Clinical Summary

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 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.

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 and IgG against the EBV nuclear antigen is useful.

CAUTIONS 
Specimens collected too early during the course of the disease may not contain detectable antibodies to Epstein-Barr virus (EBV). Another specimen collected 1 to 2 weeks later may be required.

Test results should be evaluated in relation to patient symptoms, clinical history, and other laboratory findings.

The timing of the appearance of IgG antibodies to viral capsid antigen (VCA) or Epstein-Barr nuclear antigen or IgM antibodies to VCA is subject to variations among individuals and serological assays.

This assay's performance characteristics with immunosuppressed individuals, newborns, cord blood, or matrices other than human serum have not been established.

Assay performance characteristics have not been established for the diagnosis of nasopharyngeal carcinoma, Burkitt lymphoma, and other EBV-associated lymphomas.

Anti-VCA-specific IgG may compete with IgM for binding sites, leading to false-negative results. Rheumatoid factor (RF), in the presence of specific IgG, may contribute to false-positive results. The absorbent in the VCA IgM diluent is intended to neutralize the effects of RF and specific IgG. Studies have shown that the absorbent was able to neutralize up to 98% of the activity in a specimen known to contain 3328 IU/mL of RF activity.

Testing for VCA IgM should not be performed as a screening procedure on the general population. The predictive value of positive or negative results depends on the pretest likelihood of Epstein-Barr-associated disease being present. Testing should only be performed when clinical evidence suggests the diagnosis of this syndrome.