Sebastian Haller

Large multistate outbreak of norovirus gastroenteritis associated with frozen strawberries, Germany, 2012

From 20 September through 5 October 2012, the largest recorded food-borne outbreak in Germany occurred. Norovirus was identified as the causative agent. We conducted four analytical epidemiological studies, two case–control studies and two surveys (in total 150 cases) in secondary schools in three different federal states. Overall, 390 institutions in five federal states reported nearly 11,000 cases of gastroenteritis. They were predominantly schools and childcare facilities and were supplied almost exclusively by one large catering company. The analytical epidemiological studies consistently identified dishes containing strawberries as the most likely vehicle, with estimated odds ratios ranging from 2.6 to 45.4. The dishes had been prepared in different regional kitchens of the catering company and were served in the schools two days before the peaks of the respective outbreaks. All affected institutions had received strawberries of one lot, imported frozen from China. The outbreak vehicle was identified within a week, which led to a timely recall and prevented more than half of the lot from reaching the consumer. This outbreak exemplifies the risk of large outbreaks in the era of global food trade. It underlines the importance of timely surveillance and epidemiological outbreak investigations for food safety.

Burden of Six Healthcare-Associated Infections on European Population Health: Estimating Incidence-Based Disability-Adjusted Life Years through a Population Prevalence-Based Modelling Study

Background Estimating the burden of healthcare-associated infections (HAIs) compared to other communicable diseases is an ongoing challenge given the need for good quality data on the incidence of these infections and the involved comorbidities. Based on the methodology of the Burden of Communicable Diseases in Europe (BCoDE) project and 2011–2012 data from the European Centre for Disease Prevention and Control (ECDC) point prevalence survey (PPS) of HAIs and antimicrobial use in European acute care hospitals, we estimated the burden of six common HAIs. Methods and Findings The included HAIs were healthcare-associated pneumonia (HAP), healthcare-associated urinary tract infection (HA UTI), surgical site infection (SSI), healthcare-associated Clostridium difficile infection (HA CDI), healthcare-associated neonatal sepsis, and healthcare-associated primary bloodstream infection (HA primary BSI). The burden of these HAIs was measured in disability-adjusted life years (DALYs). Evidence relating to the disease progression pathway of each type of HAI was collected through systematic literature reviews, in order to estimate the risks attributable to HAIs. For each of the six HAIs, gender and age group prevalence from the ECDC PPS was converted into incidence rates by applying the Rhame and Sudderth formula. We adjusted for reduced life expectancy within the hospital population using three severity groups based on McCabe score data from the ECDC PPS. We estimated that 2,609,911 new cases of HAI occur every year in the European Union and European Economic Area (EU/EEA). The cumulative burden of the six HAIs was estimated at 501 DALYs per 100,000 general population each year in EU/EEA. HAP and HA primary BSI were associated with the highest burden and represented more than 60% of the total burden, with 169 and 145 DALYs per 100,000 total population, respectively. HA UTI, SSI, HA CDI, and HA primary BSI ranked as the third to sixth syndromes in terms of burden of disease. HAP and HA primary BSI were associated with the highest burden because of their high severity. The cumulative burden of the six HAIs was higher than the total burden of all other 32 communicable diseases included in the BCoDE 2009–2013 study. The main limitations of the study are the variability in the parameter estimates, in particular the disease models’ case fatalities, and the use of the Rhame and Sudderth formula for estimating incident number of cases from prevalence data. Conclusions We estimated the EU/EEA burden of HAIs in DALYs in 2011–2012 using a transparent and evidence-based approach that allows for combining estimates of morbidity and of mortality in order to compare with other diseases and to inform a comprehensive ranking suitable for prioritization. Our results highlight the high burden of HAIs and the need for increased efforts for their prevention and control. Furthermore, our model should allow for estimations of the potential benefit of preventive measures on the burden of HAIs in the EU/EEA.

Contamination during production of heater-cooler units by Mycobacterium chimaera potential cause for invasive cardiovascular infections: results of an outbreak investigation in Germany, April 2015 to February 2016

Invasive infections with Mycobacterium chimaera were reported in patients with previous open chest surgery and exposure to contaminated heater-cooler units (HCUs). We present results of the surveillance of clinical cases and of contaminated HCUs as well as environmental investigations in Germany up until February 2016. Clinical infections occurred in five male German cases over 50 years of age (range 53-80). Cases had been exposed to HCUs from one single manufacturer during open chest surgery up to five years prior to onset of symptoms. During environmental investigations, M. chimaera was detected in samples from used HCUs from three different countries and samples from new HCUs as well as in the environment at the manufacturing site of one manufacturer in Germany. Our investigation suggests that at least some of the M. chimaera infections may have been caused by contamination of HCUs at manufacturing site. We recommend that until sustainable measures for safe use of HCUs in operation theatres are implemented, users continue to adhere to instructions for use of HCUs and Field Safety Notices issued by the manufacturer, implement local monitoring for bacterial contamination and continuously check the websites of national and European authorities for current recommendations for the safe operation of HCUs.

Results from the First 12 Months of the National Surveillance of Healthcare Associated Outbreaks in Germany, 2011/2012

Background In August 2011, the German Protection against Infection Act was amended, mandating the reporting of healthcare associated infection (HAI) outbreak notifications by all healthcare workers in Germany via local public health authorities and federal states to the Robert Koch Institute (RKI). Objective To describe the reported HAI-outbreaks and the surveillance system’s structure and capabilities. Methods Information on each outbreak was collected using standard paper forms and notified to RKI. Notifications were screened daily and regularly analysed. Results Between November 2011 and November 2012, 1,326 paper forms notified 578 HAI-outbreaks, between 7 and 116 outbreaks per month. The main causative agent was norovirus (n = 414/578; 72%). Among the 108 outbreaks caused by bacteria, the most frequent pathogens were Clostridium difficile (25%) Klebsiella spp. (19%) and Staphylococcus spp. (19%). Multidrug-resistant bacteria were responsible for 54/108 (50%) bacterial outbreaks. Hospitals were affected most frequently (485/578; 84%). Hospital outbreaks due to bacteria were mostly reported from intensive care units (ICUs) (45%), followed by internal medicine wards (16%). Conclusion The mandatory HAI-outbreak surveillance system describes common outbreaks. Pathogens with a particular high potential to cause large or severe outbreaks may be identified, enabling us to further focus research and preventive measures. Increasing the sensitivity and reliability of the data collection further will facilitate identification of outbreaks able to increase in size and severity, and guide specific control measures to interrupt their propagation.

Effectiveness of routine and booster pertussis vaccination in children and adolescents, federal state of Brandenburg, Germany, 2002-2012.

Background: In Germany, whole-cell pertussis vaccines were rapidly replaced by high-concentration acellular pertussis-containing vaccines (3+1 doses from 2 months of age) starting in 1995. Boosters were recommended for 9- to 17-year-olds (2000) and for 5- to 6-year-olds (2006). Pertussis incidence remains high despite rising vaccination coverage (VC). Therefore, we analyzed VC and vaccine effectiveness (VE) in the federal state of Brandenburg. Methods: In a stratified case–cohort analysis, we compared VC of reported pertussis cases with VC assessed in schools and kindergartens in the following strata: Children aged 2–3 years born 2005–2009 (toddlers), 5–7 years born 1995–2006 (pre-schoolers) and 15–16 years born 1995–1996 (adolescents). We calculated VE for primary and booster vaccination using Poisson regression. Results: Four-dose VE decreased from 96.9% in toddlers [95% confidence interval (CI): 72.2–99.3] to 87.8% in pre-schoolers (95% CI: 79.7–92.7) to 81.7% in adolescents (95% CI: 40.6–92.8). Four-dose VE was lower in pre-schoolers born after 1996 (75.4%) than in those born 1995–1996, ~1% and ~21% of whom had received ≥1 dose of whole-cell pertussis vaccines, respectively. VE was higher in pre-schoolers and adolescents who received a booster (92.8%and 96.5%, respectively). However, overall booster VC was only 19% and 76% in these age groups, respectively. Conclusions: We observed high VE of routine pertussis vaccination, with evidence of waning over time and improved VE after booster vaccination. Increased uptake and monitoring of recommended pertussis boosters is urgently recommended to decrease high pertussis morbidity particularly in older children and adolescents.

Neurological sequelae of healthcare-associated sepsis in very-low-birthweight infants: Umbrella review and evidence-based outcome tree

Sepsis is a frequent cause of death in very-low-birthweight infants and often results in neurological impairment. Its attributable risk of sequelae has not been systematically assessed. To establish an outcome tree for mapping the burden of neonatal sepsis, we performed systematic literature searches to identify systematic reviews addressing sequelae of neonatal sepsis. We included cohort studies and performed meta-analyses of attributable risks. Evidence quality was assessed using GRADE. Two systematic reviews met inclusion criteria. The first included nine cohort studies with 5,620 participants and five outcomes (neurodevelopmental impairment, cerebral palsy, vision impairment, hearing impairment, death). Pooled risk differences varied between 4% (95% confidence interval (CI):2-10) and 13% (95% CI:5-20). From the second review we analysed four studies with 472 infants. Positive predictive value of neurodevelopmental impairment for later cognitive impairment ranged between 67% (95% CI:22-96) and 83% (95% CI:36-100). Neonatal sepsis increases risk of permanent neurological impairment. Effect size varies by outcome, with evidence quality being low to very low. Data were used to construct an outcome tree for neonatal sepsis. Attributable risk estimates for sequelae following neonatal sepsis are suitable for burden estimation and may serve as outcome parameters in interventional studies.

Letter to the editor: Is there a need for special treatment of refugees at hospital admission?

To the editor: Two recent publications by Reinheimer et al. and Heudorf et al. in Eurosurveillance, provided data on multidrug-resistant bacteria obtained from screening of different refugee populations and concluded that additional screening or surveillance for refugees at hospital admission in Germany should be undertaken [1,2]. The high number of people currently migrating to Europe from disaster areas has sparked a debate, whether or not refugees should be screened at hospital admission for colonisation with multidrug-resistant bacteria to limit spread of antibiotic resistance within Europe. The possible negative consequences of screening and lacking data make this a more complex issue than it may seem at first.

Incidence of invasive meticillin-resistant Staphylococcus aureus infections in Germany, 2010 to 2014.

Voluntary surveillance systems in Germany suggest a recent decline in the incidence of infections (subsequent to at least 2010) with meticillin-resistant Staphylococcus aureus (MRSA) from various types of specimens and settings. We asked whether this decline is reflected by data from the mandatory national surveillance system for invasive MRSA infections. Our analysis is based on the population in Germany in 2010 to 2014. Cases were identified from passive reporting by microbiological laboratories of the diagnosis of MRSA from blood culture or cerebrospinal fluid. Respective clinical data were subsequently added to the notification. We calculated risk ratios (RR) between consecutive years, stratifying cases by sex, age and federal state of residence. The national incidence increased from 4.6 episodes per 100,000 persons in 2010 to 5.6 in 2012 (2011 vs 2010: RR: 1.13, 95% confidence interval (CI): 1.08-1.18; 2012 vs 2011: RR: 1.08, 95% CI: 1.04-1.13). It stagnated at 5.4 per 100,000 in 2013 (RR: 0.97, 95% CI: 0.93-1.01) before declining to 4.8 in 2014 (RR: 0.88, 95% CI: 0.84-0.91). This trend was observed in most, but not all federal states and strata of sex and age groups. Only 204 of 20,679 (1%) episodes of infection were notified as belonging to an outbreak. Our analysis corroborates previous findings that the incidence of invasive MRSA infections in Germany may be declining.

Whole Genome Sequence Analysis of CTX-M-15 Producing Klebsiella Isolates Allowed Dissecting a Polyclonal Outbreak Scenario

Extended-spectrum β-lactamase (ESBL) producing Klebsiella pneumoniae pose an important threat of infection with increased morbidity and mortality, especially for immunocompromised patients. Here, we use the rise of multidrug-resistant K. pneumoniae in a German neurorehabilitation center from April 2015 to April 2016 to dissect the benefit of whole genome sequencing (WGS) for outbreak analyses. In total, 53 isolates were obtained from 52 patients and examined using WGS. Two independent analysis strategies (reference-based and -free) revealed the same distinct clusters of two CTX-M-15 producing K. pneumoniae clones (ST15, n = 31; ST405, n = 7) and one CTX-M-15 producing Klebsiella quasipneumoniae strain (ST414, n = 8). Additionally, we determined sequence variations associated with antimicrobial resistance phenotypes in single isolates expressing carbapenem and colistin resistance, respectively. For rapid detection of the major K. pneumoniae outbreak clone (ST15), a selective triplex PCR was deduced from WGS data of the major outbreak strain and K. pneumoniae genome data deposited in central databases. Moreover, we introduce two novel open-source applications supporting reference genome selection (refRank; https://gitlab.com/s.fuchs/refRank) and alignment-based SNP-filtering (SNPfilter; https://gitlab.com/s.fuchs/snpfilter) in NGS analyses.

Predicting late-onset sepsis by routine neonatal screening for colonisation by gram-negative bacteria in neonates at intensive care units: a protocol for a systematic review

Introduction Hospitals conduct extensive screening procedures to assess colonisation of the body surface of neonates by gram-negative bacteria to avoid complications like late-onset sepsis. However, the benefits of these procedures are controversially discussed. Until now, no systematic review has investigated the value of routine screening for colonisation by gram-negative bacteria in neonates for late-onset sepsis prediction. Methods and analysis We will conduct a systematic review, considering studies of any design that include infants up to an age of 12 months. We will search MEDLINE and EMBASE (inception to 2016), reference lists and grey literature. Screening of titles, abstracts and full texts will be conducted by two independent reviewers. We will extract data on study characteristics and study results. Risk of bias will be assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Quality in Prognosis Studies (QUIPS) tools. Subgroup analyses are planned according to characteristics of studies, participants, index tests and outcome. For quantitative data synthesis on prognostic accuracy, sensitivity and specificity of screening to detect late-onset sepsis will be calculated. If sufficient data are available, we will calculate summary estimates using hierarchical summary receiver operating characteristics and bivariate models. Applying a risk factor approach, pooled summary estimates will be calculated as relative risk or OR, using fixed-effects and random-effects models. I-squared will be used to assess heterogeneity. All calculations will be performed in Stata V14.1 (College Station, Texas, USA). The results will be used to calculate positive and negative predictive value and number needed to be screened to prevent one case of sepsis. Grading of Recommendations Assessment, Development and Evaluation (GRADE) will be used to assess certainty in the evidence. The protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guideline. Ethics and dissemination This study will not require ethical approval since it is not carried out in humans. The systematic review will be published in an open-access peer-reviewed journal. Trial registration number CRD42016036664.