Central European tickborne encephalitis (TBE) is a viral disease of
the central nervous system [1,2]. This infection due to the central
European subtype of TBE virus usually progresses biphasically (viraemic
phase, then neurological phase). Often, the infection is asymptomatic
or influenza-like,. It develops to the second phase only a third of
cases. Patients are hospitalised mainly during the neurological phase.
Symptomatic syndromes of TBE include aseptic meningitis, meningoencephalitis,
and meningoencephalomyelitis. To confirm the diagnosis of TBE, serological
testing and demonstration of specific IgM in the acute phase, or a significant
rise in antibody titre is required. All serological IgG tests show cross-reaction
with other flaviviruses . In Poland only enzyme-linked immunosorbent
assay (ELISA) tests are used. Diagnostic procedures to confirm TBE infection
based on available tests were published by the National Institute of
Hygiene . Because of the lack of a commonly accepted case definition,
regional health providers use different diagnostic protocols to confirm
the diagnosis of TBE.
In Poland, serologic surveys of more then 20 000 foresters and 17 000
blood donors were done in the 1960s and 1970s . Antibodies against
the TBE virus were found in 0.5-6.5% of population in different regions
and in 7.0-27.0% of foresters. Serologic data has enabled the identification
of regions with particularly high infection rates.
Reporting of TBE cases is mandatory in all central European countries.
Thus, cases have been reported in Austria, Byelorussia, Bulgaria, Croatia,
Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece,
Hungary, Italy, Latvia, Lithuania, Norway, Poland, Russia, Romania,
Slovenia, Slovakia, Sweden and Switzerland [6,7]. The largest number
of cases are reported from countries in central Europe. Increasing
reports from areas that were previously disease-free (Norway, northern
Russia, the Netherlands) have been attributed to global warming and
increases in rodent and tick populations .
Most of the previous descriptive TBE studies were of hospitalised
TBE patients with a neurological presentation [9,10]. Asymptomatic
or forms with few symptoms are probably not diagnosed and/or taken
into account during consultation. There is a notion of tick bite in
56% to 90% of cases . Patients had often been involved in professional
forest activity (56%) or occasional forest activity (48%) . There
were also several prospective follow-up studies gathering information
about long-term prognosis and possible risk factors [11,12]. The primary
weakness of these follow-up studies was the lack of control groups
needed to assess risk factors.
TBE surveillance in Poland is integrated into the ongoing communicable
disease reporting system. Reporting of TBE cases as a separate syndrome
began in 1970, but no uniform case definition was used. Typically,
after a medical provider reports a clinically suspected case of TBE-related
encephalitis, an epidemiologist from the District Health Department
completes the standardised TBE surveillance report. The forms are sent
to the National Institute of Hygiene (NIH) in Warsaw, where they are
processed. The incidence information is published in bi-weekly surveillance
reports sent to all local health departments and subscribed healthcare
providers. Annual reports on tickborne encephalitis are prepared in
the Department of Epidemiology of the National Institute of Hygiene.
The annual number of reported cases changed dramatically with the introduction
of new serologic tests and a countrywide educational campaign in 1993
[FIGURE 1]. Between 1970-1992, only 5 to 50 cases were reported each
year. From 1993, 100-350 cases have been reported annually. More than
80% of cases were reported from two northeastern provinces of Poland:
Podlaskie and Warminsko-mazurskie. These two provinces are mostly rural
and have more tourist traffic, compared with country average. Their
forestation rate is similar to country average.
The aim of the study was to assess the usefulness of the newly introduced
case definitions for differentiation of confirmed, probable and possible
cases within the Polish communicable disease reporting system. A descriptive
analysis of data was performed, with a comparison of cases by case
The TBE reports from the years 1999-2002 were analysed using a new
case definition, developed by a working group at national level [TABLE
1]. These case definitions will be implemented in 2005. The forms for
years 1999-2002 were used in this study because there were administration
reforms in 1998, which affect geographical comparisons of data before
and after 1998. Based on data obtained, TBE cases were classified as
confirmed, probable and possible cases. Newly defined case groupings
were compared by year, season of onset, gender, age group, residential
area type, occupation, clinical course and geographic location. Geographic
comparisons were performed only for provinces where more than 10 cases
were reported during the period 1999-2002.
Data was analysed using SAS software (version 8.2, SAS Institute,
Carey, NC, USA). All variables were categorised. Cases were compared
using case definition groups with the chi-square test. A logistic model
was used to detect factors predicting the probability of being classified
as a confirmed case.
From 1999 to 2002, 607 cases of TBE were reported to Poland’s
national surveillance system. A total of 386 (63.6%) patients were
males and 221 (36.4%) were females. Three hundred thirty one (54.5%)
cases lived in rural areas and 276 (45.5%) in urban areas. There were
no large differences in the number of cases by age group. By occupation,
the largest groups were unemployed (108 cases; 17.8%), retired (106
cases; 17.5%), students (95 cases; 15.7%) and farmers (74 cases; 12.2%).
All patients with TBE were hospitalised. The most common signs and
symptoms in TBE cases were fever (581 cases, 95.7%), headache (580
cases, 95.6%), meningeal symptoms (479 cases, 78.9%), vomiting (385
cases, 63.4%), muscle pain (151 cases, 24.9%), and respiratory infection
(105 cases, 17.3%).
More severe signs and symptoms were less common, including loss of
consciousness (85 cases, 14.0%), cerebellar symptoms (38 cases, 6.3%),
pyramidal symptoms (22 cases, 3.6%), limb paresis (22 cases, 3.6%),
and cranial nerve palsy (12 cases, 2.0%). Based on these clinical signs
and symptoms, 606 (99.8% of cases) could be classified into one of
three clinical syndromes [TABLE 2]. Three patients died, giving a four
year case fatality rate of 0.5%.
Of the 607 cases reported, 602 (99.2%) could be classified as a possible,
probable, or confirmed case [TABLE 3]. Four cases could not be classified
because their symptoms started after the tick activity season. One
person didn’t meet the clinical compatibility requirement and
had been diagnosed exclusively on serologic results. 153 patients (25.4%)
were confirmed TBE cases, 343 (57.0%) were probable cases and 106 (17.6%)
were possible cases.
There was a significant difference in case classification by gender
with 28.6% of male cases classified as confirmed, compared with 19.7%
of female cases (chi2=10.48, p=0.0053) [FIGURE 2]. There was a significant
difference in case classification by clinical diagnosis: 32.4% of cases
with meningoencephalitis were classified as confirmed cases, compared
with 24.7% of cases with aseptic meningitis (chi2=11.79, p=0.019) [FIGURE
3]. The comparison of case classification by province showed highly
significant differences by region (chi2=94.36, p<0.0001) [FIGURE
4. The comparison of case classification for other demographic factors,
such as year of onset, season of onset, age, occupation, type of residence
(urban/rural), revealed no significant differences.
The probability of being classified as a confirmed case was modelled.
Controlling for geographic location, males were more likely to be classified
as confirmed cases, compared to females (OR=1.92, 95% CI: 1.21–3.11).
Compared with other provinces, patients living in Warminsko-mazurskie
(OR=3.99, 95% CI: 1.65–10.76) and Podlaskie province (OR=1.68,
95% CI: 1.04–2.69) were more likely to be classified as a probable
or possible case. Geographical differences in case classification were
directly linked to important differences in diagnostic tests used to
confirm TBE. The serum IgM test was used extensively in Warminsko-mazurskie
(81.3% of cases were classified as probable) and in Podlaskie (45.1%
of cases were classified as probable). IgM and IgG tests of cerebrospinal
fluid were used to confirm a higher proportion of cases in Opolskie
(58.8%), Mazowieckie (52.6%), and Malopolskie (50.0%) provinces.
TBE is an emerging disease spreading from central Europe to western
and northern Europe, possibly because of climate change. The disease
is endemic in the northeast of Poland with approximately 200 cases
a year reported countrywide. For appropriate monitoring of TBE trends,
a uniform and valid case definition should be used in European countries.
This need is illustrated by the observation that only 25% of cases
reported in Poland in 1999-2002 had sufficient diagnostic tests to
meet the criteria of a confirmed TBE case. The fact that male TBE cases
were more likely to receive a confirmatory diagnosis, needs to be further
investigated. The higher incidence of TBE among males may reflect more
rigorous investigation. Interview, follow-up and diagnostic procedures
were not uniform across various regions of Poland.
Local health departments used different surveillance forms and hospital
laboratories used different ELISA tests, resulting in reporting differences.
Some endemic northeastern regions of Poland, particularly Warminsko-mazurskie
province, were less likely to perform confirmatory diagnostic testing
of the cerebrospinal fluid and were more likely to rely on serologic
results. The introduction of a new case definition will help to standardise
procedures and encourage proper diagnostic methods. Finally, a more
accurate surveillance system is crucial to better focus preventive
campaigns including immunisation.
The case report form needs to be modified to collect missing information
(e.g. residing or visiting an endemic area). Forms of infection that
are not symptomatic and which are typically not hospitalised should
be included as probable illnesses, based on epidemiological or serological
evidence. Also, the case report should include the presence of tick
bite and risk factors related to exposure (i.e. forest activities).
The present criteria for suspect cases are insufficient to differentiate
TBE from other illnesses involving meningitis. Additionally, since
a viral isolation test was never used to confirm TBE over a 4 year
period, the usefulness of this diagnostic test should be reviewed.
The implementation of the new case definition needs to be linked to
better education about the appropriate diagnosis of the disease and
the need for standard, uniform diagnostic protocols. There is a need
to modify diagnostic procedures in clinical settings. Carrying out
lumbar puncture should be more systematic for diagnosis confirmation
and for the elimination of potential differential diagnosis (herpetic
meningoencephalitis, neuroborreliosis, etc.). Moreover, an effort to
carry out a second serologic examination seems necessary, especially
in cases with no neurological symptoms that are not hospitalised.