Estimates of protection levels against SARS-CoV-2 infection and severe COVID-19 in Germany before the 2022/2023 winter season: the IMMUNEBRIDGE project.

PURPOSE: Despite the need to generate valid and reliable estimates of protection levels against SARS-CoV-2 infection and severe course of COVID-19 for the German population in summer 2022, there was a lack of systematically collected population-based data allowing for the assessment of the protection level in real time. METHODS: In the IMMUNEBRIDGE project, we harmonised data and biosamples for nine population-/hospital-based studies (total number of participants n = 33,637) to provide estimates for protection levels against SARS-CoV-2 infection and severe COVID-19 between June and November 2022. Based on evidence synthesis, we formed a combined endpoint of protection levels based on the number of self-reported infections/vaccinations in combination with nucleocapsid/spike antibody responses ("confirmed exposures"). Four confirmed exposures represented the highest protection level, and no exposure represented the lowest. RESULTS: Most participants were seropositive against the spike antigen; 37% of the participants ≥ 79 years had less than four confirmed exposures (highest level of protection) and 5% less than three. In the subgroup of participants with comorbidities, 46-56% had less than four confirmed exposures. We found major heterogeneity across federal states, with 4-28% of participants having less than three confirmed exposures. CONCLUSION: Using serological analyses, literature synthesis and infection dynamics during the survey period, we observed moderate to high levels of protection against severe COVID-19, whereas the protection against SARS-CoV-2 infection was low across all age groups. We found relevant protection gaps in the oldest age group and amongst individuals with comorbidities, indicating a need for additional protective measures in these groups.

[Integrating Public Health Expertise in Research: a Series of Workshops about Vector-Borne and Other Zoonotic Diseases]. / ÖGD-Expertise in die Forschung bringen: eine Workshop-Reihe zu vektorübertragenen und weiteren zoonotischen Erkrankungen.

Research groups must understand the needs and requirements of the public health service to be able to develop tools and strategies for supporting it in risk assessment and risk communication. The zoonotic research consortia RoBoPub, Q-GAPS, TBENAGER and ZooBoCo used the format of workshops to include the expertise of the public health service system in their work. We present the results of three workshops that were held with representatives of the German public health service as part of the annual congress of the Federal Association of Physicians of German Public Health Departments in 2018, 2019 and 2022. Each workshop, held in a world-café format, lasted 90 minutes and had its own thematic focus. In the first workshop, information on the goals, problems, solutions and expectations of the public health service from the research consortia concerning exposure to rodent-borne infections during their occupational and leisure-time activities as well as the use of risk maps was collected. In the second and third workshops, participants developed risk communication strategies based on scenarios of outbreaks and identifications of new risk areas. Each workshop had more than 20 participants, of which at least half worked for local public health authorities. Foremost, participants expected practical, target group-specific material for risk communication from the research groups. According to the experience of most participants, direct contact with the affected groups was essential for risk communication. To raise awareness of the situation and establish contact with the relevant target groups, social media can complement traditional media, especially for hard-to-reach groups. However, their use should be considered and planned carefully. The workshop format was appropriate for integrating the public health expertise in the research activities. The expectations of the public health service on material for risk communication could be translated into a guideline, a risk management plan and pathogen descriptions by the research groups. When integrating the expertise of the public health authorities in their work, research groups should consider how to reach a suitable panel of representatives and how to keep the workload for those at an acceptably low level.

Dried blood spot eluates are suitable for testing of SARS-CoV-2 IgG antibodies targeting Spike protein 1 and Nucleocapsid protein.

Dried blood spots (DBS) provide easy handling and are thus a beneficial tool for data collection, e.g. for epidemiological studies. The suitability of DBS for the assessment of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was analyzed with regards to the use in future studies addressing seroprevalence in the population. 121 volunteers gave a venous blood sample and capillary blood samples on two DBS cards (PerkinElmer and Ahlstrom-Munksjö) via self-sampling under supervision. All samples were analyzed using the Anti-SARS-CoV-2 ELISA (IgG) and the Anti-SARS-CoV-2 NCP ELISA (IgG) from EUROIMMUN performed on the EUROIMMUN EUROLabWorkstation ELISA. Correlation coefficients between ELISA results based on the different sampling methods were calculated. Results of DBS analysis for SARS-CoV-2 IgG S1 and NCP highly correlated with the serum values (r = 0.96). In addition, the calculation of the phi coefficient showed no significant difference between the qualitative results of both sampling methods (rφ = 0.98-1.0). Further analysis of DBS eluates after prolonged storage of 6-8 h also showed a high correlation with serum results (r = 0.97 and r = 0.93, respectively). The study results indicate suitability of DBS for the analysis of antibodies against SARS-CoV-2 S1 and NCP. For DBS eluate, a stability of 6-8 h for measurement of SARS-CoV-2 antibodies can be assumed.

Immunity Against SARS-CoV-2 in the German Population.

BACKGROUND: Early during the SARS-CoV-2 pandemic, national population-based seroprevalence surveys were conducted in some countries; however, this was not done in Germany. In particular, no seroprevalence surveys were planned for the summer of 2022. In the context of the IMMUNEBRIDGE project, the GUIDE study was carried out to estimate seroprevalence on the national and regional levels. METHODS: To obtain an overview of the population-wide immunity against SARS-CoV-2 among adults in Germany that would be as statistically robust as possible, serological tests were carried out using self-sampling dried blood spot cards in conjunction with surveys, one by telephone and one online. Blood samples were analyzed for the presence of antibodies to the S and N antigens of SARS-CoV-2. RESULTS: Among the 15 932 participants, antibodies to the S antigen were detected in 95.7%, and to the N antigen in 44.4%. In the higher-risk age groups of persons aged 65 and above and persons aged 80 and above, anti-S antibodies were found in 97,4% and 98.8%, respectively. Distinct regional differences in the distribution of anti-S and anti-N antibodies emerged. Immunity gaps were found both regionally and in particular subgroups of the population. High anti-N antibody levels were especially common in eastern German states, and high anti-S antibody levels in western German states. CONCLUSION: These findings indicate that a large percentage of the adult German population has formed antibodies against the SARS-CoV-2 virus. This will markedly lower the probability of an overburdening of the health care system by hospitalization and high occupancy of intensive care units due to future SARS-CoV-2 waves, depending on the viral characteristics of then prevailing variants.

Risk factors for Leptospira seropositivity in rural Northern Germany, 2019.

We investigated seroprevalence and factors associated with Leptospira spp. infections in humans in rural Northern Germany. Sera of 450 participants were tested for leptospira-reactive IgG antibodies by two enzyme-linked immunosorbent assays (ELISA). A narrow (specific) and a broad (sensitive) case definition were applied and results compared in the analysis. Personal data were collected via questionnaire and associations with the serostatus were investigated by multivariable logistic regression. The seroprevalence estimates were 1.6% (95%-confidence interval (CI) = 0.63-3.2) under the narrow and 4.2% (95%-CI = 2.6-6.5%) under the broad case definition. Few (14%) participants knew about the pathogen. No seropositive participant recalled a prior leptospirosis diagnosis. Spending more than two hours a week in the forest was significantly associated with anti-leptospira IgG in both models (broad case definition: adjusted odds ratio (aOR) = 2.8, 95%-CI = 1.2-9.1; narrow case definition: aOR = 11.1, 95%-CI = 1.3-97.1). Regular cleaning of storage rooms was negatively associated in the broad (aOR = 0.17, 95%-CI = 0.03-0.98) and touching a dead rodent in the past 10 years in the narrow case definition model (aOR = 0.23, 95%-CI = 0.05-1.04). Our findings support risk factors identified in previous investigations. To counter the low awareness for the pathogen, we recommend that health authorities communicate risks and preventive measures to the public by using target-group specific channels.

Cluster of human Puumala orthohantavirus infections due to indoor exposure?-An interdisciplinary outbreak investigation.

Puumala orthohantavirus (PUUV) is the most important hantavirus species in Europe, causing the majority of human hantavirus disease cases. In central and western Europe, the occurrence of human infections is mainly driven by bank vole population dynamics influenced by beech mast. In Germany, hantavirus epidemic years are observed in 2- to 5-year intervals. Many of the human infections are recorded in summer and early autumn, coinciding with peaks in bank vole populations. Here, we describe a molecular epidemiological investigation in a small company with eight employees of whom five contracted hantavirus infections in late 2017. Standardized interviews with employees were conducted to assess the circumstances under which the disease cluster occurred, how the employees were exposed and which counteractive measures were taken. Initially, two employees were admitted to hospital and serologically diagnosed with hantavirus infection. Subsequently, further investigations were conducted. By means of a self-administered questionnaire, three additional symptomatic cases could be identified. The hospital patients' sera were investigated and revealed in one patient a partial PUUV L segment sequence, which was identical to PUUV sequences from several bank voles collected in close proximity to company buildings. This investigation highlights the importance of a One Health approach that combines efforts from human and veterinary medicine, ecology and public health to reveal the origin of hantavirus disease clusters.

Symptom Burden and Factors Associated with Acute Respiratory Infections in the First Two Years of Life-Results from the LoewenKIDS Cohort.

Acute respiratory infections (ARIs) are the most common childhood illnesses worldwide whereby the reported frequency varies widely, often depending on type of assessment. Symptom diaries are a powerful tool to counteract possible under-reporting, particularly of milder infections, and thus offer the possibility to assess the full burden of ARIs. The following analyses are based on symptom diaries from participants of the German birth cohort study LoewenKIDS. Primary analyses included frequencies of ARIs and specific symptoms. Factors, which might be associated with an increased number of ARIs, were identified using the Poisson regression. A subsample of two hundred eighty-eight participants were included. On average, 13.7 ARIs (SD: 5.2 median: 14.0 IQR: 10-17) were reported in the first two years of life with an average duration of 11 days per episode (SD: 5.8, median: 9.7, IQR: 7-14). The median age for the first ARI episode was 91 days (IQR: 57-128, mean: 107, SD: 84.5). Childcare attendance and having siblings were associated with an increased frequency of ARIs, while exclusive breastfeeding for the first three months was associated with less ARIs, compared to exclusive breastfeeding for a longer period. This study provides detailed insight into the symptom burden of ARIs in German infants.

Analytical performance evaluation of the Elecsys Epstein-Barr virus immunoassay panel.

We evaluated the analytical performance of the Elecsys® Epstein-Barr virus (EBV) immunoassay panel for the in vitro detection of EBV immunoglobulin M (IgM), EBV viral capsid antigen immunoglobulin G (VCA IgG), and EBV nuclear antigen immunoglobulin G (EBNA IgG). Relative sensitivity/specificity were assessed using 1,734 human blood samples (1,068 residual samples from routine EBV testing; 467 presumed acute infection; 199 presumed seronegative) tested with the Elecsys EBV and 2 comparator panels (ARCHITECT EBV; Liaison EBV). EBV infection status was defined by majority approach. The three panels demonstrated comparable relative sensitivities/specificities, ranging between values (%) of 98.3-99.5 / 96.9-97.4 (EBV IgM); 96.3-98.4 / 98.4-98.7 (EBV VCA IgG); and 98.1-99.5 / 99.1-99.5 (EBV EBNA IgG). The Elecsys EBV IgM assay demonstrated superior analytical specificity in samples containing potential interferents. Utilizing the Elecsys EBV panel for the EBNA-first approach showed 97.5% overall agreement versus the majority approach in samples with clear EBV status.

Antibiotic use on paediatric inpatients in a teaching hospital in the Gambia, a retrospective study.

Background: Antibiotics are useful but increasing resistance is a major problem. Our objectives were to assess antibiotic use and microbiology testing in hospitalized children in the Gambia. Methods: We conducted a retrospective analysis of paediatric inpatient data at The Edward Francis Small Teaching Hospital in Banjul, The Gambia. We extracted relevant data from the admission folders of all patients (aged > 28 days to 15 years) admitted in 2015 (January-December), who received at least one antibiotic for 24 h. We also reviewed the microbiology laboratory record book to obtain separate data for the bacterial isolates and resistance test results of all the paediatric inpatients during the study period. Results: Over half of the admitted patients received at least one antibiotic during admission (496/917) with a total consumption of 670.7 Days of Antibiotic Therapy/1000 Patient-Days. The clinical diagnoses included an infectious disease for 398/496, 80.2% of the patients on antibiotics, pneumonia being the most common (184/496, 37.1%). There were 51 clinically relevant bacterial isolates, Klebsiella species being the most common (12/51, 23.5%), mainly from urine (11/12, 91.7%). Antibiotic resistance was mainly to ampicillin (38/51, 74.5%), mainly reported as Coliform species 11/51, 21.6%. Conclusions: More than half of the admitted patients received antibiotics. The reported antibiotic resistance was highest to the most commonly used antibiotics such as ampicillin. Efforts to maximize definitive antibiotic indication such as microbiological testing prior to start of antibiotics should be encouraged where possible for a more rational antibiotic use.

[Competing Validity of Developmental Diagnostic in School Entry Examination: Results of a Census in an Upper Bavarian District]. / Konkurrierende Validität der Entwicklungsdiagnostik zum Zeitpunkt der Schuleingangsuntersuchung ­ Ergebnisse einer Vollerhebung in einem oberbayerischen Landkreis.

AIM OF THE STUDY: Evaluation of the concurrent validity of a modified Bavarian model (BM) compared to the social-paediatric screening of developmental status for school entry (SOPESS) as a reference tool. METHODS: A total of 407 preschoolers to be enrolled for the school year 2015 in an Upper Bavarian District were examined by BM and SOPESS. As a measure of the concurrent validity, the Kappa by Cohen (ĸ) was used. RESULTS: The agreement of both instruments was moderate and was less pronounced for single dimensions than globally. The agreement in the dimensions of "prepositions" vs. "grammatism" (ĸ=0.46) was highest and for the dimensions "numbers and quantities" vs. "calculus" (ĸ=0.05). Stratification by age, gender, nationality and mode of the study programs had no significant influence on the strength of the effects. CONCLUSION: The moderate agreement between the 2 instruments raises the question of the validity of BM used so far in school enrollment examinations.

Knowledge, attitude and practice of Gambian health practitioners towards antibiotic prescribing and microbiological testing: a cross-sectional survey.

Background: Inappropriate antibiotic use is the leading cause of antibiotic resistance worldwide. At the same time, the practice of antibiotic prescribing in Africa is less well documented when compared to developed countries. The objective of the study was to assess the knowledge, attitude, and practice (KAP) of health practitioners towards antibiotic prescribing and microbiological testing in The Gambia. Methods: A KAP survey was conducted in The Gambia from March to May 2016. Self-administered paper-based questionnaires were distributed to health practitioners working in 12 health facilities. Results: Out of 241 questionnaires distributed, 216 (89.6%) were returned. One third of respondents reported making a request for microbiological tests or using results as a guide in less than 25% of patients with possible infectious disease. Thirty-two percent of the participants reported that '25-50%' of antibiotic prescriptions in their departments were inappropriate. Only 16.1% of the participants had some training on antibiotic prescribing in the last 12 months. Respondents agreed with the options 'inadequate supervision' (82.6%) and 'insufficient laboratory support' (82.5%) as the main causes of inappropriate antibiotic use in their settings. Conclusions: There are deficits related to antibiotic prescriptions in The Gambia. Availability and use of microbiological services and training should be emphasized.

Incidence and comparison of retrospective and prospective data on respiratory and gastrointestinal infections in German households.

BACKGROUND: Acute respiratory infections (ARI) and acute gastrointestinal infections (AGI) are the most common childhood infections, and corresponding data can either be collected prospectively or retrospectively. The aim of this study was to estimate the incidence of respiratory and gastrointestinal episodes in German households with children attending day care and to compare results of prospective and retrospective data collection. METHODS: We conducted a 4 months prospective cohort study in the winter period 2014/2015 and recruited parents of children aged 0-6 years in 75 day care centers in Braunschweig, Lower Saxony, Germany. For all household members, we collected information on episodes of ARI and AGI. We applied prospective data collection in one study arm and retrospective data collection with a reporting period of 2 months in the other. Poisson regression was used to model monthly incidence rates for both study arms. RESULTS: In total, 100 households (including 404 persons) participated in the retrospective group and 77 households (282 persons) in the prospective group. Incidence estimates for ARI (retrospective group: 0.52 per person month, prospective group: 0.47) were higher than for AGI (retrospective group: 0.14, prospective group: 0.13). The adjusted incidence estimates were similar in both study arms for ARI (incidence rate ratio for retrospective versus prospective data collection: 1.11 [confidence interval (CI) 95% 0.99; 1.24], p = 0.42) as well as for AGI (1.10 [CI 95% 0.89; 1.37], p = 0.27). CONCLUSION: If there is no need to collect biomaterials or data on severity of the diseases, incidence of infections in the household setting over a short time period (2 months) can be assessed retrospectively.

Sociodemographic determinants of spatial disparities in early childhood caries: An ecological analysis in Braunschweig, Germany.

OBJECTIVES: To identify spatial disparities in dental caries experience (measured by dmft (decayed missing filled teeth) index) of children in the city of Braunschweig and to evaluate whether these disparities can be explained by sociodemographic characteristics. METHODS: We examined the dental health of children aged 3-6 years visiting a daycare centre (DCC) in the metropolitan area of Braunschweig between 2009 and 2014 by combining data on dental health from the annual visits of the local health service with aggregated data on sociodemographic factors for Braunschweig's city districts. We assessed longitudinal patterns of change in average dmft index at district level from 2009 to 2014 using a finite mixture model. We analysed spatial autocorrelation of the district's average dmft indices by Moran's I to identify spatial clusters. With a spatial lag model, we evaluated whether sociodemographic risk factors (data from 2012) were associated with high dmft scores (data from 2014) and whether spatial disparities remained after adjusting for these sociodemographic characteristics. RESULTS: The average dmft index decreased slightly (ß=-0.048; P<.03; CI 95% [-0.079; -0.017]) from 2009 to 2014. The finite mixture model resulted in four different groups of trajectories over time. While three groups showed a decrease in dmft score, one group showed an increase from 2009 to 2014. Moran's I test statistic showed strong evidence for spatial clustering (Moran's I 0.30, P=.002). A cluster of districts with high dmft values was identified in the centre of the city. The spatial lag model showed that both the proportion of unemployed persons (aged 16-65) and the proportion of persons with migration background were associated with the dmft values at district level. After adjusting for these, no further spatial heterogeneity was observed. CONCLUSION: We identified regional clusters for poor dental health in a German city and showed that these clusters can be explained by sociodemographic characteristics. The findings support the need of targeted interventions and prevention measures in regions with less favourable sociodemographic characteristics.