Steininger et al.
Results of tick-borne encephalitis virus (TBEV) diagnostics in an endemic area in southern Germany, 2007 to 2022.
Viruses. 2023; 15(12):2357. doi: 10.3390/v15122357

Laboratory diagnostic of TBE is usually done by means of ELISA technique and relies on the detection of IgM and/or IgG antibodies in serum and cerebrospinal fluid (CSF). Diagnosis based on detection of viral RNA using PCR assays is only possible during the first febrile phase but is rarely successful. A retrospective analysis has been carried out by a diagnostic laboratory in Bavaria, Germany, which has tested 3992 serum samples for TBE IgM and IgG antibodies during 2007 to 2022. In addition, 892 CSF samples were tested for neurotropic viruses including TBE virus from August 2016 to December 2017.

In total, 126 TBE cases were identified between 2007 and 2022 among 3713 patients from whom samples for TBE virus diagnostic were submitted. In 124 of 126 patients, TBE diagnostic was based on antibody detection. 121 patients had TBE antibodies already on admission. In 2 of 126 patients, TBE IgM and IgG antibody testing was negative, but was positive by detection of TBE virus RNA in CSF.

4 of 126 patients with confirmed TBE tested false-negative for IgM in serum due to prior rituximab treatment (n=2) or vaccine breakthrough infection (n=2). Overall, the sensitivity and specificity of TBE IgM ELISA assays were 96.8% and 99.7%, respectively, underlying the high sensitivity and specificity of TBE antibody detection in serum in a TBE endemic area.

These results confirm that diagnostic of TBE in immunocompetent patients can rely on the detection of TBE and IgG antibodies alone. None of the 87 immunocompetent TBE patients tested had detectable TBE virus RNA in serum or CSF.

TBE virus PCR from CSF has no additional diagnostic value in immunocompetent patients but is necessary for the diagnosis in patients with humoral immunodeficiencies such as previous treatment with B cell depleting antibodies like rituximab.

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