Reusken et al.
An evaluation of serological methods to diagnose tick-borne encephalitis from serum and cerebrospinal fluid
J. Clin. Virol. 2019, 120: 78-83
Diagnosis of TBE is usually done by detection of TBE virus specific antibodies in serum and/or cerebrospinal fluid (CSF). IgM specific antibodies can be detected in serum, when neurological symptoms are present; IgM in CSF peaks later than in serum. In a second step, specific IgG antibodies can be detected in serum and may persist for its lifetime. Unfortunately, the interpretation of TBE virus serology is affected by cross-reactivity among flaviviruses – especially in ELISA assays – and this has already been discussed earlier (see Snapshots of week 11, 18, 22 and 52/2019).
Here, the performance of five commercially available ELISAs have been analyzed in an international collaboration using 18 serum and plasma samples from TBE patients, for which TBE infection has been confirmed by the presence of neutralizing antibodies and TBE virus specific RNA in three patients. Assay specificity was assessed using a total of 42 sera from 42 patients with various flavivirus infections: dengue virus, Japanese encephalitis virus (JEV), zika virus, or using 17 sera or plasma samples from vaccinated individuals: JEV or yellow fever virus, or using sera or plasma samples from humans with an acute cytomegalovirus or Epstein-Barr virus infection.
Three of the five assessed ELISAs had an acceptable sensitivity of 94% and two tests showed a sensitivity of 83% for IgG. For IgM, the five ELISAs demonstrated a comparable sensitivity of 94-100% and can be regarded as a reliable diagnostic tool in patients with neurological disease attributable to the TBE virus. However, all ELISAs showed a low specificity when measuring IgG with the flavivirus panel. The authors concluded that neutralization tests (the gold standard) are warranted in case infection is presumed on basis of IgG response, especially in patients with presumed exposure to multiple flaviviruses in the past and/or depending the geographic location of exposure to the TBE virus.