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).

Long-Term Trends in the Protection Against Severe Courses of COVID-19 by Vaccination.

BACKGROUND: The long-term course of protection against severe COVID-19 courses by vaccine-induced or hybrid immunity in Germany is unclear. METHODS: We studied 146 457 cases aged 60-99 years in the German federal state of Bavaria who were immunized against COVID-19 and tested positive for it from February 2022 to January 2023. We calculated adjusted hazard ratios for a severe course (hospitalization or death due to COVID-19) for different intervals between the onset of full primary or booster immunity and the date of the infection. RESULTS: 3342 (2.3%) severe courses of COVID-19 were observed in the first 60 days after the infection. The risk of a severe course rose with the interval between the onset of immune protection and the infection (adjusted hazard ratios and 95% confidence intervals at 6, 9, 12, and 15 months: 1.14 [1.08; 1.20]; 1.33 [1.24; 1.42]; 1.39 [1.25; 1.54]; 1.61 [1.35; 1.93]). The risk rose more slowly when mRNA-based vaccines were used exclusively. In a previous study, we observed 82% initial efficacy in cases aged 60 and above who received a booster vaccination (compared to unvaccinated cases) and an absolute risk reduction of 2.1%. If one extrapolates these findings to the current study, the residual efficacy and absolute risk reduction are found to be approximately 71% and 1.8% (respectively) at 6 months, and 32% and 0.8% at 15 months. CONCLUSION: These results indicate that, during the Omicron wave, the protection of older persons against a severe COVID-19 course gradually declined from six months after vaccination onward. The limitations of this study include confounders that could not be taken into account, possible misclassification of the cause of death, and selection bias due to missing information about vaccination status and severe COVID-19 courses.

Epidemiology of common infectious diseases before and during the COVID-19 pandemic in Bavaria, Germany, 2016 to 2021: an analysis of routine surveillance data.

BackgroundUnprecedented non-pharmaceutical interventions to control the COVID-19 pandemic also had an effect on other infectious diseases.AimWe aimed to determine their impact on transmission and diagnosis of notifiable diseases other than COVID-19 in Bavaria, Germany, in 2020 and 2021.MethodsWe compared weekly cases of 15 notifiable infectious diseases recorded in Bavaria between 1 January 2016 and 31 December 2021 in time series analyses, median age and time-to-diagnosis using Wilcoxon rank sum test and hospitalisation rates using univariable logistic regression during three time periods: pre-pandemic (weeks 1 2016-9 2020), pandemic years 1 (weeks 10-52 2020) and 2 (2021).ResultsWeekly case numbers decreased in pandemic year 1 for all diseases assessed except influenza, Lyme disease and tick-borne encephalitis; markedly for norovirus gastroenteritis (IRR = 0.15; 95% CI: 0.12-0.20) and pertussis (IRR = 0.22; 95% CI: 0.18-0.26). In pandemic year 2, influenza (IRR = 0.04; 95% CI: 0.02-0.09) and pertussis (IRR = 0.11; 95% CI: 0.09-0.14) decreased markedly, but also chickenpox, dengue fever, Haemophilus influenzae invasive infection, hepatitis C, legionellosis, noro- and rotavirus gastroenteritis and salmonellosis. For enterohaemorrhagic Escherichia coli infections, median age decreased in pandemic years 1 and 2 (4 years, interquartile range (IQR): 1-32 and 3 years, IQR: 1-18 vs 11 years, IQR: 2-42); hospitalisation proportions increased in pandemic year 1 (OR = 1.60; 95% CI: 1.08-2.34).ConclusionReductions for various infectious diseases and changes in case characteristics in 2020 and 2021 indicate reduced transmission of notifiable diseases other than COVID-19 due to interventions and under-detection.

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.

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.

Epidemiological and Serological Analysis of a SARS-CoV-2 Outbreak in a Nursing Home: Impact of SARS-CoV-2 Vaccination and Enhanced Neutralizing Immunity Following Breakthrough Infection.

Background: Despite a vaccination rate of 82.0% (n = 123/150), a SARS-CoV-2 (Alpha) outbreak with 64.7% (n = 97/150) confirmed infections occurred in a nursing home in Bavaria, Germany. Objective: the aim of this retrospective cohort study was to examine the effects of the Corminaty vaccine in a real-life outbreak situation and to obtain insights into the antibody response to both vaccination and breakthrough infection. Methods: the antibody status of 106 fully vaccinated individuals (54/106 breakthrough infections) and epidemiological data on all 150 residents and facility staff were evaluated. Results: SARS-CoV-2 infections (positive RT-qPCR) were detected in 56.9% (n = 70/123) of fully vaccinated, compared to 100% (n = 27/27) of incompletely or non-vaccinated individuals. The proportion of hospitalized and deceased was 4.1% (n = 5/123) among fully vaccinated and therewith lower compared to 18.5% (n = 5/27) hospitalized and 11.1% (n = 3/27) deceased among incompletely or non-vaccinated. Ct values were significantly lower in incompletely or non-vaccinated (p = 0.02). Neutralizing antibodies were detected in 99.1% (n = 105/106) of serum samples with significantly higher values (p < 0.001) being measured post-breakthrough infection. α-N-antibodies were detected in 37.7% of PCR positive but not in PCR negative individuals. Conclusion: Altogether, our data indicate that SARS-CoV-2 vaccination does provide protection against infection, severe disease progression and death with regards to the Alpha variant. Nonetheless, it also shows that infection and transmission are possible despite full vaccination. It further indicates that breakthrough infections can significantly enhance α-S- and neutralizing antibody responses, indicating a possible benefit from booster vaccinations.

First cross-border outbreak of foodborne botulism in the European Union associated with the consumption of commercial dried roach (Rutilus rutilus).

Botulism outbreaks due to commercial products are extremely rare in the European Union. Here we report on the first international outbreak of foodborne botulism caused by commercial salt-cured, dried roach (Rutilus rutilus). Between November and December 2016, an outbreak of six foodborne botulism type E cases from five unrelated households was documented in Germany and Spain. The outbreak involved persons of Russian and Kazakh backgrounds, all consumed unheated salt-cured, dried roach-a snack particularly favored in Easter-European countries. The implicated food batches had been distributed by an international wholesaler and were recalled from Europe-wide outlets of a supermarket chain and other independent retailers. Of interest, and very unlike to other foodborne disease outbreaks which usually involves a single strain or virus variant, different Clostridium botulinum strains and toxin variants could be identified even from a single patient's sample. Foodborne botulism is a rare but potentially life-threatening disease and almost exclusively involves home-made or artisan products and thus, outbreaks are limited to individual or few cases. As a consequence, international outbreaks are the absolute exception and this is the first one within the European Union. Additional cases were likely prevented by a broad product recall, underscoring the importance of timely public health action. Challenges and difficulties on the diagnostic and epidemiological level encountered in the outbreak are highlighted.

Is the BNT162b2 COVID-19 vaccine effective in elderly populations? Results from population data from Bavaria, Germany.

BACKGROUND: The efficacy of the BioNTech-Pfizer BNT162b2 vaccination in the elderly (≥80 years) could not be fully assessed in the BioNTech-Pfizer trial due to low numbers in this age group. We aimed to evaluate the effectiveness of the BioNTech-Pfizer (BNT162b2) vaccine to prevent SARS-CoV-2 infection and severe outcomes in octo- and novo-generians in a German state setting. METHODS AND FINDINGS: A prospective observational study of 708,187 persons aged ≥80 years living in Bavaria, Germany, was conducted between Jan 9 to Apr 11, 2021. We assessed the vaccine effectiveness (VE) for two doses of the BNT162b2 vaccine with respect to SARS-CoV-2 infection and related hospitalisations and mortality. Additionally, differences in VE by age groups ≥80 to ≤89 years and ≥90 years were studied. Analyses were adjusted by sex. By the end of follow-up, 63.8% of the Bavarian population ≥80 years had received one dose, and 52.7% two doses, of the BNT162b2 vaccine. Two doses of the BNT162b2 vaccine lowered the proportion of SARS-CoV-2 infections and related outcomes, resulting in VE estimates of 68.3% (95% confidence interval (CI) 65.5%, 70.9%) for infection, 73.2% (95% CI 65.3%, 79.3%) for hospitalisation, and 85.1% (95% CI 80.0%, 89.0%) for mortality. Sex differences in the risk of COVID-19 outcomes observed among unvaccinated persons disappeared after two BNT162b2 vaccine doses. Overall, the BNT162b2 vaccine was equally effective in octo- and novo-genarians. CONCLUSIONS: Two doses of BioNTech-Pfizer's BNT162b2 vaccine is highly effective against COVID-19 outcomes in elderly persons.

Detection and viral RNA shedding of SARS-CoV-2 in respiratory specimens relative to symptom onset among COVID-19 patients in Bavaria, Germany.

We assessed severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) diagnostic sensitivity and cycle threshold (Ct) values relative to symptom onset in symptomatic coronavirus disease-2019 (COVID-19) patients from Bavaria, Germany, of whom a subset was repeatedly tested. Locally weighted scatterplot smoothing method was used to assess the relationship between symptom onset and Ct-values. Kaplan-Meier plots were used to visualise the empirical probability of detecting viral ribonucleic acid (RNA) over time and estimate the time until clearance of viral RNA among the repeatedly tested patients. Among 721 reported COVID-19 cases, the viral RNA was detected in specimens taken between three days before and up to 48 days after symptom onset. The mean Ct-value was 28.6 (95% confidence interval (CI) 28.2-29.0) with the lowest mean Ct-value (26.2) observed two days after symptom onset. Up to 7 days after symptom onset, the diagnostic sensitivity of the RT-PCR among repeatedly sampled patients (n = 208) remained above 90% and decreased to 50% at day 12 (95% CI 10.5-21.5). Our data provide valuable estimates to optimise the timing of sampling of individuals for SARS-CoV-2 detection. A considerable proportion of specimens sampled before symptom onset had Ct-values comparable with Ct-values after symptom onset, suggesting the probability of presymptomatic transmission.

Virological COVID-19 surveillance in Bavaria, Germany suggests no SARS-CoV-2 spread prior to the first German case in January 2020.

The Bavarian Influenza Sentinel (BIS) monitors the annual influenza season by combining virological and epidemiological data. The 2019/2020 influenza season overlapped with the beginning COVID-19 pandemic thus allowing to investigate whether there was an unnoticed spread of SARS-CoV-2 among outpatients with acute respiratory infections in the community prior to the first COVID-19 cluster in Bavaria. Therefore, we retrospectively analysed oropharyngeal swabs obtained in BIS between calendar week (CW) 39 in 2019 and CW 14 in 2020 for the presence of SARS-CoV-2 RNA by RT-PCR. 610 of all 1376 BIS swabs-contained sufficient material to test for SARS-CoV-2, among them 260 oropharyngeal swabs which were collected prior to the first notified German COVID-19 case in CW 04/2020. In none of these swabs SARS-CoV-2 RNA was detected suggesting no SARS-CoV-2 spread prior to late January 2020 in Bavaria.

Nowcasting the COVID-19 pandemic in Bavaria.

To assess the current dynamics of an epidemic, it is central to collect information on the daily number of newly diseased cases. This is especially important in real-time surveillance, where the aim is to gain situational awareness, for example, if cases are currently increasing or decreasing. Reporting delays between disease onset and case reporting hamper our ability to understand the dynamics of an epidemic close to now when looking at the number of daily reported cases only. Nowcasting can be used to adjust daily case counts for occurred-but-not-yet-reported events. Here, we present a novel application of nowcasting to data on the current COVID-19 pandemic in Bavaria. It is based on a hierarchical Bayesian model that considers changes in the reporting delay distribution over time and associated with the weekday of reporting. Furthermore, we present a way to estimate the effective time-varying case reproduction number Re(t) based on predictions of the nowcast. The approaches are based on previously published work, that we considerably extended and adapted to the current task of nowcasting COVID-19 cases. We provide methodological details of the developed approach, illustrate results based on data of the current pandemic, and evaluate the model based on synthetic and retrospective data on COVID-19 in Bavaria. Results of our nowcasting are reported to the Bavarian health authority and published on a webpage on a daily basis (https://corona.stat.uni-muenchen.de/). Code and synthetic data for the analysis are available from https://github.com/FelixGuenther/nc_covid19_bavaria and can be used for adaption of our approach to different data.

Dynamics of Borrelia burgdorferi-Specific Antibodies: Seroconversion and Seroreversion between Two Population-Based, Cross-Sectional Surveys among Adults in Germany.

Lyme borreliosis (LB) caused by Borrelia burgdorferi spp. is the most common human tick-borne disease in Europe. Although seroprevalence studies are conducted in several countries, rates of seroconversion and seroreversion are lacking, and they are essential to determine the risk of infection. Seropositivity was determined using a two-step approach-first, a serological screening assay, and in the event of a positive or equivocal result, a confirmatory immunoblot assay. Seroconversion and seroreversion rates were assessed from blood samples taken from participants included in two nation-wide population-based surveys. Moreover, the impact of antigen reactivity on seroreversion rates was assessed. The seroprevalence of antibodies reacting against B. burgdorferi spp. in the German population was 8.5% (95% CI 7.5-9.6) in 1997-99 and 9.3% (95% CI 8.3-10.4) in 2008-2011. Seroprevalence increased with age, up to 20% among 70-79 year-olds. The age-standardized seroprevalence remained the same. The yearly seroconversion rate was 0.45% (95% CI: 0.37-0.54), and the yearly seroreversion rate was 1.47% (95% CI: 1.24-2.17). Lower levels of antibodies were associated with seroreversion. Participants with a strong response against antigen p83 had the lowest odds on seroreversion. Given the yearly seroreversion rate of 1.47% and a seroprevalence up to 20% in the oldest age groups, at least 20% of the German population becomes infected with B. burgdorferi in their lifetime. The slight increase in seroprevalence between the two serosurveys was caused by an aging population.

Investigation of a COVID-19 outbreak in Germany resulting from a single travel-associated primary case: a case series.

BACKGROUND: In December, 2019, the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, causing COVID-19, a respiratory disease presenting with fever, cough, and often pneumonia. WHO has set the strategic objective to interrupt spread of SARS-CoV-2 worldwide. An outbreak in Bavaria, Germany, starting at the end of January, 2020, provided the opportunity to study transmission events, incubation period, and secondary attack rates. METHODS: A case was defined as a person with SARS-CoV-2 infection confirmed by RT-PCR. Case interviews were done to describe timing of onset and nature of symptoms and to identify and classify contacts as high risk (had cumulative face-to-face contact with a confirmed case for ≥15 min, direct contact with secretions or body fluids of a patient with confirmed COVID-19, or, in the case of health-care workers, had worked within 2 m of a patient with confirmed COVID-19 without personal protective equipment) or low risk (all other contacts). High-risk contacts were ordered to stay at home in quarantine for 14 days and were actively followed up and monitored for symptoms, and low-risk contacts were tested upon self-reporting of symptoms. We defined fever and cough as specific symptoms, and defined a prodromal phase as the presence of non-specific symptoms for at least 1 day before the onset of specific symptoms. Whole genome sequencing was used to confirm epidemiological links and clarify transmission events where contact histories were ambiguous; integration with epidemiological data enabled precise reconstruction of exposure events and incubation periods. Secondary attack rates were calculated as the number of cases divided by the number of contacts, using Fisher's exact test for the 95% CIs. FINDINGS: Patient 0 was a Chinese resident who visited Germany for professional reasons. 16 subsequent cases, often with mild and non-specific symptoms, emerged in four transmission generations. Signature mutations in the viral genome occurred upon foundation of generation 2, as well as in one case pertaining to generation 4. The median incubation period was 4·0 days (IQR 2·3-4·3) and the median serial interval was 4·0 days (3·0-5·0). Transmission events were likely to have occurred presymptomatically for one case (possibly five more), at the day of symptom onset for four cases (possibly five more), and the remainder after the day of symptom onset or unknown. One or two cases resulted from contact with a case during the prodromal phase. Secondary attack rates were 75·0% (95% CI 19·0-99·0; three of four people) among members of a household cluster in common isolation, 10·0% (1·2-32·0; two of 20) among household contacts only together until isolation of the patient, and 5·1% (2·6-8·9; 11 of 217) among non-household, high-risk contacts. INTERPRETATION: Although patients in our study presented with predominately mild, non-specific symptoms, infectiousness before or on the day of symptom onset was substantial. Additionally, the incubation period was often very short and false-negative tests occurred. These results suggest that although the outbreak was controlled, successful long-term and global containment of COVID-19 could be difficult to achieve. FUNDING: All authors are employed and all expenses covered by governmental, federal state, or other publicly funded institutions.

Two measles clusters in connection with short inner-European air travels indicating impediments to effective measles control: A cluster analysis.

Importation and transmission of measles via air travel is a public health concern to countries, which are close to or have achieved elimination, i.e., to the majority of countries in Europe. In 2018, two measles cases occurred in Berlin residents, who flew within Europe while being infectious. In addition to contact tracing through passenger manifests, we contacted national authorities in flight destination countries or embarking countries and inquired about epidemiologically linked measles cases to the two Berlin index cases. We identified eight epidemiologically linked cases (six males, median age: 32 years) from three countries associated with three air-travels. Consequently measles was imported to Germany (Bavaria), Denmark and possibly Sweden. Our investigations revealed impediments to an effective public health response indicating the need to revisit current guidelines and methods to better control transmission of measles related to air travel.