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Vaccine 29 (2011) 4556– 4564

Contents lists available at ScienceDirect

Vaccine

j ourna l ho me pag e: www.elsev ier .com/ locate /vacc ine

eview

he current perspective on tick-borne encephalitis awareness and prevention inix Central and Eastern European countries: Report from a meeting of expertsonvened to discuss TBE in their region

erwig Kollaritscha,∗, Václav Chmelíkb, Irina Dontsenkoc, Anna Grzeszczukd,aciej Kondrusike, Vytautas Usonis f, András Lakosg

Institute of Specific Prophylaxis and Tropical Medicine, Medical University, Vienna, AustriaDepartment of Infection, Hospital Ceske Budejovice, Czech RepublicHealth Board, Paldiski Road 81, 10617 Tallinn, EstoniaDepartment of Infectious Diseases and Hepatology, Medical University of Białystok, PolandDepartment of Infectious Diseases and Neuroinfections, Medical University, Białystok, PolandVilnius University Centre of Paediatric Disease, 01001 Vilnius, LithuaniaCentre for Tick-borne Diseases, Visegrádi 14, H-1132 Budapest, Hungary

r t i c l e i n f o

rticle history:eceived 8 November 2010eceived in revised form 5 April 2011ccepted 18 April 2011vailable online 5 May 2011

a b s t r a c t

Tick-borne encephalitis (TBE) is a potentially life-threatening disease in humans and is caused by a fla-vivirus spread by infected ticks (Ixodes ricinus and Ixodes persulcatus). TBE is endemic across much ofCentral and Eastern Europe and the incidence is increasing, with numbers estimated to be as many as8755 cases per year. The reasons for this increase are multi-faceted and may involve improvements indiagnosis and reporting of TBE cases, increases in recreational activities in areas inhabited by infected

eywords:ick-borne encephalitisBElavivirus

ticks and changes in climatic conditions affecting tick habitats. Vaccination is the most effective methodof preventing TBE; following a successful nationwide vaccination campaign in Austria, the annual numberof TBE cases fell to about 10% of those reported in the pre-vaccination era.

This report describes the findings of a group of leading experts from six Central and Eastern Europeancountries who convened to discuss TBE in their region during the 28th Annual Meeting of the EuropeanSociety for Paediatric Infectious Diseases (ESPID) Nice, France, 4–8 May 2010.

© 2011 Elsevier Ltd. All rights reserved.

ontents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45572. Case definitions of TBE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45573. Serological confirmation of TBE cases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45574. TBE reporting across six countries in Central and Eastern Europe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45585. An overview of the TBE landscape across six countries in Central and Eastern Europe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4558

5.1. Austria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45585.2. Czech Republic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45595.3. Estonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45595.4. Hungary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45605.5. Lithuania . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45605.6. Poland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4560

6. TBE vaccination recommendations and reimbursement . . . . . . . . . . . . . . . . . .

7. Raising awareness of TBE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

7.1. TBE awareness in the general public . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

∗ Corresponding author at: Institut für Spez. Prophylaxe und Tropenhygiene, Kinderspiax: +43 1 404 9064 899.

E-mail address: herwig.kollaritsch@meduniwien.ac.at (H. Kollaritsch).

264-410X/$ – see front matter © 2011 Elsevier Ltd. All rights reserved.oi:10.1016/j.vaccine.2011.04.061

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4560. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4562. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4562

talgasse 15, 1095 Vienna, Austria. Tel.: +43 1 403 8343 22;

H. Kollaritsch et al. / Vaccine 29 (2011) 4556– 4564 4557

7.2. TBE awareness in healthcare professionals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45637.3. TBE awareness in government, healthcare policy makers and medical insurance companies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4563

8. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4563Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4563

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References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. Introduction

The tick-borne encephalitis (TBE) virus is a pathogenic flavivirushat is carried by ticks (primarily Ixodes ricinus and Ixodes persul-atus) and is endemic across much of Europe and Asia (Fig. 1) [1].n most European countries TBE is a notifiable disease and, whilehe case definition and reporting of TBE varies across the region,he overall number of cases in European countries and Russia haseen estimated to be as many as 8755 cases per year (1990–2007)1]. Countries considered to have a particularly high risk of TBE areussia, Latvia, Lithuania and Estonia; however, TBE is also endemic

n areas of Central and Eastern Europe including Germany, Austria,he Czech Republic, Poland, Switzerland, Slovakia and Hungary [2].he incidence of TBE has been increasing in recent years, and therere a number of possible reasons for this:

Improvements in awareness, reporting and diagnosis [3].Increase in outdoor activities in endemic areas (both socioeco-nomic and recreational) [4].Warmer climates resulting in ticks living at higher altitudes andbeing active for longer throughout the year [5–7].Additional, unknown factors.

There are three main subtypes of the TBE virus that result inarying disease severity [2,8,9]. The Western subtype commonlyccurs across Central and Eastern Europe; the Siberian subtypes found in Eastern Europe, Russia and Northern Asia; while thear Eastern subtype (resulting in the most severe disease) is lim-ted mainly to Eastern Asia [2,10]. Recently the Far Eastern subtypeas been isolated from wild mammals in Estonia [10] and patients

n Latvia [11]; these results demonstrate that all known subtypesre co-circulating in Europe. Humans are accidental hosts of TBEnd may become infected when they are bitten by a tick carryinghe virus or, less commonly, if they consume unpasteurized dairyroducts from infected animals [9,12–16].

The TBE virus has an incubation period of 2–28 days after whichatients present with symptoms such as fever, myalgia, arthral-ia and headache that can last up to 7 days [17]. The majority ofatients make a full recovery, but about a quarter will enter ansymptomatic phase that can last for 2–10 days before a secondebrile phase follows, accompanied by serious neurological seque-ae (including meningitis and encephalitis) [9,17]. In some casesBE can be fatal with reported case fatality rates of 1–2% for theestern subtype, 2–3% for the Siberian subtype and up to 40% for

he Far Eastern subtype [18]. Preventative measures against TBEnfection involve avoiding exposure to tick bites by using repel-ents and covering the body to prevent questing ticks attaching tohe skin; however, the most effective way to prevent TBE infections vaccination [1,19]. Following a nationwide campaign in Austria,he annual number of TBE cases fell to about 10% of those reportedn the pre-vaccination era [19]. However, especially in some East-rn European countries where TBE is endemic, national vaccinationampaigns are not in place, resulting in low vaccine coverage and

high incidence of TBE [6,19].

During the 28th Annual Meeting of the European Society for

aediatric Infectious Diseases (ESPID), Nice, France, 4–8 May 2010, group of leading experts from six Central and Eastern Euro-ean countries convened to discuss TBE in their regions. Apart

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4563

from Austria and Hungary, where the incidence of TBE cases hasimproved, these countries have seen notable increases in the num-ber of TBE cases. The authors of this article were participants of themeeting and the objectives were to:

• Describe and discuss the epidemiological landscape of TBE andthe current recommendations for TBE vaccination across the sixcountries in Central and Eastern Europe.

• Discuss ways in which to raise awareness of TBE and improvevaccination rates.

2. Case definitions of TBE

TBE is a notifiable disease across much of Europe [2]; how-ever, case definitions for TBE vary [20]. Table 1 presents the casedefinitions in the six countries reported here. The published casedefinition for TBE in Austria is based on hospitalization due tothe onset of central nervous system (CNS) disease and laboratory-confirmed TBE infection by the presence of TBE-specific IgM andIgG antibodies in the blood using enzyme-linked immunosorbentassay (ELISA) [19].

The participants at the meeting agreed that the case definitionof TBE needs to be improved and that establishing a single Euro-pean case definition, including the recommendation of appropriatediagnostic tools, would be useful. This opinion is in agreement withthe conclusions from a recently published survey of TBE across28 countries in Europe, including Scandinavia [20]. The ideal stan-dard for the case definition of TBE should be identification of theclinical symptoms followed by laboratory analysis of cerebrospinalfluid (CSF) and serum. The definition of probable, possible and con-firmed infection was not considered to be clinically helpful, but aclear clinical definition based on neurological symptoms is essen-tial, particularly in countries where laboratory diagnosis is difficultto obtain. As described, fever after a tick bite is a characteristic signof TBE and in north-eastern Poland (a known TBE endemic area) astudy in febrile patients following a tick bite was described and TBEwas confirmed in 49 of the 68 patients evaluated [21]. In this regionTBE was found to be the most prevalent febrile illness occurringafter a tick bite [21].

3. Serological confirmation of TBE cases

While the clinical symptoms of TBE characterize the disease,some cases are atypical and therefore difficult to diagnose clini-cally. In such cases, laboratory confirmation of TBE is necessaryand is usually based on serological measurements. The estab-lishment of a European TBE laboratory reference centre wheresamples from suspected TBE cases could be sent and evaluated isessential to harmonize TBE reporting and diagnosis across Europe.Indeed, in Poland, only hospitals in endemic regions routinelytest serological samples for TBE, which makes it difficult to iden-tify new foci and ensure that all cases of TBE are recorded (A.Grzeszczuk, personal communication). Austria requires serologi-cal confirmation of hospitalized cases, while the Czech Republic,

Estonia, Hungary, Lithuania and Poland also require laboratoryconfirmation of cases [22]. In Hungary, hospitalization is not arequirement for TBE testing. A previous study shows that there aresignificant differences in specificity and sensitivity in different lab-

4558 H. Kollaritsch et al. / Vaccine 29 (2011) 4556– 4564

London

Paris Luxembourg

Amsterdam

Copenhagen

Berlin

Riga

Prague

Oslo

Vienna Bratislava

Budapest

Sarajevo

Zagreb Ljbljana

Bucharest

Athens

Rome

Nicosia

Ankara

Warsaw

Vilnius

Stockholm Tallinn

Helsinki

Andorra la Vella

Madrid

Vaduz

Berne

Dublin

Lisbon

Chisinau

Kiev

Minsk

Prodgorica

Belgrade

Sofia

Skopje Tirana

Brussels

ReykjavÌk

Valletta Areas where TBE virus has been detected

demic

odl

4E

vi(ipttapttIpdnlT

Fig. 1. Map of TBE-en

ratories [23]; as such, the discrepancies between epidemiologicalata across European countries may be due, in part, to differences in

aboratory testing.

. TBE reporting across six countries in Central and Easternurope

Along with differences in case definitions, reporting of TBE alsoaries considerably between countries. In Austria, TBE reportings based on serologic diagnosis by a central reference laboratoryInstitute of Virology, Medical University of Vienna) and every clin-cal case of meningitis is routinely tested for TBE. In Estonia, generalractitioners, hospitals and laboratories report diagnosed TBE caseso Health Board local offices either on paper or through the elec-ronic registration system NAKIS; monthly and annual reportsre prepared by the national Health Board [24]. In Poland, everyhysician who diagnoses TBE is obliged to report their findingso epidemiological centres within their district; these records arehen collected by the Department of Epidemiology at the Nationalnstitute of Public Health, where monthly and annual reports arerepared. In Poland, almost all registered cases (99.5–100%) were

iagnosed within hospitals, indicating that less severe cases areot tested and thus not diagnosed. This can be confirmed by sero-

ogical evaluation of samples from individuals with no history ofBE in endemic areas [25]. In Hungary, non-specified encephalitis

areas across Europe.

and TBE is mandatorily reported; serological examination is alsomandatory in every suspected case of TBE. In addition, TBE casesidentified by serology are collected by a centralized reference lab-oratory in Hungary (National Centre for Epidemiology, Laboratoryfor Viral Infections) and the data are regularly published. In Lithua-nia, there is no reference laboratory for TBE infections; however, allcases of TBE are mandatorily reported and an official database ofthe annual number of cases is held by the Centre for CommunicableDiseases and AIDS, which generates monthly and yearly reports onall communicable diseases [26]. In the Czech Republic, it is manda-torily required that TBE cases are reported to the National Institutefor Health.

5. An overview of the TBE landscape across six countries inCentral and Eastern Europe

5.1. Austria

Before the introduction of a nationwide vaccination campaignin the 1980s, the number of TBE cases in Austria may have beenas high as 700 hospitalized cases per year [1,27]. However, dur-

ing the 5-year period between 2003 and 2007, an average of 73cases of TBE were reported per year, equalling an incidence rateof 0.82 cases per 100,000 population and a significant reduction innumbers compared with the pre-vaccination era [1]. A total of 88%

H. Kollaritsch et al. / Vaccine 29 (2011) 4556– 4564 4559

Table 1Case definition of TBE in six countries in Central and Eastern Europe.

Country Current TBEdefinitions

Case definition Clinical diagnosis Laboratory diagnosis

Austria [27,43] The case definition of TBE in Austriaincludes both clinical and laboratorydiagnosis [19,52]

Hospitalization due to CNS disease Confirmation of infection with TBE virus bylaboratory diagnosis (IgM and IgGantibodies detected by ELISA)

Czech Republic Proven neuroinfection (clinical symptoms)Presence of anti-TBE IgM antibodies

Proven TBE neuroinfection: clinicalpresentation in CSF

Anti-TBE IgM and IgG antibodiesReference laboratory: Státní zdravotníústav, Praha (SZU; National HealthInstitute, Prague)

Estonia Probable caseCharacteristic clinical picture andepidemiological link

Characteristic two-phase clinical picture:initial high fever, second phase withmeningitis or meningoencephalitis

Four-fold antibody titres Elevation in pairsera or IgM antibodies in serum or liquoror positive RT-PCRNo official reference laboratory nominatedin Estonia

Confirmed caseCharacteristic clinical picture with positivelaboratory test

Hungary [31,32] Clinical suspicion of CNS infection plusserological confirmation

Hospitalization is not an essentialcondition for the diagnosis of TBE

Presence of TBE IgM antibodies in serumand CSFIf the first sample is negative, a secondsample is tested and a significant(four-fold) increase is accepted in IgGantibodies using an immunofluorescenceassayThe reference laboratory is the NationalCentre for Epidemiology, Laboratory forViral Infections

Lithuania There is no official case definition of TBE Clinical diagnostic criteria vary in differentclinics

Not available

Poland Clinical case (neurological symptoms) andlaboratory diagnosis

Signs of CNS involvement Laboratory criteria of confirmed case

Presence of specific IgM and IgG (serum,CSF) or

Proven intrathecal synthesis of specificantibodies or

Positive neutralization test forTBE-specific antibodiesLaboratory criteria of probable case

oTciiib

5

copobnyavIuosq

f the Austrian population are vaccinated at least once against theBE virus (approximately 60% had completed a basic immunizationourse by 2007), with more than 90% of the population vaccinatedn high-risk areas [19,27]. While vaccination coverage remains highn Austria, there is evidence suggesting that the TBE virus is spread-ng to higher altitudes as well as areas where it has not previouslyeen endemic [1,14,28].

.2. Czech Republic

TBE is a notifiable disease in the Czech Republic and the wholeountry is considered to be a risk area [1]. The national incidencef TBE infection is increasing in the Czech Republic (Fig. 2) andeaked in 2006 at 10 cases per 100,000 population with an averagef 666 cases per year between 2003 and 2007 [1]. Cases of TBE haveeen reported in highland areas (>500 m above sea level) where theumber has been greater than the country-wide average in recentears, which correlates with increased tick populations in thesereas [5]. Vaccination is recommended for all age groups and theaccination rate has increased in the traditional high-risk areas.n South Bohemia, one-third of people are vaccinated, in partic-

lar children and younger adults. In older adults (aged 50 yearsr older), the vaccination rate is low and, due to recreational andocioeconomic behaviour in the natural foci, this age group is fre-uently exposed to the TBE virus [29]. Indeed, recreational outdoor

Serum presence of specific IgM (notvaccinated against TBE and/or otherflavivirus during the last 3 months)

activities have increased in the older generation and as chronic con-ditions are more common in the elderly, a more serious course ofTBE with sequelae is often observed in these patients (V. Chmelík,personal communication).

5.3. Estonia

In the 1980s, TBE was identified only in southern regions ofEstonia, whereas now TBE is endemic throughout the country and iscurrently a notifiable disease [24]. The incidence of TBE in 2008 was6.7 cases per 100,000 population [24]. In 2005, an outbreak of 37TBE cases in Estonia was linked to the consumption of unpasteur-ized goat’s milk. All cases had consumed untreated goat’s milk ata supermarket promotional event. Investigations conducted by theVeterinary and Food Board identified serum specimens from goatsof the milk suppliers to be positive for the TBE virus [15]. In 2009,one cluster of three TBE cases was also linked to the consumptionof raw goat’s milk. These independent incidents highlight the con-sumption of unpasteurized dairy products as an important route ofinfection in Estonia [15], accounting for up to 29.3% of cases (2005)[24]. Between 2006 and 2008, the proportion of ticks carrying the

TBE virus varied, according to the region, from 0.2% (Puhtu) to 6.4%(Jarvselja) [24]. Recently the Far Eastern subtype was identified inLäänemaa; therefore, all three known subtypes of the TBE virushave now been observed in Estonia.

4560 H. Kollaritsch et al. / Vaccine 29 (2011) 4556– 4564

Num

ber o

f Cas

es

Years

% Vaccinated

1000

900

800

700

600

500

400

300

200

100

1980 1985 1990 1995 2000 20050 0

10

20

30

40

50

60

70

80

90

100

F (blacT i M, FiE

5

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5

wsoma

ig. 2. Annual numbers of TBE cases in Austria (dashed line) and the Czech Republichis figure was published in Vaccine, volume 25, Heinz FX, Holzmann H, Essl A, Kundlsevier 2007.

.4. Hungary

Between 1997 and 2006, there were 667 cases reported inungary (the average incidence was 0.67 per 100,000 per year)

30]. Prior to this (1977–1996), the average incidence was approx-mately 2.70 per 100,000 serologically confirmed TBE cases perear [31]. This dramatic decrease in the recorded cases after 1997ay be as a result of under-reporting because the costs associ-

ted with serological examination had not been charged directly toospitals before this year. However, the mortality rate attributedo TBE did not increase over the last decade [32], which suggestshat these data reflect the actual situation in Hungary. Before thencidence of TBE cases decreased, it was noted that the severityf the disease had also decreased [31]. Although this decline inases and severity is not fully understood, it may be due in part toaccination. Between 1991, when the TBE vaccine FSME-IMMUN®

Baxter International Inc., Deerfield, IL, USA) was registered inungary, and 1997, more than two million doses of TBE vaccinead been administered. It must be noted however, that estimatesf vaccine coverage in Hungary are low, ranging from 5 to 15%f the total population. The known TBE risk areas are generallyn the forested, rural regions located in the north and west ofhe country [33,34], in parallel with the big-game distribution inungary (A. Lakos, unpublished data). Approximately two-thirdsf the Hungarian population live in high-risk areas, but most ofhe low-risk population travels to these areas for recreational pur-oses. Ticks which carry the TBE virus have also been found up to000 m above sea level (Mátra mountains) [34]. In Hungary, theonsumption of unpasteurized dairy products carries a high riskf infection – in 2007, 25 TBE patients were infected due to con-uming unpasteurized milk [12], and approximately one-quarterf cows in Hungary are known to be seropositive for the TBEirus [35].

.5. Lithuania

Lithuania has the highest rate of TBE of the Baltic countries,ith an incidence as high as 51 cases per 100,000 reported in

ome areas [1,26]. Between 1997 and 2008, more than 4500 casesf TBE were reported [26,36], and in 2009, 447 cases were docu-ented between August and October alone [26]. While TBE cases

re reported throughout Lithuania, northern and central regions

k line) and vaccination coverage in Austria (grey line) between 1979 and 2006 [19].eld effectiveness of vaccination against tick-borne encephalitis, 7559–67. Copyright

have the highest incidence and account for 80% of cases [1]. Inthe past, cases of TBE have been attributed to the consumption ofunpasteurized goat’s milk, with 22 cases (from four separate clus-ters) identified in 2003 [1]. The TBE virus is endemic across much ofLithuania, and it has been estimated that 3% of the population havebeen exposed to it [37]; however, vaccine coverage is consideredto be too low to control the disease adequately [38,39].

5.6. Poland

In 2009, the number of recorded TBE cases in Poland was 335(incidence of 0.52 per 100,000 population) [39], with the high-est incidence in the north-east and south-west of the country[1,21,40,41]. Despite TBE being endemic across much of Poland,only 0.34% of the population have been vaccinated against the virus(1999–2007), and more than half of those vaccinated lived in north-eastern Poland [42].

6. TBE vaccination recommendations and reimbursement

Recommendations for TBE vaccination in the six countries arepresented in Table 2. In 1976 a vaccine against TBE was madecommercially available in Austria, and by 1979 there was high vac-cination coverage of those people with an occupational risk of TBE(e.g., forestry workers and farmers). However, 677 cases of patientshospitalized due to TBE were still recorded in that year, and it hadbecome clear that TBE was also acquired during leisure activities.As a result, a nationwide vaccination campaign was introduced inAustria in 1981 [27]. The people considered most at risk of TBEinfection are all individuals residing, working or travelling in anendemic area, although the whole population is encouraged to bevaccinated against TBE. Currently in Austria, TBE vaccination is onlyfully reimbursed for people with an occupational risk of TBE [27].For the rest of the Austrian population, the vaccine is available forthe first 6 months of the year at a reduced price, with doctors charg-ing less for administration and healthcare costs, which are partiallycovered by health insurance [27]. Following the introduction of thecampaign, the number of TBE cases per year has declined to approx-

imately 10% of those recorded in the pre-vaccination era (Fig. 2)[19]. It has been estimated that 2800 cases of TBE and 20 deaths(0.7% lethality of TBE in Austria) have been prevented in Austriabetween 2000 and 2006 due to vaccination [19].

H. Kollaritsch et al. / Vaccine 29 (2011) 4556– 4564 4561

Table 2Overview of TBE in six countries in Central and Eastern Europe.

Country TBEnotifiable

TBE incidence TBE risk (assessed by nationalauthorities)

TBE vaccination recommendations

Austria [27]√

Incidence: 0.82 per 100,000population per year(2003–2007) [1]

National reference centre for TBE:Department of Virology, MedicalUniversity of Vienna (data collectionand diagnosis)

National vaccination programme [43]

Mortality rate: 0.7% [19] National Advisory Committee onImmunization Practices (immunizationrecommendation)

Initial dose: adults and children >1year of age

All individuals residing, working ortravelling in an endemic area

Boosters

First booster dose after 3 yearsSubsequent booster doses every 5

yearsBooster dose every 3 years for

those >60 years of age

Czech Republic√

Incidence: 5.42 per 100,000population per year (2007)[1]

National Institute of Public Health,Prague (Státní zdravotní ústav, Praha,SZU):

Vaccination recommended for:

Mortality rate: 1–5% [53] Recreational outdoor activities Residents in endemic areasNo professional risk People visiting endemic areas (for

recreation)Endemic areas expanding in the last

30 years – new fociFamilies often ask for children to bevaccinated

Not only full-time residents but alsothose from distant cities with holidayhouses, retired people living in foci forthe summer months (May–September)

Increasing age of TBE patients:Increasing numbers of vaccinated

children and youngstersRetired people being more active

Estonia√

Incidence: 13.3 per 100,000population per year (2009)

National Health Board Estonia(Tervis-eamet)

No national TBE vaccination policy

Risk areas at the present time:Saaremaa, Pärnumaa, Ida-Virumaa,Läänemaa

TBE vaccination is recommended forthe risk groups (as already indicated,people who participate in recreationalor occupational outdoor activities)

No official monitoring of risk areasbut Health Development Institutecollected samples in these areas

Risk groups: people withrecreational or occupational outdooractivities:

Forest workersFarmersHuntersCampersMilitaryOther populations living in

endemic areasHungary [31,32]

√Incidence: 2.7 per 100,000population per year(1977–1996); 0.68 per100.000 population peryear (1997–2008)

Western Hungary is homogenously atrisk of TBE; one-third of the Easternpart of the country is also infected.

Vaccination against TBE is mandatoryin groups whose work puts them at adefinitive risk for TBE (e.g., forestryworkers and farmers, since 1998)

Mortality: 0.7%(1997–2008) No lethalcases in 2008.

There are no relevant data on thespreading of TBE-endemic areas.

5–15% of the total population isimmunized

Tick infection rate is 1/10,000–1/1000 Significant decrease in TBE incidencefollowing introduction of vaccinationcampaign

Lithuania√

Incidence: Average 1.7cases per 100,000inhabitants per year(January–October 2009)[26]

All of Lithuania is considered endemicfor TBE

There is no official vaccinationprogramme

There are no specified high risk groups Vaccines are given on a private basisonly

The incidence of TBE is randomlydistributed among different groups ofthe population

Vaccination rates in Lithuania are verylow

Additional risk might be associatedwith the common consumption ofunpasteurized dairy products

4562 H. Kollaritsch et al. / Vaccine 29 (2011) 4556– 4564

Table 2 (Continued)

Country TBEnotifiable

TBE incidence TBE risk (assessed by nationalauthorities)

TBE vaccination recommendations

Poland [39,42]√

Incidence: Approximately0.5 cases per 100,000population per year(1998–2008)

TBE incidence is highest innorth-eastern Poland (10–15 timeshigher in comparison with the rest ofthe country, particularly in Podlaskieand Warminsko-Mazurskievoivodships)

TBE vaccination is recommended forresidents of established endemic areas,in particular for military personnel,border guards, fire fighters, farmersand tourists

Mortality rate:(1998–2006) <0.5 cases per100,000 inhabitants peryear

Fatal outcome of TBE is rare (0.3% of allcases) but late sequelae observed up toa quarter of patients [54,55]

Compulsory vaccination for forestryworkers employed by National Forests(since 1994)

Additional risk might be associatedith thnpast

TBE vaccination coverage has steadily

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The majority of the six countries reported here do not have aBE vaccination programme in place (Table 2) or national guide-ines available to them; consequently, vaccination rates differramatically, with Austria having the highest rate (88%) and otherBE-endemic countries ranging from 6% to 38% vaccination cover-ge [6].

Reimbursement policies for TBE vaccination in the six countriesre presented in Table 3. Reimbursement varies between countries,ith Austria having full reimbursement for those people at occu-ational risk of TBE and partial reimbursement for the rest of theopulation [27]. In Hungary, people at risk due to their occupa-ion must be vaccinated by order of the epidemiological statuteJune 1998), and the total cost is covered by the governor. Theational Centre for Epidemiology advises vaccination for everyerson who lives in or visits endemic regions of Hungary [32]. In

ractical terms, this implies that almost every person who lives inungary should be vaccinated, because the majority of the popu-

ar recreational/holiday areas are within endemic regions. For the

able 3BE vaccination reimbursement in six countries in Central and Eastern Europe.

Country TBE vaccination reimbursement

Austria [27] Vaccination is fully reimbursed for people whoare at risk due to their occupation (e.g., forestryworkers and farmers)For the general public, vaccination is offered ata reduced cost for the first 6 months of the year

Czech Republic Reimbursement of the third dose of vaccineonly

Estonia TBE vaccination is not reimbursed for thegeneral population, although the military isroutinely vaccinated

Hungary [57] For Encepur® (Novartis Vaccines andDiagnostics GmbH, Marburg, Germany) 25% ofthe vaccine cost is covered by the NationalHealth Insurance CassaFSME-IMMUN® (Baxter International Inc.,Deerfield, IL, USA) is not currently reimbursed

Lithuania Forestry workers may have costs of TBEvaccination covered by their employer

Poland [42] TBE vaccination is recommended but notreimbursed generallyCompulsory vaccination for forestry workersemployed by National Forests (since 1994) isreimbursed by employerTBE vaccination is recommended in thenational vaccination programme for 2009 forresidents in established endemic areas, inparticular for military personnel, borderguards, fire fighters, farmers and tourists, but isnot universally reimbursed

e consumption ofeurized dairy products [56]

increased (based on official reports)from about 7500 vaccine doses in 1999to about 30,800 doses in 2008

general population, 25% of the cost of Encepur® (Novartis Vaccinesand Diagnostics GmbH, Marburg, Germany) is covered by NationalHealth Insurance, while the cost of the other available vaccine,FSME-IMMUN, is not currently subsidized.

In many countries, TBE vaccination is recommended in endemicareas, but does not form part of the national vaccination sched-ule, nor is it reimbursed. These factors may prove to be a majorbarrier for increasing vaccination uptake in these countries andthe involvement and support of governments and health insurancecompanies is paramount if nationwide vaccination programmes areto be introduced.

7. Raising awareness of TBE

As already noted, there are certain occupations (mainly the mili-tary, agricultural and forestry workers) which take place in areas oftick inhabitation and therefore place these people at an increasedrisk of tick bites and TBE infection [44–47]. In many countries whereTBE is endemic, these individuals are already aware of the risk andemployers and governments target these groups for vaccination.However, an increased interest in recreational outdoor activitiessuch as hiking and camping is placing more people in the natu-ral habitat of ticks and these groups may be unaware of the risksof tick-borne diseases [48,49]. In addition, wild berry and mush-room harvesting is a popular pastime in many countries in EasternEurope; this, combined with the socioeconomic changes followingthe dissolution of the Soviet Union and the resulting alterations inagricultural activity, have led to more people harvesting wild foodin TBE-endemic areas (specifically the elderly and unemployed)[4,50]. Travellers to TBE-endemic areas (particularly those fromcountries where TBE is not endemic) are often unaware of thedisease and the need for TBE vaccination when travelling withinEurope. As a result, travellers are not always adequately protectedagainst TBE [48,49]. The mobility of the population in general isalso resulting in greater numbers of people than before coming intocontact with ticks [48,49].

When considering the ways in which to raise awareness ofTBE, the general public, physicians and healthcare workers (inboth endemic and non-endemic areas), travellers and travel clinics(including those in non-endemic countries) as well as medicalinsurance companies, government and healthcare policy makersall need to be targeted with specific and directed educationalmaterials.

7.1. TBE awareness in the general public

In many countries TBE awareness is low among the general pub-lic; however, a nationwide campaign in Austria, using TV and radioadvertisements which included testimonials that appeared prior

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H. Kollaritsch et al. / Va

o the tick season, has led to a much greater awareness among theeneral public. A similar approach in Hungary utilized the popularress and national advertising campaigns. While media campaignsre undoubtedly a successful way to reach the public, in some coun-ries, such as Lithuania, it is difficult for healthcare professionalso target the media due to issues with funding such campaigns.his is because there are very limited resources provided by gov-rnment institutions for TBE informational campaigns; most oftenhese campaigns are supported by pharmaceutical companies (V.sonis, personal communication). National programmes on tick-orne diseases, often sponsored by vaccine manufacturers, haveeen implemented in Poland; these included a ‘tick bus’ that vis-

ted towns, providing vaccinations against TBE, which became theubject of much media coverage. Awareness of the general public inoland regarding TBE and its prophylaxis is, however, fairly limitednd people often confuse Lyme borreliosis and TBE, the two mostrequent tick-borne diseases in Poland (A. Grzeszczuk, personalommunication). In Estonia, the general public were encouragedo collect ticks and hand them in for testing during the season toighlight the importance of monitoring and reporting tick activity.owever, the public were required to pay for the testing service

hemselves. In the Czech Republic, the National Institute of Publicealth (NIPH) provides information to the public on TBE and theollaboration between the NIPH and the Czech Hydrometeorologi-al Institute produces 4-day forecasts of tick host-seeking activity,hich are also publically available.

Informing the general public about TBE, particularly in areasere the virus is endemic, is considered to be one of the most

mportant factors in increasing awareness. Advertising campaignssing the popular press, patient information resources (such asebsites, leaflets and posters) and direct recommendations byealthcare professionals are vital to remind people of the needo protect themselves against TBE. In addition to awareness ofhe disease, reimbursement (both government and private sec-or), affordability and accessibility of TBE vaccines are essential ifaccination rates are to increase across Central and Eastern Europe.

.2. TBE awareness in healthcare professionals

Healthcare professionals who reside and work in endemic areasre often aware of the seriousness and epidemiology of TBE inheir region, and effectively communicate the need for patients toake preventative measures. However, in countries where TBE isndemic only in certain regions (such as Poland), physicians fromutside these endemic areas may not be as familiar with TBE andts prevention, leaving those patients travelling to endemic areasnadvised and unprotected. As such, there is a need to educatehysicians nationwide – not just those in endemic areas. Devel-pment of European or national guidelines and case definitions,n combination with accurate TBE reporting, are essential if health-are professionals are to be kept abreast of the latest developments.here is no official TBE awareness campaign in Hungary but health-are professionals would see the regular media articles that informeople about the dangers of TBE and the preventative measureshat are available.

.3. TBE awareness in government, healthcare policy makers andedical insurance companies

Demonstrating the importance of TBE to government officialsnd healthcare policy makers is complicated and timely; in Austria,t took more than 20 years for government bodies to realise the seri-

usness of TBE (H. Kollaritsch, personal communication). In orderor TBE awareness campaigns and vaccination programmes to beredible to both the public and healthcare professionals, govern-ent backing is essential. In addition, discussion of quality-of-life

29 (2011) 4556– 4564 4563

issues in people living with the long-term neurological sequelaeassociated with TBE is important. In Austria, it has been estimatedthat the cost of TBE might have been as much as 60 million Eurosper year, if a vaccination campaign had not been in place [51];as such, careful analyses of the cost:benefit ratio of TBE vaccina-tion are required if reimbursement issues are to be overcome. ForHungary, preliminary estimations suggest that TBE vaccination is acost-effective procedure (A. Lakos, unpublished data). One way inwhich to address reimbursement issues is to open a dialogue withhealth insurance companies to educate them on the importance ofTBE vaccination.

8. Summary

While the incidence of TBE is increasing across much of Cen-tral and Eastern Europe, awareness of this disease remains lowin many countries, and the appropriate preventative measuresrequired to minimize the risk of infection largely unknown. Thesuccess of the vaccination campaign in Austria can be used as apersuasive and powerful case for national TBE vaccination pro-grammes in endemic countries, and provides an example of howsuch a campaign can work in practice. The development of consis-tent case definitions and vaccination recommendations betweencountries and nationwide disease awareness campaigns need tobe supported by both national and European bodies as wellas government agencies. Appropriate diagnosis, surveillance andreporting, combined with targeted and effective TBE awareness,is needed to help raise the profile of this important and seriousdisease.

Acknowledgements

The meeting and publication were sponsored by an unrestrictededucational grant from Novartis Vaccines and Diagnostics. Medicalwriting services were provided by Lucy Richardson, PhD, of HealthInteractions, UK.

Conflicts of interest: Herwig Kollaritsch, MD PhD has receivededucational grants from Novartis, Pfizer and Baxter and speaker andconsultancy fees from Novartis, Baxter, GlaxoSmithKline, Sanofiand Pfizer. Václav Chmelík, MD has given postgraduate lectures andreceived speaker fees. Irina Dontsenko, MD has received speakerand consultancy fees from Novartis Vaccines and Diagnostics. AnnaGrzeszczuk, MD, PhD has received financial support from Novar-tis Vaccines and Diagnostics. Maciej Kondrusik, MD, PhD, hasreceived financial support from Novartis Vaccines and Diagnos-tics. András Lakos, MD, PhD, Head of the Centre for Tick-borneDiseases, Budapest, Hungary regularly gives postgraduate lecturessponsored by Novartis Vaccines Hungary Ltd and has receivedspeaker and consultancy fees. He had a contract with Immuno-Baxter for development of a new Lyme disease vaccine (1998–2008)and has received speaker and consultancy fees. Vytautas Usonis,MD, PhD has received speaker and consultancy fees from Glaxo-SmithKline, Merck Sharp & Dohme Ltd (MSD), Novartis, Pfizer andSanofi Pasteur.

References

[1] Suss J. Tick-borne encephalitis in Europe and beyond – the epidemiologi-cal situation as of 2007. Euro Surveill 2008;13:pii=18916. Available from:www.eurosurveillance.org [accessed 1 October 2010].

[2] Donoso Mantke O, Schädler R, Niedrig M. A survey on cases of tick-borneencephalitis in European countries. Euro Surveill 2008;13:pii=18848. Available

from: www.eurosurveillance.org [accessed 1 October 2010].

[3] Arnez M, Avsic-Zupanc T. Tick-borne encephalitis in children: an update onepidemiology and diagnosis. Expert Rev Anti Infect Ther 2009;7:1251–60.

[4] Randolph SE. Tick-borne encephalitis incidence in Central and Eastern Europe:consequences of political transition. Microbes Infect 2008;10:209–16.

4 ccine

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

564 H. Kollaritsch et al. / Va

[5] Danielová V, Kliegrová S, Daniel M, Benes C. Influence of climate warmingon tickborne encephalitis expansion to higher altitudes over the last decade(1997–2006) in the Highland Region (Czech Republic). Cent Eur J Public Health2008;16:4–11.

[6] Kunze U. Tick-borne encephalitis: from epidemiology to vaccination recom-mendations in 2007. New issues – best practices. Wien Med Wochenschr2007;157:228–32.

[7] Lukan M, Bullova E, Petko B. Climate warming and tick-borne encephalitis,Slovakia. Emerg Infect Dis 2010;16:524–6.

[8] Charrel RN, Attoui H, Butenko AM, Clegg JC, Deubel V, Frolova TV, et al.Tick-borne virus diseases of human interest in Europe. Clin Microbiol Infect2004;10:1040–55.

[9] Gritsun TS, Lashkevich VA, Gould EA. Tick-borne encephalitis. Antiviral Res2003;57:129–46.

10] Golovljova I, Vene S, Sjölander KB, Vasilenko V, Plyusnin A, Lundkvist A.Characterization of tick-borne encephalitis virus from Estonia. J Med Virol2004;74:580–8.

11] Lundkvist K, Vene S, Golovljova I, Mavtchoutko V, Forsgren M, Kalnina V, et al.Characterization of tick-borne encephalitis virus from Latvia: evidence for co-circulation of three distinct subtypes. J Med Virol 2001;65:730–5.

12] Balogh Z, Ferenczi E, Szeles K, Stefanoff P, Gut W, Szomor KN, et al. Tick-borneencephalitis outbreak in Hungary due to consumption of raw goat milk. J VirolMethods 2010;163:481–5.

13] Gresiková M, Sekeyová M, Stúpalová S, Necas S. Sheep milk-borne epidemic oftick-borne encephalitis in Slovakia. Intervirology 1975;5:57–61.

14] Holzmann H, Aberle SW, Stiasny K, Werner P, Mischak A, Zainer B, et al. Tick-borne encephalitis from eating goat cheese in a mountain region of Austria.Emerg Infect Dis 2009;15:1671–3.

15] Kerbo N, Donchenko I, Kutsar K, Vasilenko V. Tickborne encephalitis out-break in Estonia linked to raw goat milk, May–June 2005. Euro Surveill2005;10:pii=2730. Available from: www.eurosurveillance.org [accessed 1October 2010].

16] Sixl W, Stunzner D, Withalm H, Köck M. Rare transmission mode of FSME (tick-borne encephalitis) by goat’s milk. Geogr Med Suppl 1989;2:11–4.

17] Dumpis U, Crook D, Oksi J. Tick-borne encephalitis. Clin Infect Dis1999;28:882–90.

18] Mansfield KL, Johnson N, Phipps LP, Stephenson JR, Fooks AR, Solomon T.Tick-borne encephalitis virus – a review of an emerging zoonosis. J Gen Virol2009;90:1781–94.

19] Heinz FX, Holzmann H, Essl A, Kundi M. Field effectiveness of vaccinationagainst tick-borne encephalitis. Vaccine 2007;25:7559–67.

20] Stefanoff P, Polkowska A, Giambi C, Levy-Bruhl D, O’Flanagan D, Damatte L,et al. Reliable surveillance of tick-borne encephalitis in European countriesis necessary to improve the quality of vaccine recommendations. Vaccine2011;29:1283–8.

21] Grzeszczuk A, Ziarko S, Kovalchuk O, Stanczak J. Etiology of tick-borne febrileillnesses in adult residents of North-Eastern Poland: report from a prospectiveclinical study. Int J Med Microbiol 2006;296(Suppl. 40):242–9.

22] Petri E, Gniel D, Zent O. Tick-borne encephalitis (TBE) trends in epidemiologyand current and future management. Travel Med Infect Dis 2010;8:233–45.

23] Niedrig M, Avsic T, Aberle SW, Ferenczi E, Labuda M, Rozentale B, et al. Qualitycontrol assessment for the serological diagnosis of tick borne encephalitis virusinfections. J Clin Virol 2007;38:260–4.

24] Epstein E, Kutsar K. Epidemiological trends of tick-borne encephalitis inEstonia. EpiNorth 2009;10:58–62.

25] Bobrowska E, Bobrowski M, Grzeszczuk A, Prokpowicz D. Immunity againsttick-borne encephalitis in healthy residents of endemic areas. Wiad Parazytol1995;41:63–70.

26] ULAC: The Centre for Communicable Diseases and AIDS. TBE inci-dence in Lithuania; 2010. Available from http://www.ulac.lt/index en.php?pl=7&#inkaras [accessed 1 October 2010].

27] Kunz C. TBE vaccination and the Austrian experience. Vaccine 2003;21(Suppl.1):S50–5.

28] Walder G, Dierich MP, Wurzner R. First documented case of infection withthe tick-borne encephalitis virus in Vorarlberg, Austria. Wien Klin Wochenschr2001;113:454–8.

29] Kríz B, Benes È, Danielová V, Daniel M. Socio-economic conditions and otheranthropogenic factors influencing tick-borne encephalitis incidence in theCzech Republic. Int J Med Microbiol 2004;293(Suppl. 37):63–8.

30] European Commission Health and Consumers Directorate-General. Tick Borne

Encephalitis. Directorate C – Public Health and Risk Assessment C2 –Health information; 2010. Available from: http://ec.europa.eu/health/phinformation/dissemination/echi/docs/TBE en.pdf [accessed 1 October 2010].

31] Lakos A, Ferenczi E, Ferencz A, Tóth E. Tick-borne encephalitis 1996–1997.Parasit Hung 2010;29–30:5–16.

[

29 (2011) 4556– 4564

32] Zöldi V, Erdõs G, Szlobodnyik J. Second guideline for protection against ticks.EPINFO 2009;16:1–61.

33] Racz GR, Ban E, Ferenczi E, Berencsi G. A simple spatial model to explain thedistribution of human tick-borne encephalitis cases in Hungary. Vector BorneZoonotic Dis 2006;6:369–78.

34] Hornok S, Farkas R. Influence of biotope on the distribution and peak activityof questing ixodid ticks in Hungary. Med Vet Entomol 2009;23:41–6.

35] Sikutová S, Hornok S, Hubálek Z, Dolezálková I, Juricová Z, Rudolf I. Serologicalsurvey of domestic animals for tick-borne encephalitis and Bhanja viruses innortheastern Hungary. Vet Microbiol 2009;135:267–71.

36] European Commission Health and Consumers Directorate-General. TickBorne Encephalitis – Number of Cases; 2009. Available from: http://ec.europa.eu/health/ph information/dissemination/echi/docs/TBE en.pdf[accessed 1 October 2010].

37] Han X, Aho M, Vene S, Brummer-Korvenkontio M, Juceviciene A, Leinikki P, et al.Studies on TBE epidemiology in Finland (and Lithuania). Int J Med Microbiol2002;291(Suppl. 33):48–9.

38] Asokliene L. Tickborne encephalitis in Lithuania. Euro Surveill 2004;8:pii=2494.Available from: www.eurosurveillance.org [accessed 1 October 2010].

39] National Institute of Public Health. Infectious Diseases and Poison-ings in Poland in 2009; 2010. Available from http://www.pzh.gov.pl/oldpage/epimeld/2009/INF 09 12B.pdf [accessed 1 October 2010].

40] Kicman-Gawlowska A, Chrzescijanska I, Stefanoff P. Meningitis and encephali-tis in Poland in 2006. Przegl Epidemiol 2008;62:253–60.

41] Prokopowicz D, Bobrowska E, Bobrowski M, Grzeszczuk A. Prevalence ofantibodies against tick-borne encephalitis among residents of north-easternPoland. Scand J Infect Dis 1995;27:15–6.

42] National Institute of Public Health. Reports on Vaccinations in Poland1999–2007; 2010. Available from: http://www.pzh.gov.pl/oldpage/epimeld/index a.html#05 [accessed 1 October 2010].

43] Impfplan 2007 Österreich; 2010. Available from: http://www.bluter.at/aktuell/Impfplan Oesterreich 2007.pdf [accessed 1 October 2010].

44] Cinco M, Barbone F, Grazia Ciufolini M, Mascioli M, Anguero Rosenfeld M, Ste-fanel P, et al. Seroprevalence of tick-borne infections in forestry rangers fromnortheastern Italy. Clin Microbiol Infect 2004;10:1056–61.

45] Cisak E, Sroka J, Zwolinski J, Uminski J. Seroepidemiologic study on tick-borneencephalitis among forestry workers and farmers from the Lublin region (east-ern Poland). Ann Agric Environ Med 1998;5:177–81.

46] Cisak E, Chmielewska-Badora J, Dutkiewicz J, Zwolinski J. Preliminary stud-ies on the relationship between Ixodes ricinus activity and tick-borne infectionamong occupationally-exposed inhabitants of eastern Poland. Ann Agric Envi-ron Med 2001;8:293–5.

47] Tomao P, Ciceroni L, D’Ovidio MC, De Rosa M, Vonesch N, Iavicoli S, et al. Preva-lence and incidence of antibodies to Borrelia burgdorferi and to tick-borneencephalitis virus in agricultural and forestry workers from Tuscany, Italy. EurJ Clin Microbiol Infect Dis 2005;24:457–63.

48] Suss J, Kahl O, Aspöck H, Hartelt K, Vaheri A, Oehme R, et al. Tick-borne encephalitis in the age of general mobility. Wien Med Wochenschr2010;160:94–100.

49] Banzhoff A, Broker M, Zent O. Protection against tick-borne encephalitis (TBE)for people living in and travelling to TBE-endemic areas. Travel Med Infect Dis2008;6:331–41.

50] Sumilo D, Bormane A, Asokliene L, Vasilenko V, Golovljova I, Avsic-Zupanc T,et al. Socio-economic factors in the differential upsurge of tick-borne encephali-tis in Central and Eastern Europe. Rev Med Virol 2008;18:81–95.

51] Schwarz B. Health economics of early summer meningoencephalitis in Austria.Effects of a vaccination campaign 1981 to 1990. Wien Med Wochenschr1993;143:551–5.

52] Holzmann H. Diagnosis of tick-borne encephalitis. Vaccine 2003;21(Suppl.1):S36–40.

53] Beran J. Tickborne encephalitis in the Czech Republic. Euro Surveill2004;8:pii=2493. Available from: www.eurosurveillance.org [accessed 1 Octo-ber 2010].

54] Jezyna C, Ciesielski T. Late neurological sequelae of tick-borne encephalitisin the population of the Olsztyn province. Neurol Neurochir Pol 1977;11:505–10.

55] Jezyna C, Zajac W, Ciesielski T, Pancewicz S. Epidemiologic and clinical studiesof patients with tick-borne encephalitis from northeastern Poland. ZentralblBakteriol Mikrobiol Hyg B 1984;178:510–21.

56] Jezyna C, Weglinska T, Nawrocka E, Falecka W, Wielizcko-Gebska L, Rodkiewicz

T, et al. Milk-borne outbreak of tick-borne encephalitis in Olsztyn Province.Przegl Epidemiol 1976;30:479–89.

57] Országos Egészségbiztosítási Pénztár. Végleges Publikus Gyógyszertörzs; 2010.Available from: http://www.oep.hu/portal/page? pageid=35,20982634& dad=portal& schema=PORTAL [accessed 1 October 2010].