Infectious mononucleosis is an acute infectious disease caused by the Epstein-Barr virus (EBV), a member of the herpes group. It primarily affects young adults and children, although in children it is usually so mild that it is often overlooked.
Characteristically, infectious mononucleosis produces fever, sore throat and cervical lymphadenopathy, as well as hepatic dysfunction, increased lymphocytes and monocytes, and development of heterophil antibodies. Prognosis is excellent, and major complications are uncommon.
Infectious mononucleosis is fairly common and both sexes are affected equally. Symptoms of mononucleosis mimic those of other infectious diseases, including hepatitis, rubella and toxoplasmosis. Early symptoms include headache, malaise, and fatigue followed by a triad of symptoms: sore throat, cervical lymphadenopathy, and temperature fluctuations. Symptoms usually subside about 6 to 10 days after onset of the disease but may persist for weeks.
Chronic EBV Infection (?)
It is important to note that symptoms related to infectious mononucleosis caused by EBV infection seldom last for more than 4 months. When such an illness lasts more than 6 months, it is frequently called chronic EBV infection. However, valid laboratory evidence for continued active EBV infection is seldom found in these patients. The illness should be investigated further to determine if it meets the criteria for chronic fatigue syndrome (CFS). This process includes ruling out other causes of chronic illness or fatigue.
In the early 1990’s several papers were published that described patients with CFS and serologic test results consistent with reactivated or persistent Epstein-Barr virus (EBV) infection. This proposed connection led to the use of terms such as “chronic mononucleosis”, “chronic EBV infection” and “postviral fatigue syndrome”. Further investigation failed to establish a pattern of disease and chronic infection with EBV.
Diagnosis and Testing
In most cases of infectious mononucleosis, the clinical diagnosis can be made from the characteristic triad of fever, pharyngitis, and lymphadenopathy lasting for 1 to 4 weeks. Serologic test results include a normal to moderately elevated white blood cell count, an increased total number of lymphocytes, greater than 10% atypical lymphocytes, and a positive reaction to a “mono spot” test. In patients with symptoms compatible with infectious mononucleosis, a positive Paul-Bunnell heterophile antibody test result is diagnostic, and no further testing is necessary.
Laboratory tests are not always foolproof. For various reasons, false-positive and false-negative results can occur for any test. However, the laboratory tests for EBV are for the most part accurate and specific. Because the antibody response in primary EBV infection appears to be quite rapid, in most cases testing paired acute- and convalescent-phase serum samples will not demonstrate a significant change in antibody level. Effective laboratory diagnosis can be made on a single acute-phase serum sample by testing for antibodies to several EBV-associated antigens simultaneously. In most cases, a distinction can be made as to whether a person is susceptible to EBV, has had a recent infection, has had infection in the past, or has a reactivated EBV infection.
Antibodies to several antigen complexes may be measured. These antigens are the viral capsid antigen, the early antigen, and the EBV nuclear antigen (EBNA). In addition, differentiation of immunoglobulin G and M subclasses to the viral capsid antigen can often be helpful for confirmation. When the “mono spot” test is negative, the optimal combination of EBV serologic testing consists of the antibody titration of four markers: IgM and IgG to the viral capsid antigen, IgM to the early antigen, and antibody to EBNA.
IgM to the viral capsid antigen appears early in infection and disappears within 4 to 6 weeks. IgG to the viral capsid antigen appears in the acute phase, peaks at 2 to 4 weeks after onset, declines slightly, and then persists for life. IgG to the early antigen appears in the acute phase and generally falls to undetectable levels after 3 to 6 months. In many people, detection of antibody to the early antigen is a sign of active infection, but 20% of healthy people may have this antibody for years.
Antibody to EBNA determined by the standard immunofluorescent test is not seen in the acute phase, but slowly appears 2 to 4 months after onset, and persists for life. This is not true for some EBNA enzyme immunoassays, which detect antibody within a few weeks of onset.
Finally, even when EBV antibody tests, such as the early antigen test, suggest that reactivated infection is present, this result does not necessarily indicate that a patient’s current medical condition is caused by EBV infection. A number of healthy people with no symptoms have antibodies to the EBV early antigen for years after their initial EBV infection.
Therefore, interpretation of laboratory results is somewhat complex and should be left to physicians who are familiar with EBV testing and who have access to the entire clinical picture of a person. To determine if EBV infection is associated with a current illness, consult with an experienced physician.
Signs, symptoms & indicators of Epstein-Barr virus (EBV)
(Frequent) painful cervical nodes
(Frequent) cervical node swelling
Conditions that suggest Epstein-Barr virus (EBV)
Chronic Fatigue / Fibromyalgia Syndrome
EBV, and other viruses, may ultimately be found to play some role in CFS in many patients. At the same time, many CFS patients have had no exposure to EBV at all.
Increased Risk of Mouth/Throat Cancer
The Epstein-Barr virus is also known to be a risk factor in the development of cancer of the throat. The Epstein-Barr virus is the virus that causes mononucleosis. However, infection with the virus alone is not sufficient to cause cancer, since this cancer is quite rare and mononucleosis is quite common.
History of Epstein-Barr/Epstein-Barr virus infection or Epstein-Barr virus suggested
Counter Indicators
Absence of Epstein-Barr virus
Risk factors for Epstein-Barr virus (EBV)
Having low CD8 count
A low CD8 T cell population may represent a long-term, low-level response driven by chronic and/or repeated antigen exposure, such as from EBV.
Epstein-Barr virus (EBV) suggests the following may be present
CMV Infection
14 patients with chronic symptoms of disabling fatigue in association with serologic evidence of active Epstein-Barr virus (EBV) infection were studied. Two thirds were women, and the average age at onset was 29 years. Forty-three percent were known to have had previous infectious mononucleosis, but the usual criteria for that diagnosis were not helpful with the present syndrome. Eighty-six percent had serologic evidence of cytomegalovirus (CMV) infection. Profound immunodeficiency was not present, but 71% had partial hypogammaglobulinemia, and minor abnormalities of T cell subsets were noted in six of seven patients studied. Fifty-seven percent achieved temporary serologic and symptomatic remission after an average duration of 33 months. Only one patient has a sustained remission. [South Med J. 1984 ov;77(11): pp.1376-82]
Recommendations for Epstein-Barr virus (EBV)
BHT (Butylated Hydroxytoluene)
Butylated hydroxytoluene (BHT) is a potent inactivator of lipid-enveloped viruses.
Coconut
May be an effective aid in the destruction of lipid-enveloped viruses, such as HIV, HHV-6 (strains A and B), EBV, CMV, and herpes. See also Monolaurin.
Artificial Sweetener Avoidance
Aspartame use has been reported to trigger or mimic symptoms of Epstein-Barr virus (EBV) infection.
Lithium (low dose)
One research group reported that lithium inhibits the reproduction of several viruses, including herpes simplex viruses (HSV 1, HSV 2), adenovirus (the “common cold” virus), cytomegalovirus, Epstein-Barr virus (associated with mononucleosis and many cases of chronic fatigue), and the measles virus.
Ozone / Oxidative Therapy
The inactivation of viral particles by ozone may take place by a variety of mechanisms which range from direct physical-chemical effects to a more indirect immunological effect. Viruses coated by a lipid glycoprotein envelope such as Epstein-Barr are vulnerable to the influence of ozone by its intense oxidizing properties.
Key
| Weak or unproven link |
| Strong or generally accepted link |
| Proven definite or direct link |
| Very strongly or absolutely counter-indicative |
| May do some good |
| Likely to help |
| Highly recommended |
Glossary
Acute
An illness or symptom of sudden onset, which generally has a short duration.
Epstein Barr virus
(EBV): A virus that causes infectious mononucleosis and that is possibly capable of causing other diseases in immunocompromised hosts.
Mononucleosis
An acute, infectious disease caused by the herpes virus, Epstein-Barr virus, with fever and inflamed swelling of the lymph nodes around the neck, under the arms, and in the groin.
Virus
Any of a vast group of minute structures composed of a protein coat and a core of DNA and/or RNA that reproduces in the cells of the infected host. Capable of infecting all animals and plants, causing devastating disease in immunocompromised individuals. Viruses are not affected by antibiotics, and are completely dependent upon the cells of the infected host for the ability to reproduce.
Lymphadenopathy
A lymph gland enlargement in response to any foreign substance or disease.
Antibody
A type of serum protein (globulin) synthesized by white blood cells of the lymphoid type in response to an antigenic (foreign substance) stimulus. Antibodies are complex substances formed to neutralize or destroy these antigens in the blood. Antibody activity normally fights infection but can be damaging in allergies and a group of diseases that are called autoimmune diseases.
Hepatitis
Inflammation of the liver usually resulting in jaundice (yellowing of the skin), loss of appetite, stomach discomfort, abnormal liver function, clay-colored stools, and dark urine. May be caused by a bacterial or viral infection, parasitic infestation, alcohol, drugs, toxins or transfusion of incompatible blood. Can be life-threatening. Severe hepatitis may lead to cirrhosis and chronic liver dysfunction.
Malaise
A vague feeling of bodily discomfort, as at the beginning of an illness. A general sense of depression or unease.
Chronic
Usually Chronic illness: Illness extending over a long period of time.
Chronic Fatigue Syndrome
CFS (Chronic Fatigue Syndrome) is a disorder of unknown cause that lasts for prolonged periods and causes extreme and debilitating exhaustion as well as a wide range of other symptoms such as fever, headache, muscle ache and joint pain, often resembling flu and other viral infections. Also known as Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS), Chronic Epstein-Barr Virus (CEBV), Myalgic Encephalomyelitis (ME), "Yuppy Flu" and other names, it is frequently misdiagnosed as hypochondria, psychosomatic illness, or depression, because routine medical tests do not detect any problems.
White Blood Cell
(WBC): A blood cell that does not contain hemoglobin: a blood corpuscle responsible for maintaining the body's immune surveillance system against invasion by foreign substances such as viruses or bacteria. White cells become specifically programmed against foreign invaders and work to inactivate and rid the body of a foreign substance. Also known as a leukocyte.
Serum
The cell-free fluid of the bloodstream. It appears in a test tube after the blood clots and is often used in expressions relating to the levels of certain compounds in the blood stream.
Antigen
A substance, usually protein or protein-sugar complex in nature, which, being foreign to the bloodstream or tissues of an animal, stimulates the formation of specific blood serum antibodies and white blood cell activity. Re-exposure to similar antigen will reactivate the white blood cells and antibody programmed against this specific antigen.
Enzymes
Specific protein catalysts produced by the cells that are crucial in chemical reactions and in building up or synthesizing most compounds in the body. Each enzyme performs a specific function without itself being consumed. For example, the digestive enzyme amylase acts on carbohydrates in foods to break them down.
Cancer
Refers to the various types of malignant neoplasms that contain cells growing out of control and invading adjacent tissues, which may metastasize to distant tissues.
CD8
CD8 cells, also called suppressor and cytotoxic T-cells, play a role in fighting viral infections such as HIV. A T lymphocyte that secretes large amounts of gamma-interferon, a lymphokine involved in the body's defense against viruses. CD8 cells prevent the unnecessary formation of antibodies. A healthy adult usually has between 150 and 1,000 CD8 cells per cubic millimeter. In contrast to CD4 cells, people with HIV often have elevated numbers of CD8 cells, the significance of which is not well understood. Lab reports may also list the T-cell ratio, which is the number of CD4 cells divided by the number of CD8 cells. Since the CD4 count is usually lower and the CD8 count higher than normal, the ratio is usually low in people with HIV. A normal T-cell ratio is usually between 1.5 and 2.5 to 1. The expected response to effective combination anti-HIV treatment is an increase in CD4 count, a decrease in CD8 count, and an increase in the T-cell ratio.
Cytomegalovirus
(CMV): A member of the herpes virus family which may induce the immune-deficient state or cause active illness, such as pneumonia, in a patient already immune-deficient due to chronic illness, such as cancer or organ transplantation therapy.