COVID-19 Vaccine Effectiveness and Digital Pandemic Surveillance in Germany (eCOV Study): Web Application-Based Prospective Observational Cohort Study.

BACKGROUND: The COVID-19 pandemic posed significant challenges to global health systems. Efficient public health responses required a rapid and secure collection of health data to improve the understanding of SARS-CoV-2 and examine the vaccine effectiveness (VE) and drug safety of the novel COVID-19 vaccines. OBJECTIVE: This study (COVID-19 study on vaccinated and unvaccinated subjects over 16 years; eCOV study) aims to (1) evaluate the real-world effectiveness of COVID-19 vaccines through a digital participatory surveillance tool and (2) assess the potential of self-reported data for monitoring key parameters of the COVID-19 pandemic in Germany. METHODS: Using a digital study web application, we collected self-reported data between May 1, 2021, and August 1, 2022, to assess VE, test positivity rates, COVID-19 incidence rates, and adverse events after COVID-19 vaccination. Our primary outcome measure was the VE of SARS-CoV-2 vaccines against laboratory-confirmed SARS-CoV-2 infection. The secondary outcome measures included VE against hospitalization and across different SARS-CoV-2 variants, adverse events after vaccination, and symptoms during infection. Logistic regression models adjusted for confounders were used to estimate VE 4 to 48 weeks after the primary vaccination series and after third-dose vaccination. Unvaccinated participants were compared with age- and gender-matched participants who had received 2 doses of BNT162b2 (Pfizer-BioNTech) and those who had received 3 doses of BNT162b2 and were not infected before the last vaccination. To assess the potential of self-reported digital data, the data were compared with official data from public health authorities. RESULTS: We enrolled 10,077 participants (aged ≥16 y) who contributed 44,786 tests and 5530 symptoms. In this young, primarily female, and digital-literate cohort, VE against infections of any severity waned from 91.2% (95% CI 70.4%-97.4%) at week 4 to 37.2% (95% CI 23.5%-48.5%) at week 48 after the second dose of BNT162b2. A third dose of BNT162b2 increased VE to 67.6% (95% CI 50.3%-78.8%) after 4 weeks. The low number of reported hospitalizations limited our ability to calculate VE against hospitalization. Adverse events after vaccination were consistent with previously published research. Seven-day incidences and test positivity rates reflected the course of the pandemic in Germany when compared with official numbers from the national infectious disease surveillance system. CONCLUSIONS: Our data indicate that COVID-19 vaccinations are safe and effective, and third-dose vaccinations partially restore protection against SARS-CoV-2 infection. The study showcased the successful use of a digital study web application for COVID-19 surveillance and continuous monitoring of VE in Germany, highlighting its potential to accelerate public health decision-making. Addressing biases in digital data collection is vital to ensure the accuracy and reliability of digital solutions as public health tools.

Strengthening the role of hospital leadership in infection control (LEAD-IC) - a multimodal educational intervention in German acute care hospitals.

BACKGROUND: The effect of leadership support for adherence to infection control and prevention (IPC) measures has been demonstrated. To expand this support, a target group-specific educational study for chief medical officers (CMO) was implemented and its influence on IPC indicators was investigated. METHODS: A controlled cohort study was conducted between 2018 and 2019. The intervention based on an initial workshop, an e-learning course, and a final meeting. Participants' activities involving IPC management were surveyed. Consumption of alcohol hand rub (AHR) and incidence density of hospital-associated (HA) Clostridioides difficile-associated infections (CDI) were analyzed. RESULTS: Eight percent of 360 CMOs invited participated in the initial workshop; 70% of those participants registered for the online course. Overall, 43% completed the post-intervention questionnaire, in which 85% of respondents reported increased collaboration with relevant stakeholders. The pre-intervention median AHR consumption was higher in the intervention group than in the control group. Both groups showed an increase (38.6 (interquartile range (IQR) 33.6; 45.0) to 41.9 ml/patient day (PD) (IQR 35.0; 56.6) and 33.4 (IQR 28.3; 40.8) to 35.8 ml/ PD (IQR 31.6; 43.2), respectively). Pre-intervention median HA CDI cases were lower in the intervention group than in the control group. Both groups reported a decrease (0.22 (IQR 0.17; 0.33) to 0.19 cases/1000 PD (IQR 0.15; 0.26) and 0.32 (IQR 0.2; 0.48) to 0.22 cases/1000 PD (IQR 0.11; 0.33), respectively). CONCLUSION: Multimodal IPC training of CMOs is worthwhile and can lead to changes in IPC-relevant cooperation in hospitals. IPC training of hospital management should be further intensified.

Participatory disease surveillance for a mass gathering - a prospective cohort study on COVID-19, Germany 2021.

BACKGROUND: Mass gatherings (MGs) such as music festivals and sports events have been associated with a high risk of SARS-CoV-2 transmission. On-site research can foster knowledge of risk factors for infections and improve risk assessments and precautionary measures at future MGs. We tested a web-based participatory disease surveillance tool to detect COVID-19 infections at and after an outdoor MG by collecting self-reported COVID-19 symptoms and tests. METHODS: We conducted a digital prospective observational cohort study among fully immunized attendees of a sports festival that took place from September 2 to 5, 2021 in Saxony-Anhalt, Germany. Participants used our study app to report demographic data, COVID-19 tests, symptoms, and their contact behavior. This self-reported data was used to define probable and confirmed COVID-19 cases for the full "study period" (08/12/2021 - 10/31/2021) and within the 14-day "surveillance period" during and after the MG, with the highest likelihood of an MG-related COVID-19 outbreak (09/04/2021 - 09/17/2021). RESULTS: A total of 2,808 of 9,242 (30.4%) event attendees participated in the study. Within the study period, 776 individual symptoms and 5,255 COVID-19 tests were reported. During the 14-day surveillance period around and after the MG, seven probable and seven PCR-confirmed COVID-19 cases were detected. The confirmed cases translated to an estimated seven-day incidence of 125 per 100,000 participants (95% CI [67.7/100,000, 223/100,000]), which was comparable to the average age-matched incidence in Germany during this time. Overall, weekly numbers of COVID-19 cases were fluctuating over the study period, with another increase at the end of the study period. CONCLUSION: COVID-19 cases attributable to the mass gathering were comparable to the Germany-wide age-matched incidence, implicating that our active participatory disease surveillance tool was able to detect MG-related infections. Further studies are needed to evaluate and apply our participatory disease surveillance tool in other mass gathering settings.

Is the impact of childhood influenza vaccination less than expected: a transmission modelling study.

BACKGROUND: To reduce the burden of severe influenza, most industrialized countries target specific risk-groups with influenza vaccines, e.g. the elderly or individuals with comorbidities. Since children are the main spreaders, some countries have recently implemented childhood vaccination programs to reduce overall virus transmission and thereby influenza disease in the whole population. The introduction of childhood vaccination programs was often supported by modelling studies that predicted substantial incidence reductions. We developed a mathematical transmission model to examine the potential impact of childhood influenza vaccination in Germany, while also challenging established modelling assumptions. METHODS: We developed an age-stratified SEIR-type transmission model to reproduce the epidemic influenza seasons between 2003/04 and 2013/14. The model was built upon German population counts, contact patterns, and vaccination history and was fitted to seasonal data on influenza-attributable medically attended acute respiratory infections (I-MAARI) and strain distribution using Bayesian methods. As novelties we (i) implemented a stratified model structure enabling seasonal variability and (ii) deviated from the commonly assumed mass-action-principle by employing a phenomenological transmission rate. RESULTS: According to the model, by vaccinating primarily the elderly over ten seasons 4 million (95% prediction interval: 3.84 - 4.19) I-MAARI were prevented which corresponds to an 8.6% (8.3% - 8.9%) reduction compared to a no-vaccination scenario and a number-needed-to-vaccinate (NNV) to prevent one I-MAARI of 37.1 (35.5 - 38.7). Additional vaccination of 2-10 year-old children at 40% coverage would have led to an overall I-MAARI reduction of 17.8% (17.1 - 18.7%) mostly due to indirect effects with a NNV of 20.7 (19.6 - 21.6). When employing the traditional mass-action-principle, the model predicted a more than 3-fold higher I-MAARI reduction (55.6%) due to childhood vaccination. CONCLUSION: In Germany, the introduction of routine childhood influenza vaccination could considerably reduce I-MAARI among all age-groups and improve the NNV. However, the predicted impact is much lower compared to previous studies, which is primarily caused by our phenomenological approach to modelling influenza virus transmission.

Effectiveness, immunogenicity and safety of 23-valent pneumococcal polysaccharide vaccine revaccinations in the elderly: a systematic review.

BACKGROUND: In many industrialized countries routine vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV-23) is recommended to prevent pneumococcal disease in the elderly. However, vaccine-induced immunity wanes after a few years, and there are controversies around revaccination with PPSV-23. Here, we systematically assessed the effectiveness and safety of PPSV-23 revaccination. METHOD: We conducted a systematic literature review in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from inception to June 2015. We included all study types that compared effectiveness, immunogenicity and/or safety of PPSV-23 as a primary vs. a revaccination dose in persons aged 50 years and older. With respect to immunogenicity, we calculated the ratio of geometric mean antibody concentrations and opsonophagocytic indexes at identical time-points after primary and revaccination. Additionally, we compared rates and severity of adverse events (AEs) after primary and revaccination. RESULTS: We included 14 observational studies. 10 studies had a prospective design and analysed data on (i) the same individuals after a first and a second dose of PPSV-23 given 1 to 10 years later (n = 5) or (ii) two groups consisting of participants receiving PPSV-23 who were either vaccine-naïve or had received a first PPSV-23 dose 3 to 13 years earlier (n = 5). Three studies used electronic data bases to compare AEs after primary vs. revaccination doses of PPSV-23 after 1 to 10 years and one study had a cross-sectional design. Number of participants in the non-register-based and register-based studies ranged from 29 to 1414 and 360 to 316,000, respectively. 11 out of 14 included studies were at high risk of bias, three studies had an unclear risk of bias. None of the studies reported data on clinical effectiveness. Immunogenicity studies revealed that during the first two months antibody levels tended to be lower after revaccination as compared to primary vaccination. Thereafter, no obvious differences in antibody levels were observed. Compared to primary vaccination, revaccination was associated with an increased risk of local and systemic AEs, which, however, were usually mild and self-limiting. The risk and severity of AEs appeared to decrease with longer intervals between primary and revaccination. CONCLUSION: Data comparing the effectiveness of primary vs. revaccination with PPSV-23 are still lacking, because there are no studies with clinical endpoints. Data from observational studies indicates that revaccination with PPSV-23 is likely to induce long-term antibody levels that are comparable to those after primary vaccination. Given the high disease burden and the waning of vaccine-induced immunity, revaccination with PPSV-23 could be considered in the elderly. The increased risk of local and systemic AEs can likely be mitigated when giving revaccination at least five years after the primary dose. Adequately powered randomized controlled trials using clinical endpoints are urgently needed.

Vaccines for the prevention of seasonal influenza in patients with diabetes: systematic review and meta-analysis.

BACKGROUND: Patients with diabetes are at increased risk of severe influenza disease; influenza vaccination for these patients is therefore recommended by the World Health Organization and several National Immunization Technical Advisory Groups. However, no systematic review has evaluated the effects of influenza vaccines for patients with diabetes. METHODS: We conducted a systematic review and meta-analysis by searching Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception until November 2014. We included all types of studies reporting on the efficacy, effectiveness, and/or safety of influenza vaccination in patients with type 1 and type 2 diabetes of all ages. We used the Newcastle-Ottawa scale to assess risk of bias in observational studies. Residual confounding was addressed by comparing estimates of vaccine effectiveness (VE) during influenza seasons to those obtained during off-seasons. Quality of the evidence for each outcome was assessed using the GRADE methodology. RESULTS: Following review of 1,444 articles, 11 observational studies with a total of 170,924 participants were included. In diabetic patients of working-age (18-64 years), influenza vaccination prevented all-cause hospitalization with a pooled VE of 58% (95% CI, 6-81%) and hospitalization due to influenza or pneumonia (VE 43%; 95% CI, 28-54%), whereas no effects on all-cause mortality and influenza-like illness (ILI) were observed. In the elderly (65+), influenza vaccination prevented all-cause mortality (VE 38%; 95% CI, 32-43%), all-cause hospitalization (VE 23%; 95% CI, 1-40%), hospitalization due to influenza or pneumonia (VE 45%; 95% CI, 34-53%), and ILI (VE 13%; 95% CI, 10-16%). However, significant off-season estimates for several outcomes indicated residual confounding, particularly in elderly patients. Quality of the evidence was low to very low for all outcomes. Laboratory-confirmed influenza infections were not reported. CONCLUSIONS: Due to strong residual confounding in most of the identified studies, the available evidence is insufficient to determine the magnitude of benefit that diabetic people derive from seasonal influenza vaccination. Adequately powered randomized controlled trials or quasi-experimental studies using laboratory-confirmed influenza-specific outcomes are urgently needed.

Frequency and impact of confounding by indication and healthy vaccinee bias in observational studies assessing influenza vaccine effectiveness: a systematic review.

BACKGROUND: Evidence on influenza vaccine effectiveness (VE) is commonly derived from observational studies. However, these studies are prone to confounding by indication and healthy vaccinee bias. We aimed to systematically investigate these two forms of confounding/bias. METHODS: Systematic review of observational studies reporting influenza VE and indicators for bias and confounding. We assessed risk of confounding by indication and healthy vaccinee bias for each study and calculated ratios of odds ratios (crude/adjusted) to quantify the effect of confounder adjustment. VE-estimates during and outside influenza seasons were compared to assess residual confounding by healthy vaccinee effects. RESULTS: We identified 23 studies reporting on 11 outcomes. Of these, 19 (83 %) showed high risk of bias: Fourteen due to confounding by indication, two for healthy vaccinee bias, and three studies showed both forms of confounding/bias. Adjustment for confounders increased VE on average by 12 % (95 % CI: 7-17 %; all-cause mortality), 9 % (95 % CI: 4-14 %; all-cause hospitalization) and 7 % (95 % CI: 4-10 %; influenza-like illness). Despite adjustment, nine studies showed residual confounding as indicated by significant off-season VE-estimates. These were observed for five outcomes, but more frequently for all-cause mortality as compared to other outcomes (p = 0.03) and in studies which indicated healthy vaccinee bias at baseline (p = 0.01). CONCLUSIONS: Both confounding by indication and healthy vaccinee bias are likely to operate simultaneously in observational studies on influenza VE. Although adjustment can correct for confounding by indication to some extent, the resulting estimates are still prone to healthy vaccinee bias, at least as long as unspecific outcomes like all-cause mortality are used. Therefore, cohort studies using administrative data bases with unspecific outcomes should no longer be used to measure the effects of influenza vaccination.

Application of the screening method to monitor influenza vaccine effectiveness among the elderly in Germany.

BACKGROUND: Elderly people are at increased risk for severe influenza illness and constitute therefore a major target-group for seasonal influenza vaccination in most industrialized countries. The aim of this study was to estimate influenza vaccine effectiveness (VE) among individuals aged 60+ years over three seasons and to assess if the screening method is a suitable tool to monitor influenza VE in this particular target-group in Germany. METHODS: We identified laboratory-confirmed influenza cases aged 60+ years through the national communicable disease reporting system for seasons 2010/11, 2011/12 and 2012/13. Vaccination coverage (VC) data were retrieved from a database of health insurance claims representing ~85% of the total German population. We applied the screening method to calculate influenza subtype-specific VE and compared our results with VE estimates from other observational studies in Europe. RESULTS: In total, 7,156 laboratory-confirmed influenza cases were included. VE against all influenza types ranged between 49% (95% confidence interval [CI]: 39-56) in 2011/12 and 80% (95% CI: 76-83%) in 2010/11. In 2010/11 subtype-specific VE against influenza A(H1N1)pdm and B was 76% and 84%, respectively. In the following seasons, VE against influenza A(H1N1)pdm, A(H3N2) and B was 87%, -9% , 74% (2011/12), and 74%, 39%, 73% (2012/13). VE was higher among hospitalized compared to non-hospitalized influenza A cases. Seventeen observational studies from Europe reporting subtype-specific VE among the elderly were identified for the respective seasons (all applying the test-negative design) and showed comparable subtype-specific VE estimates. CONCLUSIONS: According to our study, influenza vaccination provided moderate protection against laboratory-confirmed influenza A(H1N1)pdm and B in individuals aged 60+ but no or only little protection against A(H3N2). Higher VE among hospitalized cases might indicate higher protection against severe influenza disease. Based on the available data, the screening method allowed us to assess subtype-specific VE in hospitalized and non-hospitalized elderly persons. Since controlling for several important confounders was not possible, the applied method only provided crude VE estimates. However, given the precise VC-data and the large number of cases, the screening method provided results being in line with VE estimates from other observational studies in Europe that applied a different study design.

Why are older adults and individuals with underlying chronic diseases in Germany not vaccinated against flu? A population-based study.

BACKGROUND: Older adults and individuals with underlying chronic diseases are at increased risk of developing influenza-related complications and are target groups for seasonal influenza vaccination in many countries. In Germany, an annual national information campaign is conducted to increase influenza vaccination uptake in the target groups. However, data are lacking on knowledge and attitudes toward influenza vaccination among older adults and those with chronic diseases. The present study aimed to (i) estimate influenza vaccination uptake for the 2012/13 and 2013/14 seasons, (ii) assess knowledge and attitudes about influenza vaccination, and (iii) identify factors associated with vaccination uptake in two risk groups. METHODS: Between March and June 2014, we conducted a nationwide cross-sectional survey in adults (≥18 years) living in Germany using computer-assisted telephone interviewing. We calculated weighted vaccination coverage rates in two at-risk groups. Group 1 comprised participants aged 18-59 years with underlying chronic diseases. Group 2 comprised participants aged 60+, irrespective of underlying disease. We used univariate and multivariable logistic regression analyses to identify associations between influenza vaccination uptake and sociodemographic characteristics, and to evaluate attitudes and knowledge. RESULTS: In total, 1,519 interviews were conducted. Seasonal influenza vaccination uptake in people with underlying chronic diseases aged 18-59 years was 24 % in 2012/2013 and 23 % in 2013/2014. In older adults, uptake was 50 % and 49 % in 2012/13 and 2013/14 respectively. There were considerable vaccination-related knowledge gaps among respondents. For example, about half of the participants who aged ≥60 years and/or suffered from underlying chronic diseases believed that influenza vaccination could cause influenza. The most commonly stated reasons for not being immunized were mistrust of the vaccination (22 %) and the perception that influenza is not dangerous (21 %). For both groups, vaccination uptake was independently associated with sex, perceived severity of influenza, perceived vaccination effectiveness, and the perceived likelihood or severity of vaccination side effects. For older adults, additional factors influencing vaccination uptake were age, underlying chronic diseases, and recent advice through physician consultation. CONCLUSIONS: Influenza vaccination coverage rates in Germany remain low. Individual perceptions regarding harms and benefits are crucial in the decision-making process. Communication strategies should focus on improving understanding and perception of personal risks arising from the disease and the vaccination.

German outbreak of Escherichia coli O104:H4 associated with sprouts.

BACKGROUND: A large outbreak of the hemolytic-uremic syndrome caused by Shiga-toxin-producing Escherichia coli O104:H4 occurred in Germany in May 2011. The source of infection was undetermined. METHODS: We conducted a matched case-control study and a recipe-based restaurant cohort study, along with environmental, trace-back, and trace-forward investigations, to determine the source of infection. RESULTS: The case-control study included 26 case subjects with the hemolytic-uremic syndrome and 81 control subjects. The outbreak of illness was associated with sprout consumption in univariable analysis (matched odds ratio, 5.8; 95% confidence interval [CI], 1.2 to 29) and with sprout and cucumber consumption in multivariable analysis. Among case subjects, 25% reported having eaten sprouts, and 88% reported having eaten cucumbers. The recipe-based study among 10 groups of visitors to restaurant K included 152 persons, among whom bloody diarrhea or diarrhea confirmed to be associated with Shiga-toxin-producing E. coli developed in 31 (20%). Visitors who were served sprouts were significantly more likely to become ill (relative risk, 14.2; 95% CI, 2.6 to ∞). Sprout consumption explained 100% of cases. Trace-back investigation of sprouts from the distributor that supplied restaurant K led to producer A. All 41 case clusters with known trading connections could be explained by producer A. The outbreak strain could not be identified on seeds from the implicated lot. CONCLUSIONS: Our investigations identified sprouts as the most likely outbreak vehicle, underlining the need to take into account food items that may be overlooked during subjects' recall of consumption.

Influenza vaccination in patients with end-stage renal disease: systematic review and assessment of quality of evidence related to vaccine efficacy, effectiveness, and safety.

BACKGROUND: Vaccination against influenza is recommended in patients with end-stage renal disease (ESRD). However, so far, no systematic review has summarized the available evidence on the effectiveness and safety of influenza vaccination in this patient group. METHODS: We conducted a systematic review and meta-analysis and assessed the quality of evidence using the GRADE methodology. We searched MEDLINE, EMBASE, Cochrane Library databases, ClinicalTrials.gov, and reference lists for studies on efficacy, effectiveness, and/or safety of seasonal influenza vaccination in patients with ESRD receiving dialysis. All reported clinical outcomes were considered, including all-cause mortality, cardiac death, infectious death, all-cause hospitalization, hospitalization due to influenza or pneumonia, hospitalization due to bacteremia, viremia, or septicemia, hospitalization due to respiratory infection, ICU admission, and influenza-like illness. RESULTS: Five observational studies and no randomized-controlled trial were identified. In four studies, risk of bias was high regarding all reported outcomes. Strong residual confounding was likely to be present in one study reporting on three outcomes, as indicated by significant protective effects of vaccination outside influenza seasons. Therefore, the statistically significant protective effects on all-cause mortality (vaccine effectiveness (VE), 32%; 95% CI, 24-39%), cardiac death (VE, 16%; 95% CI, 1-29%), hospitalization due to influenza or pneumonia (VE, 14%; 95% CI, 7-20%), ICU admission (VE, 81%; 95% CI, 63-86%), and influenza-like illness (VE, 12%; 95% CI, 10-14%) have to be taken with caution. According to GRADE, the quality of the body of evidence was considered very low for all outcomes. No study reported on laboratory-confirmed influenza virus infections or on safety endpoints. CONCLUSIONS: Evidence on the protective effects of influenza vaccination in patients with ESRD is limited and of very low quality. Since VE estimates in the available literature are prone to unmeasured confounding, studies using randomization or quasi-experimental designs are needed to determine the extent by which vaccination prevents influenza and related clinical outcomes in this at-risk population. However, given the high rates of health-endangering events in these patients, even a low VE can be considered as sufficient to recommend annual influenza vaccination.

Human Papillomavirus prevalence and probable first effects of vaccination in 20 to 25 year-old women in Germany: a population-based cross-sectional study via home-based self-sampling.

BACKGROUND: Estimates of Human Papillomavirus (HPV) prevalence in a population prior to and after HPV vaccine introduction are essential to evaluate the short-term impact of vaccination. METHODS: Between 2010 and 2012 we conducted a population-based cross-sectional study in Germany to determine HPV prevalence, genotype distribution and risk factors for HPV-infection in women aged 20-25 years. Women were recruited by a two-step cluster sampling approach. A home-based self-collection of cervicovaginal lavages was used. Specimens were analysed using a general primer GP5+/GP6+-based polymerase chain reaction and genotyped for 18 high-risk and 6 low-risk HPV- strains by Luminex-based multiplexed genotyping. RESULTS: Among 787 included women, 512 were not vaccinated against HPV. In the non-vaccinated population, HPV prevalence of any type was 38.1%, with HPV 16 (19.5%) being the most prevalent genotype. Prevalence of any high-risk type was 34.4%, and in 17.4% of all women, more than one genotype was identified. A higher number of lifetime sexual partners and low educational status were independently associated with HPV-infection. In 223 vaccinated women, prevalence of HPV 16/18 was significantly lower compared to non-vaccinated women (13.9% vs. 22.5%, p = 0.007). When stratifying by age groups, this difference was only significant in women aged 20-21 years, who at time of vaccination were on average younger and had less previous sexual contacts than women aged 22-25 years. CONCLUSION: We demonstrate a high prevalence of high-risk HPV genotypes in non-vaccinated women living in Germany that can be potentially prevented by vaccination. Probable first vaccination effects on the HPV prevalence were observed in women who were vaccinated at younger age. This finding reinforces the recommendation to vaccinate girls in early adolescence.

Sexual behavior and factors associated with young age at first intercourse and HPV vaccine uptake among young women in Germany: implications for HPV vaccination policies.

BACKGROUND: In Germany, immunization against human papillomaviruses (HPV) is free of charge for all females aged 12 to 17 years. Since HPV infection rates rise soon after first intercourse, immunization against HPV should be completed before sexual debut. Knowledge of country-specific data on age at first intercourse and related risk factors is important to optimize prevention of HPV and other sexually transmitted infections. Therefore, the primary aim of this study was to describe sexual behavior in young women in Germany. Secondary aims were to identify factors that are (i) associated with younger age at first intercourse and (ii) with HPV vaccine uptake. METHODS: Between 2010 and 2012, we conducted a cross-sectional study among randomly selected women aged 20 to 25 years in Germany. We used a structured, self-administered questionnaire to collect sociodemographic data, information on sexual habits such as age at first intercourse, and information on HPV vaccine uptake. We used univariate and multivariate logistic regression analyses to identify factors associated with younger age at first intercourse and with HPV vaccine uptake. RESULTS: A total of 823 women (response rate: 14.2%) participated, 785 (95.4%) of which reported having had intercourse already. 70% of these women experienced first intercourse before the age of 18 years. However, less than 5% were younger than 14 years at sexual debut. Younger age at first intercourse was independently associated with a higher number of sexual partners, smoking, and past pregnancies. HPV vaccine uptake was associated with higher education, whereas smoking and a migrant background reduced the chance of being vaccinated. CONCLUSION: In Germany, only a small proportion of women experienced first intercourse before the age of 14 years. Younger age at first intercourse was associated with behavior that might increase the risk of HPV infections or other sexually transmitted infections. Therefore, to optimize the HPV vaccination strategy, HPV vaccination series should be completed before the age of 14 years in Germany.

Feasibility Study on Menstrual Cycles With Fitbit Device (FEMFIT): Prospective Observational Cohort Study.

BACKGROUND: Despite its importance to women's reproductive health and its impact on women's daily lives, the menstrual cycle, its regulation, and its impact on health remain poorly understood. As conventional clinical trials rely on infrequent in-person assessments, digital studies with wearable devices enable the collection of longitudinal subjective and objective measures. OBJECTIVE: The study aims to explore the technical feasibility of collecting combined wearable and digital questionnaire data and its potential for gaining biological insights into the menstrual cycle. METHODS: This prospective observational cohort study was conducted online over 12 weeks. A total of 42 cisgender women were recruited by their local gynecologist in Berlin, Germany, and given a Fitbit Inspire 2 device and access to a study app with digital questionnaires. Statistical analysis included descriptive statistics on user behavior and retention, as well as a comparative analysis of symptoms from the digital questionnaires with metrics from the sensor devices at different phases of the menstrual cycle. RESULTS: The average time spent in the study was 63.3 (SD 33.0) days with 9 of the 42 individuals dropping out within 2 weeks of the start of the study. We collected partial data from 114 ovulatory cycles, encompassing 33 participants, and obtained complete data from a total of 50 cycles. Participants reported a total of 2468 symptoms in the daily questionnaires administered during the luteal phase and menses. Despite difficulties with data completeness, the combined questionnaire and sensor data collection was technically feasible and provided interesting biological insights. We observed an increased heart rate in the mid and end luteal phase compared with menses and participants with severe premenstrual syndrome walked substantially fewer steps (average daily steps 10,283, SD 6277) during the luteal phase and menses compared with participants with no or low premenstrual syndrome (mean 11,694, SD 6458). CONCLUSIONS: We demonstrate the feasibility of using an app-based approach to collect combined wearable device and questionnaire data on menstrual cycles. Dropouts in the early weeks of the study indicated that engagement efforts would need to be improved for larger studies. Despite the challenges of collecting wearable data on consecutive days, the data collected provided valuable biological insights, suggesting that the use of questionnaires in conjunction with wearable data may provide a more complete understanding of the menstrual cycle and its impact on daily life. The biological findings should motivate further research into understanding the relationship between the menstrual cycle and objective physiological measurements from sensor devices.

Risk factors for cervical human papillomavirus infection and high-grade intraepithelial lesion in women aged 20 to 31 years in Germany.

BACKGROUND: Persistent infection with high-risk human papillomaviruses (HPVs) can lead to cervical intraepithelial lesion and cervical cancer. Sexual behavior and smoking have been identified as risk factors for HPV infection. However, it is unclear which factors account for the persistence of HPV infection and for high-grade squamous intraepithelial lesions (HSIL). Therefore, we conducted a study to identify epidemiological risk factors for the following: (1) the presence of HPV among women without a recent diagnosis of HSIL and (2) HSIL. MATERIALS AND METHODS: Participants aged 20 to 31 years were recruited at 2 study sites. All women received a cervical Papanicolaou test, were tested for HPV, and categorized into 1 of 3 different groups: The women of the first group had negative cytological test results and a negative HPV test result (HPV-negative group), and the women of the second group had negative cytological test result but positive HPV test result (HPV-positive group). The third group consisted of women with a diagnosis of HSIL (HSIL group). We first compared the HPV-negative group with the HPV-positive group, and then the HPV-positive group with the HSIL group. RESULTS: One hundred forty-seven women were included: 53 women in the HPV-negative group, 46 women in the HPV-positive group, and 48 women in the HSIL group. Comparing the HPV-negative with the HPV-positive group, we found that more than 5 sexual partners during a lifetime were independently associated with cervical HPV infection, whereas the chance of being infected decreased with older age. Irregular condom use during one-night stands or smoking was associated with HPV infection only in univariable but not multivariable analysis. In contrast, older age and having had genital warts were independently associated with an HSIL diagnosis when comparing the HPV-positive group with the HSIL group. DISCUSSION: Although the study was hampered by its relatively small sample size, our data suggest that main risk factors for the acquisition of HPV infection are a higher number of sexual partners and younger age, whereas older age and genital warts may be epidemiological cofactors in the development of HSIL.

The role of facemasks and hand hygiene in the prevention of influenza transmission in households: results from a cluster randomised trial; Berlin, Germany, 2009-2011.

BACKGROUND: Previous controlled studies on the effect of non-pharmaceutical interventions (NPI) - namely the use of facemasks and intensified hand hygiene - in preventing household transmission of influenza have not produced definitive results. We aimed to investigate efficacy, acceptability, and tolerability of NPI in households with influenza index patients. METHODS: We conducted a cluster randomized controlled trial during the pandemic season 2009/10 and the ensuing influenza season 2010/11. We included households with an influenza positive index case in the absence of further respiratory illness within the preceding 14 days. Study arms were wearing a facemask and practicing intensified hand hygiene (MH group), wearing facemasks only (M group) and none of the two (control group). Main outcome measure was laboratory confirmed influenza infection in a household contact. We used daily questionnaires to examine adherence and tolerability of the interventions. RESULTS: We recruited 84 households (30 control, 26 M and 28 MH households) with 82, 69 and 67 household contacts, respectively. In 2009/10 all 41 index cases had a influenza A (H1N1) pdm09 infection, in 2010/11 24 had an A (H1N1) pdm09 and 20 had a B infection. The total secondary attack rate was 16% (35/218). In intention-to-treat analysis there was no statistically significant effect of the M and MH interventions on secondary infections. When analysing only households where intervention was implemented within 36 h after symptom onset of the index case, secondary infection in the pooled M and MH groups was significantly lower compared to the control group (adjusted odds ratio 0.16, 95% CI, 0.03-0.92). In a per-protocol analysis odds ratios were significantly reduced among participants of the M group (adjusted odds ratio, 0.30, 95% CI, 0.10-0.94). With the exception of MH index cases in 2010/11 adherence was good for adults and children, contacts and index cases. CONCLUSIONS: Results suggest that household transmission of influenza can be reduced by the use of NPI, such as facemasks and intensified hand hygiene, when implemented early and used diligently. Concerns about acceptability and tolerability of the interventions should not be a reason against their recommendation. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (Identifier NCT00833885).

Continuous increase of vancomycin resistance in enterococci causing nosocomial infections in Germany - 10 years of surveillance.

Background: Enterococci are frequent pathogens causing nosocomial infections in Germany. Infections due to strains with vancomycin resistance are high when compared with other European states. Therefore, the study aimed to describe the recent progression of nosocomial infections due to vancomycin-resistant enterococci (VRE) in Germany. Methods: We analyzed data from two components of the German national nosocomial infection surveillance system for the period 2007-2016. For primary bloodstream infections (BSIs) and urinary tract infections (UTIs) we used data from intensive care units and for surgical site infections (SSIs) data from surgical departments. In a sensitivity analysis, we considered only data from participants that participated continuously from 2007 to 2016 ("core group"). We calculated proportions of VRE among all nosocomial enterococcal infections with 95% confidence intervals (95% CIs) and trends over time. A multivariable logistic regression was used to compare occurrence of VRE proportions among German federal states. Results: Enterococcal infections from 857 ICUs and 1119 surgical departments were analyzed. On ICUs, the proportion of vancomycin resistance in enterococci causing nosocomial infections significantly increased for BSIs from 5.9 to 16.7% and for UTIs from 2.9 to 9.9%; for surgical site infections, the proportion of VRE increased from 0.9 to 5.2% (P < 0.001 for all). In the core group, the increase of VRE was more pronounced in ICUs (BSIs: 5.5 to 21.6%; UTIs: 2 to 11.2%) but was not seen in surgical departments (SSIs: 1.5 to 2.8%). Compared with the most populous German federal state North Rhine Westphalia, enterococcal infections in Hesse (Odds Ratio (OR) 2.3, 95% CI 1.7-3.1), Saxony (OR 2.5, 95% CI 1.8-3.5) and Thuringia (OR 1.9, 95% CI 1.4-2.6) were more likely to be caused by vancomycin-resistant strains. Conclusion: In Germany, the proportion of VRE in nosocomial infection due to enterococci is still increasing. It remains unclear, why a large variation in the proportion of VRE exists between German federal states.

The importance of adjusting for enterococcus species when assessing the burden of vancomycin resistance: a cohort study including over 1000 cases of enterococcal bloodstream infections.

Background: Infections caused by vancomycin-resistant enterococci (VRE) are on the rise worldwide. Few studies have tried to estimate the mortality burden as well as the financial burden of those infections and found that VRE are associated with increased mortality and higher hospital costs. However, it is unclear whether these worse outcomes are attributable to vancomycin resistance only or whether the enterococcal species (Enterococcus faecium or Enterococcus faecalis) play an important role. We therefore aimed to determine the burden of enterococci infections attributable to vancomycin resistance and pathogen species (E. faecium and E. faecalis) in cases of bloodstream infection (BSI). Methods: We conducted a retrospective cohort study on patients with BSI caused by Enterococcus faecium or Enterococcus faecalis between 2008 and 2015 in three tertiary care hospitals. Data was collected on true hospital costs (in €), length of stay (LOS), basic demographic parameters, and underlying diseases including the results of the Charlson comorbidity index (CCI). We used univariate and multivariable regression analyses to compare risk factors for in-hospital mortality and length of stay (i) between vancomycin-susceptible E. faecium- (VSEm) and vancomycin-susceptible E. faecalis- (VSEf) cases and (ii) between vancomycin-susceptible E. faecium- (VSEm) and vancomycin-resistant E. faecium-cases (VREm). We calculated total hospital costs for VSEm, VSEf and VREm. Results: Overall, we identified 1160 consecutive cases of BSI caused by enterococci: 596 (51.4%) cases of E. faecium BSI and 564 (48.6%) cases of E. faecalis BSI. 103 cases of E. faecium BSI (17.3%) and 1 case of E. faecalis BSI (0.2%) were infected by vancomycin-resistant isolates. Multivariable analyses revealed (i) that in addition to different underlying diseases E. faecium was an independent risk factor for in-hospital mortality and prolonged hospital stay and (ii) that vancomycin-resistance did not further increase the risk for the described outcomes among E. faecium-isolates. However, the overall hospital costs were significantly higher in VREm-BSI cases as compared to VSEm- and VSEf-BSI cases (80,465€ vs. 51,365€ vs. 31,122€ p < 0.001). Conclusion: Our data indicates that in-hospital mortality and infection-attributed hospital stay in enterococci BSI might rather be influenced by Enterococcus species and underlying diseases than by vancomycin resistance. Therefore, future studies should consider adjusting for Enterococcus species in addition to vancomycin resistance in order to provide a conservative estimate for the burden of VRE infections.

Factors associated with parental acceptance of seasonal influenza vaccination for their children - A telephone survey in the adult population in Germany.

INTRODUCTION: Influenza vaccination of children with underlying chronic diseases is currently recommended in Germany, but targeting all children constitutes an alternative approach to control seasonal influenza. To inform the modelling of vaccination impact and possible communication activities, we aimed to assess among parents the acceptance of universal childhood vaccination against seasonal influenza and possible modifiers. METHODS: We conducted a telephone survey in households in Germany using random digit dialing. We interviewed parents with children aged <18 years by constructing three hypothetical scenarios in subsequent order: (1) hearing about the influenza vaccination recommendation through the media, (2) the vaccine being recommended by a physician, and (3) being informed about the availability of the vaccine as a nasal spray. We calculated the proportion of parents who would immunize their child and used univariable and multivariable logistic regression to identify factors associated with influenza vaccination intention. RESULTS: Response was between 22 and 46%. Of 518 participants, 74% were female, mean age was 41.3 years. Participants had on average 1.6 children with a mean age of 8.9 years. In scenario 1, 52% of parents would immunize their child, compared to 64% in scenario 2 (p<0.01) and to 45% in scenario 3 (p=0.20). Factors independently associated with vaccination acceptance in scenario 1 were previous influenza vaccination of the child or parent (adjusted odds ratio [aOR] 4.5 and 8.6, respectively), perceived severity of influenza (aOR=5.1) and living in eastern Germany (aOR=2.4). CONCLUSION: If seasonal influenza vaccination was recommended for all children, more than half of the parents would potentially agree to immunize their child. Involving physicians in future information campaigns is essential to achieve high uptake. As intranasal vaccine administration is non-invasive and easily done, it remains unclear why scenario 3 was associated with low acceptance among parents, and the underlying reasons should be further explored.