Table of contents :

• Latvia : in 1993, annual incidence quadrupled from the mean level of the previous 2 decades (nearly 8 cases per 100 000 population), reaching the highest levels in 1994 and 1995 at 53 cases per 100 000. Since 1999 the incidence has been significantly lower, down to 6.5 cases in 2002, but back up to 15.7 per 100 000 in 2003 (Figure). About 60% of TBE cases over the last 10 years affected the meninges, about 30% were febrile and 10% had the most severe clinical course, meningoencephalitis. I. ricinus has 2 seasonal activity peaks in the western and central part of Latvia. I. persulcatus has only one spring activity peak and predominates in the eastern part of the country. According to monitoring data, the abundance of ticks has increased since 1994, with the highest peaks of I. ricinus tick activity recorded in 1998 and 2000, which does not match the epidemiological pattern exactly. The highest TBE virus (TBEV) prevalence in field-collected ticks was observed in 1995 (28.4%), 1996 (10.8%) and 2002 (9.2%). Apart from these 3 years, over the whole observation period since 1973, the mean annual TBEV prevalence rate in field-collected ticks was about 3%. Tests on ticks engorged with human blood, brought to the vaccination service by members of the public, started in 1998. The TBEV prevalence rate in these ticks was  found to be much higher, about 30%. Typing of TBEV isolated from ticks and patient serum samples in collaboration with German and Swedish virologists revealed that the viruses belong to Far Eastern and Western subtypes and are highly homologous with the Vasilchenko, Neudoerfl and Sofyn strains previously described^{ref1, ref2, ref3}. Annual changes in TBE morbidity depend on factors other than tick activity, such as vaccination, awareness campaigns, changes in usual recreation due to weather, etc. There is a significant correlation between marked decreases in TBE morbidity and increases in vaccination coverage. According to the incomplete data from vaccination services, which are mostly privately run and not obliged to submit statistical data, the number of completely vaccinated people since 1993 rose 3-5-fold. Vaccine uptake according to the recommended vaccination schedule improved during the last decade, when the number of 2nd and 3rd doses came nearer to the number of 1st doses. The number of booster doses also increased significantly. Each year, the demand for immunisation is usually highest during April, May and June, when tick activity first peaks and awareness of the problem is higher. In 1994, a campaign to vaccinate children against TBE began in areas of high TBE risk in Latvia. There are 5 rural areas where child TBE incidence level exceeded the mean level in country by > 6 times (20 cases per 100 000 children). These became a vaccination priority and 75% of children in these rural districts are now covered. Vaccination in the 2 highest-risk groups of infected territories was completed in 1998. Altogether, children have been vaccinated in more than 100 rural districts. The childhood vaccination campaign was funded by humanitarian aid (51%) and national budget (49%), and this has brought the child TBE incidence in high-risk areas down to a rate similar to the mean in the whole country since 1999. However, according to predictions (which were calculated using the child TBE incidence rate over previous 5 years), the theoretical morbidity in high-risk rural districts could exceed the rate from notified data > 5 times. According to official statistics, the immunisation coverage for the whole population of Latvia is about 5%, but results of a population survey of TBE prophylaxis awareness (1000 respondents) suggested the percentage of vaccinated adults was higher: 15% people on low incomes and 26% of all respondents reported that they had been vaccinated^ref.
• Lithuania : in 2003, the epidemiology of tick-borne encephalitis (TBE) was very unusual. The incidence rate (763 cases, 22 per 100 000 population) was double the average incidence over the last 10 years, and was the highest annual rate recorded since notification began at the end of the 1960s. This rate was also the highest of all the Baltic countries in 2003. 4 lethal cases of TBE were notified in 2003. TBE is normally transmitted by a tick bite, but in 2003, 22 cases of TBE (4 clusters), were acquired by consuming unpasteurised goat's milk, a well-recognised transmission route. From 1993, the TBE incidence rate in Lithuania suddenly increased to >5 per 100 000 population, a 10-fold increase compared with the previous 2 decades. There was a further 3-fold increase in 1997/98, followed by a decrease to nearer the 1993 level, before the dramatic increase last year. One explanation for the high incidence in 2003 may be that there were higher numbers of ticks this particular year. TBE has a strict seasonal pattern, probably due largely to seasonal patterns of tick activity and human visits to the forests. In 2003 most TBE cases were registered in September and October, as usual. The highest incidences of TBE, about 80% of all notified cases, are recorded every year in the northern and central part of the country, mainly in 3 counties: Kaunas, Panevezys and Siauliai. In 2003, the incidence rate in these areas was the same, but incidence rates were much higher in many other counties. 8 districts out of 44 reported a 2-5-times higher incidence rate than the average incidence in Lithuania. The highest incidence rate was in Panevezys, at about 100 per 100 000 population. In Lithuania, TBE affects 1.4 times as many males as females. People from rural areas are 1.7 times more affected than people living in urban areas. This has stayed constant over the last 10 years. About 40% of all cases of TBE were in retired and unemployed people, who constitute a particular risk group. This number has stayed relatively constant over the past few years. One reason could be that these people are more likely to collect mushrooms and berries, which can serve as an additional source of income. TBE incidence is about 2-3 times higher in adults than in children. Typically, 20% of all cases of TBE in Lithuania are in people over 60. In 2003, people aged 40-49 also made up nearly 20% and the increased incidence rate affected all age groups. Despite TBE being a very big problem in Lithuania, vaccine coverage is too low to control the disease: about 20 000 doses of TBE vaccine are given each year, according to official statistics. Vaccination is recommended but the government does not provide financial assistance for this, and people have to pay the full costs themselves. Some employers provide vaccination for employees such as forest workers, who, through their occupation, have a higher risk of TBE^ref.
• Estonia : recent outbreaks of tickborne encephalitis associated with the consumption of raw goat and cow milk notified in Estonia include:
• 1990: household outbreak involving 3 family members
• 1992: outbreak involving 10 military recruits
• 2004: household outbreak involving 3 family members and one guest.
• 2005 : in May and June 2005, 27 cases of tickborne encephalitis (TBE) were reported to the Estonia Tervisekaitseinspektsioon (Health Protection Inspectorate). All the cases occurred in 2 administrative territories: Tallinn city and Harju county. Of the 27 patients was 15 were female and 12 were male, and their ages ranged between 4 and 69 years. The dates of symptom onset ranged from 9 May to 1 June. 15 patients had influenza-like symptoms (fever and/or headache); 4 patients reported vomiting and 8 patients were admitted to hospital with neurological symptoms. A total of 24 patients were admitted to hospital. All clinical cases were laboratory confirmed, and no deaths have been reported. None of the patients had been vaccinated against TBE, and none of them reported being bitten by ticks before symptom onset. Based on the results of the descriptive epidemiological investigation, all cases were associated with consumption of raw (unpasteurised) goat milk that had been offered to customers to taste at a supermarket in Tallinn on 7 and 8 May 2005 as part of promotion. Serum specimens of 5 goats from the private breeding farm that supplied the milk were investigated for TBE virus neutralisation by the virology department of Smittskyddsinstitutet (the Swedish Institute for Infectious Disease Control) in Stockholm, Sweden. The results showed that one goat was clearly positive for TBE infection, and one goat showed borderline neutralisation. Information about the outbreak was disseminated to ministries of health and public health institutes throughout Europe via the Early Warning and Response System (EWRS), in order to seek information on TBE cases in tourists who may have visited a supermarket in Tallinn and tasted raw goat milk. No additional cases in other countries have yet been identified^ref.
• Austria : meningoencephalitis is a notifiable disease in Austria. There were 87 cases of TBE in Austria in 2003: an incidence rate of 1.09 per 100 000. In 2002, there were 51 cases, and, in 2002, 60 cases. Regions most affected by TBE are in the south: Steiermark (Styria) and Karnten (Carinthia). All of these cases were in unvaccinated people, or, in people who had not had the vaccine according to the recommended schedule. In the past 5 years, vaccine coverage of the entire population has risen from 79% to 87%. The coverage rate for very young children, and people over 65, is under 70%. This lower coverage in older people represents the biggest challenge for prevention of TBE in Austria. Vaccination is not free, but, health insurance companies pay part of the cost (this varies according to region).
• Denmark : TBE is not a notifiable disease in Denmark. The only area where there is a risk of acquiring TBE is on the island of Bornholm. People who live on Bornholm permanently, or have a summer holiday home there, are advised to get vaccinated, if they do activities which involve leaving the designated paths in woods or scrub land. Tourists and school parties are not considered to require vaccination unless participating in activities that take place in a fixed location in the woods
• Finland : TBE is a notifiable disease in Finland. The absolute number of TBE cases has risen from an annual 10-20 in the 1990s to over 40 cases in 2001 (population 5.2 million). The incidence of identified cases is highest (i.e. over 100/100 000/year) on the island of Aland, which is situated between Finland and Sweden. According to antibody analyses, approximately 20% of Alanders becomes infected during his or her lifetime. TBE infections are rare in children and adolescents. In addition to the Alanders, approximately 10 Swedes annually fall ill with TBE after visiting Aland. Foci of TBE also exist elsewhere in Finland, for example, in the Turku archipelago, and, in some areas of southeast Finland, around Kokkola, and on Isosaari, which is close to Helsinki. The National Public Health Institute (KTL) recommends vaccination against TBE for all those over 7 years of age who reside in, or spend long periods in, the known endemic areas. The vaccine is not, however, currently part of the Finnish national immunization program. A TBE vaccination subcommittee of KTL has recently completed an analysis of the TBE disease burden on Aland, and, the impact of the different vaccination strategies, including cost-effectiveness, and, whether the vaccine should be given free of charge.
• Germany : TBE is notifiable in Germany. In 2003, 276 cases of TBE were reported (2002: 239; 2001: 256). These occurred mainly in southern Germany in the federal states of Baden-Wurttemberg (42%) and Bavaria (38%). Counties in Germany are classified according to 3 levels of TBE risk. A county is classified as a high risk area if at least 25 TBE cases occurred within a 5-year period between 1984-2003, and as a risk area if at least 2 cases occurred within a single year, or, at least 5 cases occurred within a 5-year period between 1984-2003. Areas are declared to be TBE endemic areas based on elevated TBE seroprevalence in studies in non-immunized forestry workers. In 2003, 3 new districts were identified as risk areas. 74 of Germany's 440 counties are currently classified as TBE risk areas, and 9 as high risk areas. They are located in Baden-Wurttemberg (30), Bavaria (45), Hesse (4), Thuringia (3) and Rhineland-Palatinate. A further 5 counties in Baden-Wurttemberg are classified as endemic for TBE based on seroprevalence studies^ref. The Standing Committee on Vaccination (STIKO) recommends TBE vaccination for persons at risk of tick exposure in high risk and risk areas
• Hungary : TBE has been mandatory notifiable in Hungary since 1977, and data are collected by the Bela Johan National Center for Epidemiology (formerly, the National Institute of Public Health). Samples from patients with aseptic meningitis and encephalitis have been regularly tested for TBE at the center's division of virology since 1958, which is the only diagnostic laboratory for TBE in Hungary. The average yearly incidence between 1977 and 1996 was 2.5 per 100 000 population (range 1.3 to 3.8), with the highest incidences between 1981 and 1990. From 1997 to 2000, a significant decrease in the number of the registered/diagnosed TBE cases were observed, with incidence of 0.5 per 100 000 in 2000. Since 2001, the incidence has been slowly increasing again. In the last 3 years, the yearly average of the reported cases was 63. The high risk areas are the counties of Zala, Somogy, Vas (western Hungary) and Nograd (northern Hungary), which are in the areas of the known natural foci (Central and Western Transdanubia, and the northern central mountain chain). Vaccination for the highest risk groups (forestry and agriculture workers, etc.) was introduced in 1977. Vaccination is carried out by campaigns that are organized and controlled by the state. Since 1991, TBE vaccine has been available for all, through purchase at pharmacies, and employers must ensure the vaccination of employees. No detailed data on TBE vaccination coverage is currently available, although a rough estimate is that 5% of the population has been vaccinated, mostly people living in high risk areas.
• Norway : all cases of encephalitis are notifiable in Norway, including TBE. In 2003, one case of TBE was reported. Only 8 cases of TBE acquired in Norway have so far ever been reported. The 1st case was identified in 1998. All cases were acquired within a limited area on the southern coast, and 4 were diagnosed in the municipality of Tromoy. A study done among regular patients attending a health center in Tromoy showed a seroprevalence of 2.4% with TBEV antibodies^ref. This area probably represents a small focus of the disease in Norway. In addition, 2 cases of imported TBE have been reported since 1994. These were acquired in endemic areas in Sweden and Austria. Due to low incidence in Norway, vaccination is currently not recommended as protection against transmission within the country. It is only recommended for travelers planning outdoor activities in forested endemic areas abroad
• Poland : TBE is a notifiable disease in Poland, where it has been endemic for more than 30 years. Since 1993, the number of reported cases at country level ranged from 100 to 350 cases per year. In 2002 the number of reported cases was 126 (incidence 0.33 per 100 000), and in 2003, the number of reported cases was 339 (incidence 0.89 per 100 000). 80% of cases occurred in 2 northeastern provinces of Poland adjacent to Lithuania and Belarus. A 2nd focus of the disease was in the southwestern part of Poland, in districts adjacent to the Czech Republic. Vaccination, using a 3-dose schedule, is recommended for high-risk groups living in endemic areas, and, tourists visiting endemic places. Certain risk groups (foresters, soldiers, timber industry employees) are immunized in regular campaigns paid for by their employers.
• Slovakia : TBE is a compulsory notifiable disease in Slovakia. The number of reported cases at country level has ranged from 54 to 101 cases per year in the last 10 years. In 2002, the number of reported cases was 62 (incidence 1.15 per 100 000), and in 2003, the number of reported cases was 74 (incidence 1.38 per 100 000). Some of the reported cases were caused by drinking raw goat and sheep milk (home production). Longitudinal monitoring of TBE virus in ticks, and vertebrate hosts (including humans), between 1964-1997 resulted in identification of 37 natural endemic foci. Vaccination using a 3-dose schedule is recommended for high risk groups living, or working in, endemic areas, and, for tourists visiting endemic areas. The cost of vaccination for those who work in TBE endemic foci is reimbursed by health insurance.
• Slovenia : TBE, and Lyme borreliosis, are endemic in the northern part of Slovenia, and are notifiable diseases. In 2003, 272 cases of TBE were reported, an incidence of 13.6 / 100 000. Similar numbers of cases were reported in 2002 (262 cases) and 2001 (260 cases). Efforts are being directed towards early diagnostics, antibiotic treatment, and awareness campaigns. A vaccination campaign coordinated by the National Institute of Public Health is in place throughout the country, from late autumn to spring, annually. TBE immunization is recommended by ministry of health, and, offered by general practitioners and epidemiologists to anybody who spends time outdoor in the endemic areas, including short-term visitors. Vaccination is obligatory for those carrying out military service and other professionally exposed persons, including forestry and agriculture students. The cost of vaccination is covered by health insurance for students only. Coverage in those professionally exposed, and in students, is very high (98%). Coverage in the general population is, unfortunately, below 10%
• Sweden : TBE infection is included in voluntary laboratory reporting for infectious disease surveillance in Sweden. To gather more information about the spread of TBE in the country, a questionnaire is sent from the laboratories to the physicians, who are requested to identify probable place of infection and known tick bite. By the late 1980s and early 1990s, around 50 to 70 TBE cases were being reported annually. The majority of the patients were diagnosed through hospital care. Since the end of the 1990s, around 100 cases have been reported annually, of which, approximately 20% were treated through primary health care. During the same period, the disease attracted increased public attention. It is, therefore, difficult to say whether there has been a real increase in the number of cases, or, increased diagnosis due to a higher clinical awareness, or, that samples have been taken to a greater extent. Apart from the fact that more cases have been observed by primary health care, several cases were reported in recent years from areas where, previously, only occasional cases had been detected. In 2003, 107 cases of TBE were notified (in 75 men and 32 women). Most of the infections were acquired in the counties of Stockholm (56%), Sodermanland (15%) and Uppsala (6%). In the county of Vastra Gotaland (to the south of Lake Vanern), 5 to 10 cases are notified annually. Sporadic cases occur in the rest of Sweden every year. Vaccination is recommended for high risk groups residing in endemic areas, and, for people who live in endemic areas during the summer.
• Switzerland : the number of notifications of TBE was the highest ever recorded in 2004, with 134 cases, and a further significant increase in 2005 is already apparent. By mid-August 2005, 141 cases had been notified (provisional data). This is an increase of 55% compared with the same time period in 2004, when 91 cases had been notified. A total of about 200 cases (180-230) is projected to be notified by the end of 2005. This is about double the average number of cases notified annually between 1999 and 2004. The increase has been observed in all affected regions of Switzerland. Analysis of the data from the last year has shown that 96% of patients live in a district (canton) with TBE-endemic areas, and 85% were probably infected where they live. 8% were probably infected in another region which has endemic TBE areas, and 6% were probably infected in another country. Only 1% of tick bites were reported by patients to have occurred in regions without known risk areas. Other risk factors for exposure in 2004 were as follows. 50% of the patients in 2004 reported leisure walking in the countryside, 11%t were hikers, and 4% were mushroom pickers. 20% had occupational exposure to ticks, for example, as forestry workers and farmers. 10% of cases were in joggers and orienteers, 4% were in boy scouts and campers, and another 13% were probably exposed through other activities, such as sports activities or living near a forest. This increase in TBE cases is evidence that the general public in affected regions is still insufficiently aware of TBE, and that the use of the safe and reliable vaccine needs to be increased. A working group of experts is currently looking at ways to do this. There is growing opinion that all people over 5 years old in endemic areas should be vaccinated, with the exception of people who are never likely to be exposed. Since children under the age of 6 rarely suffer serious complications from TBE (an average of 2 children per year are admitted to hospital with TBE), vaccination is not recommended for young children^{ref1, ref2}

• bite from vectors (Ixodes ricinus; reservoir : small mammals and Capra hircus). The virus can chronically infect ticks and is transmitted both transtadially (from larva to nymph to adult ticks) and transovarially (from adult female tick through eggs). TBE cases occur during the highest period of tick activity (between April and November), when humans in rural areas are infected through tick bites, hence the name spring-summer encephalitis.
• consumption of raw milk from Capra hircus, Ovis aries, or Bos taurus has been recognised as a transmission route since at least the 1950s^{ref1, ref2, ref3}
• laboratory infections were common before the use of vaccines and availability of biosafety precautions to prevent exposure to infectious aerosols
• person-to-person transmission has not been reported
• vertical transmission from an infected mother to fetus has occurred.

Central European tick-borne (acute) encephalitis (TBE) (CEE / CETE)

• an initial phase that lasts 2 to 4 days and corresponds to the viremic phase. It is non-specific, with symptoms that may include fever, malaise, anorexia, muscle aches, headache, nausea and/or vomiting, leukopenia and thrombocytopenia. Liver enzymes in the serum may also be mildly elevated.
• 4-10 days of remission (apyrexia)
• second phase of the disease occurs in 20-30% of patients and involves the return of fever and CNS symptoms of aseptic meningitis (e.g., headache and a stiff neck) or encephalitis (e.g. drowsiness, confusion, sensory disturbances, and/or motor abnormalities such as polio-like paralysis) or meningoencephalitis or encephalomyelitis^ref. In contrast to RSSE, TBE is more severe in adults than in children. Leukocytosis in the blood and the CSF is usually found.

• prevention of tick bites (repellents like DEET being less effective than against mosquitoes)
• killed vaccine
• administration of immunoglobulin carries a specific risk: besides the usual risks associated with immunoglobulin products if given too late (that is, in our recommendation, > 96 hours after the tick bite, which in fact only rarely can be determined precisely, especially in people with a great deal of outdoor activity), use of specific hyperimmunoglobulin might lead to some kind of antibody-dependent enhancement (ADE), which may in turn aggravate the clinical picture. Therefore the criteria for the use of gamma globulin as a means of post-exposure prophylaxis were very strict, and as a result -- after decades of use -- this product is no longer available in Austria, although there have been several studies on its use. The recommendation was: up to 48 hours after the tick bite, 0.1 ml/kg body weight; after 48 to 96 hours, 0.2 ml/kg IM, which in the case of a 70 kg individual at 72 hours would mean administration of 14 (!!!) ml hyperimmunoglobulin IM. As far as I know a statistically significant benefit of TBE hyperimmunoglobulin has never been proven. Enhancement with Langat virus was described many years ago: virus titre increased in Langat-infected mice pre-treated with antiserum against Langat virus^ref. Similarly, the virulence of yellow fever virus (related to TBEV but less closely than Langat virus) in mice increased in the presence of specific monoclonal antibodies against the envelope protein of yellow fever virus.^{ref1, ref2, ref3}