Herpes

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Herpes
SpecialtyInfectious diseases, dermatology Edit this on Wikidata
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.

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. Cite error: The <ref> tag has too many names (see the help page). This is not necessarily good, as prior HSV-1 infection has the tendency to ameliorate the effects of symptomatic HSV-2 reoccurrences.

Orofacial infection

Herpes
SpecialtyInfectious diseases, dermatology Edit this on Wikidata

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.[2]

Herpes infections are largely asymptomatic; when symptoms appear they will typically resolve within two weeks.[2] 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.[2] 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).[2] 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.[2]

Genital infection

Herpes
SpecialtyInfectious diseases, dermatology Edit this on Wikidata
Genital herpes in a male

Following the classification HSV into two distinct categories of HSV-1 and HSV-2 in the 60s, [3][4]It 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, [5][6][7] 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.[8] 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. Cite error: The <ref> tag has too many names (see the help page).In 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.[8] 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.[9] 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.[10][11] It is also often observed in thumb-sucking children with primary HSV-1 oral infection (autoinoculation) prior to seroconversion,[9] and in adults aged 20 to 30 following contact with HSV-2-infected genitals.[12]

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.[13]

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 wrestlers. Lesions were on the head in 73 percent of the wrestlers, the extremities in 42%, and the trunk in 28%.[14] Physical symptoms sometimes recur in the skin.[15] 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

Herpes
SpecialtyInfectious diseases, dermatology Edit this on Wikidata

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.[16] 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.[17] 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.[17] 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.[17] 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,[17] resulting in loss of vision due to opacification of the cornea. This is known as immune-mediated stromal keratitis. }}

Herpes Simplex Encephalitis

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.[18] 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.[19]

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.[18] 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.[20] 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.[18] 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.[18]

Without treatment, HSE results in rapid death in approximately 70% of cases.[18] 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.[19]

Neonatal herpes simplex

Herpes
SpecialtyInfectious diseases, dermatology Edit this on Wikidata

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%[21] 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.[22] 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.[23][24]However, shedding of HSV-1 from both primary genital infection and reactivations is associated with higher transmission from mother to infant.[23]

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.[21] 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,[23][25]. 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 herpes(CNS).[26] 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).[27]DIS 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.[23] 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.[26][28][29][30] 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.[31] 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.[32] 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.[33][34] 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.[35]

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).[36][37] 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.[38]

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.[39] 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.[40][41] 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.[42]

Alzheimer's disease

Scientists discovered a link between HSV-1 and Alzheimer’s disease in 1979.[43] 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.[44] This research identifies HSVs as the pathogen most clearly linked to the establishment of Alzheimer’s.[45]

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.[46]

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).[47]

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.[48] Changes in the immune system during menstruation may play a role in HSV-1 reactivation.[49][50] 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.[51][52][53][54][55]

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.[56] 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.[57] 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] While herpes virus type 2 has been demonstrated to remain viable on toilet seats for 2 to 4 hours after contact and on dry gauze for up to 72 hours, as of the submission of those findings (1984) there were no documented cases of infection via an inanimate object (e.g. a towel, toilet seat, drinking vessels). [58] 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.[59] 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.[59] 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.[60] 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.[59]

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.[61] 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.

For genital herpes, condoms are highly effective in limiting transmission of herpes simplex infection.[62][63] 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,[64] 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.[65]

As with almost all sexually transmitted infections, women are more susceptible to acquiring genital HSV-2 than men.[66] 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%. [67][61] 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.[67] Suppressive antiviral therapy reduces these risks by 50%. [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%.[62][63][69] Condom use is much more effective at preventing male to female transmission than vice-versa.[62] 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.[70][24] 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.[15] 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.[15]

Genital herpes can be more difficult to diagnose than oral herpes since most HSV-2-infected persons have no classical symptoms.[15] Further confusing diagnosis, several other conditions resemble genital herpes, including lichen planus, atopic dermatitis, and urethritis.[15] 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.[15]

Serological tests for antibodies to HSV are rarely useful to diagnosis and not routinely used in clinical practice[15], 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-2[73]
Location Year(s) 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
Mali[74] 1991-7 93 43 -
Morocco[74] 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 Korea[75] 2004 - 28 22
Philippines 1991-3 - 9 -
Syria 1995-8 80-100 0 0-1
Thailand[74][73] 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 -
Colombia[74] 1985-97 89 57 -
Costa Rica 1984-5 - 39 -
Haiti <1992 - 54 -
Mexico 1992-7 - 30 -
Peru[74] 1991-7 92 36 -
Europe
Bulgaria[76] 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.[15] 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.[6][77] 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.[15] 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.[79][80][81][82] Women are at higher risk than men for acquiring HSV-2 infection, and the chance of being infected increases with age.[15]

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-1[86]

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%.[73][87] 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.[74][73] 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. [94]An 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.[97]HSV-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.[59] 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.[103][104]

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, or(IDU) 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: Heparin [112], trifluorothymidine (TFT)[113], Ribivarin,[114] interferon,[115] Virazole,[116] and 5-methoxymethyl-2'-deoxyuridine (MMUdR).[117] The introduction of 9-(2-hydroxyethoxymethyl)guanine, AKA acyclovir, in the late 1970s[118] raised antiviral treatment another notch and led to vidarabine vs. acyclovir trials in the late 1980s.[119] 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.[120] 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.[120] 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.[120]

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.[121]

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.[121] 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.[122] 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.[123][124][125] 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.[126] 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.[127]

Antiviral medications are also available as topical creams for treating recurrent outbreaks on the lips, although their effectiveness is disputed.[128] Penciclovir cream has a 7-17 hour longer cellular half-life than aciclovir cream, increasing its effectiveness relative to aciclovir when topically applied.[129]

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.[130] 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.[131]

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 virus[132]

Other drugs

Cimetidine, a common component of heartburn medication, has been shown to lessen the severity of herpes zoster outbreaks in several different instances.[133][134][135] This is an off-label use of the drug. It and probenecid have been shown to reduce the renal clearance of aciclovir.[136] 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.[137] 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.[138]

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.[139] 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.[139] 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.[139] 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.[139] 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.[139]

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.[140]

Natural compounds

File:RedoxonVitaminC.jpg
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.[141]

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.[142][143][144]

Aloe vera, available as a cream or gel, makes an affected area heal faster and may prevent recurrences.[145]

Lemon balm (Melissa officinalis) has antiviral activity against HSV-2 in cell culture and may reduce HSV symptoms in herpes infected people.[146][147][147]

Carrageenans—linear sulphated polysaccharides extracted from red seaweeds—have been shown to have antiviral effects in HSV-infected cells and in mice.[148] [149]

There is conflicting evidence on a possible benefit from extracts from the plant echinacea in treating oral[150], but not genital, herpes.[151]

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.[152][153]

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.[154]

The plant Prunella vulgaris, commonly known as selfheal, also prevents expression of both type 1 and type 2 herpes in cultured cells.[155]

Lactoferrin, a component of whey protein, has been shown to have a synergistic effect with aciclovir against HSV in vitro.[156]

Some dietary supplements have been suggested to positively treat herpes. These include vitamin C, vitamin A, vitamin E, and zinc.[157][158]

Butylated hydroxytoluene (BHT), commonly available as a food preservative, has been shown in cell culture and animal studies to inactivate herpes virus.[159][160] 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.[161] 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.[162][163][164][165][166][167][168][169]

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.[170] 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

  1. ^ 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/S0140-6736(07)61908-4. PMID 18156035.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ 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.
  3. ^ Dowdle Wr, Nahmias AJ, Harwell RW, Pauls FP. (1967). "Association of antigenic type of Herpesvirus hominis with site of viral recovery". J Immunol. 99(5): 974–80. PMID 4295116.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Nahmias Aj, Dowdle W.R. (1968). "Antigenic and biologic differences in herpesvirus hominis". Prog Med Virol. 10: 110–59. PMID 4304588.
  5. ^ 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. 39(9): 3321–5. PMID 11526170. {{cite journal}}: Check date values in: |year= (help)CS1 maint: multiple names: authors list (link)
  6. ^ 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?" (PDF). Sex Trans Dis. 30(10): 801–802. PMID 14520182. {{cite journal}}: Check date values in: |year= (help)CS1 maint: multiple names: authors list (link)
  7. ^ 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. 27(1): 22–9. PMID 12727525. {{cite journal}}: Check date values in: |year= (help)CS1 maint: multiple names: authors list (link)
  8. ^ a b "STD Facts - Genital Herpes". Retrieved 2008-02-22.
  9. ^ a b Clark DC (2003). "Common acute hand infections". Am Fam Physician. 68 (11): 2167–76. PMID 14677662.
  10. ^ Lewis MA (2004). "Herpes simplex virus: an occupational hazard in dentistry". Int Dent J. 54 (2): 103–11. PMID 15119801.
  11. ^ Avitzur Y, Amir J (2002). "Herpetic whitlow infection in a general pediatrician--an occupational hazard". Infection. 30 (4): 234–6. doi:10.1007/s15010-002-2155-5. PMID 12236568.
  12. ^ Wu IB, Schwartz RA (2007). "Herpetic whitlow". Cutis. 79 (3): 193–6. PMID 17674583.
  13. ^ Anonymous (1971). "Herpetic whitlow: a medical risk". Br Med J. 4 (5785): 444. PMID 5125276.
  14. ^ Belongia EA, Goodman JL, Holland EJ; et al. (1991). "An outbreak of herpes gladiatorum at a high-school wrestling camp". N. Engl. J. Med. 325 (13): 906–10. PMID 1652687. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  15. ^ 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.
  16. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ^ a b c d Suresh PS, Tullo AB (1999). "Herpes simplex keratitis". Indian J Ophthalmol. 47 (3): 155–65. PMID 10858770.
  18. ^ 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.
  19. ^ a b Whitley RJ, Gnann JW (2002). "Viral encephalitis: familiar infections and emerging pathogens". Lancet. 359 (9305): 507–13. PMID 11853816.
  20. ^ Dinn J (1980). "Transolfactory spread of virus in herpes simplex encephalitis". Br Med J. 281 (6252): 1392. PMID 7437807.
  21. ^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)
  22. ^ Brown ZA, Gardella C, Wald A, Morrow RA, Corey L (2005). "Genital herpes complicating pregnancy". Obstet Gynecol. 106 (4): 845–56. doi:10.1097/01.AOG.0000180779.35572.3a. PMID 16199646. {{cite journal}}: Unknown parameter |doi_brokendate= ignored (|doi-broken-date= suggested) (help)CS1 maint: multiple names: authors list (link)
  23. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  24. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  25. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  26. ^ 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.
  27. ^ Prober CG. Herpes simplex virus. p. 1138. {{cite book}}: Unknown parameter |Editor= ignored (|editor= suggested) (help); Unknown parameter |Publisher= ignored (|publisher= suggested) (help); Unknown parameter |Year= ignored (|year= suggested) (help)
  28. ^ Kesson AM (2001). "Management of neonatal herpes simplex virus infection". Paediatr Drugs. 3 (2): 81–90. PMID 11269641.
  29. ^ {{cite web |url=http://www.merck.com/mmpe/sec19/ch279/ch279h.html |title=The Merck Manual, Neonatal Herpes Simplex Virus (HSV) Infection
  30. ^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)
  31. ^ Jacobs RF (1998). "Neonatal herpes simplex virus infections". Semin. Perinatol. 22 (1): 64–71. PMID 9523400.
  32. ^ Ch. 6, "Medical Disorders during Pregnancy," in Harrison's Principles of Internal Medicine, 16th ed., 2005
  33. ^ 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.
  34. ^ "Recurring viral meningitis & herpes II". Med Help International. Retrieved 2006-11-21.
  35. ^ Sendi P, Graber P (2006). "Mollaret's meningitis". CMAJ. 174 (12): 1710. doi:10.1503/cmaj.051688. PMID 16754896.
  36. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  37. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  38. ^ Lazarini PR, Vianna MF, Alcantara MP, Scalia RA, Caiaffa Filho HH (2006). "Herpes simplex virus in the saliva of peripheral Bell's palsy patients". Rev Bras Otorrinolaringol (Engl Ed) (in Portuguese). 72 (1): 7–11. PMID 16917546.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  39. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  40. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  41. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  42. ^ Tiemstra JD, Khatkhate N (2007). "Bell's palsy: diagnosis and management". Am Fam Physician. 76 (7): 997–1002. PMID 17956069.
  43. ^ 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/S0140-6736(80)91490-7.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  44. ^ Dobson, C.B. (1999). "Herpes simplex virus type 1 and Alzheimer's disease". Neurobiol Aging. 20 (4): 457–65. doi:10.1016/S0197-4580(99)00055-X. Retrieved 2008-03-15. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  45. ^ Pyles, R.B. (2001). "The association of herpes simplex virus and Alzheimer's disease: a potential synthesis of genetic and environmental factors" (PDF). Herpes. 8 (3): 64–68. Retrieved 2008-03-15.
  46. ^ Itzhaki, R.F. (1997). "Herpes simplex virus type 1 in brain and risk of Alzheimer's disease". Lancet. 349 (9047): 241–4. doi:10.1016/S0140-6736(96)10149-5. Retrieved 2008-03-15. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  47. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  48. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  49. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  50. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  51. ^ 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.
  52. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  53. ^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  54. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  55. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  56. ^ Martinez V, Caumes E, Chosidow O (2008). "Treatment to prevent recurrent genital herpes". Curr Opin Infect Dis. 21 (1): 42–48. doi:10.1097/QCO.0b013e3282f3d9d3. PMID 18192785. {{cite journal}}: Unknown parameter |doi_brokendate= ignored (|doi-broken-date= suggested) (help)CS1 maint: multiple names: authors list (link)
  57. ^ "AHMF: Preventing Sexual Transmission of Genital herpes". Retrieved 2008-02-24.
  58. ^ Neinstein LS, Goldenring J, Carpenter S (1984). "Nonsexual transmission of sexually transmitted diseases: an infrequent occurrence". Pediatrics. 74 (1): 67–76. PMID 6610855. {{cite journal}}: More than one of |PMID= and |pmid= specified (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  59. ^ 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.
  60. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  61. ^ a b Mertz, G.J. (1993). "Epidemiology of genital herpes infections". Infect Dis Clin North Am. 7 (4): 825–39. PMID 8106731. Cite error: The named reference "Mertz1993" was defined multiple times with different content (see the help page).
  62. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  63. ^ a b Casper C, Wald A. (2002). "Condom use and the prevention of genital herpes acquisition," (PDF). Herpes. 9 (1): 10–14. PMID 11916494.
  64. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  65. ^ Seppa, Nathan (2005-01-05). "One-Two Punch: Vaccine fights herpes with antibodies, T cells". Science News. p. 5. Retrieved 2007-03-29.
  66. ^ Carla K. Johnson (August 23, 2006). "Percentage of people with herpes drops". Associated Press.
  67. ^ 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. 326(14): 916–20. PMID 1311799.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  68. ^ Corey L, Wald A, Patel R; et al. (2004). "Once-daily valacyclovir to reduce the risk of transmission of genital herpes" (PDF). N Engl J Med. 350(1): 11–20. PMID 1402423. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  69. ^ 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. 143(10): 707–13. PMID 16287791.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  70. ^ Whitley RJ, Kimberlin DW, Roizman B (1998). "Herpes simplex viruses". Clin Infect Dis. 26 (3): 541–53. PMID 9524821.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  71. ^ 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.
  72. ^ Handsfield HH (2000). "Public Health Strategies to Prevent Genital Herpes: Where Do We Stand?". Curr Infect Dis Rep. 2 (1): 25–30. PMID 11095834.
  73. ^ 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.
  74. ^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  75. ^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  76. ^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  77. ^ 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" (PDF). Sex Transm Dis. 30 (10): 797–800. PMID 14520181.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  78. ^ Malkin JE (2004). "Epidemiology of genital herpes simplex virus infection in developed countries" (PDF). Herpes. 11 Suppl 1: 2A–23A. PMID 15115626.
  79. ^ "Herpes simplex" (HTML). University of Maryland Medical Center. Retrieved 2007-09-03.
  80. ^ "LEARN ABOUT HERPES > Fast Facts" (HTML). ASHA Herpes Resource Center. Retrieved 2007-09-03.
  81. ^ "STD Facts - Genital Herpes" (HTML). Centers for Disease Control and Prevention. Retrieved 2007-09-03.
  82. ^ "Herpes" (HTML). Stanford University Sexual Health Peer Resource Center. Retrieved 2007-09-03.
  83. ^ 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. 41(1): 84–89. PMID 12517830.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  84. ^ Patrick DM, Dawar M, Cook DA, Krajden M, Ng HC, Rekart ML (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  85. ^ Singh AE, Romanowski B, Wong T; et al. (2005). "Herpes simplex virus seroprevalence and risk factors in 2 Canadian sexually transmitted disease clinics". Sex Transm Dis. 32 (2): 95–100. PMID 15668615. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  86. ^ Forward KR, Lee SH (2003). "Predominance of herpes simplex virus type 1 from patients with genital herpes in Nova Scotia". Can J Infect Dis. 14 (2): 94–6. PMC 2094909. PMID 18159431. {{cite journal}}: Unknown parameter |month= ignored (help)
  87. ^ 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.
  88. ^ 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 Kundi". Saudi Med J. 27 (8): 1139–45. PMID 16883441.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  89. ^ Meguenni S, Djenaoui T, Bendib A; et al. (1989). "Herpes simplex virus infections in Algiers". Arch Inst Pasteur Alger (in French). 57: 61–72. PMID 2562258. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  90. ^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  91. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  92. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  93. ^ 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.
  94. ^ 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" (PDF). Sex Transm Dis. 33(11): 641-5. {{cite journal}}: Check date values in: |year= (help); Unknown parameter |pubmed= ignored (help)CS1 maint: multiple names: authors list (link)
  95. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  96. ^ 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" (PDF). Sex Transm Dis. 30(11): 835–8. PMID 14603091.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  97. ^ 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" (PDF). Isr Med Assoc J. 5(9): 626–8. {{cite journal}}: Unknown parameter |Pubmed= ignored (help)CS1 maint: multiple names: authors list (link)
  98. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  99. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  100. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  101. ^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  102. ^ Lyttle PH (1994). "Surveillance report: disease trends at New Zealand sexually transmitted disease clinics 1977-1993". Genitourin Med. 70 (5): 329–35. PMID 8001945.
  103. ^ "Local anesthetic creams". BMJ. 297 (6661): 1468. 1988. PMID 3147021.
  104. ^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  105. ^ a b Chow AW, Roland A, Fiala M; et al. (1973). "Cytosine arabinoside therapy for herpes simplex encephalitis--clinical experience with six patients". Antimicrob. Agents Chemother. 3 (3): 412–7. PMC 444424. PMID 4790599. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  106. ^ Kaufman HE, Howard GM (1962). "Therapy of experimental herpes simplex keratitis". Invest Ophthalmol. 1: 561–4. PMID 14454441. {{cite journal}}: Unknown parameter |month= ignored (help)
  107. ^ Ch'ien LT, Whitley RJ, Alford CA, Galasso GJ (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  108. ^ McKelvey EM, Kwaan HC (1969). "Cytosine arabinoside therapy for disseminated herpes zoster in a patient with IgG pyroglobulinemia". Blood. 34 (5): 706–11. PMID 5352659. {{cite journal}}: Unknown parameter |month= ignored (help)
  109. ^ Fiala M, Chow A, Guze LB (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. PMC 444221. PMID 4364937. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  110. ^ Allen LB, Hintz OJ, Wolf SM; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  111. ^ Juel-Jensen BE (1970). "Varicella and cytosine arabinoside". Lancet. 1 (7646): 572. PMID 4190397. {{cite journal}}: Unknown parameter |month= ignored (help)
  112. ^ Nahmias AJ, Kibrick S (1964). "Inhibitory effect of heparin on herpes simplex virus". J. Bacteriol. 87 (5): 1060–6. PMC 277146. PMID 4289440. {{cite journal}}: Unknown parameter |month= ignored (help)
  113. ^ Allen LB, Sidwell RW (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. PMC 444296. PMID 4790562. {{cite journal}}: Unknown parameter |month= ignored (help)
  114. ^ Allen LB, Wolf SM, Hintz CJ, Huffman JH, Sidwell RW (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  115. ^ Allen LB, Cochran KW (1972). "Target-organ treatment of neurotropic virus disease with interferon inducers". Infect. Immun. 6 (5): 819–23. PMC 422616. PMID 4404669. {{cite journal}}: Unknown parameter |month= ignored (help)
  116. ^ Sidwell RW, Huffman JH, Khare GP, Allen LB, Witkowski JT, Robins RK (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  117. ^ Babiuk LA, Meldrum B, Gupta VS, Rouse BT (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. PMC 429441. PMID 1239978. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  118. ^ O'Meara A, Deasy PF, Hillary IB, Bridgen WD (1979). "Acyclovir for treatment of mucocutaneous herpes infection in a child with leukaemia". Lancet. 2 (8153): 1196. PMID 91931. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  119. ^ Whitley R, Arvin A, Prober C; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  120. ^ a b c Kimberlin DW, Lin CY, Jacobs RF; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  121. ^ 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.
  122. ^ 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.
  123. ^ 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 treatment"[1]"
  124. ^ Famciclovir and Valaciclovir Differ in the Prevention of Herpes Simplex Virus Type 1 Latency in Mice: a Quantitative Study"[2]"
  125. ^ Persistence of Infectious Herpes Simplex Virus Type 2 in the Nervous System in Mice after Antiviral Chemotherapy"[3]"
  126. ^ Observation May Indicate A Possible Clinical Effect On Latency"[4]"
  127. ^ 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.
  128. ^ Worrall G (1996). "Evidence for efficacy of topical acyclovir in recurrent herpes labialis is weak". BMJ. 313 (7048): 46. PMID 8664786.
  129. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  130. ^ "Drug Name: ABREVA (docosanol) - approval". centerwatch.com. July 2000. Retrieved 2007-10-17.
  131. ^ "California Court Upholds Settlement Of Class Action Over Cold Sore Medicationl". BNA Inc. July 2000. Retrieved 2007-10-17.
  132. ^ Bishop, C.D. (1995). "Anti-viral Activity of the Essential Oil of Melaleuca alternifolia". Journal of Essential Oil Research: 641–644.
  133. ^ 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.
  134. ^ Hayne ST, Mercer JB (1983). "Herpes zoster:treatment with cemetidine". Can Med Assoc J. 129 (12): 1284–1285. PMID 6652595.
  135. ^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  136. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  137. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  138. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  139. ^ a b c d e "Herpevac Trial for Women". Retrieved 2008-02-25. Cite error: The named reference "titleHerpevac Trial for Women" was defined multiple times with different content (see the help page).
  140. ^ "Molecular Therapy - Abstract of article: 801. RNA Gene Therapy Targeting Herpes Simplex Virus".
  141. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  142. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  143. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  144. ^ Griffith RS, Norins AL, Kagan C. (1978). "A multicentered study of lysine therapy in Herpes simplex infection". Dermatologica. 156 (5): 257–267. PMID 640102.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  145. ^ Vogler BK and Ernst E. "Aloe vera: a systematic review of its clinical effectiveness". British Journal of General Practice. 49: 823–828.
  146. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  147. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  148. ^ 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.
  149. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  150. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  151. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  152. ^ 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/S0166-3542(99)00042-X. PMID 10551373.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  153. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  154. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  155. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  156. ^ 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/S0166-3542(02)00214-0. PMID 12767468.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  157. ^ Gaby AR (2006). "Natural remedies for Herpes simplex". Altern Med Rev. 11 (2): 93–101. PMID 16813459.
  158. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  159. ^ Snipes W, Person S, Keith A, Cupp J. (1985). "Butylated hydroxytoluene inactivates lipid-containing viruses" Science. 1975;188(4183):64-6
  160. ^ 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. {{cite journal}}: Missing pipe in: |volume= (help); horizontal tab character in |volume= at position 3 (help); line feed character in |title= at position 99 (help)CS1 maint: multiple names: authors list (link)
  161. ^ Vezina C, Steben M. (2001). "Genital Herpes: Psychosexual Impacts and Counselling" (PDF). The Canadian Journal of CME (June): 125–134.
  162. ^ "HWerks.com Herpes Dating, HPV Dating, Information, Events and Support Community".
  163. ^ "NationalHClub.com Local and National Herpes Events".
  164. ^ "A to Z Herpes Support Groups".
  165. ^ "Herpes Support Groups".
  166. ^ "Herpes Viruses Association".
  167. ^ "Herpes & Cold Sore Support Forum".
  168. ^ "Herpes Dating H-Date.com - genital herpes dating/HPV picture".
  169. ^ "Herpes Dating, HPV Dating, and Support on Antopia's MPwH.net".
  170. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)

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