~Herpes and Shingles
In their lifetimes, most human beings will be exposed to a herpes virus. This family of viruses (Herpesviridae) has been implicated in a wide range of diseases and conditions, including chickenpox, oral or facial herpes, genital herpes, mononucleosis, and corneal blindness. It is also likely that we haven’t yet discovered all herpes viruses. One variety was discovered as recently as 1990, and researchers still aren’t sure which diseases, if any, it causes in humans.
Herpes viruses are distinguished by their ability to lay dormant, or “hide” in the human body after primary infection. They then reappear during periods of reactivation. Researchers don’t really understand the mechanism of reactivation. Although there is no effective cure for herpes, many studies have shown that herpes reactivation is more common among patients who have compromised immune systems, suggesting that a strong immune system is a good defense against herpes reactivation. To manage herpes, physicians try to reduce the number and severity of outbreaks.
Among the most well-known herpes viruses are:
Although infection with herpes is primarily associated with oral, facial, or genital herpes, the herpes viruses can also cause infections in the following ways:
- Herpes simplex virus 1 (HSV1) — HSV1 is extremely common, with the vast majority of adults showing evidence of exposure to the virus (eg, antibodies in their blood), even if they are not positive for HSV1 (Kasper DL et al 2004). This form of the virus is most often associated with oral or facial lesions that appear during childhood, although it can also cause genital infection.
- Herpes simplex virus 2 (HSV2) — Researchers estimate that about 20 percent of the US population has antibodies to HSV2 (Kasper DL et al 2004). This form of the virus is closely associated with genital herpes. Genital herpes caused by HSV2 is twice as likely to reactivate and recurs 8 to 10 times more frequently than genital infection with HSV1 (Kasper DL et al 2004).
- Varicella-zoster virus — This relatively common virus is responsible for chickenpox infections (varicella) and shingles (herpes zoster). The varicella-zoster virus is extremely common. Up to 90 percent of people are attacked by this virus, about half of them between the ages of 5 and 9 years. Almost all of the clinical cases of chickenpox are diagnosed in children and adolescents younger than 14 years.
Genital herpes, which may be the most highly publicized form of the disease, is a widely misunderstood condition. Many people believe that genital herpes is only transmissible during active outbreaks of herpes (when herpes lesions are visible). They may also believe that herpes is relatively rare. In fact, herpes is much more common than many assume. Many people who have antibodies to herpes (they have been exposed to the virus) are not aware they have the disease; they suspect the condition only when they have seen pictures of herpetic lesions (Kasper DL et al 2004). Also contrary to popular belief, herpes is not transmitted only by direct contact with active lesions. It can be transmitted by people who do not have manifestations of the disease but who are shedding the virus or have subclinical symptoms or tiny lesions that are not visible to the naked eye. Studies have shown that HSV2 can be located on the genital tract on regardless of the presence of symptoms (Kasper DL et al 2004). Condoms have been shown to reduce the transmission of herpes during periods of nonsymptomatic shedding.
- Herpetic whitlow — Infection of the finger.
- Herpes gladiatorum — Also known as traumatic herpes. Infection anywhere on the chest, ears, face, and hands. This form of herpes is sometimes associated with wrestling because the rough contact between wrestlers helps spread the virus.
- Herpes of the eye — The most common cause of corneal blindness in the United States.
- Infection of the central or peripheral nervous systems — The herpes viruses accounts for up to 20 percent of the cases of sporadic viral encephalitis (swelling of the brain due to a virus) in the United States. Herpes can also cause herpetic meningitis.
- Infection of the internal organs — This includes herpes infection of the esophagus (HSV esophagitis), the lung (HSV pneumonitis), and the liver.
- Neonatal herpes — Neonates (infants younger than 6 weeks) can contract herpes during birth (if their mothers are infected with the virus) or if they are handled by someone who has oral or facial herpes. Neonates are the most likely to have herpes infections that affect the central nervous system or internal organs. Mortality among neonates with untreated herpes is 65 percent (Kasper DL et al 2004).
Herpes symptoms depend on the form of the disease. Oral or facial herpes is often accompanied by inflammation of the gums and throat during the initial outbreak. Children who have this condition may have fever, malaise, inability to eat, irritability, and lesions in and around the mouth. Genital herpes is accompanied by similar symptoms, as well as lesions on the genitals. Among newly infected women, the cervix and urethra are usually involved. If the central or peripheral nervous systems are infected, a fever and neurological symptoms are often present during periods of virus activation.
Because herpes sometimes resembles other diseases (especially herpes that affects the skin, mouth, or central nervous system), it can be challenging to correctly diagnose. The most common method used to diagnose herpes is to isolate the virus in a tissue culture or to demonstrate HSV antibodies or DNA in scrapings from active lesions.
Conventional treatment of herpes relies on antiviral drugs that have been shown to reduce the severity of outbreaks and, in some cases, reduce the likelihood of transmission. These drugs include:
These antiviral drugs may be given intravenously or orally, depending on the severity of the outbreak and the location. They are effective in treating both herpes and shingles. In addition to these antiviral drugs, a number of topical medications are used in the treatment of herpes infections of the eye. These include trifluridine, vidarabine, idoxuridine, acyclovir, penciclovir, and interferon.
- Acyclovir—Acyclovir interferes with the virus’ ability to replicate (Kasper DL et al 2004). Common side effects include nausea, vomiting, headache, diarrhea, dizziness, fatigue, anorexia, edema, and sore throat (Sra KK et al 2004).
- Valacyclovir—Valacyclovir is the salt version of acyclovir; it becomes acyclovir after being metabolized by the liver. Valacyclovir has a bioavailability three to five times greater than oral acyclovir. Common side effects, such as nausea, vomiting, headache, dizziness, and abdominal pain, are similar to those of acyclovir (Sra et al 2004).
- Famciclovir—Famciclovir is a precursor to the antiviral drug penciclovir. Penciclovir works in a similar manner to acyclovir. Side effects are the same as those for acyclovir and valacyclovir.
In recent years, clinicians have discovered strains of herpes that are resistant to acyclovir. Because the drugs are closely related, acyclovir-resistant strains of herpes are also cross-resistant to valacyclovir and famciclovir. These strains are most often detected in patients who have weakened immune systems, such as those with HIV or AIDS (Kasper DL et al 2004). In these cases, treatment with a very powerful antiviral called foscarnet, which must be administered with an intravenous (IV) pump, is sometimes effective. Foscarnet can cause severe adverse effects, including kidney disorders.
Herpes Vaccines on the Horizon
Although it is possible to lower the risk of contracting herpes through the use of condoms and antiviral drugs, the ultimate prevention goal is a herpes vaccine that would inoculate the population against the virus.
While there is no herpes vaccine yet, researchers have made significant progress in developing one. Recently, an investigational vaccine has resulted in a significant reduction in genital herpes in women who had never been exposed to the virus (Tyler I 2005). For reasons that are not known, this particular vaccine did not protect men (Jones CA et al 2003).
While it appears that effective herpes vaccines are on the horizon, there are still significant research questions to answer, such as who should be vaccinated and when, and whether or not a vaccination that suppresses symptoms prevents transmission of the virus to other people (Stanberry LR 2004).
Chickenpox and Shingles
Chickenpox and shingles are both caused by the varicella-zoster virus, and infection is strongly reminiscent of infection with either HSV1 or HSV2. However, unlike HSV1 or HSV2, the virus is often transmitted through the respiratory tract.
Chickenpox is an extremely common and highly contagious childhood disease. It is usually benign, with an incubation period of up to 21 days after initial infection, and a disease course of 14 to 17 days. During the time the varicella-zoster virus is most active, the patient has characteristic skin lesions. The lesions cause intense itching, and there is a risk that the lesions will become infected due to scratching. The severity of the disease and the number of lesions varies from person to person. Adults with the disease who have weakened immune systems might run a fever. In fact, chickenpox in adults is considerably more dangerous than the benign childhood variety. Adults are more likely to have symptoms such as headache and pain as a result of chickenpox. A form of pneumonia (varicella pneumonia) is seen in about 20 percent of adults who contract chickenpox (Kasper DL et al 2004). The virus can also cause brain inflammation.
In the future, chickenpox will likely become less of a health issue. Since 1995, children in large numbers across the United States have been vaccinated against the varicella-zoster virus. The results of this vaccination program have been dramatic: hospitalizations have declined by 88 percent and direct medical expenditures by 74 percent (Zhou F et al 2005). These benefits were seen across all age groups.
However, researchers still don’t know the impact of the chickenpox vaccine on shingles. Shingles occurs when the varicella-zoster virus reactivates, usually in adulthood, and it characterized by a painful skin rash. Reactivation occurs in about 15 percent of people who have had chickenpox, and most often occurs in people aged 60 to 69, although it can occur in any age group.
Some researchers have hypothesized that vaccination in childhood would actually make an adult more susceptible to shingles later in life. However, this has yet to be proven in clinical studies (Jumaan AO et al 2005). In the meantime, vaccination against herpes zoster in adults has been shown to reduce the incidence of shingles (Oxman MN et al 2005).
Shingles is nine times more likely to develop in those infected with HIV. In the early stages of HIV infection, shingles symptoms are fairly typical (Wilkerson MG et al 1987). In more advanced infection, herpes zoster may take the form of repeated episodes of severe, prolonged, and sometimes atypical disease (such as varicella-zoster virus retinitis). Shingles is also more common in immunocompromised children and adults (including organ recipients and chemotherapy patients). It is important to treat these patients early and aggressively with antiviral drugs.
Like chickenpox, shingles is characterized by skin lesions. The lesions may be accompanied by severe, sometimes debilitating pain. An outbreak of shingles usually lasts between 7 and 10 days. It can take up to 2 weeks for the skin to appear and feel normal. Herpes zoster can also infect the nerves in the eye. This serious condition can result in blindness if not treated with antiviral therapy (Cunningham AL et al 2000; Liesegang TJ 1984; Liesegang TJ 2004; Ostler HB 1976; Schmader K 2001; Weinhoff ML 1976).
Pain associated with shingles that persists more than 3 months after other symptoms subside is known as postherpetic neuralgia. The characteristics of postherpetic neuralgia are spontaneous aching and burning, intermittent shooting pains, and extreme sensitivity (Johnson RW 2003). Postherpetic neuralgia is more common in older people. However, at least 50 percent of patients older than age 50 who had shingles report some degree of pain months after the resolution of the skin rashes (Kasper DL et al 2004). Several drug classes are used to treat postherpetic neuralgia, including tricyclic antidepressants (Baldessarini RJ 2001) and painkillers such as acetaminophen, glucocorticoids, and lidocaine.
The Herpes Family of Viruses
The herpes family also includes the following viruses:
Herpes and the Immune System
- Cytomegalovirus (CMV)—Initial infection with CMV usually occurs during childhood and adolescence, but typically goes undetected. In healthy adults, the primary infection is usually mild and may present as fever, muscle pain, fatigue, and elevated liver enzymes. CMV may be dangerous in people who have weakened immune systems, such as organ transplant recipients and people with HIV/AIDS. The virus is spread from person to person through direct contact, sexual intercourse, or blood transfusions. CMV is excreted in saliva, urine, semen, cervical secretions, and feces (Crumpacker CS 2000).
- Human herpes viruses 6 (HHV6)—Human herpes viruses 6 is the primary cause of roseola infantum, a common childhood disease that is characterized by high fever and a red, raised rash on the neck and trunk (Straus SE 2000). Among older adults, it can also cause a mononucleosis-like syndrome. HHV6 can be found in secretions of healthy people (Straus SE 2000).
- Human herpes viruses 7 (HHV7)—HHV7 was discovered in 1990. Although no diseases have been conclusively linked to HHV7, it might be associated with pityriasis rosea, a benign skin condition characterized by scaly, pink, or dry raised capsules. Like HHV6, HHV7 can also be found in secretions of healthy individuals (Straus SE 2000a).
- Human herpes viruses 8 (HHV8)—HHV8 is associated with Kaposi’s sarcoma (Schulz TF et al 1999; Straus SE 2000b). Latent HHV8 may target tumor suppressor pathways, leading to cell proliferation and tumor formation in people who have immune systems weakened by diseases such as HIV (Mesri EA et al 1996; Moore PS 2000; Sarid R et al 1999).
- Epstein-Barr virus (EBV)—EBV is the most common cause of infectious mononucleosis, which is characterized by fever, sore throat, and swollen lymph nodes. Complete recovery may take months (Niedobitek G et al 1997). Infection is common, with about 95 percent of the population having antibodies against the virus by age 30. Transmission of EBV is through exchange of saliva containing the virus.
It appears that herpes-specific T-cell immunity might be related to reactivation. Animal studies have shown that ultraviolet light, a weakened immune system, and trauma all contribute to reactivation of the virus (Kasper DL et al 2004). At this time, there are no drugs or agents that can cause a latent virus to stay hidden forever. The number and frequency of reactivation events depends on the site and on the nutrition and immune status of the host (Isada CM et al 2003; Murray PR et al 2002).
The Life Extension Foundation’s approach to herpes management is based on the premise that a strong immune system can help reduce viral reactivation. People who have herpes can benefit from a nutritional regimen of supplements that studies suggest may fight the virus directly, as well as support a healthy immune system.
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