Research Open Access
Like 0



Tick-borne encephalitis (TBE) is a potentially severe neurological disease caused by TBE virus (TBEV). In Europe and Asia, TBEV infection has become a growing public health concern and requires fast and specific detection.


In this observational study, we evaluated a rapid TBE IgM test, ReaScan TBE, for usage in a clinical laboratory setting.


Patient sera found negative or positive for TBEV by serological and/or molecular methods in diagnostic laboratories of five European countries endemic for TBEV (Estonia, Finland, Slovenia, the Netherlands and Sweden) were used to assess the sensitivity and specificity of the test. The patients’ diagnoses were based on other commercial or quality assured in-house assays, i.e. each laboratory’s conventional routine methods. For specificity analysis, serum samples from patients with infections known to cause problems in serology were employed. These samples tested positive for e.g. Epstein–Barr virus, cytomegalovirus and , or for flaviviruses other than TBEV, i.e. dengue, Japanese encephalitis, West Nile and Zika viruses. Samples from individuals vaccinated against flaviviruses other than TBEV were also included. Altogether, 172 serum samples from patients with acute TBE and 306 TBE IgM negative samples were analysed.


Compared with each laboratory’s conventional methods, the tested assay had similar sensitivity and specificity (99.4% and 97.7%, respectively). Samples containing potentially interfering antibodies did not cause specificity problems.


Regarding diagnosis of acute TBEV infections, ReaScan TBE offers rapid and convenient complementary IgM detection. If used as a stand-alone, it can provide preliminary results in a laboratory or point of care setting.


Article metrics loading...

Loading full text...

Full text loading...



  1. Lindquist L, Vapalahti O. Tick-borne encephalitis. Lancet. 2008;371(9627):1861-71.  https://doi.org/10.1016/S0140-6736(08)60800-4  PMID: 18514730 
  2. Süss J. Tick-borne encephalitis 2010: epidemiology, risk areas, and virus strains in Europe and Asia-an overview. Ticks Tick Borne Dis. 2011;2(1):2-15.  https://doi.org/10.1016/j.ttbdis.2010.10.007  PMID: 21771531 
  3. Lindquist L. Tick-borne encephalitis. Handb Clin Neurol. 2014;123:531-59.  https://doi.org/10.1016/B978-0-444-53488-0.00025-0  PMID: 25015503 
  4. Beauté J, Spiteri G, Warns-Petit E, Zeller H. Tick-borne encephalitis in Europe, 2012 to 2016. Euro Surveill. 2018;23(45):1800201.  https://doi.org/10.2807/1560-7917.ES.2018.23.45.1800201  PMID: 30424829 
  5. Dai X, Shang G, Lu S, Yang J, Xu J. A new subtype of eastern tick-borne encephalitis virus discovered in Qinghai-Tibet Plateau, China. Emerg Microbes Infect. 2018;7(1):74.  https://doi.org/10.1038/s41426-018-0081-6  PMID: 29691370 
  6. Kovalev SY, Mukhacheva TA. Reconsidering the classification of tick-borne encephalitis virus within the Siberian subtype gives new insights into its evolutionary history. Infect Genet Evol. 2017;55:159-65.  https://doi.org/10.1016/j.meegid.2017.09.014  PMID: 28919548 
  7. Taba P, Schmutzhard E, Forsberg P, Lutsar I, Ljøstad U, Mygland Å, et al. EAN consensus review on prevention, diagnosis and management of tick-borne encephalitis. Eur J Neurol. 2017;24(10):1214-e61.  https://doi.org/10.1111/ene.13356  PMID: 28762591 
  8. Gritsun TS, Nuttall PA, Gould EA. Tick-borne flaviviruses. Adv Virus Res. 2003;61:317-71.  https://doi.org/10.1016/S0065-3527(03)61008-0  PMID: 14714436 
  9. Ruzek D, Avšič Županc T, Borde J, Chrdle A, Eyer L, Karganova G, et al. Tick-borne encephalitis in Europe and Russia: Review of pathogenesis, clinical features, therapy, and vaccines. Antiviral Res. 2019;164(X):23-51.  https://doi.org/10.1016/j.antiviral.2019.01.014  PMID: 30710567 
  10. Jaenson TG, Värv K, Fröjdman I, Jääskeläinen A, Rundgren K, Versteirt V, et al. First evidence of established populations of the taiga tick Ixodes persulcatus (Acari: Ixodidae) in Sweden. Parasit Vectors. 2016;9(1):377.  https://doi.org/10.1186/s13071-016-1658-3  PMID: 27370406 
  11. Estrada-Peña A, de la Fuente J. The ecology of ticks and epidemiology of tick-borne viral diseases. Antiviral Res. 2014;108:104-28.  https://doi.org/10.1016/j.antiviral.2014.05.016  PMID: 24925264 
  12. Charrel RN, Attoui H, Butenko AM, Clegg JC, Deubel V, Frolova TV, et al. Tick-borne virus diseases of human interest in Europe. Clin Microbiol Infect. 2004;10(12):1040-55.  https://doi.org/10.1111/j.1469-0691.2004.01022.x  PMID: 15606630 
  13. Hudopisk N, Korva M, Janet E, Simetinger M, Grgič-Vitek M, Gubenšek J, et al. Tick-borne encephalitis associated with consumption of raw goat milk, Slovenia, 2012. Emerg Infect Dis. 2013;19(5):806-8.  https://doi.org/10.3201/eid1905.121442  PMID: 23697658 
  14. Bogovic P, Strle F. Tick-borne encephalitis: A review of epidemiology, clinical characteristics, and management. World J Clin Cases. 2015;3(5):430-41.  https://doi.org/10.12998/wjcc.v3.i5.430  PMID: 25984517 
  15. World Health Organization. Vaccines against tick-borne encephalitis: WHO position paper. Wkly Epidemiol Rec. 2011;86(24):241-56. PMID: 21661276 
  16. Kaiser R. Langzeitprognose bei primär myelitischer Manifestation der FSME: Eine Verlaufsanalyse über 10 Jahre. [Long-term prognosis of patients with primary myelitic manifestation of tick-borne encephalitis: a trend analysis covering 10 years]. Nervenarzt. 2011;82(8):1020-5.  https://doi.org/10.1007/s00115-011-3254-2  PMID: 21424414 
  17. Bogovič P, Stupica D, Rojko T, Lotrič-Furlan S, Avšič-Županc T, Kastrin A, et al. The long-term outcome of tick-borne encephalitis in Central Europe. Ticks Tick Borne Dis. 2018;9(2):369-78.  https://doi.org/10.1016/j.ttbdis.2017.12.001  PMID: 29275872 
  18. European Commission. Commission implementing decision of 8 August 2012 amending Decision 2002/253/EC laying down case definitions for reporting communicable diseases to the Community network under Decision No 2119/98/EC of the European Parliament and of the Council. Official Journal of the European Union. 2012;55(L 262/1):1-57.
  19. Günther G, Haglund M, Lindquist L, Sköldenberg B, Forsgren M. Intrathecal IgM, IgA and IgG antibody response in tick-borne encephalitis. Long-term follow-up related to clinical course and outcome. Clin Diagn Virol. 1997;8(1):17-29.  https://doi.org/10.1016/S0928-0197(97)00273-0  PMID: 9248655 
  20. Holzmann H. Diagnosis of tick-borne encephalitis. Vaccine. 2003;21(Suppl 1):S36-40.  https://doi.org/10.1016/S0264-410X(02)00819-8  PMID: 12628812 
  21. Puchhammer-Stöckl E, Kunz C, Mandl CW, Heinz FX. Identification of tick-borne encephalitis virus ribonucleic acid in tick suspensions and in clinical specimens by a reverse transcription-nested polymerase chain reaction assay. Clin Diagn Virol. 1995;4(4):321-6.  https://doi.org/10.1016/0928-0197(95)00022-4  PMID: 15566853 
  22. Saksida A, Jakopin N, Jelovšek M, Knap N, Fajs L, Lusa L, et al. Virus RNA Load in Patients with Tick-Borne Encephalitis, Slovenia. Emerg Infect Dis. 2018;24(7):1315-23.  https://doi.org/10.3201/eid2407.180059  PMID: 29912706 
  23. Gritsun TS, Frolova TV, Zhankov AI, Armesto M, Turner SL, Frolova MP, et al. Characterization of a siberian virus isolated from a patient with progressive chronic tick-borne encephalitis. J Virol. 2003;77(1):25-36.  https://doi.org/10.1128/JVI.77.1.25-36.2003  PMID: 12477807 
  24. Jääskeläinen A, Han X, Niedrig M, Vaheri A, Vapalahti O. Diagnosis of Tick-Borne Encephalitis by a μ-Capture Immunoglobulin M-Enzyme Immunoassay Based on Secreted Recombinant Antigen Produced in Insect Cells. J Clin Microbiol. 2003;41(9):4336-42.  https://doi.org/10.1128/JCM.41.9.4336-4342.2003  PMID: 12958266 
  25. Mansfield KL, Horton DL, Johnson N, Li L, Barrett ADT, Smith DJ, et al. Flavivirus-induced antibody cross-reactivity. J Gen Virol. 2011;92(Pt 12):2821-9.  https://doi.org/10.1099/vir.0.031641-0  PMID: 21900425 
  26. Lotrič-Furlan S, Bogovič P, Avšič-Županc T, Jelovšek M, Lusa L, Strle F. Tick-borne encephalitis in patients vaccinated against this disease. J Intern Med. 2017;282(2):142-55.  https://doi.org/10.1111/joim.12625  PMID: 28440879 
  27. Reusken C, Boonstra M, Rugebregt S, Scherbeijn S, Chandler F, Avšič-Županc T, et al. An evaluation of serological methods to diagnose tick-borne encephalitis from serum and cerebrospinal fluid. J Clin Virol. 2019;120:78-83.  https://doi.org/10.1016/j.jcv.2019.09.009  PMID: 31590114 
  28. Niedrig M, Klockmann U, Lang W, Roeder J, Burk S, Modrow S, et al. Monoclonal antibodies directed against tick-borne encephalitis virus with neutralizing activity in vivo. Acta Virol. 1994;38(3):141-9. PMID: 7817895 
  29. Albinsson B, Vene S, Rombo L, Blomberg J, Lundkvist Å, Rönnberg B. Distinction between serological responses following tick-borne encephalitis virus (TBEV) infection vs vaccination, Sweden 2017. Euro Surveill. 2018;23(3).  https://doi.org/10.2807/1560-7917.ES.2018.23.3.17-00838  PMID: 29386094 
  30. Velay A, Solis M, Kack-Kack W, Gantner P, Maquart M, Martinot M, et al. A new hot spot for tick-borne encephalitis (TBE): A marked increase of TBE cases in France in 2016. Ticks Tick Borne Dis. 2018;9(1):120-5.  https://doi.org/10.1016/j.ttbdis.2017.09.015  PMID: 28988602 
  31. Kuivanen S, Smura T, Rantanen K, Kämppi L, Kantonen J, Kero M, et al. Fatal Tick-Borne Encephalitis Virus Infections Caused by Siberian and European Subtypes, Finland, 2015. Emerg Infect Dis. 2018;24(5):946-8.  https://doi.org/10.3201/eid2405.171986  PMID: 29664395 
  32. Jääskeläinen A, Tonteri E, Pieninkeroinen I, Sironen T, Voutilainen L, Kuusi M, et al. Siberian subtype tick-borne encephalitis virus in Ixodes ricinus in a newly emerged focus, Finland. Ticks Tick Borne Dis. 2016;7(1):216-23.  https://doi.org/10.1016/j.ttbdis.2015.10.013  PMID: 26548609 
  33. Dekker M, Laverman GD, de Vries A, Reimerink J, Geeraedts F. Emergence of tick-borne encephalitis (TBE) in the Netherlands. Ticks Tick Borne Dis. 2019;10(1):176-9.  https://doi.org/10.1016/j.ttbdis.2018.10.008  PMID: 30385073 
  34. Agergaard CN, Rosenstierne MW, Bødker R, Rasmussen M, Andersen PHS, Fomsgaard A. New tick-borne encephalitis virus hot spot in Northern Zealand, Denmark, October 2019. Euro Surveill. 2019;24(43).  https://doi.org/10.2807/1560-7917.ES.2019.24.43.1900639  PMID: 31662158 
  35. Holding M, Dowall SD, Medlock JM, Carter DP, Pullan ST, Lewis J, et al. Tick-borne encephalitis virus, United Kingdom. Emerg Infect Dis. 2020;26(1):90-6.  https://doi.org/10.3201/eid2601.191085  PMID: 31661056 
  36. Dobler G, Erber W, Schmitt HJ. TBE-The Book. Singapore: Global Health Press; 2017. ISBN: 978-981-1903-3. Available from: https://id-ea.org/tbe.
  37. Ackermann-Gäumann R, Tritten ML, Hassan M, Lienhard R. Comparison of three commercial IgG and IgM ELISA kits for the detection of tick-borne encephalitis virus antibodies. Ticks Tick Borne Dis. 2018;9(4):956-62.  https://doi.org/10.1016/j.ttbdis.2018.03.031  PMID: 29610047 
  38. Ackermann-Gäumann R, Eyer C, Leib SL, Niederhauser C. Comparison of Four Commercial IgG-Enzyme-Linked Immunosorbent Assays for the Detection of Tick-Borne Encephalitis Virus Antibodies. Vector Borne Zoonotic Dis. 2019;19(5):358-64.  https://doi.org/10.1089/vbz.2018.2359  PMID: 30523740 
  39. Velay A, Solis M, Barth H, Sohn V, Moncollin A, Neeb A, et al. Comparison of six commercial tick-borne encephalitis IgM and IgG ELISA kits and the molecular characterization of their antigenic design. Diagn Microbiol Infect Dis. 2018;90(4):286-92.  https://doi.org/10.1016/j.diagmicrobio.2017.12.012  PMID: 29366629 
  40. Schwaiger M, Cassinotti P. Development of a quantitative real-time RT-PCR assay with internal control for the laboratory detection of tick borne encephalitis virus (TBEV) RNA. J Clin Virol. 2003;27(2):136-45.  https://doi.org/10.1016/S1386-6532(02)00168-3  PMID: 12829035 
  41. Lotrič-Furlan S, Rojko T, Petrovec M, Avsic-Zupanc T, Strle F. Epidemiological, clinical and laboratory characteristics of patients with human granulocytic anaplasmosis in Slovenia. Wien Klin Wochenschr. 2006;118(21-22):708-13.  https://doi.org/10.1007/s00508-006-0700-4  PMID: 17160612 
  42. Vene S, Mangiafico J, Niklasson B. Indirect immunofluorescence for serological diagnosis of dengue virus infections in Swedish patients. Clin Diagn Virol. 1995;4(1):43-50.  https://doi.org/10.1016/0928-0197(94)00060-8  PMID: 15566826 
  43. Vene S, Haglund M, Vapalahti O, Lundkvist A. A rapid fluorescent focus inhibition test for detection of neutralizing antibodies to tick-borne encephalitis virus. J Virol Methods. 1998;73(1):71-5.  https://doi.org/10.1016/S0166-0934(98)00041-X  PMID: 9705177 
  44. van der Eijk AA, van Genderen PJ, Verdijk RM, Reusken CB, Mögling R, van Kampen JJ, et al. Miscarriage Associated with Zika Virus Infection. N Engl J Med. 2016;375(10):1002-4.  https://doi.org/10.1056/NEJMc1605898  PMID: 27463941 
  45. van den Doel P, Volz A, Roose JM, Sewbalaksing VD, Pijlman GP, van Middelkoop I, et al. Recombinant modified vaccinia virus Ankara expressing glycoprotein E2 of Chikungunya virus protects AG129 mice against lethal challenge. PLoS Negl Trop Dis. 2014;8(9):e3101.  https://doi.org/10.1371/journal.pntd.0003101  PMID: 25188230 
  46. Niesters HG, van Esser J, Fries E, Wolthers KC, Cornelissen J, Osterhaus AD. Development of a real-time quantitative assay for detection of Epstein-Barr virus. J Clin Microbiol. 2000;38(2):712-5.  https://doi.org/10.1128/JCM.38.2.712-715.2000  PMID: 10655372 

Data & Media loading...

Submit comment
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error