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Epstein-Barr Virus

Epstein-Barr virus

Definition

Epstein-Barr Virus, or EBV, is the name given to a member of the herpesvirus family that is associated with a variety of illnessesfrom infectious mononucleosis (IM), to nasal-pharyngeal cancer, and Burkitt's lymphoma .

Description

Herpesviruses have long been known. The name actually comes from the Greek adjective herpestes, which means creeping. Many herpesvirus species appear to establish a life-long presence in the human body, remaining dormant for long periods and becoming active for some, often inexplicable, reason. EBV is only one of several members of the Herpesvirus family that have similar traits. Others include varicella zoster virusthe cause of both chickenpox and shingles, and the herpes simplex virus responsible for both cold sores and genital herpes. EBV is usually transmitted through saliva but not blood, and is not normally an airborne infection.

EBV occurs in nearly all regions of the world, and is considered among the most common infectious viruses known to humankind. In the United States, the Center for Disease Control (CDC) estimates that 95% of adult Americans between the ages of 35 and 40 years have been infected, but it is less prevalent in children and teenagers. This pattern of infecting adults more than children persists throughout other prosperous western countries, but does not hold true in underdeveloped regions such as Africa and Asia. In Africa, most children have been infected by EBV by the age of three years

Individuals with EBV infections typically show some elevation in the white blood cell count and a noticeable increase in lymphocyteswhite blood cells associated with the immune response of the body. IM is a time-limited infection that usually lasts from one to two months. Symptoms include fever , malaise, sore throat, swollen glands and (sometimes) swollen spleen and/or liver. EBV infections that lead to Burkitt's lymphoma in Africa typically affect the jaw and mouth area, while the (very rare) incidences of Burkitt's lymphoma found in developed countries are more apt to manifest tumors in the abdominal region. Nasopharyngeal cancer is uncommon in the West but more prevalent in the Far East. It affects more men than women, and usually occurs between the ages of 40 and 50 years.

Causes

EBV has been linked to IM in the Western world for decades. It has also become associated consistently with nasopharyngeal cancers in Asia (especially China) and Burkitt's lymphoma in Africa and Papua New Guinea. According to the CDC, EBV is not the sole cause of these two malignancies, but does play an important role in the development of both cancers. The mechanism that allows Epstein-Barr Virus to at least help in producing such diverse illnesses in diverse regions of the world has been the subject of increasing research and scrutiny.

It is known that, once it infects a person, EBV is one of the herpesviruses that remain in the human body for life. Under certain, still not-understood conditions, it alters white blood cells normally associated with the immune system, changing B lymphocytes (those normally associated with making antibodies), and causing them to reproduce rampantly. EBV can bind to these white blood cells to produce a solid mass made up of B lymphocytes called Burkitt's lymphomaor to the mucous membranes of the mouth and nose and cause nasopharyngeal cancer. Since Burkitt's lymphoma typically occurs in people living in moist, tropical climates, the same regions where people usually contract malaria, it has been speculated that the immune system is altered by its response to malaria. When EBV infection occurs, the altered immune system's reaction is the production of a tumor.

Special concerns

Though studies about the hereditary tendency of abnormal cell development after EBV infection are incomplete, some studies have shown it to be a hereditary trait based upon the X chromosome.

Treatments

Because EBV infections are viral in origin, antibiotics are ineffective against them. Much research is geared toward the development of a vaccines effective against both the virus and cancer.

Anticancer drugs, such as cyclophosphamide , or radiation therapy have been shown to be effective against Burkitt's lymphoma in four out of five cases.

Alternative and complementary therapies

The goal of alternative treatment is to lower the white blood cell count to normal levels. Treatment often includes nutritional supplements such as flaxseed oil or shark cartilage, vitaminsincluding vitamins C and K, and mineral supplements containing magnesium and potassium. Well-conducted randomized clinical trials have not yet been conducted to prove efficacy of these therapies.

Resources

BOOKS

Clayman, Charles. The American Medical Association Home Medical Encyclopedia New York: Random House, 1989

Cotran, R. S., et al. Robbins Pathologic Basis of Disease. 5th ed. Philadelphia: W. B. Saunders, 1994.

Diamond, John W., W. Lee Cowden, and Burton Goldberg. An Alternative Medicine Definitive Guide to Cancer Puyallup, WA:: Future Medicine Publishing, Inc., 1997.

ORGANIZATIONS

Queensland Institute of Medical Research <http:[email protected]> 12/7/99

Center for Disease Control, National Center for Infectious Diseases Epstein-Barr Virus and Infectious Mononucleosis <http://www.cdc.gov.org> 3/26/01

Joan Schonbeck, R.N.

KEY TERMS

Lymphocyte

Any of a group of white blood cells of crucial importance to the immune system's production of a tailor-made defense against specific invading organisms.

Lymphoma

A group of cancers in which the cells of tissue usually found in the lymph nodes or spleen multiply abnormally.

Malaria

A serious disease prevalent in the tropics. It is caused by parasites and produces severe fever and sometimes complications affecting the kidneys, liver, brain, and blood. It is spread by the Anopheles mosquito and can be fatal.

Nasopharyngeal

Affecting the passage connecting the nasal cavity behind the nose to the top of the throat behind the soft palate.

QUESTIONS TO ASK THE DOCTOR

  • What tests can be done if Epstein-Barr Virus infection is suspected?
  • Have any vaccines against Epstein-Barr Virus been developed?

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Epstein-Barr Virus

Epstein-Barr virus

Epstein-Barr virus (EBV) is part of the family of human herpes viruses . Infectious mononucleosis (IM) is the most common disease manifestation of this virus, which once established in the host, can never be completely eradicated. Very little can be done to treat EBV; most methods can only alleviate resultant symptoms.

In addition to infectious mononucleosis, EBV has also been identified in association withalthough not necessarily believed to causeas many as 50 different illnesses and diseases, including chronic fatigue syndrome, rheumatoid arthritis, arthralgia (joint pain without inflammation ), and myalgia (muscle pain). While studying aplastic anemia (failure of bone marrow to produce sufficient red blood cells), researchers identified EBV in bone marrow cells of some patients, suggesting the virus may be one causative agent in the disease. Also, several types of cancer can be linked to presence of EBV, particularly in those with suppressed immune systems, for example, suffering from AIDS or having recently undergone kidney or liver transplantation. The diseases include hairy cell leukemia, Hodgkin's and non-Hodgkin lymphoma, Burkitt's lymphoma (cancer of the lymphatic system endemic to populations in Africa), and nasopharyngeal carcinoma (cancers of the nose, throat, and thymus gland, particularly prevalent in East Asia). Recently, EBV has been associated with malignant smooth-muscle tissue tumors in immunocompromised children. Such tumors were found in several children with AIDS and some who had received liver transplants. Conversely, it appears that immunosuppressed adults show no elevated rates of these tumors.

Epstein-Barr virus was first discovered in 1964 by three researchersEpstein, Achong, and Barrwhile studying a form of cancer prevalent in Africa called Burkitt's lymphoma. Later, its role in IM was identified. A surge of interest in the virus has now determined that up to 95% of all adults have been infected with EBV at some stage of their lives. In seriously immunocompromised individuals and those with inherited immune system deficiencies, the virus can become chronic, resulting in "chronic Epstein-Barr virus" which can be fatal.

EBV is restricted to a very few cells in the host. Initially, the infection begins with its occupation and replication in the thin layer of tissue lining the mouth, throat, and cervix, which allow viral replication. The virus then invades the B cells , which do not facilitate the virus's replication but do permit its occupation. Infected B cells may lie dormant for long periods or start rapidly producing new cells. Once activated in this way, the B cells often produce antibodies against the virus residing in them. EBV is controlled and contained by killer cells and suppressor cells known as CD4 T lymphocytes in the immune system. Later, certain cytotoxic (destructive) CD8 T lymphocytes with specific action against EBV also come into play. These cells normally defend the host against the spread of EBV for the life of the host.

A healthy body usually provides effective immunity to EBV in the form of several different antibodies, but when this natural defense mechanism is weakened by factors that suppress its normal functioningfactors such as AIDS, organ transplantation, bone marrow failure, chemotherapy and other drugs used to treat malignancies, or even extended periods of lack of sleep and overexertionEBV escape from their homes in the B cells, disseminate to other bodily tissue, and manifest in disease.

Infection is determined by testing for the antibodies produced by the immune system to fight the virus. The level of a particular antibodythe heterophile antibodyin the blood stream is a good indicator of the intensity and stage of EBV infection. Even though EBV proliferates in the mouth and throat, cultures taken from that area to determine infection are time-consuming, cumbersome, and usually not accurate.

Spread of the virus from one person to another requires close contact. Because of viral proliferation and replication in the lining of the mouth, infectious mononucleosis is often dubbed "the kissing disease." Also, because it inhabits cervical cells, researchers now suspect EBV may be sexually transmitted. Rarely is EBV transmitted via blood transfusion.

EBV is one of the latent viruses, which means it may be present in the body, lying dormant often for many years and manifesting no symptoms of disease. The percentage of shedding (transmission) of the virus from the mouth is highest in people with active IM or who have become immunocompromised for other reasons. A person with active IM can prevent transmission of the disease by avoiding direct contactsuch as kissingwith uninfected people. However, shedding has been found to occur in 15% of adults who test positive for antibodies but who show no other signs of infection, thus allowing the virus to be transmitted. Research efforts are directed at finding a suitable vaccine .

The prevalence of antibodies against EBV in the general population is high in developing countries and lower socioeconomic groups where individuals become exposed to the virus at a very young age. In developed countries, such as the United States, only 50% of the population shows traces of antibody by the age of five years, with an additional 12% in college-aged adolescents, half of whom will actually develop IM. This situation indicates that children and young persons between the ages of 10 and 21 years are highly susceptible to IM in developed countries, making it a significant health problem among students.

See also Latent viruses and diseases; Mononucleosis, infectious; Viruses and responses to viral infection

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Epstein-Barr virus

Epstein-Barr virus (EBV), herpesvirus that is the major cause of infectious mononucleosis and is associated with a number of cancers, particularly lymphomas in immunosuppressed persons, including persons with AIDS. Epstein-Barr is a ubiquitous virus, so common that it has been difficult to determine whether it is the cause of certain diseases or whether it is simply there as an artifact. In Third World nations, most children are infected with EBV; in most industrialized nations, about 50% of the people are infected. Research has found that all of the lymphomas associated with AIDS and most lymphomas in other immunocompromised persons are connected with latent EBV infection. EBV has been found in biopsy tissue of patients with Hodgkin's disease, breast cancer, and some smooth muscle tumors. EBV also was formerly suspected as the cause of chronic fatigue syndrome (originally named chronic EBV syndrome).

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Epstein-Barr virus

Epstein-Barr virus (EB virus, EBV) (ep-styn bar) n. the virus, belonging to the herpesvirus group, that is the causative agent of glandular fever. It is also implicated in Burkitt's lymphoma, Hodgkin's disease, and hepatitis. [ Sir M. A. Epstein (1921– ) and Y. M. Barr (1932– ), British pathologists]

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Epstein-Barr Virus

Epstein-Barr Virus

Resources

Epstein-Barr virus (EBV) is part of the family of human herpes viruses. Infectious mononucleosis (IM) is the most common disease manifestation of this virus, which once established in the host, can never be completely eradicated. Very little can be done to treat EBV; most methods can only alleviate resultant symptoms.

In addition to infectious mononucleosis, EBV has also been identified in association withalthough not necessarily believed to causeas many as 50 different illnesses and diseases, including chronic fatigue syndrome, rheumatoid arthritis, arthralgia (joint pain without inflammation), and myalgia (muscle pain). While studying aplastic anemia (failure of bone marrow to produce sufficient red blood cells), researchers identified EBV in bone marrow cells of some patients, suggesting the virus may be one causative agent in the disease. Also, several types of cancer can be linked to presence of EBV, particularly in those with suppressed immune systems, for example, suffering from AIDS or having recently undergone kidney or liver transplantation. The diseases include hairy cell leukemia, Hodgkins and non-Hodgkin lymphoma, Burkitts lymphoma (cancer of the lymphatic system endemic to populations in Africa), and nasopharyngeal carcinoma (cancers of the nose, throat, and thymus gland, particularly prevalent in East Asia). Recently, EBV has been associated with malignant smooth-muscle tissue tumors in immunocompromised children. Such tumors were found in several children with AIDS and some who had received liver transplants. Conversely, it appears that immunosuppressed adults show no elevated rates of these tumors.

EBV was first discovered in 1964 by three researchersEpstein, Achong, and Barrwhile studying a form of cancer prevalent in Africa called Burkitts lymphoma. Later, its role in IM was identified. A surge of interest in the virus has now determined that up to 95% of all adults have been infected with EBV at some stage of their lives. In seriously immunocompromised individuals and those with inherited immune system deficiencies, the virus can become chronic, resulting in chronic Epstein-Barr virus which can be fatal.

EBV is restricted to a very few cells in the host. Initially, the infection begins with its occupation and replication in the thin layer of tissue lining the mouth, throat, and cervix, which allow viral replication. The virus then invades the B cells, which do not facilitate the viruss replication but do permit its occupation. Infected B cells may lie dormant for long periods or start rapidly producing new cells. Once activated in this way, the B cells often produce antibodies against the virus residing in them. EBV is controlled and contained by killer cells and suppressor cells known as CD4 T lymphocytes in the immune system. Later, certain cytotoxic (destructive) CD8 T lymphocytes with specific action against EBV also come into play. These cells normally defend the host against the spread of EBV for the life of the host.

A healthy body usually provides effective immunity to EBV in the form of several different antibodies, but when this natural defense mechanism is weakened by factors that suppress its normal functioningfactors such as AIDS, organ transplantation, bone marrow failure, chemotherapy and other drugs used to

KEY TERMS

Arthralgia Joint pain that occurs without inflammation.

Immunosuppressed/immunocompromised Reduced ability of the immune system to fight disease and infection.

Myalgia Muscular aches and pain.

Nasopharyngeal Of the nose and throat.

treat malignancies, or even extended periods of lack of sleep and overexertionEBV escape from their homes in the B cells, disseminate to other bodily tissue, and manifest in disease.

Infection is determined by testing for the antibodies produced by the immune system to fight the virus. The level of a particular antibodythe heterophile antibodyin the blood stream is a good indicator of the intensity and stage of EBV infection. Even though EBV proliferates in the mouth and throat, cultures taken from that area to determine infection are time-consuming, cumbersome, and usually not accurate.

Spread of the virus from one person to another requires close contact. Because of viral proliferation and replication in the lining of the mouth, infectious mononucleosis is often dubbed the kissing disease. Also, because it inhabits cervical cells, researchers now suspect EBV may be sexually transmitted. Rarely is EBV transmitted via blood transfusion.

EBV is one of the latent viruses, which means it may be present in the body, lying dormant often for many years and manifesting no symptoms of disease. The percentage of shedding (transmission) of the virus from the mouth is highest in people with active IM or who have become immunocompromised for other reasons. A person with active IM can prevent transmission of the disease by avoiding direct contactsuch as kissingwith uninfected people. However, shedding has been found to occur in 15% of adults who test positive for antibodies but who show no other signs of infection, thus allowing the virus to be transmitted. Research efforts are directed at finding a suitable vaccine.

Resources

BOOKS

Richman, D.D., and R.J. Whitley. Clinical Virology. 2nd ed. Washington: American Society for Microbiology, 2002.

Robertson, Erie S. Epstein-Barr Virus. Wymondham, UK: Caister Academic Press, 2005.

Tselis, Alex and Hal B. Jenson (eds.). Epstein-Barr Virus. London: Informa Healthcare, 2006.

Marie L. Thompson

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Epstein-Barr Virus

Epstein-Barr Virus

Introduction

Disease History, Characteristics, and Transmission

Scope and Distribution

Treatment and Prevention

Impacts and Issues

BIBLIOGRAPHY

Introduction

Epstein-Barr Virus (EBV) is also known as the Human Herpesvirus 4 (HHV-4). It is one of the most common viruses present in humans. The Centers for Disease control and Prevention (CDC) estimates that 95% of all adults aged 35–40 in the United States have been infected by EBV. Most people infected with EBV during childhood either show no symptoms or suffer a brief illness with symptoms indistinguishable from other mild, common illnesses.

In teenagers and young adults, EBV can result in mononucleosis, commonly called mono, with prolonged and more severe symptoms. Teenagers and young adults typically acquire EBV from infected cells in the mouth. EBV is present in saliva, also earning mononucleosis the nickname “the kissing disease.”

Disease History, Characteristics, and Transmission

Epstein-Barr virus was first discovered in 1964 by Michael Epstein and Yvonne Barr while they were studying Burkett's lymphoma, a form of cancer that is relatively common in Africa. The virus was named after these discoverers. Its role as the cause of infectious mononucleosis was later identified.

The virus is extremely prevalent in humans. The infection can persist, as the virus may remain latent for years. In response to triggers that are still not fully known, EBV can reinitiate an active infection. Latency and recurrence occur most often in individuals with compromised immune systems.

Initially, an EBV infection begins when the virus infects and then makes new copies of the virus in the thin layer of epithelial cells that line the mouth, throat, and cervix. The infection then expands to include B cells—cells that are components of the immune system. It is within the B cells that the virus becomes latent by integrating its DNA into the DNA of the host cells. As the host DNA duplicates by cell division, so does the viral DNA. Virus particles that are made in the B cells can escape to other cell sin the body. Virus production in these other cells affects the functioning of the tissue, producing some of the symptoms of infection.

EBV is contagious—it can be spread from person to person. Transmission of EBV typically occurs through contact with saliva. Contact with infected cervical cells through sexual activity may transmit EBV. Transmission via blood transfusions is possible but rare.

Scope and Distribution

Epstein-Barr virus can be present in almost any person, in any country. However, studies that have examined the prevalence of antibodies against the virus have shown that EBV is almost universally present in adults in developing countries. Worldwide, most people are exposed to EBV early in life, when infection is most likely to cause only mild illness. In the United States, 50% of the population is positive for antibodies to the virus by the age of five.

WORDS TO KNOW

ANTIBODY: Antibodies, or Y-shaped immunoglobulins, are proteins found in the blood that help to fight against foreign substances called antigens. Antigens, which are usually proteins or polysaccharides, stimulate the immune system to produce antibodies. The antibodies inactivate the antigen and help to remove it from the body. While antigens can be the source of infections from pathogenic bacteria and viruses, organic molecules detrimental to the body from internal or environmental sources also act as antigens. Genetic engineering and the use of various mutational mechanisms allow the construction of a vast array of anti-bodies (each with a unique genetic sequence).

HETEROPHILE ANTIBODY: A heterophile antibody is an antibody that is found in the blood of someone with infectious mononucleosis, also known as glandular fever.

LATENT: A condition that is potential or dormant, not yet manifest or active, is latent.

Treatment and Prevention

Infection is determined by detecting the presence of the antibodies that have been produced by the immune system in response to the presence of the virus. The level of a particular antibody in the blood called the heterophile antibody is a reliable indicator of the intensity of the infection. Even though the virus is common in the cells of the mouth and throat, samples of cells taken from the areas are not a reliable means of detecting the virus.

Treatment of Epstein-Barr virus infection is difficult, as the virus can become latent for months or years. There are no available vaccines or antiviral drugs to prevent or treat EBV. Teenagers and young adults suffering from infectious mononucleosis are typically given medications to ease symptoms such as fever, aches, and fatigue that can persist for up to four weeks.

Impacts and Issues

Epstein-Barr virus affects just about everyone at some time. In most people, the infection is brief and may either produce no symptoms or brief, mild illness. The most severe symptoms associated with EBV occur in people aged 10–21 who were not previously exposed to EBV in early childhood and who develop mononucleosis. Infectious mononucleosis can have more serious impacts on people living in underdeveloped regions because the condition can leave persons more susceptible to other infections.

From the mid–1980s through the early 1990s, researchers identified EBV as a possible cause of chronic fatigue syndrome (CFS) in adults. Many persons who displayed the symptoms of CFS—headaches, memory loss, and severe, prolonged exhaustion—also carried EBV. The CDC embarked on a four-year study of CFS, eventually finding no link between EBV and CFS. The scientific community now disregards EBV as a direct cause of chronic fatigue syndrome.

EBV has also been linked to the formation of certain types of cancer. EBV is linked to a cancer of the upper respiratory tract, nasopharyngeal carcinoma. This type of cancer occurs most commonly in Africa and parts of China, however, researcher have noted that the increase of nasopharyngeal carcinoma in China could also be influenced by environmental factors and diet. In equatorial Africa, malaria infections can reduce the body's ability to respond to chronic EBV infection. The two diseases in tandem have been linked to Burkitt's lymphoma, a cancer that often forms large tumors on the jaw.

IN CONTEXT: TRENDS AND STATISTICS

The National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC) states the Epstein-Barr virus (EBV) is “one of the most common human viruses. The virus occurs worldwide, and most people become infected with EBV sometime during their lives. In the United States, as many as 95% of adults between 35 and 40 years of age have been infected. Infants become susceptible to EBV as soon as maternal antibody protection (present at birth) disappears. Many children become infected with EBV, and these infections usually cause no symptoms or are indistinguishable from the other mild, brief illnesses of childhood. In the United States and in other developed countries, many persons are not infected with EBV in their childhood years. When infection with EBV occurs during adolescence or young adulthood, it causes infectious mononucleosis 35% to 50% of the time.”

SOURCE: National Center for Infectious Diseases, Centers for Disease Control and Prevention

See AlsoMononucleosis; Viral Disease.

BIBLIOGRAPHY

Books

Hoffman, Gretchen. Mononucleosis. New York: Benchmark Books, 2006.

Powell, Michael, and Oliver Fischer. 101 Diseases You Don't Want to Get. New York: Thunder's Mouth Press, 2005.

Tselis, Alex, and Hal B. Jenson. Epstein-Barr Virus. London: Informa Healthcare, 2006.

Web Sites

Centers for Disease Control and Prevention. “Epstein-Barr Virus and Infectious Mononucleosis.” <http://www.cdc.gov/ncidod/diseases/ebv.htm> (accessed April 10, 2007).

Brian Hoyle

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Epstein-Barr Virus

Epstein-Barr virus

Epstein-Barr virus (EBV) is part of the family of human herpes viruses. Infectious mononucleosis (IM) is the most common disease manifestation of this virus which, once established in the host, can never be completely eradicated. Very little can be done to treat EBV; most methods can only alleviate resultant symptoms. Sleep and rest—complete bedrest in severe cases—is still the best medicine for sufferers of this virus.

In addition to infectious mononucleosis, EBV has also been identified in association with—although not necessarily believed to cause—as many as 50 different illnesses and diseases, including chronic fatigue syndrome , rheumatoid arthritis , arthralgia (joint pain without inflammation ), and myalgia (muscle pain). While studying aplastic anemia (failure of bone marrow to produce sufficient red blood cells), researchers identified EBV in bone marrow cells of some patients, suggesting the virus may be one causative agent in the disease. Also, several types of cancer can be linked to presence of EBV, particularly in those with suppressed immune systems, for example, suffering from AIDS or having recently undergone kidney or liver transplantation. The diseases include hairy cell leukemia , Hodgkin's and non-Hodgkin lymphoma, Burkitt's lymphoma (cancer of the lymphatic system endemic to populations in Africa ), and nasopharyngeal carcinoma (cancers of the nose, throat, and thymus gland, particularly prevalent in East Asia ). Very recently, EBV has been associated with malignant smooth-muscle tissue tumors in immunocompromised children. Such tumors were found in several children with AIDS and some who had received liver transplants. Conversely, it appears that immunosuppressed adults show no elevated rates of these tumors.


Discovery, disease, and research

EBV was first discovered in 1964 by three researchers—Epstein, Achong, and Barr—while studying a form of cancer prevalent in Africa called Burkitt's lymphoma. Later, its role in IM was identified. A surge of interest in the virus has now determined that up to 95% of all adults have been infected with EBV at some stage of their lives. In seriously immunocompromised individuals and those with inherited immune system deficiencies, the virus can become chronic, resulting in "chronic Epstein-Barr virus" which is extremely serious and can be fatal.

Age and the health of the immune system play important roles in EBV-related illnesses. Infectious mononucleosis is the most common illness resulting from primary EBV infection . In young children, it often takes on mild flu-like symptoms that improve with time, or the symptoms are so mild they go unnoticed. However, ill or older people, IM can become a debilitating infection, and complications can affect almost every organ of the body, including possible rupture of the spleen. In fewer than 1% of IM cases, neurologic complications develop, and the patient can develop encephalitis , meningitis , Guillian-Barre syndrome, or other serious conditions. Very rarely, IM causes complications like aplastic anemia, thrombocytopenia (reduced numbers of platelets, the clotting factor in blood, resulting in bleeding), and granulocytopenia (severe reduction in white cells in the blood allowing the potential for "superinfection"). More commonly, however, IM causes persistent fevers; swollen and tender lymph glands in the neck, groin, and armpits; sore throat and even severe tonsillitis ; and sometimes a rash. Because the sore throat is so prominent, and because it may in fact become secondarily infected with strep, some patients are treated with ampicillin. Almost all of these individuals will break out in a rash which is often mistaken for evidence of a penicillin allergy . IM is almost always accompanied by fatigue and general malaise which can be quite severe initially, but bouts of which become less severe and prolonged over several weeks or months. Inflammation of the spleen and liver are also common in IM. The spleen in particular may grow very large, and may rupture spontaneously in about 0.5% of patients.

EBV is also implicated in another immune system-related illness called chronic fatigue syndrome (CFS). In several communities throughout the world, several epidemic-type outbreaks of what became known as CFS, including one in Lake Tahoe in 1985, baffled the medical community. There have been many conflicting theories in the ongoing search for the role of EBV in CFS. Initially, EBV was thought to be the causative factor; however, following intense studies performed during an outbreak of CFS in New York in 1985, it was determined that not everyone suffering from CFS developed antibodies to EBV. In cases where several children in one family all showed the same symptoms, only thee out of four showed infection by EBV. Further studies revealed that about one-third of the individuals affected by CFS had experienced primary infection with EBV years earlier and were once again fighting the virus. This syndrome became known as "active chronic EBV infection." In the other two-thirds of CFS sufferers, EBV levels were no different to those shown by the general population. It therefore seemed inaccurate to conclude EBV was the causative agent in CFS. Because some CFS patients experience reactivation of latent EBV, while in others EBV becomes active for the first time, it is possible that the effect of CFS on the immune system allows activation and reactivation of EBV. One theory about the interrelatedness of EBV and CFS is that, rather than causing CFS, EBV may, instead, trigger it.

Origin and development

EBV is restricted to a very few cells in the host. Initially, the infection begins with its occupation and replication in the thin layer of tissue lining the mouth, throat, and cervix, which allow viral replication. The virus then invades the B cells, which do not facilitate the virus's replication but do permit its occupation. Infected B cells may lie dormant for long periods or start rapidly producing new cells. Once activated in this way, the B cells often produce antibodies against the virus residing in them. EBV is controlled and contained by killer cells and suppressor cells known as CD4+ T lymphocytes in the immune system. Later, certain cytotoxic (destructive) CD8+ T lymphocytes with specific action against EBV also come into play. These cells normally defend the host against the spread of EBV for the life of the host.

A healthy body usually provides effective immunity to EBV in the form of several different antibodies, but when this natural defense mechanism is weakened by factors that suppress its normal functioning—factors such as AIDS, organ transplantation, bone marrow failure, chemotherapy and other drugs used to treat malignancies, or even extended periods of lack of sleep and overexertion—EBV escape from their homes in the B cells, disseminate to other bodily tissue, and manifest in disease.

Diagnostic blood tests cannot detect the virus itself. Infection is determined by testing for the antibodies produced by the immune system to fight the virus. The level of a particular antibody—the heterophile antibody—in the blood stream is a good indicator of the intensity and stage of EBV infection. Even though EBV proliferates in the mouth and throat, cultures taken from that area to determine infection are time-consuming, cumbersome, and usually not accurate.

Treatment is primarily supportive; encouraging rest and recuperation. When spleen enlargement is present, activities may need to be restricted to avoid the complication of splenic rupture. Antibiotics should be used only to treat documented bacterial infections which complicate the course of IM. Anti-viral medications do not seem to be helpful. Steroids should only be given in the rare instance of such complications as hemolytic anemia, severely swollen tonsils which are causing airway obstruction, or platelet destruction.


Disease transmission and prevention

Spread of the virus from one person to another requires close contact. Because of viral proliferation and replication in the lining of the mouth, infectious mononucleosis is often dubbed "the kissing disease." Also, because it inhabits cervical cells, researchers now suspect EBV may be sexually transmitted. Rarely is EBV transmitted via blood transfusion.

EBV is one of the latent viruses, which means it may be present in the body, lying dormant often for many years and manifesting no symptoms of disease. The percentage of shedding (transmission) of the virus from the mouth is highest in people with active IM or who have become immunocompromised for other reasons. A person with active IM can prevent transmission of the disease by avoiding direct contact—such as kissing—with uninfected people. However, shedding has been found to occur in 15% of adults who test positive for antibodies but who show no other signs of infection, thus allowing the virus to be transmitted. Research efforts are directed at finding a suitable vaccine .

The prevalence of antibodies against EBV in the general population is high in developing countries and lower socioeconomic groups where individuals become exposed to the virus at a very young age. In developed countries, such as the United States, only 50% of the population shows traces of antibody by the age of five years, with an additional 12% in college-aged adolescents, half of whom will actually develop IM. This situation indicates that children and adolescents between the age of 10 to 20 years are highly susceptible to IM in developed countries, making it a significant health problem among young students and those in the military.


Resources

books

Bell, David S. The Doctor's Guide to Chronic Fatigue Syndrome: Understanding, Treating, and Living with CFIDS. Reading, MA: Addison-Wesley, 1993.

Flint, S.J., et al. Principles of Virology: Molecular Biology,Pathogenesis, and Control Washington: American Society for Microbiology, 1999.

Richman, D.D., and R.J. Whitley. Clinical Virology. 2nd ed. Washington: American Society for Microbiology, 2002.

periodicals

Liebowitz, David. "Epstein-Barr Virus—An Old Dog With New Tricks." The New England Journal of Medicine 332, no. 1 (5 January 1995): 55-57.


Marie L. Thompson

KEY TERMS

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Antibody

—A molecule created by the immune system in response to the presence of an antigen (a foreign substance or particle). It marks foreign microorganisms in the body for destruction by other immune cells.

Arthralgia

—Joint pain without inflammation.

B cell

—Immune system white blood cell that produces antibodies.

Immunosuppressed/immunocompromised

—Reduced ability of the immune system to fight disease and infection.

Myalgia

—Muscular aches and pain.

Nasopharyngeal

—Of the nose and throat.

T cells

—Immune-system white blood cells that enable antibody production, suppress antibody production, or kill other cells.

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