Herpes Simplex

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Herpes Simplex

WHAT IS HERPES SIMPLEX?

Herpes simplex virus (HSV) is a common cause of infections of the skin and mucous membranes and an uncommon cause of more serious infections in other parts of the body. The word "herpes" is derived from the Greek word "herpein," which means "to creep." It may be a reference to the unique characteristic pattern of all herpes viruses to travel up local nerves to the clusters at the end (the dorsal root ganglia ), where they remain in an inactive (latent) state for some indeterminate time. (Herpes simplex should not be confused with other herpes viruses, including human herpesvirus 8, now believed to cause Kaposi's sarcoma, and herpes zoster, the virus responsible for shingles and chicken pox.)

Herpes Types

HSV is one of the most difficult viruses to control and has plagued mankind for thousands of years. There are two distinct types of the virus:

Herpes simplex virus 1 (HSV-1).
Herpes simplex virus 2 (HSV-2).

They can occur separately or can infect the same individual. Although the general rule has been to assume that HSV-1 infections occur in the oral cavity and are not sexually transmitted, while HSV-2 attacks the genital area and is sexually transmitted, it is now widely accepted that either type can be found in either area and at other sites. In fact, in new cases of genital herpes the number of HSV-1 cases now matches and even exceeds that of HSV-2. For purposes of this report, HSV-2 refers to genital herpes and HSV-1 to oral herpes, unless the distinctions are specifically discussed.

The Disease Process

When HSV enters the body, the infection process typically takes place as follows:

The virus penetrates vulnerable cells in the lower layers of skin tissue and attempts to replicate itself in the cell nuclei. Scientists are close to decoding the genetic structure of HSV and to discovering how the virus works its way into specific cells. Researchers have also isolated proteins that may facilitate the entry of HSV into healthy cells. For example, protein receptors on cells called nectin 1 and 2 may bind to some subtypes of HSV and promote the transmission of the infection from cell to cell.
Even after it has penetrated the cells, in many, if not most, cases, the virus never causes symptoms.
However, if the HSV's replication process destroys the host cells, symptoms erupt in the form of inflammation and fluid-filled blisters or ulcers. Once the fluid is absorbed, scabs form and the blisters disappear without scarring.
After the initial replication, the viral particles are carried from the skin through branches of nerve cells to clusters at the nerve-cell ends, the ganglia.
Here, the virus persists in an inactive ( latent) form, in which complete viral replication does not occur but both the host cells and the virus survive. Infection is not apparent during these periods.
In many cases, the virus begins multiplying again, and in symptomatic patients, skin lesions often recur.

WHAT ARE THE SYMPTOMS OF HERPES SIMPLEX VIRUS?

Symptoms vary depending on the stage of the virus: the initial or primary outbreak, latency, and recurrence. Both herpes simplex viruses 1 and 2 produce similar symptoms, but they can differ in severity depending on the site of infection. [ See Table, below.] More than 60% of new HSV-2 infections and about a third of new HSV-1 infections do not produce symptoms.

Symptom Stages of All Herpes Simplex Viruses

Symptoms of Primary Infection. A primary outbreak may take the following path:

Skin eruptions may appear two to 12 days after the initial exposure to the virus.
The first sign of infection is fluid accumulation (edema) at the infection site, which is quickly followed by small, grouped blisters, the characteristic HSV lesions.
These form on an inflamed skin base, which is more visible in dry skin areas.
The blisters then dry out and heal rapidly without scarring. Blisters in moist areas heal more slowly. The lesions may sometimes itch, but itching decreases as lesions heal.
When the crust falls off, the lesions are no longer contagious. (The virus may still be active in nearby tissue but such persistence is rare.) The primary skin infection with either HSV-1 or HSV-2 lasts up to two to three weeks, but skin pain can last one to six weeks in a primary HSV attack.
Lymph glands near the site may be swollen as well.
Primary herpes is often accompanied by fever rising to about 102°F, muscle aches, headache, and flu-like malaise. These general symptoms usually resolve within a week.
Once HSV gains entry to a site in the body, the virus spreads to nearby mucosal areas through nerve cells. This characteristic spreading can cause fairly large infected areas to erupt at some distance from the initial crop of sores.

Latency. During the phase known as latency, HSV produces no symptoms at all. In fact, in one study, although 20% of American Caucasian and 65% of African American adults harbored HSV-2, only 2.6% had symptomatic infection. During latency, the virus is not transmissible.

Shedding. At times, however, this latent period ends and the virus goes through a process called shedding. When shedding, the virus begins to multiply and becomes transmittable, but without any apparent symptoms. HSV-2, particularly in women, is more likely to shed. It is estimated that over half of people with HSV-2 shed the virus at some time without having visible evidence of blisters or inflammation. Shedding is an especially insidious stage, and studies indicate that asymptomatic shedding with subsequent viral transmission to another person possibly accounts for one-third of all HSV-2 infections.

Symptoms of Recurring Infections. Recurrent attacks of HSV feature most of the same symptoms at the same sites as the primary attack, but they tend to be milder and briefer. Fever is rarely present in recurrent episodes, although nearby lymph glands may become involved. The anatomic site and the type of virus influence the frequency of recurrences.

Recurrences may occur at intervals of days, weeks, or years, but for most people, they are more frequent during the first year. The body does mount an immune response to HSV, and in most healthy people recurring infections tend to become progressively less severe and less frequent. The immune system, however, cannot eradicate the virus completely.

Symptoms of Oral Herpes

Oral herpes (herpes labialis) is most often caused by HSV-1 and usually affects the lips and, in some primary attacks, the mucous membranes in the mouth. A facial herpes infection on the cheeks or in the nose may occur, but this condition is very uncommon.

Primary Oral Herpes Infection. If the primary (or initial) oral HSV-1 infection causes symptoms, they can be very painful, particularly in small children.

Blisters form on the lips but may also erupt on the tongue.
The blisters eventually rupture as painful open sores, develop a yellowish membrane before healing, and disappear within three to 14 days.
Increased salivation and foul breath may be present.
Rarely, the infection may be accompanied by difficulty in swallowing, chills, muscle pain, or hearing loss.

In children, the infection usually occurs in the mouth; in adolescents, the primary infection is more apt to occur in the upper part of the throat and cause soreness.

Recurrent Oral Herpes Infection. Between 20% and 40% of oral HSV-1 infections recur within a year. Recurrences are usually much milder than primary infections and are known commonly as cold sores or fever blisters. They usually show up on the lower lip and rarely affect the gums or throat. Reactivation can be provoked within about three days of intense dental work, particularly root canal or tooth extraction.

Symptoms of Genital Herpes

Genital herpes, which typically affects the penis, vulva, and rectum, is usually caused by HSV-2, although the rate of HSV-1 genital infection is increasing. Studies now report, in fact, that the cases of new symptomatic genital infections are equally split between HSV-1 and HSV-2. Some studies even report a higher incidence of genital HSV-1 cases. (The distinction may not matter, however, since there is no difference in treatments.)

Primary Genital Herpes Infection. Primary infection usually occurs in or around the genital area two to eight days after exposure to the virus.

Blisters in men are usually on the head or shaft of the penis and only rarely at the base.

In women, the pattern of infection is often more complicated:

Flu-like discomfort and fever, nerve pain, itching, lower abdominal pain, urinary difficulties, and yeast infections in women may precede or accompany the eruption of the characteristic skin blisters.
Lesions may appear around the vaginal opening, on the buttocks, in the vagina, or on the cervix. These lesions ulcerate almost immediately.
Later they become crusted and fill with a grayish-white fluid.
A new crop often occurs during the second week and is accompanied by swollen lymph glands in the groin.
In many cases, women whose lesions occur inside the vagina may be unaware that they have genital herpes. Lesions here can cause a discharge but are not visible and cause minimal nerve pain.
Lesions develop in places other than the genital region in 10% to 18% of primary HSV-2 infections. In such cases, blisters and sores in the urethra (the channel that carries urine) are particularly common and can cause painful burning during urination. Inflammation of the internal reproductive organs, including the uterus lining (endometrium) and the fallopian tubes, is rare.
The symptoms may last as long as six weeks.

If an HSV-2 infection has persisted for a long time without symptoms, the first active episode may be quite mild because the immune system has produced antibodies to the virus by that time. In general, such primary infections are less transmissible, heal faster, and produce fewer symptoms.

It is very important that women with vaginal discharge be tested, since as many as 23% are able to transmit the virus within a three-month period of a first episode, even after the lesions have healed. The virus is less likely to be contagious after this period of time.

Recurrent Genital Herpes Infection. HSV-2 genital infections recur more often than HSV-1, and up to 90% recur within the first year after primary infection. Many patients report five to eight recurrences in the first year, but some experience them as often as every two weeks. Others have only one initial outbreak without any subsequent recurrences. According to one study, patients usually notice a significant reduction in recurrence by the seventh year after infection. Some patients, however, particularly those with genital HSV-2, may actually face an increase in recurrence during the first five years.

The symptoms of recurring herpes infection may present as follows:

The outbreak of infection is often preceded by an early group of symptoms known as a prodrome: Such symptoms may include itching skin, pain, or an abnormal tingling sensation.
The prodrome, which may be as brief as two hours or as long as two days, terminates when the blisters develop.
After blisters erupt, they heal in approximately six to 10 days.
Occasionally, the symptoms may not resemble those of the primary episode but produce fissures and scrapes in the skin or general genital inflammation.

Men have 20% more recurrences of genital herpes than women, although the symptoms in men are milder and of shorter duration. Even in women, recurring symptoms are milder than primary ones.

Other Forms of HSV-1 and HSV-2
Location and type	Symptoms	Treatments
Eye ( *ocular herpetic infection* ). Affects only one eye at a time. Usually HSV-1 (78% to 98% of cases). Up to 400,000 Americans have had ocular herpes. The incidence is highest in children although up to 27% of cases occur in people over 55 years old.	Primary: Inflammation of cornea ( *keratitis) causing sudden severe pain, blurred vision, or corneal lesions. Cloudy layer can form over the cornea. Swelling may occur around the eyes. Heals within 2-3 weeks. Recurrence:* About 40% have more than one recurrence, usually keratitis in a single eye, but symptoms may be present in the other eye as well. Branching, ulcerous lesions of the cornea may occur later in the disease. In the experience of some physicians, short, intense exposure to sunlight may trigger a recurrence, but there is no clear evidence concerning sunlight or any other potential triggers.	Medications. Ocular HSV should be treated carefully since certain treatments may aggravate the condition. At this time, the drug of choice for this condition is trifluridine (Viroptic), which is applied topically. Acyclovir ointment helps resolve most HSV ocular infections within five to nine days. Taking long-term oral acyclovir after an initial episode of ocular HSV reduces recurrences by about 45%. It is not as effective in preventing recurrence in ocular herpes as it is for other forms of HSV infection. Vidarabine ot trifluridine may also be helpful when infection develops. Combinations of antiviral drugs and interferon are proving to be very effective in speeding healing. Taking long-term acyclovir does appear to protect against stromal keratitis. the severe condition that can lead to corneal destruction and blindness. Trifluridine or cidofovir, however, may be protective. Neither drug, however, has any effect once stromal keratitis develops. Procedures. Patients with ocular HSV may also require *debridement*, in which the surgeon scrapes away the injured tissue with a cotton swab. A patch or soft contact lens may be worn afterward. Patients with HSV who show scarring in the cornea may require surgery. In rare cases, a corneal transplant may be necessary.
Brain ( *HSV encephalitis* ). Usually HSV-1, although HSV-2 is typically the cause in newborns. About 1,250 cases a year in the US. Fewer in Europe. About a third occur in people under 20 years old, half over 50, and the balance between ages 20 to 50.	Fever, headache, stiff neck, seizures, partial paralysis, stupor, or coma. Other symptoms: smell and taste disturbances, odd mental states, bizarre or psychotic behavior, loss of the ability to speak or understand, memory loss, confusion, emotional volatility.	Intravenous acyclovir is the treatment of choice for encephalitis and should be started immediately if this complication is suspected. It must be administered for at least 10 days.
Finger ( *herpetic whitlow* ). One finger, usually thumb or index finger in adults. Any finger in children. HSV-1 the cause in 60% and HSV-2 in 40%. HSV-1 is usually caused by finger-sucking in children or as an occupational condition in adults (usually health care workers not using gloves). HSV-2 is usually acquired by touching infected genital areas.	Primary: Itching or pain, swelling, flushing of the skin, localized tenderness of the infected finger. Clear-yellowish or pus-filled blisters may appear on fingertip lasting 2-3 weeks. Soft tissue around fingernail may become painfully infected. Finger blisters may become secondarily infected with common bacteria, causing fever and armpit swelling. Recurrence: Sometimes intense burning nerve pain or excessive sensitivity.	Topical acyclovir for acute attack and oral acyclovir for prevention of recurrences.
Lower back. Usually HSV-2 and typically in bedridden patients or AIDs patients.	Numbness, tingling of the buttocks or the area around the anus, urinary retention, constipation, and impotence. Weakness or extreme skin sensitivity in the lower extremities, possibly persisting for months. Headaches, stiff neck, and, very rarely, paralysis in lower extremities caused by inflammation of the spinal cord.	Acyclovir or foscarnet in patients resistant to acyclovir.
Peripheral nervous system (controls nerves other than brain and spine). Usually HSV-1.	Portion of the face temporarily paralyzed (Bell's palsy). Other areas of the body may exhibit numbness or loss of feeling to the touch.	Acyclovir or similar drugs in combination with oral prednisone.
Other skin areas ( herpetic erythema multiforme ). May follow any form of recurrent HSV.	Circular or irregular eruptions on backs of arms and hands. Recurrence of erythema multiforme common in same areas. This is actually an allergic reaction that lasts two to three weeks.	Usually minor and self-limiting Acyclovir and symptom relievers (common pain, cold compresses, topical steroids, saline gargles).
Esophagus. Usually HSV-1. Typically occurs in immunocompromised patients, but can occur in infected people with normal immune systems.	Difficulty swallowing or burning, squeezing throat pain while swallowing, weight loss, pain in or behind the upper chest while swallowing. Herpes lesions difficult to differentiate from other throat sores.	Intravenous acyclovir may be recommended. Usually self-limiting in patients with healthy immune symptoms.

HOW IS HERPES SIMPLEX VIRUS TRANSMITTED

Contact with bodily secretions of an infected person is the most common mode of viral transmission for both HSV-1 and HSV-2. The risk of transmission is lower during latency, but some chance always exists that the virus is shedding and transmissible at any time. After the initial episode, the infected person can transmit later infections by passing the virus on to other parts of his or her own body (most often the hands, thighs, or buttocks). This process, known as autoinoculation, is more common with HSV-2 but it can also occur with HSV-1.

Transmission of Oral Herpes

Oral herpes (usually HSV-1) is easily spread by direct exposure to saliva or even from droplets in breath. Skin to skin contact is sufficient to spread it. Transmission most often occurs through close personal contact, such as kissing or sharing common eating utensils.

Transmission of Genital Herpes

Genital herpes is most often transmitted through sexual activity, and people with multiple sexual partners are at high risk. HSV, however, can also enter through the anus, skin, and other areas. Until recently, genital herpes has mostly been caused by HSV-2; the significant increase in genital HSV-1 cases is most likely due to oral sex.

Although people with active genital herpes are well known to be at high risk for transmitting the infection, it is not clear how great a risk is posed by infected people without symptoms. In general, studies suggest that asymptomatic shedding with subsequent viral transmission to another person possibly accounts for one-third of all HSV-2 infections. In one 2000 study, 3% of asymptomatic patients had evidence of active infection. It should also be noted that in this study, 62% of patients failed to recognize symptoms when they occurred.

WHO GETS HERPES SIMPLEX VIRUS?

Everyone is at risk for herpes simplex virus. Both forms affect more than 40 million Americans, and individuals can harbor both HSV-1 and HSV-2.

Individuals at Risk for Oral Herpes

Everyone is at risk for oral herpes (usually HSV-1). It is easily transmitted and is the most common form of the herpes simplex virus. It affects between 15% and 30% of the entire population, with highest incidence first occurring between six months and three years old. Studies suggest that 62% of Americans adolescents are infected with HSV-1, and by the fourth decade of life, in some regions, 90% of people test positive for the infection.

Individuals at Risk for Genital Herpes

Some reports estimate 31 million cases, and in one study of sexually active adults, 5.1% developed herpes each year, although the incidence varies widely depending on the degree of sexual activity.

Gender. Anyone who is sexually active is at risk for genital herpes, and it is on the rise. In one study nearly 22% of Americans over 12 were infected with HSV-2, with the risk being higher in women (25.6%) than in men. The largest increases in HSV-2 occur in women after their early twenties. Women have an 80% to 90% chance of contracting HSV-2 after unprotected sexual activity with an infected partner and are 1.7 times more likely to be infected than men. Men, however, have twice as many recurrent infections as women. It should be noted that HSV-1 is becoming a major cause of genital herpes as well, and in some studies it is now a more important cause. Using only statistics on HSV-2 infection then, may underestimate the actual prevalence of genital herpes in women.

HSV-2 in Children. Less than 1% of American children younger than fifteen test positive for HSV-2, and in these cases, sexual abuse should be considered.

Ethnicity. Although African Americans are more likely to test positively for HSV-2, Caucasians have a higher risk for active genital symptoms, and over the past few years the greatest increase in HSV-2 has been observed in white adolescents.

Individuals at Risk for Specific Forms of Herpes

The following are examples of groups that may be at risk for specific forms of herpes:

Immunosuppressed patients are at increased risk for severe herpes. This includes patients infected with HIV, patients taking drugs that suppress the immune system, and transplant patients.
Healthcare professionals, including physicians, nurses, and dentists, are at higher than average risk for herpetic whitlow, which is herpes that occurs in the fingers. [ See Symptoms of Other Forms of HSV-1 and HSV-2, above.]
Wrestlers, rugby players, and other athletes who participate in direct contact sports without protective clothing are at risk for herpes gladiatorum, an unusual form of HSV-1 that is spread by skin contact with exposed herpes sores.

Triggers for Recurrence

It is not completely known what triggers renewed infection, but a number of different factors may be involved, such as sunlight, wind, fever, local physical injury, menstruation, suppression of the immune system, or emotional stress. One study linked recurrence in genital herpes to persistent stress (lasting longer than a week) and high levels of anxiety. Temporary mood changes, short-term stress, and life change events were not linked to recurrence. (A study on ocular herpes also found no association between stress and outbreaks of this eye infection and suggested that people may incorrectly recall stress being associated with herpes outbreaks.)

HOW SERIOUS IS HERPES SIMPLEX?

The severity of symptoms depends on where and how the virus gains entry into the body. Except in very rare instances and in special circumstances, the disease is not life threatening, although it can be very debilitating and cause great emotional distress.

Effects of Herpes Virus on Pregnancy

One study has indicated that HSV-1 in either men or women may be implicated in some cases of infertility. More research is needed. Pregnant women who are infected with either HSV-2 or HSV-1 genital herpes have a higher risk for miscarriage, premature labor, retarded fetal growth, or transmission of the HSV infection to the infant while in the uterus or at the time of delivery. Recurrence in women previously infected with HSV is also common during pregnancy. It should be noted, however, that about one million pregnancies occur each year in women who have been infected with HSV-2, but complications occur in only .01% to .04% of all infected pregnant women. [ See Box , Herpes in the Newborn .]

Effects on the Brain and Central Nervous System

Herpes Encephalitis. Herpes accounts for 10% to 20% of cases of acute viral encephalitis, an extremely serious brain disease. It is fatal in over 70% of untreated cases. Those who recover nearly always suffer some impairment, ranging from mild neurological damage to paralysis. Fortunately, treatment with acyclovir significantly improves both survival rates (up to about 80%) and reduces complication rates (to nearly 40%). It should also be noted that herpes encephalitis is very rare and affects only about 1,250 people in the US each year. The incidence is even lower in Northern Europe. HSV-1 is almost always the culprit, except in newborns. In about 70% of infant herpes encephalitis, the disease occurs when a latent virus is activated. In about one-quarter of HSV-1 encephalitis cases, the infection may be caused by a new strain of the virus. Respiratory arrest can occur within the first 24 to 72 hours. Recovery from HSV encephalitis is dependent on the patient's age, the level of consciousness, duration of the disease, and the promptness of treatment.

Herpes Meningitis. Herpes meningitis occurs in 4% to 8% of cases of primary genital HSV-2, and women are more likely to develop it than men are. Symptoms include headache, fever, stiff neck, vomiting, and sensitivity to light. Fortunately, herpes meningitis is self-limited, lasting for only two to seven days. Neurologic consequences are rare, but recurrences have been reported.

Alzheimer's Disease. Studies indicate a higher risk for Alzheimer's in people who have both HSV-1 and a gene called apoE4, a known risk factor for Alzheimer's. Further research suggests that interaction with the gene and herpes simplex virus may contribute to Alzheimer's disease. For example, a protein found in HSV-1 has been shown to mimic and behave just like beta-amyloid, a protein now strongly believed to be a critical player in the Alzheimer's disease process.

Other Neurologic Diseases. Other neurologic syndromes that have been linked to HSV infection include epilepsy, multiple sclerosis, atypical pain syndromes, ascending myelitis (inflammation of the spinal column), and neuralgias (severe stabbing pain along a nerve or group of nerves).

Eczema Herpeticum

Eczema herpeticum, also known as Kaposi's varicellum eruption , can afflict patients with preexisting skin disorders and immunocompromised patients. The disease tends to develop into widespread skin infection and resemble impetigo. Symptoms appear abruptly and can include fever, chills, and malaise. Clusters of dimpled blisters emerge over seven to ten days and spread widely. They can become secondarily infected with staphylococcal or streptococcal organisms. The lesions heal in two to six weeks.

Ocular Herpes and Vision Loss

Herpetic infections of the eye can cause loss of vision and damage to the upper layers over the cornea that occurs over a period of months to years. In most cases, visual impairment is very slight. In about 6% of ocular herpes, however, a condition called stroma keratitis occurs, in which deeper layers of the cornea are involved, possibly as an abnormal immune response to the original infection. In these rare cases, scarring and corneal thinning develop, which may cause the eye's globe to rupture and result in blindness. Ocular herpes is the most frequent infectious cause of corneal blindness in the world.

Gingivostomatitis

HSV can cause multiple painful ulcers on the gums and mucous membranes of the mouth, a condition called gingivostomatitis. This condition usually affects children between the ages of one and five, and typically subsides after a week. In rare cases, it can progress to a systemic viral infection. Children with gingivostomatitis commonly develop herpetic whitlow, which is herpes that occurs in the fingers. [ See Symptoms of Other Forms of HSV-1 and HSV-2, above.]

Other Disorders Linked to Herpes Simplex

A number of other conditions have been linked to HSV infections, although the association has not been substantiated in most cases.

Arthritis affecting a single joint has been sporadically reported as a result of HSV infection.
Certain kidney and blood diseases have also been reported in conjunction with HSV infection.
HSV can affect the liver and in rare cases it may cause hepatitis. This is an uncommon complication in people with healthy immune systems, but in rare cases can cause life-threatening complications. It is important to be aware of its possibility, since this emergency condition is treatable when diagnosed promptly. Early symptoms may include nausea, vomiting, and abdominal pain. People with HSV-2 may have an increased susceptibility for sexually transmitted hepatitis C.
Some studies have reported an association between HSV-1 and 2 with a higher risk for coronary artery disease.

Emotional and Social Effects

Not least among the damaging effects of HSV-2 is its impact on the social and emotional life of patients. In one survey of herpes patients, 82% felt depressed and 75% were worried about rejection. Over a quarter had suicidal thoughts. In nearly 80% of the respondents, the disease had a profound effect on their sexual life. The patient must notify sexual partners, past and present, about their condition, a deeply humiliating experience. Guilt and anger are common emotions, and relationships may be shattered. It is important to note that the condition is often dormant for many years and may not have been transmitted by a current sexual partner. Support groups or couple therapy can be very helpful.

Herpes in the Immunocompromised Patients

Herpes simplex is particularly devastating when it occurs in immunocompromised patients. These include people who are HIV positive, cancer or burn patients, or patients who are using immunosuprresant drugs (those used after organ transplantation, long-term or high-dose steroids).

Patients with HIV, the virus that causes AIDS, are particularly vulnerable to complications. When both viruses are present, there appears to be a synergy between them, with each increasing the severity of the other. (The presence of HSV also increases the risk for contracting AIDS.)

Herpes simplex in any patient with a seriously compromised immune system can cause serious and even life-threatening complications, including the following:

Pneumonia.
Liver damage, including hepatitis. Hepatitis caused by primary or recurrent HSV can sometimes develop into a life-threatening condition called fulminant liver failure.
Inflammation of the esophagus.
Encephalitis.
Destruction of the adrenal glands.
Increased risk for disseminated herpes and herpes encephalitis.

Less serious conditions include stomach and anal ulcers, inflammation in the colon, and eczema herpeticum.

HERPES IN THE PREGNANT WOMAN AND THE NEWBORN

HSV infection in a newborn is a very serious and even-life threatening condition if it goes undiagnosed and untreated. Fortunately, since the introduction of acyclovir the outlook for these children has significantly improved.

Transmission of HSV to Newborns

HSV infection is uncommon, occurring in between one in 3,500 to 20,000 depending on the population group. The greatest danger to the newborn occurs in women who have a primary genital infection with an outbreak at the time of delivery. In such cases, about half of the newborns become infected. The lowest risk (less than 4%) to the child of an infected mother is from shedding during a recurring non-symptomatic infection.

Unfortunately, many women whose newborn infants develop HSV infection have no history of herpes and or fail to recognize symptoms at the time of delivery. Occasionally, lesions on the mother's buttocks may help indicate the presence of the virus. The risk for transmission increases if infants with infected mothers are born prematurely or instruments are required 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. Very rarely, the virus is transmitted across the placenta, a form of the infection known as congenital herpes.

Approach to the Pregnant HSV Patient

The approach to a pregnant woman who has been infected by either HSV-1 or 2 in the genital area is usually determined by when the infection was acquired and the mother's condition around the time of delivery.

Infection occurring well before time of delivery appears to pose little or no risk to the newborn.
The most dangerous time for infection is when it occurs in the last term.

The approach in the latter cases if as follows:

If lesions are present at the time of birth, Cesarean section is usually recommended. Even a Cesarean section is no guarantee that the child will be HSV-free and the newborn must still be tested.
If lesions erupt shortly before the baby is due then samples must be taken and sent to the laboratory. Samples are cultured to detect the virus at three- to five-day intervals prior to delivery to ascertain whether viral shedding is occurring. If no lesions are present and cultures indicate no viral shedding, the delivery is normal and the newborn is examined and cultured after delivery.
Acyclovir or other similar agents are generally not used during pregnancy for either primary infection or to prevent recurrences unless the HSV infection is life threatening. Suppression therapy during late pregnancy, however, can prevent herpes infection and some physicians now recommend it for patients with a known history of genital herpes. Small studies to date indicate that acyclovir does not harm the fetus under these circumstances. In general, however, evidence supporting anti-viral suppression treatment during pregnancy is not strong and the risks are still unknown.
It should be noted, however, that there are no preventive measures for women with a history of symptoms but who still may harbor the virus.

HSV Categories in the Newborn

In general there are three categories of HSV in the newborn:

Disseminated disease can affect internal organs, such as the liver, the lungs, and the adrenal glands. It is fatal in up to 80% of newborns if left untreated and those who survive are at high risk for complications, particularly in the eyes. If infants are treated, however, survival rates are close to 90%.
Central nervous system infection can cause meningitis or encephalitis. This form is also highly fatal and complications that affect learning and mental functions are common in surviving children.
Localized infection affects the skin, eyes, and mucus membrane. This condition is rarely fatal but can cause some later complications in between 5% and 10% of infants. If it is untreated, it may also progress to disseminated or central nervous system infection.

Conditions Affecting Complications from HSV Infection in the Newborn

Factors that Indicate a Higher Risk for Severe Complications:

Acute infection in the mother at delivery.
Prematurity.
Seizures in the infant.
Disseminated intravascular coagulopathy, a disorder of the blood-clotting mechanism in response to the infection.

Factors that Indicate a Lower Risk for Severe:

Newborn infection caused by a recurring HSV-2 infection in the mother. (Mothers with such infections appear to pass along protective antibodies to the newborn. It should be noted that antibodies to HSV-1 do not appear to offer similar protection to the newborn.)
Newborn infections that are confined to the skin and do not cause frequent outbreaks within the first six months.

Tests for the Newborn at Risk

Any newborn with an infected or high-risk mother should be tested and checked carefully for symptoms. (Experts are divided, however, over whether the high cost of testing mothers specifically for HSV before delivery, even in high-risk groups, is worth the benefit for such a small group of mothers and infants.)

In the asymptomatic newborn delivered from an infected mother, cultures should be taken between 24 and 48 hours after birth. A culture taken right at the time of delivery may give a false indication of infection in the baby, simply because it can carry some of the mother's virus from the birth canal.
Testing specimens for viral DNA using a test called polymerase chain reaction (PRC) is proving to be very important in newborns, particularly when central nervous system infection is suspected, since it eliminates the need for brain biopsies.
While results are pending, the baby should be checked regularly for rash and blisters, particularly in areas where the skin is broken, along with any signs of illness including fever, lethargy, respiratory distress, and poor feeding.

Symptoms

Although treatments have improved the outlook of infected newborns, there has been little change over the past 20 years in the time between the onset of symptoms and the initiation of treatments. Physicians and parents should be suspicious of any signs if there is any risk of infection to the newborn.

When symptoms occur in newborns, they usually become apparent within five to 17 days of life, but they may develop as early as 24 hours or as late as 34 days.

An unstable temperature can be the first indication of the infection.
About half of infected infants develop lesions, which may range from raised spots to large isolated blisters. They can be anywhere on the skin, eyes, or in the mouth.
The other half of infected infants do not develop lesions until later in the course of the infection. The absence of lesions, therefore, in high-risk infants should not be considered a guarantee that HSV has not been transmitted.
Other symptoms to watch for include irritability, blotchy skin, discharge in the eyes, sensitivity to light, tearing, lethargy, jaundice, pallor, coughing, rapid breathing, enlarged spleen, seizures, or tremors.

Treatment

If HSV infection in a newborn infant is suspected, intravenous acyclovir treatment should begin immediately, since the potential dangers of the condition far outweigh any risks associated with the drug. (The newer agents valaciclovir and famciclovir offer no additional advantage.) Vidarabine (Vira-A) is sometimes used as an alternative to acyclovir, but it is much less effective and should be used only if the baby is resistant to acyclovir.

The following are recommendations for treating infants who have been infected or are at risk for infection:

If disseminated or central nervous system infection has developed or is suspected, intravenous acyclovir treatment should be for 21 days. A 2001 study suggested that using higher doses than standard ones may prove to be safe and to improve outcome.
If the infection is limited to the skin, eyes, or mouth and the infant is at low risk for more serious complications, treatment may be given for 10 to 14 days.

Investigators are studying whether taking long-term oral acyclovir following the initial infection will improve the outcome for newborns.

WHAT TESTS ARE USED TO DETECT HERPES SIMPLEX?

Generally, the herpes simplex virus is identifiable by the characteristic lesion: a thin-walled blister on an inflamed base of skin. If the diagnosis is uncertain, more tests will be needed. Patients diagnosed with genital herpes should be tested for other sexually-transmitted diseases.

Microscopic Examination of Tissue Scrapings (Tzanck Test)

The standard test for herpes is the Tzanck test:

This test uses scrapings from herpes lesions.
They are stained and microscopically examined.
Findings of specific giant cells with many nuclei or distinctive particles that carry the virus (called inclusion bodies ) indicate HSV infection.

The test is quick but accurate in only 50% to 70% of cases. It cannot distinguish between the HSV types or between herpes simplex and herpes zoster.

Viral Cultures

Although the lesions of herpes simplex virus are distinctive, they can be confused with other skin infections. An accurate diagnosis of HSV is best made by taking a fluid sample from the lesions as early as possible (ideally within the first three days of appearance). The viruses reproduce in this fluid sample (called culture). Results usually take a few days, although technology exists that can shorten this period to 24 hours (if cases of infection are severe).

It is almost 100% accurate if lesions are still in the clear blister stage. Such tests are not as effective for older ulcerated sores, recurrent lesions, or latency. At these stages the virus may not be active enough to reproduce sufficiently to produce a visible culture.

Immunologic Tests

Other tests are occasionally performed that make use of the properties of the immune system. Such tests typically use antibodies that hunt out and specifically identify the herpes virus. A test called ELISA (enzyme-linked immunosorbent assay) is 85% accurate in detecting the herpes virus and 100% accurate in determining the relevant strain. Results are available in two hours. A form of the test can also distinguish between HSV-1 and HSV-2 and is very promising for newborns at high risk for HSV. The test normally requires a blood sample, but a test using saliva, which would be particularly useful for testing children, is in trials.

Polymerase Chain Reaction (PCR)

Polymerase chain reaction (PCR) assay uses a piece of the DNA of the virus and then replicates millions of times until the virus is detectable. This test can identify specific strains of the virus and asymptomatic viral shedding. Sensitivity is almost equal to viral culture and results are also much quicker. It may prove to be particularly useful in detecting HSV in the central nervous system (CNS) and eye, but it is very expensive, and experts are seeking ways of testing patients most likely to harbor the infection. It is particularly useful for infants with suspected CNS infection and has helped avoid the need for brain biopsies.

Tests for HSV Encephalitis

Diagnosis of HSV encephalitis may require a number of tests. Electroencephalography traces brain waves and can identify about 80% of cases. Computed tomography (CT) or magnetic resonance imaging (MRI) scans may be used to differentiate encephalitis from other conditions. Brain biopsy is the most reliable method of diagnosing HSV encephalitis, but it is also the most invasive and is generally performed only if the diagnosis is uncertain. PCR identifies HSV in cerebrospinal fluid and gives a rapid diagnosis of HSV encephalitis.

WHAT OTHER CONDITIONS ARE SIMILAR TO HERPES SIMPLEX?

Oral Sores

Canker Sores (Aphthous Ulcers). Common canker sores (known medically as aphthous ulcers ) are often confused with HSV-1. These sores can appear frequently on the inside of the mouth and are usually grayish with a sharp edge. They usually heal in two 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 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.

Genital Disorders

Conditions that may be confused with HSV-2 are bacterial and yeast infections, genital warts, herpes zoster (shingles), molluscum (a virus disease which produces small rounded swellings), scabies, syphilis, and certain cancers.

Urinary Tract Infections

In a few cases, HSV-2 may occur without lesions and resemble cystitis and urinary tract infections.

Eye Injuries

Simple corneal scratches can cause the same pain as herpetic infection but these usually resolve within 24 hours and don't exhibit the corneal lesions characteristic of herpes simplex.

Skin Disorders

Skin disorders that may mimic herpes simplex include shingles and chicken pox (both caused by varicella-zoster, another herpes virus), impetigo, and Steven-Johnson syndrome, a serious inflammatory disease usually caused by a drug allergy.

WHAT ARE THE HOME TREATMENTS AND PREVENTIVE MEASURES FOR HERPES SIMPLEX?

Most herpes simplex infections that develop on the skin can be managed at home with over-the-counter pain killers and symptomatic relief.

Symptomatic Relief

A number of simple steps can produce some relief:

Hygiene is important. Avoid touching the sores. Wash hands frequently during the day. Fingernails should be scrubbed daily. Keep the body clean.
Drink plenty of water.
Blisters or sores should be kept clean and dry with an agent such as cornstarch. (Talcum power should never be used because of its association with an increased risk for ovarian cancer.)
Some people report that drying the genital area with a blow dryer on the cool setting offers relief.
Void tight-fitting clothing, which restricts air circulation and slows healing of the sores.
Choose cotton underwear, rather than synthetic materials.
Local application of ice packs may alleviate the pain and help reduce recurrences by suppressing the virus.
Lukewarm baths may be helpful. (For people who have pain in urination, some experts recommend urinating in the bath water at the end of the bathing time. This dilutes the urine and prevents burning the sores. Urinating in a cool shower is also helpful and is less offensive to many people. )
Wearing sun block helps prevent sun-triggered recurrence of HSV-1.
Sex should be avoided both during the outbreaks and the prodromes (the early symptoms of herpes), which include tingling, itching, or tenderness in the infected areas.
Over-the-counter medications such as aspirin, acetaminophen (Datril, Panadol, Tylenol), or ibuprofen (Advil, Medipren, Motrin, Nuprin), can be used to reduce fever and local tenderness. Children should take acetaminophen; they should never be given aspirin.

Stress Management

In one study, stress management techniques developed using cognitive-behavioral methods were not only effective in reducing depression in those with HSV-2 but blood test results also revealed lower levels of HSV-2 antibodies. In any case, reducing stress using relaxation techniques does no harm.

Special Diets or Foods

L-lysine. No special diet has been proven to reduce symptoms of herpes virus. Some people take supplements of L-lysine to prevent cold sores; 1,000 mg per day seems to help sores heal rapidly.

There are unproven claims that eating certain foods that are both high in L-lysine and low in arginine (both are amino acids) will help prevent outbreaks of oral HSV-1. Such foods include most dairy products (especially yogurt), beets, apples, pears, mangos, oily fish (such as salmon, haddock, snapper, and swordfish), soybean sprouts, chicken, and tomatoes.

No one, however, should avoid the many healthy foods that have the reverse ratio ( low L-lysine and high arginine) because of any unsubstantiated claims. Such foods include nuts, many fruits, garlic, onions, whole grains, and green vegetables. (Some people have even found that garlic capsules are helpful.)

Caffeine. Caffeine has some anti-herpesvirus properties, although it is not known whether drinking caffeinated beverages would have any effect on HSV-1.

Herbal and Other Alternative Remedies

There are many unproven claims for numerous alternatives and unconventional remedies for herpes simplex. Among those that have shown no additional advantages are vitamins, minerals, and light therapy.

There are anecdotal reports of relief from other herbal or over-the-counter remedies, including the following:

Cream made from Melissa, an herb from the mint family.
Aloe vera ointments for genital herpes.
Watkins Medicated Ointment. Some people report good success from this very old home remedy.
A dropper-full of an extract of echinacea applied to the sores every few hours. A 2001 study reported no benefits from echinacea purpura (Echinoforce) compared to a placebo, however, but the study had limitations. A product called viracea (ViraMedx) contains echinacea and other natural compounds. It appeared to have some activity against herpes virus simplex in a 1998 study. More research is needed.
Tea tree oil for mouth sores.
An ointment for genital herpes made from propolis, a substance made by bees from tree resin.
An extract from the plant Prunella vulgaris is showing promise for stopping HSV-1 and 2 viral growth in cells, even in acyclovir resistant strains. More research is warranted on this interesting substance.
One interesting study reported that an edible mushroom called the gypsy mushroom (Rozites caperata) has been found to have chemicals that inhibit HSV-1 and HSV-2.

It should be noted, however, that many herbal treatments are not harmless, they are not regulated, and they can be very potent. Few have been tested for benefits or side effects. No alternative treatment should be tried without discussing it first with the physician. [ See warning Box.]

Warnings on Alternative and So-Called Natural Remedies

It should be strongly noted that alternative or natural remedies are not regulated and their quality is not publicly controlled. In addition, any substance that can affect the body's chemistry can, like any drug, produce side effects that may be harmful. Even if studies report positive benefits from herbal remedies, the compounds used in such studies are, in most cases, not what are being marketed to the public.

There have been a number of reported cases of serious and even lethal side effects from herbal products. In addition, some so-called natural remedies were found to contain standard prescription medication. Most problems reported occur in herbal remedies imported from Asia, with one study reporting a significant percentage of such remedies containing toxic metals.

The following website is building a database of natural remedy brands that it tests and rates. Not all are available yet. http://www.ConsumerLab.com/

The Food and Drug Administration has a program called MEDWATCH for people to report adverse reactions to untested substances, such as herbal remedies and vitamins (call 800-332-1088).

Preventing Transmission

There are a number of steps that infected people should take to avoid transmitting the virus to others. It should be noted that it is almost impossible to defend against the transmission of oral HSV-1 since it can be transmitted by very casual contact.

When an outbreak of herpes occurs the following precautions are useful:

Persons carrying any herpes virus should carefully wash their hands after contact with the infected area so as not to transmit the virus to other sites on the body.
Although transmission from objects such as toilet seats and towels is unlikely, keeping personal items separate during an active infection may help to reduce transmission to other household members. The virus can live for up to two hours on cloth and for four hours on plastic.
If genital lesions are present, infected persons should abstain from sexual intercourse.
Any infected man or a partner of an infected woman should wear a condom during any sexual activity, even when symptoms are not present. (Women with HSV-2 who have frequent attacks are at particular risk for transmitting the virus during asymptomatic periods. In fact, most new cases of infection are spread during these asymptomatic periods. The use of latex condoms are effective in preventing transmission of HSV-2, but they are not fool proof. Even a small tear can permit passage of the virus. Condoms made from animal membrane do not protect against HSV infection because the herpes viruses can pass through them. Plastic condoms, such as the Avanti or eZ-on male condoms, are alternatives for those allergic to latex, but studies indicate that they break or slip 6% of the time.
The female condom may be the best option for infected women or partners of infected men. The female condom in fact may be a superior form of protection because it covers a larger area. There are virtually no obstacles against its use except a negative psychologic perception and the fact that it is not completely fail-proof against pregnancy.
It should be strongly noted that spermacides (often used with condoms) are not protective. In fact, an important 2000 study of the common spermacide ingredient nonoxynol-9 reported a higher risk for HIV infection with its use in women. This may apply to other sexually transmitted agents as well, including HSV.

WHAT ARE DESCRIPTIONS OF ACYCLOVIR AND OTHER DRUGS BEING USED & TESTED FOR HERPES SIMPLEX?

No drug, to date, can actually cure herpes simplex virus. The infection may recur after treatment has been stopped, and during therapy, a patient can still transmit the virus to another person. Drugs are now available, however, that can reduce symptoms and improve healing times.

Acyclovir and Related Drugs

The best class of drugs developed to date against herpes simplex are antiviral agents called nucleosides and nucleotide analogues , which block viral reproduction.

Acyclovir. Acyclovir (Zovirax) is the standard nucleoside for treating many HSV infections. It penetrates most body tissues, including cerebrospinal fluid, but has little or no harmful effect on healthy cells. Although most effective against an active infection, acyclovir may also reduce the frequency of viral shedding. It is not known if limiting shedding prevents transmission of the virus, so the use of condoms during asymptomatic periods is still essential, even when patients are taking acyclovir.
Acyclovir is available in a number of forms, including oral, injected, and topical. The form used depends on the site and location of the infection. The oral and intravenous forms decrease both healing time for the lesions and viral shedding if taken within 24 hours of the first indication of a recurrent episode. Early treatment may prevent the development of lesions in some patients. The primary downside of oral administration is the need for multiple doses. Higher doses with less frequent preparations may help reduce this problem. Possible side effects from acyclovir include nausea and vomiting, rash, headache, fatigue, tremor, and very rarely, seizures. Intravenous administration increases the risk for kidney problems and can cause blood clots at the injection site. The topical ointment version is the least effective and may cause some pain, mostly because of other chemicals used in the preparation of the ointment.
Valacyclovir. Valacyclovir (Valtrex) is converted to acyclovir in the intestine and liver. It provides higher concentration of acyclovir in the bloodstream without added toxicity and therefore requires less frequent dosing, which may improve the patient's compliance with treatment. It is equal in effectiveness to famciclovir [ see below ] and is less expensive. The only reported serious danger is the risk for blood clots in small vessels of immunocompromised patients [ see above ] at high doses (eight grams per day or more). Valacyclovir is most effective if taken within 24 hours of the first signs of an outbreak.
Famciclovir. Famciclovir (Famvir) is converted into its active compound, penciclovir, within the infected cell by contact with an enzyme from the virus. It has a longer cellular half-life than acyclovir (10 to 20 hours), and like valacyclovir [ see above ], requires less frequent dosing. Unfortunately, famciclovir is not as potent against HSV-2 as acyclovir. It is most effective if taken within six hours of symptoms' onset.
Penciclovir. Penciclovir is active against herpes that affects the skin and is used in ointment form and may have the same benefits as an intravenous agent.

Note: As with antibiotics, physicians are concerned about signs of increasing viral resistance to acyclovir and similar drugs, particularly in immunocompromised patients (such as those with AIDS). Some experts believe, however, that the prevalence of drug-resistant viruses will be low for many years. They argue that widespread use of antiviral drugs will prevent many cases of herpes from developing and will slow the spread of the disease.

Foscarnet

Foscarnet (Foscavir) is a powerful anti-viral agent known as a pyrophophate analogue, and is the first choice for treatment for HSV strains that have become resistant to acyclovir and similar drugs. Administered intravenously, the drug can have toxic effects and impair kidney function (which is reversible) and cause seizures. Fever, nausea, and vomiting are common side effects. It can also cause ulcers on genital organs. As with other drugs, it does not cure herpes.

Cidofovir and Adefovir

Cidofovir (Vistide) is active against many viruses and may be useful in some cases of HSV. Intravenous cidofovir, for example, may be good choice for AIDS patients whose condition is resistant to acyclovir and foscarnet. Cidofovir shows promise as a topical treatment of recurrent genital herpes infections, although it can have severe side effects.

Brivudin

Brivudin (Helpin) is a nucleoside analogue and is proving to be every effective for varicella zoster virus (the cause of shingles). It may also have some effect against HSV in certain circumstances.

Immune-Response Modifying Drugs

Drugs that enhance immune factors against herpes virus are promising. Resiquimod, which is part of family called immune response-modifying drugs, is of particular interest for treating and preventing genital herpes. This agent is similar to, but far more potent than, imiquimod, an agent that is proving to be effective for genital warts (which are caused by human papillomavirus). Resiquimod is applied as a gel. In one small study, as many as a third of treated patients had no recurrences over a six-month period (compared to 94% who were treated with a placebo). And some of resiquimod-treated patients did not experience a recurrence even after two years. More research is needed, but early studies are promising.

Vaccines

Some experts believe that developing an effective HSV vaccine is the only practical way to control the disease and the spread of infection, and if such a vaccine becomes available, then universal immunization may be the best approach. Various vaccines are in clinical trials or preclinical development, including mutated strains of herpes virus that cannot replicate, inactivated herpes virus, and DNA vaccines that use genetic fragments of the virus to trigger an immune response. Creating such a vaccine, however, is complex and difficult. A 2000 study reported on a vaccine that appears to work in women with genital herpes but not in those with oral HSV1 and not in men with any herpes. A 2001 animal study suggested that vaccines which are effective against a primary infection increase latent infections.

WHAT IS THE APPROACH FOR TREATING ORAL HERPES?

Treatment of Primary Infection of Oral Herpes

Oral Agents. Acyclovir is often taken orally for a severe primary attack of HSV-1 and may even be beneficial for children. Taken preventively, it reduces frequency and severity of recurring infections.

Topical Treatments. Acyclovir ointment does not appear to be useful with HSV-1. Other topical agents, however, are now available that might be helpful.

Penciclovir (Denavir) heals HSV-1 sores on average about half a day faster than without treatment, stops viral shedding, and reduces the duration of the pain. The patient should apply the cream within the first hour of symptoms, and for four consecutive days it should be reapplied every two hours while awake.
Docosanol cream (Abreva) is an over-the-counter agent now approved by the FDA for oral-facial herpes. It helps resist infection by inhibiting the ability of the virus to become fully active after it has attached itself to the host cell. It is a unique compound that improves healing time and symptoms, perhaps more effectively than penciclovir.

Zinc Compounds. Zinc appears to be important for viral reproduction. Some studies have reported effectiveness against HSV-1 with zinc compounds, such as a topical cream containing zinc oxide-glycine. One promising agent under investigation (known as NVTL0001) prevents the viral proteins from binding to zinc.

WHAT IS THE APPROACH FOR TREATING GENITAL HERPES?

Any correct therapy for HSV depends on the site of the infection and whether the attack is primary or recurrent. To be effective against recurrent HSV infection, treatment of herpes must be initiated in the first week of a primary infection. Later treatment has limited effect in preventing recurrent infection.

Genital herpes is usually caused by HSV-2, but the percentage of genital HSV-1 case is rising and new cases now equal HSV-2 genital cases. Since there is no difference in treatment, however, differentiating between genital infections caused by HSV-1 or HSV-2 has little practical value. The treatment of infected pregnant women and newborns requires very careful attention. [ See Box Herpes in the Pregnant Woman and the Newborn , above. ]

Treatment for Primary Attacks

Oral Agents. Acyclovir is usually administered orally for genital HSV. There is no additional benefit derived from the simultaneous use of both types. Oral acyclovir may be prescribed for seven to 10 days during primary infections; benefit occurs within one to three days if the drug is started promptly. When taken early enough, acyclovir reduces the duration of the infection, its pain, and new lesion formation, and also reduces viral shedding. The newer drugs are also effective. In one study, patients who took 500 mg of the oral form of valacyclovir twice daily for five days experienced faster resolution of pain, a shorter shedding stage, and less severe lesions than those who did not take the drug. Another study reported that a three-day course of valacyclovir might be equally effective.

Topical Agents. Ointments are available for a primary attack but are not as effective as the oral form and have no benefit for recurring infection.

A penciclovir cream is effective in reducing pain and duration of the infection.
One study suggested that adding a steroid ointment to an oral anti-viral agent can reduce pain and symptoms. (Some people report that even over-the-counter cortisone ointments can be helpful.)
Topical 5% lidocaine jelly can be used as a local anesthetic for pain.
In one study, an over-the-counter local anesthetic, tetracaine (Viractin), was effective in reducing the duration of the attack compared to placebo (a dummy pill) by two days. It also relieved itching but had little effect on other symptoms.
For severe itching in adults or children, diphenhydramine (Benadryl) may be useful, or a physician can prescribe drugs such as hydroxyzine (Atarax or Vistaril).

Treatment for Recurrence

Intermittent Treatment for Recurring Outbreaks. Most recurrent infections are mild enough so that treatment is not needed. When it is, acyclovir, famciclovir, or valacylovir are all useful. Some patients may take intermittent, short-term preventive ( prophylactic) therapy of acyclovir or famciclovir during periods when outbreaks are likely.

Suppressive Therapy. Daily long-term preventive therapy, called suppressive therapy, may be appropriate in certain patients to prevent severe long-lasting recurrences and to reduce the risk of transmitting the virus. Acyclovir is the standard agent, but famciclovir and valacyclovir are also effective. In some studies, suppressive therapy using acyclovir has reduced the frequency of recurrence in 80% of patients and prevented recurrence altogether in up to 30%. In one study of famciclovir, after a year, up to 80% of patients had no recurrences.

If an infection occurs during suppressive therapy, healing time is quicker and symptoms are less severe. Suppressive therapy may also reduce the risk for development of drug-resistant viruses compared to intermittent treatments.

Once the disease is under control, some physicians gradually decrease the dose of the drug used in suppressive therapy. In general, people stop taking suppressive therapy after about two years.

Some, however, stay on this therapy for many more years. In one study, patients who started treatment with an average annual recurrence rate of 13% experienced only an 0.6% recurrence rate after 10 years on suppressive study. In another, patients reported a significant reduction in recurrence rates by the seventh year after the first infection.

The treatment is expensive. And, since the frequency of recurrences diminishes over time without suppressive therapy, lifelong use of drugs is not generally recommended. Some experts warn, however, that unless suppressive therapy becomes widespread and prolonged, transmission of the virus will remain a major health problem and the prevalence of HSV-2 infection will not significantly decrease.

Treatment of Immunosuppressed Patients

For patients with damaged or suppressed immune systems, oral acyclovir is used for primary and recurrent infections at higher doses than in patients with healthy immune systems. Suppression therapy is effective in preventing recurrences.

Intravenous acyclovir is used for serious or disseminated infections and for infections of the central nervous system. Resistant strains of the virus are being seen in immunosuppressed patients, and some experts are recommending continuous infusion of acyclovir instead of intermittent therapy for these patients.

Researchers are studying alternatives. One study reported that intravenous penciclovir was as effective as intravenous acyclovir and required less frequent doses. A 2001 study also suggested that oral valaciclovir may be a safe and effective alternative to intravenous acyclovir in certain cancer patients who are immunocompromised.

Other alternative agents are vidarabine (Vira-A), available only in intravenous form, and foscarnet (Foscavir) in ointment or intravenous forms. Foscarnet has been found to be superior to vidarabine for primary infection but was totally ineffective for recurrences at the same site.

WHERE ELSE CAN HELP BE FOUND FOR HERPES SIMPLEX VIRUS?

The American Social Health Association (ASHA), Herpes Resource Center, PO Box 13827, Research Triangle Park, NC 27709. For the National Herpes Hotline call (919) 361-8400 to speak to a counselor and call 800-230-6039 to order information. The Internet address is http://www.ashastd.org/. The organization provides up-to-date practical information, publishes a newsletter, and coordinates self-help groups across the country.

National Women's Health Network, 514 10th St. NW, Suite 400, Washington, DC 20004. Call (202) 347-1140. Excellent organization on many conditions affecting women.

Centers for Disease Control and Prevention, 1600 Clifton Road, NE, Atlanta, GA 30333. Call (404 639-3311) or on the Internet (http://www.cdc.gov/)

Internet Resources

Original Herpes Home Page (http://www.racoon.com/herpes/herpes.html)

British Herpes Management Forum (http://www.ihmf.org/)

Australian Herpes Management Forum (http://herpes.on.net)

Lists foods high in lysine and low in arginine (http://www.herpes.com/Nutrition.shtml)