From the Guidelines
Diagnostic Approach for Epstein-Barr Virus (EBV) Infection
EBV infection should be suspected and tested for using a combination of complete blood count (CBC) with differential, liver function tests (LFTs), and EBV-specific serologic tests, including IgM and IgG antibodies to viral capsid antigen (VCA) and Epstein-Barr nuclear antigen (EBNA) 1.
- Monospot test (heterophile antibody test) may also be performed to aid in diagnosis, although it may yield false-negative results in approximately 10% of patients, especially in children younger than 10 years 1.
- EBV antibody testing for IgG and IgM to VCA and EBNA is recommended when rapid Monospot or heterophile test results are negative, to differentiate EBV infection from a mononucleosis-like illness caused by other pathogens 1.
- The presence of VCA IgM (with or without VCA IgG) antibodies in the absence of antibodies to EBNA indicates recent primary infection with EBV, while the presence of EBNA antibodies indicates infection more than 6 weeks from the time of the sample 1.
- In certain cases, such as in immunocompromised patients or when monitoring disease progression, EBV polymerase chain reaction (PCR) or EBV viral load testing may be necessary to confirm the diagnosis or monitor disease progression 1.
It is essential to interpret these test results in the context of clinical presentation and other laboratory findings to ensure accurate diagnosis and appropriate management of EBV infection.
From the Research
Diagnostic Tests for Epstein-Barr Virus (EBV) Infection
To diagnose EBV infection, several tests can be ordered, including:
- Immunoglobulin G (IgG) and IgM antibodies to the viral capsid antigen (VCA) 2, 3, 4
- Heterophile antibodies (HA) 2, 3
- IgG antibodies to the EBV early antigen-diffuse (EA-D) and nuclear antigen (EBNA-1) 3
- EBV PCR to detect EBV DNA in serum 5, 6
- In situ hybridization (ISH) of EBV-encoded RNA (EBER) in biopsy tissues for histopathological lesions 6
Interpretation of EBV Serological Patterns
The interpretation of EBV serological patterns can be challenging due to the multiple possible patterns 3. However, the use of tables to interpret EBV serological patterns based on three or five markers can help to interpret >95% of BioPlex serological results 3.
Choice of Diagnostic Tests
The choice of diagnostic tests may depend on the clinical presentation and the suspected stage of EBV infection. For example:
- For primary EBV infection, EBV PCR can be used to confirm a positive IgM VCA in the absence of heterophilic antibodies 5
- For EBV reactivation, the utility of EA titers is disputed, and EBV PCR may be a more reliable method 5
- For histopathological lesions, ISH of EBER in biopsy tissues remains the gold standard for detecting EBV 6
Comparison of Diagnostic Methods
Different diagnostic methods have been compared in terms of their performance, including: