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Tick-borne encephalitis: Disease epidemiology and burden
of disease
Jochen Süss National Reference Laboratory for Tick-borne Diseases
Friedrich-Loeffler-Institute, Jena, Germany
WHO-Meeting of the Strategic Advisory Group of
Experts on Immunization (SAGE) 5-7 April 2011
CCV/CICG, Geneva
Tick-borne encephalitis (TBE)
- human TBE cases transmitted by tick bites, and – more rarely – by milk and milk products
- important viral zoonose
- the most important cause of viral infections of the central nervous system in Central and Eastern European countries and in Russia
- the most important and widespread of arbovirus diseases that can be transmitted by ticks in Europe (and Asia?)
TBEV - Host - Vector - Interactions
Pathogen
Vector
(i) (ii)
(iii) e.g. rodents, birds (humans)
e.g. Ixodes ricinus TBEV prevalence 1-3% Germany, Austria 1.7% Lithuania 14.3% special focus Switzerland 3-5% (25%) Latvia
I. persulcatus acc. to P. Nuttal, 1999, mod.
Vertebrate host
focal nature of the disease!
Ixodes ricinus and I. persulcatus in Europe and Far East
according to Lindgren, Jaenson, Sonenshine, Minar
Phylogenetic tree of flaviviruses (glycoprotein E)
Source: Heinz and Stiasny, 2010; Jääskeläinen et al., 2010; Chausov et al., 2010 (mod.)
Sofjin
Siberian/Siberian
Siberian/Baltic
Neudoerfl
Zausaev Vasilchenko
Ixodes ricinus
Ixodes persulcatus
TBEV subtype pattern in Europe and Asia
EU SI FE
EU
SI
FE SI EU
EU
FE FE SI
Alimentary transmission of TBEV (dairy products from livestock)
Raw milk: goat < sheep < dairy cow
Russia Czech Republic Hungary Austria Slovakia Lithuania Latvia Poland Lithuania Estonia Albania Bosnia Serbia
Recent alimentary outbreaks: 2007: Hungary/Lakhegy: 154 exposed individuals 25 confirmed cases (Balogh et al., 2009) 2008: Austria/Vorarlberg: 7 exposed individuals 4 confirmed cases (Holzmann et al., 2009)
XXXXX: from the 1990 more milk-borne cases and outbreaks!
Historical alimentary outbreak: 1954: Slovakia/Roznava: > 261 patients (Blaškovič, 1954)
TBE is a notifiable disease in 16 European countries (Austria, Czech Republic, Estonia, Finland, Germany, Greece, Hungary, Latvia, Lithuania, Norway, Poland, Russia, Slovak Republic, Slovenia, Sweden, Switzerland) . At present, TBE is not notifiable in Belgium, France, Italy, Portugal, Spain, Denmark, and the Netherlands. In 19 European countries TBE is endemic AND which report reliable data:
Between 1990 and 2009 169,937 TBE cases were reported, an average of 8,497 cases/year.
This is considered an underestimate due to insufficient routine diagnostics and surveillance!
In Belgium, Portugal, Spain, and the Netherlands no authochthonous TBE cases were reported; the reasons are largely unknown. (Süss, J., Eurosurveillance 2008; 13(26))
TBE: Reporting structures / surveillance activities Clinically and diagnostically confirmed AUTOCHTHONOUS TBE cases Detection (and characterization) of TBEV in unengorged ticks (selected points) Detection of TBEV in rodents (and specific antibodies) Surveillance in wildlife Surveillance in livestock sentinels (antibodies; goat and sheep flocks)
TBE risk areas have been monitored by TBE incidence since 2007 (Robert-Koch-Institute, 2007). Risk areas (districts) are defined as areas with a mean of 1 case per 100.000 inhabitants in the district (Landkreis) in the course of 5 years. Previously, TBE risk areas in Germany were determined by the number of confirmed human cases per district a year and not by incidence
Def. risk area (Germany) – Robert-Koch-Institute
TBE – case definition (Germany and other countries)
Clinical picture typical of TBE
Detection of TBEV-specific IgM and IgG antibodies in the serum
Place of exposure
Typically a biphasis course with flu-like symptoms during the first phase, signs of meningitis, encephalitis or radiculitis or mixed forms after an asymptomatic period without fever
Detection of TBEV-specific antibodies in the CSF – increased CSF serum index cross reactive antibodies against other flaviviruses (or vaccinations) – ELISA test versus neutralization test moderate pleocytosis
Further epidemiological circumstances: history, vaccination status, tick bite, exposure in known risk areas, raw milk in risk areas
However, case definitions vary in different countries
TBE – case definition (Germany and other countries)
Clinical picture typical of TBE
Detection of TBEV-specific IgM and IgG antibodies in the serum
Place of exposure
Typically a biphasis course with flu-like symptoms during the first phase, signs of meningitis, encephalitis or radiculitis or mixed forms after an asymptomatic period without fever
Detection of TBEV-specific antibodies in the CSF – increased CSF serum index cross reactive antibodies against other flaviviruses (or vaccinations) – ELISA test versus neutralization test moderate pleocytosis
Further epidemiological circumstances: history, vaccination status, tick bite, exposure in known risk areas, raw milk in risk areas
However, case definitions vary in different countries
Rhineland Palatinate
Baden- Wuerttemberg
Bavaria
Hesse Thuringia
1998 Definition risk area risk area
Development of TBE risk areas in Germany
1998
1998: 63 TBE risk districts 2010: 136 TBE risk districts
2010 (Germany:440 districts)
Recorded (!) TBE cases in Europe and Russia 1990 – 2009 (2010)
Europe without Russia
Russia
Europe including Russia
(Süss, 2011, TTBDIS)
2010 preliminary
0
1000
2000
3000
4000
5000
6000
7000
TBE in Europe 2000 – 2009
CZ 6542
LT 3848
D 2977 SLO 2620
LV 2608
PL 2362 EST 1740
S 1549 CH 1328
H A SK FIN
HR I
TBE cases
N F DK 25
without Russia
Number of TBE cases in 10 years
Czech Republic Lithuania Germany Slovenia Latvia Poland Estonia Sweden Switzerland Hungary Austria Slovakia Finland Croatia Italy Norway France Denmark
(Süss, unpublished)
0
2
4
6
8
10
12
14
RU
TBE in Europe 2000 – 2009 (incidence)
CZ
LT
D
SLO
LV
PL
EST
S CH H A SK
FIN
HR
I
TBE incidence
N
Mean value of incidence in the last 10 years
RU
Estonia 12.91 Slovenia 12.82 Latvia 11.31 Lithuania 11.15 Czech Rep. 6.19 Russia 3.02 Sweden 1.77 Switzerland 1.76 Slovakia 1.36 Austria 0.88 Hungary 0.72 Poland 0.62 Finland 0.42 Germany 0.36
(Süss, unpublished)
China: North east, Heilongjiang province, (Zhi Lu et al., Vector-borne and Zoonotic Diseases, 2008). Kazakhstan: East region and region Almaty (Pavel N. Deryabin, pers. commun., 2010)
Mongolia: North, (Walder et al., IJMM 296 S1, 69-75 (2006) (Khasnatinov et al., 2010: first fatal case, Far East subtype)
Japan: Hokkaido (Ikuo Takashima et al.)
Korea: (Su-Yeon Kim et al., Vector-borne and zoonotic diseases (2008), no cases
TBEV outside Europe
Kyrgyzstan: siberian subtype (Atkinson, 2010)
Korenberg, E., Advances in Virus Research 74 (2009) 124-144
TBE-incidence (per 100.000 inhabitants)
TBE cases (incidence) in Russia 1950 - 2009
Climate change? Anthropogenic influence? Vaccination coverage? Reporting? Diagnostics?
?
?
1990 - 2009
?
Age & Clinical Manifestation of TBE
acc. to Kaiser, 2005 (unpublished)
66 62 5441 33
14
34 38 4659 67
86
1-15 16-30 31-45 46-60 61-75 76-90Age (Years)
0%
20%
40%
60%
80%
100%
Meningitis Encephalitis/Myelitis
Long-term prognosis in TBE (encephalomyelitis)
Patients 57
n
Death due to TBE 17 (30%)
Persisting dysfunctions 29 (51%)
Recovered 11 (19%)
(R. Kaiser, submitted to TTBDIS)
Case fatality rates, TBEV subtypes and regions, a contradiction
European subtype: 1-2% Siberian subtype: 6-8% (some patients develop chronic TBE?) Far Eastern subtype: 20-40% (?)
Gritsun et al. (2003) Platonov et al. unpubl.
Siberia (south): 1.2% Far Eastern (south): 12.1% Ural: 1.5%
Postencephalitic syndrome associated with TBE Frequency and severity of TBE associated postencephalitic syndrome are related to: TBE virus subtype: European < Siberian/Far Eastern (?) Severity of acute illness
Conclusion: Clinical presentation and pathogenesis
Severe forms of TBE are associated with: - Age
- Severity of illness in the acute stage
- Low neutralising antibodies at onset
- Low early CSF IgM response
- Sequelae present after 1 year indicates a poor prognosis
- Disputed: TBEV subtype: European < Siberian/Far Eastern
C Christian Lüttich, 2007
Thank you !