Tick-borne encephalitis (TBE)
Most cases of tick-borne encephalitis (TBE) in Europe involve a biphasic presentation of the disease with fever during the first phase and neurological disorders during the second phase (Gubler, 2007). Severity of tick-borne encephalitis increases with age. TBE in children (<14 years) usually runs a more benign course (Mickiene, 2002; Kaiser, 1999). The proportion of asymptomatic cases is 66–80% (Gustafson, 1992). To calculate the burden of disease we assume that asymptomatic patients do not develop sequelae and are not included in the burden estimation.
The subtype considered is the Central European encephalitis subtype (Western tick-borne encephalitis virus) which is the dominant one in Europe. Another subtype does occur, the Russian spring-summer encephalitis subtype, however this occurs less in EU Member States and is not considered in the outcome tree.
The symptomatic infection (viraemic phase) begins after an average incubation period of eight days (range 4–28 days) (Kaiser, 1999). Symptoms of this first phase include fever, muscle pain, fatigue and headache (Gunther, 1997; Kaiser, 1999), normally lasting for five (2–7) days (Gubler, 2007).
Meningoencephalitic phase
After a symptom-free period, usually less than two weeks, a meningoencephalitic second phase occurs in 20–30% of symptomatic patients (Gustafson, 1990; 1992; Kiffner, 2010). The duration of the meningoencephalitic phase is set to 15 days (10–70) (Kaiser, 1999). The case fatality proportion of the meningoencephalitic phase is set to 0.75% (Mickiene, 2002).
Paralysis and residual paresis
Following the meningoencephalitic phase there is a latency period of six days (range 1–17 days), after which paralysis occurs in an estimated 11% of patients (Gunther, 1997). The duration is set to 3–10 days (Kaiser, 1999). Overall, 56% of paralytic patients are at risk of developing lifelong residual paresis (partial loss of or impaired movement) (Gunther, 1997).
Post-encephalitic TBE syndrome
A long-term post-encephalitic TBE syndrome, with symptoms including cognitive or neuropsychiatric complaints, balance disorders, headache, dysphasia, hearing defects and spinal paralysis, has been reported in 39–46% of meningoencephalitic patients (Gunther, 1997; Mickiene, 2002). The duration of post-encephalitic TBE syndrome is set to one year (‘Post TBE syndrome existed after 1 year in more than one third of the patients’ Gunther, 1997).
Lifelong chronic sequelae can persist in 35.7% (Haglund & Gunther, 2003) to 38.8% of post-encephalitic syndrome patients (Gunther, 1997: ‘persisting symptoms at 12 months in 33/85 patients’). Males are affected twice as much as females and 12% of patients with post-encephalitic TBE syndrome were under 14 years of age (Kaiser, 1999). However, the association between gender, age and severity still needs more research and is not considered in the outcome tree.
Model input summary
Table 1. Transition probabilities used in the outcome tree
Health outcome |
Distribution of health states in health outcome |
Transition probability |
Source/assumption |
Symptomatic infection |
|
20–34% |
Gustafson, 1992 |
Meningoencephalitic phase |
|
20–30% |
Gustafson, 1990, 1992; Kiffner, 2010 |
Paralysis |
|
11% |
Kaiser, 1999; Gunther, 1997 |
Residual paresis |
|
56% |
Gunther, 1997 |
Post-encephalitic TBE syndrome |
|
39–46% |
Gunther 1997; Mickiene, 2002 |
Chronic post-encephalitic TBE syndrome |
|
35.7–38.8% |
Haglund &
Gunther, 2003 |
Fatal cases following meningoencephalitic phase |
|
0.75% |
Mickiene, 2002 |
Table 2. Disability weights and duration
Health
outcome |
Disability Weight (DW) (Haagsma, 2015) |
Duration |
||
DW |
Label |
In years |
Source |
|
Symptomatic infection |
0.051 (0.039-0.06) |
Infectious disease, acute episode, moderate |
0.014 (0.005-0.019) |
Gubler, 2007 |
Meningoencephalitic phase |
0.447 (0.391-0.501) |
Encephalopathy - severe |
0.041 (0.027-0.192) |
Kaiser, 1999 |
Paralysis |
0.526 (0.469-0.586) |
Spinal cord lesion at neck level (treated) |
0.0137 |
Kaiser, 1999 |
Residual paresis |
0.056 (0.044-0.067) |
Motor plus cognitive impairments, mild |
Remaining life expectancy |
Remaining life expectancy |
Post-encephalitic TBE syndrome |
0.202 (0.167-0.242) |
Motor plus cognitive impairments, moderate |
1 |
Gunther, 1997 |
Chronic post-encephalitic TBE syndrome |
0.056 (0.044-0.067) |
Motor plus cognitive impairments, mild |
Remaining life expectancy |
Remaining life expectancy |
References
Gubler JD, Kuno G, Markoff L. 2007. Flaviviruses. In: Knipe, D.M., Howley, P.M. (Eds.), Fields Virology 5th ed., vol. 1. Lippincott Williams & Wilkins, London, New York, Tokyo, pp. 1043–1125.
Gustafson R, Svenungsson B, Forsgren M, Gardulf A, Granström M. Two-year survey of the incidence of Lyme borreliosis and tick-borne encephalitis in a high-risk population in Sweden. European Journal of Clinical Microbiology and Infectious Diseases, 1992 Oct;11(10):894-900. PMID: 1486884
Gustafson R, Svenungsson B, Gardulf A, Stiernstedt G, Forsgren M. Prevalence of tick-borne encephalitis and Lyme borreliosis in a defined Swedish population. Scandinavian Journal of Infectious Diseases, 1990;22(3):297-306. PMID: 2371545
Günther G, Haglund M, Lindquist L, Forsgren M, Sköldenberg B. Tick-bone encephalitis in Sweden in relation to aseptic meningo-encephalitis of other etiology: a prospective study of clinical course and outcome. Journal of Neurology, 1997 Apr;244(4):230-8. PMID: 9112591
Haglund M, Günther G. Tick-borne encephalitis--pathogenesis, clinical course and long-term follow-up. Vaccine, 2003 Apr 1;21 Suppl 1:S11-8. PMID: 12628810
Haagsma JA, Maertens de Noordhout C, Polinder S, Vos T, Havelaar AH, Cassini A, Devleesschauwer B, Kretzschmar ME, Speybroeck N, Salomon JA. Assessing disability weights based on the responses of 30,660 people from four European countries. Population Health Metrics 2015; 13: 10
Kaiser R. The clinical and epidemiological profile of tick-borne encephalitis in southern Germany 1994-98: a prospective study of 656 patients. Brain 1999; 122 (Pt 11): 2067-78. PMID: 10545392
Kiffner C, Zucchini W, Schomaker P, Vor T, Hagedorn P, Niedrig M, et al. Determinants of tick-borne encephalitis in counties of southern Germany, 2001-2008. International Journal of Health Geography, 2010 Aug 13;9:42. PMID: 20707897
Mickiene A, Laiskonis A, Gunther G, et al. Tick-borne encephalitis in an area of high endemicity in Lithuania: disease severity and long-term prognosis. Clin Infect Dis 2002; 35 (6): 650-8 PMID: 12203160