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Occurrence of TBE in areas previously considered being non-endemic: Scandinavian data generate an international study by the International Scientific Working Group for TBE (ISW-TBE)
Int.J. Med. Microbial. 291. Suppl. 33,50-54 (2002)
© Urban & Fischer Verlag http://www.urbanfischer.defjaurnals/ijmm
Mini-Review Occurrence of TBE in areas previously considered being non-endemic: Scandinavian data generate an international study by the International Scientific Working Group for TBE (lSW-TBE) Mats Haglund* Department of Infectious Diseases, Kalmar County Hospital and Research Institute for Zoonotic Ecology and Epidemiology, Kalmar, Sweden
Abstract Tick-borne encephalitis virus (TBEV) has been endemic in many countries in central, northern and eastern Europe. More than 3000 human cases are reported annually, the Baltic states included. TBEV causes CNS infections presented as meningitis or meningoencephalitis with or without myelitis. The case fatality rate in Europe is approximately 0.5 %, and up to 40 % of the patients are left with long-lasting sequelae. The endemicity ofTBE in Sweden has been stable over the years but during the last decade several new foci have been discovered. In Norway the first verified cases of TBE have now been found. The reason for this changing epidemiology of TBE is discussed. Key words: Tick-borne encephalitis - TBE - human - epidemiology
Introduction Tick-borne encephalitis virus (TBEV) belongs to the genus flavivirus within the family Flaviviridae (Rice, 1996). TBEV is the most important arbovirus in Europe causing more than 3000 human cases yearly, the Baltic states included (Dumpis et al., 1999; Anonymous, 2000). In the majority of cases the disease is characterised by a biphasic course with a first viremic phase presenting as fever with general symptoms. In up to one fourth of the infected individuals the first phase is followed by involvement of the central nervous system. The clinical picture is variable with a spectrum from mild meningitis to severe encephalitis, sometimes accompanied with myelitis resulting in paretic cases. The case fatality rate in Europe is approximately 0.5 % (Haglund, 2000). A few prospective long-time follow-up studies have been performed and they verified that TBE is a disease with high morbid-
ity causing considerable suffering for the patients and with high costs for the healthcare system (Gunther et aI., 1997; Kaiser, 1999). As much as 40 % of the patients are left with chronic sequelae where various neuropsychiatric and cognitive complaints are the most frequently reported residuals. Other common residual symptoms are dysphasia, balance disorders, headaches, hearing disorders and paretic manifestations. In the natural cycle of TBEV transmission, the tick Ixodes ricinus acts as the main vector and different small mammals act as reservoir animals, especially species belonging to the genera of Apodemus and Cletbri01l011lYs (Nuttall, 1998). Larger mammals are probably not important or not competent as reservoirs but are important as amplifying hosts for the tick itself. In TBE-endemic areas up to 5 % of the adult ticks are carriers of TBEV (Suss et al., 1999). Because of different constraining factors, most of which are still unknown,
* Corresponding author: Mats Haglund, Department of Infectious Diseases, Kalmar County Hospital, 39185 Kalmar, Sweden, Phone: 004648081000, Fax: 0046480448986, E-mail: mars.haglundtsilrkalmar.se 1438-4221/01/291/8-000 $ 15.00/0
New foci of TBE in Scandinavia
the endemicity for TBEV differs markedly from Lyme borreliosis. The endemic foci for TBEV within the endemic regions for I. ricinus are more scattered and not as widespread as the endemic foci of Lyme borreliosis (Holmgren and Forsgren, 1990).
Epidemiology The endemic regions of TBE in Europe have been investigated and mapped since the early days of TBEresearch, from the 1940's onward. The main endemic areas of TBE are located in central, eastern and northern Europe (Dumpis et aI., 1999). In the western parts of the European continent, and on the British islands and Ireland TBEV has not been found. Louping III virus is endemic on the British islands and in Ireland instead (Gao et al., 1997; McGuire et al., 1998). This f1avivirus is the closest relative to western and far eastern TBEV and causes CNS infection among sheep and more rarely clinical human infections. During the 1980's and 1990's the incidence of TBE has increased in most endemic countries (Dittmann and jilg, 1998). This can probably be explained by several factors: a true increase depending on an increased abundance of ticks carrying TBEV, climatic factors, abundance of amplifying hosts as the roe deer, higher awareness in the medical community and in the general population, improved diagnostic procedures, changing human behaviour etc. The established foci for TBE in Europe have been quite stable over the years but with some fluctuations (SUss er al., 1992; Haglund, 2000). During recent years there have been reports of so called new foci in several countries. But, whether these new foci have been truly established during the last years or have been established much earlier but have remained unnoticed because no one has been looking for the disease, are in most cases difficult to answer. In many regions considered as nonendemic there has been a tradition not to look for TBE among patients with viral CNS infections which could explain why we underestimated the true endemicity of TBE. This has been the case in the Scandinavian countries, which will be discussed below. The reported risk groups for TBE have varied in reports from different countries. They have included forest workers, farmers, unemployed, pensioners, male gender and people contracting the disease during leisure activities (Kunz, 1992; Haglund et aI., 1996). The age distribution has not been uniformly described. In most reports the incidence is higher among people of 30 to 60 years of age. But, from some regions, e. g. the Baltic states and Austria, there have been reports which show a much higher proportion of cases among children (Lucenko and Bormane, 2000).
51
A summary of the epidemiological situation of TBE in Sweden TBE was discovered during the 1950's in Sweden. Diagnostic procedures were established, the first patients were verified, the clinical picture was described and virus isolations from humans and ticks were successful. Studies on the circulation of TBEV among mammals and birds were also performed. Early epidemiological data were collected which included the geographical origin of the human clinical cases. In the beginning there has been a certain bias because this work was performed by colleagues working in Stockholm only (Holmgren et al., 1959). A prospective epidemiological surveillance has continued over the years where a majority of the cases were interviewed and mapped. The established endemic areas in Sweden were, and still are, the Stockholm archipelago from Roslagen to Trosa and the central and eastern parts of lake Malaren. More scattered cases have also been found along the east coast further south to Kalmar and from the island Gotland in the Baltic sea. A few cases were previously reported from a region south of lake Vanern and from north of Gothenburgh (Holmgren and Forsgren, 1990). The risk areas in the eastern part of the country have remained the same over the years but during the 1990's the situation has changed in other parts of the country. An interesting early seroepidemiolgical study ofTBE in cows was published in 1959 (von Zeipel et al., 1959). The investigation showed that there were seropositive cows found in all parts of southern and middle Sweden correlating well with the known endemicity of the tick I. ricinus. There was a tendency to a higher seroprevalence in the east compared to the west and the inland. These data were never followed up and human clinical cases have not been extensively looked for outside the established endemic regions in the eastern parts of the country. The reported annual number of cases in Sweden has increased over the years. Until the 1980's approximately 25 cases were reported every year. During the 1980's the annual average increased to 40 and during the last decade to 68 cases with a new all time high in the year 2000 with 153 reported cases (Arneborn, 2001). TBE is not a notifiable disease in Sweden but through voluntary laboratory reports and notifications from physicians the reporting system of diagnosed cases covers close to 100 %. The reasons for the increased number of TBE cases in Sweden are, as already shortly discussed, probably multifactorial. There are indications of an increased abundance of the tick itself, including density and an extended spread further north in the country (Tiilleklint and jaenson, 1998). Climatic factors and the high
52
M. Haglund
number of roe deer have been discussed as contributing factors (Lindgren, 2000). The impression is also that the awareness of the disease has increased, both within the medical community and among the general population. Routine serological procedures for diagnosis of acute TBE are wellfunctioning and arc established in an increasing number of virological departments.
NewTBE-endemic areas in Sweden During the 1990's approximately 35 reponed cases have been found where the patients contracted the disease after visiting areas outside the established endemic areas (Arneborn, 2000; Haglund, 2000). A majority of these cases originated from foci located in several different areas around the two big lakes Vatrern and Vanern, often from foci located close to the water. These lakes are located in the inland of the country. Around these lakes the climate is milder and the biotopes differ compared to the rest of the inland in this part of the country. This could be a partial explanation for the geographical distribution of cases around these lakes. Another explanation could be the already discussed lacking awareness of the possibility of finding TBE cases outside the established endemic areas. Additional few scattered cases have been reported from Dalsland and Bohuslan in the west and from Skane and Blekinge in. the south of Sweden. We know from discussions with our colleagues working in the areas previously considered non-endemic that TBE serology was and still is seldomly performed. This leads to the conclusion that for the moment we do not know the true endemicity for TBEV in Sweden. My personal belief is that we would find more TBE cases and also discover new local foci if all patients with viral CNS infections were screened for TBE. The absolute number of non diagnosed cases is probably moderate but, despite of this, these cases are important from an epidemiological point of view and, of course, of importance for the individual because of the high morbidity associated with TBE. How stable is the epidemiological situation for TBE in Sweden? There are concerns of the impact of a milder climate on the endemicity and transmission of vector-borne diseases, e. g. TBE, in our region of Europe. The influence of the establishment of a numerous population of roe deer in southern and middle parts of Sweden has been discussed as one potentially important factor because roe deer act as amplifying host for the tick I. ricinus. But, for the moment we can only speculate about the true epidemiological situation of TBE in Sweden and how stable the endemic foci are in a shorter or longer perspective.
Short comments on TBE in Norway Terje Traavik performed scroepidcrniological and virological studies on TBEV and other zoonotic viral agents in the western parts of Norway during the 1970's (Traavik, 1979). From Alesund and further south to Lisra in the most southern part of the country serum samples were collected from humans and cows and virus isolations were performed on collected ticks. The seroepiderniological studies indicated the circulation of a TEEV-like virus in the region. In a tick collection from Sogn and Fjordane county five virus isolates were obtained and characterised as TBEV strains (Traavik et al., 1978). Gao et al. (1993) sequenced one strain (LIINOR) isolated from a Norwegian sheep in 1984 and this isolate interestingly proved to be a strain of Louping III virus (LIV) but not TBEV. It was shown that this strain phylogenerically belonged to a cluster geographically originating from England. Different ways of transportation over the sea were discussed: migrating birds, imported animals and ticks etc. To my knowledge no further characterisation of the "Traavik strains" has been performed. In the studies performed by Traavik no verified case of human acute TEE was found. But, in 1998, the first Norwegian case of an acute TEEV-infection was diagnosed which originated from Trornoya in Agder county located in the southwest (Skarpaas er al., 2000, 2001). Five TEE cases have now been found (19972000) in total and all have originated from coastal areas of southwest Norway. These cases have been serologically diagnosed at the Swedish Institute for Infectious Disease Control by ELISA and verified by neutralisation test. It is for the moment not fully clear how well our neutralisation test distinguishes between infections caused by TBEV or LIV (Vene et al., 1998). Further studies have been initiated in Norway and we will certainly hear more about TBE in Norway in the near future.
The International Scientific Working Group for TBE (ISW-TBE) and the Meningitis study The ISW-TBE was established in 1999 as collaboration and network involving colleagues with an interest and activities in the field of TBE (Anonymous, 2001). The main aims of ISW-TBE are to promote national and international collaborations on TEE, to stimulate and co-ordinate applied and basic research on TEE, to contribute to training and educational programmes in the field, to provide high-quality information on TBE and its endemicity, to promote and align international standards on epidemiological TEE surveillance and to define and promote proposals to harmonise national and
New foci of TBE in Scandinavia international policies on TBE prevention. A hornepage is available (www.TBE-info.com) with general information concerning TBE and TBE vaccination as well as several additional so-called country reports. With ISWTBE three meetings have been held and different activities are in progress of which the Meningitis Study is one. The Meningitis Study was initiated partly because of the scenarios described regarding the changing epidemiology and endemicity ofTBE in different regions. The aim of the study is to find undiagnosed cases ofTBE in departments without routine screening for TBE. Several centers are involved in Belgium, France, Italy, the Netherlands, Sweden and Switzerland. The design of the study is a retrospective follow-up of cases treated for a verified viral CNS infection but with unknown etiology. If spared sera are available these are, after consent, screened by IgM and IgG ELISA. If positive, the results will be verified at the Virological Department at the University of Vienna using ELISA and neutralisation assays. If the positive result is verified the individual will be interviewed using a standardised questionnaire asking for epidemiological data, vaccination status (TBE, other flaviviruses) and some condensed clinical data. The study is under progress and will be finished during the autumn 2001. .
Discussion TBE is the most important arbovirus in Europe causing considerable morbidity with suffering of the patients and high costs for the healthcare system and society. Effective vaccines are available and recommended to people at risk in endemic regions. During the last two decades there has been an increase of reported TBE cases from most countries (except from Austria where a mass vaccination campaign has markedly reduced the number of cases). But the true reasons for this increase are not fully understood. There are indications of an increased number of ticks and spread of ticks further north (e. g. Sweden). There are also reports indicating that climatic factors might influence the number of annual TBE cases and also influence the geographical distribution ofTBE. Higher awareness of the disease, improved national socio-economic status and better diagnostic procedures have probably also influenced the number of diagnosed cases. Another important factor is the influence of tradition and habits and in what way colleagues have been informed of the endemicity of TBE. In many regions where TBE was suspected to be non-endemic there has been a tradition not to screen for TBE among patients with viral CNS-infection. Because of this a number of TBE cases have probably been undiagnosed, and still
53
are. There are also several examples (Sweden, Norway, Bornholm in Denmark) where earlier seroepiderniological and virological studies had proved the circulation of TBEV-like viruses outside the established endemic regions but the data were never used for a thorough search for human cases in the same areas. In conclusion, there is a need for more studies concerning the endemicity of TEE in Europe and the different factors, which are of importance for the establishment and maintenance of TBE foci.
References Anonymous: Hornepage for the International Scientific Working Group on TBE. www.TBE-info.com (2001). Arneborn, M.: Data on file. Swedish Institute for Infectious Disease Control (2001). Dittmann, S., Jilg, W.: Tick-borne encephalitis in the European region. WHO Regional Office for Europe, Copenhagen, Denmark (1998). Dumpis, U., Crook, D., Oksi, J.: Tick-borne encephalitis. Clin. Infect. Dis.28, 882-890 (1999). Gao, G., Jiang, \Y/., Hussain, M ., Venugopal, K., Gritsun, T., Reid, H., Gould, E.: Sequencing and antigenic studies of a Norwegian virus isolated from cncephalomyelitic sheep confirm the existence of louping ill virus outside Great Britain and Ireland. J. Gen. Viral. 74, 109-114 (1993). Gao, G., Zanotto, P., Holmes, E., Reid, H., Gould, E.: Molecular variation, evolution and geographical distribution of louping ill virus. Acta Virol. 41, 259-268 (1997). Gunther, G., Haglund, M., Lindquist, L., Forsgren, M., Skoldenberg, B.: Tick-borne encephalitis in Sweden in relation to aseptic meningo-encephalitis of other etiology: a prospective study of clinical course and outcome.], Neurol. 244, 230-238 (1997). Haglund, M., Forsgren, M., Lindh, G., Lindquist, L.: A 10year follow-up study of tick-borne encephalitis in the Stockholm area and a review of the References: need for a vaccination strategy. Scand.]. Infect. Dis.28, 217-224 (1996). Haglund, M.: Tick-borne encephalitis: prognosis, immunization and virus strain characterization (Thesis). Division of Infectious Diseases, Division of Virology, Huddinge University Hospital, Karolinska Institute, and Swedish Institute for Infectious Disease Control, Stockholm, Sweden (2000). Holmgren, B., Lindahl, J., von Zeipel, G., Svedmyr, A.: Tickborne mcningoencephalornyelitis in Sweden. Acta Med. Scand, 164,507-522 (1959). Holmgren, B., Forsgren, 1\1.: Epidemiology of tick-borne encephalitis in Sweden 1956-1989: a study of 1116 cases. Scand.], Infect. Dis. 22,287-295 (1990). Kaiser, R.: The clinical and epidemiological profile of tickborne encephalitis in southern German)' 1994-98: a prospective study of 656 patients. Brain 122, 2067-2078 (1999). Kunz, c.: Tick-borne encephalitis in Europe. Acta Leiden, 60, 1-14 (1992).
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Lindgren, E.: The new environmental context for disease transmission (Thesis). Department of systems ecology, Stockholm University, Stockholm, Sweden (2000). Lucenko, I., Borrnane, A.: Tick-borne encephalitis (TBE) and Lyme disease in Latvia 1999. 7th Baltic-Nordic conference on tick-borne zoonosis, Tallinn, Estonia, Uppsala County Council (2000). >McGuire, K., Holmes, E., Gao, G., Reid, H., Gould, E.: Tracing the origins of louping ill virus by molecular phylogenetic analysis.]. Gen. Virol. 79, 981-988 (1998). Nuttall, P.: Displaced tick-parasite interactions at the host interphase. Parasitology 116, S65-S72 (1998). Rice, c.: Flaviviridae: The viruses and their replication. In: Fields Virology, 3rd ed. (B. Fields, D. Knipe, P. Howley er aI., eds), pp. 931-59. Lippincott-Raven Publishers, Philadelphia, 1996. Skarpaas, T., Csango, P., Pedersen, ].: Skogsflatr-encefalitr (TBE) pa Sorlandet. MSIS-rapport no 1 (2000). Skarpaas, T., Sunday, A., Bruu, A.-L., Vene, S., Pedersen, ]., Eng, P. G., Csango, P.:Tick-borne encephalitis in Norway. Current research in tick-borne infections. Brofasrer, Kalmar, Sweden, the Research Institute for Zoonotic Ecology and Epidemiology (RIZEE; 2001). Suss, j., Sinnecker, H., Sinnecker, R., Berndt, D., Zilske, E., Dedek, G., Apitzsch, L.: Epidemiology and ecology of tick-borne encephalitis in the eastern part of Germany
between 1960 and 1990 and studies on the dynamics of a natural focus of tick-borne encephalitis. Int.], Med. Microbiol. Viral. Parasitol. Infect. Dis. 277, 224-235 (1992). Suss, J., Schrader, c., Abel, U., Voigt, W., Schosser, R.: Annual and seasonal variation of tick-borne encephalitis virus (TBEV) prevalence in ticks in selected hot spot areas in Germany using a nRT-PCR : results from 1997 and 1998. Zentralbl. Bakteriol. 289, 564-578 (1999). Traavik, T., Mehl, R., \Viger, R.: The first tick-borne encephalitis virus isolates fram Norway. Acta. Path . Microbiol. Scand. Sect. B. 86, 253-255 (1978). Traavik, T.: Arboviruses in Norway. In: Arctic and tropical arboviruses.(Kurstak, E, cd.), pp 67-81. Academic Press, New York, London 1979. Talleklint, L., ]aenson, T.: Increasing geographical distribution and density of Ixodes ricinus (Acari: Ixodidae) in central and northern Sweden.]. Mcd. Entornol. 35,521-526 (1998). Vene, 5., Haglund, M., Vapalahti, 0., Lundkvist, A.: A rapid fluorescent inhibition test for detection of neutralizing antibodies to tick-borne encephalitis virus.]. Virol. Meth, 73,71-75 (1998). von Zeipel, G., Svedmyr, A., Zetterberg, B.: The geographical distribution in Sweden of viruses belonging to the Russian spring-summer-Iouping ill group. Arch. f. Virusforschung 9, 449-459 (1959).
© Urban & Fischer Verlag http://www.urbanfischer.defjaurnals/ijmm
Mini-Review Occurrence of TBE in areas previously considered being non-endemic: Scandinavian data generate an international study by the International Scientific Working Group for TBE (lSW-TBE) Mats Haglund* Department of Infectious Diseases, Kalmar County Hospital and Research Institute for Zoonotic Ecology and Epidemiology, Kalmar, Sweden
Abstract Tick-borne encephalitis virus (TBEV) has been endemic in many countries in central, northern and eastern Europe. More than 3000 human cases are reported annually, the Baltic states included. TBEV causes CNS infections presented as meningitis or meningoencephalitis with or without myelitis. The case fatality rate in Europe is approximately 0.5 %, and up to 40 % of the patients are left with long-lasting sequelae. The endemicity ofTBE in Sweden has been stable over the years but during the last decade several new foci have been discovered. In Norway the first verified cases of TBE have now been found. The reason for this changing epidemiology of TBE is discussed. Key words: Tick-borne encephalitis - TBE - human - epidemiology
Introduction Tick-borne encephalitis virus (TBEV) belongs to the genus flavivirus within the family Flaviviridae (Rice, 1996). TBEV is the most important arbovirus in Europe causing more than 3000 human cases yearly, the Baltic states included (Dumpis et al., 1999; Anonymous, 2000). In the majority of cases the disease is characterised by a biphasic course with a first viremic phase presenting as fever with general symptoms. In up to one fourth of the infected individuals the first phase is followed by involvement of the central nervous system. The clinical picture is variable with a spectrum from mild meningitis to severe encephalitis, sometimes accompanied with myelitis resulting in paretic cases. The case fatality rate in Europe is approximately 0.5 % (Haglund, 2000). A few prospective long-time follow-up studies have been performed and they verified that TBE is a disease with high morbid-
ity causing considerable suffering for the patients and with high costs for the healthcare system (Gunther et aI., 1997; Kaiser, 1999). As much as 40 % of the patients are left with chronic sequelae where various neuropsychiatric and cognitive complaints are the most frequently reported residuals. Other common residual symptoms are dysphasia, balance disorders, headaches, hearing disorders and paretic manifestations. In the natural cycle of TBEV transmission, the tick Ixodes ricinus acts as the main vector and different small mammals act as reservoir animals, especially species belonging to the genera of Apodemus and Cletbri01l011lYs (Nuttall, 1998). Larger mammals are probably not important or not competent as reservoirs but are important as amplifying hosts for the tick itself. In TBE-endemic areas up to 5 % of the adult ticks are carriers of TBEV (Suss et al., 1999). Because of different constraining factors, most of which are still unknown,
* Corresponding author: Mats Haglund, Department of Infectious Diseases, Kalmar County Hospital, 39185 Kalmar, Sweden, Phone: 004648081000, Fax: 0046480448986, E-mail: mars.haglundtsilrkalmar.se 1438-4221/01/291/8-000 $ 15.00/0
New foci of TBE in Scandinavia
the endemicity for TBEV differs markedly from Lyme borreliosis. The endemic foci for TBEV within the endemic regions for I. ricinus are more scattered and not as widespread as the endemic foci of Lyme borreliosis (Holmgren and Forsgren, 1990).
Epidemiology The endemic regions of TBE in Europe have been investigated and mapped since the early days of TBEresearch, from the 1940's onward. The main endemic areas of TBE are located in central, eastern and northern Europe (Dumpis et aI., 1999). In the western parts of the European continent, and on the British islands and Ireland TBEV has not been found. Louping III virus is endemic on the British islands and in Ireland instead (Gao et al., 1997; McGuire et al., 1998). This f1avivirus is the closest relative to western and far eastern TBEV and causes CNS infection among sheep and more rarely clinical human infections. During the 1980's and 1990's the incidence of TBE has increased in most endemic countries (Dittmann and jilg, 1998). This can probably be explained by several factors: a true increase depending on an increased abundance of ticks carrying TBEV, climatic factors, abundance of amplifying hosts as the roe deer, higher awareness in the medical community and in the general population, improved diagnostic procedures, changing human behaviour etc. The established foci for TBE in Europe have been quite stable over the years but with some fluctuations (SUss er al., 1992; Haglund, 2000). During recent years there have been reports of so called new foci in several countries. But, whether these new foci have been truly established during the last years or have been established much earlier but have remained unnoticed because no one has been looking for the disease, are in most cases difficult to answer. In many regions considered as nonendemic there has been a tradition not to look for TBE among patients with viral CNS infections which could explain why we underestimated the true endemicity of TBE. This has been the case in the Scandinavian countries, which will be discussed below. The reported risk groups for TBE have varied in reports from different countries. They have included forest workers, farmers, unemployed, pensioners, male gender and people contracting the disease during leisure activities (Kunz, 1992; Haglund et aI., 1996). The age distribution has not been uniformly described. In most reports the incidence is higher among people of 30 to 60 years of age. But, from some regions, e. g. the Baltic states and Austria, there have been reports which show a much higher proportion of cases among children (Lucenko and Bormane, 2000).
51
A summary of the epidemiological situation of TBE in Sweden TBE was discovered during the 1950's in Sweden. Diagnostic procedures were established, the first patients were verified, the clinical picture was described and virus isolations from humans and ticks were successful. Studies on the circulation of TBEV among mammals and birds were also performed. Early epidemiological data were collected which included the geographical origin of the human clinical cases. In the beginning there has been a certain bias because this work was performed by colleagues working in Stockholm only (Holmgren et al., 1959). A prospective epidemiological surveillance has continued over the years where a majority of the cases were interviewed and mapped. The established endemic areas in Sweden were, and still are, the Stockholm archipelago from Roslagen to Trosa and the central and eastern parts of lake Malaren. More scattered cases have also been found along the east coast further south to Kalmar and from the island Gotland in the Baltic sea. A few cases were previously reported from a region south of lake Vanern and from north of Gothenburgh (Holmgren and Forsgren, 1990). The risk areas in the eastern part of the country have remained the same over the years but during the 1990's the situation has changed in other parts of the country. An interesting early seroepidemiolgical study ofTBE in cows was published in 1959 (von Zeipel et al., 1959). The investigation showed that there were seropositive cows found in all parts of southern and middle Sweden correlating well with the known endemicity of the tick I. ricinus. There was a tendency to a higher seroprevalence in the east compared to the west and the inland. These data were never followed up and human clinical cases have not been extensively looked for outside the established endemic regions in the eastern parts of the country. The reported annual number of cases in Sweden has increased over the years. Until the 1980's approximately 25 cases were reported every year. During the 1980's the annual average increased to 40 and during the last decade to 68 cases with a new all time high in the year 2000 with 153 reported cases (Arneborn, 2001). TBE is not a notifiable disease in Sweden but through voluntary laboratory reports and notifications from physicians the reporting system of diagnosed cases covers close to 100 %. The reasons for the increased number of TBE cases in Sweden are, as already shortly discussed, probably multifactorial. There are indications of an increased abundance of the tick itself, including density and an extended spread further north in the country (Tiilleklint and jaenson, 1998). Climatic factors and the high
52
M. Haglund
number of roe deer have been discussed as contributing factors (Lindgren, 2000). The impression is also that the awareness of the disease has increased, both within the medical community and among the general population. Routine serological procedures for diagnosis of acute TBE are wellfunctioning and arc established in an increasing number of virological departments.
NewTBE-endemic areas in Sweden During the 1990's approximately 35 reponed cases have been found where the patients contracted the disease after visiting areas outside the established endemic areas (Arneborn, 2000; Haglund, 2000). A majority of these cases originated from foci located in several different areas around the two big lakes Vatrern and Vanern, often from foci located close to the water. These lakes are located in the inland of the country. Around these lakes the climate is milder and the biotopes differ compared to the rest of the inland in this part of the country. This could be a partial explanation for the geographical distribution of cases around these lakes. Another explanation could be the already discussed lacking awareness of the possibility of finding TBE cases outside the established endemic areas. Additional few scattered cases have been reported from Dalsland and Bohuslan in the west and from Skane and Blekinge in. the south of Sweden. We know from discussions with our colleagues working in the areas previously considered non-endemic that TBE serology was and still is seldomly performed. This leads to the conclusion that for the moment we do not know the true endemicity for TBEV in Sweden. My personal belief is that we would find more TBE cases and also discover new local foci if all patients with viral CNS infections were screened for TBE. The absolute number of non diagnosed cases is probably moderate but, despite of this, these cases are important from an epidemiological point of view and, of course, of importance for the individual because of the high morbidity associated with TBE. How stable is the epidemiological situation for TBE in Sweden? There are concerns of the impact of a milder climate on the endemicity and transmission of vector-borne diseases, e. g. TBE, in our region of Europe. The influence of the establishment of a numerous population of roe deer in southern and middle parts of Sweden has been discussed as one potentially important factor because roe deer act as amplifying host for the tick I. ricinus. But, for the moment we can only speculate about the true epidemiological situation of TBE in Sweden and how stable the endemic foci are in a shorter or longer perspective.
Short comments on TBE in Norway Terje Traavik performed scroepidcrniological and virological studies on TBEV and other zoonotic viral agents in the western parts of Norway during the 1970's (Traavik, 1979). From Alesund and further south to Lisra in the most southern part of the country serum samples were collected from humans and cows and virus isolations were performed on collected ticks. The seroepiderniological studies indicated the circulation of a TEEV-like virus in the region. In a tick collection from Sogn and Fjordane county five virus isolates were obtained and characterised as TBEV strains (Traavik et al., 1978). Gao et al. (1993) sequenced one strain (LIINOR) isolated from a Norwegian sheep in 1984 and this isolate interestingly proved to be a strain of Louping III virus (LIV) but not TBEV. It was shown that this strain phylogenerically belonged to a cluster geographically originating from England. Different ways of transportation over the sea were discussed: migrating birds, imported animals and ticks etc. To my knowledge no further characterisation of the "Traavik strains" has been performed. In the studies performed by Traavik no verified case of human acute TEE was found. But, in 1998, the first Norwegian case of an acute TEEV-infection was diagnosed which originated from Trornoya in Agder county located in the southwest (Skarpaas er al., 2000, 2001). Five TEE cases have now been found (19972000) in total and all have originated from coastal areas of southwest Norway. These cases have been serologically diagnosed at the Swedish Institute for Infectious Disease Control by ELISA and verified by neutralisation test. It is for the moment not fully clear how well our neutralisation test distinguishes between infections caused by TBEV or LIV (Vene et al., 1998). Further studies have been initiated in Norway and we will certainly hear more about TBE in Norway in the near future.
The International Scientific Working Group for TBE (ISW-TBE) and the Meningitis study The ISW-TBE was established in 1999 as collaboration and network involving colleagues with an interest and activities in the field of TBE (Anonymous, 2001). The main aims of ISW-TBE are to promote national and international collaborations on TEE, to stimulate and co-ordinate applied and basic research on TEE, to contribute to training and educational programmes in the field, to provide high-quality information on TBE and its endemicity, to promote and align international standards on epidemiological TEE surveillance and to define and promote proposals to harmonise national and
New foci of TBE in Scandinavia international policies on TBE prevention. A hornepage is available (www.TBE-info.com) with general information concerning TBE and TBE vaccination as well as several additional so-called country reports. With ISWTBE three meetings have been held and different activities are in progress of which the Meningitis Study is one. The Meningitis Study was initiated partly because of the scenarios described regarding the changing epidemiology and endemicity ofTBE in different regions. The aim of the study is to find undiagnosed cases ofTBE in departments without routine screening for TBE. Several centers are involved in Belgium, France, Italy, the Netherlands, Sweden and Switzerland. The design of the study is a retrospective follow-up of cases treated for a verified viral CNS infection but with unknown etiology. If spared sera are available these are, after consent, screened by IgM and IgG ELISA. If positive, the results will be verified at the Virological Department at the University of Vienna using ELISA and neutralisation assays. If the positive result is verified the individual will be interviewed using a standardised questionnaire asking for epidemiological data, vaccination status (TBE, other flaviviruses) and some condensed clinical data. The study is under progress and will be finished during the autumn 2001. .
Discussion TBE is the most important arbovirus in Europe causing considerable morbidity with suffering of the patients and high costs for the healthcare system and society. Effective vaccines are available and recommended to people at risk in endemic regions. During the last two decades there has been an increase of reported TBE cases from most countries (except from Austria where a mass vaccination campaign has markedly reduced the number of cases). But the true reasons for this increase are not fully understood. There are indications of an increased number of ticks and spread of ticks further north (e. g. Sweden). There are also reports indicating that climatic factors might influence the number of annual TBE cases and also influence the geographical distribution ofTBE. Higher awareness of the disease, improved national socio-economic status and better diagnostic procedures have probably also influenced the number of diagnosed cases. Another important factor is the influence of tradition and habits and in what way colleagues have been informed of the endemicity of TBE. In many regions where TBE was suspected to be non-endemic there has been a tradition not to screen for TBE among patients with viral CNS-infection. Because of this a number of TBE cases have probably been undiagnosed, and still
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are. There are also several examples (Sweden, Norway, Bornholm in Denmark) where earlier seroepiderniological and virological studies had proved the circulation of TBEV-like viruses outside the established endemic regions but the data were never used for a thorough search for human cases in the same areas. In conclusion, there is a need for more studies concerning the endemicity of TEE in Europe and the different factors, which are of importance for the establishment and maintenance of TBE foci.
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