Epstein-Barr Virus: Clinical Diagnostics

The vast majority of the human adult population is infected with Epstein-Barr virus (EBV), and the majority of the EBV-infected individuals tolerates the infection well, without any further symptoms after primary infection. In cases of individuals which undergo primary infection in the form of an infectious mononucleosis, or which have undergone primary infection in their past, it is sometimes important to appraise symptomatic disease or differentiate infectious mononucleosis from other conditions. In these cases, serological methods, i.e., immunofluorescence, ELISA, or Western blot, are the methods of choice to come to an unequivocal diagnostic conclusion, while the detection and quantification of viral DNA through PCR plays a minor role. On the other hand, in a minority of the human population, EBV infection is associated or causally linked with autoimmune or malignant disease. Especially in the bone marrow or solid organ transplanted, or in otherwise severely immune-suppressed patients, prolonged EBV primary infection or EBV reactivation from latency may be a serious and life-threatening complication which needs to be diagnosed the faster the better, in order to take therapeutic steps in time. Determining the serostatus correctly is also important in these cases. However, the direct and quantitative detection of viral DNA are of importance for the diagnosis of serious EBV disease and its monitoring. In the following, we give an overview of diagnostic methods to accurately determine EBV serostatus and viral load. We evaluate the advantages and disadvantages of each method and report on the diagnostic significance of each and how to resolve diagnostic problems in case of uncertainties. For practical procedures, we refer to the detailed instruction manuals of the respective test kit manufacturers which have to be closely followed for reliable results.