Prevalence of primary versus reactivated Epstein-Barr virus infection in patients with VCA IgG-, VCA IgM- and EBNA-1-antibodies and suspected infectious mononucleosis

J Clin Virol. 2007 Apr;38(4):292-7. doi: 10.1016/j.jcv.2007.01.006. Epub 2007 Mar 1.


Background: In Epstein-Barr virus (EBV) infection, IgG- and IgM-antibodies to viral capsid antigen (VCA) and IgG-antibodies to Epstein-Barr nuclear antigen 1 (EBNA-1) can occur simultaneously both in late primary infection and during subclinical viral reactivation in immunocompetent persons, and the differential diagnosis is of importance.

Objectives: To study the prevalence of primary infection and serological reactivation in patients with suspected primary EBV infection and with all three parameters present.

Study design: Fifty serum samples from 43 consecutive patients referred for suspected infectious mononucleosis and positive for VCA IgG-, VCA IgM- and EBNA-1-antibodies by EIA, were tested for IgG-antibody avidity with an EBV IgG immunoblot. Sera were also tested for heterophile antibodies (HA). To verify the presence of IgM-antibodies an EBV IgM immunoblot was performed when high-avidity IgG-antibodies were found.

Results and conclusions: Of 43 patients with suspected primary EBV infection and VCA IgG-, VCA IgM- and EBNA-1-antibodies present, only 18 patients (42%) had a late primary infection. Twenty-one patients (49%) had high-avidity IgG-antibodies, indicating an IgM response due to reactivation, thus suggesting other causes for their symptoms. In 10 of these 21 patients the presence of IgM-antibodies was confirmed by immunoblot, indicating reactivation as a cause of IgM-antibodies in at least 23% of the 43 patients studied. Of 18 patients with primary infection, HA were detected in 16 (94%) of 17 patients tested. Only one (5%) of the patients with high-avidity antibodies had HA. Absence of HA in patients with this serological pattern is therefore a good indicator of reactivation, and conversely, the presence of HA is a good indicator of primary infection. In HA negative patients, avidity testing could be used for differential diagnosis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Heterophile / blood
  • Antibodies, Viral / blood*
  • Antibody Affinity
  • Antigens, Viral / immunology*
  • Capsid Proteins / immunology*
  • Child
  • Cross-Sectional Studies
  • Diagnosis, Differential
  • Epstein-Barr Virus Infections / epidemiology
  • Epstein-Barr Virus Infections / immunology*
  • Epstein-Barr Virus Nuclear Antigens / immunology*
  • Herpesvirus 4, Human / immunology
  • Humans
  • Immunoblotting
  • Immunoenzyme Techniques
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Infectious Mononucleosis / epidemiology
  • Infectious Mononucleosis / immunology*
  • Middle Aged
  • Prevalence
  • Virus Activation / immunology*


  • Antibodies, Heterophile
  • Antibodies, Viral
  • Antigens, Viral
  • Capsid Proteins
  • Epstein-Barr Virus Nuclear Antigens
  • Epstein-Barr viral capsid antigen
  • Immunoglobulin G
  • Immunoglobulin M
  • EBV-encoded nuclear antigen 1