Tick-borne encephalitis virus infections in Germany. Seasonality and in-year patterns. A retrospective analysis from 2001-2018

Autoři: Johannes P. Borde aff001;  Klaus Kaier aff003;  Philip Hehn aff003;  Merle M. Böhmer aff004;  Teresa M. Kreusch aff005;  Gerhard Dobler aff006
Působiště autorů: Division of Infectious Diseases, Department of Medicine II, University of Freiburg Medical Center and Faculty of Medicine, Freiburg i.Br., Germany aff001;  Praxis PD Dr. J. Borde & Kollegen / Gesundheitszentrum Oberkirch, Am Marktplatz, Oberkirch, Germany aff002;  Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center–University of Freiburg, Stefan-Meier-Straße, University of Freiburg, Freiburg, Germany aff003;  Bavarian Health and Food Safety Authority, Department of Infectious Disease Epidemiology & Taskforce Infectiology/Airport Veterinaerstraße, Oberschleissheim, Germany aff004;  Immunization Unit, Robert Koch Institute, Seestraße, Berlin, Germany aff005;  Bundeswehr Institute of Microbiology, German National Reference Laboratory for TBEV, Neuherbergstraße, München, Germany aff006
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224044



Little is known regarding the changing seasonality of infections with the tick-borne encephalitis virus (TBEV) and the incidence of the resulting disease over the last two decades. Seasonal patterns have to our knowledge not previously been systematically investigated and are poorly understood. We investigate emerging seasonal changes in clinical aspects like potentially increasing hospitalization during the year, variations in clinical symptoms and disease severity during the season and seasonal dynamics of fatal outcomes.

Material and methods

TBEV infection became a notifiable disease in Germany in 2001. We used the national reporting dataset spanning from 2001–2018, provided by the Robert Koch-Institute (RKI). There were general epidemiological variables available, including “symptom onset”, “age” and “sex”. Furthermore, several variables documented disease severity. These included “CNS symptoms”, “myelitis”, “fatal outcome” and “hospitalization”. Potential factors influencing the occurrence of CNS symptoms, myelitis, hospitalizations and fatal outcome were analyzed using logistic regression models. Linear trends, including the “time point in year” at which TBEV infection related symptoms were detected, were tested using calendar year as a continuous covariate. In addition, seasonal trends and age and sex specific differences were exploratively tested for non-linear effects using restricted cubic splines with knot locations based on Harrell's recommended percentiles. Finally, the dynamic relationship between in-seasonal trends year of detection, sex and age was tested using interaction terms.


6,073 TBEV infection cases from 2001–2018 were included in our analysis. We find that from 2001–2018 TBEV infections are reported 0.69 days earlier each year (p<0.001). There was no detectable seasonal variation regarding the occurrence of fatal outcome, CNS and myelitis. However, there was a significant changing trend regarding hospitalizations over the course of the year: The risk for hospitalization increases until August, decreases again from October on.


We present epidemiological evidence that the TBE season in Germany has shifted to start earlier over the last years, beginning approximately 12 days earlier in 2018 than it did in 2001. There are seasonal patterns regarding a higher risk of hospitalization during August.

Klíčová slova:

Autumn – Central nervous system – Germany – Hospitalizations – Seasons – Vaccination and immunization – Myelitis – Tick-borne encephalitis


1. Bogovic P, Strle F. Tick-borne encephalitis: A review of epidemiology, clinical characteristics, and management. World J Clin Cases. 2015;3: 430. doi: 10.12998/wjcc.v3.i5.430 25984517

2. Riccardi N, Antonello RM, Luzzati R, Zajkowska J, Di Bella S, Giacobbe DR. Tick-borne encephalitis in Europe: a brief update on epidemiology, diagnosis, prevention, and treatment. Eur J Intern Med. 2019; doi: 10.1016/j.ejim.2019.01.004 30678880

3. 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: 23–51. doi: 10.1016/j.antiviral.2019.01.014 30710567

4. Zlobin VI, Pogodina V V., Kahl O. A brief history of the discovery of tick-borne encephalitis virus in the late 1930s (based on reminiscences of members of the expeditions, their colleagues, and relatives). Ticks Tick Borne Dis. 2017;8: 813–820. doi: 10.1016/j.ttbdis.2017.05.001 28526419

5. Eyer L, Šmídková M, Nencka R, Neča J, Kastl T, Palus M, et al. Structure-activity relationships of nucleoside analogues for inhibition of tick-borne encephalitis virus. Antiviral Res. 2016;133: 119–129. doi: 10.1016/j.antiviral.2016.07.018 27476046

6. Šmit R, Postma MJ. The Burden of Tick-Borne Encephalitis in Disability-Adjusted Life Years (DALYs) for Slovenia. Munderloh UG, editor. PLoS One. 2015;10: e0144988. doi: 10.1371/journal.pone.0144988 26672751

7. Šmit R. Reviewing estimates of the burden in disability-adjusted life years (DALYs) of tick-borne encephalitis in Slovenia. Expert Rev Pharmacoecon Outcomes Res. 2019; 1–5. doi: 10.1080/14737167.2019.1573677 30686078

8. Fafangel M, Cassini A, Colzani E, Klavs I, Grgič Vitek M, Učakar V, et al. Estimating the annual burden of tick-borne encephalitis to inform vaccination policy.: 1. doi: 10.2807/1560-7917.ES.2017.22.16.30509

9. Kunz C. TBE vaccination and the Austrian experience. Vaccine. 2003;21 Suppl 1: S50–5. Available: http://www.ncbi.nlm.nih.gov/pubmed/12628814

10. Erber W, Schmitt H-J. Self-reported tick-borne encephalitis (TBE) vaccination coverage in Europe: Results from a cross-sectional study. Ticks Tick Borne Dis. 2018;9: 768–777. doi: 10.1016/j.ttbdis.2018.02.007 29501619

11. Hellenbrand W, Kreusch T, Böhmer MM, Wagner-Wiening C, Dobler G, Wichmann O, et al. Epidemiology of Tick-Borne Encephalitis (TBE) in Germany, 2001−2018. Pathog (Basel, Switzerland). 2019;8: 42. doi: 10.3390/pathogens8020042 30934855

12. Beauté J, Spiteri G, Warns-Petit E, Zeller H. Tick-borne encephalitis in Europe, 2012 to 2016. Euro Surveill. 2018;23. doi: 10.2807/1560-7917.ES.2018.23.45.1800201 30424829

13. 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: 1214–e61. doi: 10.1111/ene.13356 28762591

14. Harrell FE. Regression Modeling Strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis. Springer New York; 2001.

15. Kriz B, Maly M, Benes C, Daniel M. Epidemiology of Tick-Borne Encephalitis in the Czech Republic 1970–2008. Vector-Borne Zoonotic Dis. 2012;12: 994–999. doi: 10.1089/vbz.2011.0900 23025693

16. Randolph SE, Asokliene L, Avsic-Zupanc T, Bormane A, Burri C, Gern L, et al. Variable spikes in tick-borne encephalitis incidence in 2006 independent of variable tick abundance but related to weather. Parasit Vectors. 2008;1: 44. doi: 10.1186/1756-3305-1-44 19068106

17. Stefanoff P, Rosinska M, Samuels S, White DJ, Morse DL, Randolph SE. A National Case-Control Study Identifies Human Socio-Economic Status and Activities as Risk Factors for Tick-Borne Encephalitis in Poland. Munderloh UG, editor. PLoS One. 2012;7: e45511. doi: 10.1371/journal.pone.0045511 23029063

18. Randolph SE, EDEN-TBD sub-project team. Human activities predominate in determining changing incidence of tick-borne encephalitis in Europe. Euro Surveill. 2010;15: 24–31. Available: http://www.ncbi.nlm.nih.gov/pubmed/20630144 doi: 10.2807/ese.15.27.19606-en 20630144

19. Palo RT. Tick-Borne Encephalitis Transmission Risk: Its Dependence on Host Population Dynamics and Climate Effects. Vector-Borne Zoonotic Dis. 2014;14: 346–352. doi: 10.1089/vbz.2013.1386 24745813

20. Bogovic P, Logar M, Avsic-Zupanc T, Strle F, Lotric-Furlan S. Quantitative Evaluation of the Severity of Acute Illness in Adult Patients with Tick-Borne Encephalitis. 2014; doi: 10.1155/2014/841027

Článek vyšel v časopise


2019 Číslo 10