Comparison of Four Commercial IgG-Enzyme-Linked Immunosorbent Assays for the Detection of Tick-Borne Encephalitis Virus Antibodies. 2019

Rahel Ackermann-Gäumann, and Claudia Eyer, and Stephen L Leib, and Christoph Niederhauser
1 Spiez Laboratory, Federal Office for Civil Protection, Spiez, Switzerland.

Tick-borne encephalitis (TBE) is the most important arboviral disease in many parts of Europe and Asia. Both the diagnosis of TBE as well as the conduction of surveillance studies are based on the demonstration of specific antibodies. For reasons of simplicity, automatization, and quick availability of test results, enzyme-linked immunosorbent assays (ELISAs) are the method of choice for anti-TBE virus antibody detection. In this study, we evaluated four commercial IgG-ELISAs using 876 epidemiological plasma samples: the Enzygnost Anti-TBE/FSME Virus IgG assay (Siemens; assay 1), the Anti-FSME/TBE Virus ELISA (IgG) assay (Euroimmun; assay 2), the Anti-FSME/TBE Virus ELISA "Vienna" (IgG) assay (Euroimmun; assay 3), and the RIDASCREEN® FSME/TBE IgG EIA assay (R-Biopharm; assay 4). In total, discrepant results were observed for 37.2% of all samples. The evaluated assays significantly differed in qualitative data (p < 0.0001, Cochran-Mantel-Haenszel test) and showed Spearman's rank correlation coefficients ranging between 0.88 and 0.97 for quantitative data. The degree of disagreement between the different assays was exceptionally high for samples originating from blood donors with vaccination against TBE virus. For this sample group, the proportion of positive results was considerably higher for assay 3 (52.7%) and assay 4 (57%) than for assay 1 (7.5%) and assay 2 (6.4%), respectively, indicating that assays 1 and 2 are less suitable for the detection of vaccination antibodies than assays 3 and 4. Indirect immunofluorescence testing data available for a subset of samples (n = 238) mostly originating from nonflavivirus-vaccinated blood donors (n = 234) revealed problems in both sensitivity and specificity of the evaluated assays; whereas sensitivity issues were most prominent for the Euroimmun assay, specificity concerns were most pronounced for the Euroimmun Vienna and the RIDASCREEN assays.

UI MeSH Term Description Entries
D007074 Immunoglobulin G The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B. Gamma Globulin, 7S,IgG,IgG Antibody,Allerglobuline,IgG(T),IgG1,IgG2,IgG2A,IgG2B,IgG3,IgG4,Immunoglobulin GT,Polyglobin,7S Gamma Globulin,Antibody, IgG,GT, Immunoglobulin
D009500 Neutralization Tests The measurement of infection-blocking titer of ANTISERA by testing a series of dilutions for a given virus-antiserum interaction end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50). Neutralization Test,Test, Neutralization,Tests, Neutralization
D001782 Blood Donors Individuals supplying blood or blood components for transfer to histocompatible recipients. Blood Donor,Donor, Blood,Donors, Blood
D004669 Encephalitis Viruses, Tick-Borne A subgroup of the genus FLAVIVIRUS that causes encephalitis and hemorrhagic fevers and is found in eastern and western Europe and the former Soviet Union. It is transmitted by TICKS and there is an associated milk-borne transmission from viremic cattle, goats, and sheep. Hemorrhagic Fever Virus, Omsk,Kyasanur Forest disease virus,Langat virus,Louping ill virus,Omsk hemorrhagic fever virus,Powassan virus,Al-Khurma Hemorrhagic Fever Virus,Al-Khurma virus,Al-Khurma virus (ALKV),Alkhurma Hemorrhagic Fever Virus,Alkhurma virus,Alkhurma virus (ALKV),Encephalitis Virus, Tick-Borne,Tick-Borne Encephalitis Virus,Tick-Borne Encephalitis Viruses,Viruses, Tick-Borne Encephalitis,Al Khurma Hemorrhagic Fever Virus,Al Khurma virus,Al Khurma virus (ALKV),Encephalitis Virus, Tick Borne,Encephalitis Viruses, Tick Borne,Louping ill viruses,Tick Borne Encephalitis Virus,Tick Borne Encephalitis Viruses
D004675 Encephalitis, Tick-Borne Encephalitis caused by neurotropic viruses that are transmitted via the bite of TICKS. In Europe, the diseases are caused by ENCEPHALITIS VIRUSES, TICK-BORNE, which give rise to Russian spring-summer encephalitis, central European encephalitis, louping ill encephalitis, and related disorders. Powassan encephalitis occurs in North America and Russia and is caused by the Powassan virus. ASEPTIC MENINGITIS and rarely encephalitis may complicate COLORADO TICK FEVER which is endemic to mountainous regions of the western United States. (From Joynt, Clinical Neurology, 1996, Ch26, pp14-5) Far Eastern Russian Encephalitis,Powassan Encephalitis,Central European Encephalitis,Encephalitis, Central European,Encephalitis, European Tick-Borne,Encephalitis, Far Eastern Russian,Encephalitis, Louping Ill,Encephalitis, Russian Spring-Summer,European Tick-Borne Encephalitis,Louping Ill Encephalitis,Powassan Virus Disease,Russian Spring-Summer Encephalitis,Tick-Borne Encephalitis,Disease, Powassan Virus,Encephalitis, European Tick Borne,Encephalitis, Powassan,Encephalitis, Russian Spring Summer,Encephalitis, Tick Borne,European Tick Borne Encephalitis,Powassan Encephalitides,Powassan Virus Diseases,Russian Spring Summer Encephalitis,Spring-Summer Encephalitis, Russian,Tick Borne Encephalitis,Tick-Borne Encephalitis, European,Virus Disease, Powassan,Virus Diseases, Powassan
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000914 Antibodies, Viral Immunoglobulins produced in response to VIRAL ANTIGENS. Viral Antibodies
D012680 Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed) Specificity,Sensitivity,Specificity and Sensitivity

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