Reliability of the Siemens Enzygnost and Novagnost Epstein–Barr Virus assays for routine laboratory diagnosis: agreement with clinical diagnosis and comparison with the Merifluor Epstein–Barr Virus immunofluorescence assay

Christina Kreuzer,H Roma Levy,Klaus Udo Nabeck,Elisabeth Daghofer

doi:10.1186/1471-2334-13-260

Christina Kreuzer, H Roma Levy + Show 2 more

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https://doi.org/10.1186/1471-2334-13-260

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Abstract

BackgroundDiagnosis of Epstein–Barr virus (EBV) infection is routinely conducted by clinical laboratories, especially to diagnose infectious mononucleosis. At an estimated general population incidence of 1:200, this represents a potentially significant testing burden. We evaluated the reliability of the Siemens Novagnost® and Enzygnost® EBV microtiter assays measuring VCA IgM and IgG, and EBNA-1 IgG for clinical diagnosis of EBV-related infectious mononucleosis.MethodsRemnant sera from 537 patients tested for EBV infection were used to compare the Siemens assays to each other and to the Merifluor assay. The Siemens assays are qualitative/semiquantitative, automatable enzyme immunoassays. The Merifluor assays are manual, qualitative indirect immunofluorescent assays. Testing was conducted on the Siemens and Merifluor assays in parallel. All assays were conducted and interpreted according to each manufacturer’s specifications. Agreement of serostatus between each of the three assays was assessed. Discrepant results were resolved using a third method (Mikrogen recomLine).ResultsFinal EBV serostatus indicated 2.9% of the population had an acute infection, 89.6% had a past infection, and 7.5% were EBV naive. All three assays demonstrated 100% agreement with acute infection. Agreement with past-infection serostatus was 99.1% for Enzygnost, between 86% and 98.8% for Novagnost, and 98.1% for Merifluor. Seronegative agreement was 100% for Enzygnost, 89.7% for Novagnost, and 92.3% for Merifluor.ConclusionsThe Siemens Enzygnost and Novagnost EBV microtiter assays are suitable for clinical rule-in of acute EBV infection and for identifying EBV-naive individuals. Both assays also adequately identify remote EBV infections. Because these assays can be automated, they can improve speed and efficiency of EBV testing, especially in high-volume laboratories.

Highlights

Diagnosis of Epstein–Barr virus (EBV) infection is routinely conducted by clinical laboratories, especially to diagnose infectious mononucleosis
While the presence of viral capsid proteins (VCA) IgM with or without VCA IgG typically signals acute infection, and the persistence of VCA IgG along with the appearance of IgG to the late protein Epstein–Barr nuclear antigens (EBNA)-1 indicates past or resolving infection, unusual serological patterns such as isolated EBNA-1 or isolated VCA IgG can confound interpretation. To determine their usefulness for regular diagnostic laboratory testing, we evaluated the serological profiles interpreted from the combined results of the Siemens Novagnost VCA IgM, VCA IgG, and EBNA-1 IgG assays, and the combined results of the Enzygnost Anti-EBV/IgG and Anti-EBV/IgM II microtiter assays to rule in, or rule out, acute EBV infection
The serological assignments derived from combined analysis of the three Novagnost EBV enzyme immunoassays (VCA IgM, VCA IgG, and EBNA-1 IgG) were compared to the serological assignments derived from combined analysis of the two Enzygnost enzyme immunoassays (Anti-EBV IgG and Anti-EBV/IgM II)

Summary

Introduction

Diagnosis of Epstein–Barr virus (EBV) infection is routinely conducted by clinical laboratories, especially to diagnose infectious mononucleosis. According to the World Health Organization (WHO), approximately 95% of the adult population is infected, and in developed nations approximately 50% to 70% of exposures occur in adolescents or young adults. EBV-related IM is typically a fairly benign disease, early and accurate diagnosis is valuable as it is highly communicable and can spread quickly in populations with a high density of young adults (such as among university students and military personnel). Specific serology to detect antibodies to viral proteins is used as both an adjunct and alternative to the heterophile test, and is most commonly directed at the antibodies made againsts viral capsid proteins (VCA) and Epstein–Barr nuclear antigens (EBNA)

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