Epstein-Barr Virus and Infectious Mononucleosis : Part 2

by CDC

(Page 2 of 2)

EBV-Specific Laboratory Tests

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.

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.

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 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.

About the Author

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