Clinical Information

Epstein-Barr virus (EBV), a member of the herpesvirus group, is the etiologic agent of infectious mononucleosis. Infection with EBV usually occurs early in life. For several weeks to months after acute onset of the infection, EBV is spread by upper respiratory secretions that contain the virus. Among the EBV-associated clinical manifestations, infectious mononucleosis (IM) is the most common. EBV infection can be severe in immunosuppressed patients who may develop lymphoproliferative syndromes, especially in patients with advanced HIV and in patients who have undergone kidney or bone marrow transplantation. Other rare manifestations include African-type Burkitt lymphoma and nasopharyngeal carcinoma (NPC).

EBV does not grow in standard cell cultures and molecular testing is the primary means of diagnosis and monitoring response to therapy in immunosuppressed patients. Serologic testing for EBV remains important for diagnosis of infectious mononucleosis in otherwise healthy individuals and for pre-transplant or pre-immunosuppression screening purposes.

The majority of infections in healthy individuals can be identified by testing patient sera for heterophile antibodies using a rapid latex slide agglutination test (MONOS / Infectious Mononucleosis, Rapid Test, Serum). Heterophile antibodies usually appear within the first 3 weeks of illness but decline rapidly within thereafter. However, heterophile antibodies fail to develop in about 10% of adults and in more than 75% of infants and young children under the age of 4. In cases where EBV is suspected but the heterophile antibody is not detected or if confirmation is needed, or if patients are undergoing pre-immunosuppression screening, evaluation of EBV-specific antibodies, including assessment for IgM and IgG against the EBV viral capsid antigen (VCA) and IgG against the EBV nuclear antigen (EBNA) is useful.

The EBV early antigen (EA) has two forms, including the diffuse (ie, present in cytoplasm and nucleus of infected cells [EA-D]) and restricted (ie, present only in the cytoplasm of infected cells [EA-R]) forms. Generally, IgG antibodies to the EA, specifically the EA-D form, are only detected during active EBV infection, such as in patients with IM.

Additionally, IgG antibodies to EA-D are also found in patients with NPC. Of patients with type 2 or 3 NPC (World Health Organization classification), 94% and 83% respectively, have positive antibody responses to EA. Only 35% of patients with type 1 NPC have a positive response. The specificity of the test is such that 82% to 91% of healthy blood donor controls and patients who do not have NPC have negative responses (9%-18% false-positive results). Although this level of specificity is useful for diagnostic purposes, the false-positive rate indicates that the test is not useful for NPC screening.