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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. Keywords: Human papillomavirus, Prevalence, Serology, Vaccine, General population, Seroepidemiologic studies, Predictors, Germany

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.

Background: With the absence of immunization, public health interventions are the basis for curbing the spread of the SARS-CoV-2 virus. Evidence of impact of non-pharmaceutical interventions (NPI) on SARS-CoV-2 spread in Germany is scarce. The objectives of this study were to use a Delphi-panel based assessment of the effectiveness of different COVID-19 specific prevention measures in order to retrospectively approximate and to prospectively predict the SARS-CoV-2 pandemic progression via a SEIR model (SEIR: Susceptible - Exposed - Infectious - Removed). The SEIR model will be made available with a modifiable user interface. Methods: We applied an evidence-educated Delphi-panel approach to elicit the impact of NPIs being discussed in Germany on the SARS-CoV-2 transmission rate R0. Initial estimates were discussed and agreed upon in two Delphi stages resulting in a final set of average efficacy and compliance estimates for each NPI. 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 pandemic course. The model was populated with the Delphi-panel results and varied in sensitivity analyses. Results: Efficacy and compliance estimates were obtained as follows (ranked by effectiveness): test and isolate 49% (efficacy)/78% (compliance), keeping distance 42%/74%, personal protection masks (cloth masks or other face masks) 33%/79%, ban of large public events 26%/96%, contact reduction 33%/59%, closure of non-essential stores 10%/97%, closure of schools 10%/100%, working from home 12%/66%, closure of restaurants 8%/96%, and improved hand hygiene 7%/54%. Applying these NPI effectiveness estimates to the SEIR model resulted in a valid replication of reported occurrence of the German SARS-CoV-2 pandemic. Conclusion: Employing an evidence-educated Delphi-panel approach for generating NPI effectiveness estimates is feasible and could help to generate model simulations with close replication of reported infected cases in Germany. 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. Funding Statement: None. Declaration of Interests: None declared. Ethics Approval Statement: Not applicable.

Objectives To assess the admission prevalence of third-generation cephalosporin-resistant Enterobacterales (3GCREB) and to assess whether risk factors vary by β-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 β-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 β-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.

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.

Background Infections caused by third generation cephalosporin-resistant Enterobacteriaceae (3GCREB) are an increasing healthcare problem. We aim to describe the 3GCREB infection incidence and compare it to prevalence upon admission. In addition, we aim to describe infections caused by 3GCREB, which are also carbapenem resistant (CRE). Methods In 2014–2015, we performed prospective 3GCREB surveillance in clinically relevant patient specimens (screening specimens excluded). Infections counted as hospital-acquired (HAI) when the 3GCREB was detected after the third day following admission, otherwise as community-acquired infection (CAI). Results Of 578,420 hospitalized patients under surveillance, 3367 had a 3GCREB infection (0.58%). We observed a similar 3GCREB CAI and HAI incidence (0.28 and 0.31 per 100 patients, respectively). The most frequent pathogen was 3GCR E. coli, in CAI and HAI (0.15 and 0.12 per 100 patients). We observed a CRE CAI incidence of 0.006 and a HAI incidence of 0.008 per 100 patients (0.014 per 1000 patient days). Conclusions Comparing the known 3GCREB admission prevalence of the participating hospitals (9.5%) with the percentage of patients with a 3GCREB infection (0.58%), we conclude the prevalence of 3GCREB in university hospitals to be about 16 times higher than suggested when only patients with 3GCREB infections are considered. Moreover, we find the HAI and CAI incidence caused by CRE in Germany to be relatively low.

Background: Infection with cytomegalovirus (CMV) remains asymptomatic in most immunocompetent hosts, but is the leading cause of congenital viral infection worldwide and can be life-threatening in immunocompromised individuals. We aimed to assess CMV seroprevalence in a nationally representative sample of adults in Germany and to identify sociodemographic factors associated with CMV seropositivity. Methods: Blood samples from 6552 participants (18–79 years) of the “German National Health Interview and Examination Survey 1998”, a population-based sample of the adult population in Germany, were tested for the presence of CMV antibodies using an Ig-multiplex assay. Weighted seroprevalence was calculated and weighted binomial regression was used to identify factors associated with CMV seropositivity. Results: Overall CMV seroprevalence was 56.7% (95%CI: 54.8–58.7%), with a higher seroprevalence in women (62.3%) than in men (51.0%). Seroprevalence increased with age: from 31.8% to 63.7% in men and from 44.1% to 77.6% in women when comparing the 18–29 with the 70–79 year age-group, respectively. CMV seroprevalence in women of childbearing age (18–45 years) was 51.7%. Factors significantly associated with CMV seropositivity were age, country of birth, smoking status, education, living in northern Germany and number of household members. In addition, having attended child care was associated with seropositivity in men, and number of siblings and living in East Germany in women. Conclusion: Our results indicate that half the women of childbearing age were susceptible for primary CMV infection during pregnancy. CMV screening during pregnancy and informing seronegative women about CMV risk reduction measures could prevent congenital CMV infections with its serious consequences.

Background In 2004, universal childhood varicella vaccination was introduced in Germany. We aimed to determine the age-specific prevalence of anti-varicella zoster virus (VZV) IgG-antibodies among children in the pre-varicella vaccine era in Germany, to identify factors associated with VZV seropositivity, and to assess the suitability of a commercially available ELISA for VZV seroepidemiological studies by comparing it with an in-house fluorescent antibody to membrane antigen test (FAMA) as the gold standard. Methods Serum samples of 13,433 children and adolescents aged 1–17 years included in the population-based German Health Interview and Examination Survey for Children and Adolescents (KiGGS; conducted 2003–2006) were tested for anti-VZV IgG by ELISA. All samples with equivocal ELISA results and a random selection of ELISA-negative and -positive samples were tested by FAMA. Statistical analyses were conducted using a weighting factor adjusting the study population to the total population in Germany. Seroprevalences were calculated as percentages (%) with a 95% confidence interval (CI). Odds ratios (OR) were computed by multivariate logistic regression to determine the association between socio-demographic factors and VZV seropositivity. Results The VZV seropositivity rate was 80.3% (95% CI: 79.3–81.3) in varicella-unvaccinated children and adolescents. VZV seropositivity rates differed significantly between age groups up to age 6 years, but not by gender. Of 118 retested serum samples with an equivocal ELISA result, 45.8% were FAMA-positive. The proportion of samples tested as false-negative in by ELISA varied by age group: 2.6% in children aged 1–6 and 9% in children aged 7–17 years. Multivariate analyses showed that age, having older siblings, and early daycare start were associated with seropositivity in preschoolers; migration background reduced the chance of VZV seropositivity in schoolchildren (OR: 0.65; 0.43–0.99) and adolescents (OR: 0.62; 0.4–0.97). Conclusion In the pre-varicella vaccine era, most children in Germany contracted varicella by age six. Schoolchildren with a migration background and children without siblings have an increased risk of being VZV seronegative and should be targeted for catch-up vaccination, if they have no history of chickenpox. ELISAs are suitable for use in population-level serosurveys on VZV, but samples with equivocal ELISA results should be retested by FAMA.

Erratum zu: Bundesgesundheitsbl 2018 https://doi.org/10.1007/s00103-018-2761-8 Die Originalveroffentlichung dieses Artikels enthielt einen Fehler in der Autorenliste, in der der beitragende Autor Herr Professor Johannes G. Liese fehlte. Die Autorenliste wurde nun …

Two rotavirus (RV) vaccines were introduced to the European market in 2006. To support the decision-making process of the German Standing Committee on Vaccination ("Standige Impfkommission", STIKO) regarding adoption of routine RV vaccination into the national vaccination schedule in Germany relevant scientific background was reviewed. According to STIKO’s Standard Operating Procedures for the development of evidence-based vaccination recommendations, a set of key questions was addressed and systematic reviews were performed with a focus on the efficacy, effectiveness, impact and safety of RV vaccines. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to assess the quality of available evidence. Data from 5 randomized controlled trials demonstrated a high efficacy of RV vaccines in preventing severe RV-associated gastroenteritis (91%) and hospitalization (92%) in settings comparable to Germany. Post-marketing observational studies confirmed these findings. In several countries, impact studies suggest that age groups not eligible for vaccination might also benefit from herd effects and demonstrated a decrease in the number of nosocomial RV infections after RV vaccine introduction. The vaccines were considered safe, except for a slightly increased risk of intussusception shortly after the first dose, corresponding to 1-2 additional cases per 100,000 infants vaccinated (relative risk =1.21, 95% confidence interval [CI] 0.68-2.14). RV case-fatality is extremely low in Germany. However, RV incidence among children aged

Seit Februar bzw. Juni 2006 stehen in Deutschland 2 Rotavirusimpfstoffe zur Verfugung, deren Vertraglichkeit, Wirksamkeit und Sicherheit in grosen klinischen Studien nachgewiesen wurde. Die Standige Impfkommission (STIKO) hat die Impfung gegen Rotaviren fur Sauglinge bisher nicht generell empfohlen. Auf Grundlage der Meldedaten am Robert Koch-Institut sowie nationalen und internationalen epidemiologischen Studien kann die Relevanz von Rotaviruserkrankungen – insbesondere fur Sauglinge und Kleinkinder – eingeschatzt werden. Die Krankheitslast von Rotaviruserkrankungen in Deutschland ergibt sich dabei aus der Haufigkeit der Erkrankung und der Anzahl der Hospitalisierungen, jedoch nicht aus der Schwere der Erkrankung. Eine generelle Impfung gegen Rotaviren konnte zwar zu einer Minderung der Morbiditat von Sauglingen und Kleinkindern sowie zu einer Reduktion der entstehenden Kosten im Zusammenhang mit Rotaviruserkrankungen fuhren; sie ist aber bei den derzeitigen Impfstoffkosten nicht kostenneutral.

In 2003, a nationwide cross-sectional study was conducted to assess the current influenza vaccination coverage of the adult population of Germany, especially in persons belonging to defined target groups. Of 666 surveyed persons, 190 (adjusted 24%) had received influenza vaccination and 419 participants belonged to at least one target group. Of those, 28% (95% confidence interval (CI) 22–35%) in former West Germany and 45% (95% CI 38–52%) in former East Germany had received influenza vaccination. The offer for vaccination by a physician was associated with a high likelihood for vaccination (odds ratio (OR) 19.0; 95% CI 8.9–40.6). Another important factor influencing vaccination uptake was having received influenza vaccination in prior seasons (OR 7.1; 95% CI 3.8–13.2). Vaccination coverage in the adult population of Germany remains unsatisfactory. Physicians have an important role and should be targeted for campaigns to offer the vaccination more frequently in particular to persons belonging to target groups.

Background: Rotavirus (RV) infection is the leading cause of acute gastroenteritis in young children worldwide. In 2006, 2 live-attenuated RV-vaccines became available for use in infants ≤6 months of age. In Germany, a statutory notification system for RV infection has been in place since 2001 to monitor RV epidemiology. Our objective was to assess RV disease burden in German children

Vaccination is an effective means of preventing infectious diseases. In Germany, the Standing Vaccination Committee at the Robert Koch Institute (Ständige Impfkommission, STIKO) issues recommendations on vaccination to prevent the occurrence and spread of infectious diseases in the nation's population.Selective literature review, including consideration of the current STIKO recommendations.The annually updated vaccination calendar currently includes recommendations for vaccination against diphtheria, tetanus, pertussis, type b Haemophilus influenzae, hepatitis B, poliomyelitis, and pneumococci, beginning at the age of eight weeks. From the age of twelve months onward, children should be vaccinated against measles, mumps, rubella, varicella, and serogroup C meningococci. In later childhood and adolescence, booster vaccinations are recommended, in addition to the provision of any vaccinations that may have been missed. Girls aged 12 to 17 years should be vaccinated against human papilloma virus. Adults should have their tetanus and diphtheria vaccinations refreshed regularly, and their pertussis vaccination refreshed once; from age 60 onward, they should be vaccinated against pneumococci and influenza.The vaccinations recommended by the STIKO are available to all German citizens free of charge and provide effective protection against infectious disease.

In July 2009, the German Standing Committee on Vaccination (STIKO) modified its recommendations for varicella and pertussis vaccination, based on newly available data on disease epidemiology, vaccine effectiveness (VE) and safety, and an evaluation of the feasibility of the recommended immunisation strategy. The recommendation for varicella vaccine now includes a routine two-dose schedule with the administration of the first dose at the age of 11 to 14 months and the second dose at the age of 15 to 23 months, with a minimum interval of four weeks between these doses. Furthermore, STIKO recommended adding a one-time pertussis booster to the adult vaccination schedule to expand the cocoon strategy in place since 2004. The recommendation of a booster vaccination with an acellular pertussis vaccine every 10 years for persons employed in the care of pre-school children and for healthcare personnel in paediatric, gynaecologic and obstetric health facilities was extended to persons employed in schools and in other institutions caring for older children, and to all healthcare personnel. These recommendations were based on available epidemiological data showing an increase in incidence from 7-10 cases per 100,000 inhabitants in 2002-2004 to over 30 by 2007. Moreover, the high burden of pertussis in infants at 94 hospitalised cases per 100,000 infants in 2007 suggested that the previous cocoon strategy was insufficient.

Immunisation schedules are developed by national committees on immunisation and may differ considerably between the European Union (EU) member states (MS). The European Commission has launched an initiative for a council recommendation with the aim to establish a scientifically substantiated reference childhood immunisation schedule for the EU. In our view this initiative implies the establishment of one European childhood immunisation schedule, which could lead to the perception that this schedule is the only one scientifically justified. The expectations that one uniform immunisation schedule will facilitate mobility of EU residents, improve data collection and increase vaccination coverage are either quantitatively or qualitatively not relevant or even ethically problematic. Arguments that uniform schedules would lead to lower vaccine prices and reduce the need for clinical trials appear to be more relevant but could be addressed more effectively by other measures. On the other hand the following factors may differ substantially between MS and thus support different immunisation schedules, such as (a) values and goals, (b) epidemiological situation, (c) health care delivery system, (d) logistics of vaccine delivery and (e) economic situation. We argue that uniform schedules should not be perceived as a goal in itself but rather as a possibly desired by-product following increasing agreement on goals and values between MS and improved evidence base to be used by national committees on immunisation.

Routine varicella vaccination for children11 months was introduced in Germany in 2004 with three different vaccine brands available. In 2008 and 2009, we investigated seven varicella outbreaks in day-care centres (DCC).Varicella disease and vaccination status of 1084 children was reviewed to evaluate vaccination coverage (VC), brand-specific varicella vaccine effectiveness (VE), and risk factors of breakthrough varicella (BV,42 days after vaccination). A case was defined as a child with acute onset of varicella attending one of the respective DCC at the time of outbreak. Children with a previous history of varicella, age11 months, vaccinated at age11 months or42 days before disease onset or during the outbreak were excluded from VE and BV risk factors analyses (adjusted for gender, age and DCC).Of 631 children with available vaccination information, 392 (62%) were vaccinated at least once. Overall VE among 352 children eligible was 71% (95% confidence interval (CI) 57-81, p0.001) and differed significantly by disease severity and number of doses administered. Risk for BV was higher for 1 dose of Varilrix (RR=2.8, 95%CI 1.0-7.8, p=0.05) or Priorix-Tetra (RR=2.4, 95%CI 0.7-8.3, p=0.18) but lower for 2 doses of Priorix-Tetra (RR=0.5, 95%CI 0.1-2.7, p=0.41) than for 1 dose of Varivax.Enhanced efforts to increase VC in Germany and 2 doses varicella vaccine might be successful to reduce the risk for BV. The evidence that VE and risk of BV are associated with vaccine brand needs further investigation.

An increasing incidence in disease caused by nontuberculous mycobacteria is being reported. We investigated the burden of disease in immunocompetent German children in a prospective nationwide study from April 2003 to September 2005. Ninety-seven percent of children presented with lymphadenitis; median age was 2.5 years. Using the capture-recapture method, we estimated a cumulative incidence rate of 3.1/100000 children.

Background. Skin infections due to Staphylococcus aureus have recently become a public concern, mainly because of emerging resistance against widely used antibiotics and specific virulence determinants. Strains harboring the lukS-lukF gene (which codes for Panton-Valentine leukocidin) are frequently associated with severe furunculosis. Generally applicable strategies for the control of community outbreaks of furunculosis have not been defined. Methods. We report the investigation and successful termination of an outbreak of furunculosis due to lukSlukF–positive S. aureus in a German village ( ). Nasal swab specimens were obtained from village residents. n p 144 A retrospective cohort study was conducted. Nasally colonized persons, persons who had current furuncles or who had experienced relapsing furuncles since 2002, and their family members underwent stringent decolonization measures using mupirocin nasal ointment and disinfecting wash solution. Multiple nasal swab specimens were obtained to monitor the long-term outcome of decolonization measures. Results. From January 1998 through December 2004, 42 cases and 59 relapses of furunculosis were identified by active case finding. Of 140 participants tested, 51 (36%) were found to be nasally colonized with S. aureus .I n 9 participants, the strain was positive for lukS-lukF. No methicillin resistance was detected. Risk of furunculosis was associated with contact with case patients (relative risk, 6.8; 95% confidence interval, 3.2–14.3) and nasal colonization with a lukS-lukF–positive strain of S. aureus (relative risk, 3.6; 95% confidence interval, 2.3–5.9). Passive surveillance implemented in January 2005 did not detect any case of lukS-lukF–positive, S. aureus–associated furuncles in this village. Conclusion. This report describes a successful strategy for terminating the transmission of epidemic strains of S. aureus among a nonhospitalized population.

In July 2006, vaccination against meningococcal C and pneumococcal disease was added to the routine childhood immunisation programme in Germany

This admission prevalence survey is part of the multicenter study ATHOS (antibiotic therapy optimisation study). ATHOS aims at collecting prevalence and incidence data for nosocomial carriage of multi-drug resistant organisms (MDROs) and to intervene in the inpatient and outpatient setting.