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Chapter 10



                                     Diagnosis





                                         Gerhard Dobler

          Key Points

           •  TBE appears with non-characteristic clinical symptoms, which cannot be distinguished from oth-
              er forms of viral encephalitis or other diseases.

           •  Cerebrospinal fluid and neuro-imaging may give some evidence of TBE, but ultimately cannot
              confirm the diagnosis.
           •  Thus, proving the diagnosis “TBE” necessarily requires confirmation of TBEV-infection by detec-
              tion of the virus or by demonstration of specific antibodies from serum and/or cerebrospinal
              fluid.

           •  During the phase of clinic symptoms from the CNS, the TBEV can only rarely be detected in the
              cerebrospinal fluid of  patients.
           •  Most routinely used serological tests for diagnosing TBE (ELISA, HI, IFA) show cross reactions
              resulting from either  Infection with other flaviviruses or with other flavivirus vaccines.




          Clinical confirmation of suspected TBEV infection

          Tick-borne  encephalitis  (TBE)  manifests  as  a   The most common method of detecting TBEV
          non-specific  disease  with  symptoms  of  a   infection  nowadays  is  via  serological  assays,
          febrile,  influenza-like  illness  and,  in  some   which  have  developed  from  complement
          cases, an inflammatory infection of the central   fixation  or  hemagglutination  inhibition  tests
          nervous system (CNS) that follows a few days   through  to  modern  immuno-globulin  (Ig)-
          later. Due to the lack of specific symptoms, a   specific  tests  such  as  ELISAs  and  immuno-
          definitive  confirmation  of  the  diagnosis   fluorescence (IF) assays.
          requires taking the history of the patient with
          regard  to  a  possible  tick  bite  or  ingestion  of   Understanding  of  the  pathogenesis  and
          unpasteurized  milk  in  a  known  or  suspected   immunology of TBEV infection is essential for
          endemic  area,  plus  a  positive  result  from  a   the  selection  and  interpretation  of  appropri-
          classical  virological  test  that  confirms  TBEV-  ate  diagnostic  tests  (Figure  1).  For  example,
          infection  either  directly  by  the  detection  of   the European subtype of TBEV often induces a
          virus or indirectly via detection of specific anti-  biphasic  clinical  course,  whereas  a  mono-
                        1
          virus antibodies.  Prior to the introduction of   phasic  course  may  be  more  prominent  in
          molecular  detection  technologies  such  as   those infected with the Far Eastern subtype or
                                                                    2
          polymerase  chain  reaction  (PCR),  the  only   Siberian  subtype.   Following  a  bite  from  an
          technique  available  to  detect  TBEV  infection   infected tick, the virus is assumed to replicate
          was  virus  isolation,  but  this  is  rarely  used   locally  within  antigen-presenting  cells  and
          today.                                      then  subsequently  within  nearby  lymph
                                                      nodes.  After  replicating  within  the  lymph

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