National Center for Infectious Diseases 

Epstein-Barr Virus and

Infectious Mononucleosis

DISEASE INFORMATION

Epstein-Barr virus, frequently referred to as EBV, is a member of the herpesvirus family and

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.

Symptoms of infectious mononucleosis are fever, sore throat, and swollen lymph glands.

Sometimes, a swollen spleen or liver involvement may develop. Heart problems or

involvement of the central nervous system occurs only rarely, and infectious mononucleosis

is almost never fatal. There are no known associations between active EBV infection and

problems during pregnancy, such as miscarriages or birth defects. Although the symptoms of

infectious mononucleosis usually resolve in 1 or 2 months, EBV remains dormant or latent in

a few cells in the throat and blood for the rest of the person's life. Periodically, the virus can

reactivate and is commonly found in the saliva of infected persons. This reactivation usually

occurs without symptoms of illness.

EBV also establishes a lifelong dormant infection in some cells of the body's immune system.

A late event in a very few carriers of this virus is the emergence of Burkitt's lymphoma and

nasopharyngeal carcinoma, two rare cancers that are not normally found in the United States.

EBV appears to play an important role in these malignancies, but is probably not the sole

cause of disease.

Most individuals exposed to people with infectious mononucleosis have previously been

infected with EBV and are not at risk for infectious mononucleosis. In addition, transmission

of EBV requires intimate contact with the saliva (found in the mouth) of an infected person.

Transmission of this virus through the air or blood does not normally occur. The incubation

period, or the time from infection to appearance of symptoms, ranges from 4 to 6 weeks.

Persons with infectious mononucleosis may be able to spread the infection to others for a

period of weeks. However, no special precautions or isolation procedures are recommended,

since the virus is also found frequently in the saliva of healthy people. In fact, many healthy

people can carry and spread the virus intermittently for life. These people are usually the

primary reservoir for person-to-person transmission. For this reason, transmission of the virus

is almost impossible to prevent.

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The clinical diagnosis of infectious mononucleosis is suggested on the basis of the symptoms

of fever, sore throat, swollen lymph glands, and the age of the patient. Usually, laboratory

tests are needed for confirmation. Serologic results for persons with infectious mononucleosis

include an elevated white blood cell count, an increased percentage of certain atypical white

blood cells, and a positive reaction to a "mono spot" test.

There is no specific treatment for infectious mononucleosis, other than treating the symptoms.

No antiviral drugs or vaccines are available. Some physicians have prescribed a 5-day course

of steroids to control the swelling of the throat and tonsils. The use of steroids has also been

reported to decrease the overall length and severity of illness, but these reports have not been

published.

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, or CFS.

This process includes ruling out other causes of chronic illness or fatigue.

DIAGNOSIS OF EBV INFECTIONS

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. Moderate-to-high levels of heterophile antibodies are seen during

the first month of illness and decrease rapidly after week 4. False-positive results may be

found in a small number of patients, and false-negative results may be obtained in 10% to

15% of patients, primarily in children younger than 10 years of age. True outbreaks of

infectious mononucleosis are extremely rare. A substantial number of pseudo-outbreaks have

been linked to laboratory error, as reported in CDC's Morbidity and Mortality Weekly Report,

vol. 40, no. 32, on August 16, 1991.

When "mono spot" or heterophile test results are negative, additional laboratory testing may

be needed to differentiate EBV infections from a mononucleosis-like illness induced by

cytomegalovirus, adenovirus, or Toxoplasma gondii. Direct detection of EBV in blood or

lymphoid tissues is a research tool and is not available for routine diagnosis. Instead,

serologic testing is the method of choice for diagnosing primary infection.

EBV-Specific Laboratory Tests

Laboratory tests are not always foolproof. For various reasons, false-positive and falsenegative 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 EBVassociated 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.

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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.

Additional Information about EBV Antibody Tests and Interpretation

Antibody tests for EBV can measure the presence and/or the concentration of at least six

specific EBV antibodies. By evaluating the results of these different tests, the stage of EBV

infection can be determined. However, these tests are expensive and not usually needed for

the diagnosis of infectious mononucleosis.

It is not appropriate for CDC to interpret test results or to handle counseling for the public.

We suggest that questions be directed to a local physician who is familiar with the patient's

history and laboratory test results. In addition, CDC cannot recommend specific physicians

for referral. Our general recommendation is for patients to consult with an infectious disease

specialist or their local or state public health department.

SUMMARY OF INTERPRETATION

The diagnosis of EBV infection is summarized as follows:

Susceptibility

If antibodies to the viral capsid antigen are not detected, the patient is susceptible to EBV

infection.

Primary Infection

Primary EBV infection is indicated if IgM antibody to the viral capsid antigen is present and

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National Center for Infectious Diseases

Centers for Disease Control and Prevention

URL:http://www.cdc.gov/ncidod/diseases/ebv.htm

Updated:05/16/2006 14:04:08

antibody to EBV nuclear antigen, or EBNA, is absent. A rising or high IgG antibody to the

viral capsid antigen and negative antibody to EBNA after at least 4 weeks of illness is also

strongly suggestive of primary infection. In addition, 80% of patients with active EBV

infection produce antibody to early antigen.

Past Infection

If antibodies to both the viral capsid antigen and EBNA are present, then past infection (from

4 to 6 months to years earlier) is indicated. Since 95% of adults have been infected with EBV,

most adults will show antibodies to EBV from infection years earlier. High or elevated

antibody levels may be present for years and are not diagnostic of recent infection.

Reactivation

In the presence of antibodies to EBNA, an elevation of antibodies to early antigen suggests

reactivation. However, when EBV antibody to the early antigen test is present, this result does

not automatically indicate that a patient's current medical condition is caused by EBV. A

number of healthy people with no symptoms have antibodies to the EBV early antigen for

years after their initial EBV infection. Many times reactivation occurs subclinically.

Chronic EBV Infection

Reliable laboratory evidence for continued active EBV infection is very seldom found in

patients who have been ill for more than 4 months. When the illness lasts more than 6

months, it should be investigated to see if other causes of chronic illness or CFS are present.

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