herpes

1 viral diseases causing eruptions of the skin or mucous membrane

2 any of the animal viruses that cause painful blisters on the skin [syn: herpes virus]

English

Noun

1. A viral infection, caused by the Herpes simplex virus, marked by painful, watery blisters in the skin or mucous membranes or on the genitals

Translations

• Chinese:

  Mandarin: (pàozhěn)

Herpes simplex is a viral disease caused by Herpes simplex viruses (HSV). 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. Infection of the genitals, commonly known as herpes, is the second most common form of herpes. Disorders such as herpetic whitlow, herpes gladiatorum, ocular herpes, herpes encephalitis, Mollaret's meningitis, neonatal herpes, and possibly Bell's palsy are also caused by herpes simplex viruses. Herpes simplex is not typically life-threatening for immunocompetent people.

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.

HSV is most easily transmitted by direct contact with a sore or the body fluid of an infected individual. Transmission may also occur through skin-to-skin contact when no symptoms are present if the infected person is experiencing asymptomatic shedding. Despite this risk, barrier protection methods are the most reliable method of preventing transmission of herpes. Oral herpes is easily diagnosed if the patient presents with the common 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. Socioeconomic status appears to be an important factor associated with infection levels. Additionally, studies have identified several increased risk factors for both strains of herpes.

There is currently no cure for herpes; no vaccine is currently available to prevent or eliminate herpes. Treatments are available to reduce viral reproduction and shedding, prevent the virus from entering the skin, and reduce the severity of herpetic symptoms.

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 newborn infants, transplant recipients, or AIDS patients are prone to severe complications from HSV infections.

In all cases HSVs are never removed from the body by the immune system. Following the cessation of active symptoms, the virus enters the nerves surrounding the primary lesion, migrates to the cell body of the neuron, and becomes latent in the trigeminal ganglion.

Herpes infections are largely asymptomatic, but when symptoms appear, they will typically resolve within two weeks. 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 be confused with canker sores, fever, and sore throat.

Genital infection

Clusters of inflamed papules and vesicles on the outer surface of the genitals resembling cold sores, 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. 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. It 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. It is also often observed in thumb-sucking children with primary HSV-1 infection, and in adults aged 20 to 30 following contact with HSV-2-infected genitals. Herpes whitlow is also caused by autoinoculation of HSV into an already infected person's broken skin, prior to the individual developing antibodies against the virus.

Herpes gladiatorum

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, and include skin ulceration on the face, ears, and neck. This disorder may cause fever, headache, sore throat and swollen glands, and occasionally affects the eyes. Physical symptoms sometimes recur in the skin. 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. 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.

Herpes simplex encephalitis

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. HSE is thought to be caused by the retrograde transmission of virus from a peripheral site on the face to the brain along a nerve axon following HSV-1 reactivation. About 1 in 3 cases of HSE result from primary HSV-1 infection predominantly occurring 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. 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.

Without treatment, HSE results in rapid death in around 70% of cases. Among young adults, genital herpes infections are increasingly caused by HSV-1. The risk of transmission is 30-57% in cases of primary infection acquisition by the mother 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 presence of significant titer of protective maternal antibodies in the fetus from about the seventh month of pregnancy. However, shedding of HSV-1 from both primary genital infection and reactivation is associated with high transmission from mother to infant. 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. 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 (SEM) herpes, disseminated (DIS) herpes, and central nervous system (CNS) herpes. 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). 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 20-40% of infected neonates that have no visible lesions. Herpes simplex virus infection in the newborn "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 labor be delivered by cesarean section. Women whose herpes is not active can be managed with acyclovir.

Viral meningitis

HSV-2 is the most common cause of Mollaret's meningitis, a type of recurrent viral meningitis. 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.

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. 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.

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. 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. 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.

Alzheimer's disease

Scientists discovered a link between Herpes Simplex Type I and Alzheimer’s disease in 1979. In the presence of a certain gene variation (APOE-epsilon4 allele carriers), HSV type 1 appears to be particularly damaging to the nervous system and increases one’s risk of developing Alzheimer’s disease. The virus interacts with lipoproteins, their components, and their receptors in the brain which may lead to the development of the disease. This now makes the virus the pathogen most clearly linked to the establishment of Alzheimer’s. It is important to note, however, that 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.

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).

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. Local injury to the face, lips, eyes or mouth, trauma, surgery, wind, radiotherapy, ultraviolet light or sunlight are well established triggers. Some studies suggest changes in the immune system during menstruation may play a role in HSV-1 reactivation. 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 individuals 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.

Transmission and prevention

Herpes can be contracted through direct contact with an active lesion or body fluid of an infected person. 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.

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. 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, 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.

As with almost all sexually transmitted infections, women are more susceptible to acquiring genital HSV-2 than men. 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.

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. It can occur more than a week before or after a symptomatic recurrence in 50% of cases. 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. Occasionally, 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. Since asymptomatic individuals are often 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. This information provides population prevalence of HSV viral infections in individuals with or without active disease.

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%). Thus, 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. Women are at higher risk than men for acquiring HSV-2 infection, and the chance of being infected increases with age. Women that are seropositive for only one type of HSV fall somewhere in between but are still only half as likely to transmit HSV as the seronegative mother. Genital infection caused by HSV-1, in the U.S. is now thought to be about 50% and contributes to a rate of 6 to 20 cases of neonatal herpes per 100,000 live births in the U.S. depending on region and demographics.

Canada

Following a study in Ontario, up to 55% of Canadians age of 15 to 16, and 89% of individuals in their early forties are estimated have antibodies to HSV-1. Teenagers are less likely to be seropositive for HSV-2 - antibodies against this virus is 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. 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. 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, an in men in Ethiopia, Benin and Uganda. 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.

Central and South America

HSV-2 seroprevalency is high in Central and South America, relative to rates in Europe and North America with levels estimated at 20–60%. In South Korea, incidence of HSV-2 infection in those under the age of 20 is low at only 2.7% in men and 3.0% in women.

Middle East

High levels of HSV-2 (42%) and HSV-1 (97%) were found amongst pregnant women in the city of Erzurum in Eastern Anatolia Region, Turkey. 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. HSV-1 seroprevalence is 59.8% in the population of Israel and increases with age in both genders. 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. 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 from Jewish origin, living in Israel, are less likely to possess antibodies against herpes. 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, whilst 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 that have 34% and 20% seroprevalence respectively.

Australasia

In Australia the seroprevalence of HSV-1 is 76%, with differences associated with age, gender and Indigenous status. An estimated 12% of Australian adults are seropositive for HSV-2, with higher prevalence in women (16%) than in men (8%). This was most common in females and persons under 25. In this country, HSV-2 affects 60% more women than men of similar age.

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 a monophosphate (with one phosphate group), diphosphate (with two phosphate groups) and, finally, triphosphate (with three phosphate groups) form that interferes 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, which have improved solubility in water and better bioavailability when taken orally. The use of valaciclovir and famciclovir, while potentially improving treatment compliance and efficacy, are still undergoing safety evaluation in this context. 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. Antiviral medications are also available as topical creams for treating recurrent outbreaks on the lips although their effectiveness is disputed. Penciclovir cream has a far longer cellular half-life than aciclovir cream – 10-20 hours for penciclovir versus 3 hours for aciclovir - increasing its effectiveness relative to aciclovir when topically applied.

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. 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 and was the subject of a US nationwide class-action suit in March, 2007 due to the misleading claim that it cut recovery times in half. 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, which forms a "shield" at the area of application to prevents a sore from increasing in size and decrease viral spreading during the healing process.

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. This is an off-label use of the drug. It and probenecid have been shown to reduce the renal clearance of aciclovir. 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 (also called 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. 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.

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. 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.

Lysine supplementation has been used for the prophylaxis and treatment of herpes simplex in doses exceeding 1 g/day; smaller doses appear ineffective. Aloe vera is available as cream or gel which makes an affected area heal faster, and may even prevent recurrences. Lemon balm (Melissa officinalis), has antiviral activity against HSV-2 in cell culture, and may reduce HSV symptoms in herpes infected people.However, there is no evidence for efficacy of this compound in humans. There are conflicting reports about the effectiveness of extracts from the plant echinacea in treating herpes infections, suggesting a possible benefit for treating oral, but not genital, herpes. 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 although, used alone, it is not considered potent enough to be an effective treatment. 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. The plant Prunella vulgaris, commonly known as "selfheal", also prevents expression of both type 1 and type 2 herpes in cultured cells.

Lactoferrin, a component of whey protein, has been shown to have a synergistic effect with aciclovir against HSV in vitro. Some dietary supplements have been suggested to positively treat herpes. These include vitamin C, vitamin A, vitamin E, and zinc. Butylated hydroxytoluene (BHT), commonly available as a food preservative, has been shown in cell culture and animal studies to inactivate herpes virus. However BHT has not been clinically tested and approved to treat herpes infections in humans.

Psychological and social effects

Since there is currently no cure for herpes, some people experience negative feelings related to the condition following diagnosis, particularly if they have acquired the genital form of the disease. Though these feelings lessen over time, they can include depression, fear of rejection, feelings of isolation, fear of being found out, self-destructive feelings, and fear of masturbation. In order to improve the well-being of people with 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.

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'. 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

External links

General

• Genital Herpes Fact Sheet at The Centers for Disease Control and Prevention
• Paper - Genital Herpes: A Hidden Epidemic at FDA

Images

• Links to genital herpes pictures (Hardin MD/University of Iowa
• Herpes photo library at Dermnet
• Pictures of Orofacial Herpes (Coldsores) (VisualDxHealth)
• Genital Herpes Pictures

Other

• Herpes Blood Tests Quick Reference Guide
• Updated Herpes Handbook from Westover Heights Clinic
• "The Importance and Practicalities of Patient Counseling in the Prevention and Management of Genital Herpes" (2004) at Medscape
• International Herpes Management Forum
• Provides Ratios of Lysine to Arginine in Common Foods

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