Herpes simplex

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The term herpes is used colloquially in English to refer to a (usually) sexually transmitted, double-stranded DNA virus called herpes simplex virus (HSV) type 2 (also known as human herpesvirus 2, or HHV2). This virus is closely related to herpes simplex virus type 1 (HSV-1 or HHV1), which is the cause of common nonsexually transmitted cold sores. These two viruses are among the eight members of the herpes virus family that infect humans and cause a variety of illnesses such as cold sores, brain infection (encephalitis), chickenpox, various cancers and up to 70% of the cases of Bell's palsy (facial paralysis) [1].

A significant number of medical institutions place the incidence of oral herpes (HSV-1), commonly called cold sores, between 50 and 80 percent among the American population in the fifth decade of life. The overall HSV-1 seroprevalence is dropping a few points per decade in the US, as in all industrialized countries. African-Americans and immigrants from undeveloped countries typically have HSV-1 rates in adolescence that are two or three times higher than that of whites. As a result of lower HSV-1 seroprevalence, more 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 serious risk of vertical transmission to the neonate if contracted 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 child, whereas a recurrent infection in a woman seropositive for both HSV-1 and HSV-2 is thought to be around 1-3%.

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" other at risk groupings are people with multiple sexual partners, and those who become sexually active at a young age are all higher-risk populations for the transmission of HSV-2. <ref name = "ummc"> Herpes simplex

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. University of Maryland Medical Center  
 

 

. Retrieved on 2007-09-03.

</ref><ref name = "asha"> LEARN ABOUT HERPES > Fast Facts

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. ASHA Herpes Resource Center  
 

 

. Retrieved on 2007-09-03.

</ref><ref name = "cdc"> STD Facts - Genital Herpes

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. Centers for Disease Control and Prevention  
 

 

. Retrieved on 2007-09-03.

</ref><ref name = "stanford"> Herpes

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. Stanford University Sexual Health Peer Resource Center  
 

 

. Retrieved on 2007-09-03.

</ref> According to the American Social Health Association (ASHA), most infected people (up to 90%) don’t know they are infected because their symptoms are too mild to notice or are mistaken for another condition. <ref name = "asha" />

Herpes simplex 1 and 2 viruses are similar in that they are both transmitted by direct contact and can sometimes cause intensely painful fluid-filled blisters, containing millions of infectious virus particles. The primary difference between the two infections is the principal site of infection—mucous membranes of the lips and nearby oro-facial skin for HSV-1, and the genital skin for HSV-2. After initial infection, these viruses both travel to sensory nerves, where they reside as life-long, latent viruses. HSV-1 often infects the trigeminal ganglia that provides sensation to the lips, lower mouth and neck; while HSV-2 often infects the sacral ganglia supplying sensation to the pelvic area including the genitals, perineum and upper legs. When the viruses reactivate to cause symptomatic disease, they travel back to the respective skin areas served by these nerves, leading to the different (oral vs. genital) distributions of cold sores.

Both HSV-1 and HSV-2 are transmitted by contact with a herpetic sore (usually through kissing or touching, and possibly from objects such as shared drinking glasses.^{[citation needed]}) Transmission of these two viruses can be more complicated in that both HSV-1 and HSV-2 are shed (to a much lesser extent) from persons without active sores.

While both oral and genital herpes are characteristically "nuisance infections" that are not life-threatening, they can cause rare severe or fatal disease if they travel to the eyes or brain. This is of particular concern in the case of newborns infected by genital herpes during passage through the birth canal (the risk of this occurring is by far higher when the mother has a primary infection just prior to birth and lacks protective antibodies that would otherwise reduce viable virus shedding). HSV-1 genital herpes has been shown to be more infectious in primary episodes than HSV-2. Both oral and genital herpes infections have periods of active cold sore disease lasting 2-10 days and then remission when the cold sores disappear. The majority of cases however are asymptomatic, but asymptomatic shedding has been shown to occur. Over time, periods of remission generally increase in length, and the duration of cold sores decrease, until the person rarely has active disease. This is regulated by specific immunity developed by the patient against the virus. A previous HSV-1 infection tends to ameliorate the symptoms of a subsequent HSV-2 infection. The virus infection is, however, life-long and can be retriggered in some individuals by specific events, such as sunburn, ultraviolet light, wind, trauma, surgery, stress or other infections. Being that the virus is present but held in check by antibodies in an immunocompetent person, the weakening of the immune system in HIV or transplant patients can trigger serious HSV infections such as keratitis.

The ways in which herpes simplex infections manifest themselves vary tremendously among individuals. The following are general descriptions of the courses outbreaks may take in the oral and genital regions.

Orofacial infection

Modèle:Infobox Disease

1. Prodromal symptoms
2. Skin appears irritated and red
3. Sore or cluster of fluid-filled blisters appear
4. Lesion begins to heal, usually without scarring <ref>{{| title =Herpes Online: Exploring the "H" Community | pages =1-4 | format = PDF| language =English | publisher =American Social Health Association | date= 1996 | url =http://www.ashastd.org/pdfs/HELPER_SPRING_05.pdf | accessdate = 2007-03-29 }}</ref>

In the absence of a coldsore one may also transmit the virus through the skin. Oral herpes lesions occur on the lips, on the fixed mucosa inside the mouth, including the hard palate (roof of the mouth), and gingiva (gums)^{[citation needed]}, but can occur almost anywhere on the face. Oral herpes and cold sores can sometimes be confused with canker sores.

Genital infection

Modèle:Infobox Disease

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. Symptoms can be confused with those 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 or 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 the body's immune system cannot effect its standard eliminations. 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.<ref>Center for Disease Control (CDC) - Herpes Fact Sheet Accessed February 7, 2007.</ref>

Herpes simplex encephalitis

Modèle:DiseaseDisorder infobox Herpes simplex encephalitis is a very serious disorder, thought to be caused by the retrograde transmission of the virus from a peripheral site to the central nervous system along a nerve axon. It is known that the virus lies dormant in the ganglion of the trigeminal or fifth cranial nerve. The reason for reactivation remains unclear. It has also been proposed that the olfactory nerve may be involved.<ref>

Modèle:Cite journal</ref> Without treatment, it results in rapid death in around 70% of cases. 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. A small population of survivors, perhaps 20%, show little long-term damage. It is most common in children and middle-aged adults. Although herpes simplex is by no means the most common cause of viral encephalitis (accounting for about 10% of cases in the US), because of the high risk associated with it if it is not treated as well as being one of the few encephalitis to which definitive treatment is available, patients presenting with encephalitis symptoms are likely to be treated against this disorder without waiting for a positive diagnosis. A positive diagnosis can be obtained by CSF PCR for herpes simplex DNA, CSF viral culture or a rising titre for antibodies. The fact that the electroencephalogram is abnormal in >90% of the patients with herpes simplex encephalitis further aids the diagnosis.

The virus usually infects through the mouth and enters the nucleus of the nerve cell during the first 7 days, and will remain latent for 10 days to 10 years, and will then reactivate from common stress, fever, or a sunburn. The virus will soon be contagious through more cold sores, and the disease will start to attack the brain.

Neonatal herpes simplex

Modèle:DiseaseDisorder infobox

Neonatal HSV disease is rare but serious, usually the consequence of vertical HSV transmission from mother to newborn child, although an estimated 10% of cases are thought to be acquired postnatally from a parent, caretaker, or sibling. Primary infection of a seronegative mother in the third trimester has a 30-57% transmission rate whereas recurring infection in a seropositive mother has 1-3% transmission rate. This in part is due to the protective nature of maternal antibodies. HSV-1 neonatal herpes is extremely rare in underdeveloped countries because seroconversion to HSV-1 usually occurs in childhood or adolescence, precluding a genital HSV-1 infection. HSV-2 Infections are much more common. In developing countries 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 sizes. The resulting increase of young woman entering the child bearing years HSV-1 seronegative, has been a harbinger of increased HSV-1 neonatal herpes in developed countries, now thought to be about 50% in the U.S. and as high as 70% in Japan. Prospective active surveillance data indicate an incidence rate of 3.61 per 100,000 live births in Australia, with similar rates in the UK; but much lower than the USA which is estimated to be 6-20 per 100,000 live births depending on region and demographics. <ref name=Elliot>Modèle:Cite journal</ref><ref name=Jones>Modèle:Cite journal</ref> A recent three year study in Canada revealed a NHSV rate of 5.9 per 100,000 live births. Among the surprises in the study, 62.5 percent of cases were HSV-1 and 98.7% of transmission was asymptomatic. <ref name=Kropp>Modèle:Cite journal</ref>

Neonatal herpes manifests itself in three forms. Skin, eyes, mouth, herpes (SEM) which is characterized by external lesions but no internal organ invovment, and has the best prognosis. Lesions are likely to appear on trauma sites such as the attachment location of fetal scalp electrodes, the location of forceps or vacuum extractors, the margin of the eyes, the circumcision, or surgey locations. Disseminated Herpes, (DIS) which involves internal organ infection noteably the liver; and Central Nervous System herpes (CNS) which involves the nervous system and the brain, possibly leading to encephalitis . CNS has the highest morbidity when treated because Disseminated herpes has a higher mortality rate. SEM herpes untreated, may spread to internal organs and result in mortality or morbidity due to disseminated HSV disease and/or HSV encephalitis due to CNS Herpes. The mortality rate from neonatal HSV disease in the US is down to about 25% from as high as 85% a few decades ago, due to the advent of vidarabine, and later acyclovir antiviral therapy. The morbidity and mortality still remain high due to the inability to diagnose DIS and CNS herpes earlier and to administer anti-viral therapies earlier, in part because 20-40% of infected neonates to not have lesions, making early diagnosis difficult.

Ocular herpes

Modèle:Infobox Disease Ocular herpes (generally HSV-1) is a special case of herpes infection (herpes viral keratitis) that affects the nerves serving the cornea of the eye. It usually manifests as small white itchy lesions on the surface of the cornea, known as dendritic ulcers because they show a branching pattern. Additional symptoms include dull pain deep inside the eye, mild to acute dryness and sinusitis. Most first 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 symptoms (with or without visible lesions) include chronic dry eye, low grade intermittent conjunctivitis or chronic unexplained sinusitis. When the patient is immunocompromised or 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 the patient's own system destroying the corneal stroma. This usually results in loss of vision due to opacification of the cornea. Treatment with corneal transplants may be ineffective, as reinfection of the transplant is common; however, with concurrent use of antivirals the chance of graft acceptance is higher.

As with orofacial or genital herpes, trauma to the eye increases the chance of a recurrence.^{[citation needed]} Thus herpes viral keratitis can produce complications in the case of patients undergoing radial keratotomy by laser (lasik) to correct vision defects, and patients undergoing this procedure should be carefully screened.

Bell's Palsy

Up to 70% of the cases of Bell's palsy can be linked to the presence of HSV-1. The virus seems to cause an inflammation of the facial nerve CN-VII that controls the muscles of the face, causing paralysis of the face and inability to blink an eye. Bell's palsy is also linked to Lyme disease, chickenpox (shingles), brain tumor, or just physical trauma. In the case of an infection by HSV-1, treatment with an anti-viral and a steroid-based anti-inflammatory are recommended and improvement should be expected in 2 to 4 weeks, and full recovery within 3 to 6 months in 90% of the cases[2].

Herpes Whitlow

Herpes Whitlow is typically contracted by healthcare workers that come in contact with virus. The most common are dental workers who contract Herpes Whitlow at the rate of about 2% a year in the U.S.^{[citation needed]} Again it is the seronegative person who is at risk. It will typically manifest itself on fingers, cuticle, and is usually associated with HSV-1. A person who has already seroconverted cannot get a herpetic Whitlow.

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, wind, ultraviolet light, 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".

Genital herpes

Controversy exists about triggers of recurrent outbreaks of genital herpes, typically due to HSV-2. 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 are virtually never effective in controlling symptomatic outbreaks of genital herpes. Similarly, neither objective data nor biological plausibility support the notion that excessive usage of antibiotics affects 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 usually appear within 2 weeks. The sores usually heal within 2 - 4 weeks. This varies greatly on the individual however, as some may not exhibit any symptoms for years, and some may not show symptoms at all. <ref>http://www.cdc.gov/std/Herpes/STDFact-Herpes.htm#signs</ref>

Symptoms

Herpes infections, whether initial or recurring, are usually first felt as a tingling and/or itching sensation (like chicken pox) in the affected location. The very first outbreak is often much more severe than any recurrence.^{[citation needed]} 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 can be contracted through direct skin contact with an infected person. There are no documented cases of infection via an inanimate object (e.g. a towel, toilet seat, soap) although such infection is theoretically possible but highly unlikely due to the fragility of the virus itself.Modèle:Verify source The virus travels through tiny breaks in the skin or mucous membranes in the mouth (HSV-1) and genital areas (HSV-2), though 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). Herpes can also be transmitted by using a razor on the genital area that has previously been used on the genital area of an infected person during an outbreak. The virus can survive in the moist areas between razor blades and can then be transmitted to anyone who unknowingly uses that same razor. An important risk factor in the transmission of herpes (types 1 & 2) but particularly genital HSV-1 and the accompanying risk of neonatal herpes, is a discordant partner, i.e., a person with a history of infection (seropositive), having relations with a seronegative partner. Because a herpetic infection usually infects one site, such as the mouth in the case of HSV-1, following the initial infection, the patient develops antibodies (seroconversion) and cannot get another HSV-1 infection elsewhere, such as a herpes whitlow or genital HSV-1 infection. However even a monogamous couple, where the female is seronegative with a discordant partner (seropositive) she runs a 30% per year risk of contracting an HSV-1 infection. If she contracts an oral HSV-1 infection first, after seroconversion, she cannot get a genital HSV-1 infection.

Recurrence

The herpes virus can establish a latent state in sensory and autonomic ganglia. Although the frequency and severity of recurrent outbreaks may vary greatly depending upon the individual, physical and/or mental stress have been commonly noted as contributors to an outbreak.

Outbreaks may occur at the original site of the infection or in close proximity to nerve endings that reach out from the base of the spine. The individual may have sores in any region near the base of the spine or they may outbreak at the original site of infection.

The human body is able to build up an immunity to the virus over time. Suppressive drugs may interfere with the immune system's ability to fight the virus; however, antiviral medication has been proven to shorten the duration and/or frequency of the outbreak in the first year or so.

Studies have been conducted by major pharmaceutical companies to determine therapy results, however, the resultant claims are vague, and there hasn't been an objective governing body to determine the exact nature of the disease or its cure.

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 vulva during vigorous sexual activity), it is quite common to spread an initial lesion to other sites, which then become highly virulent initial infections.

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.<ref>

Modèle:Cite journal</ref> 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.<ref>

  Carla K. Johnson
     
   
  . 
 "
   Percentage of people with herpes drops 
     
 " , Associated Press
  , Aug 23, 2006
 
 . </ref> 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. <ref name=Wald>

Modèle:Cite journal</ref> 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.

A 2004 study of 1484 couples showed condom usage reduced transmission by 96% and suppressive therapy with valacyclovir further reduced transmission by 50% resulting in a 98% reduction in transmission over an eight month period.^{[citation needed]}

Prevention

For genital herpes, condoms are a highly recommended way to limit transmission of herpes simplex infection, as demonstrated in research. <ref name=Wald>Modèle:Cite journal</ref><ref name=Casper>Modèle:Cite journal</ref> 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 <ref name=Visser>Modèle:Cite journal</ref>; 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 his partner if they are suffering from an outbreak and the sexual activity spreads this infection from one site to another on their 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. <ref> Seppa , Nathan

  . 
 "
   One-Two Punch: Vaccine fights herpes with antibodies, T cells 
     
 " , Science News
  , 2005-01-05
  , pp. 5
    . Retrieved on 2007-03-29
 .  (English) 
  </ref>

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) <ref>Modèle:Cite journal</ref>

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-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.

Treatment

Currently, there is no cure for herpes, or 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 diarrhea several times a day so patients are advised to take non prescribed diarrhea 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.<ref>Modèle:Cite journal- Letter</ref> Likewise oral therapy for episodes is inappropriate for most non-immunocompromised patients, whilst there is evidence for oral prophylactic role in preventing recurrences.<ref>Modèle:Cite journal - Editorial</ref>

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. <ref name="Leung">

Modèle:Cite journal</ref> 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. <ref name=Thackray>

Modèle:Cite journal</ref>

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.

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.

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 <ref name=kapinska>

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.

Modèle:Cite journal</ref> <ref name=hayne>

Modèle:Cite journal</ref> <ref name=komlos>

Modèle:Cite journal </ref> . This is an off-label use of the drug.

It and probenecid have been shown to reduce the renal clearance of aciclovir. <ref name=debony>

Modèle:Cite journal</ref> 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

• Valaciclovir (GlaxoSmithKline) is protected under Modèle:US patent protection expiring June 2009
• Famciclovir (Novartis) is protected under Modèle:US patent protection expiring Sept 2010
• Penciclovir (GlaxoSmithKline) is protected under Modèle:US patent protection expiring Sept 2010
• Docosanol (Avanir) is protected under Modèle:US patent protection expiring April 2014

Availability of generic prescriptions

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

Drugs in development

• BAY 57-1293, a helicase-primase inhibitor researched by Bayer AG scientist Gerald Kleymann's team in Wuppertal, Germany. <ref name=Winstead>

  Winstead ER.
   
 

.    Two new anti-herpes drugs tested 
. Genome News Network 
   

. Retrieved on 2006-03-20. </ref><ref name=Kleymann>

Modèle:Cite journal</ref>

• 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. <ref name=Crute>

Modèle:Cite journal</ref><ref name=Liuzzi>

Modèle:Cite journal</ref>

• Roscovitine is an inhibitor of cellular cyclin-dependent kinase and seems to prevent transcription of viral genomes. Roscovitine has entered clinical trials for HIV infection. <ref name=Schang>

Modèle:Cite journal</ref><ref name=Diwan>

Modèle:Cite journal</ref><ref name=Schang2>

Modèle:Cite journal</ref>

Natural compounds

Aloe Vera

Aloe vera may benefit those with genital herpes. A double-blind trial using a 0.5% Aloe vera cream found that applying the cream three times a day shortened the healing time of genital herpes outbreaks. All but 3 of 22 persons in the study who showed healing with the aloe cream had no recurrences 15 months after stopping treatment. <ref name=Syed>

Modèle:Cite journal</ref> <ref>"

   Genital Herpes 
     
 " , Vitacost
  , 2006
 
  . Retrieved on 2007-07-16
 .  (English) 
  </ref>

Lactoferrin

Lactoferrin, a component of whey protein, has been shown to have a synergistic effect with aciclovir against HSV in vitro.<ref name=Andersen>

Modèle:Cite journal</ref> 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 sevenfold."

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. <ref name=McCune>

Modèle:Cite journal</ref> 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. <ref name=Griffith>

Modèle:Cite journal</ref>

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. <ref name=Griffith2>

Modèle:Cite journal</ref>

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 apples may slow the spread of lesions, and reduce virus shedding and self-reinfection. Eating 100g (~3.5oz) 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. <ref name=Griffith>

Modèle:Cite journal</ref> 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. <ref name=Lo>

Modèle:Cite journal</ref>

Arginine

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 and raw grains.

Melissa officinalis L. (Lemon Balm)

Of the many practical applications for Melissa officinalis L. (Lemon Balm), one is anti-viral activity against HSV-2.<ref name=Allahverdiyev>

Modèle:Cite journal</ref> The tincure may be taken orally and used topically.

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.<ref name=Zacharopoulos>

Modèle:Cite journal</ref> 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.<ref name=Carlucci>

Modèle:Cite journal</ref>

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.<ref name=Docherty99>

Modèle:Cite journal</ref> A more recent in vivo study in mice showed the efficacy of topical resveratrol cream in preventing cutaneous HSV lesion formation.<ref name=Docherty04>

Modèle:Cite journal</ref> 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.

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. <ref name=Karadi>

Modèle:Cite journal</ref> A recent animal study found that aspirin inhibited thermal stress-induced ocular viral shedding of HSV-1, and a possible benefit in reducing recurrences. <ref name=Gebhardt>

Modèle:Cite journal</ref> 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. <ref name=Altmedex>

Modèle:Cite book</ref> 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. Vitamin A from natural sources, such as cod liver oil, are neither toxic or teratogenic and can safely be taken during pregnancy. 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.<ref>Snipes W, Person S, Keith A, Cupp J. "Butylated hydroxytoluene inactivates lipid-containing viruses" Science. 1975;188(4183):64-6</ref> In-vivo studies in animals confirmed the anti-viral activity of BHT against genital herpes.<ref>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</ref> However BHT has not been clinically tested and approved to treat herpes infections in humans.

. Med Help International  
 

 

  Myths and Facts about Genital Herpes 
. Famciclovir 
 
   (2007)
     
   
 

. American Journal of Epidemiology 
 
   (1983)
     
   
 

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