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P. 415

Chapter 12b



                             TBE in Sweden





                                          Åke Lundkvist

          History and Current Situation

          Tick-borne  encephalitis  virus  (TBEV)  was   The   sequence   was   characterized   and
          isolated  for  the  first  time  in  Sweden  in  1958   compared  with  those  of  other  tick-borne
          (from ticks and from 1 tick-borne encephalitis   flaviviruses,  which  led  to  classification  of  the
                       1
          [TBE]  patient).   In  2003,  Haglund  and   virus as TBEV-EU. The same group reported in
          colleagues  reported  the  isolation  and   2011  on  the  first  complete  genome  of  a
          antigenic  and  genetic  characterization  of  14   Swedish TBEV strain by completing the earlier
                                                                               4
          TBEV  strains  from  Swedish  patients  (samples   partial sequencing (see above).  The total RNA
                              2
          collected  1991–1994).   The  first  serum   was  sufficient  for  the  sequencing  of  a
          sample,  from  which  TBEV  was  isolated,  was   complete  TBEV  genome  (Torö-2003),  without
          obtained 2–10 days after onset of disease and   conventional  enrichment  procedures  such  as
          found   to   be   negative   for   anti-TBEV   cell  culture  or  amplification  in  suckling  mice.
          immunoglobulin  M  (IgM)  by  enzyme-linked   Sequence  analyses  also  revealed  that  Torö-
          immunosorbent assay (ELISA), whereas TBEV-  2003 belonged to the TBEV-EU subtype, being
          specific  IgM  (and  TBEV-specific  immuno-  most similar to TBE 263 with 97.4% and 98.8%
          globulin  G/cerebrospinal  fluid  [IgG/CSF]   homologies at the nucleotide and amino acid
          activity)  was  demonstrated  in  later  serum   levels, respectively.
          samples taken during the second phase of the
          disease.                                    In 2014, Veje and coworkers reported 2 cases
                                                      of TBE in which TBEV RNA could be detected
          Of  20  patient  serum  samples  inoculated  into   in  urine  by  real-time  polymerase  chain
                                                                                           5
          the brain of suckling mice, 14 induced obvious   reaction (PCR) during the encephalitic phase.
          signs of illness (death or clear physical signs in   The  TBEV  RNA  quantities  from  1  patient
          all cases, 5–7 days after inoculation), and TBEV   allowed sequencing of 10,432 nucleotides (nt),
          was isolated in all cases. Three earlier Swedish   which confirmed the PCR finding in urine, and
                                      1
          TBEV  patient  isolates  from  1958,   1959,  and   phylogenetic  analysis  showed  that  the  virus
          1966, respectively, were included in the same   belonged to the TBEV-EU clade.
          study.  Phylogenetic  analyses  of  the  partial
          sequence (domain III) of the E gene revealed   In 2016, Henningsson and associates reported
          that  all  Swedish  TBEV  strains  grouped   isolation and a complete TBEV sequence from
                                                                6
          together  with  the  previously  characterized   a biting tick.  By performing nt sequencing of
          strains  (Neudoerfl,  Kumlinge-A52,  Hypr,  and   the virus strain (Tick/SWE/ Habo/2011/1) via 2
          TBE 263) of the Western or European subtype   different  strategies  (deep  sequencing  of  the
          of TBEV (TBEV-EU).                          A549  isolate  and  direct  sequencing  of  PCR
                                                      amplicons  of  RNA  extracted  from  the  tick,
          In   2007,   a   partial   TBEV   sequence   respectively),  the  authors  showed  that  the  2
          (approximately one-third of the viral genome)   sequences  were  identical  over  3,382  nt,
          from  a  small  pool  of  ticks  collected  in  the   thereby  suggesting  that  the  virus  isolation
          Stockholm  archipelago  on  the  island  of  Torö   procedure  did  not  introduce  a  selection  bias
                     3
          was reported.                               with regard to the compared nt sequences.


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