.1038/sj.bjp.0706446. PMID 16284630. ^ Leung DT, Sacks SL. 2003. Current treatment options to prevent perinatal transmission of herpes simplex virus. Expert Opin. Pharmacother. 4 10: 1809-1819. doi:10.1517/14656566.4.10.1809. PMID 14521490. ^ The effects of antiviral therapy on the distribution of herpes simplex virus type 1 to ganglionic neurons and its consequences during, immediately following and several months after treatment1 ^ Famciclovir and Valaciclovir Differ in the Prevention of Herpes Simplex Virus Type 1 Latency in Mice: a Quantitative Study2 ^ Persistence of Infectious Herpes Simplex Virus Type 2 in the Nervous System in Mice after Antiviral Chemotherapy3 ^ Observation May Indicate A Possible Clinical Effect On Latency4 ^ Thackray AM, Field HJ. 1996. Differential effects of famciclovir and valaciclovir on the pathogenesis of herpes simplex virus in a murine infection model including reactivation from latency. J. Infect. Dis. 173 2: 291-299. PMID 8568288. ^ Worrall G 1996. Evidence for efficacy of topical acyclovir in recurrent herpes labialis is weak. BMJ 313 7048: 46. PMID 8664786. ^ Spruance SL, Rea TL, Thoming C, Tucker R, Saltzman R, Boon R 1997. Penciclovir cream for the treatment of herpes simplex labialis. A randomized, multicenter, double-blind, placebo-controlled trial. Topical Penciclovir Collaborative Study Group. JAMA 277 17: 1374-9. PMID 9134943. ^ Drug Name: ABREVA docosanol - approval. centerwatch.com July 2000. Retrieved on 2007-10-17. ^ California Court Upholds Settlement Of Class Action Over Cold Sore Medicationl. BNA Inc. July 2000. Retrieved on 2007-10-17. ^ Bishop, C.D. 1995. Anti-viral Activity of the Essential Oil of Melaleuca alternifolia. Journal of Essential Oil Research: 641-644. ^ Kapinska-Mrowiecka M, Toruwski G 1996. Efficacy of cimetidine in treatment of herpes zoster in the first 5 days from the moment of disease manifestation.. Pol Tyg Lek. 51 23-26: 338-339. PMID 9273526. ^ Hayne ST, Mercer JB 1983. Herpes zoster:treatment with cemetidine.. Can Med Assoc J 129 12: 1284-1285. PMID 6652595. ^ Komlos L, Notmann J, Arieli J, et.al. 1994. In vitro cell-mediated immune reactions in herpes zoster patients treated with cimetidine.. Asian Pac J Allelrgy Immunol 12 1: 51-58. PMID 7872992. ^ De Bony F, Tod M, Bidault R, On NT, Posner J, Rolan P. 2002. Multiple interactions of cimetidine and probenecid with valaciclovir and its metabolite acyclovir. Antimicrob. Agents Chemother. 46 2: 458-463. doi:10.1128/AAC.46.2.458-463.2002. PMID 11796358. ^ Karadi I, Karpati S, Romics L. 1998. Aspirin in the management of recurrent herpes simplex virus infection. Ann. Intern. Med. 128 8: 696-697. PMID 9537952. ^ Gebhardt BM, Varnell ED, Kaufman HE. 2004. Acetylsalicylic acid reduces viral shedding induced by thermal stress. Curr. Eye Res. 29 2-3: 119-125. doi:10.1080/02713680490504588. PMID 15512958. ^ a b c d e Herpevac Trial for Women. Retrieved on 2008-02-25. ^ Molecular Therapy - Abstract of article: 801. RNA Gene Therapy Targeting Herpes Simplex Virus. ^ Perfect MM, Bourne N, Ebel C, Rosenthal SL 2005. Use of complementary and alternative medicine for the treatment of genital herpes. Herpes 12 2: 38-41. PMID 16209859. ^ McCune MA, Perry HO, Muller SA, O'Fallon WM. 2005. Treatment of recurrent herpes simplex infections with L-lysine monohydrochloride. Cutis. 34 4: 366-373. PMID 6435961. ^ Griffith RS, Walsh DE, Myrmel KH, Thompson RW, Behforooz A. 1987. Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica. 175 4: 183-190. PMID 3115841. ^ Griffith RS, Norins AL, Kagan C. 1978. A multicentered study of lysine therapy in Herpes simplex infection. Dermatologica. 156 5: 257-267. PMID 640102. ^ Vogler BK and Ernst E.. Aloe vera: a systematic review of its clinical effectiveness.. British Journal of General Practice 49: 823-828. ^ Allahverdiyev A, Duran N, Ozguven M, Koltas S. 2004. Antiviral activity of the volatile oils of Melissa officinalis L. against Herpes simplex virus type-2.. Phytomedicine. 11 7-8: 657-661. doi:10.1016/j.phymed.2003.07.014. PMID 15636181. ^ a b Koytchev R, Alken RG, Dundarov S 1999. Balm mint extract Lo-701 for topical treatment of recurring herpes labialis. Phytomedicine 6 4: 225-30. PMID 10589440. ^ Zacharopoulos VR, Phillips DM. 1997. Vaginal formulations of carrageenan protect mice from herpes simplex virus infection. Clin. Diagn. Lab. Immunol. 4 4: 465-468. PMID 9220165. ^ Carlucci MJ, Scolaro LA, Damonte EB. 1999. Inhibitory action of natural carrageenans on Herpes simplex virus infection of mouse astrocytes. Chemotherapy 45 6: 429-436. doi:10.1159/000007236. PMID 10567773. ^ Binns SE, Hudson J, Merali S, Arnason JT 2002. Antiviral activity of characterized extracts from echinacea spp. Heliantheae: Asteraceae against herpes simplex virus HSV-I. Planta Med. 68 9: 780-3. doi:10.1055/s-2002-34397. PMID 12357386. ^ Vonau B, Chard S, Mandalia S, Wilkinson D, Barton SE 2001. Does the extract of the plant Echinacea purpurea influence the clinical course of recurrent genital herpes?. Int J STD AIDS 12 3: 154-8. PMID 11231867. ^ Docherty JJ, Fu MM, Stiffler BS, Limperos RJ, Pokabla CM, DeLucia AL. 1999. Resveratrol inhibition of herpes simplex virus replication. Antiviral Res. 43 3: 145-155. doi:10.1016/S0166-35429900042-X. PMID 10551373. ^ Docherty JJ, Smith JS, Fu MM, Stoner T, Booth T. 2004. Effect of topically applied resveratrol on cutaneous herpes simplex virus infections in hairless mice. Antiviral Res. 61 1: 19-26. doi:10.1016/j.antiviral.2003.07.001. PMID 14670590. ^ Weber ND, Andersen DO, North JA, Murray BK, Lawson LD, Hughes BG 1992. In vitro virucidal effects of Allium sativum garlic extract and compounds. Planta Med. 58 5: 417-23. PMID 1470664. ^ Chiu LC, Zhub W, Oo VE 2004. A polysaccharide fraction from medicinal herb Prunella vulgaris downregulates the expression of herpes simplex virus antigen in Vero cells. Journal of Ethnopharmacology 93 1: 63-68. doi:10.1016/j.jep.2004.03.024. ^ Andersen JH, Jenssen H, Gutteberg TJ. 2003. Lactoferrin and lactoferricin inhibit Herpes simplex 1 and 2 infection and exhibit synergy when combined with acyclovir. Antiviral Res. 58 3: 209-215. doi:10.1016/S0166-35420200214-0. PMID 12767468. ^ Gaby AR 2006. Natural remedies for Herpes simplex. Altern Med Rev 11 2: 93-101. PMID 16813459. ^ Yazici AC, Baz K, Ikizoglu G 2006. Recurrent herpes labialis during isotretinoin therapy: is there a role for photosensitivity?. J Eur Acad Dermatol Venereol 20 1: 93-5. doi:10.1111/j.1468-3083.2005.01358.x. PMID 16405618. ^ Snipes W, Person S, Keith A, Cupp J. 1985. Butylated hydroxytoluene inactivates lipid-containing viruses Science. 1975;1884183:64-6 ^ Richards JT, Katz ME, Kern ER. Topical butylated hydroxytoluene treatment of genital herpes simplex virus infections of guinea pigs. Antiviral Res 5 issue=5; pages=281-90. ^ Vezina C, Steben M. 2001. Genital Herpes: Psychosexual Impacts and Counselling. The Canadian Journal of CME June: 125-134. ^ A to Z Herpes Support Groups. ^ Herpes Support Groups. ^ Herpes Viruses Association. ^ Herpes Cold Sore Support Forum. ^ Herpes Dating H-Date.com - genital herpes dating/HPV picture. ^ Herpes Dating, HPV Dating, and Support on Antopia's MPwH.net. ^ 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. doi:10.1136/sti.79.1.42. PMID 12576613. External links General Genital Herpes Fact Sheet at The Centers for Disease Control and Prevention Genital Herpes: A Hidden Epidemic at FDA Images Links to genital herpes pictures Hardin MD/University of Iowa Herpes photo library at Dermnet Pictures of Orofacial Herpes Coldsores VisualDxHealth Genital Herpes Pictures Atlas of Ophthalmology UoIowa, annotations under herpes simplex Other Herpes Blood Tests Quick Reference Guide Updated Herpes Handbook from Westover Heights Clinic The Importance and Practicalities of Patient Counseling in the Prevention and Management of Genital Herpes 2004 at Medscape International Herpes Management Forum Provides Ratios of Lysine to Arginine in Common Foods v d e Sexually transmitted diseases and infections STD/STI primarily A50-A64, 090-099 Bacterial Chancroid Haemophilus ducreyi Chlamydia Chlamydia trachomatis Donovanosis Granuloma Inguinale Lymphogranuloma venereum LGV Gonorrhea Neisseria gonorrhoeae Syphilis Treponema pallidum Ureaplasma urealyticum Protozoal Trichomoniasis Trichomonas vaginalis Parasitic Crab louse/crabs Scabies Viral AIDS HIV-1/HIV-2 Cervical cancer Genital warts condyloma Human papillomavirus HPV Hepatitis B Herpes simplex virus HSV1/HSV2 Molluscum contagiosum MCV General inflammation female: Cervicitis Pelvic inflammatory disease PID male: Epididymitis Prostatitis either: Proctitis Urethritis/Non-gonococcal urethritis NGU Other Ectopic pregnancy Premature birth Infertility Reactive arthritis v d e Infectious diseases - Virus diseases A80-B34, 042-079 CNS Encephalitis/ meningitis DNA virus: Progressive multifocal leukoencephalopathy RNA virus: Subacute sclerosing panencephalitis - Lymphocytic choriomeningitis - Tick-borne meningoencephalitis unknown: Encephalitis lethargica Eye DNA virus: Cytomegalovirus retinitis Other RNA virus: Rabies - Myelitis: Poliomyelitis Post-polio syndrome - Tropical spastic paraparesis Skin and mucous membrane lesions DNA virus, Herpesviridae: Herpes simplex - Chickenpox - Herpes zoster - KSHV DNA virus, other: Poxviridae Smallpox, Monkeypox, Cowpox, Vaccinia, Molluscum contagiosum - exanthem Roseola, Fifth disease - HPV Wart RNA virus: exanthem Measles, Rubella - picornavirus Hand, foot and mouth disease, Foot-and-mouth disease Digestive system Hepatitis DNA virus: B RNA virus: A - D - C - E - G Gastroenteritis DNA virus: Adenovirus RNA virus: Rotavirus - Norovirus - Astrovirus - Coronavirus Respiratory system RNA virus, IV: Acute viral nasopharyngitis - Severe acute respiratory syndrome RNA virus, V: Influenza/Avian influenza - Human parainfluenza viruses - RSV - hMPV Other/varied: Infectious mononucleosis - Viral pneumonia Sexually transmitted DNA virus: HPV Genital warts, Cervical cancer RNA virus, retrovirus: HIV AIDS, AIDS dementia complex - Adult T-cell leukemia Oncovirus DNA virus: Hepatitis B - HPV - Kaposi's sarcoma-associated herpesvirus RNA virus: Hepatitis C - HTLV Systemic DNA virus: Cytomegalovirus RNA virus: Mumps - Bornholm disease - Coxsackie B Retrieved from http://en..org/wiki/Herpes_simplex Categories: Sexually transmitted diseases and infections | Viral diseasesHidden categories: Pages with DOIs broken since 2008 | All articles with statements | Articles with statements since July 2008 | Articles with statements since May 2008 Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages العربية Česky Dansk Deutsch Español Esperanto Français 한국어 Bahasa Indonesia Italiano עברית Bahasa Melayu Nederlands 日本語 ‪Norsk bokmål‬ Polski Português Ру�?�?кий Sloven�?ina Срп�?ки / Srpski Tagalog ไทย 中文 This page was last modified on 29 August 2008, at 10:17

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