Coverage and determinants of COVID-19 child vaccination in Munich, Germany in October 2022-January 2023: Results of the COVIP-Virenwächter study.

COVID-19 vaccination reduces the risk of severe disease, in children as well as adults. We studied COVID-19 vaccination coverage among children, parental COVID-19 vaccination intent for their children and determinants of vaccination among children to inform communication strategies. We invited parents of children aged 6 months-11 years in Munich, Germany, to an anonymous online survey between 13.10.2022 and 15.01.2023. Parents reported COVID-19 vaccination status and, for unvaccinated children, vaccination intent per child. We determined vaccination coverage (≥ 1 dose) and parental intent, and subsequently used logistic regression to identify determinants of vaccination, including the 5C psychological antecedents of vaccination (confidence, complacency, constraints, calculation, collective responsibility). In total, 339 parents reported on 591 children. Vaccination coverage was 7% (6/86) amongst 6-months-4-year-olds and 59% (295/498) amongst 5-11-year-olds. For unvaccinated 6-months-4-year-olds, 31% of parents reported high, 13% medium, 56% low vaccination intent; for 5-11-year-olds 8% reported high, 20% medium, 71% low intent. Positive determinants of vaccination were older child age, child belonging to a clinically vulnerable group, as well as parental COVID-19 vaccination, higher education level, country of birth Germany, and high level of trust in official guidelines; a negative determinant was previous vaccination refusal. For 5-11-year-olds, additional positive determinants were higher confidence and lower complacency.    Conclusion: While a substantial proportion of 5-11-year-olds were vaccinated against COVID-19, coverage was low among 6-months-4-year-olds. Parental vaccination intent for unvaccinated children was low. Vaccination communication should take into account parental socio-demographic characteristics and specifically address individual risks and benefits of child vaccination. What is Known: • COVID-19 vaccination lowers severe disease risk in all ages. • Germany recommends vaccination for 5-11-years-olds since December 2021 and for 6 months-4 year-olds since November 2022. What is New: • In Munich, vaccine uptake was high in 5-11-year-olds but parental intent for not yet vaccinated children was low; the opposite was the case for 6-months-4-year-olds; vaccination determinants were eligibility, parental education, birth country and general vaccination hesitancy; psychological antecedents were confidence and complacency. • Tailored interventions should address guidelines, health literacy, cultural sensitivity, and boost confidence in vaccines and institutions while raising awareness of COVID-19 risks for children.

Correction: Nygren et al. Tick-Borne Encephalitis Risk Increases with Dog Ownership, Frequent Walks, and Gardening: A Case-Control Study in Germany 2018-2020. Microorganisms 2022, 10, 690.

In the original publication [...].

Detection of virus-specific T cells via ELISpot corroborates early diagnosis in human Borna disease virus 1 (BoDV-1) encephalitis.

BACKGROUND: Within endemic regions in southern and eastern Germany, Borna disease virus 1 (BoDV-1) causes rare zoonotic spill-over infections in humans, leading to encephalitis with a high case-fatality risk. So far, intra-vitam diagnosis has mainly been based on RT-qPCR from cerebrospinal fluid (CSF) and serology, both being associated with diagnostic challenges. Whilst low RNA copy numbers in CSF limit the sensitivity of RT-qPCR from this material, seroconversion often occurs late during the course of the disease. CASE PRESENTATION: Here, we report the new case of a 40 - 50 year-old patient in whom the detection of virus-specific T cells via ELISpot corroborated the diagnosis of BoDV-1 infection. The patient showed a typical course of the disease with prodromal symptoms like fever and headaches 2.5 weeks prior to hospital admission, required mechanical ventilation from day three after hospitalisation and remained in deep coma until death ten days after admission. RESULTS: Infection was first detected by positive RT-qPCR from a CSF sample drawn four days after admission (viral load 890 copies/mL). A positive ELISpot result was obtained from peripheral blood collected on day seven, when virus-specific IgG antibodies were not detectable in serum, possibly due to previous immune adsorption for suspected autoimmune-mediated encephalitis. CONCLUSION: This case demonstrates that BoDV-1 ELISpot serves as additional diagnostic tool even in the first week after hospitalisation of patients with BoDV-1 encephalitis.

One Health in action: Investigation of the first detected local cluster of fatal borna disease virus 1 (BoDV-1) encephalitis, Germany 2022.

BACKGROUND: Zoonotic Borna disease virus 1 (BoDV-1) causes fatal encephalitis in humans and animals. Subsequent to the detection of two paediatric cases in a Bavarian municipality in Germany within three years, we conducted an interdisciplinary One Health investigation. We aimed to explore seroprevalence in a local human population with a risk for BoDV-1 exposure as well as viral presence in environmental samples from local sites and BoDV-1 prevalence within the local small mammal population and its natural reservoir, the bicoloured white-toothed shrew (Crocidura leucodon). METHODS: The municipality's adult residents participated in an anonymised sero-epidemiological study. Potential risk factors and clinical symptoms were assessed by an electronic questionnaire. Small mammals, environmental samples and ticks from the municipality were tested for BoDV-1-RNA. Shrew-derived BoDV-1-sequences together with sequences of the two human cases were phylogenetically analysed. RESULTS: In total, 679 citizens participated (response: 41 %), of whom 38 % reported shrews in their living environment and 19 % direct shrew contact. No anti-BoDV-1 antibodies were detected in human samples. BoDV-1-RNA was also undetectable in 38 environmental samples and 336 ticks. Of 220 collected shrews, twelve of 40 C. leucodon (30%) tested BoDV-1-RNA-positive. BoDV-1-sequences from the previously diagnosed two paediatric patients belonged to two different subclades, that were also present in shrews from the municipality. INTERPRETATION: Our data support the interpretation that human BoDV-1 infections are rare even in endemic areas and primarily manifest as severe encephalitis. Sequence analysis linked both previous paediatric human infections to the local shrew population, but indicated independent infection sources. FUNDING: The project was partly financed by funds of the German Federal Ministry of Education and Research (grant numbers: 01KI2005A, 01KI2005C, 01KI1722A, 01KI1722C, 01KI2002 to MaBe, DR, RGU, DT, BS) as well as by the ReForM-A programme of the University Hospital Regensburg (to MaBa) and by funds of the Bavarian State Ministry of Health, Care and Prevention, project "Zoonotic Bornavirus Focal Point Bavaria - ZooBoFo" (to MaBa, MaBe, BS, MMB, DR, PS, RGU).

Seroprevalence, seroconversion and seroreversion of Borrelia burgdorferi-specific IgG antibodies in two population-based studies in children and adolescents, Germany, 2003 to 2006 and 2014 to 2017.

BackgroundLyme borreliosis (LB), caused by Borrelia burgdorferi (Bb), is the most common tick-borne infection in Germany. Antibodies against Bb are prevalent in the general population but information on temporal changes of prevalence and estimates of seroconversion (seroincidence) and seroreversion are lacking, especially for children and adolescents.AimWe aimed at assessing antibodies against Bb and factors associated with seropositivity in children and adolescents in Germany.MethodsWe estimated seroprevalence via two consecutive cross-sectional surveys (2003-2006 and 2014-2017). Based on a longitudinal survey component, we estimated annual seroconversion/seroreversion rates.ResultsSeroprevalence was 4.4% (95% confidence interval (CI): 3.9-4.9%) from 2003 to 2006 and 4.1% (95% CI: 3.2-5.1%) from 2014 to 2017. Seroprevalence increased with age, was higher in male children, the south-eastern regions of Germany and among those with a high socioeconomic status. The annual seroconversion rate was 0.3% and the annual seroreversion rate 3.9%. Males were more likely to seroconvert compared with females. Low antibody levels were the main predictor of seroreversion.ConclusionWe did not detect a change in seroprevalence in children and adolescents in Germany over a period of 11 years. Potential long-term changes, for example due to climatic changes, need to be assessed in consecutive serosurveys. Seroconversion was more likely among children and adolescents than among adults, representing a target group for preventive measures. Seroreversion rates are over twice as high in children and adolescents compared with previous studies among adults. Thus, seroprevalence estimates and seroconversion rates in children are likely underestimated.

[Viral zoonoses in Germany: a One Health perspective]. / Virale Zoonosen in Deutschland aus der One Health-Perspektive.

The COVID-19 pandemic and the increasing occurrence of monkeypox (mpox) diseases outside Africa have illustrated the vulnerability of populations to zoonotic pathogens. In addition, other viral zoonotic pathogens have gained importance in recent years.This review article addresses six notifiable viral zoonotic pathogens as examples to highlight the need for the One Health approach in order to understand the epidemiology of the diseases and to derive recommendations for action by the public health service. The importance of environmental factors, reservoirs, and vectors is emphasized, the diseases in livestock and wildlife are analyzed, and the occurrence and frequency of diseases in the population are described. The pathogens selected here differ in their reservoirs and the role of vectors for transmission, the impact of infections on farm animals, and the disease patterns observed in humans. In addition to zoonotic pathogens that have been known in Germany for a long time or were introduced recently, pathogens whose zoonotic potential has only lately been shown are also considered.For the pathogens discussed here, there are still large knowledge gaps regarding the transmission routes. Future One Health-based studies must contribute to the further elucidation of their transmission routes and the development of prevention measures. The holistic approach does not necessarily include a focus on viral pathogens/diseases, but also includes the question of the interaction of viral, bacterial, and other pathogens, including antibiotic resistance and host microbiomes.

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.

PURPOSE: Despite 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. METHODS: Routinely 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). RESULTS: Of 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. CONCLUSION: Half 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.

SARS-CoV-2 Prevalence on and Incidence after Arrival in Travelers on Direct Flights from Cape Town, South Africa to Munich, Germany Shortly after Occurrence of the Omicron Variant in November/December 2021: Results from the OMTRAIR Study.

The highly transmissible SARS-CoV-2-variant B.1.1.529 (Omicron) first appeared in South Africa in November 2021. In order to study Omicron entry to Germany, its occurrence related to incoming airline travel, symptomatology and compliance with entry regulations and recommendations, we conducted a cross-sectional study, followed by a retrospective cohort study among passengers and crew on 19 direct flights from Cape Town, South Africa, to Munich, Germany, between 26 November and 23 December 2021. Travelers were mandatorily PCR-tested on arrival and invited to complete an online questionnaire. SARS-CoV-2-prevalence on arrival was 3.3% (n = 90/2728), and 93% were Omicron. Of the passengers, 528 (19%) completed the questionnaire. Among participants who tested negative on arrival, self-reported SARS-CoV-2-incidence was 4.3% within 14 days, of whom 74% reported a negative PCR-test ≤ 48 h before boarding, 77% were fully vaccinated, and 90% reported wearing an FFP2/medical mask during flight. We found multiple associations between risk factors and infection on and after arrival, among which having a positive-tested travel partner was the most noteworthy. In conclusion, PCR testing before departure was insufficient to control the introduction of the Omicron variant. Additional measures (e.g., frequent testing, quarantine after arrival or travel ban) should be considered to delay virus introduction in such settings.

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

In 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.

First detected geographical cluster of BoDV-1 encephalitis from same small village in two children: therapeutic considerations and epidemiological implications.

BACKGROUND: The Borna disease virus (BoDV-1) is an emerging zoonotic virus causing severe and mostly fatal encephalitis in humans. METHODS AND RESULTS: A local cluster of fatal BoDV-1 encephalitis cases was detected in the same village three years apart affecting two children. While the first case was diagnosed late in the course of disease, a very early diagnosis and treatment attempt facilitated by heightened awareness was achieved in the second case. Therapy started as early as day 12 of disease. Antiviral therapy encompassed favipiravir and ribavirin, and, after bioinformatic modelling, also remdesivir. As the disease is immunopathogenetically mediated, an intensified anti-inflammatory therapy was administered. Following initial impressive clinical improvement, the course was also fatal, although clearly prolonged. Viral RNA was detected by qPCR in tear fluid and saliva, constituting a possible transmission risk for health care professionals. Highest viral loads were found post mortem in the olfactory nerve and the limbic system, possibly reflecting the portal of entry for BoDV-1. Whole exome sequencing in both patients yielded no hint for underlying immunodeficiency. Full virus genomes belonging to the same cluster were obtained in both cases by next-generation sequencing. Sequences were not identical, indicating viral diversity in natural reservoirs. Specific transmission events or a common source of infection were not found by structured interviews. Patients lived 750m apart from each other and on the fringe of the settlement, a recently shown relevant risk factor. CONCLUSION: Our report highlights the urgent necessity of effective treatment strategies, heightened awareness and early diagnosis. Gaps of knowledge regarding risk factors, transmission events, and tailored prevention methods become apparent. Whether this case cluster reflects endemicity or a geographical hot spot needs further investigation.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

[Parental intention to vaccinate their children against COVID-19]. / COVID-19-Impfintention von Eltern bezogen auf ihre Kinder.

BACKGROUND: With the start of the vaccination campaign, a new phase in the management of the coronavirus pandemic has begun. Approval and recommendation for COVID-19 vaccination of children followed gradually; to date (4 October 2022), vaccination for children under five years of age has not been approved in Germany. AIM OF THE STUDY: The aim was to investigate how parents' intention to vaccinate their children against COVID-19 developed from May 2020 to February 2021 (from the first to the second wave of the COVID-19 pandemic) and to analyse the determinants of the intention to vaccinate. METHODS: In May 2020, 612 families participating with their children aged 1.5-6 years in the KUNO Kids Health Study completed an online survey (participation rate 51%), and 507 completed the second survey in February 2021. Determinants of the intention to vaccinate were analysed for both time points using univariable and multivariable logistic regression models. RESULTS: While 51% of parents reported wanting their children vaccinated against COVID-19 in May 2020, this proportion decreased to 41% by February 2021. At least at one of the two time points, health literacy and perceived competence regarding protective measures against the virus were significantly positively associated with higher vaccination intentions, while belonging to a risk group and the perception that the political measures were exaggerated were associated with lower vaccination intentions. DISCUSSION: Parents' intention to have their children vaccinated against COVID-19 was low and decreased further from the first to the second wave of the coronavirus pandemic. Attitudinal and competence-related determinants were important at both time points and could be targeted in a future vaccination campaign addressing parents of younger children.

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.

Tick-Borne Encephalitis Risk Increases with Dog Ownership, Frequent Walks, and Gardening: A Case-Control Study in Germany 2018-2020.

In Germany, tick-borne encephalitis (TBE) infections mainly occur in southern regions. Despite recent increases in incidence, TBE vaccination coverage remains low, necessitating additional preventive strategies against TBE. Our case-control study in Southern Germany from 2018 to 2020 mapped knowledge/application of tick-protective strategies and identified TBE risk factors. We calculated odds ratios (OR), with 95% confidence intervals (CI). We interviewed 581 cases and 975 matched controls. Most participants recalled lifetime tick bites, mainly while walking, gardening, or hiking. However, only 45% of cases noticed ticks during exposure time; another 12% reported unpasteurized milk intake. While tick-protection knowledge was satisfactory, application lagged behind. Risk factors included dog ownership (OR = 2.45, 95% CI: 1.85−3.24), walks ≥ 4×/week (OR = 2.11, 95% CI: 1.42−3.12), gardening ≥ 4×/week (OR = 1.83, 95% CI: 1.11−3.02), and garden proximity < 250 m of forests (OR = 2.54, 95% CI: 1.82−3.56). Applying ≥2 tick-protective strategies (OR = 0.52, 95% CI: 0.40−0.68) and keeping lawns mowed (OR = 0.63, 95% CI: 0.43−0.91) were inversely associated with TBE. In 2020 (likely pandemic-related), cases reported significantly more walks than previously, potentially explaining the record high case numbers. Our findings provide guidance on targets for TBE prevention. Persons with gardens near forests, frequent outdoor activities, or dogs could particularly benefit from targeted information, including on vaccination and preventing tick bites.

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.

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 conducted an epidemiological outbreak investigation, including a retrospective cohort study among hunting participants, to identify likely transmission routes and activities 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 infection was highest when directly involved (RR = 10.0; 95%CI: 2.6-392). F. tularensis was isolated from 1/4 hares. Only two individuals reported using some of the recommended personal protective equipment (PPE). Occurrence of mainly non-specific symptoms, likely due to early treatment, was not indicative of a specific transmission route. Transmissions via direct (skin/mucosa) contact and by inhalation of contaminated aerosols seem plausible. Promoting and increasing appropriate use of PPE among people processing hares is crucial to prevent future outbreaks.

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.