Differential diagnosis of primary and reactivated Epstein-Barr virus infection

Abstract

Background: In Epstein-Barr virus (EBV) infection, VCA IgG-, VCA IgMand EBNA-1antibodies can occur simultaneously both in late primary infection and during subclinical viral reactivation. The presence of all three parameters is commonly interpreted as representing a late primary infection, but supplemental testing is needed to differentiate between these stages of infection. Aim: To study the occurrence of primary infection and reactivation in patients suspected of primary EBV infection and with all three parameters present. Methods: Fifty serum samples from 43 consecutive patients referred for suspected infectious mononucleosis and positive for VCA IgG-, VCA IgMand EBNA-l-antibodies by Novitec EIA (Hiss Diagnostics, Freiburg, Germany), were tested for IgG-antibody avidity with recomLine EBV immunoblot (Mikrogen, Martinsried, Germany). Sera were also tested for heterophile antibodies (HA) with Clearview rapid test (Unipath limited, Bedford, UK). Results and Discussion: Immunoblot with avidity testing gave conclusive results in 39 (91%) patients, of which 18 (46%) had a primary infection, and 21 patients (54%) had high-avidity IgGantibodies, indicating an IgM response due to reactivation. Of the 18 patients with primary infection, HA was detected in 16 (94%) of the 17 patients tested. Only one (5%) of the patients with high-avidity antibodies had HA. Conclusion: In 39 patients with suspected primary EBV infection and both VCA IgG-, VCA IgMand EBNA-l-antibodies present, less than half (46%) had a late primary infection, whereas 52% had a probable reactivation with reappearance of VCA IgM-antibodies or past infection. The presence of HA is a good indicator of primary infection. In HA-negative patients, avidity testing should be used for differential diagnosis.