Tick-borne encephalitis vaccine effectiveness and barriers to vaccination in Germany

Tick-borne encephalitis (TBE) vaccination coverage remains low in Germany. Our case–control study (2018–2020) aimed to examine reasons for low vaccine uptake, vaccine effectiveness (VE), and vaccine breakthrough infections (VBIs). Telephone interviews (581 cases, 975 matched controls) covered vaccinations, vaccination barriers, and confounders identified with directed acyclic graphs. Multivariable logistic regression determined VE as 1—odds ratio with 95% confidence intervals (CI). We additionally calculated VE with the Screening method using routine surveillance and vaccination coverage data. Main vaccination barriers were poor risk perception and fear of adverse events. VE was 96.6% (95% CI 93.7–98.2) for ≥ 3 doses and manufacturer-recommended dosing intervals. Without boosters, VE after ≥ 3 doses at ≤ 10 years was 91.2% (95% CI 82.7–95.6). VE was similar for homologous/heterologous vaccination. Utilising routine surveillance data, VE was comparable (≥ 3 doses: 92.8%). VBIs (n = 17, 2.9% of cases) were older, had more comorbidities and higher severity than unvaccinated cases. However, only few VBIs were diagnostically confirmed; 57% of re-tested vaccinated cases (≥ 1 dose, n = 54) proved false positive. To increase TBE vaccine uptake, communication efforts should address complacency and increase confidence in the vaccines’ safety. The observed duration of high VE may inform decision-makers to consider extending booster intervals to 10 years.Peer Reviewe

Effectiveness of TBE vaccination in southern Germany and Latvia

Funding Information: This study was sponsored by Pfizer Inc. Publisher Copyright: © 2022 The AuthorsBackground: 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.publishersversionPeer reviewe

Factors associated with generic health-related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD): a cross-sectional study

Background: Health-related quality of life (HRQOL) is impaired in chronic obstructive pulmonary disease (COPD) patients, but determining factors for HRQOL are still not unequivocal. This study measures HRQOL among patients with COPD and aims to determine factors associated with HRQOL. Methods: Data for cross-sectional analyses were obtained from the baseline of a cohort study. The study population includes adult COPD patients (disease duration >= 3 months), recruited from primary and secondary care settings in Germany, without acute psychiatric/neurologic disease (exception: affective/anxiety disorders). HRQOL was assessed using the Short-Form 12 (SF-12) Health Survey Questionnaire, comprising a physical and mental component. Independent variables encompass socio-demographic, disease-specific, treatment-related and psychological factors. Multivariable linear regression analyses were conducted. Results: In total, 206 COPD patients (60.7% male; mean age: 65.3 years) took part in the study. In multivariable analysis, the physical component score showed a significant negative association with the COPD Assessment Test (CAT) (P<0.001) and a higher total number of prescribed medications (P=0.001). A higher forced expiratory volume in 1 second (FEV1) value in percent predicted was significantly related to the physical component score in a positive manner (P=0.006). The mental component score was significantly associated with elevated patient-reported symptoms of anxiety (P=0.002) or depression (P<0.001), measured by the hospital anxiety and depression scale (HADS) in a negative way. Like for the physical component score (P<0.001), a worse CAT score was significantly associated with a lower mental component score (P=0.033). Conclusions: Focusing on patient reported outcomes and screening for depression and anxiety with potential successive treatment might be promising approaches to improve HRQOL in patients with COPD

Parents’ intention to get vaccinated and to have their child vaccinated against COVID-19: cross-sectional analyses using data from the KUNO-Kids health study

A COVID-19 vaccine can be an important key for mitigating the spread of the pandemic, provided that it is accepted by a sufficient proportion of the population. This study investigated parents’ intention to get vaccinated and to have one’s child vaccinated against COVID-19. In May 2020, 612 parents participating with their child in the KUNO-Kids health study completed an online survey. Multivariable logistic regression models were calculated to analyze predictors of intention to vaccinate. Fifty-eight percent of parents intended to get vaccinated against COVID-19, and 51% intended to have their child vaccinated. Significant predictors for the intention to get vaccinated and for having the child vaccinated included stronger parental confidence in one’s knowledge about prevention measures and lower beliefs that policy measures were exaggerated. Conclusion: COVID-19 vaccination hesitancy was considerable in our sample of parents in Germany. However, our study revealed some potentially modifiable factors which should be addressed by a comprehensive and tailored communication and education strategy

Antibodies against viral nucleo-, phospho-, and X protein contribute to serological diagnosis of fatal Borna disease virus 1 infections

Borna disease virus 1 (BoDV-1) causes rare but often fatal encephalitis in humans. Late diagnosis prohibits an experimental therapeutic approach. Here, we report a recent case of fatal BoDV-1 infection diagnosed on day 12 after hospitalization by detection of BoDV-1 RNA in the cerebrospinal fluid. In a retrospective analysis, we detect BoDV-1 RNA 1 day after hospital admission when the cell count in the cerebrospinal fluid is still normal. We develop a new ELISA using recombinant BoDV-1 nucleoprotein, phosphoprotein, and accessory protein X to detect seroconversion on day 12. Antibody responses are also shown in seven previously confirmed cases. The individual BoDV-1 antibody profiles show variability, but the usage of three different BoDV-1 antigens results in a more sensitive diagnostic tool. Our findings demonstrate that early detection of BoDV-1 RNA in cerebrospinal fluid and the presence of antibodies against at least two different viral antigens contribute to BoDV-1 diagnosis. Physicians in endemic regions should consider BoDV-1 infection in cases of unclear encephalopathy and initiate appropriate diagnostics at an early stage

Epidemiology of Tick-Borne Encephalitis (TBE) in Germany, 2001–2018

We reviewed tick-borne encephalitis (TBE) surveillance and epidemiology in Germany, as these underlie public health recommendations, foremost vaccination. We performed descriptive analyses of notification data (2001–2018, n = 6063) according to region, demographics and clinical manifestations and calculated incidence trends using negative binomial regression. Risk areas were defined based on incidence in administrative districts. Most cases (89%) occurred in the federal states of Baden-Wurttemberg and Bavaria, where annual TBE incidence fluctuated markedly between 0.7–2.0 cases/100,000 inhabitants. A slight but significantly increasing temporal trend was observed from 2001–2018 (age-adjusted incidence rate ratio (IRR) 1.02 (95% confidence interval (CI): 1.01–1.04)), primarily driven by high case numbers in 2017–2018. Mean incidence was highest in 40–69-year-olds and in males. More males (23.7%) than females (18.0%, p = 0.02) had severe disease (encephalitis or myelitis), which increased with age, as did case-fatality (0.4% overall; 2.1% among ≥70-year-olds). Risk areas increased from 129 districts in 2007 to 161 in 2019. Expansion occurred mainly within existent southern endemic areas, with slower contiguous north-eastern and patchy north-western spread. Median vaccination coverage at school entry in risk areas in 2016–2017 ranged from 20%–41% in 4 states. Increasing TBE vaccine uptake is an urgent priority, particularly in high-incidence risk areas.Peer Reviewe

Risk factors for Borna disease virus 1 encephalitis in Germany – a case–control study

ABSTRACTIn 2018, Borna Disease Virus 1 (BoDV-1) was confirmed as a human zoonotic pathogen causing rare but fatal encephalitis in Germany. While diagnostic procedures and the clinical picture have been described, epidemiology remains mysterious. Though endemic areas and a natural reservoir host have been identified with the shrew Crocidura leucodon shedding virus in secretions, transmission events, routes and risk factors are unclear. We performed the first comprehensive epidemiological study, combining a large case series with the first case–control study: We interviewed family members of 20 PCR-confirmed BoDV-1 encephalitis cases deceased in 1996–2021 with a standardized questionnaire covering medical history, housing environment, profession, animal contacts, outdoor activities, travel, and nutrition. Cases’ median age was 51 (range 11–79) years, 12/20 were female, and 18/20 lived in the federal state of Bavaria in Southeastern Germany. None had a known relevant pre-existing medical condition. None of the interviews yielded a transmission event such as direct shrew contact, but peridomestic shrew presence was confirmed in 13 cases supporting environmental transmission. Residency in rural areas endemic for animal BoDV-1 was the common denominator of all cases. A subsequent individually matched case–control study revealed residence close to nature in a stand-alone location or on the fringe of the settlement as a risk factor for disease in multivariable analysis with an adjusted OR of 10.8 (95% CI 1.3–89.0). Other variables including keeping cats were not associated with disease. Targeted prevention, future post-exposure-prophylaxis, and timely diagnosis remain challenging

Tick-borne encephalitis virus infections in Germany. Seasonality and in-year patterns. A retrospective analysis from 2001-2018

Background Little is known regarding the changing seasonality of infections with the tick-borne encephalitis virus (TBEV) and the incidence of the resulting disease over the last two decades. Seasonal patterns have to our knowledge not previously been systematically investigated and are poorly understood. We investigate emerging seasonal changes in clinical aspects like potentially increasing hospitalization during the year, variations in clinical symptoms and disease severity during the season and seasonal dynamics of fatal outcomes. Material and methods TBEV infection became a notifiable disease in Germany in 2001. We used the national reporting dataset spanning from 2001–2018, provided by the Robert Koch-Institute (RKI). There were general epidemiological variables available, including “symptom onset”, “age” and “sex”. Furthermore, several variables documented disease severity. These included “CNS symptoms”, “myelitis”, “fatal outcome” and “hospitalization”. Potential factors influencing the occurrence of CNS symptoms, myelitis, hospitalizations and fatal outcome were analyzed using logistic regression models. Linear trends, including the “time point in year” at which TBEV infection related symptoms were detected, were tested using calendar year as a continuous covariate. In addition, seasonal trends and age and sex specific differences were exploratively tested for non-linear effects using restricted cubic splines with knot locations based on Harrell's recommended percentiles. Finally, the dynamic relationship between in-seasonal trends year of detection, sex and age was tested using interaction terms. Results 6,073 TBEV infection cases from 2001–2018 were included in our analysis. We find that from 2001–2018 TBEV infections are reported 0.69 days earlier each year (p<0.001). There was no detectable seasonal variation regarding the occurrence of fatal outcome, CNS and myelitis. However, there was a significant changing trend regarding hospitalizations over the course of the year: The risk for hospitalization increases until August, decreases again from October on. Conclusion We present epidemiological evidence that the TBE season in Germany has shifted to start earlier over the last years, beginning approximately 12 days earlier in 2018 than it did in 2001. There are seasonal patterns regarding a higher risk of hospitalization during August.Peer Reviewe

Epidemiological investigation of a tularaemia outbreak after a hare hunt in Bavaria, Germany, 2018

In November 2018, a tularaemia outbreak occurred in Bavaria, Germany, among participants of a hare hunt and butchery employees handling the hares. We con-ducted an epidemiological outbreak investigation, including a retrospective cohort study among hunting participants, to identify likely transmission routes and activi-ties associated with infection. Twelve of 41 participants were antibody- positive for Francisella (F.) tularensis (attack rate: 29%). Cases reported influenza- like symptoms (n= 11), lymphadenopathy (n= 1) and conjunctivitis (n= 1). Infection only occurred in those hunting participants present while hares were processed, while risk of infec-tion was highest when directly involved (RR = 10.0; 95%CI: 2.6–392). F. tularensiswas isolated from 1/4 hares. Only two individuals reported using some of the rec-ommended personal protective equipment (PPE). Occurrence of mainly non-specific symptoms, likely due to early treatment, was not indicative of a specific transmis-sion route. Transmissions via direct (skin/mucosa) contact and by inhalation of con-taminated aerosols seem plausible. Promoting and increasing appropriate use of PPE among people processing hares is crucial to prevent future outbreaks.Peer Reviewe

Specific, but not general beliefs about medicines are associated with medication adherence in patients with COPD, but not asthma: Cohort study in a population of people with chronic pulmonary disease

Background: Beliefs about medicines are regarded as influencing factors on medication adherence (Horne, 1997). Adherence levels in patients with chronic pulmonary diseases are low (Bourbeau and Bartlett, 2008; Sumino and Cabana, 2013). A better understanding of the predictive role of patients' beliefs about medicines for adherence might be a crucial step to improve medication adherence. Objective: This prospective study investigated the association between beliefs about medicines and medication adherence in patients with asthma and COPD. Methods: The Beliefs about Medicines Questionnaire (BMQ) and the Medication Adherence Rating Scale (MARS) were administered to 402 patients (49% asthma, 51% COPD, 50% female, mean age 56.7 years (SD = 15.9)) at baseline. Follow-ups were carried out after 3 (N = 255) and 12 months (N = 171). Multivariable logistic regression analyses were performed analysing the association between the BMQ subscales at baseline and adherence at each follow-up inquiry. Sociodemographic, psychosocial, and disease related factors were considered as potential confounders. Results: One third of the patients showed adherent behavior (18% and 46% of people with asthma and COPD). In the COPD sample, the subscale Specific-necessity showed a significant positive association with adherence at the 3-months-follow-up (OR = 2.6, 95% CI 1.4-5.1) and the subscale Specific-concerns showed a significant inverse association with adherence at the 3-months-follow-up (OR = 0.6, 95% CI 0.3-0.95) and the 12-months-followup (OR = 0.4, 95% CI 0.2-0.8). No significant association was found for the asthmatic sample. Conclusions: Beliefs about medicines are important factors predicting future medication adherence in patients with COPD, but not asthma. Physicians should primarily focus on the specific beliefs of their patients in order to diminish medication non-adherence