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Herpes Simplex Virus

 

Herpes simplex virus
Virus classification
Group: Group I (dsDNA)
Family: Herpesviridae
Subfamily: Alphaherpesvirinae
Genus: Simplexvirus
Species: Herpes simplex virus 1 (HSV-1)
Species: Herpes simplex virus 2 (HSV-2)

The Herpes simplex virus infection (common names: herpes, cold sores) is a common, contagious, incurable, and in some cases sexually transmitted disease caused by a double-stranded DNA virus. The infection can also affect the brain, in which case the consequent disease is called herpes simplex encephalitis

Symptoms

The most obvious symptom of herpes is blisters anywhere on the body, but especially near the mouth or genital areas. Some people may experience prodromal symptoms: tingling, pain, burning, or itching in the area a few days before the blisters appear. The period from the time the blisters appear until the sores heal is known as an active outbreak.

HSV disease

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

Orofacial infection

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

These infections may appear on the lips, nose or in surrounding areas. The sores may appear to be either weeping or dry, and may resemble a pimple, insect bite, or large chicken-pox lesion. Lesions typically heal after a few days to a week (or more); this varies among individuals.

Genital infection

  1. Prodromal symptoms
  2. Sore appears
  3. Lesion begins to heal, usually without scarring

In men, the lesions may occur on the shaft of the penis, in the genital region, on the inner thigh, buttocks, or anus. In women, lesions may occur on or near the pubis, labia, clitoris, vulva, buttocks, or anus.

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

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

Other skin infections

Other forms of herpes simplex infection are rarer, but well characterized, and are sometimes given distinctive names, such as herpes gladiatorum, a skin infection spread by through wrestling and other sports involving close skin-to-skin contact

Herpes simplex encephalitis

Herpes Simplex encephalitis is a very serious disorder, thought to be caused by transmission of the infection from a peripheral site by nerve cells. 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 longterm neurological damage in over half the survivors. A small population (perhaps 20%) of survivors show little long term damage. It is most common in children and middle-aged adults. Although herpes simplex is by no means the commonest cause of viral encephalitis (accounting for about 10% of cases in the US), because of the high risk associated with it if its not treated, patients presenting with encephalitis symptoms are likely to be treated against this disorder without waiting for a positive diagnosis.

Neonatal herpes simplex

Neonatal HSV disease is a rare, but serious, consequence of vertical HSV transmission from mother to neonate. Prospective active surveillance data indicates 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. (Elliot & Rose, 2004; Jones, 2004) 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 neonate

Transmission

Herpes is contracted through direct skin contact (not necessarily in the genital area) with an infected person. The virus travels through tiny breaks in the skin or through moist areas, but symptoms may not appear for up to a month or more after infection. Transmission was thought to be most common during an active outbreak, however in the early 1980s scientists and doctors realized that the virus can be shed from the skin in the absence of symptoms. It is estimated that between 50 and 80% of new HSV-2 cases are from asymptomatic viral shedding.

HSV assymptomatic 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 HSV2. There are some indications that some individuals may have much lower patterns of shedding, but evidence supporting this is not fully supported. Sex should always be avoided in the presence of symptomic lesions.

Women are more susceptible to acquiring genital HSV-2 than men. On an annual basis, without the use of antivirals or condoms, the transmission risk 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. Supressive 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. (Wald et al., 2001) The effects of combining antiviral and condom use is roughly additive, thus resulting in approximately a 75% combined reduction in annual transmission risk. It is important to note that 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.

HSV-1 and HSV-2

There are two main kinds of herpes simplex virus; types 1 (HSV-1) and 2 (HSV-2). Both types of HSV can infect either the oral or genital regions. It is easier to acquire an HSV-1 infection in the oral region, and for most people with HSV-1, that is where outbreaks occur. It is easier to acquire an HSV-2 infection in the genital region, and for most people with HSV-2, that is where outbreaks occur.

The terminology of herpes can be quite confusing; the two viruses are sometimes referred to by the sites they preferentially infect. Thus, HSV-1 can be called "oral herpes," (or sometimes "cold sores") and HSV-2 can be called "genital herpes." However, it is perfectly possible to have an HSV-1 infection of the genitals, or an HSV-2 infection of the oral area.

Another factor adds to the confusion; herpes is also sometimes described by the site of the infection. Thus, a herpes infection located in the genital region may be called "genital herpes," and a herpes infection located in the oral region may be called "oral herpes," irrespective of which virus is actually present.

People whose herpes infections are not located in the virus's "preferred" location may experience fewer, less severe outbreaks. For example, if Alfred has an HSV-1 infection of the mouth, and Bill has an HSV-1 infection of the genitals, Alfred is likely to experience more frequent and/or severe outbreaks than Bill.

Prevalence

The incidence of herpes simplex in the United States rose 30% between 1976 and 1994. Data from National Health and Nutrition Examination Surveys (NHANES) indicate an HSV-2 seroprevalence of 21.9% of the United States population. This rate was higher among women (25.9%) than men (17.8%). Independent risk factors for HSV-2 seropositivity were female sex, African American or Mexican-American ethnic background, older age, less education, poverty, cocaine use, and a greater lifetime number of sexual partners. (Fleming et al., 1997)

Prevention

Condoms can help prevent contracting herpes, but do not work consistently because some blisters might not be covered by the condom. Abstinence is an effective way to prevent contracting or spreading this disease (including abstinence from oral sex). When one partner has herpes simplex infection and the other doesn't, the use of valaciclovir, in conjunction with a condom, has been demonstrated to further decrease the chances of transmission to the uninfected partner, and the FDA approved this as a new indication for the drug in August 2003.

The National Institutes of Health (NIH) are currently in the midst of phase III trials of a vaccine against HSV-2. The vaccine has only been shown to be effective for women who have never been exposed to HSV-1. Overall, the vaccine is approxmiately 48% effective in preventing HSV-2 seropositivity and about 78% effective in preventing symptomatic HSV-2. Assuming FDA approval, a commerical version of the vaccine is estimated to become available around 2008

Treatments

Pharmacotherapy

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. Valaciclovir and famciclovir are prodrugs of aciclovir and penciclovir respectively, with improved oral bioavailability.

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. (Thackray & Field, 1996)

Docosanol (Abreva) is another treatment that may be effective.

Non-prescription analgesics can reduce pain and fever during initial outbreaks.

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. (Leung & Sacks, 2003

Complementary

Since herpes is a viral infection, a daily multi-vitamin to maintain immune system health can help lessen and shorten outbreaks. Eating dairy products and other foods high in lysine and low in arginine might also help; additionally, many pharmacies and health food stores carry lysine supplements.

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. (Docherty et al., 1999) A more recent in vivo study in mice showed the efficacy of resveratrol cream in preventing cutaneous HSV lesion formation. (Docherty et al., 2004) Research on a much more potent derivative of resveratol, named stil-5, is ongoing.

Lactoferrin, a component of whey protein, has been shown to have a synergistic effect when combined with aciclovir therapy. (Andersen, Jenssen, Gutteberg 2003) Ongoing research on combining lactoferrin with an aciclovir regimen are aimed at increasing the efficiency of aciclovir thus allowing for dosage reductions and decreasing the opportunity for aciclovir resistant HSV strains to develop.

Other supplements with anecdotal benefits include zinc, garlic, and echinacea.

Experimental

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. (Karadi, Karpati & Romics, 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. (Gebhardt, Varnell, & Kaufman, 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 effects

The long-term effects of herpes are not well known, but the blisters may leave scars, and historically it was thought to contribute to the risk of cervical cancer in women. Subsequently, another virus, human papillomavirus (HPV), has been shown to be the 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

Myths

Some common myths and misconceptions about herpes are that it is fatal (only true for newborns, where it is rare, or if it infects the brain, which is again unusual), that it only affects the genital areas (it can affect any part of the body), that condoms are completely effective in preventing the spread of this disease, that it is transmittable only in the presence of symptoms, that it can make you sterile, that Pap smears detect herpes, and that only promiscuous people get it (it is so common that anyone having sex is at risk). There is a basis in truth 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 (brief time, high heat, high moisture, and exposure) make it highly unlikely. Although there has never been a known case of this type of transmission, sharing a towel with somebody with active lesions should be avoided.

Other herpesviruses

There are eight members of the herpesvirus family that are known to cause human disease, including not only the Herpes Simplex virus (HSV-1 and HSV-2), but also the varicella-zoster virus (VZV), Epstein-Barr virus (EBV) and the cytomegalovirus (CMV).

References

  • Docherty JJ, Fu MM, Stiffler BS, Limperos RJ, Pokabla CM, DeLucia AL (1999). Resveratrol inhibition of herpes simplex virus replication. Antiviral Res 43 (3), 145-55. PMID 10551373
  • Docherty JJ, Smith JS, Fu MM, Stoner T, Booth T (2004). Effect of topically applied resveratrol on cutaneous herpes simplex virus infections in hairless mice. Antiviral Res 61 (1), 19-26. PMID 14670590
  • Elliott E, Rose D (2004). Australian Paediatric Surveillance Unit. Reporting of communicable disease conditions under surveillance by the APSU, 1 January to 30 September 2003. Commun Dis Intell 28 (1), 90-1. PMID 15072162
  • Fleming DT, McQuillan GM, Johnson RE, Nahmias AJ, Aral SO, Lee FK, et al. (1997). Herpes simplex virus type 2 in the United States, 1976 to 1994. New Engl J Med 337 (16), 1105-11. PMID 9329932
  • Gebhardt BM, Varnell ED, Kaufman HE (2004). Acetylsalicylic acid reduces viral shedding induced by thermal stress. Curr Eye Res 29 (2-3), 119-25. PMID 15512958
  • Jones CA. (2004). Vaccines to prevent neonatal herpes simplex virus infection. Expert Rev Vaccines 3 (4), 363-4. PMID 15270635
  • Karadi I, Karpati S, Romics L (1998). Aspirin in the management of recurrent herpes simplex virus infection (http://www.annals.org/cgi/content/full/128/8/696-b). Ann Intern Med 128 (8), 696-7.
  • Leung DT, Sacks SL (2003). Current treatment options to prevent perinatal transmission of herpes simplex virus. Expert Opin Pharmacother 4 (10), 1809-19. PMID 14521490
  • Thackray AM, Field HJ (1996). Differential effects of famciclovir and valaciclovir on the pathogenesis of herpes simplex virus in a murine infection model including reactivation from latency. J Infect Dis 173 (2), 291-9. PMID 8568288
  • Wald A, Langenberg AG, Link K, Izu AE, Ashley R, Warren T, et al. (2001). Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women. JAMA 285 (24), 3100-6. PMID 11427138

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