(Redirected from Cold sores)
The term 'herpes' generally refers to a 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 to infect humans, causing a variety of illnesses ranging from cold sores to brain infection (
encephalitis) to
chickenpox to various cancers.
Herpes virus
HSV-1 and HSV-2 are members of the
Alphaherpesvirus subfamily. HSV-1 (usually the cause of oral herpes which many people call "cold sores") can also be spread to the genitals via oral sex. HSV-2 (usually the cause of genital herpes) can also be spread to the oral region, although this is somewhat less common. For most people who carry the HSV-1 and/or HSV-2 virus, symptoms are mild, infrequent, or altogether un-noticeable.
A significant number of medical institutions place the incidence of oral herpes (HSV-1), which is commonly called cold sores, between 50 and 80 percent among the American population and the incidence of genital herpes (HSV-2) over 15 percent or about one in five adults.
[ Herpes simplex ]
[ LEARN ABOUT HERPES > Fast Facts ]
[ STD Facts - Genital Herpes ]
[ Herpes ]
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 mistaken for another condition.
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 or 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 their 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 (kissing, touching, and possibly from objects such as shared drinking glasses.) 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 disseminate to the eyes or brain. This is a particular concern for newborns who might be infected by genital herpes during passage through the birth canal (the risk of this occurring is by far higher when the mother is newly infected with HSV-2 just prior to birth and lacks protective antibodies that would otherwise reduce viable virus shedding). 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. 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. The virus infection is, however, life-long and can be retriggered in some individuals by specific events, such as sunburn, stress or other infections.
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
#
Prodromal symptoms
#Skin appears irritated
#Sore or cluster of fluid-filled
blisters appear
#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,
[1] many of whom will never exhibit any symptoms of infection. Similarly, 50% of Americans have HSV-1 antibodies in their blood by the time they have become young adults, and by age 50 or over, 80-90% of Americans have HSV-1 antibodies.
[2] In the absence of a coldsore one may also transmit the virus through the skin. Oral herpes lesions typically occur on the lips, on the fixed mucosa inside the mouth, including the
hard palate (roof of the mouth), and
gingiva (gums), but can occur almost anywhere on the face. Oral herpes and cold sores can sometimes be confused with
canker sores.
Genital infection
#Prodromal symptoms
#Itching in affected area
#Sore appears
#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 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 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.
[3]
Herpes simplex encephalitis
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.
[4] 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, and causes serious long-term neurological damage in over half the survivors. Again, 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 100 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
HSV at newborn child.
Neonatal HSV disease is a rare, but serious, consequence of vertical HSV transmission from mother to newborn child. 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.
[ Australian Paediatric Surveillance Unit. Reporting of communicable disease conditions under surveillance by the APSU, 1 January to 30 September 2003, Elliott E, Rose D., , , Commun. Dis. Intell., 2003 ][ Vaccines to prevent neonatal herpes simplex virus infection, Jones CA, , , Expert Rev. Vaccines, 2004 ] Preliminary studies indicate the epidemiology in Canada is closer to Europe than to the United States. The mortality rate from neonatal HSV disease is high (up to 25%) despite current interventions with antiviral therapies. Death results from disseminated HSV disease and/or HSV encephalitis in the newborn children.
Ocular herpes
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. 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.
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. 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 oubreaks 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.
[5]
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 concactenate 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 etc.) although such infection is theoretically possible but highly unlikely due to the fragility of the virus itself. The virus travels through tiny breaks in the skin or mucous membranes in the mouth (HSV-1) and genital areas (HSV-2), however 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).
Recurrence
When genital herpes is in remission it resides at the base of the spine, in the spinal fluid. 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 two.
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.
[6] 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.
[7] 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.
Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women, Wald A, Langenberg AG, Link K, Izu AE, Ashley R, Warren T, Tyring S, Douglas JM Jr, Corey L., , , JAMA, 2001 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.
Prevention
For genital herpes,
condoms are a highly recommended way to limit transmission of herpes simplex infection, as demonstrated in research.
[ Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women, Wald A, Langenberg AG, Link K, Izu AE, Ashley R, Warren T, Tyring S, Douglas JM Jr, Corey L., , , JAMA, 2001 ][ Condom use and the prevention of genital herpes acquisition., Casper C, Wald A., , , Herpes, 2002 ] 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
[ Sex in Australia: safer sex and condom use among a representative sample of adults, de Visser RO, Smith AM, Rissel CE, Richters J, Grulich AE., , , Aust. N. Z. J. Public Health., 2003 ]; 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.
[8]
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)
[9]
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 20% 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, 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 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.
[10]
Likewise oral therapy for episodes is inappropriate for most non-immunocompromised patients, whilst there is evidence for oral prophylactic role in preventing recurrences.
[11]
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.
[12] 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.
Differential effects of famciclovir and valaciclovir on the pathogenesis of herpes simplex virus in a murine infection model including reactivation from latency, Thackray AM, Field HJ., , , J. Infect. Dis., 1996 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
[ ]
Efficacy of cimetidine in treatment of herpes zoster in the first 5 days from the moment of disease manifestation., Kapinska-Mrowiecka M, Toruwski G, , , Pol Tyg Lek., 1996.
[ ]
Herpes zoster:treatment with cemetidine., Hayne ST, Mercer JB, , , Can Med Assoc J, 1983
[ ]
In vitro cell-mediated immune reactions in herpes zoster patients treated with cimetidine., Komlos L, Notmann J, Arieli J, et.al., , , Asian Pac J Allelrgy Immunol, 1994
. This is an
off-label use of the drug.
It and
probenecid have been shown to reduce the renal clearance of aciclovir.
Multiple interactions of cimetidine and probenecid with valaciclovir and its metabolite acyclovir, De Bony F, Tod M, Bidault R, On NT, Posner J, Rolan P., , , Antimicrob. Agents Chemother., 2002 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 protection expiring June 2009
★
Famciclovir (
Novartis) is protected under protection expiring Sept 2010
★
Penciclovir (
GlaxoSmithKline) is protected under protection expiring Sept 2010
★
Docosanol (
Avanir) is protected under 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.
Two new anti-herpes drugs tested Winstead ER.
New helicase-primase inhibitors as drug candidates for the treatment of herpes simplex disease, Kleymann G, Fischer R, Betz UA, Hendrix M, Bender W, Schneider U, Handke G, Eckenberg P, Hewlett G, Pevzner V, Baumeister J, Weber O, Henninger K, Keldenich J, Jensen A, Kolb J, Bach U, Popp A, Maben J, Frappa I, Haebich D, Lockhoff O, Rubsamen-Waigmann H., , , Nat. Med., 2002 ★ ''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.
Herpes simplex virus helicase-primase inhibitors are active in animal models of human disease, Crute JJ, Grygon CA, Hargrave KD, Simoneau B, Faucher AM, Bolger G, Kibler P, Liuzzi M, Cordingley MG., , , Nat. Med., 2002
Isolation and characterization of herpes simplex virus type 1 resistant to aminothiazolylphenyl-based inhibitors of the viral helicase-primase, Liuzzi M, Kibler P, Bousquet C, Harji F, Bolger G, Garneau M, Lapeyre N, McCollum RS, Faucher AM, Simoneau B, Cordingley MG., , , Antiviral Res., 2004 ★
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.
Cdk inhibitory nucleoside analogs prevent transcription from viral genomes., Schang LM, Coccaro E, Lacasse JJ., , , Nucleosides Nucleotides Nucleic Acids., 2005
Roscovitine inhibits activation of promoters in herpes simplex virus type 1 genomes independently of promoter-specific factors, Diwan P, Lacasse JJ, Schang LM., , , J. Virol., 2004
Advances on cyclin-dependent kinases (CDKs) as novel targets for antiviral drugs, Schang LM., , , Curr. Drug Targets Infect. Disord., 2005 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.
Management of genital herpes in men with 0.5% Aloe vera extract in a hydrophylic cream: a placebo-controlled, double-blind study., Syed TA, Afzal M, Ahmad SA, et al., , , J Dermatol Treat., 1997 Lactoferrin
Lactoferrin, a component of whey protein, has been shown to have a synergistic effect with aciclovir against HSV ''in vitro''.
Lactoferrin and lactoferricin inhibit Herpes simplex 1 and 2 infection and exhibit synergy when combined with acyclovir, Andersen JH, Jenssen H, Gutteberg TJ., , , Antiviral Res., 2003 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 EC
50 for each substance was reduced "two- to seven-fold."
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.
Treatment of recurrent herpes simplex infections with L-lysine monohydrochloride, McCune MA, Perry HO, Muller SA, O'Fallon WM., , , Cutis., 2005 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.
Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis, Griffith RS, Walsh DE, Myrmel KH, Thompson RW, Behforooz A., , , Dermatologica., 1987
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.
A multicentered study of lysine therapy in Herpes simplex infection, Griffith RS, Norins AL, Kagan C., , , Dermatologica., 1978
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 (~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.
Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis, Griffith RS, Walsh DE, Myrmel KH, Thompson RW, Behforooz A., , , Dermatologica., 1987 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.
Fanconi's syndrome and tubulointerstitial nephritis in association with L-lysine ingestion., Lo JC, Chertow GM, Rennke H, Seifter JL., , , Am. J. Kidney Dis., 1996 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.
Vaginal formulations of carrageenan protect mice from herpes simplex virus infection, Zacharopoulos VR, Phillips DM., , , Clin. Diagn. Lab. Immunol., 1997 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.
Inhibitory action of natural carrageenans on Herpes simplex virus infection of mouse astrocytes, Carlucci MJ, Scolaro LA, Damonte EB., , , Chemotherapy, 1999 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.
Resveratrol inhibition of herpes simplex virus replication, Docherty JJ, Fu MM, Stiffler BS, Limperos RJ, Pokabla CM, DeLucia AL., , , Antiviral Res., 1999 A more recent ''
in vivo'' study in mice showed the efficacy of topical resveratrol cream in preventing cutaneous HSV lesion formation.
Effect of topically applied resveratrol on cutaneous herpes simplex virus infections in hairless mice, Docherty JJ, Smith JS, Fu MM, Stoner T, Booth T., , , Antiviral Res., 2004 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.
Aspirin in the management of recurrent herpes simplex virus infection, Karadi I, Karpati S, Romics L., , , Ann. Intern. Med., 1998 A recent animal study found that aspirin inhibited thermal stress-induced ocular viral shedding of HSV-1, and a possible benefit in reducing recurrences.
Acetylsalicylic acid reduces viral shedding induced by thermal stress, Gebhardt BM, Varnell ED, Kaufman HE., , , Curr. Eye Res., 2004 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.
AltMedDex System, Unknown, , , Thomson Micromedex, 2005, 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.
[14] ''In-vivo'' studies in animals confirmed the anti-viral activity of BHT against genital herpes.
[15] 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 the 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.
Herpes simplex virus 1 gene expression is accelerated by inhibitors of histone deacetylases in rabbit skin cells infected with a mutant carrying a cDNA copy of the infected-cell protein no. 0, Poon AP, Liang Y, Roizman B., , , J. Virol., 2003 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.
randomised placebo controlled trial of suppressive acyclovir in late pregnancy in women with recurrent genital herpes infection, Brocklehurst P, Kinghorn GA et al., , , , 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).
[ Recurring viral meningitis & herpes II ]
Psychological and social effects
The herpes virus can have a dramatic effect on an individual's mental well-being and sexual behaviour.
Quality of life issues
Upon diagnosis of the herpes virus, people can experience a number of negative feelings related to the condition. Though these feelings lessen over time, they can include:
[ Genital Herpes: Psychosexual Impacts and Counselling, Vezina C, Steben M., , , The Canadian Journal of CME, 2001 ]
★ depression 81%
★ fear of rejection 75%
★ feeling of isolation 69%
★ fear of being found out 55%
★ self-destructive feelings 28%
★ fear of masturbation 13%
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
[16], communities
[17] and dating sites
[18][19] have formed a presence on the Internet.
Media portrayal
Media portrayals of genital herpes - which might help to destigmatise the condition - remain few and, when they occur, are often negative.
[20]
Examples of such portrayals in the main types of media include:
★ in the mainstream press, a 1982 article in ''Time'' magazine called “Herpes: Today’s Scarlet Letter”;
[21]
★ on television, a 1983 telefilm called “Intimate Agony”;
[22]
★ in music, a 1993
Marilyn Manson song called “Herpes”;
[23]
★ in the cinema, a 2005 film called “Merry Christmas… I Got You Herpes”;
[24]
★ in literature, a 2006 novel called “Stigma”;
[25]
Disclosure to new partners
People with the herpes virus are often hesitant to divulge to other people that they have the virus, including friends and family but especially new or potential sexual partners. People may be less likely to inform what they consider to be 'casual' partners.
[ Determinants of disclosure of genital herpes to partners., Green J, Ferrier S, Kocsis A, Shadrick J, Ukoumunne OC, Murphy S, Hetherton J., , , Sex. Transm. Infect., 2003 ]
In addition, the perception of the likely reaction is sometimes taken into account before making a decision about whether to inform new partners and at what point in the relationship. Many people choose not to disclose their herpes status when they first begin dating someone, but wait until it later becomes clear that they are moving towards a sexual relationship. Other people disclose their herpes status upfront. Still others choose only to date other people who already have herpes.
Reactions by sexual partners may not always be negative, and individuals often use various strategies to mitigate the impact of disclosure such as keeping the issue "low key," choosing a relaxed environment and suggesting the couple being tested jointly for a range of sexually transmitted infections.
Legal redress
Whether the law can help a person who catches herpes depends on the
jurisdiction where it was contracted as legal jurisdictions define their own rules regarding the transmission of STIs such as herpes.
[26] There can be both criminal and civil possibilities. For example, in the 'criminal' case of R. v. Sullivan heard in
England and Wales, a man was prosecuted for
sexual assault after his partner experienced a primary outbreak of genital herpes, on the basis that he had failed to reveal the fact that he had herpes. Ultimately, the man was discharged due to an inability to prove prior knowledge. 'Civil' claims for transmission of herpes are, for their part, usually based on
negligence if transmission was accidental and
battery if deliberate. The first successful case to allow such a claim in the
United States was Kathleen K. v. Robert B., decided by the California Court of Appeals.
Myths
Some common misconceptions about the herpes are:
★ 'Myth:' 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.
★ 'Myth:' 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.
★ 'Myth:' Condoms are completely effective in preventing the spread of this disease.
: 'Fact:' They do greatly improve protection but may not provide complete protection. A 2005 study showed a significant decrease in risk of HSV-2 infection in individuals who used condoms 75-100% of the time over individuals who used condoms 0-25% of the time. However, it should be noted that this study (like many condom studies) underestimates the efficacy of condoms, as it is difficult to accertain that condoms were used appropriately.
[27]
★ 'Myth:' 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.
★ 'Myth:' It can cause sterility.
: 'Fact:' Genital Herpes cannot cause sterility.
★ 'Myth:'
Pap smears can 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.
★ 'Myth:' It cannot be transmitted between the genitals and the mouth.
: 'Fact:' Cross infection between strains is possible. The virus can be spread by touching an infected area and then touching another area of the body. In sexual terms, the use of a condom may not prevent transmission between genital and oral regions.
★ 'Myth:' Only promiscuous people get it.
: 'Fact:' Anyone can contract it. The more sexual partners an individual has, however, the more likely they are to contract the disease, as they are more likely to encounter a partner who has the virus.
[28]
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
1. U.K Herpes Viruses Association - [1] ''Accessed March 15, 2007''.
2. Herpes Online: Exploring the "H" Community
3. Center for Disease Control (CDC) - Herpes Fact Sheet ''Accessed February 7, 2007''.
4.
Transolfactory spread of virus in herpes simplex encephalitis., Dinn J, , , Br Med J, 1980
5. http://www.cdc.gov/std/Herpes/STDFact-Herpes.htm#signs
6.
Oral herpes simplex virus type 2 reactivation in HIV-positive and -negative men., Kim H, Meier A, Huang M, Kuntz S, Selke S, Celum C, Corey L, Wald A, , , J Infect Dis, 2006
7.
Percentage of people with herpes drops
8. One-Two Punch: Vaccine fights herpes with antibodies, T cells Nathan Seppa
9. Inactivation of HSV-2 by ascorbate-Cu(II) and its protecting evaluation in CF-1 mice against encephalitis., , G, Betanzos-, Journal of virological methods,
10. Evidence for efficacy of topical acyclovir in recurrent herpes labialis is weak, Graham Worrall, , , BMJ, 1996 - Letter
11. Acyclovir in recurrent herpes labialis, Graham Worrall, , , BMJ, 1996 - Editorial
12.
Current treatment options to prevent perinatal transmission of herpes simplex virus, Leung DT, Sacks SL., , , Expert Opin. Pharmacother., 2003
13. Genital Herpes
14. Snipes W, Person S, Keith A, Cupp J. "Butylated hydroxytoluene inactivates lipid-containing viruses" Science. 1975;188(4183):64-6
15. 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
16. Herpes Support Groups & Clinics
17. Herpes message forum with over 4000 members
18. H-Date, a dating site for persons with either or both of HSV-1 or HSV-2
19. MPwH - Meeting People with Herpes, a dating site with over 65000 members
20. Webpage on social aspects of genital herpes
21. ''Time'' Magazine archives
22. Film Database description of ''Intimate Agony''
23. Wikipedia article including reference to the song ''Herpes''
24. Film Database description of ''Merry Christmas...''
25. Description of novel ''Stigma''
26. Webpage on social aspects of genital herpes
27.
The relationship between condom use and herpes simplex virus acquisition, , Anna, Wald, Ann Intern Med,
28.
Myths and Facts about Genital Herpes
Further reading
★
Genital shedding of herpes simplex virus among men, Wald A, Zeh J, Selke S, Warren T, Ashley R, Corey L, , , J. Infect. Dis., 2002
External links
General
★
Genital Herpes Fact Sheet at
Center for Disease Control
★
Paper - Genital Herpes: A Hidden Epidemic at
FDA
Studies
★
Herpevac Trial for Women at
NIH
Images
★
Links to genital herpes pictures (Hardin MD/
University of Iowa)
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
العربية
中国
Français
Deutsch
Ελληνική
हिन्दी
Italiano
日本語
Português
Русский
Español
![Don\](images/articles/thumbs/beachrainthumb.jpg "Don\")
