Jump to content

Herpes

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by 74.56.41.210 (talk) at 00:26, 29 February 2008 (→‎Transmission and prevention). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

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 that primarily infect mucosal tissues and skin. Infection of the genitals is commonly known as herpes and is predominantly caused by the type 2 strain of herpes simplex virus (HSV-2) that is usually sexually transmitted. The type 1 strain of herpes simplex virus (HSV-1) is the usual cause oral herpes, colloquially called cold sores. HSV-1 and HSV-2 are transmitted by direct contact with an infected sore or body fluid of an infected individual, and can cause painful fluid-filled blisters, containing millions of infectious virus particles. Following initial infection, these viruses travel from cells in the skin to sensory nerves, where they reside as life-long, latent viruses. HSV-1 lies dormant in trigeminal ganglia that provide sensation to the lips, lower mouth and neck; HSV-2 resides in sacral ganglia that supply sensation to the genitals, perineum and upper legs. Following reactivation, the viruses travel down the same nerves to reinfecte the same area of skin initially infected.

HSV-1 genital herpes is more infectious during primary episodes than HSV-2, but reoccurs less frequently than genital HSV-2. Both herpes infections have periods of active disease lasting 2-21 days and then remission when the sores disappear. The majority of cases are asymptomatic, however, although shedding may still occur. Over time, periods of remission generally increase in length, and the duration of lesions and viral shedding also decreases leading to reduced episodes of active disease. The frequency of recurrences is regulated by specific immunity developed against the virus. Previous HSV-1 infection tends to ameliorate the symptoms of a subsequent HSV-2 infection.

HSV-1 and HSV-2 belong to a family of herpes viruses called herpesviridae. Eight members of herpesviridae infect humans to cause a variety of illnesses including cold sores, chickenpox or varicella, shingles or herpes zoster (VZV), cytomeglovirus (CMV), and various cancers, and can cause brain inflammation (encephalitis). All viruses in the herpes family produce life-long infections. Recurrences can be triggered in some individuals by specific events, such as sunburn, ultraviolet light, wind, trauma, surgery, stress or other infections. Since viral reactivation is controlled by the immune system, in immunocompetent persons, oral and genital herpes are not typically life-threatening. However, individuals with HIV or transplant patients, with compromised immune systems, can develop serious HSV infections such as keratitis or encephalitis. Additionally, immuno-incompetent newborns, infected by genital herpes at birth or shortly thereafter, are at highest risk if they acquire CNS (central nervous system) HSV infection that can cause brain damage or disseminated HSV which often results in liver failure and death. SEM (Skin eyes mouth) HSV infection usually involves only external lesions but can progress to CNS or diseminated if untreated. The risk of neonatal HSV occurring is higher when the mother has a primary infection just prior to birth and lacks protective antibodies that would otherwise reduce viable virus shedding. While great strides have been made in the treatment of neonatal herpes with the advancement of acyclovir antiviral therapy, the major impediment to its eradication remains late diagnosis with lesions appearing late in the course of the disease, or not at all.[citation needed] Infection is asymptomatic in up 40% of cases.

Oral herpes (HSV-1) affects 50-80% of the U.S. population by the time they are in their 40s, and genital herpes caused by HSV-2 affects approximately 20-30%. In recent years, a decline in adolescent HSV-1 seroprevalence by a few percent per decade has been observed in the US and other industrialized countries. [1] However, the incidence of HSV-1 genital herpes is increasing as result of more women entering their child bearing years while seronegative for HSV-1.[1] Despite the apparent declines in HSV seroprevalence, the American Social Health Association (ASHA) predict that since up to 90% of HSV infected people are unaware of their infection due to mild or misdiagnosed symptoms up to 40% of all men and 50% of all women could be infected with genital herpes by 2025.[2]


Disorders

Several distinct disorders are caused by HSV infection of the skin or mucosa including those that affect the face and mouth (orofacial herpes), genitalia (genital herpes), or hands (herpes whitlow). More serious problems arise when the virus infects and damages the eye (herpes keratitis) or invades the central nervous system to damage the brain (herpes encephalitis). Newborn infants, with reduced capacity to fight viral infections, are also prone to serious complications following HSV infection (neonatal herpes).

Orofacial infection

Herpes
SpecialtyInfectious diseases, dermatology Edit this on Wikidata

Infection by HSV-1 is the most common cause of herpes that effects the face and mouth (orofacial herpes) although recent years are seeing an increase in oral HSV-2 infections.[3] A majority of primary HSV-1 infections occur during childhood and, if the virus has come into contact with the mucosa or abraded skin, can cause acute herpetic gingivostomatitis (inflammation of the mucosa of the cheek and gums) within 5–10 days. Some other symptoms may also develop, including fever and sore throat, and painful ulcers may appear.[3] Primary HSV infection in adolescents frequently manifests a severe pharyngitis with lesions developing on the cheek and gums. Some individuals develop difficulty in swallowing (dysphagia) and swollen lymph nodes (lymphadenopathy).[3] Primary HSV infections in adults often presents as pharyngitis similar to that observed in glandular fever (infectious mononucleosis), but gingivostomatitis is less likely. The symptoms of primary HSV infection generally resolve within two weeks.[3]

Once a primary infection has resolved, the HSV enters the nerves surrounding the primary lesion, migrates to the cell body of the neuron, and becomes latent. In some people, the virus reactivates to cause recurrent infection - this is more common with HSV-1 than HSV-2. Prodromal symptoms often precede a recurrance, which typically begins with reddening of the skin around the infected site, with eventual ulceration to form fluid-filled blisters that affect 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 occassions of reinfections occur inside the mouth (intraoral HSV stomatitis) affecting the gums, alveolar ridge, hard palate, and the back of the tongue - this may be accompanied with herpes labialis.[3][4] Oral herpes is spread by direct contact with an active sore in an infected person, for instance, during kissing. However virus can be transmitted through the skin in the absence of a lesion. Oral herpes and cold sores can sometimes be confused with canker sores.

Genital infection

Herpes
SpecialtyInfectious diseases, dermatology Edit this on Wikidata

Clusters of inflammed papules and vesicles on the outer surface of the genitals represent the typical symptoms of a primary HSV-1 or HSV-2 genital infection. These usually appear 4–7 days after sexual exposure to HSV for the first time,[5] and may resemble cold sores.[6] 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.[6] 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. Women often experience additional symptoms that include painful urination (dysuria) and cervicitis, while herpetic proctitis (inflammation of the anus and rectum) is common for individuals participating in anal intercourse. After 2–3 weeks, existing lesions progress into ulcers and then crust and heal, although lesions on mucosal surfaces may never form crusts.[5] The virus is not removed from the body by immune system, but enters nerve ganglia that serve the infected dermatome where it becomes dormant.

Many HSV infected people experience a recurrence within the first year of infection, when the virus reactivates from its latent state. Development of lesions follows prodrome - which warns of a recurrence and includes tingling (paresthesia), itching, and pain where lumbosacral nerves innervate the skin - by hours to days. In some individuals, starting to take antiviral treatment when prodrome is experienced can reduce the appearance and duration of lesions. Fewer lesions are likely to develop that cause less pain and heal faster (5–10 days without antiviral treatment) than during the primary infection.[5] Subsequent outbreaks tend to be periodic or episodic, occur on average four to five times a year when not using antiviral therapy, and may be triggered by stress, illness, fatigue, menstruation. HSV-2 is widespread, affecting an estimated 1 in 4 females and 1 in 5 males in the United States. Although certain therapies can prevent outbreaks or reduce the risk of transmission to partners, no cure is yet available.[6][5]

Herpes whitlow

Herpes whitlow (herpetic whitlow) is a painful infection that typically manifest itself on fingers or thumbs and occassionally on the toes, or on the nail cuticle, and is caused by HSV-1 or HSV-2.[7] It is typically contracted by healthcare workers that come in contact with the virus; it is most commonly contracted by dental workers and medical workers exposed to oral secretions.[8][9] Again, the HSV seronegative person is at highest risk of acquiring this condition. Herpes whitlow is also caused by autoinoculation of HSV into broken skin prior to an infected person having antibodies against the virus (e.g. during primary infection).[7] It is often observed in thumb-sucking children with primary HSV-1 infection, and in adults aged 20 to 30 following contact with by HSV-2-infected genitals.[10]

Symptoms of herpetic whitlow include swelling, reddening and tenderness of the the skin of infected finger. This may be accompanied by fever and swollen lymph nodes. Small, clear vesicles initially form that merge and becomes cloudy. Associated pain often seems large relative to the physical symptoms. The herpes whitlow lesion usually heals in two to three weeks.[11]

Ocular herpes

Herpes
SpecialtyInfectious diseases, dermatology Edit this on Wikidata

Ocular herpes is generally caused by HSV-1 and is a special case of facial herpes infection known as herpes keratitis. It begins with infection of epithelial cells on the surface of the eye and retrograde infection of nerves serving the cornea.[12] 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, which vary from minor damage to the epithelium (superficial punctate keratitis) to formation of dendritic ulcers.[13] 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 or with the use of oral and topical antivirals. However, the virus continues to inhabit the neurons of the eye and to multiply.

Subsequent recurrences may be more severe, with infected epithelial cells showing larger dendritic ulceration and lesions forming white plaques.[13] 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.[13] This may be accompanied by chronic dry eye, low grade intermittent conjunctivitis or chronic unexplained sinusitis. When the concentration of viral DNA reaches a critical limit, the presence of the virus can trigger a massive autoimmune response in the eye, resulting in an individual's immune system destroying the corneal stroma.[13] This usually results in loss of vision due to opacification of the cornea and is a result of an antibody responses against the viral antigen expression in the stroma following persistent infection.[13] This is known as immune-mediated stromal keratitis.

Treatment with corneal transplants was once ineffective (with only 14%-61% rate of survival without antiviral therapy), as reinfection of the transplant is common when the virus reactivates. However, with concurrent use of antivirals the chance of graft acceptance has improved.[14]

Herpes simplex encephalitis

Herpes
SpecialtyInfectious diseases, dermatology Edit this on Wikidata

Herpes simplex encephalitis (HSE) is a very serious disorder and 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.[15] HSE is thought to be caused by the retrograde transmission of HSV from a peripheral site on the face to the brain along a nerve axon. Approximately 50% of individuals that develop HSE are over 50 years of age.[16] About 1 in 3 cases of HSE result from primary HSV-1 infection predominantly occuring in individuals under the age of 18. Although 2 in 3 cases occur in seropositive persons, few of these individuals have history of recurrent orofacial herpes. It is believed these seropositive individuals develop HSE as a consequence of HSV-1 reactivation.[15] The virus lies dormant in the ganglion of the trigeminal or fifth 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.[17]

Without treatment, HSE results in rapid death in around 70% of cases.[15] Even with the best modern treatment, it is fatal in around 20% of cases treated, and causes serious long-term neurological damage in over half the survivors. For unknown reasons the virus seems to target the temporal lobes of the brain. Only a small population of survivors (2.5%) regain completely normal brain function.[16] 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 their cerebrospinal fluid without the presence of pathogenic bacteria and fungi, and they typically have a fever.[15] Approximately 2 in patients with HSE will have seizures. The electrical activity of the brain (detected using EEG, CT, or MRI scans) 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.[15]

Neonatal herpes simplex

Herpes
SpecialtyInfectious diseases, dermatology Edit this on Wikidata

Neonatal HSV disease is a rare but serious condition, usually the consequence of vertical transmission of the virus from mother to newborn child, although an estimated 10% of cases may be acquired postnatally from a parent, caretaker, or sibling. Approximately 22% of pregnant women have had a previous exposure HSV-2, and a further 2% or more women acquire the virus during pregnancy.[18] Particularly among young adults, genital herpes infections are increasing caused by HSV-1.[19] The virus is transmitted in 30-57% cases of primary infection acquisition in the mother during the third trimester of pregnancy. Infection in 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 presence of signifigant titer of protective maternal antibodies in the fetus from about the seventh month of pregnancy.[20] However, shedding of HSV-1 from both primary genital infection and reactivation is associated with high transmission from mother to infant.[20]

Herpes simplex virus infection in the newborn can be "devastating," and carries "high mortality and morbidity rates from central nervous system involvement," according to Harrison's Principles of Internal Medicine, which recommends that pregnant women with active genital herpes lesions at the time of presentation in labor be delivered by cesarean section. Women whose herpes is not active can be managed with acyclovir.[21]From 1/3,000 to 1/20,000 of live births are infected with neonatal herpes. Mortality with untreated disease is 50-85%, and 95% of survivors have "severe neurologic sequelae." Treatment with acyclovir decreases the mortality by 50% and increases the percentage who develop normally from 10% to 50%.[22][23]

HSV-1 neonatal herpes is extremely rare in developing countries because primary exposure to HSV-1 (and therefore development of HSV-1 specific antibodies) usually occurs in childhood or adolescence, precluding a genital HSV-1 infection; HSV-2 infections are much more common in these countries. In industrialized nations the adolescent HSV-1 seroprevalance has been steadily dropping for the last 5 decades as a result of better hygiene, less over-crowding, and smaller family size. The resulting increase in the number of young women entering the sexually active/child bearing years as HSV-1 seronegative, has been a harbinger of increased HSV-1 genital herpes, and as a result, HSV-1 neonatal herpes in developed nations. A recent three year study in Canada revealed neonatal HSV infecions in 5.9 per 100,000 live births. HSV-1 was the cause of 62.5% of cases and 98.7% of transmission was asymptomatic.[24]

Neonatal herpes manifests itself in three forms: skin, eyes and mouth (SEM) herpes, disseminated (DIS) herpes, and central nervous system (CNS) herpes.[25] SEM herpes is characterized by external lesions but no internal organ involvement, and has the best prognosis. 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).[20] DIS herpes affects internal organs, especially 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.[20] CNS herpes is associated with highest morbidity, and DIS herpes has a higher mortality rate. Untreated, SEM herpes may spread to the internal organs and cause DIS or CNS herpes resulting in higher mortality or morbidity. Death from neonatal HSV disease in the US is currently decreasing; as high as 85% of HSV infected neonates died a few decades ago whereas the current death rate is about 25%. Reduction in mortality is due to the use of antiviral treatments such as vidarabine and acyclovir.[25][26] However, morbidity and mortality still remain high due to diagnosis of DIS and CNS herpes coming too late for effective antiviral adminstration; early diagnosis is difficult in 20-40% of infected neonates that have no visible lesions.[27]

Viral Meningitis

Herpes simplex virus 2 (HSV-2) is the most common cause of recurrent viral meningitis called Mollaret's meningitis.[28] [29]

Bell's Palsy

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 known as geniculate ganglia, particularly in a mouse model.[30][31] 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.[32] 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.[33] Other studies, which fail to detect HSV-1 DNA in the cerebrospinal fluid of Bell's palsy sufferers, also question whether HSV-1 is the causative agent in this type of facial paralysis.[34][35] 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.[36]

Recurrences and triggers

Following active infection, herpes viruses become quiescent to establish a latent infection in sensory and autonomic ganglia of the nervous system. The double-stranded DNA of the virus is incorporated into the cell physiology by infection of the cell nucleus of a nerve's cell body. HSV latency is static - no virus is produced - and is controlled by a number of viral genes including Latency Associated Transcript (LAT).[37]

The causes of reactivation from latency are uncertain but several potential triggers have been documented. Physical or psychological stress can trigger an outbreak of herpes.[38] Local injury to the face, lips, eyes or mouth, trauma, surgery, wind, radiotherapy, ultraviolet light or sunlight are well established triggers.[39][40][41][42][43] Some studies suggest changes in the immune system during menstruation may play a role in HSV-1 reactivation.[44][45] In addition, concurrent infections, such as viral upper respiratory tract infection or other febrile diseases, can cause outbreaks, hence the historic terms "cold sore" and "fever blister".

The frequency and severity of recurrent outbreaks may vary greatly depending upon the individual. Outbreaks may occur at the original site of the infection or in close proximity to nerve endings that reach out from the infected ganglia. In the case of a genital infection, sores can appear near the base of the spine, the buttocks, back of the thighs, or they may appear at the original site of infection. Immunocompromised indiduals may experience episodes that are longer, more frequent and more severe. The human body is able to build up an immunity to the virus over time and antiviral medication has been proven to shorten the duration and/or frequency of the outbreaks.[46]

Transmission and prevention

Herpes can be contracted through direct contact with an active lesion or body fluid of an infected person.[47] Infected people that show no visible symptoms may still shed and transmit virus through their skin, and this asymptomatic shedding may represent the most common form of HSV-2 transmission.[48] There are no documented cases of infection via an inanimate object (e.g. a towel, toilet seat, drinking vessels). To infect a new individual, HSV travels through tiny breaks in the skin or mucous membranes in the mouth or genital areas. Even microscopic abrasions on mucous membranes are sufficient to allow viral entry. Herpes transmission occurs between discordant partners; a person with a history of infection (HSV seropositive) can pass the virus to an HSV seronegative person.[5] Antibodies that develop following an initial infection with that type of HSV prevents reinfection with the same herpes type - a person with a history of a cold sore caused by HSV-1 cannot contract a herpes whitlow or genital infection caused by HSV-1. In a monogamous couple, a seronegative person runs a 30% per year risk of contracting an HSV-1 infection from a seropositive partner. If an oral HSV-1 infection is contracted first, seroconversion will have occurred after 6 weeks to provide protective antibodies against a futue genital HSV-1 infection.

For genital herpes, condoms are a highly effective in limiting transmission of herpes simplex infection.[49][50] However, condoms are by no means completely effective. The virus cannot get through latex, but their effectiveness is somewhat limited on a public health scale by the limited use of condoms in the community,[51] and on an individual scale because the condom may not completely cover blisters on the penis of an infected male, or base of the penis or testicles not covered by the condom may come into contact with free virus in vaginal fluid of an infected female. In 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 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.[5] Topical microbicides contain chemicals that directly inactivate the virus and block viral entry are currently being investigated.[5] 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. [52]

Women are more susceptible to acquiring genital HSV-2 than men; in the US, 11% of men and 23% of women carry HSV-2.[53] On an annual basis, without the use of antivirals or condoms, the transmission risk of HSV-2 from infected male to female is approximately 8-10%. This is believed to be due to the increased exposure of mucosal tissue to potential infection sites. Transmission risk from infected female to male is approximately 4-5% annually. Suppressive antiviral therapy reduces these risks by 50%. Antivirals also help prevent the development of symptomatic HSV in infection scenarios by about 50%, meaning the infected partner will be seropositive but symptom free. Condom use also reduces the transmission risk by 50%. Condom use is much more effective at preventing male to female transmission than vice-versa. [49] The effects of combining antiviral and condom use is roughly additive, thus resulting in approximately a 75% combined reduction in annual transmission risk. These figures reflect experiences with subjects having frequently-recurring genital herpes (>6 recurrences per year). Subjects with low recurrence rates and those with no clinical manifestations were excluded from these studies.

To prevent neonatal infections, seronegative women are recommended to avoid unprotected oral-genital contact during the last trimester of pregnancy. Mothers infected with HSV, are advised to avoid procedures that would cause trauma to the infant during birth (e.g. fetal scalp electrodes, forceps and vacuum extractors) and, should lesions be present, to elect caesarean section to reduce exposure of the child to infected secretions in the birth canal.[5] The use of antiviral treatments, such as aciclovir, given from the 36th week of pregnancy prevents HSV recurrence and shedding during childbirth, thereby reducing the need for caesarean section.[5]

HSV seropositive individuals practising unprotected sex with HIV positive persons pose a high risk of HIV transmission, and are even more susceptible to HIV during an outbreak with active sores.

Asymptomatic shedding

HSV asymptomatic shedding occurs at some time in most individuals infected with herpes. It is believed to occur on 2.9% of days while on antiviral therapy, versus 10.8% of days without and is estimated to account for one third of the total days of viral shedding.[48] Asymptomatic shedding is more frequent within the first 12 months of acquiring HSV-2, and concurrent infection with HIV also increases the frequency and duration of asymptomatic shedding.[54] It can occur more than a week before or after a symptomatic recurrence in 50% of cases.[48] There are some 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.[48]

Diagnosis

Primary orofacial herpes is readily identified by clinical examination in persons without a previous history of lesions, and with reported contact with an individual with known HSV-1 infection. The appearance and distribution of sores, in these individuals, typically presents as multiple, round, and superficial oral ulcers, accompanied by acute gingivitis. Adults with non-typical presentation are more difficult to diagnose. However, prodromal symptoms that occur before the appearance of herpetic lesions helps to differentiate HSV symptoms from the similar symptoms of, for example, allergic stomatitis. Occassionally, when lesions do not appear inside the mouth, primary orofacial herpes is mistaken for a bacterial infection known as impetigo. Common mouth ulcers (aphthous ulcer), also resemble intraoral herpes, but do not present a vesicular stage.[55]

Genital herpes is more difficult to diagnose than oral herpes since most HSV-2-infected persons have no classical signs and symptoms. To confuse diagnosis, several other conditions resemble genital herpes, including lichen planus, atopic dermatitis, or urethritis.[55] Laboratory testing is, therefore, often used to confirm genital herpes. Laboratory tests include culture of the virus, direct fluorescent antibody (DFA) studies to detect virus, skin biopsy, polymerase chain reaction (PCR) to test for presence of viral DNA and serology assays to detect the presence of antibodies the blood that react against the virus. A Tzanck test (or smear), can also be performed although this cannot differentiate between herpes simplex or herpes zoster (the causative virus of chicken pox and shingles). Although these procedures produce highly sensitive and specific diagnoses, their high costs and time constraints limit their regular use in clinical practice.[55]

Epidemiology

African-Americans and immigrants from undeveloped countries typically have an HSV-1 adolescenct seroprevalance that is two or three times higher than that of American caucasians. As a result of lower HSV-1 seroprevalence, more white Americans are entering marriage/sexual activity/child bearing years seronegative for HSV-1. The absence of antibodies to HSV-1 from a prior oral HSV-1 infection leaves them susceptible to primary HSV-1 genital infections. This brings with it a risk of vertical transmission to the neonate if primary infection the mother contracts a in the third trimester, due to lack of time for full seroconversion before childbirth. The seronegative mother (who lacks antibodies) has up to a 57% chance of conveying the infection to her baby during childbirth; whereas a recurrent infection in a woman seropositive for both HSV-1 and HSV-2 is thought to be around 1-3%. Women that are`seropositive for only one type of HSV are somewhere in between but still only half as likely to transmit HSV as the seronegative mother.

The incidence of genital herpes (HSV-2) in the US is estimated to be between 25 and 30 percent or about one in four adults. "Although African Americans are more likely to test positively for HSV-2, Caucasians have a higher risk for active genital symptoms, and over the past few years the greatest increase in HSV-2 has been observed in white adolescents." People with multiple sexual partners and those who become sexually active at a young age are also higher-risk populations for the transmission of HSV-2. [56][2][57][58]

HSV-1 genital infection is now thought to be about 50% in the U.S. and as high as 70% in Japan. Prospective active surveillance data indicate a low incidence rate of 3.61 per 100,000 live births in Australia, with similar rates in the UK; in the USA the rate is somewhat higher, estimated to be 6 to 20 per 100,000 live births depending on region and demographics. [59][60]

Treatment

Currently, there is no treatment that can eradicate any of the herpes viruses from the body. Non-prescription analgesics can reduce pain and fever during initial outbreaks. Topical anesthetic treatment (such as prilocaine, lidocaine or tetracaine) can relieve itching and pain.[61][62]

Antiviral Medication

The antiviral medication acyclovir

Antiviral medications 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 thymidine kinase to convert the drug to a monophosphate form and subsequently interfere with viral DNA replication.

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 and is now available in generic brands at a greatly reduced cost. Valaciclovir and famciclovir are prodrugs of aciclovir and penciclovir respectively, with improved oral bioavailability (55% vs 20% and 75% vs 5% respectively). Some herpes antiviral treatments may cause diarrhea requiring additional the use of diarrhea medication. Aciclovir is the recommended antiviral for suppressive therapy in the last months of pregnancy to prevent transmission of herpes simplex to the neonate. The use of valaciclovir and famciclovir, while potentially improving treatment compliance and efficacy, are still undergoing safety evaluation in this context.[63] There is evidence in mice that treatment with famciclovir, rather than aciclovir, during an initial outbreak can help lower the incidence of future outbreaks by reducing the amount of latent virus in the neural ganglia. This potential effect on latency over aciclovir drops to zero a few months post-infection.[64]

Topical antiviral creams are available for treating recurrent labial outbreaks but their effectiveness is disputed.[65] Penciclovir's primary advantage over aciclovir cream is that it has a far longer cellular half-life – 10 hours (HSV-1)/20 hours (HSV-2) for penciclovir versus 3 hours (HSV-1/2) for aciclovir.[66]

Topical treatments

Docosanol (Abreva) is available as a cream for direct application to the affected area of skin. Docosanol prevents the virus 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.[67] Marketed by Avanir Pharmaceuticals under the brand name Abreva, it was the first over-the-counter antiviral drug approved for sale in the United States and Canada. In March, 2007 it was the subject of a US nationwide class-action suit against Avanir and GlaxoSmithKline as the claim that it cut recovery times in half was found to have been misleading in a California court.[68] Tromantadine is available as a gel that inhibits entry and spreading 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. It forms a "shield" at the area of application that prevents a sore from increasing in size and stops spreading of the virus by breakage or oozing during the healing process. Aloe Vera is available as cream or gel which makes affected area heal faster, and may even prevent recurrences.[69]

Other drugs

Cimetidine, a common component of heartburn medication, has been shown to lessen the severity of herpes zoster outbreaks in several different instances, and offered some relief from herpes simplex. [70] [71] [72] This is an off-label use of the drug. It and probenecid have been shown to reduce the renal clearance of aciclovir.[73] The study showed these compounds reduce the rate, but not the extent, at which valaciclovir is converted into aciclovir. Renal clearance of aciclovir was reduced by approximately 24% and 33% respectively. In addition, respective increases in the peak plasma concentration of acyclovir of 8% and 22% were observed. The authors concluded that these effects were "not expected to have clinical consequences regarding the safety of valaciclovir". Due to the tendency of aciclovir to precipitate in renal tubules, combining these drugs should only occur under the supervision of a physician.

Limited evidence suggests that low dose aspirin (125 mg daily) might be beneficial in patients with recurrent HSV infections. It reduces the level of prostaglandins which are essential in creating an inflammation. A small study of 21 volunteers with recurrent HSV indicated a significant reduction in duration of active HSV infections, milder symptoms, and longer symptom-free periods as compared to a control group. [74] A recent animal study found that aspirin inhibited thermal stress-induced ocular viral shedding of HSV-1, and a possible benefit in reducing recurrences. [75] Aspirin is not recommended in persons under 18 years of age with herpes simplex due to the increased risk of Reye's syndrome. Long term daily doses of aspirin have a side effect of reduced blood coagulation, facilitating bruising. A single 81 mg "daily dose" aspirin is a safer regimen given that there are no studies of the correlation between dosage and antiviral effects of aspirin.

Vaccines

The National Institutes of Health (NIH) in the United States is currently in the midst of phase III trials of a vaccine against HSV-2, called Herpevac.[76] 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. Assuming FDA approval, a commercial version of the vaccine is estimated to become available around 2008. During initial trials, the vaccine did not exhibit any evidence in preventing HSV-2 in males. 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. 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.

Natural compounds

Despite numerous testimonials, no controlled trials of acceptable scientific design, and few if any other types of objective data, support a clinically significant benefit of treatment of genital or oral herpes with compounds other than the antiviral drugs discussed above. For most if not all "natural" or "alternative" agents, the biological basis for presumptive therapeutic benefit is poorly documented or, in some cases, overtly specious. To the extent that anecdotal reports suggest occasional individual benefit or that hypothetical benefit can be anticipated from laboratory research, the quantitative effects - in reduction of recurrence frequency, speed of healing of lesions, and similar outcomes - are trivial compared with antiviral therapy. In addition, only antiviral therapy has been shown to reduce subclinical shedding of HSV or to reduce the frequency of sexual transmission to uninfected partners, perhaps the greatest concern of most persons with genital herpes. Natural and alternative remedies should be considered minor adjunts to routine management, if used at all.

  • Lactoferrin, a component of whey protein, has been shown to have a synergistic effect with aciclovir against HSV in vitro.[77]
  • Lysine supplementation has been proposed as a complementary therapy for the prophylaxis and treatment of herpes simplex. Lysine supplementation is highly dose-dependent, with beneficial effects apparent only at doses exceeding 1000 mg per day. A small randomised controlled trial indicated a decrease in recurrence rates in nonimmunocompromised patients at a dose of 1248 mg of lysine monohydrochloride, but no effect at 624 mg daily. This study did not show any evidence of shortening the healing time compared to placebo.[78] Another small randomised controlled trial indicated the benefit of 3000 mg lysine daily for the reduction of occurrence, severity and healing time for recurrent HSV infection.[79][80]
  • Tissues culture studies have shown the suppression of viral replication when the lysine to arginine ratio in vitro favors lysine. The therapeutic consequence of this finding is unclear, but dietary arginine may affect the effectiveness of lysine supplementation. Some rich sources of Arginine include peanuts, peanut butter and other nuts, chocolate and raw grains.
  • Of the many practical applications for Melissa officinalis L. (Lemon balm), one is antiviral activity against HSV-2.[81] The tincture may be taken orally and used topically. A cream made with lemon balm extract is a popular treatment for cold sores and genital herpes in Germany (Lomaherpan) and UK (Lomabrit)
  • Carrageenans, linear sulphated polysaccharides extracted from red seaweeds, have been shown to have antiviral effects in HSV-infected cells. There are indications that a carrageenan based gel may offer some protection against HSV-2 transmission by binding to the receptors on the herpes virus thus preventing the virus from binding to cells. Researchers have shown that a carrageenan-based gel effectively prevented HSV-2 infection at a rate of 85% in a mouse model.[82] There is an ongoing large-scale trial of the efficacy of a similar formulation on humans results are expected to be published in 2007. The natural carrageenans 1T1, 1C1, 1C3 isolated from the red alga Gigartina skottsbergii inhibit the replication activity of HSV-1 and HSV-2 in infected mouse astrocyte nerve cells and vero cells.[83]
  • Resveratrol, a compound in red wine, prevents HSV replication in vitro by inhibiting a protein needed by the virus to replicate. Resveratrol alone is not considered potent enough to be an effective treatment.[84] A more recent in vivo study in mice showed the efficacy of topical resveratrol cream in preventing cutaneous HSV lesion formation.[85] Research on a much more potent derivative of resveratrol, named stil-5, is ongoing. There is no evidence that red wine consumption provides any similar benefits.
  • The evidence for the effectiveness of zinc and Vitamin C supplementation is poor. [86] Other supplements with anecdotal evidence of benefits include monolaurin, vitamin A, vitamin B12, garlic, and echinacea. Daily multivitamin intake may be beneficial through maintenance of immune system health. High doses of synthetic vitamin A should not be taken in early pregnancy due to linkage with birth defects. In addition, some anecdotal reports indicate that placing ice in contact with an emerging cold sore for 5-10 minutes throughout the day can help shorten the duration of the outbreak, or prevent it from developing further.
  • Butylated Hydroxytoluene (BHT), commonly available as a food preservative, has been shown in in-vitro laboratory studies to inactivate the herpes virus.[87] In-vivo studies in animals confirmed the antiviral activity of BHT against genital herpes.[88] However BHT has not been clinically tested and approved to treat herpes infections in humans.

Psychological and social effects

Due to the social stigma attached to having genital herpes, it can be difficult for an individual to initially come to terms with the changes that carrying the virus may present. Negative attitudes towards the virus have developed within society through mis-information and ignorance thus causing the many anxieties felt by those diagnosed. Initial diagnosis can cause dramatic psychological and emotional stress, due to fears about future relationships and loss of self-confidence. The fears and anxieties born out of contracting genital herpes are themselves a result of poor education on the subject and prejudices surrounding STI's. Genital herpes (HSV2) is medically a condition no different to that of facial herpes (HSV1) yet both evoke such contrasting attitudes. People are generally very accepting of facial coldsores but are horrified at the thought of genital coldsores. With more education and openly discussing herpes simplex it is hoped that modern society (in the UK at least) will come to accept the two equally for what they are; no more than minor skin conditions.

Quality of life issues

Upon diagnosis of the herpes virus, people can experience a number of negative feelings related to the condition. Though these feelings lessen over time, they can include depression, fear of rejection, feelings of isolation, fear of being found out, self-destructive feelings, and fear of masturbation.[89] In order to improve the well-being of people with herpes, support groups have been formed in the United States and the UK, providing supporting communities and information about herpes of message forums and dating websites.[90][91][92][93][94]

Disclosure to new partners

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'.[95] The perception of the likely 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. It is found that reactions from sexual partners are more commonly positive than not, even though negative reactions are greatly feared and this fear is usually what constitutes the 'problem' of having herpes; rather than the physical implications it causes. However, rejection can happen, usually through mis-information and/or false notions on how herpes simplex will affect ones life. Negative reactions can be prevented through education and the spreading of correct information.

Whether the law can help a person who catches herpes depends on the jurisdiction where it was contracted as legal jurisdictions define their own rules regarding the transmission of STIs such as herpes.[96] There can be both criminal and civil possibilities. For example, in the criminal case of R. v. Sullivan heard in England and Wales, an attempt was made to prosecute Sullivan for sexual assault after his partner experienced a primary outbreak of genital herpes, on the basis that he had failed to reveal the fact that he had herpes. The presiding judge dismissed the prosecution case during preliminary hearings, citing inability to prove prior knowledge and the trial did not take place. Civil claims for transmission of herpes are, for their part, usually based on negligence if transmission was accidental and battery if deliberate. The first successful case to allow such a claim in the United States was Kathleen K. v. Robert B., decided by the California Court of Appeals.

References

  1. ^ a b Xu F, Sternberg MR, Kottiri BJ; et al. (2006). "Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States". JAMA. 296 (8): 964–73. doi:10.1001/jama.296.8.964. PMID 16926356. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  2. ^ a b American Social Health Association - Learn about STDs/STIs Cite error: The named reference "asha" was defined multiple times with different content (see the help page).
  3. ^ 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.
  4. ^ [who?]
  5. ^ a b c d e f g h i 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)
  6. ^ a b c "STD Facts - Genital Herpes". Retrieved 2008-02-22.
  7. ^ a b Clark DC (2003). "Common acute hand infections". Am Fam Physician. 68 (11): 2167–76. PMID 14677662.
  8. ^ Lewis MA (2004). "Herpes simplex virus: an occupational hazard in dentistry". Int Dent J. 54 (2): 103–11. PMID 15119801.
  9. ^ Avitzur Y, Amir J (2002). "Herpetic whitlow infection in a general pediatrician--an occupational hazard". Infection. 30 (4): 234–6. PMID 12236568.
  10. ^ Wu IB, Schwartz RA (2007). "Herpetic whitlow". Cutis. 79 (3): 193–6. PMID 17674583.
  11. ^ Anonymous (1971). "Herpetic whitlow: a medical risk". Br Med J. 4 (5785): 444. PMID 5125276.
  12. ^ 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)
  13. ^ a b c d e Suresh PS, Tullo AB (1999). "Herpes simplex keratitis". Indian J Ophthalmol. 47 (3): 155–65. PMID 10858770.
  14. ^ Halberstadt M, Machens M, Gahlenbek KA, Böhnke M, Garweg JG (2002). "The outcome of corneal grafting in patients with stromal keratitis of herpetic and non-herpetic origin". Br J Ophthalmol. 86 (6): 646–52. PMID 12034687.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ 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.
  16. ^ a b Whitley RJ, Gnann JW (2002). "Viral encephalitis: familiar infections and emerging pathogens". Lancet. 359 (9305): 507–13. PMID 11853816.
  17. ^ Dinn J (1980). "Transolfactory spread of virus in herpes simplex encephalitis". Br Med J. 281 (6252): 1392. PMID 7437807.
  18. ^ 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}}: CS1 maint: multiple names: authors list (link)
  19. ^ Baker DA (2007). "Consequences of herpes simplex virus in pregnancy and their prevention". Curr. Opin. Infect. Dis. 20 (1): 73–6. doi:10.1097/QCO.0b013e328013cb19. PMID 17197885.
  20. ^ 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)
  21. ^ Ch. 6, "Medical Disorders during Pregnancy," in Harrison's Principles of Internal Medicine, 16th ed., 2005
  22. ^ The Merck Manual, Neonatal Herpes Simplex Virus (HSV) Infection
  23. ^ Brocklehurst P, Kinghorn GA; et al. "randomised placebo controlled trial of suppressive acyclovir in late pregnancy in women with recurrent genital herpes infection". 105 (3): 275–80. {{cite journal}}: Cite journal requires |journal= (help); Explicit use of et al. in: |author= (help); Unknown parameter |Journal= ignored (|journal= suggested) (help); Unknown parameter |Year= ignored (|year= suggested) (help)
  24. ^ 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}}: Cite has empty unknown parameter: |1= (help); Explicit use of et al. in: |author= (help)
  25. ^ 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.
  26. ^ Kesson AM (2001). "Management of neonatal herpes simplex virus infection". Paediatr Drugs. 3 (2): 81–90. PMID 11269641.
  27. ^ Jacobs RF (1998). "Neonatal herpes simplex virus infections". Semin. Perinatol. 22 (1): 64–71. PMID 9523400.
  28. ^ 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.
  29. ^ "Recurring viral meningitis & herpes II". Med Help International. Retrieved 2006-11-21.
  30. ^ 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)
  31. ^ 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)
  32. ^ 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)
  33. ^ 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)
  34. ^ 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)
  35. ^ 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)
  36. ^ Tiemstra JD, Khatkhate N (2007). "Bell's palsy: diagnosis and management". Am Fam Physician. 76 (7): 997–1002. PMID 17956069.
  37. ^ 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)
  38. ^ 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)
  39. ^ 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.
  40. ^ 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)
  41. ^ 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)
  42. ^ 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)
  43. ^ 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)
  44. ^ 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)
  45. ^ 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)
  46. ^ 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}}: CS1 maint: multiple names: authors list (link)
  47. ^ "AHMF: Preventing Sexual Transmission of Genital Herpes". Retrieved 2008-02-24.
  48. ^ 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.
  49. ^ a b Wald A, Langenberg AG, Link K, Izu AE, Ashley R, Warren T, Tyring S, Douglas JM Jr, Corey L. (2001). "Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women". JAMA. 285 (24): 3100–3106. PMID 11427138.{{cite journal}}: CS1 maint: multiple names: authors list (link) Cite error: The named reference "Wald" was defined multiple times with different content (see the help page).
  50. ^ Casper C, Wald A. (2002). "Condom use and the prevention of genital herpes acquisition". Herpes. 9 (1): 10–14. PMID 11916494.
  51. ^ de Visser RO, Smith AM, Rissel CE, Richters J, Grulich AE. (2003). "Sex in Australia: safer sex and condom use among a representative sample of adults". Aust. N. Z. J. Public Health. 27 (2): 223–229. PMID 14696715.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  52. ^ Seppa, Nathan (2005-01-05). "One-Two Punch: Vaccine fights herpes with antibodies, T cells". Science News. p. 5. Retrieved 2007-03-29.
  53. ^ Carla K. Johnson (August 23, 2006). "Percentage of people with herpes drops". Associated Press.
  54. ^ 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. PMID 16845624.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  55. ^ a b c 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.
  56. ^ "Herpes simplex" (HTML). University of Maryland Medical Center. Retrieved 2007-09-03.
  57. ^ "STD Facts - Genital Herpes" (HTML). Centers for Disease Control and Prevention. Retrieved 2007-09-03.
  58. ^ "Herpes" (HTML). Stanford University Sexual Health Peer Resource Center. Retrieved 2007-09-03.
  59. ^ Elliott E, Rose D. (2003). "Australian Paediatric Surveillance Unit. Reporting of communicable disease conditions under surveillance by the APSU, 1 January to 30 September 2003". Commun. Dis. Intell. 28 (1): 90–91. PMID 15072162.
  60. ^ Jones CA (2004). "Vaccines to prevent neonatal herpes simplex virus infection". Expert Rev. Vaccines. 3 (4): 363–364. PMID 15270635.
  61. ^ "Local anesthetic creams". BMJ. 297 (6661): 1468. 1988. PMID 3147021.
  62. ^ 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)
  63. ^ Leung DT, Sacks SL. (2003). "Current treatment options to prevent perinatal transmission of herpes simplex virus". Expert Opin. Pharmacother. 4 (10): 1809–1819. PMID 14521490.
  64. ^ 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.
  65. ^ Worrall G (1996). "Evidence for efficacy of topical acyclovir in recurrent herpes labialis is weak". BMJ. 313 (7048): 46. PMID 8664786.
  66. ^ 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)
  67. ^ "Drug Name: ABREVA (docosanol) - approval". centerwatch.com. July 2000. Retrieved 2007-10-17.
  68. ^ "California Court Upholds Settlement Of Class Action Over Cold Sore Medicationl". BNA Inc. July 2000. Retrieved 2007-10-17.
  69. ^ Vogler BK and Ernst E. "Aloe vera: a systematic review of its clinical effectiveness". British Journal of General Practice. 49: 823–828.
  70. ^ Another treatment, if not very medical, is the use of vaseline, or any other type of fat. This will ban water, or saliva, from reaching the cold sore. as the cold sore "feeds" itself from water, this will end its existence in a day or two. 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. {{cite journal}}: Check date values in: |year= (help)CS1 maint: year (link)
  71. ^ Hayne ST, Mercer JB (1983). "Herpes zoster:treatment with cemetidine". Can Med Assoc J. 129 (12): 1284–1285. PMID 6652595.
  72. ^ 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)
  73. ^ 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. PMID 11796358.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  74. ^ 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)
  75. ^ Gebhardt BM, Varnell ED, Kaufman HE. (2004). "Acetylsalicylic acid reduces viral shedding induced by thermal stress". Curr. Eye Res. 29 (2–3): 119–125. PMID 15512958.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  76. ^ "Herpevac Trial for Women". Retrieved 2008-02-25.
  77. ^ 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. PMID 12767468.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  78. ^ 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)
  79. ^ 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)
  80. ^ 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)
  81. ^ 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. PMID 15636181.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  82. ^ 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.
  83. ^ 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. PMID 10567773.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  84. ^ 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. PMID 10551373.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  85. ^ 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. PMID 14670590.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  86. ^ Unknown (2005). "Herpes simplex virus oral". In Klasco RK (ed.) (ed.). AltMedDex System. Greenwood Village, CO: Thomson Micromedex. {{cite book}}: |editor= has generic name (help); Cite has empty unknown parameter: |chapterurl= (help)
  87. ^ Snipes W, Person S, Keith A, Cupp J. "Butylated hydroxytoluene inactivates lipid-containing viruses" Science. 1975;188(4183):64-6
  88. ^ Richards JT, Katz ME, Kern ER. "Topical butylated hydroxytoluene treatment of genital herpes simplex virus infections of guinea pigs" Antiviral Res 1985;5(5):281-90
  89. ^ Vezina C, Steben M. (2001). "Genital Herpes: Psychosexual Impacts and Counselling". The Canadian Journal of CME (June): 125–134.
  90. ^ Herpes Support Groups & Clinics
  91. ^ Herpes Viruses Association - a patient run group
  92. ^ Herpes message forum with over 4000 members
  93. ^ H-Date, a dating site for persons with either or both of HSV-1 or HSV-2
  94. ^ MPwH - Meeting People with Herpes, a dating site with over 65000 members
  95. ^ Green J, Ferrier S, Kocsis A, Shadrick J, Ukoumunne OC, Murphy S, Hetherton J. (2003). "Determinants of disclosure of genital herpes to partners". Sex. Transm. Infect. 79 (1): 42–44. PMID 12576613.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  96. ^ Webpage on social aspects of genital herpes

General

Pictures

Other

Retrieved from "https://en.wikipedia.org/w/index.php?title=Herpes&oldid=194785600"