Herpes simplex
Encyclopedia
Herpes simplex is a viral disease caused by both Herpes simplex virus
type 1 (HSV-1) and type 2 (HSV-2). Infection with the herpes virus is categorized into one of several distinct disorders based on the site of infection. Oral herpes
, the visible symptoms of which are colloquially called cold sores or fever blisters, infects the face and mouth. Oral herpes is the most common form of infection. Genital herpes
, known simply as herpes, is the second most common form of herpes. Other disorders such as herpetic whitlow
, herpes gladiatorum, ocular herpes (keratitis
), cerebral herpes infection encephalitis
, Mollaret's meningitis
, neonatal herpes
, and possibly Bell's palsy
are all caused by herpes simplex viruses.
Herpes viruses cycle between periods of active disease—presenting as blisters containing infectious virus
particles—that last 2–21 days, followed by a remission period. Genital herpes, however, is often asymptomatic
, though viral shedding
may still occur. After initial infection, the viruses are transported along sensory nerves
to the sensory nerve cell bodies, where they become latent
and reside life-long. Causes of recurrence are uncertain, though some potential triggers have been identified, including immunosuppressant drugs (see below). The previously latent virus then multiplies new virus particles in the nerve cell and these are transported along the axon
of each neuron
to the nerve terminals in the skin, where they are released. Over time, episodes of active disease reduce in frequency and severity.
Herpes simplex is most easily transmitted by direct contact with a lesion or the body fluid of an infected individual. Transmission may also occur through skin-to-skin contact during periods of asymptomatic shedding. Barrier protection methods are the most reliable method of preventing transmission of herpes, but they merely reduce rather than eliminate risk. Oral herpes is easily diagnosed if the patient presents with visible sores or ulcers. Early stages of orofacial herpes and genital herpes are harder to diagnose; laboratory testing is usually required.
A cure for herpes has not yet been developed. Once infected, the virus remains in the body for life. Recurrent infections (outbreaks) may occur from time to time, especially in times of immune
impairment such as HIV
and cancer
-related immune suppression. However, after several years, some people will become perpetually asymptomatic
and will no longer experience outbreaks, though they may still be contagious to others. Treatments with antivirals can reduce viral shedding and alleviate the severity of symptomatic episodes. Vaccines are in clinical trials but have not demonstrated effectiveness. It should not be confused with conditions caused by other viruses in the herpesviridae
family such as herpes zoster
, which is caused by varicella zoster virus
. The differential diagnosis includes hand, foot and mouth disease
due to similar lesions on the skin.
infections, while HSV2 primarily causes anogenital infections. However, each may cause infections in all areas.
). More serious disorders occur when the virus infects and damages the eye (herpes keratitis), or invades the central nervous system, damaging the brain (herpes encephalitis). Patients with immature or suppressed immune systems, such as newborns, transplant recipients, or AIDS patients are prone to severe complications from HSV infections. HSV infection has also been associated with cognitive deficits of bipolar disorder
, and Alzheimer's disease
, although this is often dependent on the genetics
of the infected person.
In all cases HSV is never removed from the body by the immune system
. Following a primary infection, the virus enters the nerves at the site of primary infection, migrates to the cell body of the neuron, and becomes latent in the ganglion
. As a result of primary infection, the body produces antibodies to the particular type of HSV involved, preventing a subsequent infection of that type at a different site. In HSV-1 infected individuals, seroconversion
after an oral infection will prevent additional HSV-1 infections such as whitlow
, genital herpes, and keratitis
. Prior HSV-1 seroconversion seems to reduce the symptoms of a later HSV-2 infection, although HSV-2 can still be contracted. Most indications are that an HSV-2 infection contracted prior to HSV-1 seroconversion will also immunize that person against HSV-1 infection.
Many people infected with HSV-2 display no physical symptoms—individuals with no symptoms are described as asymptomatic or as having subclinical
herpes.
, a type of facial paralysis
, is unknown it may be related to reactivation of herpes simplex virus type 1. This theory has been contested, however since HSV is detected in large numbers of individuals who never experienced facial paralysis, and higher levels of antibodies for HSV are not found in HSV-infected individuals with Bell's palsy compared to those without. Regardless antivirals have been found to not improve outcomes.
. In the presence of a certain gene variation (APOE
-epsilon4 allele carriers), HSV-1 appears to be particularly damaging to the nervous system and increases one’s risk of developing Alzheimer’s disease. The virus interacts with the components and receptors of lipoproteins, which may lead to the development of Alzheimer's disease. Without the presence of the gene allele, HSV type 1 does not appear to cause any neurological damage and thus increase the risk of Alzheimer’s. Herpes simplex virus type 1 DNA is localized within the beta-amyloid plaques that characterize Alzheimer's disease. It suggests that this virus is a major cause of the plaques and hence probably a significant aetiological factor in Alzheimer's disease.
HSV asymptomatic shedding
occurs at some time in most individuals infected with herpes. It can occur more than a week before or after a symptomatic recurrence in 50% of cases. Virus enters into susceptible cells via entry receptors
such as nectin-1, HVEM and 3-O sulfated heparan sulfate. Infected people that show no visible symptoms may still shed and transmit virus through their skin; asymptomatic shedding may represent the most common form of HSV-2 transmission. Asymptomatic shedding is more frequent within the first 12 months of acquiring HSV. Concurrent infection with HIV increases the frequency and duration of asymptomatic shedding. There are indications that some individuals may have much lower patterns of shedding, but evidence supporting this is not fully verified; no significant differences are seen in the frequency of asymptomatic shedding when comparing persons with one to twelve annual recurrences to those who have no recurrences.
Antibodies that develop following an initial infection with a type of HSV prevents reinfection with the same virus type—a person with a history of orofacial infection caused by HSV-1 cannot contract herpes whitlow or a genital infection caused by HSV-1. In a monogamous
couple, a seronegative female runs a greater than 30% per year risk of contracting an HSV infection from a seropositive male partner. If an oral HSV-1 infection is contracted first, seroconversion will have occurred after 6 weeks to provide protective antibodies against a future genital HSV-1 infection.
. Adults with non-typical presentation are more difficult to diagnose. Prodromal symptoms that occur before the appearance of herpetic lesions help differentiate HSV symptoms from the similar symptoms of other disorders, such as allergic
stomatitis
. When lesions do not appear inside the mouth, primary orofacial herpes is sometimes mistaken for impetigo
, a bacterial infection
. Common mouth ulcers (aphthous ulcer
) also resemble intraoral herpes, but do not present a vesicular stage.
Genital herpes can be more difficult to diagnose than oral herpes since most HSV-2-infected persons have no classical symptoms. Further confusing diagnosis, several other conditions resemble genital herpes, including fungal infection, lichen planus
, atopic dermatitis
, and urethritis
. Laboratory
testing is often used to confirm a diagnosis of genital herpes. Laboratory tests include: culture of the virus, direct fluorescent antibody
(DFA) studies to detect virus, skin biopsy
, and polymerase chain reaction
(PCR) to test for presence of viral DNA. Although these procedures produce highly sensitive and specific diagnoses, their high costs and time constraints discourage their regular use in clinical practice.
Until recently, serological
tests for antibodies to HSV were rarely useful to diagnosis and not routinely used in clinical practice. The older IgM serologic assay could not differentiate between antibodies generated in response to HSV-1 or HSV-2 infection. However, the new Immunodot glycoprotein G-specific (IgG) HSV test is more than 98% specific at discriminating HSV-1 from HSV-2.
It is the opinion of some modern medical professionals that the new IgG test should always be clinically preferred to the old IgM test, however not all doctors appear to be informed of the availability of the newer, reliable IgG tests.
As with almost all sexually transmitted infections, women are more susceptible to acquiring genital HSV-2 than men. On an annual basis, without the use of antivirals or condoms, the transmission risk of HSV-2 from infected male to female is approximately 8-11%.
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—meaning the infected partner will be seropositive but symptom free—by about 50%. Condom use also reduces the transmission risk significantly. Condom use is much more effective at preventing male to female transmission than vice-versa. 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. Previous HSV-1 infection appears to reduce the risk for acquisition of HSV-2 infection among women by a factor of 3.
However, asymptomatic carriers of the HSV-2 virus are still contagious. In many infections, the first symptom a person will have of their own infection is the horizontal transmission to a sexual partner or the vertical transmission of neonatal herpes to a newborn at term. Since most asymptomatic individuals are unaware of their infection, they are considered at high risk for spreading HSV.
In October 2011, it was reported that the anti-HIV drug tenofovir, when used topically in a microbicidal vaginal gel, prevented herpes virus infections.
s offer moderate protection against HSV-2 in both men and women, with consistent condom users having a 30% lower risk of HSV-2 acquisition compared with those who never use condoms. A female condom
can provide greater protection than the male condom, as it covers the labia. The virus cannot pass through a synthetic condom, but a male condom's effectiveness is limited because herpes ulcers may appear on areas not covered by the male condom. Neither type of condom prevents contact with the scrotum, anus, buttocks, or upper thighs, areas which may come in contact with ulcers or genital secretions during sexual activity. Protection against herpes simplex depends on the site of the ulcer; therefore if ulcers appear on areas not covered by condoms, abstaining from sexual activity until the ulcers are fully healed is one way to limit risk of transmission. The risk is not eliminated, however, as viral shedding capable of transmitting infection may still occur while the infected partner is asymptomatic. The use of condoms or dental dams also limits the transmission of herpes from the genitals of one partner to the mouth of the other (or vice versa) during oral sex
. When one partner has a herpes simplex infection and the other does not, the use of antiviral medication, such as valaciclovir, in conjunction with a condom further decreases the chances of transmission to the uninfected partner. Topical microbicide
s which contain chemicals that directly inactivate the virus and block viral entry are being investigated.
to reduce exposure of the child to infected secretions in the birth canal. The use of antiviral treatments, such as acyclovir, given from the 36th week of pregnancy, limits HSV recurrence and shedding during childbirth, thereby reducing the need for caesarean section.
Acyclovir is the recommended antiviral for herpes suppressive therapy during the last months of pregnancy. The use of valaciclovir and famciclovir, while potentially improving compliance have less well determined safety in pregnancy.
s such as ibuprofen
and acetaminophen can reduce pain and fever. Topical anesthetic treatments such as prilocaine
, lidocaine
, benzocaine
or tetracaine
can also relieve itching and pain.
There are several antiviral
s that are effective for treating herpes including: aciclovir
(acyclovir), valaciclovir (valacyclovir), famciclovir
, and penciclovir. Aciclovir was the first discovered and is now available in generic.
Evidence supports the use of aciclovir and valaciclovir in the treatment of herpes labialis as well as herpes infections in people with cancer
. The evidence to support the use of acyclovir in primary herpetic gingivostomatitis is less strong.
antivirals are effective for herpes labialis including acyclovir, penciclovir, and docosanol
. Docosanol can be purchased over the counter in Canada and the USA.
s and alternative remedies are claimed to be beneficial in the treatment of herpes. There is however insufficient evidence to support use of many of these compounds including echinacea
, eleuthero, L-lysine, zinc
, bee products and aloe vera
.
A single study indicates possible benefit from laser
treatment.
infection in sensory and autonomic ganglia of the nervous system. The double-stranded DNA of the virus is incorporated into the cell physiology by infection of the nucleus
of a nerve's cell body
. HSV latency is static—no virus is produced—and is controlled by a number of viral genes, including Latency Associated Transcript (LAT).
Many HSV-infected people experience recurrence within the first year of infection. Prodrome
precedes development of lesions. Prodromal symptoms include tingling (paresthesia
), itching, and pain where lumbosacral nerves innervate the skin. Prodrome may occur as long as several days or as short as a few hours before lesions develop. Beginning antiviral treatment when prodrome is experienced can reduce the appearance and duration of lesions in some individuals. During recurrence, fewer lesions are likely to develop, lesions are less painful and heal faster (within 5–10 days without antiviral treatment) than those occurring during the primary infection. Subsequent outbreaks tend to be periodic or episodic, occurring on average four to five times a year when not using antiviral therapy.
The causes of reactivation are uncertain, but several potential triggers have been documented. A recent study (2009) showed that the protein VP16 plays a key role in reactivation of the dormant virus. Changes in the immune system during menstruation
may play a role in HSV-1 reactivation. Concurrent infections, such as viral upper respiratory tract infection
or other febrile diseases, can cause outbreaks. Reactivation due to infection is the likely source of the historic terms cold sore and fever blister.
Other identified triggers include: local injury to the face, lips, eyes, or mouth, trauma, surgery, radiotherapy, and exposure to wind, ultraviolet light, or sunlight.
The frequency and severity of recurrent outbreaks vary greatly between patients. Some individuals' outbreaks can be quite debilitating with large, painful lesions persisting for several weeks, while others will experience only minor itching or burning for a few days. There is some evidence that genetics plays a role in the frequency of cold sore outbreaks. An area of human chromosome 21 that includes 6 genes has been linked to frequent oral herpes outbreaks. An immunity to the virus is built over time. Most infected individuals will experience fewer outbreaks and outbreak symptoms will often become less severe. After several years, some people will become perpetually asymptomatic
and will no longer experience outbreaks, though they may still be contagious to others. Immuno-compromised individuals may experience episodes that are longer, more frequent, and more severe. Antiviral medication has been proven to shorten the frequency and duration of outbreaks. Outbreaks may occur at the original site of the infection or in proximity to nerve endings that reach out from the infected ganglia. In the case of a genital infection, sores can appear at the original site of infection or near the base of the spine, the buttocks, or the back of the thighs.
HSV-2 infected individuals are at higher risk for acquiring HIV
when practicing unprotected sex with HIV-positive persons, particularly during an outbreak with active lesions.
In the US, 57.7% of the population is infected with HSV-1 and 16.2% are infected with HSV-2. Among those HSV-2 seropositive, only 18.9% were aware that they were infected.
banned kissing in Rome for a time due to so many people having cold sores. In the 16th century Romeo and Juliet
, it is mentioned that there are blisters "o'er ladies' lips." In 18th century it was so common among prostitutes that it was called "a vocational disease of women."
The term Herpes Simplex appeared in Richard Boulton
's A System of Rational and Practical Chirurgery in 1713, where the terms Herpes miliaris and Herpes exedens also appeared.
Herpes was not found to be a virus until the 1940s.
Herpes antiviral therapy began in the early 1960s with the experimental use of medication that interfered with viral replication called deoxyribonucleic acid (DNA) inhibitors. The original use was against normally fatal or disabilitating illness such as adult encephalitis, keratitis, in immunocompromised (transplant) patients, or disseminated herpes zoster. The original compounds used were 5-iodo-2'-deoxyuridine, AKA idoxuridine, IUdR, or(IDU) and 1-β-D-arabinofuranosylcytosine or ara-C, later marketed under the name cytosar or cytorabine. The usage expanded to include topical treatment of herpes simplex, zoster, and varicella. Some trials combined different antivirals with differing results. The introduction of 9-β-D-arabinofuranosyladenine, AKA ara-A or vidarabine, considerably less toxic than Ara-C, in the mid 1970s, heralded the way for the beginning of regular neonatal antiviral treatment. Vidarabine was the first systemically administered antiviral medication with activity against HSV for which therapeutic efficacy outweighed toxicity for the management of life-threatening HSV disease. Intravenous vidarabine was licensed for use by the U.S. Food and Drug Administration (FDA) in 1977. Other experimental antivirals of that period included: Heparin, trifluorothymidine (TFT), Ribivarin, interferon, Virazole, and 5-methoxymethyl-2'-deoxyuridine (MMUdR). The introduction of 9-(2-hydroxyethoxymethyl)guanine, AKA acyclovir, in the late 1970s raised antiviral treatment another notch and led to vidarabine vs. acyclovir trials in the late 1980s. The lower toxicity and ease of administration over vidarabine has led to acyclovir becoming the drug of choice for herpes treatment after it was licensed by the FDA in 1998. Another advantage in the treatment of neonatal herpes included greater reductions in mortality and morbidity with increased dosages, something that did not occur when compared with increased dosages of vidarabine. On the other side of the equation, acyclovir seems to inhibit antibody response and newborns on acyclovir antiviral treatment experienced a slower rise in antibody titer than those on vidarabine.
In the Journal of Clinical Investigation, Pedro Cuatrecasas states, “during the R&D of acyclovir (Zovirax), marketing [department of Burroughs Wellcome] insisted that there were ‘no markets’ for this compound. Most had hardly heard of genital herpes...” Thus marketing the medical condition – separating the ‘normal cold sore’ from the ‘stigmatized genital infection’ was to become the key to marketing the drug, a process now known as ‘disease mongering’.
Since the creation of the herpes hype, some people experience negative feelings related to the condition following diagnosis, particularly if they have acquired the genital form of the disease. Feelings can include depression
, fear of rejection, feelings of isolation
, fear of being found out, self-destructive feelings, and fear of masturbation. These feelings usually lessen over time. Much of the hysteria and stigma surrounding herpes stems from a media campaign beginning in the late 1970s and peaking in the early 1980s. There were multiple articles worded in fear-mongering and anxiety-provoking terminology, such as the now ubiquitous "attacks," "outbreaks," "victims," and "sufferers." At one point the term "herpetic" even entered the popular lexicon. The articles were published by Reader's Digest, U.S. News, and Time magazine, among others. A made-for-TV movie was named Intimate Agony. The peak was when Time magazine had 'Herpes: The New Scarlet Letter' on the cover in August 1982, forever stigmatizing the word in the public mind. The scientific reality is that most people are asymptomatic, the virus causes no real health problems for a vast majority of people, and a vast majority (around 90%) of the Earth's population carries HSV-1, 2, or both. Herpes support groups
have been formed in the United States and the UK, providing information about herpes and running message forums and dating websites for "sufferers." People with the herpes virus are often hesitant to divulge to other people, including friends and family, that they are infected. This is especially true of new or potential sexual partners whom they consider casual.
have made a Hammerhead ribozyme
that targets and cleaves the mRNA of essential genes in HSV-1. The hammerhead which targets the mRNA of the UL20 gene greatly reduced the level of HSV-1 ocular infection in rabbits and reduced the viral yield in vivo. The gene-targeting approach uses a specially designed RNA enzyme to inhibit strains of the herpes simplex virus. The enzyme disables a gene responsible for producing a protein involved in the maturation and release of viral particles in an infected cell. The technique appears to be effective in experiments with mice and rabbits, but further research is required before it can be attempted in people who are infected with herpes.
Another possibility to eradicate the HSV-1 variant is being pursued by a team at Duke University
. By figuring out how to switch all copies of the virus in the host from latency to their active stage at the same time, rather than the way the virus copies normally stagger their activity stage, leaving some dormant somewhere at all times, it is thought that conventional anti-viral drugs can kill the entire virus population completely, since they can no longer hide in the nerve cells. One class of drugs called antagomir
could serve this purpose. These are chemically engineered oligonucleotides or short segments of RNA, that can be made to mirror their target genetic material, namely herpes microRNAs. They could be engineered to attach and thus 'silence' the microRNA, thus rendering the virus incapable to keep latent in their host. Professor Cullen believes a drug could be developed to block the microRNA whose job it is to suppress HSV-1 into latency.
One vaccine that was under trial was Herpevac, a vaccine against HSV-2. The National Institutes of Health
(NIH) in the United States
conducted phase III trials
of Herpevac. In 2010, it was reported that, after 8 years of study in more than 8000 women in the United States and Canada, there was no sign of positive results against the sexually transmitted disease caused by HSV-2 (and this despite earlier favorable interim reports).
A laboratory at Harvard Medical School
has developed dl5-29 (now known as ACAM-529), a replication-defective mutant virus that has proved successful both in preventing HSV-2/HSV-1 infections, and in combating the virus in already infected hosts, in animal models. It has been shown that the replication-defective vaccine induces strong HSV-2-specific antibody and T-cell responses; protects against challenge with a wild-type HSV-2 virus; greatly reduces the severity of recurrent disease; provides cross-protection against HSV-1, and renders the virus unable to revert to a virulent state or to become latent. His vaccine is now being researched and developed by Accambis (acquired by Sanofi Pasteur
in September 2008), and is due to be applied as an Investigational New Drug in 2009. However, the status of ACAM-529 became after the acquisition somewhat unclear. According to Jim Tartaglia, a company representative of Sanofi Pasteur, ACAM-529 is still under development and should be enter phase I clinical testing in 2012.
A private company called BioVex began Phase I clinical trials for ImmunoVEX, another proposed vaccine, in March 2010. A completely new approach has the "HSV-2 ICP0 live-attenuated HSV-2 vaccine" investigated by Dr. William Halford at the Southern Illinois University (SIU) School of Medicine
.
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
type 1 (HSV-1) and type 2 (HSV-2). Infection with the herpes virus is categorized into one of several distinct disorders based on the site of infection. Oral herpes
Herpes labialis
Herpes labialis or "orolabial herpes" is an infection of the lip by herpes simplex virus . An outbreak typically causes small blisters or sores on or around the mouth commonly known as cold sores or fever blisters...
, the visible symptoms of which are colloquially called cold sores or fever blisters, infects the face and mouth. Oral herpes is the most common form of infection. Genital herpes
Herpes genitalis
Herpes genitalis refers to a genital infection by Herpes simplex virus.Following the classification HSV into two distinct categories of HSV-1 and HSV-2 in the 1960s, it was established that "HSV-2 was below the waist, HSV-1 was above the waist"...
, known simply as herpes, is the second most common form of herpes. Other disorders such as herpetic whitlow
Herpetic whitlow
A herpetic whitlow is a lesion on a finger or thumb caused by the herpes simplex virus. It is a painful infection that typically affects the fingers or thumbs. Occasionally infection occurs on the toes or on the nail cuticle. Herpes whitlow can be caused by infection by HSV-1 or HSV-2...
, herpes gladiatorum, ocular herpes (keratitis
Keratitis
Keratitis is a condition in which the eye's cornea, the front part of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves impaired eyesight.-Types:...
), cerebral herpes infection encephalitis
Encephalitis
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...
, Mollaret's meningitis
Mollaret's meningitis
Mollaret's meningitis is a recurrent inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges...
, neonatal herpes
Neonatal herpes simplex
Neonatal herpes simplex is a rare but serious condition, usually caused by vertical transmission of herpes simplex virus from mother to newborn.-Transmission:...
, and possibly Bell's palsy
Bell's palsy
Bell's palsy is a form of facial paralysis resulting from a dysfunction of the cranial nerve VII that results in the inability to control facial muscles on the affected side. Several conditions can cause facial paralysis, e.g., brain tumor, stroke, and Lyme disease. However, if no specific cause...
are all caused by herpes simplex viruses.
Herpes viruses cycle between periods of active disease—presenting as blisters containing infectious virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
particles—that last 2–21 days, followed by a remission period. Genital herpes, however, is often asymptomatic
Asymptomatic
In medicine, a disease is considered asymptomatic if a patient is a carrier for a disease or infection but experiences no symptoms. A condition might be asymptomatic if it fails to show the noticeable symptoms with which it is usually associated. Asymptomatic infections are also called subclinical...
, though viral shedding
Viral shedding
Viral shedding refers to the successful reproduction, expulsion, and host-cell infection caused by virus progeny. Once replication has been completed and the host cell is exhausted of all resources in making viral progeny, the viruses may begin to leave the cell by several methods.The term is used...
may still occur. After initial infection, the viruses are transported along sensory nerves
Sensory neuron
Sensory neurons are typically classified as the neurons responsible for converting external stimuli from the environment into internal stimuli. They are activated by sensory input , and send projections into the central nervous system that convey sensory information to the brain or spinal cord...
to the sensory nerve cell bodies, where they become latent
Virus latency
Virus latency is the ability of a pathogenic virus to lie dormant within a cell, denoted as the lysogenic part of the viral life cycle. A latent viral infection is a type of persistent viral infection which is distinguished from a chronic viral infection...
and reside life-long. Causes of recurrence are uncertain, though some potential triggers have been identified, including immunosuppressant drugs (see below). The previously latent virus then multiplies new virus particles in the nerve cell and these are transported along the axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
of each neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
to the nerve terminals in the skin, where they are released. Over time, episodes of active disease reduce in frequency and severity.
Herpes simplex is most easily transmitted by direct contact with a lesion or the body fluid of an infected individual. Transmission may also occur through skin-to-skin contact during periods of asymptomatic shedding. Barrier protection methods are the most reliable method of preventing transmission of herpes, but they merely reduce rather than eliminate risk. Oral herpes is easily diagnosed if the patient presents with visible sores or ulcers. Early stages of orofacial herpes and genital herpes are harder to diagnose; laboratory testing is usually required.
A cure for herpes has not yet been developed. Once infected, the virus remains in the body for life. Recurrent infections (outbreaks) may occur from time to time, especially in times of immune
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
impairment such as HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
and cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
-related immune suppression. However, after several years, some people will become perpetually asymptomatic
Asymptomatic
In medicine, a disease is considered asymptomatic if a patient is a carrier for a disease or infection but experiences no symptoms. A condition might be asymptomatic if it fails to show the noticeable symptoms with which it is usually associated. Asymptomatic infections are also called subclinical...
and will no longer experience outbreaks, though they may still be contagious to others. Treatments with antivirals can reduce viral shedding and alleviate the severity of symptomatic episodes. Vaccines are in clinical trials but have not demonstrated effectiveness. It should not be confused with conditions caused by other viruses in the herpesviridae
Herpesviridae
The Herpesviridae are a large family of DNA viruses that cause diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word herpein , referring to the latent, recurring infections typical of this group of viruses...
family such as herpes zoster
Herpes zoster
Herpes zoster , commonly known as shingles and also known as zona, is a viral disease characterized by a painful skin rash with blisters in a limited area on one side of the body, often in a stripe...
, which is caused by varicella zoster virus
Varicella zoster virus
Varicella zoster virus is one of eight herpes viruses known to infect humans . It commonly causes chicken-pox in children and Herpes zoster in adults and rarely in children.-Nomenclature:...
. The differential diagnosis includes hand, foot and mouth disease
Hand, foot and mouth disease
Hand, foot and mouth disease is a human syndrome caused by intestinal viruses of the Picornaviridae family. The most common strains causing HFMD are Coxsackie A virus and Enterovirus 71 ....
due to similar lesions on the skin.
Classification
Herpes simplex is divided into two types: HSV type 1 and HSV type 2. HSV1 primarily causes mouth, throat, face, eye, and central nervous systemCentral nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
infections, while HSV2 primarily causes anogenital infections. However, each may cause infections in all areas.
Signs and symptoms
HSV infection causes several distinct medical disorders. Common infection of the skin or mucosa may affect the face and mouth (orofacial herpes), genitalia (genital herpes), or hands (herpetic whitlowHerpetic whitlow
A herpetic whitlow is a lesion on a finger or thumb caused by the herpes simplex virus. It is a painful infection that typically affects the fingers or thumbs. Occasionally infection occurs on the toes or on the nail cuticle. Herpes whitlow can be caused by infection by HSV-1 or HSV-2...
). More serious disorders occur when the virus infects and damages the eye (herpes keratitis), or invades the central nervous system, damaging the brain (herpes encephalitis). Patients with immature or suppressed immune systems, such as newborns, transplant recipients, or AIDS patients are prone to severe complications from HSV infections. HSV infection has also been associated with cognitive deficits of bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
, and Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, although this is often dependent on the genetics
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
of the infected person.
In all cases HSV is never removed from the body by the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
. Following a primary infection, the virus enters the nerves at the site of primary infection, migrates to the cell body of the neuron, and becomes latent in the ganglion
Ganglion
In anatomy, a ganglion is a biological tissue mass, most commonly a mass of nerve cell bodies. Cells found in a ganglion are called ganglion cells, though this term is also sometimes used to refer specifically to retinal ganglion cells....
. As a result of primary infection, the body produces antibodies to the particular type of HSV involved, preventing a subsequent infection of that type at a different site. In HSV-1 infected individuals, seroconversion
Seroconversion
Seroconversion is the development of detectable specific antibodies to microorganisms in the blood serum as a result of infection or immunization. Serology is used to determine antibody positivity...
after an oral infection will prevent additional HSV-1 infections such as whitlow
Whitlow
A whitlow or felon is an infection of the tip of the finger. The terms are also sometimes misapplied to paronychia, which is an infection of the tissue at the side or base of the nail....
, genital herpes, and keratitis
Keratitis
Keratitis is a condition in which the eye's cornea, the front part of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves impaired eyesight.-Types:...
. Prior HSV-1 seroconversion seems to reduce the symptoms of a later HSV-2 infection, although HSV-2 can still be contracted. Most indications are that an HSV-2 infection contracted prior to HSV-1 seroconversion will also immunize that person against HSV-1 infection.
Many people infected with HSV-2 display no physical symptoms—individuals with no symptoms are described as asymptomatic or as having subclinical
Subclinical infection
A subclinical infection is the asymptomatic carrying of an by an individual of an agent that usually is a pathogen causing illness, at least in some individuals. Many pathogens spread by being silently carried in this way by some of their host population...
herpes.
| Condition | Description | Illustration |
|---|---|---|
| Herpetic gingivostomatitis Gingivostomatitis Gingivostomatitis is a combination of gingivitis and stomatitis, or an inflammation of the oral mucosa and gingiva. Herpetic gingivostomatitis is often the initial presentation during the first herpes simplex infection. It is of greater severity than herpes labialis which is often the subsequent... |
Herpetic gingivostomatitis is often the initial presentation during the first herpes infection. It is of greater severity than herpes labialis which is often the subsequent presentations. | |
| Herpes labialis Herpes labialis Herpes labialis or "orolabial herpes" is an infection of the lip by herpes simplex virus . An outbreak typically causes small blisters or sores on or around the mouth commonly known as cold sores or fever blisters... |
Infection occurs when the virus comes into contact with oral mucosa or abraded skin. |  |
| Herpes genitalis Herpes genitalis Herpes genitalis refers to a genital infection by Herpes simplex virus.Following the classification HSV into two distinct categories of HSV-1 and HSV-2 in the 1960s, it was established that "HSV-2 was below the waist, HSV-1 was above the waist"... |
When symptomatic, the typical manifestation of a primary HSV-1 or HSV-2 genital infection is clusters of inflamed papule Papule A papule is a circumscribed, solid elevation of skin with no visible fluid, varying in size from a pinhead to 1 cm.With regard to the quote "...varying in size from a pinhead to 1cm," depending on which text is referenced, some authors state the cutoff between a papule and a plaque as 0.5cm,... s and vesicles on the outer surface of the genitals resembling cold sores. |
 |
| Herpetic whitlow Herpetic whitlow A herpetic whitlow is a lesion on a finger or thumb caused by the herpes simplex virus. It is a painful infection that typically affects the fingers or thumbs. Occasionally infection occurs on the toes or on the nail cuticle. Herpes whitlow can be caused by infection by HSV-1 or HSV-2... |
Herpes whitlow is a painful infection that typically affects the fingers or thumbs. Occasionally infection occurs on the toes or on the nail cuticle. | |
| Herpes gladiatorum | Individuals that participate in contact sport Contact sport Many sports involve a degree of player-to-player or player-to-object contact. The term "contact sport" is used in both team sports and combat sports, medical terminology and television game shows, such as the Gladiators and Wipeout, to certain degrees... s such as wrestling Wrestling Wrestling is a form of grappling type techniques such as clinch fighting, throws and takedowns, joint locks, pins and other grappling holds. A wrestling bout is a physical competition, between two competitors or sparring partners, who attempt to gain and maintain a superior position... , rugby Rugby football Rugby football is a style of football named after Rugby School in the United Kingdom. It is seen most prominently in two current sports, rugby league and rugby union.-History:... , and soccer sometimes acquire a condition caused by HSV-1 known as herpes gladiatorum, scrumpox, wrestler’s herpes, or mat herpes, which presents as skin ulceration on the face, ears, and neck. Symptoms include fever, headache, sore throat and swollen glands. It occasionally affects the eyes or eyelids. |
|
| Herpetic keratoconjunctivitis | Primary infection typically presents as swelling of the conjunctiva Conjunctiva The conjunctiva covers the sclera and lines the inside of the eyelids. It is composed of rare stratified columnar epithelium.-Function:... and eyelids (blepharoconjunctivitis), accompanied by small white itchy lesions on the surface of the cornea Cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is... . |
|
| Herpesviral encephalitis Herpesviral encephalitis Herpesviral encephalitis is encephalitis associated with herpes simplex virus.Herpes simplex encephalitis is a rare, but severe viral infection of the human central nervous system. It is estimated to affect at least 1 in 500,000 individuals per year. The majority of cases of herpes encephalitis... |
A herpetic infection of the brain that is thought to be caused by the retrograde transmission Retrograde infection Retrograde is defined as "In reverse action", therefore a retrograde infection is an infection that enters or spreads through the body through a means that is usually considered backwards. An example is spreading into the salivary glands through the saliva ducts.... of virus from a peripheral site on the face following HSV-1 reactivation, along the trigeminal nerve Trigeminal nerve The trigeminal nerve contains both sensory and motor fibres. It is responsible for sensation in the face and certain motor functions such as biting, chewing, and swallowing. Sensory information from the face and body is processed by parallel pathways in the central nervous system... axon Axon An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma.... , to the brain. HSV is the most common cause of viral encephalitis. When infecting the brain, the virus shows a preference for the temporal lobe Temporal lobe The temporal lobe is a region of the cerebral cortex that is located beneath the Sylvian fissure on both cerebral hemispheres of the mammalian brain.... . |
 |
| Herpesviral meningitis Herpesviral meningitis Herpesviral meningitis is meningitis associated with herpes simplex virus .HSV-2 is the most common cause of Mollaret's meningitis, a type of recurrent viral meningitis. This condition was first described in 1944 by French neurologist Pierre Mollaret. Recurrences usually last a few days or a few... |
HSV-2 is the most common cause of Mollaret's meningitis, a type of recurrent viral meningitis. | |
| Neonatal herpes simplex Neonatal herpes simplex Neonatal herpes simplex is a rare but serious condition, usually caused by vertical transmission of herpes simplex virus from mother to newborn.-Transmission:... |
Neonatal Infant A newborn or baby is the very young offspring of a human or other mammal. A newborn is an infant who is within hours, days, or up to a few weeks from birth. In medical contexts, newborn or neonate refers to an infant in the first 28 days after birth... HSV infection is a rare but serious condition, usually caused by vertical transmission Vertical transmission Vertical transmission, also known as mother-to-child transmission, is the transmission of an infection or other disease from mother to child immediately before and after birth during the perinatal period. A pathogen's transmissibility refers to its capacity for vertical transmission... of HSV (type 1 or 2) from mother to newborn. |
|
| During immunodeficiency Immunodeficiency Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,... |
In patients with a weakened immune system, herpes simplex can cause unusual lesions in the skin. One of the most striking is the appearance of clean linear erosions in skin creases, with the appearance of a knife cut. | |
| Herpetic sycosis Herpetic sycosis Herpetic sycosis is a recurrent or initial herpes simplex infection affecting primarily the hair follicle.... |
Herpetic sycosis is a recurrent or initial herpes simplex infection affecting primarily the hair follicle. | |
| Eczema herpeticum Eczema herpeticum Eczema herpeticum is a rare but severe disseminated herpes infection that generally occurs at sites of skin damage produced by, for example, atopic dermatitis, burns, or eczema... |
Infection with herpesvirus in patients with chronic atopic dermatitis Atopic dermatitis Atopic dermatitis is an inflammatory, chronically relapsing, non-contagious and pruritic skin disorder... may result in spread of herpes simples throughout the eczematous areas. |
|
| Herpes esophagitis Herpes esophagitis Herpes esophagitis is a viral infection of the esophagus caused by Herpes simplex virus .While the disease most often occurs in immunocompromised patients, including post-chemotherapy, immunosuppression with organ transplants and in AIDS, herpes esophagitis can also occur in immunocompetent... |
Symptoms may include painful swallowing (odynophagia Odynophagia Odynophagia is painful swallowing, in the mouth or esophagus. It can occur with or without dysphagia, or difficult swallowing.... ) and difficulty swallowing (dysphagia Dysphagia Dysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their dysphagia.... ). It is often associated with impaired immune function (e.g. HIV HIV Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive... /AIDS AIDS Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus... , immunosuppression Immunosuppression Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other... in solid organ transplants). |
Bell's palsy
Although the exact cause of Bell's palsyBell's palsy
Bell's palsy is a form of facial paralysis resulting from a dysfunction of the cranial nerve VII that results in the inability to control facial muscles on the affected side. Several conditions can cause facial paralysis, e.g., brain tumor, stroke, and Lyme disease. However, if no specific cause...
, a type of facial paralysis
Paralysis
Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...
, is unknown it may be related to reactivation of herpes simplex virus type 1. This theory has been contested, however since HSV is detected in large numbers of individuals who never experienced facial paralysis, and higher levels of antibodies for HSV are not found in HSV-infected individuals with Bell's palsy compared to those without. Regardless antivirals have been found to not improve outcomes.
Alzheimer's disease
HSV-1 has been proposed as a possible cause of Alzheimer's diseaseAlzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
. In the presence of a certain gene variation (APOE
Apolipoprotein E
Apolipoprotein E is a class of apolipoprotein found in the chylomicron and IDLs that binds to a specific receptor on liver cells and peripheral cells. It is essential for the normal catabolism of triglyceride-rich lipoprotein constituents.-Function:...
-epsilon4 allele carriers), HSV-1 appears to be particularly damaging to the nervous system and increases one’s risk of developing Alzheimer’s disease. The virus interacts with the components and receptors of lipoproteins, which may lead to the development of Alzheimer's disease. Without the presence of the gene allele, HSV type 1 does not appear to cause any neurological damage and thus increase the risk of Alzheimer’s. Herpes simplex virus type 1 DNA is localized within the beta-amyloid plaques that characterize Alzheimer's disease. It suggests that this virus is a major cause of the plaques and hence probably a significant aetiological factor in Alzheimer's disease.
Pathophysiology
Herpes is contracted through direct contact with an active lesion or body fluid of an infected person. Herpes transmission occurs between discordant partners; a person with a history of infection (HSV seropositive) can pass the virus to an HSV seronegative person. The only way to contract Herpes simplex virus 2 is through direct skin-to-skin contact with an infected individual. To infect a new individual, HSV travels through tiny breaks in the skin or mucous membranes in the mouth or genital areas. Even microscopic abrasions on mucous membranes are sufficient to allow viral entry.| HSV-2 genital | 15-25% of days |
| HSV-1 oral | 6-33% of days |
| HSV-1 genital | 5% of days |
| HSV-2 oral | 1% of days |
HSV asymptomatic shedding
Viral shedding
Viral shedding refers to the successful reproduction, expulsion, and host-cell infection caused by virus progeny. Once replication has been completed and the host cell is exhausted of all resources in making viral progeny, the viruses may begin to leave the cell by several methods.The term is used...
occurs at some time in most individuals infected with herpes. It can occur more than a week before or after a symptomatic recurrence in 50% of cases. Virus enters into susceptible cells via entry receptors
such as nectin-1, HVEM and 3-O sulfated heparan sulfate. Infected people that show no visible symptoms may still shed and transmit virus through their skin; asymptomatic shedding may represent the most common form of HSV-2 transmission. Asymptomatic shedding is more frequent within the first 12 months of acquiring HSV. Concurrent infection with HIV increases the frequency and duration of asymptomatic shedding. There are indications that some individuals may have much lower patterns of shedding, but evidence supporting this is not fully verified; no significant differences are seen in the frequency of asymptomatic shedding when comparing persons with one to twelve annual recurrences to those who have no recurrences.
Antibodies that develop following an initial infection with a type of HSV prevents reinfection with the same virus type—a person with a history of orofacial infection caused by HSV-1 cannot contract herpes whitlow or a genital infection caused by HSV-1. In a monogamous
Monogamy
Monogamy /Gr. μονός+γάμος - one+marriage/ a form of marriage in which an individual has only one spouse at any one time. In current usage monogamy often refers to having one sexual partner irrespective of marriage or reproduction...
couple, a seronegative female runs a greater than 30% per year risk of contracting an HSV infection from a seropositive male partner. If an oral HSV-1 infection is contracted first, seroconversion will have occurred after 6 weeks to provide protective antibodies against a future genital HSV-1 infection.
Diagnosis
Primary orofacial herpes is readily identified by clinical examination of persons with no previous history of lesions and contact with an individual with known HSV-1 infection. The appearance and distribution of sores in these individuals typically presents as multiple, round, superficial oral ulcers, accompanied by acute gingivitisGingivitis
Gingivitis is a term used to describe non-destructive periodontal disease. The most common form of gingivitis is in response to bacterial biofilms adherent to tooth surfaces, termed plaque-induced gingivitis, and is the most common form of periodontal disease...
. Adults with non-typical presentation are more difficult to diagnose. Prodromal symptoms that occur before the appearance of herpetic lesions help differentiate HSV symptoms from the similar symptoms of other disorders, such as allergic
Allergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
stomatitis
Stomatitis
Stomatitis is an inflammation of the mucous lining of any of the structures in the mouth, which may involve the cheeks, gums, tongue, lips, throat, and roof or floor of the mouth...
. When lesions do not appear inside the mouth, primary orofacial herpes is sometimes mistaken for impetigo
Impetigo
Impetigo is a highly contagious bacterial skin infection most common among pre-school children. People who play close contact sports such as rugby, American football and wrestling are also susceptible, regardless of age. Impetigo is not as common in adults. The name derives from the Latin impetere...
, a bacterial infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
. Common mouth ulcers (aphthous ulcer
Aphthous ulcer
An aphthous ulcer , also known as a canker sore, is a type of mouth ulcer which presents as a painful open sore inside the mouth or upper throat characterized by a break in the mucous membrane. Its cause is unknown, but they are not contagious...
) also resemble intraoral herpes, but do not present a vesicular stage.
Genital herpes can be more difficult to diagnose than oral herpes since most HSV-2-infected persons have no classical symptoms. Further confusing diagnosis, several other conditions resemble genital herpes, including fungal infection, lichen planus
Lichen planus
Lichen planus is a chronic mucocutaneous disease that affects the skin, tongue, and oral mucosa. The disease presents itself in the form of papules, lesions, or rashes. Lichen planus does not involve lichens, the fungus/algae symbionts that often grow on tree trunks; the name refers to the dry and...
, atopic dermatitis
Atopic dermatitis
Atopic dermatitis is an inflammatory, chronically relapsing, non-contagious and pruritic skin disorder...
, and urethritis
Urethritis
Urethritis is inflammation of the urethra. The most common symptom is painful or difficult urination.-Causes:The disease is classified as either gonococcal urethritis, caused by Neisseria gonorrhoeae, or non-gonococcal urethritis , most commonly caused by Chlamydia trachomatis...
. Laboratory
Laboratory
A laboratory is a facility that provides controlled conditions in which scientific research, experiments, and measurement may be performed. The title of laboratory is also used for certain other facilities where the processes or equipment used are similar to those in scientific laboratories...
testing is often used to confirm a diagnosis of genital herpes. Laboratory tests include: culture of the virus, direct fluorescent antibody
Direct fluorescent antibody
Direct fluorescent antibody is a laboratory test that uses antibodies tagged with fluorescent dye that can be used to detect the presence of microorganisms. This method offers straightforward detection of antigens using fluorescently labeled antigen-specific antibodies...
(DFA) studies to detect virus, skin biopsy
Skin biopsy
Skin biopsy is a biopsy technique in which a skin lesion is removed and sent to the pathologist to render a microscopic diagnosis. It is usually done under local anesthetic in a physician's office, and results are often available in 4 to 10 days. It is commonly performed by dermatologists. Skin...
, and polymerase chain reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....
(PCR) to test for presence of viral DNA. Although these procedures produce highly sensitive and specific diagnoses, their high costs and time constraints discourage their regular use in clinical practice.
Until recently, serological
Serology
Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...
tests for antibodies to HSV were rarely useful to diagnosis and not routinely used in clinical practice. The older IgM serologic assay could not differentiate between antibodies generated in response to HSV-1 or HSV-2 infection. However, the new Immunodot glycoprotein G-specific (IgG) HSV test is more than 98% specific at discriminating HSV-1 from HSV-2.
It is the opinion of some modern medical professionals that the new IgG test should always be clinically preferred to the old IgM test, however not all doctors appear to be informed of the availability of the newer, reliable IgG tests.
Prevention
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—meaning the infected partner will be seropositive but symptom free—by about 50%. Condom use also reduces the transmission risk significantly. Condom use is much more effective at preventing male to female transmission than vice-versa. 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. Previous HSV-1 infection appears to reduce the risk for acquisition of HSV-2 infection among women by a factor of 3.
However, asymptomatic carriers of the HSV-2 virus are still contagious. In many infections, the first symptom a person will have of their own infection is the horizontal transmission to a sexual partner or the vertical transmission of neonatal herpes to a newborn at term. Since most asymptomatic individuals are unaware of their infection, they are considered at high risk for spreading HSV.
In October 2011, it was reported that the anti-HIV drug tenofovir, when used topically in a microbicidal vaginal gel, prevented herpes virus infections.
Barrier methods
CondomCondom
A condom is a barrier device most commonly used during sexual intercourse to reduce the probability of pregnancy and spreading sexually transmitted diseases . It is put on a man's erect penis and physically blocks ejaculated semen from entering the body of a sexual partner...
s offer moderate protection against HSV-2 in both men and women, with consistent condom users having a 30% lower risk of HSV-2 acquisition compared with those who never use condoms. A female condom
Female condom
A female condom is a device that is used during sexual intercourse as a barrier contraceptive and to reduce the risk of sexually transmitted infections and unintended pregnancy...
can provide greater protection than the male condom, as it covers the labia. The virus cannot pass through a synthetic condom, but a male condom's effectiveness is limited because herpes ulcers may appear on areas not covered by the male condom. Neither type of condom prevents contact with the scrotum, anus, buttocks, or upper thighs, areas which may come in contact with ulcers or genital secretions during sexual activity. Protection against herpes simplex depends on the site of the ulcer; therefore if ulcers appear on areas not covered by condoms, abstaining from sexual activity until the ulcers are fully healed is one way to limit risk of transmission. The risk is not eliminated, however, as viral shedding capable of transmitting infection may still occur while the infected partner is asymptomatic. The use of condoms or dental dams also limits the transmission of herpes from the genitals of one partner to the mouth of the other (or vice versa) during oral sex
Oral sex
Oral sex is sexual activity involving the stimulation of the genitalia of a sex partner by the use of the mouth, tongue, teeth or throat. Cunnilingus refers to oral sex performed on females while fellatio refer to oral sex performed on males. Anilingus refers to oral stimulation of a person's anus...
. When one partner has a herpes simplex infection and the other does not, the use of antiviral medication, such as valaciclovir, in conjunction with a condom further decreases the chances of transmission to the uninfected partner. Topical microbicide
Microbicide
Microbicides for sexually transmitted diseases, are pharmacologic agents and chemical substances that are capable of killing or destroying certain microorganisms that commonly cause human infection, for example the human immunodeficiency virus....
s which contain chemicals that directly inactivate the virus and block viral entry are being investigated.
Vaccine
Vaccines for HSV are undergoing trials. Once developed, they may be used to help with prevention or minimize initial infections as well as treatment for existing infections.Antivirals
Antivirals may reduce asymptomatic shedding; it is believed asymptomatic genital HSV-2 viral shedding occurs on 20% of days per year in patients not undergoing antiviral treatment, versus 10% of days while on antiviral therapy.Pregnancy
The risk of transmission from mother to baby is highest if the mother becomes infected at around the time of delivery (30% to 60%), but the risk falls to 3% if it is a recurrent infection, and is less than 1% if there are no visible lesions. To prevent neonatal infections, seronegative women are recommended to avoid unprotected oral-genital contact with an HSV-1 seropositive partner and conventional sex with a partner having a genital infection during the last trimester of pregnancy. A seronegative mother who contracts HSV at this time has up to a 57% chance of conveying the infection to her baby during childbirth, since insufficient time will have occurred for the generation and transfer of protective maternal antibodies before the birth of the child, whereas a woman seropositive for both HSV-1 and HSV-2 has around a 1-3% chance of transmitting infection to her infant. Women who are seropositive for only one type of HSV are only half as likely to transmit HSV as infected seronegative mothers. Mothers infected with HSV are advised to avoid procedures that would cause trauma to the infant during birth (e.g. fetal scalp electrodes, forceps, and vacuum extractors) and, should lesions be present, to elect caesarean sectionCaesarean section
A Caesarean section, is a surgical procedure in which one or more incisions are made through a mother's abdomen and uterus to deliver one or more babies, or, rarely, to remove a dead fetus...
to reduce exposure of the child to infected secretions in the birth canal. The use of antiviral treatments, such as acyclovir, given from the 36th week of pregnancy, limits HSV recurrence and shedding during childbirth, thereby reducing the need for caesarean section.
Acyclovir is the recommended antiviral for herpes suppressive therapy during the last months of pregnancy. The use of valaciclovir and famciclovir, while potentially improving compliance have less well determined safety in pregnancy.
Treatment
There is no method to eradicate herpes virus from the body, but antiviral medications can reduce the frequency, duration, and severity of outbreaks. AnalgesicAnalgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
s such as ibuprofen
Ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug used for relief of symptoms of arthritis, fever, as an analgesic , especially where there is an inflammatory component, and dysmenorrhea....
and acetaminophen can reduce pain and fever. Topical anesthetic treatments such as prilocaine
Prilocaine
Prilocaine is a local anesthetic of the amino amide type first prepared by Claes Tegner and Nils Lofgren. In its injectable form , it is often used in dentistry. It is also often combined with lidocaine as a preparation for dermal anesthesia , for treatment of conditions like paresthesia...
, lidocaine
Lidocaine
Lidocaine , Xylocaine, or lignocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery.- History :Lidocaine, the first amino...
, benzocaine
Benzocaine
Benzocaine is a local anesthetic commonly used as a topical pain reliever, or in cough drops. It is the active ingredient in many over-the-counter anesthetic ointments...
or tetracaine
Tetracaine
Tetracaine is a potent local anesthetic of the ester group...
can also relieve itching and pain.
Antiviral
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
s that are effective for treating herpes including: aciclovir
Aciclovir
Aciclovir or acyclovir , chemical name acycloguanosine, abbreviated as ACV,is a guanosine analogue antiviral drug, marketed under trade names such as Cyclovir, Herpex, Acivir, Acivirax, Zovirax, and Zovir...
(acyclovir), valaciclovir (valacyclovir), famciclovir
Famciclovir
Famciclovir is a guanine analogue antiviral drug used for the treatment of various herpesvirus infections, most commonly for herpes zoster . It is a prodrug form of penciclovir with improved oral bioavailability...
, and penciclovir. Aciclovir was the first discovered and is now available in generic.
Evidence supports the use of aciclovir and valaciclovir in the treatment of herpes labialis as well as herpes infections in people with cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. The evidence to support the use of acyclovir in primary herpetic gingivostomatitis is less strong.
Topical
A number of topicalTopical
In medicine, a topical medication is applied to body surfaces such as the skin or mucous membranes such as the vagina, anus, throat, eyes and ears.Many topical medications are epicutaneous, meaning that they are applied directly to the skin...
antivirals are effective for herpes labialis including acyclovir, penciclovir, and docosanol
Docosanol
Docosanol, also known as behenyl alcohol, is a saturated fatty alcohol used traditionally as an emollient, emulsifier, and thickener in cosmetics, nutritional supplement , and more recently, in a Food and Drug Administration approved pharmaceutical, Abreva, approved as an antiviral agent for...
. Docosanol can be purchased over the counter in Canada and the USA.
Alternative medicine
Certain dietary supplementDietary supplement
A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
s and alternative remedies are claimed to be beneficial in the treatment of herpes. There is however insufficient evidence to support use of many of these compounds including echinacea
Echinacea
Echinacea is a genus of herbaceous flowering plants in the daisy family, Asteraceae. The nine species it contains are commonly called purple coneflowers. They are endemic to eastern and central North America, where they are found growing in moist to dry prairies and open wooded areas. They have...
, eleuthero, L-lysine, zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
, bee products and aloe vera
Aloe vera
Aloe vera, pronounced , also known as the true aloe or medicinal aloe, is a species of succulent plant in the genus Aloe that is believed to have originated in the Sudan. Aloe vera grows in arid climates and is widely distributed in Africa, India, Nepal and other arid areas.The species is...
.
A single study indicates possible benefit from laser
Laser
A laser is a device that emits light through a process of optical amplification based on the stimulated emission of photons. The term "laser" originated as an acronym for Light Amplification by Stimulated Emission of Radiation...
treatment.
Prognosis
Following active infection, herpes viruses establish a latentVirus latency
Virus latency is the ability of a pathogenic virus to lie dormant within a cell, denoted as the lysogenic part of the viral life cycle. A latent viral infection is a type of persistent viral infection which is distinguished from a chronic viral infection...
infection in sensory and autonomic ganglia of the nervous system. The double-stranded DNA of the virus is incorporated into the cell physiology by infection of the nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
of a nerve's cell body
Soma (biology)
The soma , or perikaryon , or cyton, is the bulbous end of a neuron, containing the cell nucleus. The word "soma" comes from the Greek σῶμα, meaning "body"; the soma of a neuron is often called the "cell body"...
. HSV latency is static—no virus is produced—and is controlled by a number of viral genes, including Latency Associated Transcript (LAT).
Many HSV-infected people experience recurrence within the first year of infection. Prodrome
Prodrome
In medicine, a prodrome is an early symptom that might indicate the start of a disease before specific symptoms occur. It is derived from the Greek word prodromos or precursor...
precedes development of lesions. Prodromal symptoms include tingling (paresthesia
Paresthesia
Paresthesia , spelled "paraesthesia" in British English, is a sensation of tingling, burning, pricking, or numbness of a person's skin with no apparent long-term physical effect. It is more generally known as the feeling of "pins and needles" or of a limb "falling asleep"...
), itching, and pain where lumbosacral nerves innervate the skin. Prodrome may occur as long as several days or as short as a few hours before lesions develop. Beginning antiviral treatment when prodrome is experienced can reduce the appearance and duration of lesions in some individuals. During recurrence, fewer lesions are likely to develop, lesions are less painful and heal faster (within 5–10 days without antiviral treatment) than those occurring during the primary infection. Subsequent outbreaks tend to be periodic or episodic, occurring on average four to five times a year when not using antiviral therapy.
The causes of reactivation are uncertain, but several potential triggers have been documented. A recent study (2009) showed that the protein VP16 plays a key role in reactivation of the dormant virus. Changes in the immune system during menstruation
Menstruation
Menstruation is the shedding of the uterine lining . It occurs on a regular basis in sexually reproductive-age females of certain mammal species. This article focuses on human menstruation.-Overview:...
may play a role in HSV-1 reactivation. Concurrent infections, such as viral upper respiratory tract infection
Upper respiratory tract infection
Upper respiratory tract infections are the illnesses caused by an acute infection which involves the upper respiratory tract: nose, sinuses, pharynx or larynx...
or other febrile diseases, can cause outbreaks. Reactivation due to infection is the likely source of the historic terms cold sore and fever blister.
Other identified triggers include: local injury to the face, lips, eyes, or mouth, trauma, surgery, radiotherapy, and exposure to wind, ultraviolet light, or sunlight.
The frequency and severity of recurrent outbreaks vary greatly between patients. Some individuals' outbreaks can be quite debilitating with large, painful lesions persisting for several weeks, while others will experience only minor itching or burning for a few days. There is some evidence that genetics plays a role in the frequency of cold sore outbreaks. An area of human chromosome 21 that includes 6 genes has been linked to frequent oral herpes outbreaks. An immunity to the virus is built over time. Most infected individuals will experience fewer outbreaks and outbreak symptoms will often become less severe. After several years, some people will become perpetually asymptomatic
Asymptomatic
In medicine, a disease is considered asymptomatic if a patient is a carrier for a disease or infection but experiences no symptoms. A condition might be asymptomatic if it fails to show the noticeable symptoms with which it is usually associated. Asymptomatic infections are also called subclinical...
and will no longer experience outbreaks, though they may still be contagious to others. Immuno-compromised individuals may experience episodes that are longer, more frequent, and more severe. Antiviral medication has been proven to shorten the frequency and duration of outbreaks. Outbreaks may occur at the original site of the infection or in proximity to nerve endings that reach out from the infected ganglia. In the case of a genital infection, sores can appear at the original site of infection or near the base of the spine, the buttocks, or the back of the thighs.
HSV-2 infected individuals are at higher risk for acquiring HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
when practicing unprotected sex with HIV-positive persons, particularly during an outbreak with active lesions.
Epidemiology
Worldwide rates of HSV infection are between 65% and 90%. HSV1 is more common than HSV2 with rates of both increasing as people age. Rates of infection are determined by the presence of antibodies against either viral species.In the US, 57.7% of the population is infected with HSV-1 and 16.2% are infected with HSV-2. Among those HSV-2 seropositive, only 18.9% were aware that they were infected.
History
Herpes has been known for at least 2,000 years. It is said that Emperor TiberiusTiberius
Tiberius , was Roman Emperor from 14 AD to 37 AD. Tiberius was by birth a Claudian, son of Tiberius Claudius Nero and Livia Drusilla. His mother divorced Nero and married Augustus in 39 BC, making him a step-son of Octavian...
banned kissing in Rome for a time due to so many people having cold sores. In the 16th century Romeo and Juliet
Romeo and Juliet
Romeo and Juliet is a tragedy written early in the career of playwright William Shakespeare about two young star-crossed lovers whose deaths ultimately unite their feuding families. It was among Shakespeare's most popular archetypal stories of young, teenage lovers.Romeo and Juliet belongs to a...
, it is mentioned that there are blisters "o'er ladies' lips." In 18th century it was so common among prostitutes that it was called "a vocational disease of women."
The term Herpes Simplex appeared in Richard Boulton
Richard Boulton
Richard Boulton , was a physician.Boulton was educated at Brasenose College, Oxford, and for some time settled at Chester, was the author of a number of works on the medical and kindred sciences, including: 1. 'Reason of Muscular Motion,' 1697. 2. 'Treatise concerning the Heat of the Blood,' 1698....
's A System of Rational and Practical Chirurgery in 1713, where the terms Herpes miliaris and Herpes exedens also appeared.
Herpes was not found to be a virus until the 1940s.
Herpes antiviral therapy began in the early 1960s with the experimental use of medication that interfered with viral replication called deoxyribonucleic acid (DNA) inhibitors. The original use was against normally fatal or disabilitating illness such as adult encephalitis, keratitis, in immunocompromised (transplant) patients, or disseminated herpes zoster. The original compounds used were 5-iodo-2'-deoxyuridine, AKA idoxuridine, IUdR, or(IDU) and 1-β-D-arabinofuranosylcytosine or ara-C, later marketed under the name cytosar or cytorabine. The usage expanded to include topical treatment of herpes simplex, zoster, and varicella. Some trials combined different antivirals with differing results. The introduction of 9-β-D-arabinofuranosyladenine, AKA ara-A or vidarabine, considerably less toxic than Ara-C, in the mid 1970s, heralded the way for the beginning of regular neonatal antiviral treatment. Vidarabine was the first systemically administered antiviral medication with activity against HSV for which therapeutic efficacy outweighed toxicity for the management of life-threatening HSV disease. Intravenous vidarabine was licensed for use by the U.S. Food and Drug Administration (FDA) in 1977. Other experimental antivirals of that period included: Heparin, trifluorothymidine (TFT), Ribivarin, interferon, Virazole, and 5-methoxymethyl-2'-deoxyuridine (MMUdR). The introduction of 9-(2-hydroxyethoxymethyl)guanine, AKA acyclovir, in the late 1970s raised antiviral treatment another notch and led to vidarabine vs. acyclovir trials in the late 1980s. The lower toxicity and ease of administration over vidarabine has led to acyclovir becoming the drug of choice for herpes treatment after it was licensed by the FDA in 1998. Another advantage in the treatment of neonatal herpes included greater reductions in mortality and morbidity with increased dosages, something that did not occur when compared with increased dosages of vidarabine. On the other side of the equation, acyclovir seems to inhibit antibody response and newborns on acyclovir antiviral treatment experienced a slower rise in antibody titer than those on vidarabine.
Society and culture
Herpes simplex was not always stigmatised. It was merely a cold sore in an unusual place until the 1970s. As late as 1975, a study of “Psychological morbidity in a clinic for sexually-transmitted disease” (Richard Mayou, The London Hospital) does not mention herpes simplex because at that time, there was no significant morbidity problem (i.e. mental anxiety or illness) associated with the virus.In the Journal of Clinical Investigation, Pedro Cuatrecasas states, “during the R&D of acyclovir (Zovirax), marketing [department of Burroughs Wellcome] insisted that there were ‘no markets’ for this compound. Most had hardly heard of genital herpes...” Thus marketing the medical condition – separating the ‘normal cold sore’ from the ‘stigmatized genital infection’ was to become the key to marketing the drug, a process now known as ‘disease mongering’.
Since the creation of the herpes hype, some people experience negative feelings related to the condition following diagnosis, particularly if they have acquired the genital form of the disease. Feelings can include depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
, fear of rejection, feelings of isolation
Solitude
Solitude is a state of seclusion or isolation, i.e., lack of contact with people. It may stem from bad relationships, deliberate choice, infectious disease, mental disorders, neurological disorders or circumstances of employment or situation .Short-term solitude is often valued as a time when one...
, fear of being found out, self-destructive feelings, and fear of masturbation. These feelings usually lessen over time. Much of the hysteria and stigma surrounding herpes stems from a media campaign beginning in the late 1970s and peaking in the early 1980s. There were multiple articles worded in fear-mongering and anxiety-provoking terminology, such as the now ubiquitous "attacks," "outbreaks," "victims," and "sufferers." At one point the term "herpetic" even entered the popular lexicon. The articles were published by Reader's Digest, U.S. News, and Time magazine, among others. A made-for-TV movie was named Intimate Agony. The peak was when Time magazine had 'Herpes: The New Scarlet Letter' on the cover in August 1982, forever stigmatizing the word in the public mind. The scientific reality is that most people are asymptomatic, the virus causes no real health problems for a vast majority of people, and a vast majority (around 90%) of the Earth's population carries HSV-1, 2, or both. Herpes support groups
Herpes support groups
For information about the disease see Herpes simplex.Herpes Support Groups are organized groups, some grass roots and some official nonprofit or medical groups, that provide support and information for people who have been diagnosed with genital herpes...
have been formed in the United States and the UK, providing information about herpes and running message forums and dating websites for "sufferers." People with the herpes virus are often hesitant to divulge to other people, including friends and family, that they are infected. This is especially true of new or potential sexual partners whom they consider casual.
Research
Researchers at the University of FloridaUniversity of Florida
The University of Florida is an American public land-grant, sea-grant, and space-grant research university located on a campus in Gainesville, Florida. The university traces its historical origins to 1853, and has operated continuously on its present Gainesville campus since September 1906...
have made a Hammerhead ribozyme
Hammerhead ribozyme
Hammerhead RNAs are RNAs that self-cleave via a small conserved secondary structural motif termed a hammerhead because of its shape. Most hammerhead RNAs are subsets of two classes of plant pathogenic RNAs: the satellite RNAs of RNA viruses and the viroids. The self-cleavage reactions, first...
that targets and cleaves the mRNA of essential genes in HSV-1. The hammerhead which targets the mRNA of the UL20 gene greatly reduced the level of HSV-1 ocular infection in rabbits and reduced the viral yield in vivo. The gene-targeting approach uses a specially designed RNA enzyme to inhibit strains of the herpes simplex virus. The enzyme disables a gene responsible for producing a protein involved in the maturation and release of viral particles in an infected cell. The technique appears to be effective in experiments with mice and rabbits, but further research is required before it can be attempted in people who are infected with herpes.
Another possibility to eradicate the HSV-1 variant is being pursued by a team at Duke University
Duke University
Duke University is a private research university located in Durham, North Carolina, United States. Founded by Methodists and Quakers in the present day town of Trinity in 1838, the school moved to Durham in 1892. In 1924, tobacco industrialist James B...
. By figuring out how to switch all copies of the virus in the host from latency to their active stage at the same time, rather than the way the virus copies normally stagger their activity stage, leaving some dormant somewhere at all times, it is thought that conventional anti-viral drugs can kill the entire virus population completely, since they can no longer hide in the nerve cells. One class of drugs called antagomir
Antagomir
Antagomirs are one of a novel class of chemically engineered oligonucleotides. Antagomirs are used to silence endogenous microRNA.An antagomir is a small synthetic RNA that is perfectly complementary to the specific miRNA target with either mispairing at the cleavage site of Ago2 or some sort of...
could serve this purpose. These are chemically engineered oligonucleotides or short segments of RNA, that can be made to mirror their target genetic material, namely herpes microRNAs. They could be engineered to attach and thus 'silence' the microRNA, thus rendering the virus incapable to keep latent in their host. Professor Cullen believes a drug could be developed to block the microRNA whose job it is to suppress HSV-1 into latency.
One vaccine that was under trial was Herpevac, a vaccine against HSV-2. The National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
(NIH) in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
conducted phase III trials
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
of Herpevac. In 2010, it was reported that, after 8 years of study in more than 8000 women in the United States and Canada, there was no sign of positive results against the sexually transmitted disease caused by HSV-2 (and this despite earlier favorable interim reports).
A laboratory at Harvard Medical School
Harvard Medical School
Harvard Medical School is the graduate medical school of Harvard University. It is located in the Longwood Medical Area of the Mission Hill neighborhood of Boston, Massachusetts....
has developed dl5-29 (now known as ACAM-529), a replication-defective mutant virus that has proved successful both in preventing HSV-2/HSV-1 infections, and in combating the virus in already infected hosts, in animal models. It has been shown that the replication-defective vaccine induces strong HSV-2-specific antibody and T-cell responses; protects against challenge with a wild-type HSV-2 virus; greatly reduces the severity of recurrent disease; provides cross-protection against HSV-1, and renders the virus unable to revert to a virulent state or to become latent. His vaccine is now being researched and developed by Accambis (acquired by Sanofi Pasteur
Sanofi pasteur
Sanofi Pasteur is the vaccines division of sanofi-aventis Group. It is the largest company in the world devoted entirely to vaccines.- History :...
in September 2008), and is due to be applied as an Investigational New Drug in 2009. However, the status of ACAM-529 became after the acquisition somewhat unclear. According to Jim Tartaglia, a company representative of Sanofi Pasteur, ACAM-529 is still under development and should be enter phase I clinical testing in 2012.
A private company called BioVex began Phase I clinical trials for ImmunoVEX, another proposed vaccine, in March 2010. A completely new approach has the "HSV-2 ICP0 live-attenuated HSV-2 vaccine" investigated by Dr. William Halford at the Southern Illinois University (SIU) School of Medicine
Southern Illinois University School of Medicine
Southern Illinois University School of Medicine is an allopathic medical school located in Springfield, Illinois, the state capital. It is part of the Southern Illinois University system, which includes a campus in Edwardsville as well as the flagship in Carbondale. The medical school was founded...
.
External links
- Genital Herpes Fact Sheet at The Centers for Disease Control and Prevention
- "Genital Herpes: A Hidden Epidemic" at U.S. Food and Drug Administration
- Updated Herpes Handbook from Westover Heights Clinic
- Herpes Blood Tests Quick Reference Guide
- "The Importance and Practicalities of Patient Counseling in the Prevention and Management of Genital Herpes" (2004) at MedscapeMedscapeMedscape is a web resource for physicians and other health professionals. It features peer-reviewed original medical journal articles, CME , a customized version of the National Library of Medicine's MEDLINE database, daily medical news, major conference coverage, and drug information—including a...
- International Herpes Management Forum
- Provides Ratios of Lysine to Arginine in Common Foods
- Herpes simplex: Host viral protein interactions on WikiGenes