Tick-borne encephalitis infections without CNS involvement: An observational study in Latvia, 2007-2022.

BACKGROUND: Tick-borne encephalitis (TBE) is a human viral infectious disease involving the central nervous system (CNS). It is caused by the tick-borne encephalitis virus (TBEV). At present, there is very limited information regarding the clinical importance and health burden of TBE infections without signs of CNS inflammation. Moreover, such cases are omitted from official TBE surveillances and there are no reports of population-based studies. METHODS AND FINDINGS: A nationwide population-based study was conducted in Latvia by intensively searching for symptomatic TBEV infections recorded in outpatient and hospital settings between 2007 and 2022. In total, 4,124 symptomatic TBEV infections were identified, of which 823 (20.0%) had no CNS involvement. Despite the lack of neurological symptoms, non-CNS TBE patients still experienced severe health conditions that required management in a hospital setting for a median duration of 7 days. Furthermore, lumbar puncture information was available for 708 of these patients, with 100 (14.1%) undergoing the procedure, suggesting a high suspicion of CNS involvement. CONCLUSIONS: Clearly, non-CNS TBE has the potential to negatively impact the health of patients. The actual burden of non-CNS TBEV cases may be higher than we think as these cases are omitted from official TBE surveillances and are challenging to recognize.

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

OBJECTIVES: 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 Riga Stradins 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. DISCUSSION: 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.

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

BACKGROUND: 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. METHODS: Riga Stradins 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)]. RESULTS: 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. CONCLUSION: 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.

Effectiveness of TBE vaccination in southern Germany and Latvia.

BACKGROUND: Tick-borne encephalitis (TBE) is a vaccine-preventable disease which may cause long-term sequelae and even death. The data on the long-term effectiveness of TBE vaccines are limited. Additionally, the vaccination schedule is complex which in part contributes towards sub-optimal uptake in TBE-endemic areas. The current ecological study measures vaccine effectiveness (VE) in two European countries. METHODS: TBE VE was measured from 2007 to 2018 in Latvia and Southern German states by age group, vaccination history, and schedule compliance. TBE cases and vaccination history were obtained from the public health agencies for Latvia and the southern German federal states of Bavaria and Baden-Wuerttemberg. Cases were "within schedule" if a TBE infection was diagnosed within the time interval preceding the next scheduled dose and "outside schedule" if the diagnosis occurred after the next scheduled dose. Vaccine uptake was estimated via representative nationwide surveys. RESULTS: VE after 2, 3, and ≥4 doses was high in both countries at 97.2%, 95.0%, and 95.4% for southern Germany, and 98.1%, 99.4%, and 98.8% for Latvia while within- schedule, and only showed marginal differences outside schedule at 90.6%, 89.9%, and 95.6% for southern Germany, and 97.4%, 98.4%, and 99.0% for Latvia regardless of age groups. CONCLUSIONS: In both countries, VE after two and three primary doses within-schedule was very high in all age groups. Once receiving booster doses, high VE continued to be observed even in persons with extended intervals since the last dose received, suggesting that longer and more flexible booster intervals may be considered for sustainable long-term protection.

TBE Vaccination Breakthrough Cases-Does Age Matter?

Tick-borne encephalitis (TBE) vaccines are highly effective in preventing TBE and vaccine failures (VF) are rare events. In this study, we compared the age distribution of TBE cases and TBE VF in three endemic countries: Sweden, Southern Germany, and Latvia. While the age distribution of TBE cases was similar for those <50 years versus those ≥50 years in all three countries, in Sweden, a higher proportion of VF cases was ≥50 years, whereas most VF cases in Latvia were <50 years of age and more evenly distributed between those <50 years versus those ≥50 in Southern Germany. Here, theoretical explanations were provided, including differences in diagnostic practices, vaccine uptake between age groups, behavioral patterns and underlying medical conditions, as to why VF were generally older in Sweden than the other countries. There is no scientific rationale to give an extra priming dose of TBE vaccine to subjects ≥50 years of age.