OBJECTIVE: Tick-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.
METHODS: Study 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.
RESULTS: There 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.
CONCLUSIONS: TBE 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.

TBE vaccination failures among those past middle age have raised concern about immune response declining with age. We investigated immunogenicity of the TBE-vaccine FSME-Immun among those aged 50+ years using the standard three-dose primary series and alternative four-dose schedules.
In this single-centre, open-label, randomized controlled trial, 200 TBE-naive Swedish adults were given primary TBE vaccination with FSME-Immun. Those aged 50+ years (n = 150) were randomized to receive the standard three-dose (days 0-30-360) or one of two four-dose series (0-7-21-360; 0-30-90-360). For participants < 50 years (n = 50) the standard three-dose schedule was used. Titres of neutralizing antibodies were determined on days 0, 60, 120, 360, and 400. The main outcome was the log titre of TBE virus-specific neutralizing antibodies on day 400.
The three-dose schedule yielded lower antibody titres among those aged 50+ years than the younger participants on day 400 (geometric mean titre 41 versus 74, p < 0.05). The older group showed higher titres for the four-dose 0-7-21-360 than the standard three-dose schedule both on day 400 (103 versus 41, p < 0.01; primary end point) and at the other testing points (days 60, 120, 360). Using the other four-dose schedule (0-30-90-360), no such difference was observed on day 400 (63 versus 41, NS).
Immune response to the TBE vaccine declined with age. A four-dose schedule (0-7-21-360) may benefit those aged 50 years or older. This study is registered at ClinicalTrials.gov, NCT01361776.

Tick-borne encephalitis (TBE) is one of the most important infectious diseases of the central nervous system in dogs from endemic areas. While in humans survival rate and long-term outcomes are well described, these data are lacking in veterinary literature. The aim of the present paper is to characterize the clinical aspects of TBE and to investigate fatality rate, long-term outcome and the long-term neurological sequelae in a population of dogs infected with TBE. We performed a retrospective analysis of 54 dogs diagnosed with TBE at the veterinary hospital of the University of Zurich between 1999 and 2016. Medical data such as signalment, clinical presentation, results of diagnostic procedures, treatment and outcome were collected and analyzed. Statistical analysis including a cox proportional hazard model using a backward stepwise regression approach was performed. In 62% of the TBE cases unspecific signs were described before the onset of neurological signs, resembling a biphasic appearance that is well known in human TBE. Case fatality rate was 33% and all dogs died within the first 4 months after diagnosis. Long-term neurological sequalae were detected in 17% of the TBE cases. For each day of clinical signs before hospital entry the odds of sequalae increased by a factor of 1.88 (CI 1.04-3.15). Older dogs and dogs presented with seizure activity had an increased hazard risk of death (Hazard ration = 1.2, p = 0.03; and 9.38, p = 0.001, respectively). In conclusion, despite TBE being a life-threatening disease with severe clinical signs, the survival rate in our study was 67%. However, long-term sequalae can be of concern especially in dogs with longer clinical course.

Various animal species have been evaluated in depth for their potential as Tick-borne encephalitis virus (TBEV) sentinel species, although evidence for equine capacity is incomplete. Therefore, a comprehensive cross-sectional stratified serosurvey and PCR analysis of selected horses (n = 301) were performed in TBEV endemic localities in Lithuania. Attached and moving ticks (n = 241) have been collected from aforementioned hosts to evaluate natural infectivity of TBEV vectors (Ixodes spp.) in the recreational environments surrounding equestrian centers. All samples were screened for TBEV IgG and positive samples were confirmed by virus neutralization test (VNT). 113 (37.5%) horses from all counties of Lithuania tested positive for TBEV IgG, revealing age and sex indifferent results of equine seroprevalence that were significantly dependent on pedigree: horses of mixed breed were more susceptible to infection possibly due to their management practices. TBEV prevalence in equine species corresponded to TBEV-confirmed human cases in the precedent year. As much as 3.9% of horses were viraemic with TBEV-RNA with subsequent confirmation of TBEV European subtype. 4/38 of tested tick pools were positive for TBEV-RNA (Minimal infectious rate 1.2%). Several unknown microfoci were revealed during the study indicating areas of extreme risk close to popular human entertainment sites. The study provides important evidence in favor of horses\' usage as sentinel species, as equines could provide more detailed epidemiological mapping of TBEV, as well as more efficient collection of ticks for surveillance studies.

Southern Sweden is endemic for tick-borne encephalitis (TBE), with Stockholm County as one of the high-risk areas. Our aim in this study was to describe cases of vaccine failures and to optimize future vaccination recommendations.
Patients with TBE were identified in the notification database at the Department of Communicable Disease Control and Prevention in Stockholm County during 2006-2015. Vaccine failure was defined as TBE despite adherence to the recommended vaccination schedule with at least 2 doses. Clinical data were extracted from medical records.
A total of 1004 TBE cases were identified, 53 (5%) were defined as vaccine failures. In this latter group, the median age was 62 years (6-83). Forty-three (81%) patients were aged >50 years and 2 were children. Approximately half of the patients had comorbidities, with diseases affecting the immune system accounting for 26% of all cases. Vaccine failures following the third or fourth vaccine dose accounted for 36 (68%) of the patients. Severe and moderate TBE disease affected 81% of the cases.
To our knowledge, this is the largest documented cohort of TBE vaccine failures. Vaccine failure after 5 TBE vaccine doses is rare. Our data provide rationale for adding an extra priming dose to those aged ≥50 years.