Clinical manifestations and outcomes of Tick-borne encephalitis: A systematic literature review

Tick-borne encephalitis (TBE) is caused by a viral infection and can lead to acute and persistent damage to the central and peripheral nervous systems. Recently, the incidence of TBE in Europe has risen, and epidemiological patterns of disease have changed, emphasising the need for improved understanding of this vaccine-preventable disease. Although TBE is endemic in many countries, the disease spectrum of TBE is not well described. We sought to characterise the clinical manifestations and outcomes of TBE by estimating the proportions of TBE patients with each type of manifestation and the risk of adverse outcomes for children and adults separately. A systematic literature review was conducted on 2 August 2022 for articles published in any language since 1 January 2007. Additional relevant studies were found in reference lists of identified articles. The review was limited to countries where only the European subtype of TBEV circulates. Of the 1,632 unique titles and abstracts identified and reviewed, 21 were retained for data analysis. The 21 studies were split into a main analysis (15 studies reporting patients hospitalised with laboratory-confirmed TBE) and a secondary analysis (6 studies reporting hospitalised and non-hospitalised patients who sought medical treatment for laboratory-confirmed TBE). The main analysis included 5,012 adults and 640 children. The predominant clinical manifestation in adults was encephalitis (61 %), followed by meningitis (33 %), radiculitis (14 %), and myelitis (6 %) (the manifestations were evaluated independently, so they will not sum to 100 %). With outliers removed, similar proportions of adults had encephalitis (48 %) and meningitis (44 %). Among cases in children, meningitis (77 %) was the most common manifestation, whereas encephalitis (23 %) and myelitis (1.3 %) were less frequent. Among hospitalised patients with TBE, the proportion of intensive care unit (ICU) admissions and deaths were similar for adults (15.5 % and 0.9 %, respectively) and children (16.4 % and 0 %, respectively.) The percentage of patients with sequelae when examined >12 months from acute TBE was 39.5 % for adults and 16.2 % for children. The evidence was challenging to aggregate due to study heterogeneity, variability in categorising clinical manifestations of central nervous system disease, variability of denominator populations, and differences in healthcare systems and diagnostic practices across countries. Our study disclosed distinct patterns of clinical manifestation among hospitalised adult and child patients with TBE and a high proportion of ICU admissions and long-term neurological sequelae across both age groups. These findings reinforce the continued need for preventive measures in the populations at risk. Moreover, variability of study admission criteria, including difficulty with clinical manifestation categorisation, calls for a more standardised approach to summarising TBE manifestations and outcomes across Europe.