Tick-borne encephalitis in adults in Denmark: a nationwide prospective cohort study from 2015 to 2023

Abstract

Background: Our aim was to characterize the clinical presentation and outcome in adults with tick-borne encephalitis (TBE) and to determine the incidence and test activity of TBE in Denmark.

Methods: A nationwide prospective cohort study of all adults hospitalized with TBE at departments of infectious diseases in Denmark from 2015 to 2023. An age- and sex-matched cohort of herpes simplex virus type 1 (HSV-1) encephalitis patients was included to compare outcome.

Results: Fifty-two patients with TBE were included. Median age was 50 years, 32/52 (62%) were men, 1/52 (2%) was fully vaccinated against TBE at the time of infection, 29/52 (56%) were infected in Denmark. Upon admission 25/52 (48%) had meningitis, 27/52 (52%) encephalitis, three of the latter 3/52 (6%) with additional myelitis or radiculitis. Admission to the intensive care unit 6/52 (12%) and death 2/52 (4%) were associated with pre-existing comorbidities and older age. At 3-month follow-up, 16/50 (32%) had an unfavorable outcome (Glasgow Outcome Scale score 1-4) compared to 39/52 (75%) in the HSV-1 cohort. The most common residual symptoms at 6-month follow-up or later were headache, cognitive impairment, and fatigue. The TBE incidence increased from 0.03/100,000 in 2015 to 0.48/100,000 in 2023, and the test rate from 5.5/100,000 in 2015 to 14.4/100,000 in 2023, with a positivity rate of 0.6% in 2015 and 3.3% in 2023.

Conclusion: The incidence of TBE in Denmark increased in the study period, with clinical characteristics and outcome of adult patients comparable to reports from other European countries.

Keywords: Clinical characteristics; Herpes simplex encephalitis; Outcome; TBE; Test activity; Tick-borne encephalitis.

Fig. 1

Sankey diagram showing outcome measured as Glasgow Outcome Scale (GOS) score over time in 52 patients diagnosed with tick-borne encephalitis in Denmark from 2015 to 2023. The GOS score is divided into: (1) Death, (2) A vegetative state, (3) Severe sequelae and dependency upon others in daily life, (4) Moderate sequelae but with the ability to live independently, and 5) No or only mild sequelae. GOS score 1–4 was categorized as an unfavorable outcome. At 1-month follow-up, one patient was missing data (thus N = 51), and at 3-month follow-up, two patients were missing data (thus N = 50). Notably, the diagram shows that patients with GOS score 4 at discharge could improve to GOS score 5 within 3 months, but those with GOS score 3 remained in that group or worsened. NA not available

Fig. 2

Percentage with an unfavorable outcome (Glascow Outcome Scale score 1–4) in 52 patients with tick-borne encephalitis, and in 52 patients with herpes simplex virus type 1 encephalitis, at the three timepoints: Discharge, 1-month follow-up, and 3-month follow-up. The tick-borne encephalitis cohort had missing data for one patient at 1-month follow-up (thus N = 51) and for two patients at 3-month follow-up (thus N = 50). TBE tick-borne encephalitis; HSV-1 herpes simplex virus type 1

Fig. 3

Incidence and test rates of tick-borne encephalitis in Denmark from 2015 to 2023. Data retrieved from Statens Serum Institut and Statistics Denmark. The black line represents the test rate (per 100,000 individuals), and the blue line represents the incidence rate, scaled to the same axis. The shaded region highlights the possible impact of COVID-19 travel restrictions during 2020, resulting in fewer imported cases. The arrow points to an increase in test rates in 2018–2019, possibly due to the establishment of a new risk area in North Zealand in 2019

Fig. 4

Tick-borne encephalitis test rate in the five different regions in Denmark from 2015 to 2023. Every tested person only appears once per calendar year