Herpes Simplex Viruses
Trends in HSV Types and Genital Herpes
Genital herpes can be caused by either HSV-2 or HSV-1. In the past, most genital herpes cases were caused by HSV-2. In recent years, HSV-1 has become a significant cause in developed countries, including the United States. Oral sex with an infected partner can transmit HSV-1 to the genital area.
Transmission of Genital Herpes
Genital herpes is a sexually transmitted disease spread by skin-to-skin contact. The risk of infection is highest during outbreak periods when there are visible sores and lesions. However, genital herpes can also be transmitted when there are no visible symptoms. Most new cases of genital herpes infection do not cause symptoms, and many people infected with HSV-2 are unaware that they have genital herpes.
To help prevent genital herpes transmission:
When genital herpes symptoms do appear, they are usually worse during the first outbreak than during recurring attacks. During an initial outbreak:
Herpes, Pregnancy, and Newborn Infants
Herpes can pose serious risks for a pregnant woman and her baby. The risk is greatest for mothers with a first-time infection since the virus can be transmitted to the infant during childbirth. New guidelines from the American Academy of Pediatrics recommend using specific diagnostic tests for women in labor to determine the risk of transmission. Babies born to mothers infected with genital herpes are treated with the antiviral drug acyclovir, which can help suppress the virus.
Herpes simplex virus (HSV) is a common virus that causes infections of the skin and mucous membranes. It can sometimes cause more serious infections in other parts of the body.
HSV is part of a group of eight herpes viruses that can cause human disease. They include human herpes virus 8 (the cause of Kaposi's sarcoma) and varicella- zoster virus (also known as herpes zoster, the virus responsible for shingles and chicken pox). There are more than 80 other strains of herpes viruses that can infect various animals.
Herpes viruses differ in many ways, but the viruses share certain characteristics, notably the word "herpes," which comes from the Greek word “herpein” meaning "to creep." This refers to the unique characteristic pattern of all herpes viruses to "creep along" local nerve pathways to the nerve clusters at the end, where they remain in an inactive (dormant) state for variable periods of time. This period of inactivity is called latency.
There are two forms of the herpes simplex virus:
HSV-1 and HSV-2 are distinguished by different proteins on their surfaces. They can occur separately, or they can both infect the same individual. Until recently, the general rule was to assume that HSV-1 caused oral herpes and HSV-2 caused genital herpes. It is now clear, however, that either type of herpes virus can be found in the genital or oral areas (or other sites). In fact, HSV-1 is now responsible for more than half of all new cases of genital herpes in developed countries.
For infection to occur, the following conditions must apply:
When herpes simplex virus enters the body, the infection process typically takes place as follows:
Herpes is transmitted through close skin-to-skin contact. To infect people, the herpes simplex viruses (both HSV-1 and HSV-2) must get into the body through tiny injuries in the skin or through a mucous membrane, such as inside the mouth or on the genital area. The risk for infection is highest with direct contact of blisters or sores during an outbreak. But the infection can also develop from contact with an infected partner who does not have visible sores or other symptoms.
Once the virus has contact with the mucous membranes or skin wounds, it begins to replicate. The virus is then transported within nerve cells to their roots where it remains inactive (latent) for some period of time. During inactive periods, the virus is in a sleeping (dormant) state and cannot be transmitted to another person. However, at some point, the virus wakes up and travels along nerve pathways to the surface the skin where it begins to multiply again.
During this time, the virus can infect other people if it is passed along in body fluids or secretions. This period of reactivation, replication, and transmission is called viral shedding. Viral shedding may be accompanied by noticeable symptoms (called disease outbreak) but it can also occur without causing symptoms (called asymptomatic shedding).
Sometimes, infected people can transmit the virus and infect other parts of their own bodies (most often the hands, thighs, or buttocks). This process, known as autoinoculation, is uncommon, since people generally develop antibodies that protect against this problem.
Transmission of Oral Herpes. Oral herpes is usually caused by HSV-1. HSV-1 is the most prevalent form of herpes simplex virus, and infection is most likely to occur during preschool years. Oral herpes is easily spread by direct exposure to saliva or even from droplets in breath. Skin contact with infected areas is enough to spread it. Transmission most often occurs through close personal contact, such as kissing. In addition, because herpes simplex virus 1 can be passed in saliva, people should also avoid sharing toothbrushes or eating utensils with an infected person.
Transmission of Genital Herpes. Genital herpes is transmitted through sexual activity. People can get HSV-2 through genital contact or HSV-1 through mouth-to-genital contact with an infected partner. People with multiple sexual partners are at high risk as are those who do not use latex condoms. .
People with active symptoms of genital herpes are at very high risk for transmitting the infection. Unfortunately, evidence suggests that most cases of genital herpes infections occur when the virus is shedding but producing no symptoms. Most people either have no symptoms or don't recognize them when they appear.
In the past, genital herpes was mostly caused by HSV-2, but HSV-1 genital infection is increasing. This may be due to the increase in oral sex activity among young adults. There is also evidence that children today are less likely to get cold sores and become exposed to HSV-1 during childhood. If adolescents do not have have antibodies to HSV-1 by the time they become sexually active, they may be more susceptible to genitally acquiring HSV-1 through oral sex.
Oral herpes is usually caused by HSV-1. The first infection usually occurs between 6 months and 3 years of age. By adulthood, nearly all people have been infected with HSV-1.
According to the U.S. Centers for Disease Control and Prevention, about 1 in 6 Americans ages 14 - 49 years have genital herpes. While HSV-2 remains the main cause of genital herpes, in recent years HSV-1 has significantly increased as a cause, most likely because of oral-genital sex. Except for people in monogamous relationships with uninfected partners, everyone who is sexually active is at risk for genital herpes.
Risk factors for genital herpes include a history of a prior sexually transmitted disease, early age for first sexual intercourse, a high number of sexual partners, and loq socioeconomic status. Women are more susceptible to HSV-2 infection because herpes is more easily transmitted from men to women than from women to men. About 1 in 5 women, compared to 1 in 9 men, have genital herpes. African-American women are at particularly high risk
People with compromised immune systems, notably patients with HIV, are at very high risk for genital herpes. These patients are also at risk for more severe complications from herpes. Other immunocompromised patients include those taking drugs that suppress the immune system and patients who have received transplants.
The only definite way to prevent genital herpes is to abstain from sex or to engage in sex in a mutually monogamous relationship with an uninfected partner.
Infected people should take steps to avoid transmitting genital herpes to others. It is almost impossible to defend against the transmission of oral herpes since it can be transmitted by very casual contact, including kissing. Still, you can help reduce the risk of transmitting oral herpes by not sharing objects that touch the mouth such as eating and drinking utensils, toothbrushes, and towels.
Genital herpes is contagious from the first signs of tingling and burning (prodrome) until the time that sores have completely healed. It is best to refrain from any type of sex (vaginal, anal, oral) during periods of active outbreak. However, herpes can also be transmitted when symptoms are not present (asymptomatic shedding).
The following precautions can help reduce the risk of transmission:
To reduce the risk of passing the herpes virus to another part of your body (such as the eyes and fingers), avoid touching a herpes blister or sore during an outbreak. If you do, be sure to immediately wash your hands with hot water and soap.
The herpes virus does not live very long outside the body. While the chances of transmitting or contracting herpes from a toilet seat or towel are extremely low, it is advisable to wipe off toilet seats and not to share damp towels.
Recent studies have suggested that male circumcision may help reduce the risk of HSV-2, as well as human papillomavirus (HPV) and HIV infections. However, circumcision does not completely prevent sexually transmitted diseases. Men who are circumcised should still practice safe sex, including using condoms.
There is currently no vaccine to prevent genital herpes, but several investigational herpes vaccines are being actively studied in clinical trials.
Except in very rare instances and special circumstances, herpes simplex virus is not life threatening. However, herpes can cause significant and widespread complications in people who don’t have fully functioning immune systems.
People infected with herpes have an increased risk for acquiring and transmitting HIV, the virus that causes AIDS. The U.S. Centers for Disease Control and Prevention (CDC) recommends that all patients diagnosed with herpes simplex virus 2 (HSV-2) should get tested for HIV.
Most patients with HIV are co-infected with HSV-2 and are particularly vulnerable to its complications. When a person has both viruses, each virus increases the severity of the other. HSV-2 infection increases HIV levels in the genital tract, which makes it easier for the HIV virus to be spread to sexual partners.
Pregnant women who have genital herpes due to either herpes simplex virus 2 (HSV-2) or herpes simplex virus 1 (HSV-1) have an increased risk for miscarriage, premature labor, inhibited fetal growth, or transmission of the herpes infection to the infant either in the uterus or at the time of delivery. Herpes in newborn babies (herpes neonatalis) can be a very serious condition.
Fortunately, neonatal herpes is rare. Although about 25 - 30% of pregnant women have genital herpes, fewer than 0.1% of babies are born with neonatal herpes. The baby is at greatest risk during a vaginal delivery, especially if the mother has an asymptomatic infection that was first introduced late in the pregnancy. In such cases, 30 - 50% of newborns become infected. Recurring herpes or a first infection that is acquired early in the pregnancy pose a much lower risk to the infant.
The reasons for the higher risk with a first-time late primary infection are:
The risk for transmission also increases if infants with infected mothers are born prematurely, if there is invasive monitoring, or if instruments are used during vaginal delivery. Transmission can occur if the amniotic membrane of an infected woman ruptures prematurely, or as the infant passes through an infected birth canal. This increased risk is present if the woman is having or has recently had an active herpes outbreak in the genital area.
Very rarely, the virus is transmitted across the placenta, a form of the infection known as congenital herpes. Also rarely, newborns may contract herpes during the first weeks of life from being kissed by someone with a herpes cold sore.
Unfortunately, only about 5% of infected pregnant women have a history of symptoms, so in many cases herpes infection is not suspected, or symptoms are missed, at the time of delivery. Fortunately, for women who do show genital lesions, doctors can now use newer rapid diagnostic blood tests to quickly determine a pregnant woman’s chance of transmitting the virus to her baby during delivery.
In general, if there is evidence of an active outbreak, doctors usually advise a Cesarean section to prevent the baby from contracting the virus in the birth canal during delivery. Some women with new or recurrent herpes may also be prescribed antiviral medication during pregnancy. A woman with herpes can usually safely breastfeed her baby as long as she does not have a lesion on her breast or nipple.
Herpes infection in a newborn can cause a range of symptoms, including skin rash, fevers, mouth sores, and eye infections. If left untreated, neonatal herpes is a very serious and even life-threatening condition. Neonatal herpes can spread to the brain and central nervous system, causing encephalitis and meningitis and can lead to intellectual disability, cerebral palsy, and death. Herpes can also spread to internal organs, such as the liver and lungs.
Infants infected with herpes are treated with acyclovir. They usually receive several weeks of intravenous acyclovir treatment followed by several months or oral acyclovir. It is important to treat babies quickly, before the infection spreads to the brain and other organs.
Herpes Encephalitis. Herpes simplex encephalitis is inflammation of the brain caused by either HSV-1 or HSV-2. It is a rare but extremely serious brain disease. Untreated, herpes encephalitis is fatal over 70% of the time. Respiratory arrest can occur within the first 24 - 72 hours. Fortunately, rapid diagnostic tests and treatment with acyclovir have significantly improved survival rates and reduced complication rates. Nearly all who recover suffer some impairment, ranging from very mild neurological changes to paralysis. .
Herpes Meningitis. Herpes simplex meningitis, an inflammation of the membranes that line the brain and spinal cord, is mainly caused by HSV-2. Like encephalitis, meningitis symptoms include headache, fever, stiff neck, vomiting, and sensitivity to light. Fortunately, after lasting for up to a week, herpes meningitis usually resolves without complications, although symptoms can recur.
Ocular herpes is a recurrent infection that affects the eyes. It is mainly caused by HSV-1 but can also be caused by HSV-2. Ocular herpes is usually a simple infection that clears up in a few days, but in its more serious forms, and in severe cases, it can cause blindness.
Types of ocular herpes include:
Eczema Herpeticum. A rare form of herpes infection called eczema herpeticum, also known as Kaposi's varicellaform eruption, can affect patients with skin disorders and immunocompromised patients. The disease tends to develop into widespread skin infection that resembles impetigo. Symptoms appear abruptly and can include fever, chills, and malaise. Clusters of dimpled blisters emerge over 7 - 10 days and spread widely. They can become secondarily infected with staphylococcal or streptococcal bacteria. With treatment, lesions heal in 2 - 6 weeks. Untreated, this condition can be extremely serious and possibly fatal.
Gingivostomatitis.Herpes can cause multiple painful ulcers on the gums and mucous membranes of the mouth, a condition called gingivostomatitis. This condition usually affects children 1 - 5 years of age. It nearly always subsides within 2 weeks. Children with gingivostomatitis commonly develop herpetic whitlow (herpes of the fingers).
Herpes symptoms vary depending on whether the outbreak is initial or recurrent. The first (primary) outbreak is usually worse than recurrent outbreaks with more severe and prolonged symptoms. However, most cases of herpes simplex virus infections do not produce symptoms. In fact, studies indicate that 10 - 25% of people infected with HSV-2 are unaware that they have genital herpes. Even if infected people have mild or no symptoms, they can still transmit the herpes virus.
Symptoms of Genital Herpes
Primary Genital Herpes Outbreak. For patients with symptoms, the first outbreak usually occurs in or around the genital area 1 - 2 weeks after sexual exposure to the virus. The first signs are a tingling sensation in the affected areas (such as genitalia, buttocks, and thighs) and groups of small red bumps that develop into blisters. Over the next 2 - 3 weeks, more blisters can appear and rupture into painful open sores. The lesions eventually dry out, develop a crust, and heal rapidly without leaving a scar. Blisters in moist areas heal more slowly than others. The lesions may sometimes itch, but itching decreases as they heal.
About 40% of men and 70% of women develop other symptoms during initial outbreaks of genital herpes, such as flu-like discomfort, headache, muscle aches, fever, and swollen glands. (Glands can become swollen in the groin area as well as the neck.) Some women may have difficulty urinating and may, occasionally, require a urinary catheter. Women may also experience vaginal discharge.
Recurrent Genital Herpes Outbreak. In general, recurrences are much milder than the initial outbreak. The virus sheds for a much shorter period of time (about 3 days) compared to an initial outbreak of 3 weeks. Women may have only minor itching, and the symptoms may be even milder in men.
On average, people have about four recurrences during the first year, although this varies widely. Over time, recurrences decrease in frequency. There are some differences in frequency of recurrence depending on whether HSV-2 or HSV-1 causes genital herpes. HSV-2 genital infection is more likely to cause recurrences than HSV-1.
Symptoms of Oral Herpes
Oral herpes (herpes labialis) is most often caused by herpes simplex virus 1 (HSV-1) but can also be caused by herpes simplex virus 2 (HSV-2). It usually affects the lips and, in some primary attacks, the mucous membranes in the mouth. A herpes infection may occur on the cheeks or in the nose, but facial herpes is very uncommon.
Primary Oral Herpes Infection. If the primary (initial) oral infection causes symptoms, they can be very painful, particularly in small children.
In children, the infection usually occurs in the mouth. In adolescents, the primary infection is more apt to appear in the upper part of the throat and cause soreness.
Recurrent Oral Herpes Infection. Most patients have only a couple of outbreaks a year, although a small percentage of patients have more frequent recurrences. HSV-2 oral infections tend to recur less frequently than HSV-1. Recurrences are usually much milder than primary infections and are known commonly as cold sores or fever blisters (because they may arise during a bout of cold or flu). They usually show up on the outer edge of the lips and rarely affect the gums or throat. (Cold sores are commonly mistaken for the crater-like mouth lesions known as canker sores, which are not associated with herpes simplex virus.)
Course of Recurrence. Most cases of herpes simplex recur. The site on the body and the type of virus influence how often it comes back. Recurrences of genital herpes are more likely with HSV-2 infection than with HSV-1 infection.
The virus usually takes the following course:
Triggers of Recurrence. HSV outbreaks can be triggered by different factors. They include sunlight, wind, fever, physical injury, surgery, menstruation, suppression of the immune system, and emotional stress. Oral herpes can be triggered within about 3 days of intense dental work, particularly root canal or tooth extraction.
Timing of Recurrences. Recurrent outbreaks may occur at intervals of days, weeks, or years. For most people, outbreaks recur with more frequency during the first year after an initial attack. During that period, the body mounts an intense immune response to HSV. The good news is that in most healthy people, recurring infections tend to become progressively less frequent, and less severe, over time. However, the immune system cannot kill the virus completely. Herpes simplex virus causes lifelong infections.
The herpes simplex virus is usually identifiable by its characteristic lesion: A thin-walled blister on an inflamed base of skin. However, other conditions can resemble herpes, and doctors cannot base a herpes diagnosis on visual inspection alone. In addition, many patients who carry the virus do not have visible genital or oral lesions. Laboratory tests are needed to confirm a herpes diagnosis. These tests include:
The U.S. Centers for Disease Control (CDC) recommends that both virologic and serologic tests be used for diagnosing genital herpes. Patients diagnosed with genital herpes should also be tested for other sexually transmitted diseases. At this time, doctors do not recommend screening for herpes simplex 1 (HSV-1) or herpes simplex 2 (HSV-2) in the general population.
Genital herpes can be caused by either HSV-1 or HSV-2. It is important for doctors to determine whether the genital herpes infection is caused by HSV-1 or HSV-2, as the type of herpes infection influences prognosis and treatment recommendations. Recurrences of genital herpes, and viral shedding without overt symptoms, are much less frequent with HSV-1 infection than with HSV-2.
False-negative (testing negative when herpes infection is actually present) or false-positive (testing positive when herpes infection is not actually present) results can occur. Your doctor may recommend that you have a test repeated.
Viral culture tests are made by taking a fluid sample, or culture, from the lesions as early as possible, ideally within the first 48 hours of the outbreak. (As the lesion begins to heal, the test becomes less accurate.) These tests can be used to distinguish between HSV-1 and HSV-2.
Polymerase chain reaction (PCR) tests analyze the genetic material (DNA) of the herpes simplex virus and are helpful for differentiating HSV-1 from HSV-2. PCR tests are much faster and more accurate than viral cultures, and the CDC recommends this test for detecting herpes in spinal fluid when diagnosing herpes encephalitis. PCR can make many copies of the virus’ DNA so that even small amounts of DNA in the sample can be detected. PCR is much more expensive than viral cultures. However, because PCR is highly accurate, many labs now use it for herpes testing.
An older type of virologic testing, the Tzanck smear test, uses scrapings from herpes lesions. The scrapings are stained and examined under a microscope for the presence of giant cells with many nuclei or distinctive particles that carry the virus (called inclusion bodies). The test is quick but accurate only 50 - 70% of the time. It cannot distinguish between virus types or between herpes simplex and herpes zoster. The Tzanck test is not reliable for providing a conclusive diagnosis of herpes infection and is not recommended by the CDC.
Serologic (blood) tests can identify antibodies that are specific for either herpes virus simplex 1 (HSV-1) or herpes virus simplex 2 (HSV-2). When the herpes virus infects someone, their body’s immune system produces specific antibodies to fight off the infection. If a blood test detects antibodies to herpes, it’s evidence that you have been infected with the virus, even if the virus is in a non-active (dormant) state. The presence of antibodies to herpes also indicates that you are a carrier of the virus and might transmit it to others.
Serological tests can be especially useful for patients who do not have active symptoms but have other risk factors for herpes (such as other STDs, multiple sex partners, or a monogamous partner who has genital herpes).
Newer “type-specific” assays test for antibodies to two different proteins that are associated with the herpes virus:
Although glycoprotein (gG) type-specific tests have been available since 1999, many of the older nontype-specific tests that cannot distinguish HSV-1 from HSV-2 are still on the market. The CDC recommends only type-specific glycoprotein (gG) tests for herpes diagnosis.
Canker Sores (Aphthous Ulcers). Simple canker sores (known medically as aphthous ulcers) are often confused with the cold sores of herpes simplex virus 1 (HSV-1). Canker sores frequently crop up singly or in groups on the inside of the mouth or on or under the tongue. Their cause is unknown, and they are common in perfectly healthy people. They are usually white or grayish crater-like ulcers with a sharp edge and a red rim. They usually heal within 2 weeks without treatment.
Thrush (Candidiasis). Candidiasis is a yeast infection that causes a whitish overgrowth in the mouth. It is most common in infants but can appear in people of all ages, particularly people taking antibiotics or those with impaired immune systems.
Other conditions that may be confused with oral herpes include herpangina (a form of the Coxsackie A virus), sore throat caused by strep or other bacteria, and infectious mononucleosis.
Conditions that may be confused with genital herpes include bacterial and yeast infections (including granuloma inguinale and candidiasis), syphilis, chancroid, herpes zoster (shingles and chickenpox), and hand-foot-and-mouth disease.
Three drugs are approved to treat genital herpes:
These medications are antiviral drugs called nucleoside analogues. The drugs are used initially to treat a first attack of herpes, and then afterward to either treat recurrent outbreaks (episodic therapy) or reduce frequency of recurrences (suppressive therapy).
No drug can cure herpes simplex virus. The infection may recur after treatment has been stopped and even during therapy, a patient can still transmit the virus to another person. Drugs can, however, reduce the severity of symptoms, improve healing times, and prevent recurrences.
Antiviral drugs for genital herpes are generally given as pills that are taken by mouth. If patients experience very severe disease or complications, they need to be hospitalized and receive an antiviral drug intravenously.
The first outbreak of genital herpes is usually much worse than recurrent outbreaks. Symptoms tend to be more severe and to last longer. Your doctor will prescribe you one of the three antiviral medications to take for 7 - 10 days. If your symptoms persist, treatment may be extended.
For a recurrent episode, treatment takes 1 - 5 days depending on the type of medication and dosage. You should begin the medication as soon as you notice any signs or symptoms of herpes, preferably during the prodrome stage that precedes the outbreak of lesions. In order for episodic therapy to effective, it must be taken no later than 1 day after a lesion appears. If taken during prodrome, episodic therapy may help prevent an outbreak from occurring or reduce its severity. If taken at the first sign of a lesion, it can help speed healing.
To suppress outbreaks, treatment requires taking pills daily on a long-term basis. Acyclovir and famciclovir are taken twice a day for suppression, valacyclovir once a day.
Suppressive treatment can reduce the frequency of outbreak recurrences by 70 - 80%. It is generally recommended for patients who have frequent recurrences (6 or more outbreaks per year). Because herpes recurrences often diminish over time, patients should discuss annually with their doctors whether they should stay with drug therapy or discontinue it.
There is some evidence that valacyclovir may help prevent herpes transmission particularly in situations where one heterosexual partner has herpes simplex virus 2 (HSV-2) and the other partner does not. However, this drug does not completely prevent transmission. While taking any suppressive therapy for genital herpes, it is still important to regularly use latex condoms and to avoid any sexual activity during recurrences.
Antiviral drugs are generally safe. The most common side effects are nausea, headache, and abdominal pain.
Acyclovir (Zovirax, generic), valacyclovir (Valtrex), and famciclovir (Famvir) -- the antiviral pills used to treat genital herpes -- can also treat the cold sores associated with oral herpes (herpes labialis). A new form of acyclovir (Sitavig) is administered orally as an adhesive tablet – the patient applies the tablet to the gum region of the mouth where it dissolves during the course of the day. In addition, acyclovir is available in topical form, as is a related drug penciclovir (Denavir).
These ointments or creams can help shorten healing time and duration of symptoms. However, none are truly effective in eliminating outbreaks.
Patients can manage most herpes simplex infections that develop on the skin at home with over-the-counter painkillers and measures to relieve symptoms.
Several simple steps can produce some relief:
Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.
Many herbal and dietary supplement products claim to help fight herpes infection by boosting the immune system. There has been little research on these products, and little evidence to show that they really work. Some are capsules taken by mouth. Others come in the form of ointment that is applied to the skin. Popular herbal and supplement remedies for herpes simplex include:
The following are special concerns for people taking natural remedies for herpes simplex:
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Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.