Tick-borne Encephalitis Vaccination Research Articles

Arboviral vaccines for use in pregnant travelers

Pregnant women traveling abroad can be exposed to a variety of arboviruses, primarily spread by mosquitoes or ticks. Some arboviral infections can be of particular concern for pregnant women or their fetuses. Vaccination is one preventive measure that can reduce the risk for infection. Several arboviral vaccines have been licensed for many years and can be used to prevent infection in travelers, namely Japanese encephalitis, yellow fever, and tick-borne encephalitis vaccines. Recommendations on use of these vaccines in pregnancy vary. Other arboviral vaccines have been licensed but are not indicated for use in pregnant travelers (e.g., dengue vaccines) or are in development (e.g., chikungunya, Zika vaccines). This review describes arboviral vaccines for travelers, focusing on women who are pregnant and those planning travel during pregnancy.

Effectiveness of tick-borne encephalitis vaccination in Latvia, 2018–2020: an observational study

ObjectivesTick-borne encephalitis (TBE) is an infection by the tick-borne encephalitis virus (TBEV) that results in symptoms of central nervous system inflammation. TBE is endemic in Latvia and other European countries. TBE vaccines are commonly used in Latvia, but vaccine effectiveness estimates are limited. MethodsStudy staff at Rīga Stradinš University conducted nationwide active surveillance for TBEV infections. Serum and cerebrospinal fluid were ELISA-tested for TBEV-specific IgG and IgM antibodies. Vaccination history was collected by interview and medical record review. Utilizing data from surveillance and population surveys, vaccine effectiveness (with 95% CIs) and cases averted were estimated using the screening method. ResultsThere were 587 laboratory-identified TBE cases from 2018 to 2020; 98.1% (576/587) were unvaccinated, 1.5% (9/587) were unknown or partially vaccinated, and 0.3% (2/587) were fully vaccinated (three-dose primary series and appropriately timed boosters). TBE resulted in the death of 1.7% (10/587) of TBE cases. TBE vaccine history was ascertained from 92.0% (13 247/14 399) people from the general population: 38.6% (5113/13 247) were unvaccinated, 26.3% (3484/13 247) were fully vaccinated, and 35.1% (4650/13 247) were partially vaccinated. TBE vaccine effectiveness was 99.5% (98.0–99.9) against TBE, 99.5% (97.9–99.9) against TBE hospitalization, 99.3% (94.8–99.9) against moderate/severe TBE, and 99.2% (94.4–99.9) against TBE hospitalization >12 days. From 2018 to 2020, vaccination averted 906 TBE cases, including 20 deaths. DiscussionTBE vaccine was highly effective in preventing TBE, moderate and severe disease, and prolonged hospitalization. To prevent life-threatening TBE, TBE vaccine uptake and compliance should be increased in Latvia and other European regions where TBE is endemic.

Development of ahighly purified tick-borne encephalitis vaccine : Apersonal historical account.

Before the advent of avaccine, infections with tick-borne encephalitis (TBE) virus in Austria led to the hospitalization of several hundred and, due to underreporting, possibly more than thousand patients with severe neurological disease every year. In the late 1960s and early 1970s, this country had the highest recorded morbidity of TBE in Europe, but similar endemic risk areas exist in many other European countries as well as Central and Eastern Asia. In this article, Idescribe my personal recollections of the development of ahighly purified TBE vaccine in the late 1970s, to which Icontributed as ayoung post-doctoral scientist mentored by Christian Kunz (then director of the Institute of Virology at the Medical Faculty, University of Vienna) in acollaboration with the Austrian biopharmaceutical company Immuno. Low reactogenicity of the newly developed vaccine was aprerequisite for mass vaccination campaigns in Austria that started in the early 1980s. Because of its excellent immunogenicity, broad application of the highly purified vaccine paved the way for adramatic reduction of the incidence of TBE in Austria, which is outstanding in Europe and referred to as an Austrian success story of immunoprophylaxis.

Effectiveness of Tick-borne Encephalitis Vaccines in Children, Latvia, 2018-2020.

Tick-borne encephalitis (TBE) is an infection by the tick-borne encephalitis virus (TBEV) with symptoms of central nervous system inflammation. TBE is endemic in Latvia and other parts of Europe. TBE vaccination is recommended for children in Latvia. TBE vaccine effectiveness (VE) was estimated in Latvia, a country with high TBE incidence, providing the first VE estimates against a range of TBEV infection outcomes in children 1-15 years-of-age. Rīga Stradinš University conducted nationwide surveillance for suspected TBE cases. Serum and cerebrospinal fluid were ELISA tested for TBEV-specific IgG and IgM antibodies. A fully vaccinated child was an individual who had received the 3-dose primary series and appropriately timed boosters. The proportion of laboratory-confirmed TBE cases fully vaccinated (PCV) was determined from interviews and medical records. The proportion of the general population fully vaccinated (PPV) was determined from national surveys conducted in 2019 and 2020. TBE VE in children 1-15 years-of-age was estimated using the screening method: VE = 1 - [PCV/(1 - PCV)/PPV/(1 - PPV)]. From 2018 to 2020, surveillance identified 36 TBE cases in children 1-15 years-of-age; all were hospitalized, 5 (13.9%) for >12 days. Of the TBE cases, 94.4% (34/36) were unvaccinated compared with 43.8% of children in the general population. VE against TBE hospitalization in children 1-15 years-of-age was 94.9% (95% confidence interval 63.1-99.3). In 2018-2020, vaccination in children 1-15 years-of-age averted 39 hospitalized TBE cases. Pediatric TBE vaccines were highly effective in preventing TBE in children. Increasing TBE vaccine uptake in children is essential to maximize the public health impact of TBE vaccination.

Chapter 14: TBE-Prevention: Vaccines and Immunoglobulins

Worldwide there are 6 different TBE vaccines – two from Western Europe, three from Russia and one from China. The two western European vaccines and one of the Russian vaccines have an adult and a pediatric formulation. The products names are FSME IMMUN and FSME-IMMUN Junior; Encepur adults and Encepur children, Klesch-E-Vac, EnceVir and EnceVir Neo, Dry lyophilized TBE Moscow and Sen Tai Bao All TBE vaccines except the one from China have similar but not identical immunization schedules with primary immunization (>3 doses) and regular booster vaccinations. For FSME-IMMUN, Encepur and EnceVir rapid immunization schedules are also licensed. The Chinese vaccine is given with 2 primary doses 2 weeks apart followed by annual boosters. All vaccines induce significant immune responses. In the absence of a formal correlate of protection, the presence of neutralizing antibodies is used as a surrogate marker for protection. Recent clinical studies show long-term seropersistence of TBE antibodies after the first booster vaccination (dose 4) with the two European vaccines. An effectiveness of approximately 99% (years 2000–2006) and 98.7% (years 2000-2011) was calculated for regularly vaccinated persons in Austria, a country with established high vaccination uptake. Whereas in Western Europe post-exposure prophylaxis with immunoglobulins was discontinued in the late 1990s, in the highly endemic regions of Russia it continues to be common practice. Both – FSME-IMMUN and Encepur are well tolerated with a well-established safety profile. TBE-Moscow and EnceVir appear to be somewhat more reactogenic.

Chapter 6: TBE in children

Most cases of TBE in childhood will present similarly as in adults. However, a more diffuse clinical picture is seen especially in preschool children. Laboratory evaluation may show elevated blood inflammatory indices, but cerebrospinal fluid analysis and anti-TBEV serology are needed for establishing the diagnosis. There is no specific treatment for TBE; supportive care needs to be provided based on the individual clinical course. The mortality in pediatric TBE is very low but severe courses have been reported in a fraction of the children. Long-term somatic residua exist, but are uncommon (2%) in childhood TBE. Yet, long-term symptoms and neurodevelopmental/cognitive deficits are seen in 10–40% of infected children. Protective immunity can be elicited in children by TBE vaccines as of 1 year of age.

Sustained antibody persistence for at least 15years after a booster vaccination against tick-borne encephalitis following different primary vaccination schedules: Third 5-year follow-up.

Vaccination is the best mode of protection against tick-borne encephalitis (TBE) and its sequelae. The duration of protection and the optimal interval of repeat booster doses are still debated. The current study evaluated the persistence of the antibody response 11-15years after a first booster vaccination following different primary vaccination schedules with a TBE vaccine (Encepur Adults, manufactured by Bavarian Nordic, previously by GSK). This phase IV, open-label, mono-centric extension study enrolled adults who had received (at≥12years of age) primary vaccination with one of three randomly assigned TBE vaccine schedules (rapid [group R], conventional [group C], or accelerated conventional schedule [group A]) followed by a booster dose 3years later. The antibody response was measured annually from 11 to 15years post-booster using a TBE virus neutralization test (NT). An NT titer of≥10 was considered as a clinically meaningful threshold and surrogate for protection. In total, 194 participants were enrolled and included in the per-protocol set; 188 completed the study. The percentage of participants with an NT titer≥10 was 100% in group R and 99.0% in group A at all visits and ranged from 100% (year 11) to 95.8% (year 15) in group C. NT geometric mean titers were similar in the three study groups (181-267 in group R, 142-227 in group C, 141-209 in group A). NT geometric mean titers also remained high among participants≥50years old (98-206) and≥60years old (91-191) across study groups and time points. This study showed neutralizing antibody persistence for at least 15years after a first booster dose of the Encepur Adults TBE vaccine in all age groups evaluated, regardless of which primary vaccination schedule was given to adolescents or adults. Trialregistry: ClinicalTrials.gov: NCT03294135.

The AxBioTick Study: Borrelia Species and Tick-Borne Encephalitis Virus in Ticks, and Clinical Responses in Tick-Bitten Individuals on the Aland Islands, Finland.

The AxBioTick study was initiated to investigate the prevalence of ticks and tick-borne pathogens and their impact on antibody and clinical responses in tick-bitten individuals on the Aland Islands. This geographical area is hyperendemic for both Lyme borreliosis (LB) and Tick-borne encephalitis (TBE). Blood samples and ticks were collected from 100 tick-bitten volunteers. A total of 425 ticks was collected, all determined to Ixodes ricinus using molecular tools. Of them 20% contained Borrelia species, of which B. garinii and B. afzelii were most common. None contained the TBE virus (TBEV). Blood samples were drawn in conjunction with the tick bite, and eight weeks later. Sera were analyzed for Borrelia- and TBEV-specific antibodies using an ELISA and a semiquantitative antibody assay. In total 14% seroconverted in Borrelia C6IgG1, 3% in TBEV IgG, and 2% in TBEV IgM. Five participants developed clinical manifestations of LB. The high seroprevalence of both Borrelia (57%) and TBEV (52%) antibodies are likely attributed to the endemic status of the corresponding infections as well as the TBE vaccination program. Despite the similar prevalence of Borrelia spp. detected in ticks in other parts of Europe, the infection rate in this population is high. The AxBioTick study is continuing to investigate more participants and ticks for co-infections, and to characterize the dermal immune response following a tick bite.

Five accelerated schedules for the tick-borne encephalitis vaccine FSME-Immun® in last-minute travellers: an open-label, single-centre, randomized controlled pilot trial.

The purpose of this exploratory study was to evaluate different accelerated tick-borne encephalitis (TBE) vaccine schedules for last-minute travellers. In a single-centre, open-label pilot study, 77 TBE-naïve Belgian soldiers were randomized to one of the following five schedules with FSME-Immun®: group 1 ('classical accelerated' schedule) received one intramuscular (IM) dose at Day 0 and Day 14, group 2 two IM doses at Day 0, group 3 two intradermal (ID) doses at Day 0, group 4 two ID doses at Day 0 and Day 7 and group 5 two ID doses at Day 0 and Day 14. The last dose(s) of the primary vaccination scheme were given after 1 year: IM (1 dose) or ID (2 doses). TBE virus neutralizing antibodies were measured in a plaque reduction neutralization test (PRNT90 and 50) at Days 0, 14, 21, 28, Months 3, 6, 12 and 12+21 days. Seropositivity was defined as neutralizing antibody titres ≥10. The median age was 19-19.5 years in each group.Median time to seropositivity up to Day 28 was shortest for PRNT90 in ID-group 4 and for PRNT50 in all ID groups. Seroconversion until Day 28 peaked highest for PRNT90 in ID-group 4 (79%) and for PRNT50 in ID-groups 4 and 5 (both 100%). Seropositivity after the last vaccination after 12 months was high in all groups. Previous yellow fever vaccination was reported in 16% and associated with lower geometric mean titres of TBE-specific antibodies at all-time points.The vaccine was generally well tolerated. However, mild to moderate local reactions occurred in 73-100% of ID compared with 0-38% of IM vaccinations, and persistent discolouration was observed in nine ID vaccinated individuals. The accelerated two-visit ID schedules might offer a better immunological alternative to the recommended classical accelerated IM schedule, but an aluminium-free vaccine would be preferable.

Knowledge, Attitudes and Behaviors regarding Tick-Borne Encephalitis Vaccination and Prevention of Tick-Borne Diseases among Primary Care Physicians in Bavaria and Baden-Wuerttemberg, Germany, May-September 2022.

In 2020, a record number of tick-borne encephalitis (TBE) cases was reported in major endemic areas in Germany, i.e., the southern federal states of Baden-Wuerttemberg and Bavaria. Most cases were unvaccinated. Other tick-borne diseases (TBDs), including Lyme borreliosis and tularemia, are rising, too. Thus, strategies are needed to increase TBE vaccination uptake in risk areas and promote education on TBD prevention. Primary care physicians are key providers of both vaccinations and TBD education. The TBD-Prevention (TBD-Prev) study aimed to investigate the knowledge, attitudes and behaviors of primary care physicians in Baden-Wuerttemberg and Bavaria with regard to TBE vaccination and prevention of TBDs and to derive strategies for increasing vaccination rates and improving knowledge about TBE and other TBDs in the population and among primary care physicians. We invited all primary care physicians (N = 14,046) in both states to participate by mail. Using standardized, self-administered questionnaires, available both on paper and online, we asked physicians anonymously about their knowledge, attitudes and behaviors with respect to TBE vaccination and TBD prevention and their need for further information/educational materials. A total of 2321 physicians participated between May and September 2022 (response rate 17%), of whom 1222 (53%) worked in Baden-Wuerttemberg and 1067 (46%) in Bavaria. Among the participating physicians, 56% were male, 71% were >50 years and 51% worked in an individual practice. Furthermore, 91% were aware of the German national vaccination guidelines, and 98% perceived their knowledge of the risks and benefits of vaccination as adequate. A total of 97% offer TBE vaccinations, 67% provide vaccination counselling during initial consultations with new patients and 64% actively remind patients about due vaccinations. In addition, 24% expressed a need for further information materials, mainly traditional, analogue media such as flyers (82%) and posters (50%), and named timeliness, quality assurance, easy comprehensibility and independence from the pharmaceutical industry as the most important characteristics of such materials. Almost all participating physicians reported offering TBE vaccinations and feeling well-informed about TBE vaccination and TBDs. However, active offering of vaccinations and education could be further improved, and additional, low-threshold information materials are needed. Based on these results, we will develop and provide various materials on TBE vaccination and TBDs, in particular flyers and posters, for use by physicians during consultations.

Recovery and sequelae in 523 adults and children with tick-borne encephalitis in Germany

PurposeDespite being vaccine-preventable, tick-borne encephalitis (TBE) continues to cause considerable morbidity in Germany. Limited insight into potentially debilitating consequences of TBE may partially underly low (~ 20%) TBE vaccine uptake. We aimed to systematically assess TBE sequelae and other consequences.MethodsRoutinely notified TBE patients from 2018 to 2020 from Southern Germany were invited to telephone interviews acutely and again after 18 months. Duration of acute symptoms was prospectively assessed. Recovery was defined as score 0 on the modified RANKIN scale. Determinants of time to recovery were analysed with cox regression, adjusted for covariates identified using directed acyclic graphs, yielding hazard ratios (HR) and 95% confidence intervals (CI).ResultsOf 558 cases, 523 (93.7%) completed follow-up. Full recovery was reported by 67.3% (children: 94.9%, adults: 63.8%). Sequelae included fatigue (17.0%), weakness (13.4%), concentration deficit (13.0%), and impaired balance (12.0%). Compared with 18–39-year-olds, recovery rates were 44% lower in ≥ 50-year-olds (HR: 0.56, 95%CI 0.42–0.75) and 79% higher in children (HR: 1.79, 95%CI 1.25–2.56). The recovery rate was 64% lower after severe TBE (compared to mild; HR: 0.36, 95%CI 0.25–0.52) and 22% lower with comorbidities (HR: 0.78, 95%CI 0.62–0.99). Substantial health-care use was reported (90.1% hospitalisation, 39.8% rehabilitation). Of employed cases, 88.4% required sick leave; 10.3% planned/reported premature retirement due to sequelae.ConclusionHalf the adult and 5% of paediatric patients reported persisting sequelae after 18 months. Improved prevention could alleviate both individual (morbidity) and societal TBE burden (health-care costs, productivity losses). Insights into sequelae can help guide at-risk populations towards tick-avoidant strategies and encourage TBE vaccination.

Dairy milk from cow and goat as a sentinel for tick-borne encephalitis virus surveillance.

Tick-borne encephalitis (TBE) is one of the most severe human tick-borne diseases in Europe. It is caused by the tick-borne encephalitis virus (TBEV), which is transmitted to humans mainly via bites of Ixodes ricinus or I. persulcatus ticks. The geographical distribution and abundance of I. ricinus is expanding in Sweden as has the number of reported human TBE cases. In addition to tick bites, alimentary TBEV infection has also been reported after consumption of unpasteurized dairy products. So far, no alimentary TBEV infection has been reported in Sweden, but knowledge about its prevalence in Swedish ruminants is scarce. In the present study, a total of 122 bulk tank milk samples and 304 individual milk samples (including 8 colostrum samples) were collected from dairy farms (n=102) in Sweden. All samples were analysed for the presence of TBEV antibodies by ELISA test and immunoblotting. Participating farmers received a questionnaire about milk production, pasteurization, tick prophylaxis used on animals, tick-borne diseases, and TBE vaccination status. We detected specific anti-TBEV antibodies, i.e., either positive (>126 Vienna Units per ml, VIEU/ml) or borderline (63-126 VIEU/ml) in bulk tank milk from 20 of the 102 farms. Individual milk samples (including colostrum samples) from these 20 farms were therefore collected for further analysis. Our results revealed important information for detection of emerging TBE risk areas. Factors such as consumption of unpasteurized milk, limited use of tick prophylaxis on animals and a moderate coverage of human TBE vaccination, may be risk factors for alimentary TBEV infection in Sweden.

High neutralizing antibody mismatch as a possible reason for vaccine failure in two children with severe tick-borne encephalitis

We describe two adolescents (13 and 16 years old) with severe tick-borne encephalitis (TBE) and vaccination breakthrough (VBT). Both suffer from severe persistent neurologic sequelae. Both patients had high TBE-IgG-titers after vaccination at the beginning of the infection and a low or missing TBE-IgM response (Type 2 vaccine failure). Neutralization tests show low titers against the respective infecting TBE virus strain and higher titers against the vaccine strain at the beginning of the infection implying an individual weak or impaired immune response to the respective virus as possible cause of TBE vaccine failure.We do not know of any similar observation or explanation for the phenomenon and at the moment can only speculate of a severe course correlated to highly mismatched IgG. This constellation of high TBE IgGs, the lack of immune response and a severe course strongly resembles the severe TBE courses that occurred in the past after TBE immunoglobulin administration.To our knowledge differentiation between structural and functional antibodies by neutralization tests with a) the affecting TBE virus strain and b) the vaccine virus strain in TBE vaccine failures has never been described before. We conclude (1) to consider a TBE virus infection also in vaccinated children presenting with meningoencephalitis, (2) to perform a broad immunological work-up in severe TBE especially after VBT, (3) to further study if high mismatch IgG's are a possible reason for vaccine failure.

Tick-borne encephalitis: Acute clinical manifestations and severity in 581 cases from Germany, 2018–2020

Tick-borne encephalitis (TBE) is a growing public health problem with an average of 361 cases notified annually to Germany's passive surveillance system since 2001. We aimed to assess clinical manifestations and identify covariates associated with severity. We included cases notified 2018-2020 in a prospective cohort study and collected data with telephone interviews, questionnaires to general practitioners, and hospital discharge summaries. Covariates' causal associations with severity were evaluated with multivariable logistic regression, adjusted for variables identified via directed acyclic graphs. Of 1220 eligible cases, 581 (48%) participated. Of these, 97.1% were not (fully) vaccinated. TBE was severe in 20.3% of cases (children: 9.1%, ≥70-year-olds: 48.6%). Routine surveillance data underreported the proportion of cases with central nervous system involvement (56% vs. 84%). Ninety percent required hospitalization, 13.8% intensive care, and 33.4% rehabilitation. Severity was most notably associated with age (odds ratio (OR): 1.04, 95% confidence interval (CI): 1.02-1.05), hypertension (OR: 2.27, 95%CI: 1.37-3.75), and monophasic disease course (OR: 1.67, 95%CI: 1.08-2.58). We observed substantial TBE burden and health service utilization, suggesting that awareness of TBE severity and vaccine preventability should be increased. Knowledge of severity-associated factors may help inform patients' decision to get vaccinated.

Tick-Borne Encephalitis: An Update for the Special Operations Forces Provider.

Tick-borne encephalitis (TBE) is a severe disease caused by the tick-borne encephalitis virus (TBEV). TBEV is endemic throughout Eurasia and can cause persistent neurologic deficits and death. Special Operations Forces (SOF) participating in field exercises or operations in TBE-endemic countries are at significantly increased risk of infection. Unlike Lyme disease and other tick-borne illnesses, transmission of TBEV can be immediate, and early tick removal does not reduce the risk of infection. While there are no virus-specific treatments available, the US Food and Drug Administration (FDA) recently approved a TBE vaccine that has yet to be incorporated into formal Department of Defense (DoD) recommendations. SOF medical providers should be aware of this disease entity and consider the TBE vaccine when planning exercises and operations in areas of responsibility (AORs) with TBE-endemic countries. This review serves as a refresher and update on the epidemiology, transmission, and management of TBE for the SOF provider.

Knowledge, Attitudes, and Behaviors Regarding Lyme Borreliosis Prevention in the Endemic Area of Northeastern Poland.

(1) Background: The incidence of Lyme borreliosis (LB) is increasing in Europe. The new LB vaccine is still in clinical development, thus the dissemination of knowledge about the disease is essential. We assessed the knowledge, attitudes and preventive practices (KAP) against tick-borne diseases (TBDs) of people living in the endemic area in northeastern Poland. (2) Methods: We surveyed 406 adults using a 37-item anonymous paper survey. The data were analyzed with regression models. (3) Results: The two most popular knowledge sources were the Internet and doctors, selected by 77.8% and 53.4%, respectively. Respondents felt moderately knowledgeable about TBDs and tick bite prophylaxis (median scores 5/10, and 6/10, respectively), considered TBDs to be a significant health threat (median 8/10), attributed high risk to tick mouthparts remaining in the skin after tick removal (median 10/10), and shared multiple misconceptions regarding LB transmission, symptoms, and management. General knowledge scores (GKS) about TBDs and tick protection practices scores (TPS) were moderate (65.0%; IQR, 55.8-71.7%, 63.6%; 54.5-72.7%, respectively). Only 48.0% had a positive attitude towards TBE vaccination. A recent tick-bite was associated with higher GKS (OR, 2.55; 95% CI, 1.27-5.10; p = 0.008), higher TPS (OR 4.76, 95% CI, 2.0-11.1; p < 0.001), and a positive attitude towards TBE vaccine (OR 2.10, 1.07-4.10, p = 0.030). A positive vaccine attitude was also associated with obtaining TBD knowledge from doctors and other verified sources (OR, 2.654, 1.66-4.23; p < 0.001). Age, place of residence, and frequent exposure to ticks in green areas were not associated with GKS, TPS, nor vaccine attitude. (4) Conclusions: Increased risk perceptions are associated with adoption of behaviors preventing TBDs. Medical professionals play an important role in communicating knowledge about TBDs. There is a need to revise current communication strategies with respect to tick bites and prevention of LB and other TBDs.

Tick-Talk: Parental online discourse about TBE vaccination

This study aimed to understand parental discourse about vaccination, and to provide guidance for communication that addresses the needs of parents. We analyzed parental discourse on child vaccination in general and tick-borne encephalitis (TBE) specifically in a Swiss parental online community. For this purpose, a data set containing 105k posts written by parents between 2007 and 2019 was analyzed using a combination of linguistic discourse analysis and qualitative content analysis. Results show that parents enter into a multidimensional decision-making process, characterized by elaborate practices of negotiation, consideration of vaccination recommendations as well as six distinct influencing thematic factors (vaccination safety, development and control, effectiveness, epidemiology, necessity, alternatives or additional prevention methods). The study shows a clear pattern of seasonality, with parents talking about TBE vaccination mostly triggered by events such as tick bites in spring and summer. From a public health perspective, the study emphasizes the need for sufficient, balanced, and tailored information about TBE vaccination. Online forums provide valuable information about what matters to parents and when, which can help public health authorities and practitioners provide information according to these concerns and enhance health literacy among parents.

Vaccine uptake in 20 countries in Europe 2020: Focus on tick-borne encephalitis (TBE)

Vaccination as a highly effective measure to protect against tick-borne encephalitis (TBE) comes into new focus as known risk areas are expanding across Europe and Asia. Here we present an online household survey conducted in 20 European countries spanning endemic and non-endemic regions of TBE in 2020. With a comprehensive and standardized list of questions, this survey provided a unique opportunity to compare TBE/TBE vaccine awareness, TBE severity perception, vaccine uptake, vaccination completeness/compliance and motivators/barriers for vaccination across Europe. Among the 51,478 participants, tetanus- (72-92%), influenza- (83-98%), and measles-awareness (79-96%) were highest, but awareness was low for Lyme borreliosis, bacterial meningitis and pneumococcal pneumonia. Awareness towards TBE and a TBE vaccine was 74% and 56% in endemic countries, respectively, compared to 30% and 12% in non-endemic countries. Vaccine uptake defined as at least one TBE vaccination was found to be highly heterogenous across both endemic (range 7-81%) and non-endemic countries (range 1-8%). Compliance with the recommended vaccination schedule was 21% for the primary vaccination series and dropped to 7% for the first booster vaccination in endemic countries. The percentage of participants protected against TBE by vaccination at the time of the survey ranged from 21% in Slovakia to 69% in Lithuania. The perception of personal risk or lack thereof was found to be the most influencing factor for and against TBE vaccination. Overall, these data indicate highly heterogenous responses in different European countries regarding not only awareness towards a TBE vaccine, but also regarding TBE vaccine uptake and compliance. Regionally focused strategies to increase diagnostic completeness as well as TBE vaccination are needed across Europe.

Tick-Borne Encephalitis (TBE) - Clinical and Therapeutical Aspects

Tick-Borne Encephalitis (TBE) - Clinical and Therapeutical Aspects Abstract. Tick-borne encephalitis (TBE) is an acute inflammatory disease of the central nervous system transmitted by ticks and caused by the TBE virus, which is found in more and more parts of Europe and Asia. Only 2-30% of infections are symptomatic, and a biphasic course of fever is typical in the prodromal stage. Clinically-neurologically, 50% of cases develop meningitis, 40% meningoencephalitis, and 10% meningoencephalomyelitis. The latter is often associated with feared brainstem involvement. Encephalitis is characterized by impaired consciousness, fatigue, emotional lability, and neurocognitive deficits; myelitis is characterized by flaccid paralysis of the arms or legs. Simultaneous detection of TBEV-specific IgM and IgG antibodies in serum and a matching inflammatory CSF syndrome is required to confirm the diagnosis. Meningitis heals without sequelae; 80% of cases of encephalitis and only 20% of cases of myelitis recover completely. The overall lethality rate is 1%. Immunocompromised, elderly, and myelitic patients are at higher risk for severe disease progression and mortality. Because no specific antiviral therapy is available, active TBE vaccination remains the most important preventive measure for all persons 6 years of age and older residing in high-risk areas.

Transient Expression of Flavivirus Structural Proteins in Nicotiana benthamiana.

Flaviviruses are a threat to public health and can cause major disease outbreaks. Tick-borne encephalitis (TBE) is caused by a flavivirus, and it is one of the most important causes of viral encephalitis in Europe and is on the rise in Sweden. As there is no antiviral treatment available, vaccination remains the best protective measure against TBE. Currently available TBE vaccines are based on formalin-inactivated virus produced in cell culture. These vaccines must be delivered by intramuscular injection, have a burdensome immunization schedule, and may exhibit vaccine failure in certain populations. This project aimed to develop an edible TBE vaccine to trigger a stronger immune response through oral delivery of viral antigens to mucosal surfaces. We demonstrated successful expression and post-translational processing of flavivirus structural proteins which then self-assembled to form virus-like particles in Nicotiana benthamiana. We performed oral toxicity tests in mice using various plant species as potential bioreactors and evaluated the immunogenicity of the resulting edible vaccine candidate. Mice immunized with the edible vaccine candidate did not survive challenge with TBE virus. Interestingly, immunization of female mice with a commercial TBE vaccine can protect their offspring against TBE virus infection.