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

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. 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