Tick-Borne Encephalitis (TBE)

Tick-borne encephalitis (TBE) is a preventable disease, which is rapidly becoming a growing public health problem in Europe and other parts of the world. So far no causal treatment is possible but a very efficient, safe and well-tolerated vaccination is available to ensure the necessary protection.

At least 10.000 cases of TBE are referred to hospitals each year, yet the incidence of TBE is so far not fully recognized. The reason for this is that TBE produces clinical feature similar to those of many other types of meningitis and/or encephalitis.


Until recently TBE was believed to be a rather limited problem in a few well-defined endemic areas; however, this notion has now been revised. In addition the increasing mobility of people exacerbates the risk of infection.

In order to provide an effective contribution to public health in general and, in specific, to encourage the control of TBE, an international effort has now been launched, with the aim to alleviate this situation. As a first step towards this objective, renowned international experts on TBE have created a new body: The International Scientific Working Group On Tick-Borne-Encephalitis (ISW-TBE).

The Working Group is comprised of internationally recognised scientific experts from endemic countries with extensive personal expertise in the field of TBE and a high level of commitment to improving the region’s knowledge of and response to the issue TBE.

The main aims of the ISW-TBE are:

  • To promote national and international collaboration on TBE, both scientific, medical and regulatory
  • To stimulate and co-ordinate applied and basic research on TBE
  • To contribute to training and educational programmes in the field
  • To provide high-quality information on TBE and promote appropriate distribution
  • To promote and align international standards on epidemiological TBE surveillance
  • To define and promote proposals to harmonise national and international policies on TBE prevention
  • Through the above activities to gain recognition as an independent advisory committee to national and international health authorities as well as to scientific and medical professions.

In order to achieve its stated objectives the ISW-TBE has defined the following major activities:

  • To provide state-of-the-art reviews on TBE-immunization policies
  • To publish a semi-annual bulletin, offering news, editorials, reviews, commentaries and epidemiological reports
  • To organise appropriate national and international meetings
  • To participate in scientific meetings (presentations, workshops, symposia) appropriate for the discussion of TBE
  • To publish relevant information, guidelines and results in high-quality scientific journals

TBE: Characteristics of the problem

Tick-borne Encephalitis is a communicable disease caused by a flavi-virus, infected ticks being the main vectors. At least 10.000 cases of TBE are referred to hospitals each year, yet the incidence of TBE is so far not fully recognized. The nervous system is affected, at least four clinical features of different severity are observed: meningitis, meningoencephalitis, meningoencephalomyelitis, meningoradiculoneuritis.

Hospitalisation varies between days and months; some cases need many years of treatment and rehabilitation measures.

Just recently one patient died after two years of coma. A 20 year old male patient developed a severe TBE after being biten by a tick in an endemic region. He was not vaccinated. He stayed for inpatient treatment (9 months) in three different hospitals, survived in a apallic syndrome and finnaly died two years after onset of TBE. (Binder L.: Frühsommer-Meningoenzephalitis (FSME) in Österreich: Übersicht über Erkrankung und Impfung mit Fallbericht (In: H.Mittermayer, M.Pietsch (Hrsg.): Impfmanagement – Qualitätssicherung in der Prävention. 2. Erweiterte Auflage, 1998)

In Austria TBE used to be the most important viral disease affecting the central nervous system; this situation has changed due to the impact of vaccination.

No specific therapy for TBE is known so far.

TBE can only be diagnosed accurately by means of laboratory techniques, as the clinical symptoms are usually not specific for the disease.

  • TBE has become an international public health problem also because of increasing mobility of people travelling to risk areas.
  • Austria has gained a lot of experience by trying to control TBE and should be able to support other countries to establish and expand their own efforts.
  • TBE is very easily prevented by vaccination.
  • TBE is much easier to be prevented than the other tick borne disease namely Lyme-Borreliosis.
  • Social Marketing including public awareness campaigns is necessary to create problem awareness towards TBE.
  • Information measures are needed to reach as well the general public as the professional community; international efforts should be able to supplement the necessary local information measures.
  • New epidemiological projects could be performed on an European level by following up the hypothesis of underestimating the impact of TBE.

TBE could serve as an example of international cooperation

  • Which helps to control a preventable disease which is underestimated in Europe
  • Which allows the rapid dissemination of accumulated know how regarding vaccination programmes and public health aspects of a communicable disease
  • Which is very much related to occupational risk situation on the one hand by also to mobility of people on the other hand
  • Activities to control TBE on the level of the European Community therefore would create a considerable public health benefit.

Clinical impact of TBE

Incidence and severity of TBE in relation to other CNS viral diseases

According to a study conducted in 1958, the proportion of TBE in the total number of CNS viral diseases in Austria was 56%. Thus, before the start of the vaccination programme, it was the most important and most frequent disease of this type in adults, with several hundred cases being reported each year. In Switzerland, in 1981 TBE ranked fourth among viral infections of the central and peripheral nervous systems, only picorna, mumps and varicella zoster infections were more frequent. In some cantons, however, it was the most frequent cause of CNS diseases. In Germany, TBE accounts up to 50% of all viral diseases (Kaiser, verbal communication 1998).

Clinical course and manifestations

The clinical picture of TBE is characterized by a diphasic course. After a clinically silent incubation period, the initial stage of the disease starts with an elevated temperature, followed by an asymptomatic interval with remission of fever and symptoms. Not all patients, however, develop the initial stage of the disease. Another sudden rise of temperature to high values marks the beginning of the second stage.

  • The incubation period, in most cases, is between 7 and 14 days prior to the onset of the first stage, but may last from 2 to 28 days
  • The first stage on the average lasts 2 to 4 days (durations of 1 to 8 days have rarely been observed, and corresponds to the viraemic phase. It is associated with uncharacteristic flu-like symptoms with a temperature rising to 38°C in most cases. Sometimes exceptionally high initial temperatures may occur, reaching as much as 40.9°C.
  • An asymptomatic interval lasting about 8 days (extreme values between 1 and 20 days have been observed) follows the first stage of TBE. During this period, patients are usually without symptoms.
  • About 2 to 4 weeks following infection, 20-30% of persons carrying the TBE virus pass into the second stage of the disease, which involves the CNS and takes a far more serious clinical course. The clinical picture is that of meningitis, encephalitis, meningoencephalomyelitis or meningoencephaloradiculitis.
  • The patients run temperatures that are often higher than temperatures associated with other forms of viral meningitis or meningoencephalitis. The main symptoms of meningitis are severe headache, nausea and retching, nuchal rigidity, and high fever. Encephalitis is characterized by disturbances of consciousness ranging from somnolence to sopor and, in rare cases, coma. Other symptoms include restlessness, hyperkinesia of the muscles of limbs and face, lingual tremor, convulsions, vertigo, and speech disorders. When cranial nerves are involved, mainly ocular, facial, and pharyngeal muscles are affected. In some cases, the symptoms are dominated by mental disorders, and the patient is first sent to a psychiatric ward. Symptoms of polyradiculitis occur 5 to 10 days after the remission of fever; they are usually accompanied by a paresis of the shoulder girdle. Paralysis may progress up to 2 weeks, followed by a moderate tendency to improvement.

Blood count

The typical changes in blood count in TBE are as follows: With the onset of the meningoencephalitic stage, leukopaenia – which is observed during the first stage of the disease and the asymptomatic interval – disappears. It is followed by transient leukocytosis with leukocyte counts that are considerably higher than in other forms of viral meningitis (6.600-4.600/mm3). Usually, leukocytosis changes into leukopaenia before normalisation of the blood count is observed after some time. The blood sedimentation rate may be as high as 100 mm/hr.

Cerebrospinal fluid

Pleocytosis (mainly lymphocytes) is observed in the cerebrospinal fluid, reaching maximum values of 5,000/3 cells. Pandy´s reaction is almost invariably positive by the beginning of the second stage of the disease, with protein values ranging between 50 and 200 mg%. Usually it takes 4-6 weeks for the CSF values to normalise, but in individual cases elevated values may persist for several months.

Prognosis

Hospitalisation is usually required for about 3 weeks; however, in severe cases it may last much longer, sometimes even years. In children and juveniles, meningitis is the predominant form of the disease; this is why the infection usually takes a milder course than in adults. Nonetheless, severe cases have been reported even in young children. With rising age of the patients, especially in persons older than 60, TBE increasingly takes a severe course leading to paralysis and sometimes ending in death.

Not all persons infected with TBE virus run the entire course of the disease. In about two-thirds of them the infection remains silent, though viraemia can be demonstrated, or they show the clinical picture of the initial stage of TBE, but then the symptoms subside without developing into the second stage.

About one-third of those infected develop the second stage of TBE. 50-77% of these patients run the typical diphasic course of the infection. In the remaining 23-50% the infection is inapparent during the first stage, and the onset of clinical illness coincides with the beginning of the second phase of the disease.

Post-encephalitic syndrome

Although severe manifestations usually subside after 1 to 3 weeks the convalescence period may be very long.

The incidence of sequelae following TBE varies between 35 and 58%. In Austria, 10-20% of patients with a severe course of TBE have been reported to develop long-term or permanent neuro-psychiatric sequelae after the symptoms of the acute phase have subsided. These sequelae include severe headache, lack of concentration, depression, disorders of the autonomic nervous system, hearing impairment and mood disorders. Next in frequency are residual pareses and atrophies in 3-11%. Usually the pareses tend to remit, but muscular atrophies may persist in rare cases. In some patients a spasmophilic tendency has been observed for as long as 4 years following TBE infection. This syndrome causes major expenses both to the health care system and society as long-term working disability ensues. Moreover the long-lasting sequelae have a substantial impact on the patients´ quality of life.

Social Economic Aspects of TBE-vaccination

The incidence of TBE is underestimated, even in countries where the disease is known. There must still be European regions where TBE occurs and is not yet diagnosed properly.

The consequences of the disease including its economic impact could be prevented, especially by vaccination.

The TBE vaccine was introduced in Austria in 1967 and the vaccination programme was successful to control TBE in Austria. Most probably up to 1000 cases occurred in Austria before the TBE problem was studied in detail and control measures became effective. Now, 1999 the incidence has declined to 41 cases as a result of preventive immunization. Nevertheless it should be possible to reduce incidence in Austria further if the necessary vaccination strategies are applied consequently.

If one compares the incidence of TBE in Slovenia and Austria the impact of preventive measures becomes very obvious Slovenia (population approx. 2 million) experienced 492 hospital cases in 1994, very low immunization rates being the most important explanation; Austria (population almost 8 million) registered 178 hospital cases in the same year.

In endemic areas people need protection who are in contact which nature and enjoy outdoor life or experience high risk occupational situations.

It has been and still is an essential task of science-oriented social medicine to integrate the concept of social marketing into public health care. On principle, marketing means all measures that are oriented towards catering for the needs of target groups (this may be customers in economic life, patients in public health care, or persons who want to receive preventive measures).

Fatal consequences of the disease and the economic impact of sequelae could easily be prevented by vaccination.

As far as the safety of the vaccine used in Austria is concerned, most extensive studies including all epidemiological methods have been performed over the last couple of years demonstrating at the vaccine is not only efficient but also safe.

We mostly deal here with socio-medical aspects of vaccinations.

By further developing immunization programs into a general concept of immunization by vaccines we should be able to put the potential benefits of preventive medical care better into effect than before because such a concept based on clearly defined public health objectives provides strategic and tactical measures and, what is even more important, also includes evaluation.

So far, the basic question has been: “Who shall be vaccinated?” Very detailed recommendations have been worked out for that purpose, and some have led to highly complex definitions of which groups should be protected by a particular vaccine.

For the future, we will have to reconsider if this question should not be asked the other way round, that is: “Who should not receive a certain vaccination?” based on the hypothesis that this approach may simplify many decision making processes. This would also guarantee optimal information for different target groups in the public health care system but mostly for the general public.

TBE-Cases

For quite some time TBE (tick-borne encephalitis) was regarded as a rather local problem in some countries. Now it is becoming obvious TBE is an infection disease of increasing importance and reaches epidemic proportions in many parts of Europe and Asia.

Number of reported cases of TBE from various European countries and Russia

Country1990199119921993199419951996199719981999200020012002
Albania8
Austria8912884102178109128996241605460
Belarus220506697677826236118
Croatia23602776875957252426182730
Czech R.193356338629613744571415422490719411647
Denmark14311
Estonia376816316617717517740438718527221590
Finland91425162310191712413338
France2125461125002
Germany44142118306226114211148115133253226
Hungary22244142118306226114211148115133253226
Italy22868811515196
Latvia122227287791136613417168741029350544303153
Lithuania91417198284426309645548171419298168
Poland848249181267257201209101170205126
Slovak Rep.142416516089101765457927662
Slovenia235245210194492260406274136150190260262
Sweden547583511166844766453133128105
Switzerland26376644976062123681129110859
Ukraine12
Country19761977197819791980198119821983198419851986198719881989
Albania1073912825
Austria346318351677438294612242336300258215201131
Croatia84346963201131
Czech Rep.374309175598246139348172320350333178191166
Estonia6440263547431647693765
Finland234411556710
France1123
Germany811323097295026
Hungary287281245295351207406226372208218295
Italy113111
Latvia322347318220184103166133179152184246119117
Poland40543635251792025141024156
Russia13652912
Slovak republic2215344920254834783621242918
Slovenia11120927422610711465
Sweden2729252330222217415270654338
Switzerland3920314113155710321527343443

TBE in Europe

Endemic map

Topography

How to draw a TBE-map

TBE maps are usually drawn in order to identify areas where the tick bites have resulted in the transmission of TBE. Mountainous regions, areas where ticks do not occur, and where the human population has not settled, should also be taken into consideration for accurately assessing the risk of TBE infection.

On the example of Tyrol J. Moest et al. (OEAZ 12:1995) has evaluated the risk of TBE in Tyrol.

TBE risk in Tyrol

To accurately assess the risk of contracting TBE in Tyrol, consideration must be given to the topography of the region and the mobility of the population. When only the locations with documented TBE virus infection are entered into a map of Tyrol, the region appears to be almost TBE-free in relation to the total area of Austria.

A completely different picture, however, is obtained when Tyrol’s special topographic conditions as a mountainous area are taken into account. All the known TBE natural foci are located within the 7°C annual isotherm, which, on average and apart from single, particularly sunny locations, comprises regions below 1000 meters of altitude. It is only within that area that a tick population density sufficient for maintaining a TBE natural focus must be expected. While feeding on their host animals, ticks may be carried several kilometers through a forest area and thus cause a new natural focus to form. Therefore, TBE natural foci may be encountered also within a radius of up to approximately 10 km of a documented location of TBE infection (= areas with TBE risk). Although these TBE risk areas cover only about seven percent of the total area of Tyrol, they correspond to the major part of the area in which ticks are able to propagate. Regarding the TBE risk in the Inn valley, the question arises whether the gaps between Kufstein and Wörgl and between Innsbruck and Telfs may perhaps only seem to be TBE-free because no infections happen to have been reported from these areas. A glance across the Tyrol borders clearly shows that the endemic areas continue with almost no interruption into the inner Alpine valleys of the Inn and the Drau in the eastern part of upper Bavaria and in Carynthia, respectively. This also explains why there are TBE foci in the upper Inn valley, but not in the neighboring Lech valley in the Ausserfern (Reutte district).

The population as well has settled mainly below 1000 meters. A comparison of the three maps shows that most of the populated areas (= settlements plus adjacent recreational areas) are within the TBE risk zone. Even if TBE is markedly less frequent in Tyrol than, for example, in Styria, the majority of the population is, in principle, at a potential risk for TBE infection. Assessment of the individual risk depends not only on the place of residence, but also and above all on the type of spare time activities and the extent of mobility. This aspect in particular should be the basis on which a decision for or against a TBE vaccination should be made.

A) Location of infection

Location of infection
B) Risk areas

Risk areas
C) Population density

Population density

Screening for TBE

On an international basis it will be necessary to set up a systematic serological screening programme starting from clinical diagnosis meningitis and/or encephalitis in order to find out whether TBE is importance also in parts of Europe (and Asia) where a diseases not yet known or under estimated.

So far the TBE problem was very often discussed among virologists, preventive medicine specialists, but not too often among neurologists and psychiatrists.

Neurologists and psychiatrists experience the clinical burden and see the outcomes of TBE infections and should therefore be very important in promoting the issue of public health and prevention.

Basis analysis

The base analysis is the demonstration of the clinical relevance. Describing cases best does this. We have to go first into neurological hospitals for investigating stored patient samples. Here we have to screen the smallest number of samples. It is the cheapest way. But we have to take care, that all laboratory tests are confirmed by NT (neutralization test).
As we´ve learned, a single case in sometimes not enough to convince opinion leaders, authorities and the majority of the GP´s. But if we have a single case, we know already that the virus is present. So we have to look for proofs only.

Summarized procedures

  • To screen populations in selected areas, a stratified procedure is required. To describe the real epidemiological situation. Several surrogate markers have to be used.
  • The best one is a good described clinical case, with a whole spectrum of clinical and laboratory investigations which has to included.
  • If no cases are known in the respective areas, we have to lock for the presence of the virus. Checking various populations can do this. The proof of the virus by PCR is the strongest argument. All other investigations lead to surrogate makers only.
  • If the virus is present and no clinical cases is observed, we have to make the physician aware. It´s mostly caused by lost awareness for the disease. Other diagnoses were falsely used instead of TBEV infection: under diagnosis. How to do this? Publication in the local journals, contacting authorities, also by including them in the ongoing investigations.
  • If nothing known about the virus and case, we have to start with small investigations in neurological clinics. The second step is the investigation of the primary and animal viral hosts. The last has to be the detections of the virus itself by collecting ticks.

The registration and publication of the discovered endemic areas is also very important for whole Europe. Travelling also in the potential endemic areas like Eastern European countries is increasing.

Case Bornholm

Following a meeting in Copenhagen on the topic of TBE in February 1999, the first cases of TBE have now been reported from the island of Bornholm in Denmark. The finding of the three cases reported below; show the importance of considering also the screening for TBE induced meningitis.

In EPI-NYT 33/1999, the Department of Epidemiology of the Danish State Serum Institute reported on the first ever-confirmed cases on TBE in Denmark.

The first case was found in a 41-year-old male who was hospitalised for 12 days in June 1998. After approximately one year with persistent sequelae including tiredness and reduced memory the patient was screened and found positive for TBE. The patient lived on Bornholm were he spend much time in nature. The second case occurred in a 51-old-male, who was hospitalised in July 1999 with acute signs of TBE including fever, headache, dizziness, photophobia and neck pain. The patient was treated under suspicion of Borrelia and Herpes infection, which was subsequently disproved. On leaving hospital eleven days later tiredness and tremor persisted. Subsequently both IgG and IgM-TBE antibodies were detected. One week before first symptoms the patient had been on holiday on Bornholm. The third case of TBE was diagnosed in a 44-year-old male, who was submitted to hospital in June 1999 under suspicion of Borrelia infection. On leaving the hospital 6 days later the patient was still suffering from tiredness, light tremor in body and extremities as well as Raynaud-like symptoms in the fingers. Spinal fluid was found to be positive for IgG antibodies but negative for IgM. Serum testing was positive for both IgG and IgM antibodies. Approximately one month before hospital submission, the patient was bitten by a tick during a stay on Bornholm.

It is considered very likely that TBE had been transmitted to the three patients on the island of Bornholm, as they had not visited other known TBE areas abroad. Earlier investigations have shown that ticks on Bornholm may indeed carry TBE virus.

Travelling

Tick-borne encephalitis after a stay in South Germany

A 38-year-old man was admitted with signs of meningoencephalitis. Tick-borne encephalitis was considered because the patient reported a tick bite during a vacation in South Germany and because of the biphasic course of the symptoms. Serology for tick-borne encephalitis was positive; this constituted the first reported positive serology outcome in the National Institute for Public Health and Environment in the Netherlands. Tick-borne encephalitis is an infection with a flavivirus transmitted by an infected tick, which is endemic in parts of Central and Eastern Europe. The neurological symptoms are meningitis, meningoencephalitis or meningoradiculomyelitis. In a small percentage of patients neurological symptoms persist. A reliable vaccine is available, but is not routinely recommended for tourists.

(B.L.J.Kessels, R.van Dijl, P.H.J. van Keulen en G.P.Verburg: Teken-encefalitis na een vakantie in Zuid-Duitsland. Nederlands Tijdschrift voor Geneeskunde. 143.Jaargang, Nr. 35, 28.Augustus 1999)

Travelling is a phenomenon of increasing importance.

Especially during holiday seasons a peak in mobility of people is observed.

Travelling also means experiencing possible health risks of various kinds. Acquiring infectious is one of them, an established reason for concern when going to places e.g. in Africa or Asia.

European people are travelling more and more in the continent. But they don´t feel to be a traveller. Little attention was given so far to possible infections when travelling within Europe.

TBE is usually not mentioned in recommendations given to tourists who spend their vacation in endemic areas. Problem awareness is also related to the fact that meningitis and/or encephalitis patients are not screened for a possible TBE infection when diagnosed and treated outside endemic regions.

Taking into account the incubation period of TBE it is obvious: clinical manifestation will mainly occur when tourists have been returned to their home country. The case reported from the Netherlands is a typical example.

A systematic screening for possible TBE infections throughout Europe will for sure come up with many more mobility associated cases.

One could even try to calculate how many TBE cases among travellers are to be expected in countries where this disease is not very well known.

Variables in this respect are the following ones:

  • How many people move from a given country into a specific endemic area
  • At what time of the year
  • Performing outdoor activities at what level and therefore experiencing a risk of having tick contact followed by an infection, which is then leading to a clinical manifestation after coming home.

It will be possible to come up with rough estimates of e.g. how many cases should be expected in the Netherlands and systematic survey would then reveal whether the assumption was correct or not.

TBE is a growing international health problem as awareness increases and cases are identified in many European countries, even in regions where TBE so far was not diagnosed.

General preventive measures

Control of tick populations

Ticks being the chief vector of TBE virus, past efforts to fight TBE were concentrated on the control of tick population in TBE endemic areas. In former Czechoslovakia and USSR, large-scale control measures using Tetrachlorvinphos, DDT, or Hexachlor did not produce the desired effect. As the virus persists not only in ticks but also in wild animals, such measures are of no use in the elimination or even control the disease.

Protective clothes, repellents

As ticks attach to any spot on the host, and from there try to reach an uncovered part of the skin, adequate clothing (solid footwear, socks, close-fitting trousers, smooth fabrics, etc.) may help to make access to the skin more difficult for ticks.
In former Czechoslovakia, forestry workers were given protective clothes impregnated with DDT and were regularly disinfested after work.
Furthermore, a variety of repellents were used, such as diethyl toluamide, indalone, dimethyl carbate, dimethyl phthalate, and benzyl benzoate.
But these preparations afford protection for a few hours only. Moreover, there have been reports from the former USSR of ticks becoming resistant to repellents.
Protective clothes must be completely closed to be really effective, but this may be found intolerable by people spending their leisure time or holidays in endemic areas in the warm season.

Marking of endemic areas by warning signs

In Austria efforts were made to alert the population to the risk of infection in areas endemic for TBE by putting up signs. However, after misuses by local landowners the authorities desisted from this practice.
All these preventive measures directed at ticks have offered only limited protection. It was realised quite early that a vaccine was required for protection from the causative agent itself, the TBE virus.

Vaccination

Immunizations are among the most effective measures of preventive medicine. The smallpox vaccination shows how well vaccinations work: Despite frequent and unpleasant side effects vaccinations were consistently administered throughout a long period of time – with the result that, today, smallpox are eradicated.
Infantile paralysis (poliomyelitis) is another example: Due to consistent immunization this disease has not occurred for over 15 years in Austria, and possibly – in another 10 years – a vaccination against infantile paralysis may no longer be necessary.

How does vaccination work? Infectious diseases are caused by microorganisms penetrating the human body. When the human immune system encounters the penetrated pathogens, it generates substances for defense, so-called antibodies. If the immune system encounters these pathogens again at a later time, it already has a “supply” of adequate antibodies to fight the infection.

A vaccination usually consists of pathogens, that have been killed or weakened, so they do not cause disease. But they still stimulate the immune system to generate antibodies against the actual pathogen.

The event of antibody formation – the so-called “active immunization” – usually takes several weeks. Therefore, vaccinations following this principle, take a while to develop a reliable protection, which then persists for a longer period of time.

Vaccines functioning according to the principle of the “passive immunization”, supply the body with “ready-made” antibodies. They work immediately, but only for a few weeks.

The protection from infectious diseases is particularly important at the start of life, but is also of importance later on. Vaccination knows no age and is the most important measure of preventive medicine throughout life!