Clinical course and sequelae for tick-borne encephalitis among children in South Moravia (Czech Republic)
Abstract
This study of 170 children in the Czech Republic examines the clinical course and sequelae for tick-borne encephalitis. Evaluated were demographic and epidemiological data, signs and symptoms at admission, clinical course during hospital stay and laboratory findings. Cerebrospinal fluid was analysed for white blood cells, protein, impairment of blood–cerebrospinal fluid (CSF) barrier and tick-borne encephalitis virus (TBEV)-specific antibodies. Subjective complaints and objective neurological deficits were investigated. Tick bites were reported in 74 % of the children. The illness had a biphasic clinical course in 58 % of cases. The second phase was characterized by headache in 98 %, high fever in 86 % (more than 38.5 °C), vomiting in 64 % and meningeal signs in 92 % of children. Meningitis (77 %) dominated over meningoencephalitis (13 %). Inflammatory changes in CSF were found in 90 % of children. Immunoglobulin M (IgM) antibodies against TBEV in serum were found early in the infection in 99 %. IgM positivity lasted up to 1,126 days. Neurocognitive abnormalities were found in 19 (11 %) of children. Acquired aphasia, lasting tremor of the upper extremities, speech impairment, inversion of sleep and wakefulness, abnormal hyperkinetic movements and vertigo were found to be permanent but not progressing. Severe sequelae persisted in two children (1 %) while in three (2 %) were classified as mild or moderate.
Conclusion: Tick-borne encephalitis in children has a benign course with minimal sequelae. Meningitis with biphasic course is the prevalent involvement and the duration of IgM antibodies in serum and index of positivity are not decisive for postencephalitic disorders.
Keywords
Tick-borne encephalitis Children Cerebrospinal fluid Neurological sequelaeAbbreviations
- CSF
Cerebrospinal fluid
- CT
Computer tomography
- EEG
Electroencephalograph
- ELISA
Enzyme-linked immunosorbent assay
- HGA
Human granulocytic anaplasmosis
- FSME
Frühsommer Meningoencephalitis (Tick-borne encephalitis)
- ICU
Intensive care unit
- IgM
Immunoglobulin M
- IgG
Immunoglobulin G
- LNB
Lyme neuroborreliosis
- MRI
Magnetic resonance imaging
- Pos
Positive
- SAS
Statistical analysis software
- TBE
Tick-borne encephalitis
- TBEV
Tick-borne encephalitis virus
Notes
Acknowledgments
We thank Michal Kyr for statistical analysis of all data and physicians Lenka Klapacova and Iva Capovova who contributed data for this study.
Conflict of interest
The authors declare that they have no conflict of interest and that the study was not sponsored.
References
- 1.Andersson CHR, Vene S, Insulander M, Linquist L, Lundkvist A, Günther G (2010) Vaccine failures after active immunisation against tick-borne encephalitis. Vaccine 28:2827–2831PubMedCrossRefGoogle Scholar
- 2.Anic K, Soldo I, Peric L, Karner I, Barac B (1998) Tick-borne encephalitis in eastern Croatia. Scand J Infect Dis 30(5):509–12PubMedCrossRefGoogle Scholar
- 3.Blasko-Markic M, Socan M (2012) Tick-borne encephalitis in Slovenia: data from a questionnaire survey. Vector Borne Zoonotic Dis 12(6):496–502PubMedCrossRefGoogle Scholar
- 4.Cižman M, Rakar R, Zakotnik B, Pokorn M, Arnež M (1999) Severe forms of tick-borne encephalitis in children. Wien Klin Wochenschr 111(12):484–487PubMedGoogle Scholar
- 5.Dobler G, Gniel D, Petermann R, Pfeffer M (2012) Epidemiology and distribution of tick-borne encephalitis. Wien Med Wochenschr 162:230–238PubMedCrossRefGoogle Scholar
- 6.Donoso Mantke O, Escadafal C, Niedrig M, Pfeffer M (2011) Tick-borne encephalitis in Europe, 2007 to 2009. Euro Surveill 16(39): pii = 19976. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19976
- 7.Dumpis U, Crook D, Oksi J (1999) Tick-borne encephalitis. Clin Infect Dis 28:882–90PubMedCrossRefGoogle Scholar
- 8.Duniewicz M (1976) Clinical picture of Central European tick-borne encephalitis. Munch Med Wochenschr 118:1609–1612Google Scholar
- 9.Engman ML, Lindström K, Sallamba M, Hertz C, Sundberg B, Hansson ME et al (2012) One-year follow-up of tick-borne central nervous system infections in childhood. Pediatr Infect Dis J 31(6):570–574PubMedCrossRefGoogle Scholar
- 10.Epidat (English version) http://www.szu.cz
- 11.Epidemiological situation on tick-borne encephalitis in EU/EFTA countries. Available online: http://ecdc.europa.eu/publications/tbe-in-eu-efta.pdf
- 12.Fowler A, Forsman L, Eriksson M, Wickström R (2013) Tick-borne encephalitis carries a high risk of incomplete recovery in children. J Pediatr 162(2):555–560CrossRefGoogle Scholar
- 13.Fowler A, Stödberg T, Eriksson M, Wickström R (2010) Long-term outcomes of acute encephalitis in childhood. Pediatrics 126:828–835CrossRefGoogle Scholar
- 14.Fritsch P, Gruber-Sedlmayer U, Pansi H, Zöhrer B, Mutz I, Spork D et al (2008) Tick-borne encephalitis in Styrian children from 1981 to 2005: a retrospective study and review of the literature. Acta Paediatr 97:535–538PubMedCrossRefGoogle Scholar
- 15.Gallia F, Rampas J, Hollender L (1949) Laboratorní infekce encefalitickým virem. Cas Lek Ces 88:224–229Google Scholar
- 16.Grgič-Vítek M, Avšič-Županc T, Klavs I (2010) Tick-borne encephalitis after vaccination: vaccine failure or misdiagnosis. Vaccine 29:7396–7400CrossRefGoogle Scholar
- 17.Grubbauer HM, Dornbusch HJ, Spork D, Zobel G, Trop M, Zenz W (1992) Tick-borne encephalitis in a 3-month-old child. Eur J Pediatr 151(10):743–744PubMedCrossRefGoogle Scholar
- 18.Günther G, Haglund M (2005) Tick-borne encephalopathies: epidemiology, diagnosis, treatment and prevention. CNS Drugs 19(12):1009–1032PubMedCrossRefGoogle Scholar
- 19.Günther G, Haglund M, Lindquist L, Forsgren M, Skoldenberg B (1997) Tick-borne encephalitis in Sweden in relation to aseptic meningoencephalitis of other etiology: a prospective study and clinical outcome. J Neurol 244:230–238PubMedCrossRefGoogle Scholar
- 20.Haglund M (2002) Occurrence of TBE in areas previously considered being non-endemic: Scandinavian data generate an international study by the International Scientific Group for TBE (ISW-TBE). Int J Med Microbiol 291(Suppl 33):50–54PubMedCrossRefGoogle Scholar
- 21.Haglund M, Forsgren M, Lindh G, Lindquist L (1996) A 10-year follow-up study of tick-borne encephalitis in the Stockholm area and a review of the literature: need for a vaccination strategy. Scand J Infect Dis 28(3):217–224PubMedCrossRefGoogle Scholar
- 22.Haglund M, Günther G (2003) Tick-borne encephalitis—pathogenesis, clinical course and long-term follow-up. Vaccine 21(Suppl 1):S11–S18PubMedCrossRefGoogle Scholar
- 23.Han X, Aho M, Vene S, Brummer-Korvenkontio M, Juceviciene A, Leinikki P et al (2002) Studies on TBE epidemiology in Finland (and Lithuania). Int J Med Microbiol 291(Suppl 33):48–49PubMedCrossRefGoogle Scholar
- 24.Hansson ME, Orvell C, Engman ML, Wide K, Linquist L, Lidefelt KJ et al (2011) Tick-borne encephalitis in childhood: rare or missed? Pediatr Infect Dis J 30(4):355–357PubMedCrossRefGoogle Scholar
- 25.Heinz FX (2003) Molecular aspects of TBE virus research. Vaccine 21(Suppl1):S3–10PubMedCrossRefGoogle Scholar
- 26.Heinz FX, Holzmann H, Essl A, Kundi M (2007) Field effectiveness of vaccination against tick-borne encephalitis. Vaccine 25:7559–7567PubMedCrossRefGoogle Scholar
- 27.Heinz FX, Stiastny K, Holzmann H, Grgic-Vitek M, Křiž B, Essl A et al (2013) Vaccination and tick-borne encephalitis, Central Europe. Emerg Infect Dis 19(1):69–76PubMedCentralPubMedCrossRefGoogle Scholar
- 28.Hloucal L (1949) Abortive viral meningoencephalitis. Cas Lek Ces 88:1390–1394, CzechGoogle Scholar
- 29.Iff T, Meier R, Olah E, Schneider JFI, Tibussek D, Berger CH (2005) Tick-borne-encephalitis in a 6-week-old infant. Eur J Pediatr 164(12):787–788PubMedCrossRefGoogle Scholar
- 30.Jereb M, Muzlovič I, Avšič-Županc T, Karner P (2002) Severe tick-borne encephalitis in Slovenia: epidemiological, clinical and laboratory findings. Wien Klin Wochenschr 114:623–626PubMedGoogle Scholar
- 31.Jones N, Sperl W, Koch J, Holzmann H, Radauer W (2007) Tick-borne encephalitis in a 17-day-old newborn resulting in severe neurologic impairment. Pediatr Infect Dis J 26(2):185–186PubMedCrossRefGoogle Scholar
- 32.Kaiser R (1999) The clinical and epidemiological profile of tick-borne encephalitis in southern Germany 1994-1998: a prospective study of 656 patients. Brain 22(11):2067–78CrossRefGoogle Scholar
- 33.Kaiser R (2002) Tick-borne encephalitis in Germany and clinical course of the disease. Int J Med Microbiol 291(Suppl33):S58–61CrossRefGoogle Scholar
- 34.Kaiser R (2012) Tick-borne encephalitis: clinical findings and prognosis in adults. Wien Med Wochenschr 162(11–12):239–243PubMedCrossRefGoogle Scholar
- 35.Kaiser R, Holzmann H (2000) Laboratory findings in tick-borne encephalitis—correlation with clinical outcome. Infection 28(2):78–84PubMedCrossRefGoogle Scholar
- 36.Krech T (2002) TBE foci in Switzerland. Int J Med Microbiol 291(Suppl 33):30–33PubMedCrossRefGoogle Scholar
- 37.Kříž B, Beneš Č, Daniel M (2009) Alimentary transmission of tick-borne encephalitis in the Czech Republic (1997-2008). Epidemiol Mikrobiol Imunol 8(2):98–103Google Scholar
- 38.Kunz C (1993) Frühsommer-Meningoenzephalitis (FSME) in Europa. In: Süss J (ed) Durch Zecken übertragbare Erkrankungen. Weller Verlag, Schriesheim, pp 23–30Google Scholar
- 39.Labuda M, Elečkova E, Ličkova M, Sabó A (2002) Tick-borne encephalitis virus foci in Slovakia. Int J Med Microbiol 291(Suppl 33):43–47PubMedCrossRefGoogle Scholar
- 40.Lešničar G, Poljak M, Seme K, Lešničar J (2003) Pediatric TBE in 371 cases from an endemic area in Slovenia, 1959 to 2000. Pediatr Infect Dis J 22:612–17PubMedCrossRefGoogle Scholar
- 41.Lindquist L, Vapalahti O (2008) Tick-borne encephalitis. Lancet 371:1861–1871PubMedCrossRefGoogle Scholar
- 42.Logar M, Arnez M, Kolbl J, Avsic-Zupanc T, Strle F (2000) Comparison of the epidemiological and clinical features of tick-borne encephalitis in children and adults. Infection 28(2):74–77PubMedCrossRefGoogle Scholar
- 43.Logina I, Krumina A, Karelis G, Elsone L, Viksna L, Rozentale B et al (2006) Clinical features of double infections with tick-borne encephalitis and Lyme borreliosis transmitted by tick bite. J Neurol Neurosurg Psychiatry 77:1350–1353PubMedCentralPubMedCrossRefGoogle Scholar
- 44.Lotrič-Furlan S, Avšič-Županc T, Strle F (2002) An abortive form of tick-borne encephalitis (TBE)—A rare clinical manifestation of infection with TBE virus. Wien Klin Wochenschr 114:627–629PubMedGoogle Scholar
- 45.Lotrič-Furlan S, Avšič-Županc T, Strle F (2008) Tick-borne encephalitis after active immunisation. Int J Med Microbiol 298:309–313CrossRefGoogle Scholar
- 46.Lotrič-Furlan S, Petrovec M, Avšič-Županc T, Logar M, Strle F (2002) Epidemiological, clinical and laboratory distinction between human granulocytic ehrlichiosis an the initial phase of tick-borne encephalitis. Wien Klin Wochenschr 114:636–640PubMedGoogle Scholar
- 47.Lotrič-Furlan S, Strle F (2012) Peripheral facial palsy in patients with tick-borne encephalitis. Clin Microbiol Infect 18(10):1027–1032PubMedCrossRefGoogle Scholar
- 48.Mansfield KL, Johnson N, Phipps LP, Stephenson JR, Fooks AR, Solomon T (2009) Tick-borne encephalitis virus—a review of an emerging zoonosis. J Gen Virol 90:1781–1794PubMedCrossRefGoogle Scholar
- 49.Mickiene A, Laiskonis A, Gunther G, Vene S, Lundquist A (2002) Tick-borne encephalitis in an area of high endemicity in Lithuania: disease severity and long-term prognosis. Clin Infect Dis 35(6):650–658PubMedCrossRefGoogle Scholar
- 50.Misić-Majerus L, Bujić N, Madarić V, Avšič-Župan T (2005) Hepatitis caused by tick-borne meningoencephalitis virus (TBEV)—a rare clinical manifestation outside the central nervous system involvement. Acta Med Croatica 59(4):347–52PubMedGoogle Scholar
- 51.Oksi J, Viljanen MK, Kalimo H, Peltonen R, Marttila R, Salomaa P (1993) Fatal encephalitis caused by concomitant infection with tick-borne encephalitis virus and Borrelia burgdorferi. Clin Infect Dis 16:392–396PubMedCrossRefGoogle Scholar
- 52.Randolph S (2002) Predicting the risk of tick-borne diseases. Int J Med Microbiol 291(Suppl 33):6–10PubMedCrossRefGoogle Scholar
- 53.Schmolck H, Maritz E, Kletzin I, Korinthenberg R (2005) Neurologic, neuropsychologic, and electroencephalografic findings after European tick-borne encephalitis in children. J Child Neurol 0(6):500–8CrossRefGoogle Scholar
- 54.Sumilo D, Bormane A, Asokliene L, Lucenko I, Vasilenko V, Randolph S (2006) Tick-borne encephalitis in the Baltic States: identifying risk factors in space and time. Int J Med Microbiol 296(1):76–79PubMedCrossRefGoogle Scholar
- 55.Sundin M, Hansson ME, Engman ML, Orvell C, Lindquist L, Wide K et al (2012) Pediatric tick-borne infections of the central nervous system in an endemic region of Sweden: a prospective evaluation of clinical manifestations. Eur J Pediatr 171(2):347–352PubMedCrossRefGoogle Scholar
- 56.Süss J (2011) Tick-borne encephalitis 2010: epidemiology, risk areas, and virus strains in Europe and Asia—an overview. Ticks Tick Borne Dis 2:2–15PubMedCrossRefGoogle Scholar
- 57.Zeman P, Pazdiora P, Beneš Č (2010) Spatio-temporal variation of tick-borne encephalitis (TBE) incidence in the Czech Republic: is the current explanation of the disease’s rise satisfactory? Ticks Tick Borne Dis 1(3):129–140PubMedCrossRefGoogle Scholar
- 58.Zenz W, Pansi H, Zoehre B, Mutz I, Holzmann H, Kraigher A et al (2005) Tick-borne encephalitis in children in Styria and Slovenia between 1980 and 2003. Pediatr Inf Dis J 24(10):892–6CrossRefGoogle Scholar