The Berlin-Brandenburg Air Study-A Methodological Study Paper of a Natural Experiment Investigating Health Effects Related to Changes in Airport-Related Exposures.

Objectives: This paper presents the study design of the Berlin-Brandenburg Air study (BEAR-study). We measure air quality in Berlin and Brandenburg before and after the relocation of aircraft (AC) traffic from Tegel (TXL) airport to the new Berlin-Brandenburg airport (BER) and investigate the association of AC-related ultrafine particles (UFP) with health outcomes in schoolchildren. Methods: The BEAR-study is a natural experiment examining schoolchildren attending schools near TXL and BER airports, and in control areas (CA) away from both airports and associated air corridors. Each child undergoes repeated school-based health-examinations. Total particle number concentration (PNC) and meteorological parameters are continuously monitored. Submicrometer particle number size distribution, equivalent black carbon, and gas-phase pollutants are collected from long-term air quality monitoring stations. Daily source-specific UFP concentrations are modeled. We will analyze short-term effects of UFP on respiratory, cardiovascular, and neurocognitive outcomes, as well as medium and long-term effects on lung growth and cognitive development. Results: We examined 1,070 children (as of 30 November 2022) from 16 schools in Berlin and Brandenburg. Conclusion: The BEAR study increases the understanding of how AC-related UFP affect children's health.

Human papillomavirus prevalence and vaccine effectiveness in young women in Germany, 2017/2018: results from a nationwide study.

Background: Infections with human papillomaviruses (HPV) are sexually transmitted and can cause cancer. In Germany, vaccination against HPV is recommended for girls and boys aged 9-17 years. We aimed to investigate HPV DNA prevalence, genotype distribution and vaccine effectiveness (VE) in women aged 20-25 years 10 years after the introduction of HPV vaccination in Germany (2018-2019), and compared these data to an equally designed study from 2010-2012. Methods: Seventy six geographical clusters were randomly selected, followed by random selection of 61 women aged 20-25 years per cluster. Participants performed cervicovaginal self-sampling and answered questions on demographics, sexual behaviour and HPV vaccination. Samples were tested for 18 high risk and nine low risk HPV genotypes. We performed chi-square tests, Fisher's exact test, unpaired Student's t-test and proportion t-test, and calculated crude and adjusted prevalence ratios (PR) and 95% CIs. Results: Of 7,858 contacted women a total of 1,226 agreed to participate. Of these, 94 women were positive for HPV types 16 and/or 18. HPV16 prevalence was 7.0% (95% CI 5.6-8.6) and HPV18 prevalence was 0.8% (95% CI 0.4-1.5). HPV6 and HPV11 were rare with only five (0.4%; 0.1-0.9) and one (0%; 95% CI 0.0-0.5) positive tests. Seven hundred fifty-seven women (62%) had received at least one HPV vaccine dose and 348 (28%) were vaccinated as currently recommended. Confounder-adjusted VE was 46.4% (95% CI 4.2-70.1) against HPV16/18 infection and 49.1% (95% CI 8.2-71.8) against infection with at least one HPV genotype covered by the quadrivalent HPV vaccine. Compared with the 2010-2012 study results, HPV16/18 prevalence dropped from 22.5% (95% CI 19.0-26.3) to 10.3% (95% CI 7.5-13.9; p < 0.0001) in unvaccinated participants. Conclusion: Vaccine-covered HPV genotypes were rare among 20-25 years old women in Germany and decreased compared to the time point shortly after the start of the HPV vaccination program. HPV prevalence of almost all vaccine-covered genotypes was strongly reduced in vaccinated participants. A decrease of HPV16 and HPV18 was even observed in unvaccinated participants, compared to 2010-2012 data, suggesting indirect protection of unvaccinated women. Low VE against HPV16/18 and HPV6/11/16/18 in our study might be attributable to study design in combination with the endpoint selection of (mainly transient) HPV DNA positivity.

Appropriate antibiotic use and antimicrobial resistance: knowledge, attitudes and behaviour of medical students and their needs and preferences for learning.

BACKGROUND: The impact of an appropriate use of antibiotics on the prevention of antimicrobial resistance (AMR) has been demonstrated. Surveys have shown, however, that medical students do not feel sufficiently trained to use antibiotics wisely. The aims of our study were (1) to describe what medical students currently know about appropriate antibiotic use, and (2) to identify students' learning preferences as a basis for developing student-centred teaching modules to convey the basics of AMR prevention. METHODS: We performed an online survey at Charité Universitätsmedizin Berlin and the Julius-Maximilians-University Würzburg on the knowledge, attitudes, and behaviour (KAB) of medical students concerning AMR, antibiotic treatment options, and their perceptions of AMR topics addressed in the medical curriculum. Participants were able to fill out an online questionnaire between December 2019 and February 2020. In addition, we conducted focus group discussions with lecturers and medical students in winter 2019/2020 to identify AMR-related learning needs and preferences. Data were analysed descriptively. RESULTS: Overall, 356 students (response rate 5.1%) participated in the KAB survey. Of these, 192 (54%) strongly agreed that the topic of AMR is relevant to students' clinical practice and 48% (171/355) stated that their future antibiotic prescription behaviour will have an influence on AMR development in their region. Participating students seemed to be interested in the topic of AMR and antibiotic therapy. But even of them, only 46% answered the question about the length of antibiotic use for community-acquired pneumonia correctly and 57% the question about the appropriate use of antibiotics in Staphylococcus aureus infections. Focus group discussions with students (n = 7) and lecturers (n = 9) identified a lack of competence in the responsible use of antibiotics and the prevention of AMR. Respondents stated that the teaching formats and AMR-related content should emphasize clinical applications, interaction with peers/clinicians, and repeated formative feedback from instructors. CONCLUSIONS: Our results show that even medical students who were interested in the AMR problem were not able to use antibiotics appropriately due to gaps in knowledge and a lack of clinical skills. Based on the insights gained in the learning preferences of students and their content priorities, improved student-centred teaching materials should be developed.

Screening for Methicillin-Resistant Staphylococcus aureus.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has become less common in Germany in recent years. In this paper, we report data from the MRSA module of the Hospital Infection Surveillance System (Krankenhaus-Infektionen- Surveillance-System, KISS) for the years 2006-2021. We also describe the association of MRSA rates with the frequency of patient screening for MRSA and discuss the findings. METHODS: Participation in the MRSA KISS module is voluntary. Once a year, the participating hospitals submit structural data, information on cases in which MRSA was detected (both colonizations and infections; both detected on admission and nosocomially acquired), and the number of nasal swabs taken for the detection of MRSA to the German National Reference Center for the Surveillance of Nosocomial Infections. Statistical analyses were performed with R software. RESULTS: The number of hospitals participating in the MRSA module rose from 110 in 2006 to 525 in 2021. From 2006 onward, the overall MRSA prevalence in German hospitals increased, reaching a maximum of 1.04 cases per 100 patients in 2012. The prevalence on admission fell by 44% from 0.96 in 2016 to 0.54 in 2021. The incidence density of nosocomial MRSA fell by an average of 12% per year, from 0.27 per 1000 patient-days in 2006 to 0.06 in 2021, while MRSA screening frequency increased sevenfold by 2021. The nosocomial incidence density was stable, independently of the screening frequency. CONCLUSION: MRSA rates in German hospitals fell markedly from 2006 to 2021, reflecting a general trend. The incidence density was no higher in hospitals with a low or moderate screening frequency than in those with a high one. Thus, a targeted, riskadapted MRSA screening strategy on hospital admission can be recommended.

Impact of public health interventions to curb SARS-CoV-2 spread assessed by an evidence-educated Delphi panel and tailored SEIR model.

Aim: To use a Delphi-panel-based assessment of the effectiveness of different non-pharmaceutical interventions (NPI) in order to retrospectively approximate and to prospectively predict the SARS-CoV-2 pandemic progression via a SEIR model (susceptible, exposed, infectious, removed). Methods: We applied an evidence-educated Delphi-panel approach to elicit the impact of NPIs on the SARS-CoV-2 transmission rate R0 in Germany. Effectiveness was defined as the product of efficacy and compliance. A discrete, deterministic SEIR model with time step of 1 day, a latency period of 1.8 days, duration of infectiousness of 5 days, and a share of the total population of 15% assumed to be protected by immunity was developed in order to estimate the impact of selected NPI measures on the course of the pandemic. The model was populated with the Delphi-panel results and varied in sensitivity analyses. Results: Efficacy and compliance estimates for the three most effective NPIs were as follows: test and isolate 49% (efficacy)/78% (compliance), keeping distance 42%/74%, personal protection masks (cloth masks or other face masks) 33%/79%. Applying all NPI effectiveness estimates to the SEIR model resulted in a valid replication of reported occurrence of the German SARS-CoV-2 pandemic. A combination of four NPIs at consented compliance rates might curb the CoViD-19 pandemic. Conclusion: Employing an evidence-educated Delphi-panel approach can support SARS-CoV-2 modelling. Future curbing scenarios require a combination of NPIs. A Delphi-panel-based NPI assessment and modelling might support public health policy decision making by informing sequence and number of needed public health measures. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-021-01566-2.

Expert recommendations for prevention and management of Candida auris transmission.

Candida auris was first described as a yeast pathogen in 2009. Since then, the species has emerged worldwide. In contrast to most other Candida spp., C. auris frequently exhibits multi-drug resistance and is readily transmitted in hospital settings. While most detections so far are from colonised patients, C. auris does cause superficial and life-threatening invasive infections. During management of the first documented C. auris transmission in a German hospital, experts from the National Reference Centers for Invasive Fungal Infections (NRZMyk) and the National Reference Center for Surveillance of Nosocomial Infections screened available literature and integrated available knowledge on infection prevention and C. auris epidemiology and biology to enable optimal containment. Relevant recommendations developed during this process are summarised in this guidance document, intended to assist in management of C. auris transmission and potential outbreak situations. Rapid and effective measures to contain C. auris spread require a multi-disciplinary approach that includes clinical specialists of the affected unit, nursing staff, hospital hygiene, diagnostic microbiology, cleaning staff, hospital management and experts in diagnostic mycology / fungal infections. Action should be initiated in a step-wise process and relevant interventions differ between management of singular C. auris colonised / infected patients and detection of potential C. auris transmission or nosocomial outbreaks.

Successful control of Candida auris transmission in a German COVID-19 intensive care unit.

BACKGROUND: Candida auris a frequently multidrug-resistant yeast species that poses a global health threat due to its high potential for hospital outbreaks. While C. auris has become endemic in parts of Asia and Africa, transmissions have so far rarely been reported in Western Europe except for Great Britain and Spain. We describe the first documented patient-to-patient transmission of C. auris in Germany in a COVID-19 intensive care unit (ICU) and infection control measures implemented to prevent further spread of the pathogen. METHODS: Identification of C. auris was performed by MALDI-TOF and confirmed by internal transcribed spacer (ITS) sequencing. Antifungal susceptibility testing was carried out. We conducted repeated cross-sectional examinations for the presence of C. auris in the patients of the affected ICU and investigated possible routes of transmission. RESULTS: The index patient had been transferred to Germany from a hospital in Northern Africa and was found to be colonised with C. auris. The contact patient developed C. auris sepsis. Infection prevention and control (IPC) measures included strict isolation of the two C. auris patients and regular screening of non-affected patients. No further case occurred during the subsequent weeks. Reusable blades used in video laryngoscope-guided intubation were considered as the most likely vehicle of transmission. CONCLUSIONS: In view of its high risk of transmission, vigilance regarding C. auris colonisation in patients referred from endemic countries is crucial. Strict and immediate IPC measures may have the potential to prevent C. auris outbreaks.

Seroprevalence of mucosal and cutaneous human papillomavirus (HPV) types among children and adolescents in the general population in Germany.

BACKGROUND: In Germany, HPV vaccination of adolescent girls was introduced in 2007. Nationally representative data on the distribution of vaccine-relevant HPV types in the pre-vaccination era are, however, only available for the adult population. To obtain data in children and adolescents, we assessed the prevalence and determinants of serological response to 16 different HPV types in a representative sample of 12,257 boys and girls aged 1-17 years living in Germany in 2003-2005. METHODS: Serum samples were tested for antibodies to nine mucosal and seven cutaneous HPV types. The samples had been collected during the nationally representative German Health Interview and Examination Survey for Children and Adolescents in 2003-2006. We calculated age- and gender-specific HPV seroprevalence. We used multivariable regression models to identify associations between demographic and behavioral characteristics and HPV seropositivity. RESULTS: We found low but non-zero seroprevalence for the majority of tested HPV types among children and adolescents in Germany. The overall seroprevalence of HPV-16 was 2.6%, with slightly higher values in adolescents. Seroprevalence of all mucosal types but HPV-6 ranged from 0.6% for HPV-33, to 6.4% for HPV-31 and did not differ by gender. We found high overall seroprevalence for HPV-6 with 24.8%. Cutaneous HPV type seroprevalence ranged from 4.0% for HPV-38 to 31.7% for HPV-1. In the majority of cutaneous types, seroprevalence did not differ between boys and girls, but increased sharply with age, (e.g., HPV-1 from 1.5% in 1-3-years-old to 45.1% in 10-11-years-old). Associations between behavioral factors and type-specific HPV prevalence were determined to be heterogeneous. CONCLUSIONS: We report the first nationally representative data of naturally acquired HPV antibody reactivity in the pre-HPV-vaccination era among children and adolescents living in Germany. These data can be used as baseline estimates for evaluating the impact of the current HPV vaccination strategy targeting 9-14-years-old boys and girls.

Risk factors for nosocomial SARS-CoV-2 infections in patients: results from a retrospective matched case-control study in a tertiary care university center.

BACKGROUND: Factors contributing to the spread of SARS-CoV-2 outside the acute care hospital setting have been described in detail. However, data concerning risk factors for nosocomial SARS-CoV-2 infections in hospitalized patients remain scarce. To close this research gap and inform targeted measures for the prevention of nosocomial SARS-CoV-2 infections, we analyzed nosocomial SARS-CoV-2 cases in our hospital during a defined time period. METHODS: Data on nosocomial SARS-CoV-2 infections in hospitalized patients that occurred between May 2020 and January 2021 at Charité university hospital in Berlin, Germany, were retrospectively gathered. A SARS-CoV-2 infection was considered nosocomial if the patient was admitted with a negative SARS-CoV-2 reverse transcription polymerase chain reaction test and subsequently tested positive on day five or later. As the incubation period of SARS-CoV-2 can be longer than five days, we defined a subgroup of "definite" nosocomial SARS-CoV-2 cases, with a negative test on admission and a positive test after day 10, for which we conducted a matched case-control study with a one to one ratio of cases and controls. We employed a multivariable logistic regression model to identify factors significantly increasing the likelihood of nosocomial SARS-CoV-2 infections. RESULTS: A total of 170 patients with a nosocomial SARS-CoV-2 infection were identified. The majority of nosocomial SARS-CoV-2 patients (n = 157, 92%) had been treated at wards that reported an outbreak of nosocomial SARS-CoV-2 cases during their stay or up to 14 days later. For 76 patients with definite nosocomial SARS-CoV-2 infections, controls for the case-control study were matched. For this subgroup, the multivariable logistic regression analysis revealed documented contact to SARS-CoV-2 cases (odds ratio: 23.4 (95% confidence interval: 4.6-117.7)) and presence at a ward that experienced a SARS-CoV-2 outbreak (odds ratio: 15.9 (95% confidence interval: 2.5-100.8)) to be the principal risk factors for nosocomial SARS-CoV-2 infection. CONCLUSIONS: With known contact to SARS-CoV-2 cases and outbreak association revealed as the primary risk factors, our findings confirm known causes of SARS-CoV-2 infections and demonstrate that these also apply to the acute care hospital setting. This underscores the importance of rapidly identifying exposed patients and taking adequate preventive measures.

Prevalence and risk factors of colonisation with vancomycin-resistant Enterococci faecium upon admission to Germany's largest university hospital.

Background: Hospital-acquired infections due to vancomycin-resistant enterococci (VRE) are emerging globally. The aims of our study were to estimate VRE colonisation prevalence in patients upon admission, to determine possible risk factors for VR E. faecium acquisition that already exist in the outpatient setting, and to monitor whether VRE-colonised patients developed a VRE infection during their current hospital stay. Methods: In 2014 and 2015, patients admitted to non-intensive care units were screened for rectal VRE carriage. The study patients filled out a questionnaire on potential risk factors. Analyses were restricted to VR E. faecium carriage. All patients with VRE colonisation were retrospectively monitored for infections with VRE during their current hospital stay. Results: In 4,013 enrolled patients, the VRE colonisation prevalence upon admission was 1.2% (n=48), and colonisation prevalence was 1.1% (n=45) for VR E. faecium. Only one VRE-colonised patient developed an infection with the detection of a VRE, among others. Colonisation with VR E. faecium was associated with current antibiotic use. Risk factors of VR E. faecium colonisation upon admission were increasing age, previous colonisation or infection with multidrug resistant organisms, sampling year 2015, and, within the previous six months, antibiotic exposure, a stay at a rehabilitation center, and a hospital stay. Conclusions: We observed that antibiotic treatment which occurred prior admission influenced VR E. faecium prevalence upon admission. Thus, wise antibiotic use in outpatient settings plays a major role in the prevention of VR E. faecium acquisition.

Prevalence of third-generation cephalosporin-resistant Enterobacterales colonization on hospital admission and ESBL genotype-specific risk factors: a cross-sectional study in six German university hospitals.

OBJECTIVES: To assess the admission prevalence of third-generation cephalosporin-resistant Enterobacterales (3GCREB) and to assess whether risk factors vary by ß-lactamase genotype. METHODS: Adult patients were recruited within 72 h of admission to general wards of six university hospitals in 2014 and 2015. Rectal swabs were screened for 3GCREB and isolates were analysed phenotypically and genotypically. Patients were questioned on potential risk factors. Multivariable analyses were performed to identify risk factors for 3GCREB colonization and for specific ß-lactamases. RESULTS: Of 8753 patients screened, 828 were 3GCREB positive (9.5%). Eight hundred and thirteen isolates were available for genotyping. CTX-M-15 was the most common ESBL (38.0%), followed by CTX-M-1 (22.5%), CTX-M-14 (8.7%), CTX-M-27 (7.5%) and SHV-ESBL (4.4%). AmpC was found in 11.9%. Interestingly, 18 Escherichia coli isolates were AmpC positive, 12 of which (67%) contained AmpC on a gene of plasmid origin [CMY (n = 10), DHA (n = 2)]. Risk factors for 3GCREB colonization varied by genotype. Recent antibiotic exposure and prior colonization by antibiotic-resistant bacteria were risk factors for all ß-lactamases except CTX-M-14 and CTX-M-27. Travel outside Europe was a risk factor for CTX-M-15 and CTX-M-27 [adjusted OR (aOR) 3.49, 95% CI 2.88-4.24 and aOR 2.73, 95% CI 1.68-4.43]. A previous stay in a long-term care facility was associated with CTX-M-14 (aOR 3.01, 95% CI 1.98-4.59). A preceding hospital stay in Germany increased the risk of CTX-M-15 (aOR 1.27, 95% CI 1.14-1.41), while a prior hospital stay in other European countries increased the risk of SHV-ESBL colonization (aOR 3.85, 95% CI 1.67-8.92). CONCLUSIONS: The detection of different ESBL types is associated with specific risk factor sets that might represent distinct sources of colonization and ESBL-specific dissemination routes.

Incidence of healthcare-associated Clostridioides difficile infections and association with ward-level antibiotic consumption in a German university hospital: an ecological study.

OBJECTIVES: Clostridioides difficile infection (CDI) is one of the most important healthcare-associated infections. We aimed to describe the incidence density of healthcare-associated CDI (HA-CDI) in Germany's largest hospital and to identify associations with ward-level antimicrobial consumption. METHODS: We used surveillance data on CDI and antimicrobial consumption from 2014 to 2017 and analysed a potential association by means of multivariable regression analysis. RESULTS: We included 77 wards with 404998 admitted patients and 1850862 patient-days. Six hundred and seventy-one HA-CDI cases were identified, resulting in a pooled mean incidence density of 0.36/1000 patient-days (IQR = 0.34-0.39). HA-CDI incidence density on ICU and haematological-oncological wards was about three times higher than on surgical wards [incidence rate ratio (IRR) = 3.00 (95% CI = 1.96-4.60) and IRR = 2.78 (95% CI = 1.88-4.11), respectively]. Ward-level consumption of third-generation cephalosporins was the sole antimicrobial risk factor for HA-CDI. With each DDD/100 patient-days administered, a ward's HA-CDI incidence density increased by 2% [IRR = 1.02 (95% CI = 1.01-1.04)]. Other risk factors were contemporaneous community-associated CDI cases [IRR = 1.32 (95% CI = 1.07-1.63)] and CDI cases in the previous month [IRR = 1.27 (95% CI = 1.07-1.51)]. Furthermore, we found a significant decrease in HA-CDI in 2017 compared with 2014 [IRR = 0.68 (95% CI = 0.54-0.86)]. CONCLUSIONS: We confirmed that ward-level antimicrobial use influences HA-CDI and specifically identified third-generation cephalosporin consumption as a risk factor.

Mucosal and cutaneous Human Papillomavirus seroprevalence among adults in the prevaccine era in Germany - Results from a nationwide population-based survey.

BACKGROUND: Human Papillomavirus (HPV) vaccination of girls was introduced in Germany in 2007. However, data on the distribution of vaccine-relevant HPV types in the general population in Germany in the prevaccine era are limited. METHODS: Serum samples collected during the German National Health Interview and Examination Survey 1998 (GNHIES98), a nationally representative study including men and women aged 18-79 years, were tested for antibodies to 19 mucosal and cutaneous HPV types. Multivariable regression models were developed to identify associations between demographic and behavioral characteristics and HPV seropositivity. RESULTS: Of the 6517 serum samples tested, almost a quarter was seropositive for at least one of the nine HPV vaccine types with no clear age-pattern. HPV-6 and HPV-59 were the most common mucosal types, while HPV-1 and HPV-4 were the most common cutaneous HPV types. Factors independently associated with HPV-16 seroprevalence were seropositive to other sexually transmitted infections and lifetime number of sex partners, as well as urbanity (only among females). CONCLUSIONS: Prevalence of naturally acquired antibodies to HPV types which can be prevented by vaccination is high in both sexes and all age groups. These data can serve as baseline estimates to evaluate the population-level impact of the current vaccination strategy.

Admission prevalence of colonization with third-generation cephalosporin-resistant Enterobacteriaceae and subsequent infection rates in a German university hospital.

BACKGROUND: Many patients admitted to a hospital are already colonized with multi-drug resistant organisms (MDRO) including third-generation cephalosporin-resistant Enterobacteriaceae (3GCREB). The aim of our study was to determine the prevalence of rectal 3GCREB colonization at admission to a large German university hospital and to estimate infection incidences. In addition, risk factors for 3GCREB colonization were identified. MATERIALS/METHODS: In 2014 and 2015, patients were screened for rectal colonization with 3GCREB and filled out a questionnaire on potential risk factors at admission to a non-intensive care unit (non-ICU). All patients were retrospectively monitored for bacterial infections. Descriptive, univariable and multivariable logistic regression analyses were conducted to identify risk factors for 3GCREB colonization at admission. RESULTS: Of 4,013 patients included, 10.3% (n = 415) were rectally colonized with 3GCREB at admission. Incidence of nosocomial infections was 3.5 (95% CI 2.0-6.1) per 100 patients rectally colonized with 3GCREB compared to 2.3 (95% CI 1.8-3.0, P = 0.213) per 100 3GCREB negative patients. Independent risk factors for 3GCREB colonization were prior colonization / infection with MDRO (OR 2.30, 95% CI 1.59-3.32), prior antimicrobial treatment (OR 1.97, 95% CI 1.59-2.45), male sex (OR 1.38, 95% CI 1.12-1.70), prior travelling outside Europe (OR 2.39, 95% CI 1.77-3.22) and places of residence in the Berlin districts Charlottenburg-Wilmersdorf (OR 1.52, 95% CI 1.06-2.18), Friedrichshain-Kreuzberg (OR 2.32, 95% CI 1.44-3.74) and Mitte (OR 1.73, 95% CI 1.26-2.36). CONCLUSIONS: Admission prevalence of rectal colonization with 3GCREB was high, while infection incidence did not significantly differ between patients rectally colonized or not with 3GCREB at hospital admission. In consequence, hospitals should prioritize improvement of standard precautions including hand hygiene to prevent infections among all patients irrespective of their 3GCREB status at hospital admission.