Muna Abu Sin

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.

What caused the outbreak of ESBL-producing Klebsiella pneumoniae in a neonatal intensive care unit, Germany 2009 to 2012? Reconstructing transmission with epidemiological analysis and whole-genome sequencing

Objective We aimed to retrospectively reconstruct the timing of transmission events and pathways in order to understand why extensive preventive measures and investigations were not sufficient to prevent new cases. Methods We extracted available information from patient charts to describe cases and to compare them to the normal population of the ward. We conducted a cohort study to identify risk factors for pathogen acquisition. We sequenced the available isolates to determine the phylogenetic relatedness of Klebsiella pneumoniae isolates on the basis of their genome sequences. Results The investigation comprises 37 cases and the 10 cases with ESBL (extended-spectrum beta-lactamase)-producing K. pneumoniae bloodstream infection. Descriptive epidemiology indicated that a continuous transmission from person to person was most likely. Results from the cohort study showed that ‘frequent manipulation’ (a proxy for increased exposure to medical procedures) was significantly associated with being a case (RR 1.44, 95% CI 1.02 to 2.19). Genome sequences revealed that all 48 bacterial isolates available for sequencing from 31 cases were closely related (maximum genetic distance, 12 single nucleotide polymorphisms). Based on our calculation of evolutionary rate and sequence diversity, we estimate that the outbreak strain was endemic since 2008. Conclusions Epidemiological and phylogenetic analyses consistently indicated that there were additional, undiscovered cases prior to the onset of microbiological screening and that the spread of the pathogen remained undetected over several years, driven predominantly by person-to-person transmission. Whole-genome sequencing provided valuable information on the onset, course and size of the outbreak, and on possible ways of transmission.

Carrier Prevalence, Secondary Household Transmission, and Long-Term Shedding in 2 Districts During the Escherichia coli O104:H4 Outbreak in Germany, 2011

BACKGROUND From May through July 2011, Germany experienced a large outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 infection. Our objective was to identify the prevalence of STEC O104:H4 carriers in households in highly affected areas, the rate of secondary household transmissions, and the duration of long-term shedding. METHODS In a cross-sectional study, we recruited case and control households to determine STEC household prevalence. We then conducted a prospective cohort study (households with ≥ 2 members and ≥ 1 case) to determine rates of household transmission and shedding duration. RESULTS For part 1, we recruited 57 case households (62 case patients and 93 household contacts) and 36 control households (89 household members). We only detected cases in previously known case households and identified 1 possible adult-to-adult household transmission. For part 2, we followed 14 households and 20 carriers. No secondary household transmission was detected in the prospective follow-up period. In 1 adult carrier, shedding lasted >7 months. However, the median estimated shedding time was 10-14 days (95% confidence interval, 0-33 days). Three carriers showed intermittent shedding. CONCLUSIONS The prevalence of STEC O104:H4 carriers even in highly affected areas appears to be low. Despite prolonged shedding in some patients, secondary adult-to-adult household transmissions seem to be rare events in the postdiarrheal disease phase.

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.

Towards a framework for evaluating and grading evidence in public health.

The Project on a Framework for Rating Evidence in Public Health (PRECEPT) is an international collaboration of public health institutes and universities which has been funded by the European Centre for Disease Prevention and Control (ECDC) since 2012. Main objective is to define a framework for evaluating and grading evidence in the field of public health, with particular focus on infectious disease prevention and control. As part of the peer review process, an international expert meeting was held on 13-14 June 2013 in Berlin. Participants were members of the PRECEPT team and selected experts from national public health institutes, World Health Organization (WHO), and academic institutions. The aim of the meeting was to discuss the draft framework and its application to two examples from infectious disease prevention and control. This article introduces the draft PRECEPT framework and reports on the meeting, its structure, most relevant discussions and major conclusions.

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.

The zoonotic potential of Clostridium difficile from small companion animals and their owners

Background Clostridium difficile infections (CDI) in humans range from asymptomatic carriage to life-threatening intestinal disease. Findings on C. difficile in various animal species and an overlap in ribotypes (RTs) suggest potential zoonotic transmission. However, the impact of animals for human CDI remains unclear. Methods In a large-scale survey we collected 1,447 fecal samples to determine the occurrence of C. difficile in small companion animals (dogs and cats) and their owners and to assess potential epidemiological links within the community. The Germany-wide survey was conducted from July 2012-August 2013. PCR ribotyping, Multilocus VNTR Analysis (MLVA) and PCR detection of toxin genes were used to characterize isolated C. difficile strains. A database was defined and logistic regression used to identify putative factors associated with fecal shedding of C. difficile. Results In total, 1,418 samples met the inclusion criteria. The isolation rates for small companion animals and their owners within the community were similarly low with 3.0% (25/840) and 2.9% (17/578), respectively. PCR ribotyping revealed eight and twelve different RTs in animals and humans, respectively, whereas three RTs were isolated in both, humans and animals. RT 014/0, a well-known human hospital-associated lineage, was predominantly detected in animal samples. Moreover, the potentially highly pathogenic RTs 027 and 078 were isolated from dogs. Even though, C. difficile did not occur simultaneously in animals and humans sharing the same household. The results of the epidemiological analysis of factors associated with fecal shedding of C. difficile support the hypothesis of a zoonotic potential. Conclusions Molecular characterization and epidemiological analysis revealed that the zoonotic risk for C. difficile associated with dogs and cats within the community is low but cannot be excluded.