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Herpes Virus
Source:  http://en.wikipedia.org/wiki/Herpes

Herpes simplex is a viral infection caused by one of two Herpes Simplex Viruses (HSV), members of the Herpesviridae family. Manifestations of herpes infections vary significantly between individuals. Most cases of genital herpes are caused by HSV-2. It 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.[1]

HSV disease

There are two types of Herpes Simplex Virus: HSV Type 1 and HSV Type 2. The ways in which herpes infections manifest themselves vary tremendously among individuals. The following are general descriptions of the courses outbreaks may take in the oral and genital regions.

Infectious fluid-filled blister on lower lip (herpes labialis)
Infectious fluid-filled blister on lower lip (herpes labialis)

Herpes is also formed on the tongue as bumps or white dots

Orofacial infection (generally HSV-1)

  1. Prodromal symptoms
  2. Skin appears irritated
  3. Sore or cluster of fluid-filled blisters appear
  4. Lesion begins to heal, usually without scarring


It is estimated that 50% of adults in the United Kingdom are carriers of the Herpes Simplex Virus,[2] many of which will never exhibit any symptoms of infection. Similarly, 50% of Americans have HSV-1 antibodies in their blood by the time they're teenagers or young adults and 80-90% of Americans have HSV-1 antibodies by the time they are over age 50.[3] It is also possible for the virus to be transmitted across the skin in the absence of a coldsore. Oral herpes lesions typically occur on the lips, but can occur almost anywhere on the face. They can also occur on the fixed mucosa inside the mouth, including the
hard palate (roof of the mouth), and gingiva (gums). Oral herpes and cold sores can sometimes be confused with canker sores. Only a medical physician can provide adequate diagnosis.

 

Genital infection (generally HSV-2)

  1. Prodromal symptoms
  2. Itching in affected area
  3. Sore appears
  4. Lesion begins to heal, usually without scarring.

In males, the lesions may occur on the shaft of the penis, in the genital region, on the inner thigh, buttocks, or anus. In females, lesions may occur on or near the pubis, labia, clitoris, vulva, buttocks, or anus. This may require a very careful examination; for example, during delivery, examination by use of a flashlight may be necessary. Symptoms can be confused with that of chlamydia or gonorrhea, so careful observation by a doctor is important.

The appearance of herpes lesions and the experience of outbreaks in these areas varies tremendously among individuals. Herpes lesions on/near the genitals may look like cold sores. An outbreak may look like a paper cut, or chafing, or appear to be a yeast infection. Symptoms of a genital outbreak may include aches and pains in the area, discharge from the penis or vagina, and severe discomfort and burning when urinating.

Initial outbreaks are usually more severe than subsequent ones, and generally also involve flu-like symptoms and swollen glands for a week or so. Subsequent outbreaks tend to be periodic or episodic, typically occur four to five times a year, and can be triggered by stress, illness, fatigue, menstruation, and other changes. The virus sequesters in the nerve ganglia that serve the infected dermatome during non-eruptive periods, where it cannot be conventionally eliminated by the body's immune system.

Outbreak triggers

Oral herpes

Physical or psychological stress can trigger an outbreak. Local injury to the face, lips, eyes or mouth, as through trauma, surgery, or sunburns are well established triggers of recurrent orolabial herpes due to herpes simplex virus type 1 (HSV-1). Similarly, intercurrent infections, such as upper respiratory viral infections or other febrile diseases, can cause outbreaks, hence the historic terms "cold sore" and "fever blister". Generalized psychological stress and anxiety are also triggers.

Genital herpes

Controversy exists about triggers of recurrent outbreaks of genital herpes, typically due to HSV-2. It is often stated that stress, menstruation, diet (such as foods high in arginine, like chocolate, peanuts and walnuts) or sexual activity may increase the chance and severity of outbreaks. However, no scientific studies have clearly documented such triggers, and the objective data available suggest that outbreaks are not influenced by stressful events, anxiety, depression, or similar influences. The clinical experience of most experts involved in clinical care is that attempts by infected persons to modify external triggers is virtually never effective in controlling symptomatic oubreaks of genital herpes. Similarly, neither objective data nor biological plausibility support the notion that excessive usage of antibiotics affect the immune system's ability to keep the disease within the nerve ganglia (particularly as antibiotics are useless against viruses of any type) or otherwise affect herpes recurrences, nor the occasional assertion that "chronic" genital herpes is in any way related to low-level food allergy.

 

Symptoms

Herpes infections, whether initial or recurring, are usually first felt as a tingling and/or itching sensation in the affected location. These initial feelings are usually followed, depending on how severe the infection is, by the emergence of a raised or swollen area on the skin. This swollen area then becomes painful in general, but acutely sore when touched, stretched or moved. Eventually the sore area will abscess, and emit a virus laden clear fluid for several days before scabbing over. Once scabbed over the lesion will usually heal completely within a period of a week to ten days. In immuno-compromised individuals this cycle can be significantly protracted.

From the onset of infection/outbreak, many patients experience headaches, fatigue (sometimes extreme), and peculiar twitching sensations in the nerves that lead to the area of the outbreak. The fatigue associated with herpes infections can concatenate with depression brought on by the cosmetic or sexually compromising nature of the infection, to yield a deeply gloomy overall mental state that some believe can contribute to increasing the length and severity of an infection.

Transmission

Herpes is contracted through direct skin contact (not necessarily in the genital area) with an infected person, and less frequently by indirect contact (for instance, by sharing lip balm or a virus infested shared towel). The virus travels through tiny breaks in the skin (or mucous membranes in the mouth and genital areas), so, healthy skin and mucous membranes are normally an effective barrier to infection. However, in the case of mucous membranes, even microscopic abrasions are sufficient to expose the nerve endings into which the virus splices itself. This is why most herpes transmission happens in mucous membranes, or in areas of the body where mucous membranes and normal skin merge (e.g., the corners of the mouth).

Symptoms usually appear within 2 weeks. The sores usually heal within 2 - 4 weeks. [7]

Transmission was thought to be most common during an active outbreak; however, in the early 1980s, it was found that the virus can be shed from the skin, saliva and genital secretions in the absence of symptoms.

 

Recurrence

Herpes recurs only at a site of previous infection. The periodicity (frequency) and amplitude (severity) of recurrence varies greatly depending on the individual and various environmental factors including stress (both physical and mental). Often, for a given site, the infection will recur only two or three times, with severity attenuating (decreasing) each time. The mechanism by which the body seems to gain the upper-hand for a given recurrence site is poorly understood by the medical community.

Self reinfection

Self reinfection, known medically as autoinoculation, is more likely during intensely virulent initial infection with either HSV-1 or HSV-2 in a given infection site. The most common manifestations are herpetic whitlow, a pustular lesion typically of a finger, and herpes of the eye (keratitis, keratoconjunctivitis).

General hygiene principles suggest that persons with recurrent oral or genital herpes should avoid direct contact with active lesions and should wash their hands immediately after using the toilet or touching the area of an oral lesion, to further limit the low risk of autoinoculation.

In cases where herpes is present in an area where the dermis is subject to high abrasive forces (such as the often irritated shaved beard region, or the surfaces of the penis and vagina during vigorous sexual activity), it is quite common to spread an initial lesion to other sites, which then become highly virulent initial infections, and so on. The medical community has failed to make this very obvious fact clear to patients and this has resulted in great amplification of their general misery, not to mention the much higher likelihood that a person infected in multiple sites (whether genital, or otherwise) will spread this disease to friends, family and sexual partners.

 

Asymptomatic shedding

HSV asymptomatic shedding is believed to occur on 2.9% of days while on antiviral therapy, versus 10.8% of days without. Shedding is known to be 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.[8] There are some indications that some individuals may have much lower patterns of shedding, but evidence supporting this is not fully verified. Sex should always be avoided in the presence of symptomic lesions. Oral sex performed by someone with oral lesions or other symptoms should be avoided, to avoid transmission of HSV-1 to the partner's genitals. Even without symptoms it is possible for transmission to occur. Many people still believe Herpes cannot be transmitted through oral sex. This is a dangerous myth.

Women are more susceptible to acquiring genital HSV-2 than men; in the US, 11% of men and 23% of women carry HSV-2.[9] On an annual basis, without the use of antivirals or condoms, the transmission risk 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. [10] 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.

Prevention

For genital herpes, condoms are a highly recommended way to limit transmission of herpes simplex infection, as demonstrated in research. [10][11] However, condoms are by no means completely effective. The effectiveness of this method is somewhat limited on a public health scale by the limited use of condoms in the community [12]; and on an individual scale because some blisters may not be covered by the condom, or free virus in female vaginal fluid may enable infection around the base of the penis or testicles not covered by the condom.

Condoms do not prevent the condom wearer from spreading the infection to new sites either on himself through abrasion (if he is already infected and suffering an outbreak), or on the female partner if she is suffering from an outbreak and the sexual activity spreads this infection from one site to another on her own body (see "Self Reinfection" above).

The use of condoms or dental dams can limit 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 valaciclovir, in conjunction with a condom, has been demonstrated to decrease further the chances of transmission to the uninfected partner, and the Food and Drug Administration (FDA) approved this as a new indication for the drug in August 2003.

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. [13]

Other measures that have been suggested include:

  • Abstinence from sexual activity while HSV blisters are present
  • Avoidance of cross-infecting new sites on the body if HSV blisters are present
  • Gentle and well lubricated as opposed to vigorous, abrasive sex
  • Thorough washing of the genitals after sex
  • Not ejaculating inside a partner during sex (if herpes lesions have appeared inside the urethra)
  • Management of stress
  • Adequate sleep and nutrition
  • Use of a lip protectant or lip gloss to avoid cracks and abrasions through which the virus may infect
  • Treatment using ascorbate-Cu(II) [14]

 

Future 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. 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-1 infection at the time they got the vaccine. Because about 50% of persons in the United States have HSV-1 infection, this further reduces the population for whom this vaccine might be appropriate.

Treatment

Currently, there is no cure for herpes. There is no treatment that can eradicate herpes virus from the body at reactivations of the virus. Non-prescription analgesics can reduce pain and fever during initial outbreaks.

 

Anti-viral Medication

There are several prescription antiviral medications for controlling herpes outbreaks, including aciclovir (Zovirax), valaciclovir (Valtrex), famciclovir (Famvir), and penciclovir. Aciclovir was the original and prototypical member of this class and generic brands are now available at a greatly reduced cost. Some prescription drugs to treat herpes can cause diarrohea several times a day so patients are advised to take non prescribed diarrohea tablets as required in these cases along with the medication. It has been claimed that the evidence for the effectiveness of topically applied cream for recurrent labial outbreaks is weak.[15] Likewise oral therapy for episodes is inappropriate for most non-immunocompromised patients, whilst there is evidence for oral prophylactic role in preventing recurrences.[16]

Valaciclovir and famciclovir are prodrugs of aciclovir and penciclovir respectively, with improved oral bioavailability (55% vs 20% and 75% vs 5% respectively). These 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. Penciclovir's primary advantage over aciclovir 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.

Aciclovir is the recommended antiviral for suppressive therapy 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. [17] 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. [18]


Other drugs exhibiting anti-viral activity

Docosanol (Abreva) is another treatment that may be effective. Docosanol works by preventing the virus from fusing to cell membranes, thus barring entry into the cell for the virus. This may keep an outbreak contained to a smaller area than would otherwise be observed.

Zilactin is an early relief cold sore/fever blister gel that works by applying the gel, which when dry forms a "shield" to prevent the sore from increasing in size and prevents spreading by breakage or oozing during the healing process.

Tromantadine is another antiviral drug effective against herpes.

 

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 [19] [20] [21] . This is an off-label use of the drug.

It and probenecid have been shown to reduce the renal clearance of aciclovir. [22] 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.

Availability of non-generic prescriptions

 

Availability of generic prescriptions

  • Acyclovir is no longer under US patent protection, available in generic form

 

Drugs in development

  • BILS 179 BS, BILS 45 BS, BILS 22 BS, also inhibitors of helicase-primase enzyme, researched in Ridgefield, Connecticut, by James Crute's team at Boehringer Ingelheim Pharmaceuticals. [25][26]

 

Natural compounds

Lysine

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. [30] 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. [31]

Tissue culture studies have shown the suppression of viral replication when the lysine to arginine ratio in vitro favours lysine. The therapeutic consequence of this finding is unclear, but dietary arginine may affect the effectiveness of lysine supplementation. [32]

Lysine intake may be supplemented by varying the diet. Dairy products offer the highest ratio of lysine to arginine amino-acid content. Contrarily, nuts (and peanuts, even though they aren't true nuts), deliver a large dose of arginine. To help forestall outbreaks, you might avoid nuts during stressful periods, and eat cheese any time you do eat nuts. During an outbreak, eating cheese may slow the spread of lesions, and reduce virus shedding and self-reinfection. Eating 100g (~4oz) of Parmesan cheese supplies 3.3g of lysine, vs. 1.3g of arginine. The same amount of almonds provides 0.7g of lysine, but 2.4g of arginine. (Cf. the Danish Food Composition Databank, http://www.foodcomp.dk/fcdb_alphlist.asp)

High doses of lysine (greater than 10 grams daily) are known to cause gastrointestinal adverse effects. Dyspepsia was reported in 3 of 114 subjects treated with L-lysine in one study. [31] Prolonged and/or very high lysine doses may also have adverse effects on renal function, indeed lysine is contraindicated in lysine hypersensitivity and kidney or liver disease. (Anon., 2005) One patient, with a history of risk factors for renal impairment, developed tubulointerstitial nephritis (Fanconi's Syndrome) after taking lysine 3000 mg daily for approximately 5 years. [33]

 

Polysaccharides

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.[34] 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 Gigartina skottsbergii seaweed inhibited the replication activity of HSV-1 and HSV-2 in infected mouse astrocyte nerve cells and vero cells.[35]

 

Lactoferrin

Lactoferrin, a component of whey protein, has been shown to have a synergistic effect with aciclovir against HSV in vitro.[36] The concentration of lactoferrin which achieved 50% of maximum effectiveness observed (that is, the EC50) also acted in synergy with aciclovir; the concentration required to achieve EC50 for each substance was reduced "two- to seven-fold."

 

Resveratrol

Resveratrol, a compound in red wine, has been shown by researchers to prevent HSV replication in vitro by inhibiting a protein needed by the virus to replicate. Resveratrol alone was not considered potent enough by the researchers to be an effective treatment.[37] A more recent in vivo study in mice showed the efficacy of topical resveratrol cream in preventing cutaneous HSV lesion formation.[38] Research on a much more potent derivative of resveratol, named stil-5, is ongoing. There is no evidence that red wine consumption provides any similar benefits.

 

Unproven

Limited evidence suggests that low dose aspirin (125 mg daily) might be beneficial in patients with recurrent HSV infections. 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. [39] A recent animal study found that aspirin inhibited thermal stress-induced ocular viral shedding of HSV-1, and a possible benefit in reducing recurrences. [40] 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 anti-viral effects of aspirin.

 

Other

The evidence for the effectiveness of zinc and Vitamin C supplementation is poor. [41] 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 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.[42] In-vivo studies in animals confirmed the anti-viral activity of BHT against genital herpes.[43] However BHT has not been clinically tested and approved to treat herpes infections in humans.

 

Latent infection and biology

The herpes virus is a double-stranded DNA (dsDNA)-type virus. Herpes establishes a latent infection in cells of the nervous system. Double-stranded DNA is incorporated into the cell physiology by infection of the cell nucleus, where a loop of dsDNA is maintained. During inactive, or latent, periods of the infection, a subset of the Herpes genome termed LAT or Latency Associated Transcript is active and may be involved in maintenance of latency.

 

Long-term effects

The long-term effects of herpes are not well known, but the blisters may leave scars, and historically it was thought to contribute to the risk of cervical cancer in women. Subsequently, another virus, human papillomavirus (HPV), has been shown to be a primary cause of cervical cancer in women. Additionally, people with herpes are at a higher risk of HIV transmission because of open blisters. In newborns, however, herpes can cause serious damage: death, neurological damage, mental retardation, and blindness.

The immune system is able to destroy active herpes virus particles but the herpes virus has the ability to hide from the immune system in an inactive (or latent) state. Current research suggests that this ability to hide may be achieved via modification to cellular enzyme histone deacetylases (HDACs), namely HDAC1 and HDAC2. [44] Hypothetically, by interfering with the HDAC enzymes' effectiveness, it may be possible to block the virus's ability to hide from the immune system, leading to a complete elimination of the virus by the immune system. Studies on the impact of HDAC inhibitors on viral latency are ongoing in the HIV arena.

 

Obstetric / Neonatal risks

Recurrent genital herpes has very significant obstetrical/neonatal risks associated with it, and probably may merit treatment with acyclovir as an independent problem. [45]

 

Viral Meningitis

It is reasonably well-established in the last few years that herpes simplex virus 2 (HSV-2) is the most common cause of recurrent viral meningitis (Mollaret's meningitis). [46]

 

Psychological and social effects

Herpes can have a dramatic effect on an individual's mental well-being and sexual behaviour.

 

Quality of life issues

Upon diagnosis of genital herpes, people can experience a number of negative feelings related to the condition. Though these feelings lessen over time, they can include:[47]

  • depression 81%
  • fear of rejection 75%
  • feeling of isolation 69%
  • fear of being found out 55%
  • self-destructive feelings 28%

The impact of genital herpes included:

  • partial or complete cessation of sexual activity
  • total or partial loss of interest in sex
  • decreased sexual pleasure
  • sex life more inhibited and less spontaneous
  • anxiety related to sexual desirability
  • increased depression

In order to improve the well-being of people with herpes, a number of support groups [48], communities [49] and dating sites [50][51] have formed a presence on the Internet.

 

Myths

Some common misconceptions about herpes are:

  • that it is fatal. Fact: This is only true for newborns, which is rare, but it is fatal in 25% of all such cases. It can also possibly kill an adult if it infects the brain causing encephalitis, or infects the meninges causing meningitis.
  • that it only affects the genital areas. Fact: It can affect any part of the body. If you touch a genital herpes sore and then touch another part of your body, you can potentially spread the virus.
  • that condoms are completely effective in preventing the spread of this disease. Fact: They do greatly improve protection but are imperfect, only preventing transmission 50% of the time.
  • that it is only transmittable in the presence of symptoms. Fact: There is more viral shedding during an outbreak but it's possible to transmit any time.
  • that it can make you sterile Fact: Genital Herpes cannot make you sterile.
  • that Pap smears detect herpes Fact PAP smears are not designed to detect herpes simplex virus infections. Type-specific serology tests and viral cultures are used to diagnose genital herpes and are not normally conducted during a woman's annual gynecological examination.
  • that it can not be transmitted between the genitals and the mouth. Fact: Even the use of a condom will not prevent transmission between genital and oral regions.
  • that only promiscuous people get it. Fact: It is so common that anyone can contract it. The more sexual partners an individual has, however, the more likely they are to contract the disease.[60]

There is a basis in fact that herpes could be transmitted via an inanimate object such as a toilet seat or wet towel but the conditions required for this kind of transmission (high heat, high moisture, and a vulnerable exposure site) make it extremely unlikely. Although there are no confirmed cases of this type of transmission, sharing a towel with somebody with active lesions should be avoided. Likewise, sharing lip or mouth products (toothbrushes, lipstick, lip balm, or similar) with somebody with active lesions should also be avoided.

 

 References: Click Here (Listed in Wikipedia)

External links

Source:  http://en.wikipedia.org/wiki/Herpes