Budapest, 1997

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The authors describe the symptoms of tick-borne encephalitis (TBE) and the possibi .... In half of the cases involving paralysis, severe residual symptoms are left ...
Parasit, hung., 29-30: 5-16, 1996-1997

© Hungarian Natural History Museum Hungarian Society of Parasitologists

Tick-borne encephalitis

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András L A K O S , Emőke F E R E N C Z I , Adrienne F E R E N C Z Etelka T Ó T H

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Outpatient Clinic for Tick-borne Diseases, Dr. Lakos Unlimited Partnership, H-1132 Budapest, Visegrádi u. 14, Hungary

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Virology Department, 'Béla Johan" National Institute of Hygiene, Budapest, Hungary IVth Ward of Internal Medicine, "Szent László" Hospital, Budapest, Hungary (Received 17 January, 1997)

Abstract: Tick-borne encephalitis (TBE) is a rare disease which, however, often takes a severe course. Between 1968 and 1995, a total of 5,561 cases were diag­ nosed in Hungary, with a mortality rate ranging between 1 and 1.5%. Most of the fatal cases occur in young adult men. Half of the cases were recorded in the counties Zala, Somogy, Nógrád and Vas. In certain areas (in counties Tolna, Pest, Nógrád and Heves), few diagnostic tests are being carried out as compared to the number of diagnosed cases, which means that in a large number of patients the infection remains undetected. So far only 3-5% of the Hungarian population have received adequate preventive vaccination, which could not yet exert a pal­ pable effect on the epidemiological data. Key words: Tick-borne encephalitis, epidemiology, diagnosis, therapy, vacci­ nation, Hungary INTRODUCTION The authors describe the symptoms of tick-borne encephalitis (TBE) and the possibi­ lities of its diagnosis and therapy. A detailed account of the current epidemiological situation of Hungary regarding TBE is also presented, together with arguments for exten­ ding vaccination against the disease. HISTORY OF THE DISCOVERY A disease of the central nervous system, characterised by high mortality rate, was observed in the Far Eastern areas of the Soviet Union already in 1932. The aetiology of the disease was completely unclear, and the disease was usually regarded as a (toxic) influenza of very severe course. (The practice of medicine has not changed much since then: even today, if we do not know about a disease what it is, we will usually say it is influenza or caused by some kind of

virus.) Grigorievich and Tkachev were the first to demonstrate that mice inoculated with the brain suspension of a patient who had died of encephalitis succumbed to a disease that manifested itself in signs similar to those of the human disease. Initially it was believed that the virus was carried and infection was transmitted by healthy humans. It was thought that the pathogen colonised the throat and was transmitted by droplet infection and, thus, the disease could be prevented by rinsing the throat with permanganate solution. Excessive heat was also considered to be a predisposing factor: it was recommended that people should protect their body and especially their head from exposure to direct sunlight. This notion may have originated from the observation that the majority of cases occurred in the summer period. In 1937, a major expedition led by Silber started off for the taiga to elucidate the characteristics of the outbreaks. It became obvious already during the first expedition that the disease mostfrequentlyoccurred in the spring, and infection was contracted exclusively by people working on the taiga. A substantial proportion of people affected by the disease had never met each other. It was soon found out that the seasonal activity of ticks indigenous in the region almost exactly corresponded to the seasonal fluctuation of encephalitis cases. There was an only two-week time difference between the two curves, which corresponds to the average incubation period. By that time it had already become almost certain that the Ixodes tick species indigenous in the area was responsible for transmitting the disease. The hypothesis of Silber was proved by Tchumakov, who successfully infected animals with the help of Ixodes ticks. Soloviev demonstrated that the virus remained viable for a long time in several rodent species which could thus act as reservoirs. As the last step of the investigations, the researchers successfully detected the pathogen by multiple methods. As a tragic consequence of the expedition, the newly discovered virus infected several researchers. Despite the strict precautions taken to prevent infection, three scientists died during the research. Soon afterwards it was found out that the disease occurred not only in Siberia but also on this side of the Ural Mountains. In Central Europe, the pathogen was first isolated in 1948 in Czechoslovakia, then in 1952 also in Hungary (Fomosi and Molnár 1954).

THE CAUSATIVE AGENT Tick-borne encephalitis virus is a single-stranded positive sense RNA virus which belongs to the Flaviviridae family together with other human pathogens such as the causative agents of yellow fever, Japanese B encephalitis, and dengue. Its protein capsid has almost regular spherical shape. It is surrounded by a cell membrane like envelope. The virus is moderately resistant to environmental factors. Its resistance is markedly increased by protein-containing solutions.

CLINICAL SYMPTOMS In typical cases the disease course consists of two phases. The characteristic tempe­ rature curve is referred to as two-humped or dromedary type. The first phase corresponds to the stage of viraemia, when viruses having multiplied at the site of the tick bite are disseminated in the organism. That phase is usually accompanied by fever. The clinical symptoms resemble those of influenza, and include moderately high temperature, headache, muscle pains, backache, sometimes abdominal pain, and malaise. Although the disease is not

accompanied by sore throat, the pharyngeal structures are usually inflamed and sometimes conjunctival injection is also present. In such cases, medical examination usually yields the diagnosis of summer influenza. (Numerous textbooks describe the above signs of the first phase as respiratory symptoms. Here it is important to mention that TBE is not accompanied by coughing.) These first atypical symptoms can be expected to occur on days 7-14 after the tick bite, and disappear within one week even without treatment. It should be emphasised that in the overwhelming majority of the cases the disease does not get beyond the first phase, and disappears without raising the suspicion of TBE virus infection in anyone. In one-fourth of the cases, i f the first phase is deficient in clinical symptoms, the disease takes a monophasic course. The first phase is followed by an asymptomatic period lasting a couple of days, and then by the second phase. The second phase begins when the virus has entered the nervous system and starts to multiply there in weeks 2-4 after the tick bite. That phase starts with a pyrexial spike higher than that in the first phase, accompanied by dizziness, intense headache and, almost invariably, vomiting. The patients' movement becomes clumsy, and they easily stumble and fall. Occipital stiffness develops. The patients are usually somnolent but may as well be extremely restless and irritable. Restlessness and irritability may be followed by unconsciousness at any time. Convulsion occurs in a very small proportion of hospitalised patients. Based upon the clinical symptoms, meningitic, meningoencephalitic and meningoencephalomyelitic forms of the disease can be distinguis­ hed. Benign meningitis is more common in childhood. A polio-like clinical picture may occur at any age but is relatively uncommon. In every fifth hospitalised patient, encephalitis is accompanied by paralysis. In half of the cases involving paralysis, severe residual symptoms are left behind after recovery. The disease process most frequently affects the proximal muscle groups, almost always the shoulder girdle. Paralysis occurs more frequently in muscle groups which are subjected to stress during the prodromal phase. In the most severe cases the respiratory muscles also may become paralysed. Death usually sets in on day 2-30 of the nervous symptoms, as a consequence of progressive spino-bulbar paralysis or tetraparesis accom­ panied by respiratory paralysis (Jellinger 1981). The other extreme is when the virus infection passes off in an asymptomatic manner, which can be detected only by sero-epidemiological investigations. For each diagnosed case of TBE there are four symptom-de­ ficient cases of unrecognised infection (Gustafson et al. 1992). Some of the meningitic forms are also likely to remain undiagnosed, as after the intense headache and vomiting the symptoms disappear without any treatment. That benign form is common especially in childhood. However, even benign infections of a less severe course often leave behind a lasting headache, slight memory disturbances, narrowed cognitive functions, and depres­ sion. Permanent EEG abnormalities can be detected after apparent clinical recovery (Juhász and Szirmai 1993). The severity of the clinical picture may vary by period and region, as indicated by the experience gained at the Szent László Hospital (Tables 1-3). It must be added immediately, however, that not in all areas of the country has this "attenuation" of the disease been observed. Today we do not yet know what factors are responsible for differences in the course of TBE, as individual virus strains may also differ in infectivity, affinity to the nervous system, and invasive properties. However, so far only the virus strains originating from areas beyond the Ural Mountains and the European strains could be demonstrated to differ in the severity of clinical symptoms produced.

Table 1 Complaints and clinical symptoms observed on admission (in % of the patients examined) 1976-1980 n=100 Headache Dizziness Nausea Vomiting Diplopia Dyssomnia Disorientation Loss of consciousness Signs of meningeal irritation Extrapyramidal tremor Cerebellar ataxia Nystagmus

1987-1996 n = 93

75 59 37 63 15 15 43 3 38 21 21 13

76 20*** 17* 22*** 4* 3* 4*** 0 19* 2*** 2*** 11

Table 2 Incidence of paralyses on admission (in % of the patients examined) 1976-1980 n-100 Upper extremity Lower extremity Bladder paralysis Motor aphasia Frontal dementia Total

1987-1996 n = 93

'0 3 6

0.01 0^ u

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0 ^"^.*»

6 2 7

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0

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Table 3 Outcome of the disease (in % of the patients examined) 1976-1980 n=100 Completely recovered Transitory paralysis of upper extremity Permanent paralysis of upper extremity Lasting psychic disturbance Diabetes insipidus Died * P < 0.05; ** P < 0.01; *** P = 0.000

94 1 i 1 1 2

1987-1996 n = 93 98 0 0 2 0 0

PATHOLOGY Prior to invading the central nervous system, the virus undergoes intensive replication in muscle and fibroblast cells. Subsequently it enters the central nervous system primarily by the haematogenic route. During its replication in the nerve cells, it damages the neurons, then gets out into the extracellular space. In the meantime, intensive glial proliferation commences. The process is accompanied by the development o f cerebral oedema. The inflammatory reaction involves primarily the meninges and the perivascular cells and much less often the nerve roots and ganglions. Virus multiplication causes irreversible damage to the grey matter of the brain stem and medulla oblongata, and to motor neurons in the anterior horn of the cervical spinal cord. The encephalitic symptoms arise as a consequence of virus invasion and immunopathological events that give rise to the following changes: (1) nerve cell necrosis and consequent neuronophagia; (2) inflammatory reaction around the blood vessels, with serous exudation and cellular infiltration of the meninges and nervous tissue, followed by (3) spongiform focal necrosis which may be the result of anoxic or vascular lesions.

DIAGNOSIS The diagnosis of TBE can be suggested on the basis of a relevant history and the signs indicative of encephalitis. Examination of the cerebrospinal fluid (CSF) is obligatory in all cases when TBE is suspected. The CSF usually shows lymphocytic pleocytosis of around 100 and a mostly moderate elevation of the protein level. The glucose concentration of the CSF may be variable. CSF taken at the onset of the first symptoms may be characterised by the predominance of granulocytes; however, i f lumbar puncture is repeated 12 hours later, already lymphocytes will be the dominant cell type in the CSF. The CSF findings will start to improve in 5-10 days. A misleading picture may arise i f TBE occurs in association with Lyme borreliosis. Considering that both infections are transmitted by the same vector, Ixodes ricinus, chances of a combined infection are high. At a TBE symposium held in Baden in 1979 (i.e. 4 years after the first description of Lyme borreliosis), several cases of atypical course, mostly accompanied by chronic meningitis and facial palsy, were reported (Kunz 1981). It may be guessed that the unusual clinical picture observed in these cases resulted from Borrelia infection. Since Borrelia antibodies take much longer time to develop than those produced against TBE virus (Lakos 1991), Borrelia infection may remain undetected. Protracted meningitis, the steadily rising protein level of the CSF, and the symptoms failing to abate and still fluctuating after 2-4 weeks should raise the suspicion of Lyme borreliosis, and serological tests should be extended in that direction or testing should be repeated. There are no other routine laboratory deviations typical of TBE. Several authors have observed leukopenia and thrombocytopenia as well as mild hepatitis (LotricFurlan and Strle 1995). These three abnormalities, which can perhaps be regarded as unusual, are typical first of all of ehrlichiosis. The chance of a dual infection is at least 10% (Lakos 1997). Accurate microbiological diagnosis can be established primarily by serological methods, as virus isolation is expensive, labour intensive and slow. In Hungary, such investigations are carried out at the Virological Department of the National Institute of Hygiene. The most commonly used test is indirect immunofluorescence. In some cases the haemagglutination

inhibition test internationally accepted in the diagnosis of flavivirus infections is performed, and occasionally ELISA, virus neutralisation test, and virus isolation are also made use of. The early (IgM) type antibodies usually appear already in the first few days after the onset of clinical symptoms, and the rising level of IgG antibodies can also be detected by testing paired sera. Since the introduction of preventive vaccination (and especially since 1991 when the vaccine or, more recently, vaccines have been available to anybody without any restriction), vaccinations are being carried out also in periods when the risk of infection is high. This practice may be a source of diagnostic problems. This is the reason why in a total of275 cases during the past 5 years virological examination failed to yield interprétable results, partly because of the deficiency of the data provided, partly because of the limitations of the methods available. Interpretation of the tests was impeded by the fact that the patients had received some type of preventive vaccination against TBE already earlier. During the test, it could not be decided whether the antibodies detectable in the serum sample resulted from vaccination or perhaps from wild virus infection. Patients getting over a wild virus infection acquire lifelong immunity, while those vaccinated do not. The use o f other methods may be necessary in persons who have been vaccinated against some other flavivirus disease (yellow fever). It is therefore important to stress that in specific cases the lack of adequate data supply may render the serological diagnosis impossible.

TREATMENT As the disease is autonomous, only palliative treatment is possible. By the time the diagnosis can be established, the clinical symptoms which are to be prevented have already developed. The viruses have already invaded the cells of the central nervous system, the majority of which will be destroyed together with the virus. Thereafter the number of viruses will usually decrease rapidly. Several authors have achieved good results with dehydrating treatment combined with the use of steroids, while others could not corroborate these findings. Steroid treatment is justified by the observation made in animal experiments that the time of death coincides with the appearance of antiviral antibodies. Assisted respiration and the administration of anticonvulsive drugs may occasionally be necessary.

EPIDEMIOLOGY The only areas in Europe where the occurrence of TBE has not been demonstrated are the Benelux countries and the Spanish peninsula. Before the introduction of preventive vaccination, in numerous countries (e.g. in Austria) TBE was the commonest CNS disease of inflammatory origin, which it still is in countries like Slovenia where extensive vacci­ nation has not yet been accomplished (Cizman and Jazbec 1993). In recent years, the number of recognised TBE cases has markedly increased in Poland (Zabicka 1996), and the disease has appeared in France as well (Collard et al. 1993). The number of cases diagnosed in Hungary had doubled by the 1980s as compared to the 1970s; however, this probably resulted from the improvement of diagnostic techniques (Ferenczi and Molnár 1991). In Hungary, primarily the Transdanubian region and the Northern mountain range are endemically infected areas. TBE virus is transmitted to humans by Ixodes ticks. Therefore, the epidemiology of TBE depends basically on the prevalence of Ixodes ticks,

which are especially common in oak-forests and oak-forests with yoke-elms and beeches. The pine-forests of Hungary are free of ixodid ticks; however, in Dalmatia and on the Siberian taigas the major foci of infection can be found in evergreen and pine-forests as well as in juniper groves. The most important reservoirs of infection are rodents including the yellow-necked field mouse (Apodemusflavicollis), the common field mouse (Apodemus sylvaticus), the striped field mouse (Apodemus agrárius), and the common redbacked vole (Clethrionomys glareolus). Insectivorous small mammals, first of all the common mole (Talpa europaed) also have an important role in the circulation of the virus (Molnár 1983). Vertebrate animals have a complex role: (1) the pathogen multiplies in them; (2) they may act as permanent carriers of the pathogen; (3) they serve as a food source for the tick vector; and (4) they serve as a means of transport" for the ticks, i.e. play an important role in carrying the ticks from one place to another. I f we place the tick onto an infected animal, the virus will appear in the tick's salivary glands within a short time (36 hours) and start to multiply there rapidly. Infected ticks may infect the attacked host, i.e. humans as the case may be, already within 6 hours (!). The virus persists in the infected ticks for a long time. From the larval stage it gets into the nymph and then into the adult tick as well. Moreover, the virus is transmitted also by the transovarian route, which means that the larvae are infected already when hatching from the eggs. Thus, the tick itself acts as a reservoir, as it stores the pathogen for many years. In view of this fact, the relatively low ratio of virus-carrier ticks is the thing to be surprised at. The national average is around 0.05%. This means that only one in every 2000 ticks harbours the virus. At the same time, sero-epidemiological investigations indicate that 3-19% of the human population living in Transdanubia and at the foot of the Alps (in Western Hungary) have been exposed to the causative agent of TBE. About 150 - 400 people receive hospital treatment for TBE in Hungary every year. The number of disease cases was especially high in the years 1982 through 1986. During the time since registration of TBE cases was started, the number of cases tended to increase at 2- to 3-year intervals, up to 1993 (Fig. 1). Since then no further increase has been observed, which can perhaps be attributed to the spread of preventive vaccination. The death toll is 1-6 patients every year. In the period between 1968 and 1995, a total of 5,561 TBE cases were diagnosed, and the mortality rate ranged between 1 and 1.5%. The mortality rate observed in Austria was higher than that (Krausler 1981). The disease occurs in natural foci, first of all in counties Zala, Somogy, Vas, Nógrád, Komárom, Veszprém, and Győr-Sopron (Tóth et al. 1996; Fig. 2). Infection may take place, although less often, also in well-kept municipal parks. (We had a patient who was absolutely certain that the tick transmitting the infection had bitten him on Margaret Island.) Half of the cases were reported from counties Zala, Somogy, Nógrád and Vas. TBE is almost unknown in the Eastern part of the country. It should not be disregarded, however, that there may be a substantial difference between the actual number of disease cases and the number of diagnosed cases. Therefore, we looked for correlations, if any, between the number of TBE suspect samples submitted to the Virological Depart­ ment of the National Institute of Hygiene and the actual positivity rate of those samples. A significant correlation (p = 0.03) was found between the number of samples submitted for testing and the hit probability. Where more cases are observed, the likelihood of establishing a diagnosis will be higher, and the reverse of that thesis is also likely to be true. However, there are regions (counties Tolna, Pest, Nógrád and Heves) where a low number of tests are carried out, but their hit rate is strikingly high. It may be assumed that in these areas

450 400 350 300 250 200 150 100 50 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1977 1979 1981 1983 1985 1987 1989 1991 1993 1995

Fig. 1. Serologically verified cases of tick-borne encephalitis (TBE) in Hungary between 1977 and 1996.

Fig. 2. Incidence rate of tick-borne encephalitis by county. The size of the area co­ vered by the tick is proportional to the number of TBE cases diagnosed between 1991 and 1995.

serological tests are performed only in clinically unambiguous cases, which amounts to saying that infection remains undetected in a large number of patients. To illustrate the above correlations, we prepared a figure in which the counties are ranked according to an index obtained by multiplying the hit rate of tests by the absolute number of cases (Fig. 3). It is quite clear that the number of cases manifesting themselves in atypical, influenza-like symptoms and that of patients developing a mild CNS inflammation and not referred to hospital is a multiple of the cases reported. Encephalitis may be caused by a variety of other factors. I f the required laboratory tests are not performed, the origin of the disease will never be revealed.

Fig. 3. Number of diagnosed cases of tick-borne encephalitis by county between 1991 and 1995. The ranking of counties has been corrected on the basis of the number of positive cases as related to the number of samples submitted for testing (hit rate). See the text for more detailed explanation. The first disease cases usually occur in April every year, though that time varies depending on the actual weather conditions. The highest incidence is recorded in June and July. The number of cases declines in August and September, then rises again in October. The decisive majority of patients belong to the 20-50 years old age group, and 70% of them are men. The fatal cases occur almost invariably in men! Besides direct transmission with the tick's saliva, infection can be transmitted also by unscalded milk freshly milked from cows, ewes or goats.

PREVENTION Vaccines against TBE can be prescribed by any physician. Passive immunisation serves mainly for disease prevention after the tick bite. During passive immunisation, complete antibodies are administered into the organism. Such a preparation is FSME-Bulin (Immuno), which is prepared from the blood of humans having high antibody levels to the virus. The preparation is rather expensive. It is recommended only in exceptional cases: its administration is justified to persons who have suffered multiple tick bites in highly infected

regions. The inoculation provides protection only i f it is administered within 96 hours of the tick bite. Even in that case, the rate of protection is only 75%. When administered after day 4 as from the tick bite, FSME-Bulin is surely ineffective. Therefore, when justified, it should be administered as soon as possible. Its dose increases in direct proportion to the body weight and to the time that has elapsed since the tick bite. Within two days as of the tick bite, the dose is 0.1 ml per kg of body weight, while on days 3 - 4 it is twice higher. A corpulent man may require a dose as large as 20 ml. The administration of this preparation should be carefully considered (Aebi and Schaad 1994), but it can be given also before the expected tick bite, if there is not enough time for active immunisation. The duration of the protective effect is only one month. Vaccination is not recommended for three months after the administration of TBE immunoglobulins, as the latter impairs the efficiency of active immunisation (Hederström et al. 1995). Following active immunisation, the vaccinated persons themselves will produce the protective antibodies. The advantage of active immunisation that it provides lasting protection, while the drawback is that with vaccines prepared from inactivated virus multiple injections are needed for inducing and maintaining immunity. One of the available vaccines is FSME-Immun-Inject (Immuno) which was developed in 1993 and has been commercially available since 1976. This vaccine has been used for immunising persons at risk of TBE on account of their occupation since 1977. The vaccine has been available to anyone since 1991. As it contains inactivated virus, there are practically no dangerous side effects. In a few cases a rise in temperature, fever, local infiltration, headache or possibly articular pain may occur. These adverse events occur mostly after the first injection, they are much less common after the second injection and completely absent after the third one. Vaccines of different batch numbers have been shown to differ markedly in terms of the vaccination reactions induced (Vlasimska and Smejkalova 1995). No serious adverse events have been encountered. Two years ago a great scare was created by the suddenly increased number of reactions involving high fever; however, no serious complications occurred. As adverse events characterised by high fever were observed mainly in small children, the use of the vaccine in children below 6 years of age must be carefully considered. Earlier, the manufacturer prohibited the use of the vaccine in periods characterised by a high risk of tick bites, as infections acquired at the time of vaccination could have appeared to be vaccination reactions. Today such restrictions no longer exist, which means that vaccination may be started in any period of the year; however, it is advisable to choose the winter months. It must not be forgotten that a prolonged protection can safely be induced only by a basic immunisation consisting of a series of three injections. A booster injection is needed every three years. I f the tick bite occurs at least four days after the first vaccination but before the planned second injection, the second dose must be administered immediately to induce satisfactory protection. Last year a new vaccine was put into circulation by the name of Encepur (Behring). This preparation also serves for active immunisation. It has some advantageous properties: it does not contain human proteins and a mercury-containing preservative which could elicit an allergic reaction. It can be administered according to two different schemes. The manufacturer developed a rapid immunisation protocol which provides protection already by day 21 (Harabacz et al. 1992). Using that protocol, an injection each must be adminis­ tered on days 0, 7 and 21, and then in the 18th month. The other vaccination scheme is

based upon the conventional protocol: the first injection must be repeated one month later and then the third dose must be given 1 year after the second one. The booster injection administered at 3-year intervals provides long-term protection. As febrile reactions are more common in childhood, a separate vaccine, Encepur K, has been developed for use in children under 12 years of age. This contains half as much viral protein as the variant serving for use in children above 12 years and in adults. As in infants under 1 year of age TBE occurs only exceptionally (Grubbauer et al. 1992), we recommend that vaccination should be started only after 12 months of age. Encepur can be used for continuing the vaccination started with FSME Immun. Although the two vaccines slightly differ in the seed lot virus applied, animal experiments have shown that this cannot cause an appreciable difference in the protective immunity induced (Holzmann et al. 1992). Studies on vaccinated persons and animal experiments indicate that the serological results accurately reflect the presence or absence of protection (Ferenczi 1990). The rapid development of protective immunity after vaccination is ensured by the cell-mediated defence mechanism (Stephenson et al. 1995). For each new batch of the vaccine it seems to be essential to perform serological tests on a sufficient number of persons vaccinated with it. Whichever vaccine is selected for use, following the vaccination protocol in a consistent manner is the joint responsibility of the vaccinating physician and the person requesting the immunisation. Consistently accomplished and adequately performed vacci­ nation is capable of eliminating TBE. In Austria, a radical change has been achieved in the epidemiological data by vaccinating 60% of the people living in, or visiting, regions where the risk of infection is high (Kunz 1991). As in Hungary only 3-5% of the population have received adequate preventive vaccination, the epidemiological impact of that vaccination can hardly be felt. However, the efficacy of the vaccine is obvious also from Hungarian surveys: while only 1 out of 4,300 vaccinated persons became affected with TBE, 116 out of 7,500 unvaccinated persons working in the same area developed TBE during the same period (Lontai and Straub 1991).

Lakos, A., Ferenczi, E . , Ferencz, A. és Tóth, E.: A kullancsencephalitis A kullancsencephalitis ritka, de gyakran súlyos lefolyású betegség. Magyarországon 1968 és 1995 között 5561 esetet ismertek fel, a halálozás 1-1,5 % között ingadozott, a betegségnek többnyire fiatal felnőtt férfiak esnek áldozatul. A betegek felét Zala, Somogy, Nógrád és Vas megyében észlelték. Egyes területeken (Tolna, Pest, Nógrád és Heves megye) a diagnosztizált esetek számához képest kevés vizsgálatot végeztetnek, ami egyet jelent azzal, hogy nagyobb számú beteg nem kerül felismerésre. Magyarországon eddig a lakosság csupán 3-5 %-a részesült megfelelő védőoltásban, ennek hatása még nem hozhatott egyértelmű változásokat az epidemiológiai adatokban.

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