Vaccination against tick-borne encephalitis: instruction for use, Competently about health on iLive
Vaccination against tick-borne encephalitis
- 1 Vaccination against tick-borne encephalitis
- 2 Medical expert of the article
- 3 Indication, administration and dose
- 4 Vaccination reactions and contraindications for vaccination against tick-borne encephalitis
- 5 Vaccination against tick-borne encephalitis: characteristics of drugs
- 6 Post-exposure prophylaxis of tick-borne encephalitis
- 7 ARCHIVED — Statement on tick-borne encephalitis
- 8 We have archived this page and will not be updating it.
- 9 We have archived this page and will not be updating it.
- 9.1 Preamble
- 9.2 Introduction
- 9.3 2. Epidemiology
- 9.4 3. Routes of transmission
- 9.5 4. Clinical features of tick-borne encephalitis
- 9.6 5. Methods of prevention
- 9.7 6. Immunization
- 9.8 Special considerations for the FSME-IMMUN® and Encepur® vaccines
- 9.9 7. Recommendations
- 9.10 Expiration
- 9.11 Acknowledgements
- 9.12 References
- 9.13 Appendix 1
Medical expert of the article
Tick-borne encephalitis is caused by flavivirus, transmitted by ixodid mites, and cases of infection through fresh milk are described. After a 10-day incubation period, catarrh, fever, headache, joint pain, CNS lesions (encephalitis — 30%, meningitis — 60%, meningoencephalitis — 10%). Endemic in forest and taiga zones. Vaccination from tick-borne encephalitis in endemic areas led to a reduction in morbidity: if in 2001 in Russia there were 6401 cases of tick-borne encephalitis (incidence of 4.38 per 100 000, in children, respectively, 976 and 3.67), then in 2007, 3162 people (2.21 per 100 000), incl. Children — 405 (1.86 per 100 000). It is necessary to vaccinate against tick-borne encephalitis, in addition to risk groups, also schoolchildren, which is conducted massively in a number of regions.
Indication, administration and dose
The vaccine against tick-borne encephalitis is a culture concentrate dry for children and adults. The course consists of 2 doses (0.5 ml each) in autumn and spring at intervals of 5-7 months (minimum allowed — 2 months). The first revaccination in 1 year, then every three years. The vaccine is injected subcutaneously into the subscapular region or intramuscularly into the deltoid muscle, children — from the age of 3 years.
EnceVir is applied from the age of 3 years. The course consists of 2 / m injections of 0.5 ml at intervals of 5-7 or 1-2 months (emergency schedule). The first revaccination — in 1 year, the next — in 3 years.
FSME-IMMUN® (cultured, highly purified, sorbed) is administered to persons over 16 years of age at a dose of 0.5 ml IM, it is possible to inject simultaneously with other vaccines into different parts of the body. Children 6 months to 16 years of age are given the FSME-IMMUN® junior vaccine. The main (standard) vaccination: 2 doses with an interval of 1-3 months, emergency vaccination — with an interval of 14 days. Booster after 5-12 months, then in 3 years. Children under one year are vaccinated at a high risk of infection. Shelf life — 30 months.
Encepure-adult is used from the age of 12 years. Two schemes are used. Traditional: 2 injections with an interval of 1-2 months, the third — after 9-12 months. After the second. The protective level of antibodies is reached 2 weeks after the 2nd vaccination. Emergency scheme: 0-7-21th day, 9-12 months. Revaccination — in 3-5 years. Effective protection 3 weeks after the start of the vaccine.
Encepur-children are administered to children 1-12 years of age according to the same two schemes indicated above.
Human immunoglobulin against tick-borne encephalitis (IG) is administered 96 hours prior to visiting the foci with no vaccinated — intramuscularly 1 time at a dose of 0.1 ml / kg. The protective effect begins after 24 hours and lasts about 4 weeks, after which the same dose is repeated
Vaccination reactions and contraindications for vaccination against tick-borne encephalitis
At the injection site, soreness, swelling and denseness can occasionally be noted, sometimes with an increase in lymph nodes, and even less often a granuloma. After the 1 st dose, there is sometimes a brief increase in temperature, headache, pain in the extremities, nausea and vomiting, these doses are rarely seen on the following doses. Allergic reactions are extremely rare. According to the WHO, FSOME-Immun gives side effects with a frequency of 0.01-0.0001%. In the place of introduction of immunoglobulins, itching and pain are possible , very rarely — anaphylactic reactions.
Contraindications, in addition to common for all vaccines, are allergic to chicken eggs; Inoculation against tick-borne encephalitis is permissible after 2 weeks. After childbirth. The use of FSME-Immun is not contraindicated during pregnancy and lactation.
Vaccination against tick-borne encephalitis: characteristics of drugs
Vaccines against tick-borne encephalitis — inactivated, adsorbed on aluminum hydroxide, differ in the initial strains of the virus, the content of the antigen and protein. All vaccines are stored at 2-8 °.
Testicular encephalitis vaccines registered in Russia
Vaccine tick-borne encephalitis is dry for children and adults, Russia
Antigen (strain Sofin or 20S), kanamycin up to 75 mcg. Without a preservative. Protein up to 30 mcg. It is applied from 3 years.
EnceVir — liquid vaccine, Russia
Suspension of the virus (growth in the culture of cells of chick embryos). In 1 dose (0.5 ml) of chicken protein to 0.5 mcg, human albumin to 250 mcg, aluminum hydroxide 0.3-0.5 mg. Without antibiotics and preservatives. It is applied from 3 years.
FSME-IMMUN®-Baxter Vaccine AG, Austria. Junior (0,5-16 years)
In 1 dose (0.5 ml), 2.38 μg of Neudoerfl virus strain (growth in chicken embryonic cell culture), phosphate buffer, human albumin. Without preservatives, antibiotics and heterogeneous proteins. FSME-IMMUN® Junior — 0.25 ml / dose.
Novartis Vaccines and Diagnostics GmbH & Co., KG, Germany
In 0.5 ml (adult dose) 1.5 μg of antigen of the virus K23 strain, aluminum hydroxide (1 mg). Without preservatives, protein stabilizers and human blood components. Applied at the age of 1-11 years and over 12 years.
For emergency passive immunoprophylaxis, human immunoglobulins against tick-borne encephalitis are used.
Post-exposure prophylaxis of tick-borne encephalitis
Human immunoglobulin (IG) is injected after sucking the tick (persons not vaccinated or vaccinated less than 10 days before the bite): in the first 96 hours, 0.1-0.2 ml / kg (slowly, deep into the muscle), 5 ml in different parts of the body. After 4 days for 28 days — the incubation of tick-borne encephalitis — the drug is not injected, tk. This can make the disease worse. For the same reason, in a number of countries, children under the age of 14 are not being injected. The drug in many countries is withdrawn from sale.
The interval between the administration of specific immunoglobulin and vaccination against tick-borne encephalitis should be at least 4 weeks.
ARCHIVED — Statement on tick-borne encephalitis
We have archived this page and will not be updating it.
You can use it for research or reference.
We have archived this page and will not be updating it.
You can use it for research or reference.
Canada Communicable Disease Report
Volume 32 • ACS-3 1 April 2006
An Advisory Committee Statement (ACS)
Committee to Advise on Tropical Medicine and Travel (CATMAT)*†
The Committee to Advise on Tropical Medicine and Travel (CATMAT) provides the Public Health Agency of Canada (PHAC) with ongoing and timely medical, scientific, and public health advice relating to tropical infectious disease and health risks associated with international travel. PHAC acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge and medical practices, and is disseminating this document for information purposes to both travellers and the medical community caring for travellers.
Persons administering or using drugs, vaccines, or other products should also be aware of the contents of the product monograph(s) or other similarly approved standards or instructions for use. Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) or other similarly approved standards or instructions for use by the licensed manufacturer(s). Manufacturers have sought approval and provided evidence as to the safety and efficacy of their products only when used in accordance with the product monographs or other similarly approved standards or instructions for use.
Tick-borne encephalitis (TBE) is a viral disease affecting the central nervous system. The etiologic agent, tick-borne encephalitis virus (TBEV), belongs to the family of Flaviviridae (genus Flaviviruses). Like many flaviviruses, it is an arbovirus or arthropod-borne virus. In the tick-borne virus serocomplex, three genotypes of TBEV have been identified: the central European, Far Eastern, and Siberian subtypes 1 . The virus exists in natural foci, where it circulates between vertebrate and arthropod hosts. The vertebrate hosts of the virus are mainly rodents, but other wild or domestic animals, such as fox, deer, dogs, or cows, may also be infected. The vector-competent hosts are ticks belonging to the family Ixodidae (hard ticks). Many species of hard tick are known to transmit the virus, but two species play a major role in TBEV transmission: Ixodes ricinus and Ixodes persulcatus 2 .
Ixodes ricinus is widespread in central and western Europe, where it transmits the European TBEV subtype (Central European TBE). Ixodes persulcatus is widely distributed in Russia and the Far East, where it transmits the Siberian and Far Eastern TBEV subtypes (Russian Spring Summer Encephalitis) 1,2 . Overlapping subtypes exist in eastern European regions. Areas of risk are found through large sections of Europe from eastern France to southern Scandinavia to Croatia, and as far east as northern Japan 2-4 . The current epidemiology of TBE has recently been reviewed in detail 2 . The Web site of the International Scientific Working group on TBE can be consulted for reports and maps on TBE infections in specific European countries, including Russia (ISW-TBE Reports) 5 . Another source describing TBE epidemiology in European countries can be found in Eurosurveillance, a publication of the European Community 6 . The ticks are distributed in natural foci (hot spots) that tend to be stable over time 7 . Natural foci are usually in areas of moderate temperature, high humidity, and altitudes of up to 1000 m 8,9 . According to some reports, ticks may be found as high as 1400 m 10,11 . Preferred sites are the edges of forests and areas with deciduous trees, low-growing dense bush, and low ground cover 8 . Domestic and wild habitats with sufficient moisture, ground foliage, and vegetation litter can provide shelter for both ticks and their animal hosts 9 . Tick activity starts in March/April and ends in October/November, usually peaking in the months of May/June and September/October in central Europe 2,8 .
Surveys of virus prevalence in ticks in natural foci show considerable variability by region and across time. Prevalence rates as low as 0.9% (Bavaria 1997-1998) and as high as 26.6% (Latvia 1995) have been reported in wild-caught ticks(7,12). TBEV prevalence in ticks removed from patients can be higher: for example 31% to 41% from Latvian patients between 1998 and 2002(12). The reason for the discrepancy in prevalence rates between ticks collected in the field and those collected from patients is not certain; however, it is known that TBEV titre in tick saliva increases during the feeding process (see Routes of Transmission).
The seroprevalence of TBE in human populations in endemic areas also varies widely. A survey of 1,896 unvaccinated forestry workers in the various counties of Baden-Württemberg (south-west Germany) from 1997 to 1999 showed a mean seroprevalence of 7.3% 13 . In 2002, TBE seroprevalence rates in the general populations of Lithuania and Denmark (Island of Bornholm) were reported to be 3% and 1.4% respectively 14,15 . However, with increasing TBE immunization rates in the population, seroprevalence data become less reliable indicators of TBE infection rates.
Incidence rates, as well as the number of TBE cases, in several western and eastern European countries for the years 1976 to 2002 can be viewed on the Web site of the ISW-TBE 5 . The number of reported cases in a country depends on the prevalence of infected ticks, the outdoor activities of the population, and the diagnostic abilities and reporting system of the country. In Austria, a TBE mass vaccination program was introduced in 1981 16,17 . Until then, the average number of TBE cases per year was 500 (range 280 to 700) 16 . Since 1982, there has been a significant reduction, down to 62 TBE cases in 1998 and 41 cases in 1999(16,17). Although Austria is the only European country to have a routine vaccination program, Hungary has also reported a significant decline in cases from 1996 (n = 224) to 1999 (n = 51). The decline in Hungary is not fully understood but may be due partially to vaccination and partially to declining economic conditions resulting in decreased diagnostic testing 2 . In many countries without routine vaccination programs, such as Germany and the Czech Republic, the number of cases per year has remained high or has increased over time 5 .
3. Routes of transmission
Ixodes ticks normally have a 3-year life cycle (range 2 to 6 years) as they grow through the following four stages: egg, larva, sexually immature nymph, and sexually mature adult 9 . Larvae and nymphs feed principally on rodents, and adult ticks tend to feed on larger animals. Ticks can become infected at any stage, including infection through transovarial transmission, and they remain infected for life 2 . Ticks at all stages are known to bite humans 9 .
Once a tick finds an appropriate host, the attachment and feeding process requires several days. The tick’s saliva contains chemicals that counteract the hemostatic, inflammatory, and immune responses of the host. The bite is painless and is often not noticed 2,18 . The saliva also contains and transmits TBEV 2,18 . The virus titre in saliva can increase 10 to 100 fold from the first to the third day of the blood meal 2 . However, transmission typically occurs early in the feeding process 2,18 .
Another, less frequent, route of transmission is the ingestion of unpasteurized milk and milk products 2,19 .
The same ticks (I. ricinus and I. persulcatus) that transmit TBEV can also transmit Borrelia burgdorferi, the agent of lyme borreliosis; Anaplasma phagocytophilum, the agent of human granulocytic ehrlichiosis; Babesia, the agent of babesiosis; and other, rarer, pathogens2,9. Simultaneous infection with multiple organisms is possible. The Web site of the European Union Concerted Action on Lyme Borreliosis can be consulted for further information on Lyme disease in Europe9.
4. Clinical features of tick-borne encephalitis
Central European variety
Asymptomatic infection is common. According to different sources, 10% to 30% of infected persons develop symptoms 4,20 . The incubation period is usually 7 to14 days but ranges from 4 to 28 days 20,21 . The illness is biphasic. The first phase, which usually resolves within 1 week and correlates with viremia, is frequently subclinical, or it presents as a nonspecific illness with fever, malaise, headaches, nausea, and vomiting 20,21 . Following a temporary remission of approximately 1 week, in 10% to 30% of individuals there is a second neurologic phase after the virus has spread to the central nervous system 20,22 . The second stage presents as aseptic meningitis (especially in children) or encephalitis, myelitis, radiculitis, or some combination 8 . Studies of patients with neurologic illness report that, overall, approximately 50% have meningitis, 40% meningoencephalitis, and 10% meningoencephalomyelitis 21,23,24 .
The diagnosis is usually based on the history of exposure to ticks within the previous 3 to 4 weeks, clinical symptoms, and specific IgM and IgG antibodies to TBE, as measured by enzyme-linked immunosorbent assay (ELISA) 4,20,25 . Antiviral antibodies are usually detectable at the beginning of the second phase 20,25 . Other specific tests are nested reverse transcriptase polymerase chain reaction (nRT-PCR) to detect virus-specific nucleic acid, or Western blots, performed in specialized laboratories 20,25 . There are no effective antiviral drugs for TBEV, therefore treatment consists of supportive care(20,22). The reported case fatality rate is approximately 0.5% to 2% 20,22,23 . Long-term follow-up studies show that a significant proportion (36% to 94%) of cases have a postencephalitic syndrome for months to years after the acute illness, characterized by neuro-psychiatric symptoms such as asthenia, severe headaches, memory loss, lack of concentration, decreased stamina, depression, ataxia, incoordination, tremor, and/or hearing impairment 22,24 . Residual paresis has been reported in 0.3% to 10% of patients 21,22 . Residual neurologic sequelae are more likely to occur in the elderly and in those with severe disease 4,8 . Children have a generally better prognosis than adults 21 .
Far Eastern variety
The course of this disease is monophasic and more severe, with rapid neurologic involvement. The case fatality rate is 20%, and residual neurologic sequelae occur in up to 60% of survivors 8 .
5. Methods of prevention
The probability of human infection in an area with a natural TBEV focus depends on the prevalence of infected ticks, human exposure to ticks, and the preventive measures taken.
Environmental and personal protective measures, such as wearing clothing with a smooth weave, taping pants or tucking them inside footwear, applying DEET (N,N-diethyl-3-methylbenzamide), and using permethrin-impregnated clothing, help to minimize the risk of tick bites 26-28 . Permethrin appears to be more effective than DEET, but the combination of DEET and permethrin gives almost 100% protection 26-28 . If a tick bite has occurred, proper removal of the tick, as outlined under Recommendations, may decrease the risk of viral transmission 29 but will not prevent all cases because of early viral transmission of the virus during a blood meal 2,18 .
Recommendations regarding environmental and personal protective measures are listed under Recommendations. Personal protective measures for the prevention of arthropod bites are fully described in CATMAT’s Statement on Personal Protective Measures to Prevent Arthropod Bites 30 .
Canadians residing in or travelling to TBE-endemic areas should be evaluated for their risk of tick bites (see Recommendations). Since TBE vaccination is safe and highly immunogenic, it should be recommended for travellers considered to be at risk 31 .
6.1 Pre-exposure active immunization
Two TBE vaccines, available in Europe, will be discussed: Encepur® adults (and Encepur® children) marketed by Chiron Vaccines, Germany, and FSME-IMMUN®0.5 mL (and FSMEIMMUN ® 0.25 mL Junior) by Baxter Vaccine AG, Austria. Both are inactivated vaccines and provide safe and reliable protection 17,32,33 . Immunity is induced against all TBEV variants, including the European and Far Eastern subtypes 34 .
The antigenic components of the two available vaccines (virus strain K23 of Encepur® and strain Neudoerfl of FSMEIMMUN ®) are highly homologous and can be assumed to elicit the same immune response 35 . In one study, > 400 subjects previously vaccinated with at least three doses of FSME-IMMUN® were successfully boosted with Encepur® 36 . The result suggests that the strains are interchangeable.
The main manufacturing characteristics of the currently available vaccines are detailed in Table 1.
Table 1. Product characterization of vaccines referred to in text
Name of vaccine (availability)
FSME-IMMUN® 0.5 mL marketed 2001
Grown on chick embryo cells only,
FSME-IMMUN® 0.25 mL Junior marketed 2003
Grown on chick embryo cells only, contains human serum albumin
Encepur® adults marketed 2001
Grown on chick embryo fibroblasts, polygeline-free
Encepur® children marketed 2001
Grown on chick embryo fibroblasts, polygeline-free
The vaccination schedules, immunogenicity, and safety data of the FSME-IMMUN® and Encepur® vaccines are summarized in Table 2.
Table 2. Summary of vaccine characteristics of FSME-IMMUN® and Encepur®
1 to 33 . It was reformulated in 1999 to eliminate mouse brain passage during manufacture 33 . It is now marketed under the name FSME-IMMUN® 0.5 mL for those ≥ 16 years and FSME-IMMUN® 0.25 mL Junior for children 1 to 15 years of age (Summaries of Product Characteristics for FSME-IMMUN® 0.5 mL/FSME-IMMUN® 025 mL: unpublished work, Baxter Vaccine AG, Vienna, February 2004). It is a suspension of formaldehyde-inactivated TBEV (strain Neudoerfl) propagated in chick embryo cells. It is adsorbed onto aluminum hydroxide and contains 0.5 mg (junior 0.25 mg) human serum albumin as stabilizer and residues of protamine sulphate, gentamicin, neomycin, and formaldehyde 33 . It is thimerosal-free. Each preloaded syringe contains a 0.5 mL (junior 0.25 mL) suspension and has a shelf life of 24 months when stored at 2° C to 8° C 33 .
Many of the data upon which current recommendations are made were generated with the earlier formulation of FSME-IMMUN®. The efficacy and safety profiles of the earlier and current formulations appear to be very similar.
Scheduling and route of administration
The manufacturer’s recommendations with regard to primary and booster vaccinations for adults and children are stated in the Summaries of Products Characteristics for FSME-IMMUN® 0.5 mL and FSME-IMMUN® 0.25 mL Junior. The manufacturer recommends administration of a primary immunization series in three doses, at 0, 1 to 3 months, and 6 to 15 months (conventional schedule). The vaccine is given intra-muscularly into the deltoid muscle. If a rapid immune response is required, the second dose should be given 2 weeks after the first dose.
Recommendations regarding booster intervals have recently been published in the Austrian immunization plan 37 and are based on the results of a recent cross-sectional study 38 .
For at risk adults 37 (see section 6.3). However, this recommendation is not supported by a recent cross-sectional study, which indicated that a single booster dose is generally successful, regardless of the time interval following the last vaccination 36 . The TBE vaccines are therefore similar to other inactivated alum-adsorbed viral vaccines in that a single booster usually re-establishes full protection independently of the time interval following the primary series.
Since long-term studies are not yet available for children, booster intervals of 3 years are recommended when administering the pediatric vaccine.
The vaccination series should ideally be started in winter. Effective immunity will then be present at the start of the tick season.
Protective efficacy, immunogenicity, and safety
Protective efficacy: The efficacy (protection) rates of previous generation FSME-IMMUN® vaccines administered on day 0, at 2 weeks to 3 months, and at 9 to 15 months have been calculated for the Austrian population to be 95.6% to 100% after the second and 96% to 98.7% after the third vaccine dose 17 . No other efficacy studies could be found for TBE vaccines.
Immunogenicity after primary immunization: The immunogenicity and safety of FSME-IMMUN® in adults and children receiving primary vaccination have been evaluated in several large studies sponsored by Baxter. These studies are listed in Appendix 1. Some of them have been described in a recent review article and in brief abstracts 33,39,40 . In these studies, the adult and pediatric vaccines were administered on day 0, at 21 to 35 weeks, and between 6 months and 10 months. Seroconversions were measured by both enzyme-linked immunoassay (EIA) and neutralization test approximately 1 month after vaccination. In adults, the seroconversion rates after the second and third doses were found to be 92.9% to 97% and 100% respectively (Appendix 1: studies #062, #201, #202). In children, depending on their age, the seroconversion rates were 98.5% to 100% and 100% after the second and third doses respectively (Appendix 1: studies #199, 205, 206, 207).
The manufacturer’s recommendation for an accelerated schedule, in which the second dose is given 2 weeks after the first, is supported by one published pediatric study. In this study, of 37 children aged 8 to 14 years who were vaccinated on day 0 and 10, 95% had seroconverted at 2 weeks after the second dose, as measured by EIA 41 .
Long-term immunogenicity: Long-term immunogenicity has been assessed in a cross-sectional study of 430 previously vaccinated adults immunized with earlier generation FSME-IMMUN® vaccines. The authors concluded that, following a primary vaccination and ≥ 1 booster dose, the immune protection exceeded 3 years and appeared to be sufficient for up to 8 years after the last booster dose 38 .
FSME-IMMUN® 0.5 mL and its pediatric version, distributed in Europe, contain a small amount of human serum albumin (HSA) of European (German or Austrian) origin. As a result, there is a theoretical risk of transmitting the prion that causes variant Creutzfeldt-Jakob disease (vCJD). No risk assessment is available for vaccines containing HSA of European origin. However, a generic risk assessment of vaccines incorporating bovine biological materials in their manufacture suggests that any such risk is likely to be extremely small: 45 . Several clinical trials demonstrated the general immunogenicity and safety of these early formulations 46-48 . However, post-marketing surveillance revealed that children had an increased frequency of allergic reactions, which were likely due to polygeline, a proteinaceous stabilizer in the vaccine 33,45 . A polygeline-free TBE vaccine under the names of Encepur® adults and Encepur® children was subsequently introduced and evaluated in prospective, controlled, multi-centre clinical trials 45,49,50 . These formulations have been on the market since 2001 and are sold in several European countries. Encepur® children is recommended for children between 1 and 11 years of age 32 .
The Encepur® vaccines are a suspension of formaldehyde-inactivated TBEV (strain K23), grown on chick embryo fibroblasts 32 . The adjuvant is aluminum hydroxide. There are trace amounts of formaldehyde, chlortetracycline, gentamicin, and neomycin in the solution. The current formulations contain no proteinderived stabilizers (e.g. HSA) and no polygeline. Preloaded syringes contain 1.5 µg/0.5 mL TBE antigen (adult) and 0.75 µg/ 0.25 mL TBE antigen (children). The vaccine should be stored between +2º C and +8º C and has a shelf life of
15 months 32 (Summary of Product Characteristics Encepur® adults/Summary of Product Characteristics Encepur® children: unpublished work, Chiron Behring GMBH & Co Kg, Marburg, Germany, June 2004).
Scheduling and route of administration
The vaccine is administered intramuscularly, preferably into the deltoid muscle. Like FSME, Encepur® vaccines can be administered according to a conventional or an accelerated schedule, both offering high protection 47,49,50 .
According to the conventional vaccination schedule, the primary vaccination consists of three doses, on day 0, 1 to 3 months, and 9 to 12 months. If risk of exposure continues, the manufacturer recommends booster doses every 3 years 32 .
In most clinical trials of Encepur® vaccines, the accelerated schedule has been used with three doses given on day 0, 7, and 21. After the accelerated schedule, the first booster dose is administered at 12 to 18 months.
It should be noted that the recent recommendations of the 2005 Austrian Immunization Guide with regard to longer booster intervals for individuals 3,000) and in children 1 to 11 years old (pediatric formulation: n = 390 for immunogenicity and > 3,000 for safety). All subjects were vaccinated on day 0, 7, and 21 49,50 .
Immunogenicity after primary immunization: After the administration of the primary series, seroconversion, as measured by the neutralization test, occurred in 100% of adult and pediatric subjects 49,50 .
Long-term immunogenicity: Several studies have demonstrated the long-term persistence of high (presumably protective) titres after primary vaccination: 99.5% and 100% immediately before the first (12 to 18 month) and second (36 month) booster doses respectively 51-53 . These results support a recommended booster interval of > 3 years 54 .
Safety: The reported adverse reactions following vaccination with Encepur® vaccines include local reactions and systemic reactions such as fever, malaise, headaches, myalgia, arthralgia, nausea in children ≥ 3 years and adults 49,50 . Systemic symptoms are mostly mild and transient, and are reported in 1% (fever in adults) to 18% (myalgia in adults) 49 . A small percentage ( 49,50 . Systemic reactions in children 1 to 2 years old have been mainly fever, sleepiness, irritability, or change in eating habits (reported in 8% to 14%, depending on symptom reported) 50 . In the large clinical trials conducted to date, there were no reports in adults or children of serious clinical events, such as seizures, or of systemic allergic reactions, considered to be causally related to the vaccinations 32,49,50 .
Rare and isolated cases of central or peripheral nervous system complications, such as ascending paralysis, in severe cases with respiratory paralysis, have been reported following vaccination with previous generation Encepur® vaccines (summaries of the product characteristics of Encepur® vaccines).
Special considerations for the FSME-IMMUN® and Encepur® vaccines
The viral strains of the TBE vaccines are propagated in purified chick embryo cells(3 2,33 . Although purified, both of the available vaccines may still contain egg constituents. The summaries of product characteristics for the FSME-IMMUN® and Encepur® vaccines advise that individuals with prior anaphylactic reactions to eggs or egg products should be vaccinated only under close clinical monitoring with readiness for emergency treatment. However, FSME-IMMUN® vaccine has apparently been safely administered to > 100 persons with allergies to egg whites (note that the types of egg allergy were not described in this study) 55 .
Impaired immune system
Immunosuppressed individuals may respond poorly to TBE vaccination 56-58 . If they are at risk of TBE, it may be appropriate to determine their immune response after the primary series by serologic testing (where available) 58 (see Testing for Antibodies after TBE Vaccination). There are no guidelines for evidencebased recommendations concerning the timing of serologic testing in immunocompromised individuals.
Pregnancy and lactation
According to the summaries of product characteristics of the FSME-IMMUN® and Encepur® vaccines, the safety of the TBE vaccines during pregnancy and lactation has not been established. An individual risk-benefit assessment is required in these cases.
6.2 Availability of TBE vaccines in Canada
The FSME-IMMUN® 0.5 mL vaccine has been approved for sale in Canada as of 3 February, 2005, and is available on the Canadian market. The distributor of FSME-IMMUN® in Canada is Baxter Corporation (Mississauga) .The pediatric FSME vaccine and the Encepur® products are not licensed and not available in Canada.
Until one of the pediatric formulations is licensed in Canada, there are two options possible, namely to procure a European licensed pediatric product through the Special Access Program (SAP) or to use a half-dose of the adult FSME vaccine to immunize children 25 . A comparison of six commercial IgG ELISA kits suggests that they have generally high sensitivity (73% to 99%) 59 . However, there is extensive cross-reactivity with other flavivirus antibodies, such as West Nile fever, dengue, yellow fever, and Japanese encephalitis antibodies 25,60,61 . These crossreactive antibodies do not neutralize TBEV and are not protective against TBE infections 60,61 . Therefore, when interpreting positive EIA results, consideration must be given to possible crossreactivity with other flaviviruses. False-positive results can be minimized by taking a proper history of past flavivirus exposures and/or vaccinations. Alternatively, if available, a pre-vaccination EIA can establish a baseline, or a highly specific and sensitive neutralization test can be used 25,60,61 . The neutralization test, which measures the presence of TBE-specific neutralizing antibodies, is only available in specialized laboratories (Dr. H. Peters Dade Behring, Marburg, Germany: personal communication, 2002). In the absence of prior exposure to other flaviviruses, IgG EIA results for TBE correlate well with the results of the neutralization test 25,61,62 . According to Health Canada’s Medical Devices Active Licence Listing (http://www.mdall.ca), there are no TBE serologic tests currently licensed for sale in Canada.
To identify travellers who are at risk of contracting the TBE virus, travel medicine professionals should consider the season of travel, travel itinerary, and the activities of the traveller.
Season of travel: ticks are active from March to November.
Itinerary: several referenced Web sites 5,6 indicate risk areas. Furthermore, tick activity should be considered at altitudes up to 1400 m (see Epidemiology) 10,11 .
Activities: risk activities include fieldwork, biking, hiking or camping outdoors, particularly at the edge of forests, in parks or meadows, and where the countryside is moist and uncultivated, containing low brush and ground foliage (see Epidemiology).
Travellers meeting all of these criteria should be advised regarding prevention of tick bites, tick removal, and vaccination.
Table 3 presents the evidence-based categories for the strength and quality of evidence for the following recommendations 63 .
Table 3. Strength and quality of evidence summary sheet 63
Good evidence to support a recommendation for use.
Moderate evidence to support a recommendation for use.
Poor evidence to support a recommendation for or against use.
Moderate evidence to support a recommendation against use.
Good evidence to support a recommendation against use.
Categories for the quality of evidence on which recommendations are made.
Evidence from at least one properly randomized, controlled trial.
Evidence from at least one well-designed clinical trial without randomization, from cohort or case-controlled analytic studies, preferably frommore than one centre, from multiple time series, or from dramatic results in uncontrolled experiments.
Evidence from opinions or respected authorities on the basis of clinical experience, descriptive studies, or reports of expert committees.
- Grass around residences should be kept cut. (CIII)
- Wild animals should be kept away from residential areas. (CIII)
- Brush should be kept away from areas of human activity. (CIII)
Prevention of tick-bites
There is recent evidence that dark-coloured clothing may attract fewer ticks than light clothing 64 . (CII).
Smoothly-woven clothing makes it more difficult for ticks to attach 27 . (BII)
As much as possible, body parts should be covered by clothing. This includes taping the cuffs of pants or placing them inside footwear 27 . (BII)
For maximal effectiveness (nearly 100% protection) DEET (N,N-diethyl-mtoluamide) and permethrin on clothing should be used concurrently 26 . (AII)
Body and clothing should be inspected for ticks during and/or after risk activities. (CIII)
Personal preventive means after a tick bite has occurred
Attached ticks should be removed by grasping the tick as close as possible to the skin with blunt curved forceps or tweezers and pulling steadily upward, without twisting or jerking 29 . (BIII)
Alcohol, matches, or vaseline should not be used when removing ticks, since these methods can cause the tick to release an increased number of virus particles into the host 29 . (CIII)
Handling of the tick with bare hands should be avoided, since tick fluids containing infectious agents may enter through breaks in the skin 29 . (CIII)
The bite site should be disinfected after tick removal and hands should be washed with soap and water 29 . (CIII)
The date of the tick bite and the onset of any symptoms should be documented. (CIII)
A physician should be contacted if any signs of unusual illness occur within 28 days of a tick bite. (CIII)
Primary prevention of TBE infection
Unpasteurized milk and milk products should be avoided 2,19 . (AIII)
Vaccination of adults and children with FSME-IMMUN® 0.5 mL and FSME-IMMUN® 0.25 mL Junior respectively is safe and immunogenic (see Appendix 1). (AI)
The vaccination of adults and children with Encepur® adults or Encepur® children respectively is safe and immunogenic 49,50 . (AI)
Booster doses are recommended for persons at risk:
Following the accelerated schedule of Encepur® adults or Encepur® children, the first booster dose should be given 12 to 18 months after the primary series 51,52 . (CII)
The time interval of booster vaccinations using the pediatric vaccines of FSME-IMMUN® or Encepur® has not been evaluated. The manufacturers recommend 3 year intervals. (CIII)
Adults ≥ 60 years of age should continue to receive booster vaccinations at 3-year intervals 37,38 . (BII)
FSME-IMMUN® and Encepur® vaccines are interchangeable 35,36 . (AII)
Persons with anaphylactic reactions to eggs should be closely monitored, and emergency treatment should be kept available during vaccination with either FSME-IMMUN® or Encepur® vaccines. (CIII)
Immunosuppressed persons should consider serologic testing (where available) to determine the effectiveness of the primary series 56,58 . (CIII)
Pregnant or breast-feeding women should receive a risk-benefit assessment regarding the administration of TBE vaccine. (CIII)
In the absence of a previous flavivirus infection or vaccination, EIA results are highly correlated with those of the neutralization test 61 . (AII)
This document will be updated every 4 years or when new information becomes available.
CATMAT gratefully acknowledges the assistance in the preparation of this statement from Dr. Michael Bröker, Chiron Vaccines, Marburg; Dr. Eva Maria Poellabauer, Baxter Bioscience, Vienna; Dr. Jochen Süss, Nat. Ref.-Lab., Tick-borne Diseases, Federal Research Centre for Virus Diseases in Animals, Jena, Germany.
Heinz FX. Molecular aspects of TBE virus research. Vaccine 2003;21 (Suppl 1):S1/3-S1/10.
Süss J. Epidemiology and ecology of TBE relevant to the production of effective vaccines. Vaccine 2003;21(Suppl 1):S1/19-S1/35.
Bröker M, Gniel D. New foci of tick-borne encephalitis virus in Europe: Consequences for travellers from abroad. Travel Med and Infect Dis 2003;1:181-4.
Kaiser R. Frühsommermeningoencephalitis und Lyme Borreliosis-Prävention vor und nach Zeckenstich. Dtsch Med Wochenschr 1998;123:847-53.
International ScientificWorking Group oOn TBE. URL: Date of access: September 2005.
Tickborne encephalitis in Europe: Basic information, country by country. Eurosurveillance Weekly 2004;8(29):2-6. URL: .
Süss J, Schrader C, Abel U et coll. 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 1999;289:564-78.
Tsai TF. Flaviviruses (Yellow fever, dengue, dengue hemorrhagic fever, Japanese encephalitis, St. Louis encephalitis, tick-borne encephalitis). Dans : Mandell JL, Bennett JE, Dolin R, éds. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases, 5e éd. Philadelphia, Pennsylvania: Churchill Livingstone, 2000;1714-36.
European concerted action on Lyme borreliosis. URL: . Date of access: August 2005.
Walder G, Dierich MP,Würzner R. First documented case with the tick-borne encephalitis virus in Vorarlberg, Austria.Wien Klin Wochenschr 2001;113:454-8.
Daniel M, Danielová V, Kriz B et coll. Shift of the tick Ixodes ricinus and tick-borne encephalitis to higher altitudes in Central Europe. Eur J Clin Microbiol Infect Dis 2003;22:327-8.
Bormane A, Lucenko I, Duks A et coll. Vectors of tick-borne diseases and epidemiological situation in Latvia in 1993-2002. Int J Med Microbiol 2004;293(Suppl 37):36-47.
Oehme R, Hartelt K, Backe H et coll. Foci of tick-borne diseases in Southwest Germany. Int J Med Microbiol 2002;291(Suppl 33):22-9.
Han X, Aho M, Vene S et coll. Studies on TBE epidemiology in Finland (and Lithuania). Extended abstract. Int J Med Microbiol 2002;291 (Suppl 33):48-9.
Kristiansen K. TBE in Denmark — in particular on Bornholm. Extended abstract. Int J Med Microbiol 2002;291(Suppl 33):62-3.
Kunze U, Bernhard G, Böhm G et coll. Früsommer-meningo-encephalitis (FSME) und FSME-Schutzimpfung: Status 2000.Wiener MedWochenschr 2000;150:103-8.
Kunz C. TBE vaccination and the Austrian experience. Vaccine 2003, 21:S1/50-S1/55.
Nuttall PA. Pathogen-tick-host interactions: Borrelia burgdorferi and TBE virus. Zentralbl Bacteriol 1999;289:492-505.
Labuda M, Kozuch O, Lys J. Tickborne encephalitis virus natural foci in Slovakia: ticks, rodents, and . goats. Dans : Süss J, Kahl O, éds. 4th International Potsdam Symposium on Tick-borne Diseases: Tick-borne encephalitis and Lyme borreliosis, 1997 Feb 21-22, Potsdam, Germany. Lengerich: Pabst Science Publishers, 1997;34-46.
Robert Koch Institute. Frühsommer-meningoenzephalitis (FSME). RKI-Ratgeber Infektionskrankheiten-Merkblätter für Ärzte. URL: . Date of access: August 2005.
Kaiser R. The clinical and epidemiological profile of tick-borne encephalitis in Southern Germany 1994-98. A prospective study of 656 patients. Brain 1999;122:2067-78.
Dumpis U, Crook D, Oksi J. Tick-borne encephalitis. Clin Infect Dis 1999;28:882-90.
Kaiser R. Tick-borne encephalitis (TBE) in Germany and clinical course of the disease. Int J Med Microbiol 2002;291(Suppl 33):58-61.
Kaiser R, Vollmer H, Schmidtke K et coll. Verlauf und Prognose der FSME. Nervenarzt 1997;68:324-30.
Holzmann H. Diagnosis of tick-borne encephalitis. Vaccine 2003;21 (Suppl 1):S1/36-S1/40.
Young D, Evans SR. Safety and efficacy of DEET and permethrin in the prevention of arthropod attack. Mil Med 1998;163:324-30.
Schreck CE, Snoddy EL, Spielman A. Pressurized sprays of permethrin or DEET on military clothing for personal protection against Ixodes dammini (Acari: Ixodidae). J Med Entomol 1986;23:396-9.
Evans SR, Korch GW, Lawson MA. Comparative field evaluation of permethrin and DEET-treated military uniforms for personal protection against ticks (Acari). J Med Entomol 1990;27:829-34.
Needham GR. Evaluation of five popular methods for tick removal. Pediatrics 1985;75:997-1002.
Comité consultatif de la médecine tropicale et de la médecine des voyages (CCMTMV). Déclaration relative aux mesures de protection individuelle pour prévenir les pigûres ou morsures d’arthropodes. RMTC 2005; 31(DCC-4):1-20.
Robert Koch Institute. Risikogebiete der Frühsommer-Meningoenzephalitis (FSME) in Deutschland. Epidemiologisches Bulletin 2002;26:212-15. URL:
Kollaritsch H, Kreijs GJ, Mutz I et coll. A new generation of TBE vaccines: Encepur® children and Encepur® adults. New Drugs Statement. Int J Postgrad Train Med 2002;19:1-12.
Barrett PN, Schober-Bendixen S, Ehrlich HJ. History of TBE vaccines. Vaccine 2003;21(Suppl 1):S1/41-S1/49.
Heinz FX. Molecular aspects of TBE virus research. Vaccine 2003;21 (Suppl 1):S1/3-S1/10.
Ecker M, Allison SL, Meixner T et coll. Sequence analysis and genetic classification of tick-borne encephalitis viruses from Europe and Asia. J Gen Virol 1999;80:179-85.
Rendi-Wagner P, Kundi M, Zent O et coll. Immunogenicity and safety of a booster vaccination against tick-borne encephalitis more than 3 years following the last immunisation. Vaccine 2004;23:427-34.
Oberster Sanitätsrat. Impfplan 2006 Österreich. Vienna: Bundesministerium für Gesundheit und Frauen, 2004. URL: .
Rendi-Wagner P, Kundi M, Zent O et coll. Protective immunity following vaccination against tick-borne-encephalitis: Antibody persistence longer than expected? Vaccine 2004;22:2743-9.
Löw-Baselli A, Fritsch S, Pavlova BG et coll. Safety and immunogenicity of FSME-IMMUN® “new” vs. Encepur® in adult. Abstract. Int J Med Microbiol 2004;293(Suppl 37):128-9.
Ehrlich HJ, Löw-Baselli A, Poellabauer EM et coll. Randomized, phase II, multicenter dose-finding studies of a modified tick-borne encephalitis vaccine in children: evaluation of safety and immunogenicity of two vaccinations with FSME-IMMUN® “new”. Abstract. Int J Med Microbiol 2004; 293(Suppl)37:126-7.
Hofmann H, Haschke F, Popow C et coll. Verkürzung des Intervalls bei FSME-Impfung bei asthmakranken Kindern. Wiener Klin Wochenschr 1981;93:358-60.
Grzeszczuk A, Sokolewicz-Bobrowska E, Prokopowicz D. Adverse reactions to tick-borne encephalitis vaccine: FSME-IMMUN®. Infection 1998;26:385-8.
Hofmann H. Muß nach FSME-Impfung mit dem Auftreten neurologischer Störungen gerechnet werden? Übersichten 1995:509-15.
Goerre S, Kesselring J, Hartmann K et coll. Neurologische Nebenwirkungen nach Impfung gegen die Frühsommer-Meningo-enzephalitis. SchweizMed Wochenschr 1993;123:654-7.
Zent O. Clinical evaluation of polygeline-free TBE vaccines for children, adolescents and adults. Dans : Chiron Behring, éds. Tick-borne encephalitis in Europe — a new generation of vaccines. Abstracts and studies of the Siena Conference, 2001, Sept 30-Oct 2, Siena, Italy. Marburg: Chiron Behring; 2001;9-10.
Bock HL, Klockmann U, Jüngst C et coll. A new vaccine against tick-borne encephalitis: Initial trial in man including a dose-response study. Vaccine 1990;8:22-4.
Harabacz I, Bock H, Jüngst Ch et coll. A randomized phase II study of a new tick-borne encephalitis vaccine using three different doses and two immunization regimens. Vaccine 1992;10:145-50.
Girgsdies OE, Rosenkranz G. Tick-borne encephalitis: Development of a paediatric vaccine. A controlled randomized, double-blind and multicentre study. Vaccine 1996;14:1421-8.
Zent O, Beran J, JilgWet coll. Clinical evaluation of a polygeline-free tick-borne encephalitis vaccine for adolescents and adults. Vaccine 2003;21:738-41.
Zent O, Banzhoff A, Hilbert AK et coll. Safety, immunogenicity and tolerability of a new pediatric tick-borne encephalitis (TBE) vaccine, free of protein-derived stabilizer. Vaccine 2003;21:3584-92.
Zent O, Jilg W, Plentz A et coll. Kinetics of the immune response after primary and booster immunization against tick-borne encephalitis (TBE) in adults using the rapid immunization schedule. Vaccine 2003;21:4615-60.
Zent O, Schwarz TF, Plentz A et coll. TBE booster immunization in adults — first experience with a new tick-borne encephalitis (TBE) vaccine, free of protein-derived stabilizer. Int J Med Microbiol 2004;293(Suppl 37):134-8.
Beran J, Chlibek R, Douda P et coll. Long-term immunity after vaccination against tick-borne encephalitis with ENCEPUR® using the rapid vaccination schedule. Int J Med Microbiol 2004;293(Suppl 37):130-3.
Zent O, Plentz A, Schwarz et coll. TBE booster immunization according to the rapid immunization schedule: Are 3-year booster intervals really necessary? Vaccine 2004;23:312-5.
Kunz C, Hofmann H, Dippe H. Die FSME-Impfung, eine Maßnahme der Vorsorgemedizin mit hoher Akzeptanz in Österreich. WienMed Wochenschr 1991;141:273-6.
Zielinski CC, Stuller I, Dorner F et coll. Impaired primary, but not secondary, immune response in breast cancer patients under adjuvant chemotherapy. Cancer 1986;58:1648-52.
Wolf HM, Pum M, Jáger R et coll. Cellular and humoral immune responses in haemophiliacs after vaccination against tick-borne encephalitis. Br J Haematol 1992;82:374-83.
Dengler TJ, Zimmermann R, Meyer J et coll. Vaccination against tick-borne encephalitis under therapeutic immunosuppression. Reduced efficacy in heart transplant recipients. Vaccine 1999;17:867-74.
Niedrig M, Vaisviliene D, Teichmann A et coll. Comparison of six different commercial IgG-ELISA kits for the detection of TBEV-antibodies. J Clin Virol 2001;20:179-82.
Kaiser R, Neumann-Haefelin D, Hartmann J et coll. Impfung gegen FSME. Wie lange hält der Impfschutz und was bringt die Antikörperbestimmung zur Überprüfung der Immunitätslage? Z Allg Med 1999;75:373-4.
Holzmann H, Kundi M, Stiasny K et coll. Correlation between ELISA, hemagglutination inhibition, and neutralization tests after vaccination against tick-borne encephalitis. J Med Virol 1996;48:102-7.
Holzmann H. Pitfalls in modern TBE sero-diagnosis. Zentralbl Bakteriology 1999;289:548-9.
Macpherson DW. Une approche de la médecine fondée sur les preuves. RMTC 1994;20(17):145-7.
Stjernberg L, Berglund J. Detecting ticks on light versus dark clothing. Scand J Inf Dis 2005;37:361-4.
Immunogenicity and safety studies involving the vaccines FSME-IMMUN® 0.5 mL and FSME-IMMUN® 0.25 mL Junior, sponsored by Baxter Vaccines AG.
Clinical trials involving adults
István L. Double blind study for the investigation of the immunogenicity of a new TBE vaccine. Study IMAG-062; unpublished work, Immuno AG Vienna 1997.
De Bruyn S. Double-blind, randomized, dose-finding study to investigate the safety and immunogenicity of two vaccinationswith FSME-IMMUN® “New” in healthy volunteers aged 16 to 65 years. Study 201; unpublished work, Baxter Vaccine AG Vienna 2002.
De Bruyn S. Open follow-up phase II study to investigate the safety and immunogenicity of a third vaccination with three antigen concentrations of FSME-IMMUN® “New” in healthy volunteers aged 16 to 65 years. Study 202; unpublished work, Baxter Vaccine AG Vienna 2002.
Konior R. Single-blind, randomized,multicenter comparison of FSME-IMMUN® “New” and Encepur®: safety and tolerability of two vaccinations in healthy volunteers aged 16 to 65 years. Study 208; unpublished work, Baxter Vaccine AG, Vienna 2002.
Clinical trials involving children
Behre U. Double-blind, randomized,multicentre dose-finding study to investigate the safety and immunogenicity of two vaccinationswith FSME-IMMUN® “New” in healthy volunteers aged 1 to 6 years. Study 199; unpublished work, Baxter Vaccine AG Vienna 2002.
Behre U. Double-blind, randomized,multicentre dose-finding study to investigate the safety and immunogenicity of two vaccinationswith FSME-IMMUN® “New” in healthy volunteers aged 6 to 16 years. Study 205; unpublished work, Baxter Vaccine AG Vienna 2002.
Behre U. Follow-up study to investigate the safety and immunogenicity of a third vaccination with three different antigen concentrations of FSMEIMMUN ®“NEW” inchildrenaged 1 to 6 years. Study 206; unpublished work, Baxter Vaccine AG Vienna 2004.
Behre U. Follow-up study to investigate the safety and immunogenicity of a third vaccination with three different antigen concentrations of FSMEIMMUN ®“NEW” inchildrenaged 6 to16 years. Study 207; unpublished work, Baxter Vaccine AG 2004.
Konior R. Open-label safety study of FSME-IMMUN® New in healthy children and adolescents aged 1 to 15 years. Study 209; unpublished work, Baxter Vaccine AG 2003.
* Members: Dr. B.Ward (Chair); Dr. C. Beallor; M. Bodie-Collins (Executive Secretary); Dr. K. Gamble; Ms. A. Henteleff; Dr. S. Houston; Dr. S. Kuhn; Dr. A. McCarthy; Dr. K.L. McClean; Dr. P.J. Plourde; Dr. J.R. Salzman.
Liaison Representatives: Dr. R.J. Birnbaum; Dr. C. Greenaway; Dr. C. Hui; Dr. R. Saginur; Dr. P. Teitelbaum; Dr. M.Woo.
Ex-Officio Representatives: Dr. E. Callary; Dr. N. Gibson; Dr. J. Given, Dr. F. Hindieh; Dr. J.P. Legault; Dr. P. McDonald; Dr. R. Paradis; Dr. C.Reed; Dr. M. Smith; Dr. M. Tepper
Members Emeritus: Dr. C.W.L. Jeanes.
Consultant: Dr. S. Schofield