Tick-borne Encephalitis Vaccination Research Articles

Tick-borne encephalitis (TBE) trends in epidemiology and current and future management

Tick-borne encephalitis (TBE) is considered an international health issue, as the number of risk areas and reported cases across Europe, Russia, and parts of Asia continues to increase. The incidence of TBE has fluctuated considerably from year to year in many countries, but in the past decade the number of TBE cases has significantly increased in the Baltic states, the Czech Republic, and Germany, in addition to occurring in countries previously considered to be free from TBE, such as Denmark (specifically the main island of Zealand), France, and Italy. A number of factors have been suggested to explain the increase in incidence, including climate change, and increased travel and outdoor pursuits, placing people in increased contact with infected ticks. There is no causal treatment available once infected, but TBE can be effectively prevented by vaccination, for which several vaccines are widely available. Three vaccination schedules are available for immunization against TBE, and the recommendations for TBE vaccination vary considerably across the countries in which TBE foci are found. However, plans are in place to raise awareness of TBE and to standardize the vaccination programme across Europe, with the aim of reducing the number of future cases of TBE.

Comparison of immunogenicity and safety between two paediatric TBE vaccines

TBE vaccination strategies capable of inducing strong paediatric immunogenicity and acceptable reactogenicity are still under evaluation. This single-blind, multi-center, randomized, controlled, phase III clinical study compared the immunogenicity and safety of the two paediatric TBE vaccines available in Europe (FSME-IMMUN ® Junior and Encepur ® Children) following administration of two doses of either vaccine in 303 children aged 1–11 years. Regardless of immunological test or viral antigen used, immunological responses were consistently higher in children vaccinated with FSME-IMMUN ® Junior than those vaccinated with Encepur ® Children. FSME-IMMUN ® Junior is also non-inferior to Encepur ® Children, with respect to NT seropositivity rates ( p < 0.0001). Systemic reaction rates were low and similar between the vaccines. However, among children aged 7–11 years, local reactions were significantly higher after the first ( p < 0.01) and second ( p < 0.001) vaccination with Encepur ® Children than with FSME-IMMUN ® Junior, affecting half the children in the former group: 22.4% and 10.2% with FSME-IMMUN ® Junior vs. 49.0% and 51.0% for Encepur ® Children.

Decreased antibody titers and booster responses in tick-borne encephalitis vaccinees aged 50–90 years

Because of decreased immune functions of older people booster intervals of 3 years – instead of 5 – are recommended for tick-borne encephalitis (TBE) vaccinations for persons ≥60 years in Austria. So far, no comparative data on the immune-responsiveness of the age group 50–59 years are available. We therefore investigated the antibody titers and booster responses (in ELISA and neutralization assays) for the age groups 50–59, 60–69, and >69 years in comparison to a control group below 30 years. The age group 50–59 years displayed the same decreased antibody response, also characteristic for persons 60 years and older. Although antibody concentrations were lower after 5–7 years compared to 3–4 year intervals, antibodies were still detectable and could be sufficiently increased by booster shots in the vast majority of persons. Our results clearly indicate that the responsiveness of the immune system to vaccination is already impaired at the age of 50.

Smell impairment after tick-borne encephalitis vaccination: Case report

We present a case of hyposmia following administration of a tick-borne encephalitis (TBE) vaccine. The olfactory impairment did not recover during 1-year follow up. In the literature, there is no report of smell deterioration after vaccination against TBE. Physicians should be aware of this rare neurological complication.

Characteristics of antibody responses in tick-borne encephalitis vaccination breakthroughs

Tick-borne encephalitis (TBE) virus is an important human pathogenic flavivirus that is endemic in Europe and Asia. The disease can be effectively prevented by inactivated vaccines and vaccination breakthroughs (VBTs) are rare. We investigated the characteristics of antibody responses in such VBTs in comparison to those in unvaccinated TBE patients. In contrast to the unvaccinated controls, most of the VBTs displayed a delayed IgM antibody response and had high avidity and strongly neutralizing antibodies already in the first sample taken upon hospitalization. The antibody profile of these patients therefore had the characteristics of an anamnestic immune response. In the VBTs analyzed, immunological priming and memory were apparently not sufficient or fast enough to prevent the disease.

Comment and reply on: Serological response to tick-borne encephalitis (TBE) vaccination in the elderly – results from an observational study

Comment and reply on: Serological response to tick-borne encephalitis (TBE) vaccination in the elderly – results from an observational study

Serological response to tick-borne encephalitis (TBE) vaccination in the elderly – results from an observational study

Background: In the elderly, the incidence of tick-borne encephalitis (TBE) is higher than in younger individuals. At the same time, the responsiveness of the elderly to vaccination may be decreased. Product information for TBE vaccines therefore recommends determining antibody response after two of the three doses required for primary immunization in persons over 60. Objective: To determine the proportion of persons aged 60 years or older with insufficient antibody response after administration of two doses of TBE vaccine. Methods: A retrospective analysis of TBE-specific antibody levels as determined by Immunozym® ELISA in serum samples of 185 vaccinees > 60 years of age after the first two of the three vaccinations required for primary immunisation. Patients received either FSME-IMMUN Adult or Encepur® Adults at one vaccination centre in the Czech Republic. In a subset of 80 vaccinees, two additional ELISAs and a neutralization test (NT) were performed. Results: Overall, 33 of the 185 individuals (18%) included in the Immunozym analysis had antibody concentrations below putative protective levels after two doses. Geometric mean concentrations and seropositivity rates were higher in individuals vaccinated with FSME-IMMUN than in those vaccinated with Encepur®. While the differences in mean antibody levels and/or seropositivity rates in ELISAs for the Neudörfl strain (used in FSME-IMMUN) were significant, no significant differences were obtained for Enzygnost, which uses the Karlsruhe strain (used in Encepur). Conclusions: After two doses of TBE vaccine, one in five persons aged 60 years or older may be without protective antibodies, confirming the importance of testing the antibody response after the second vaccination and administering an additional dose in the event of insufficient response.

Schwere Frühsommermeningoencephalitis (FSME) sechs Jahre nach korrekter Impfung.

A case of severe tick-borne encephalitis (TBE) 6 years after correct vaccination – could it have been prevented by a search for seroconversion after vaccination? The case described affords evidence that even after correct vaccination against tick-borne encephalitis (TBE) it is still possible to develop a severe form of TBE. The reason may be an absent or insufficient vaccine response. For persons over 50 years of age, especially those living in TBE-endemic regions and often exposed to tick bites at work or during leisure activities, it may be useful to search for seroconversion after TBE vaccination and, if there is no vaccine response, to administer one or two further vaccine doses and recommend strict prophylactic measures against tick exposure.

Schwere Frühsommermeningoencephalitis (FSME) sechs Jahre nach korrekter Impfung.

A case of severe tick-borne encephalitis (TBE) 6 years after correct vaccination – could it have been prevented by a search for seroconversion after vaccination? The case described affords evidence that even after correct vaccination against tick-borne encephalitis (TBE) it is still possible to develop a severe form of TBE. The reason may be an absent or insufficient vaccine response. For persons over 50 years of age, especially those living in TBE-endemic regions and often exposed to tick bites at work or during leisure activities, it may be useful to search for seroconversion after TBE vaccination and, if there is no vaccine response, to administer one or two further vaccine doses and recommend strict prophylactic measures against tick exposure.

Characterization of neutralizing antibodies to Far Eastern of tick-borne encephalitis virus subtype and the antibody avidity for four tick-borne encephalitis vaccines in human

We assessed the humoral immunity of 290 vaccinated persons against tick-borne encephalitis (TBE). During the first year and 2 years after the primary three vaccinations the antibodies to the Far Eastern subtype tick-borne encephalitis virus strain P-73 were detected by neutralization test after immunization with FSME-Immune Inject vaccine (Baxter Vaccine AG, Austria) in 88.2% and 78.1% vaccinated persons, respectively; with Encepur ® Adult vaccine (Novartis Vaccines, Germany), in 100% and 100%; with the vaccine of the Chumakov Institute of Poliomyelitis and Viral Encephalitides RAMSci (Russia), in 100% and 94.1%; with EnceVir vaccine (Russia), in 88.2% and 83.9%; and after combined vaccination, in 100% and 92.7%. The dynamics of the decrease in IgG avidity index correlated with the changes of antibody titers determined by neutralization test. After the primary vaccination course, the titers of virus-neutralizing antibodies were high (6.3–7.4 log 2) when the avidity index of IgG antibodies were 31% and more; thus, this level can be considered immunologically significant. Two years after the primary vaccination course, the IgG avidity indexes of 60% and more can be regarded as significant on the background of the GMT decrease of virus-neutralizing antibodies. These results allow us to recommend all four vaccines for mass vaccination and an assay of IgG avidity, along with neutralization test, for a more adequate assessment of the level of postvaccination immune response.

Travel Medicine, 2nd Edition

The second edition of this valuable textbook highlights a dynamic specialty that integrates many disciplines. Edited by 5 internationally renowned leaders in travel medicine, the book assembles a fine group of authors and chapters. The print version is hard cover and comes with online access that is easy to use and fully searchable. Both versions include useful maps, tables, and figures, which can be exported from the online version to PowerPoint presentations to assist in teaching. The online version also links to abstracts of references, allowing readers easy access to the abstracts simply by clicking on linked references. The book consists of 57 well-organized chapters that begin with fundamental topics such as epidemiology, travel clinic management and resources, and basic disease prevention. The chapters then progress to more specialized topics such as special hosts (e.g., immunocompromised travelers), special itineraries (e.g., expatriates and persons on expeditions), health problems while traveling, and posttravel care. This edition also features a new chapter on cruise ship travel. The chapters vary greatly in length and content: chapters on jet lag and sun-associated problems are brief; chapters on topics such as immunization of healthy adults are detailed and lengthy (i.e., 36 pages). The immunization chapter covers a large amount of material that is challenging because it addresses international variations in vaccine licensure and guidelines. For instance, tick-borne encephalitis vaccine and cholera vaccine, which are described in this chapter, are available in Europe but not in the United States. However, the global nature of travel medicine necessitates practitioners’ knowledge of these vaccines. As the field of travel medicine matures and its evidence base increases, topics such as environmental aspects of travel, psychological aspects of travel, and travel injuries are gaining greater recognition. If a new edition is considered, additional topics that would be helpful to clinicians include travelers’ precautions for eye care (especially regarding certain environmental exposures), breastfeeding among travelers (currently an abbreviated section in a chapter that discusses pregnant travelers), and collaboration among practitioners of travel medicine and public health professionals. Specific policies and procedures for travel clinic management could also address the triage of posttravel illnesses. This book is a comprehensive reference on travel medicine. It is rich in information, pleasant to read, and practical. It has been updated to recommend current best practices in travel medicine. The editors have assembled an excellent textbook, and I recommend it enthusiastically to health professionals interested in this growing specialty.

Vaccines for preventing tick-borne encephalitis.

Tick-borne encephalitis (TBE) is a disease of the central nervous system caused by a tick-borne viral infection. TBE can lead to severe neurological syndromes such as meningitis, meningoencephalitis, and meningoencephalomyelitis, which can result in death. There is no treatment, and prevention with the vaccine is the only intervention currently available. To evaluate vaccines for preventing TBE in terms of effectiveness and adverse effects. In June 2008, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2008, Issue 2), MEDLINE, EMBASE, LILACS, and mRCT. We also checked reference lists of articles. Randomized and quasi-randomized controlled trials comparing TBE vaccines against placebo, control vaccines, no intervention, or a different dose or schedule of the intervention vaccine. Two authors applied the inclusion criteria, extracted data, and assessed each trial's risk of bias. We could not combine the included trials in a meta-analysis because of differences in comparisons and outcomes. Eleven trials (corresponding to 10 papers) involving 8184 participants (6586 adults and 1598 children) were included. Different versions of three types of TBE vaccines were tested (IPVE, FSME-IMMUN, and Encepur); out of which only three (Encepur children, Encepur Adults, and FSME-IMMUN "new") are currently licensed. No trials reported on cases of clinical TBE, but all reported on antibody titre (seroconversion). All the vaccines gave seroconversion rates of over 87%. Systemic and local adverse effects were common; none were severe or life threatening. Tick-borne encephalitis vaccines appear to be highly immunogenic, but the relationship between seroconversion and clinical protection has not been established. Although adverse effects were commonly reported, none were serious or life threatening.

Long-term persistence of tick-borne encephalitis antibodies in children 5 years after first booster vaccination with Encepur ® Children

Tick-borne encephalitis (TBE) is a serious viral infection, which can lead to permanent neurological sequelae in children. The incidence of TBE disease is increasing in many European countries and is particularly pronounced in some regional populations. Vaccination is the most effective method for preventing TBE disease and is recommended for all those living and working in TBE-endemic areas. Encepur ® Children is licensed for TBE vaccination in children 1–11 years of age. Following primary vaccination, booster vaccinations are recommended; however, the optimal timing for booster vaccination of children is not known. The aim of this study was to assess the persistence of TBE antibodies in children at 3 and 5 years after their first booster vaccination with Encepur ® Children and to re-evaluate booster vaccination recommendations. Children 1–11 years of age ( n = 335) who received primary TBE vaccination according to the rapid schedule (Days 0, 7, and 21) in a previous study received a booster vaccination 12–18 months later, and were invited for follow-up at 3 and 5 years post-booster. TBE antibodies were measured using a virus neutralization test (NT; in-house, Novartis Vaccines) and also using anti-TBE IgG ELISA (Enzygnost ®, Siemens, Germany). In this analysis, 275 of 278 (99%) subjects and all 190 (100%) subjects who completed the follow-up at 3 and 5 years, respectively, had NT titres ≥10. Likewise, all 275 of 278 (99%) and 188 of 190 (99%) subjects tested positive by ELISA at 3 and 5 years after the booster vaccination, respectively. Based on serological data, the interval for subsequent booster vaccinations with Encepur ® Children can be extended from 3 to 5 years after receiving primary vaccination and a first booster vaccination 12–18 months later.

Infeksjonsrisiko hos orienteringsløpere

Research on orienteers is useful for assessing the risk of infections associated with physical activity in the forest. In this paper four types of infections are reviewed, and the efficacy of preventive initiatives is discussed. The paper is based on literature retrieved from a non-systemic search in PubMed. Hepatitis B infection was more prevalent among orienteers before they were obliged to use protective clothing. In the 1980s, there was an increase of sudden unexpected death among young Swedish orienteers. Bartonella infection was later suggested as an underlying cause. No unexpected deaths have occurred among young orienteers after 1992 when specific advice was given regarding training and competitions. Orienteers do not seem to be affected by lyme borreliosis or tick-borne encephalitis (TBE) more often than others, but only two old studies have been performed. Orienteers may be at risk of acquiring infection from lyme borreliosis and TBE in Norway in the future, as the incidence of these contagions is increasing. Norwegian medical personnel should consider TBE vaccination of orienteers and others who wander in areas with a high prevalence of infected ticks.

Long-term persistence of tick-borne encephalitis antibodies in adults 5 years after booster vaccination with Encepur® Adults

Tick-borne encephalitis (TBE) is a potentially serious disease, especially in adults. There is no treatment available for TBE; supportive therapy may help to ease symptoms of the disease. Vaccination is the most effective method of preventing TBE disease and is recommended for those who live, work, or travel in TBE-endemic areas. Regular booster vaccinations are recommended every 3–5 years to maintain protection. Evidence from recent clinical studies suggests that TBE antibodies persist at high levels for longer than the current recommended intervals for TBE booster vaccination.The aim of this study was to evaluate the long-term persistence of TBE antibodies in adults after primary vaccination using a rapid schedule and a first booster dose of Encepur® Adults, an inactivated TBE vaccine. A total of 222 adults 19–51 years of age were invited for serological follow-up investigations 3 and 5 years following their first booster dose. High antibody titres were recorded throughout the follow-up period. Neutralization test (NT) titres ≥10 were noted in 99% of subjects 3 and 5 years after the first booster vaccination and 97% tested positive by enzyme-linked immunosorbent assay (ELISA). These results indicate that initially high levels of TBE antibodies following the first booster dose of the vaccine may lead to long-term persistence of TBE antibodies, confirming previous findings and suggesting it may be appropriate to extend the interval between booster doses from 3 to 5 years.

Antibody response following administration of two paediatric tick-borne encephalitis vaccines using two different vaccination schedules

Two paediatric tick-borne encephalitis vaccines, Encepur ® Children and FSME-IMMUN ® Junior, are used widely in Europe. This study compared the immunogenicity and safety of both vaccines, administered using the conventional (Days 0, 28, and 300) or accelerated (Days 0, 14, and 300) schedule and evaluated whether a third dose of Encepur ® Children can complete a primary vaccination course initiated with FSME-IMMUN ® Junior. A total of 334 children 1 to <11 years of age were enrolled in this Phase IV randomized, controlled, single-blind, multi-centre trial. All subjects, irrespective of study arm, received Encepur ® Children as the third dose on Day 300. The percentage of subjects with antibody titres ≥10, as determined by neutralization test (NT), was assessed and local and systemic reactions were monitored and solicited. Within both the conventional and accelerated schedules, the proportion of subjects achieving an NT ≥ 10 was higher in the group that received Encepur ® Children, compared with the group that received FSME-IMMUN ® Junior, at Days 42 and 300 (conventional schedule Day 300, P < 0.001 Encepur ® Children versus FSME-IMMUN ® Junior; accelerated schedule Days 42 and 300, P < 0.001 Encepur ® Children versus FSME-IMMUN ® Junior). The third dose of Encepur ® Children led to a substantial increase in the proportion of subjects in the FSME-IMMUN ® Junior groups achieving NT ≥ 10. Overall, >95% of all children achieved NT ≥ 10, on completion of the primary vaccination course. Encepur ® Children provides an immune response, measured by neutralizing TBE antibodies, that is superior to FSME-IMMUN ® Junior and can successfully be used to complete a primary vaccination course initiated with FSME-IMMUN ® Junior. Both vaccines were well tolerated, with comparable safety profiles; no vaccine-related serious adverse events were reported.

Effect of pre-existing anti-tick-borne encephalitis virus immunity on neutralising antibody response to the Vero cell-derived, inactivated Japanese encephalitis virus vaccine candidate IC51

Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis in Asia with a case fatality rate up to 35% and long-term sequelae up to 75%. This active-controlled, randomized, multi-centre, observer-blind, phase III trial investigated the neutralising antibody response to the new Japanese encephalitis (JE) vaccine IC51 in subjects with (N=81) and without (N=339) pre-existing tick-borne encephalitis (TBE) vaccine induced antibodies as determined by TBE enzyme-linked immunosorbent assay IgG (ELISA). Neutralising antibody response was statistically superior in TBE ELISA-positive subjects compared to TBE ELISA-negative subjects after the first (p<0.0001) but not after the second vaccination with IC51. Thus, pre-existing vaccine-induced TBE immunity enhances the neutralising JEV-specific antibody response after a single IC51 vaccination.

Protection against tick-borne encephalitis (TBE) for people living in and travelling to TBE-endemic areas

Once considered a local health issue confined to certain regions in Russia and Central and Eastern Europe, tick-borne encephalitis (TBE) is now considered an international health concern, and the most important and widespread viral disease transmitted by ticks in Europe. The number of reported TBE cases continues to increase in many endemic regions, and new foci have been identified. Increases in travel, access to high-risk areas, and the pursuit of leisure activities within TBE-endemic areas are placing more people at risk of TBE. Travellers from non-endemic regions are often unaware of the risk of acquiring TBE and therefore many travellers are not protected against TBE. Active immunization is the most effective way to avoid TBE and its potentially life-threatening sequelae. After a tick bite, no post-exposure treatment including active/passive vaccination is available or recommended in the immunologically naive patient. Available vaccines have undergone a series of modifications and improvement in both composition (with special formulations for children) and schedules to further enhance the safety of immunization and to meet the needs of vaccinees. Efforts to develop internationally recognized recommendations for TBE vaccination for travellers are underway.

Séroprévalence de la borréliose de Lyme et de l’encéphalite à tiques chez des professionnels exposés dans le Grand Est de la France

Objective The aim of this article was to assess the seroprevalence of Lyme Borreliosis and tick-borne encephalitis (TBE) among occupationally exposed forest workers. Methods Workers exposed to tick bites in Eastern France were interviewed by occupational health physicians of the mutualité sociale agricole (MSA) on their sociodemographic features, their occupational activity, their last tick bite, their clinical history, and their means of prevention. Blood sampling was carried out for antibody detection. Results Among the 2975 subjects included in the study, the observed seroprevalence was 14.1% for Lyme borreliosis and 3.4% for TBE. Age, occupational activity, and place of residence significantly influenced the serological status of Lyme borreliosis. The seroprevalence was significantly higher among woodcutters (17.5%) than among other occupational categories ( p < 0.001). Seroprevalence in Alsace (26.9%) and Lorraine (16.5%) were significantly higher than in other regions ( p < 0.001 and p < 0.01, respectively). The seroprevalence of TBE was significantly higher in Alsace (5.5%; p < 0.001). The rates of seroprevalence for both infections varied according to forest areas. The multifactorial analysis of prevention practices revealed three types of behaviors as far as protection was concerned: “rigorous”, “partial”, or “insufficient”. Conclusion These results do not change the present French indications for use of TBE vaccine. They highlight the importance of information on these diseases and the need for further studies on microbial ecology and risk-factors identification.

Advances in vaccination against tick-borne encephalitis

Tick-borne encephalitis (TBE) poses a growing health problem in many European countries and parts of Northern Asia. Thus, vaccination has been employed successfully for many years in endemic countries. Long-term experience gained from widespread use, however, prompted the development of improved vaccine formulations of the two licensed European TBE vaccines. Moreover, recent clinical trials also suggested the maintenance of high values of postvaccination neutralizing TBE antibodies for a longer period than expected; thus, also resulting in modifications with regards to immunization regimens. Recent advances in recombinant DNA technology have opened up future opportunities for developing novel live-attenuated vaccines against TBE virus and other flaviviruses. Animal experiments demonstrated safety and high immunogenicity profiles for these mutants; thus, making them promising vaccine candidates that will need to demonstrate a clear advantage if they are going to be alternatives to the traditional vaccines. Systematic TBE case monitoring by raising problem awareness, both inside and outside endemic regions, appears essential to provide evidence for a widely accepted TBE travel-vaccination recommendation in the future.