title: Differentiation of primary from secondary anti-EBNA-1-negative cases by determination of avidity of VCA-IgG.
abstract: BACKGROUND
  Serological techniques are used to determine Epstein Barr virus (EBV) etiology of a constellation of signs or symptoms related to lymphadenopathy, fever, respiratory tract infection, mononucleosis, hepatitis, thrombocytopenia or neurological disorder. Anti-Epstein Barr Nuclear antigen (EBNA)-1 is regularly negative during the first 3-4 weeks after the onset of clinical symptoms indicating acute EBV infection (primary anti-EBNA-1-negative). It may, however, also be negative in immunocompromised convalescent individuals (secondary anti-EBNA-1-negative) such as tumor patients, HIV-positive patients and transplant recipients.
  
  
  OBJECTIVE
  The aim of this study was to determine the frequency of secondary anti-EBNA-1-negative cases and to find a way to distinguish them from primary anti-EBNA-1-negative cases using anticomplementary immunofluorescence (ACIF) and enzyme immunoassay (EIA).
  
  
  METHODS
  All sera sent to our institute for EBV serology during one year were routinely tested for Viral Capsid antibody (VCA)-IgM, VCA-IgG and anti-EBNA-1.
  
  
  RESULTS
  VCA-IgG-positive/anti-EBNA-1-negative cases (13.5% of total VCA-IgG-positive) comprised 55% primary and 45% secondary anti-EBNA-1-negative cases. Detection of secondary anti-EBNA-1-negative cases was independent of the method used, i.e., ACIF or EIA. VCA-IgG retained its high avidity in secondary anti-EBNA-1-negative cases, whereas primary anti-EBNA-1-negative cases taken during the early phase of acute infection showed low avidity of VCA-IgG.
  
  
  CONCLUSIONS
  Determination of the avidity of VCA-IgG routinely and in concert with standard serodiagnosis (VCA-IgG, VCA-IgM, anti-EBNA-1) can enable the differentiation of primary and secondary anti-EBNA-1-negative cases.
authors.affiliation: Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universitüt Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Vetter
authors.forename: L
authors.initials: L
authors.lastname: Kreutzer
authors.forename: G
authors.initials: G
authors.lastname: Bauer