Point of Care Testing for Infectious Disease in Europe: A Scoping Review and Survey Study.

Background: Point of care testing (POCT) for infectious diseases is testing conducted near the patient. It allows clinicians to offer the most appropriate treatment more quickly. As POCT devices have increased in accuracy and become more cost-effective, their use has grown, but a systematic assessment of their use for clinical and public health management of infectious diseases in EU/EEA countries has not been previously undertaken. Methods: A scoping review of the literature on POCT in EU/ EEA countries as at November 2019, and a survey of key stakeholders. Results: 350 relevant articles were identified and 54 survey responses from 26 EU/EEA countries were analysed. POCT is available for a range of infectious diseases and in all countries responding to the survey (for at least one disease). POCT is commonly available for influenza, HIV/AIDS, Legionnaires' disease and malaria, where it is used in at least half of EU/EEA countries. While POCT has the potential to support many improvements to clinical care of infectious diseases (e.g., faster diagnosis, more appropriate use of antimicrobials), the results suggest POCT is infrequently used to support public health functions (e.g., disease surveillance and reporting). Conclusion: Although POCT is in use to some extent in all EU/EEA countries, the full benefits of POCT in wider public health functions have yet to be realised. Further research on barriers and facilitators to implementation is warranted.

COVID-19 Research: Challenges to Interpret Numbers and Propose Solutions.

The response of the scientific community to the COVID-19 pandemic has been unprecedented in size, speed and discovery output. Within months of virus emergence, the SARS-CoV-2 genomics, replication, evolution and dissemination dynamics as well as natural history, infection risk and prognostic factors and biology of the disease have been gradually deciphered. More than 250 articles on COVID-19 published in Frontiers in Public Health have contributed to these insights. We discuss here some of the key research themes and challenges that have been addressed. We provide our perspective on current research issues with surveillance data quality and limitations of epidemiological methods. We warn against the potential misuse or misleading interpretation of public data of variable quality and the use of inadequate study designs for the evaluation of effect of non-pharmaceutical interventions. We conclude by interrogating possible public health strategies for pandemic control as well as discuss the ethical responsibilities and democratic accountability of researchers in their role as experts and policy advisors.

Epidemiological situation, laboratory capacity and preparedness for carbapenem-resistant Acinetobacter baumannii in Europe, 2019.

To update information on the epidemiological situation and national capacity for detection, surveillance and containment of carbapenem-resistant Acinetobacter baumannii (CRAb) in Europe, we performed a survey in 37 countries. Nine countries reported regional or inter-regional spread and seven an endemic situation. Laboratories with a reference function, surveillance systems, and a national containment plan for CRAb existed in 30, 23 and eight countries, respectively. A pan-European molecular survey would provide in-depth understanding of the CRAb epidemiology.

Automated digital reporting of clinical laboratory information to national public health surveillance systems, results of a EU/EEA survey, 2018.

BackgroundTimely reporting of microbiology test results is essential for infection management. Automated, machine-to-machine (M2M) reporting of diagnostic and antimicrobial resistance (AMR) data from laboratory information management systems (LIMS) to public health agencies improves timeliness and completeness of communicable disease surveillance.AimWe surveyed microbiology data reporting practices for national surveillance of EU-notifiable diseases in European Union/European Economic Area (EU/EEA) countries in 2018.MethodsEuropean Centre for Disease Prevention and Control (ECDC) National Microbiology and Surveillance Focal Points completed a questionnaire on the modalities and scope of clinical microbiology laboratory data reporting.ResultsComplete data were provided for all 30 EU/EEA countries. Clinical laboratories used a LIMS in 28 countries. LIMS data on EU-notifiable diseases and AMR were M2M-reported to the national level in 14 and nine countries, respectively. In the 14 countries, associated demographic data reported allowed the de-duplication of patient reports. In 13 countries, M2M-reported data were used for cluster detection at the national level. M2M laboratory data reporting had been validated against conventional surveillance methods in six countries, and replaced those in five. Barriers to M2M reporting included lack of information technology support and financial incentives.ConclusionM2M-reported laboratory data were used for national public health surveillance and alert purposes in nearly half of the EU/EEA countries in 2018. Reported data on infectious diseases and AMR varied in extent and disease coverage across countries and laboratories. Improving automated laboratory-based surveillance will depend on financial and regulatory incentives, and harmonisation of health information and communication systems.

Cross-border spread of blaNDM-1- and blaOXA-48-positive Klebsiella pneumoniae: a European collaborative analysis of whole genome sequencing and epidemiological data, 2014 to 2019.

Analysis of sequencing data for 143 blaNDM-1- and blaOXA-48-positive Klebsiella pneumoniae isolates from 13 European national collections and the public domain resulted in the identification of 15 previously undetected multi-country transmission clusters. For 10 clusters, cases had prior travel/hospitalisation history in countries outside of the European Union including Egypt, Iran, Morocco, Russia, Serbia, Tunisia and Turkey. These findings highlight the benefit of European whole genome sequencing-based surveillance and data sharing for control of antimicrobial resistance.

Worsening epidemiological situation of carbapenemase-producing Enterobacteriaceae in Europe, assessment by national experts from 37 countries, July 2018.

A survey on the epidemiological situation, surveillance and containment activities for carbapenemase-producing Enterobacteriaceae (CPE) was conducted in European countries in 2018. All 37 participating countries reported CPE cases. Since 2015, the epidemiological stage of CPE expansion has increased in 11 countries. Reference laboratory capability, dedicated surveillance and a specific national containment plan are in existence in 33, 27 and 14 countries, respectively. Enhanced control efforts are needed for CPE containment in Europe.

Investing in Public Health Microbiology Laboratories in Western Balkan Countries Enhances Health Security From Communicable Disease Threats in Europe.

The European Centre for Disease Prevention and Control (ECDC), under the EU enlargement policy, has supported national efforts of Western Balkan countries to strengthen their communicable disease prevention and control systems. The new EU strategy "A credible enlargement perspective for and enhanced EU engagement with the Western Balkans" advocates transformation processes that will build the foundation of EU-oriented national reforms. Well-functioning public health microbiology laboratories are key for early detection and control of infectious diseases, and thus maintaining and enhancing health security in Europe. In order to help Western Balkan countries to improve their national capacities, ECDC facilitated needs assessments and identified key areas for advancement toward effective public health microbiology systems. Countries identified gaps in their laboratory data reporting and exchange systems. Harmonized and effective procedures for handling of highly contagious agents and cross-border transportation of biological samples were often lacking, as well as the systematic use of diagnostic testing at the primary care level or referral of patients, in particular for detection of antimicrobial resistance. There is a clear need to address the financial investment required for sustaining sufficient numbers of skilled laboratory workforce, laboratory supplies, and the development of new methods and techniques, including investment in emerging laboratory technologies, such as molecular typing by whole genome sequencing. This article highlights the key areas for investing in public health microbiology laboratories in Western Balkan countries needed to strengthen health security in Europe.

Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis.

BACKGROUND: Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs). METHODS: We estimated the incidence of infections with 16 antibiotic resistance-bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011-12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature. FINDINGS: From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148-763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480-38 430) attributable deaths and 874 541 (768 837-989 068) DALYs. The burden for the EU and EEA was highest in infants (aged <1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece. INTERPRETATION: Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases. FUNDING: European Centre for Disease Prevention and Control.

Candida auris: epidemiological situation, laboratory capacity and preparedness in European Union and European Economic Area countries, 2013 to 2017.

During 2013-2017, 620 cases of Candida auris were reported in the European Union/European Economic Area - 466 (75.2%) colonisations, 110 (17.7%) bloodstream infections, 40 (6.5%) other infections and four cases (0.6%) of unknown colonisation/infection status - the majority from four large outbreaks. Survey results showed that several countries lacked laboratory capacity and/or information on the occurrence of cases at national level. To prevent further spread, adequate laboratory capacity and infection control preparedness is required in Europe.

Networking of Public Health Microbiology Laboratories Bolsters Europe's Defenses against Infectious Diseases.

In an era of global health threats caused by epidemics of infectious diseases and rising multidrug resistance, microbiology laboratories provide essential scientific evidence for risk assessment, prevention, and control. Microbiology has been at the core of European infectious disease surveillance networks for decades. Since 2010, these networks have been coordinated by the European Centre for Disease Prevention and Control (ECDC). Activities delivered in these networks include harmonization of laboratory diagnostic, antimicrobial susceptibility and molecular typing methods, multicentre method validation, technical capacity mapping, training of laboratory staff, and continuing quality assessment of laboratory testing. Cooperation among the European laboratory networks in the past 7 years has proved successful in strengthening epidemic preparedness by enabling adaptive capabilities for rapid detection of emerging pathogens across Europe. In partnership with food safety authorities, international public health agencies and learned societies, ECDC-supported laboratory networks have also progressed harmonization of routinely used antimicrobial susceptibility and molecular typing methods, thereby significantly advancing the quality, comparability and precision of microbiological information gathered by ECDC for surveillance for zoonotic diseases and multidrug-resistant pathogens in Europe. ECDC continues to act as a catalyst for sustaining continuous practice improvements and strengthening wider access to laboratory capacity across the European Union. Key priorities include optimization and broader use of rapid diagnostics, further integration of whole-genome sequencing in surveillance and electronic linkage of laboratory and public health systems. This article highlights some of the network contributions to public health in Europe and the role that ECDC plays managing these networks.

Control of Infectious Diseases in the Era of European Clinical Microbiology Laboratory Consolidation: New Challenges and Opportunities for the Patient and for Public Health Surveillance.

Many new innovative diagnostic approaches have been made available during the last 10 years with major impact on patient care and public health surveillance. In parallel, to enhance the cost-effectiveness of the clinical microbiology laboratories (CMLs), European laboratory professionals have streamlined their organization leading to amalgamation of activities and restructuring of their professional relationships with clinicians and public health specialists. Through this consolidation process, an operational model has emerged that combines large centralized clinical laboratories performing most tests on one high-throughput analytical platform connected to several distal laboratories dealing locally with urgent analyses at near point of care. The centralization of diagnostic services over a large geographical region has given rise to the concept of regional-scale "microbiology laboratories network." Although the volume-driven cost savings associated with such laboratory networks seem self-evident, the consequence(s) for the quality of patient care and infectious disease surveillance and control remain less obvious. In this article, we describe the range of opportunities that the changing landscape of CMLs in Europe can contribute toward improving the quality of patient care but also the early detection and enhanced surveillance of public health threats caused by infectious diseases. The success of this transformation of health services is reliant on the appropriate preparation in terms of staff, skills, and processes that would be inclusive of stakeholders. In addition, rigorous metrics are needed to set out more concrete laboratory service performance objectives and assess the expected benefits to society in terms of saving lives and preventing diseases.

Livestock-associated meticillin-resistant Staphylococcus aureus (MRSA) among human MRSA isolates, European Union/European Economic Area countries, 2013.

Currently, surveillance of livestock-associated meticillin-resistant Staphylococcus aureus (LA-MRSA) in humans in Europe is not systematic but mainly event-based. In September 2014, the European Centre for Disease Prevention and Control (ECDC) initiated a questionnaire to collect data on the number of LA-MRSA from human samples (one isolate per patient) from national/regional reference laboratories in European Union/European Economic Area (EU/EEA) countries in 2013. Identification of LA-MRSA as clonal complex (CC) 398 by multilocus sequence typing (MLST) was preferred, although surrogate methods such as spa-typing were also accepted. The questionnaire was returned by 28 laboratories in 27 EU/EEA countries. Overall, LA-MRSA represented 3.9% of 13,756 typed MRSA human isolates, but it represented ≥ 10% in five countries (Belgium, Denmark, Spain, the Netherlands and Slovenia). Seven of the reference laboratories did not type MRSA isolates in 2013. To monitor the dispersion of LA-MRSA and facilitate targeted control measures, we advocate periodic systematic surveys or integrated multi-sectorial surveillance.

Survey on the Use of Whole-Genome Sequencing for Infectious Diseases Surveillance: Rapid Expansion of European National Capacities, 2015-2016.

Whole-genome sequencing (WGS) has become an essential tool for public health surveillance and molecular epidemiology of infectious diseases and antimicrobial drug resistance. It provides precise geographical delineation of spread and enables incidence monitoring of pathogens at genotype level. Coupled with epidemiological and environmental investigations, it delivers ultimate resolution for tracing sources of epidemic infections. To ascertain the level of implementation of WGS-based typing for national public health surveillance and investigation of prioritized diseases in the European Union (EU)/European Economic Area (EEA), two surveys were conducted in 2015 and 2016. The surveys were designed to determine the national public health reference laboratories' access to WGS and operational WGS-based typing capacity for national surveillance of selected foodborne pathogens, antimicrobial-resistant pathogens, and vaccine-preventable diseases identified as priorities for European genomic surveillance. Twenty-eight and twenty-nine out of the 30 EU/EEA countries participated in the survey in 2015 and 2016, respectively. National public health reference laboratories in 22 and 25 countries had access to WGS-based typing for public health applications in 2015 and 2016, respectively. Reported reasons for limited or no access were lack of funding, staff, and expertise. Illumina technology was the most frequently used followed by Ion Torrent technology. The access to bioinformatics expertise and competence for routine WGS data analysis was limited. By mid-2016, half of the EU/EEA countries were using WGS analysis either as first- or second-line typing method for surveillance of the pathogens and antibiotic resistance issues identified as EU priorities. The sampling frame as well as bioinformatics analysis varied by pathogen/resistance issue and country. Core genome multilocus allelic profiling, also called cgMLST, was the most frequently used annotation approach for typing bacterial genomes suggesting potential bioinformatics pipeline compatibility. Further capacity development for WGS-based typing is ongoing in many countries and upon consolidation and harmonization of methods should enable pan-EU data exchange for genomic surveillance in the medium-term subject to the development of suitable data management systems and appropriate agreements for data sharing.

Carbapenemase-producing Enterobacteriaceae in Europe: assessment by national experts from 38 countries, May 2015.

In 2012, the European Centre for Disease Prevention and Control (ECDC) launched the 'European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE)' project to gain insights into the occurrence and epidemiology of carbapenemase-producing Enterobacteriaceae (CPE), to increase the awareness of the spread of CPE, and to build and enhance the laboratory capacity for diagnosis and surveillance of CPE in Europe. Data collected through a post-EuSCAPE feedback questionnaire in May 2015 documented improvement compared with 2013 in capacity and ability to detect CPE and identify the different carbapenemases genes in the 38 participating countries, thus contributing to their awareness of and knowledge about the spread of CPE. Over the last two years, the epidemiological situation of CPE worsened, in particular with the rapid spread of carbapenem-hydrolysing oxacillinase-48 (OXA-48)- and New Delhi metallo-beta-lactamase (NDM)-producing Enterobacteriaceae. In 2015, 13/38 countries reported inter-regional spread of or an endemic situation for CPE, compared with 6/38 in 2013. Only three countries replied that they had not identified one single case of CPE. The ongoing spread of CPE represents an increasing threat to patient safety in European hospitals, and a majority of countries reacted by establishing national CPE surveillances systems and issuing guidance on control measures for health professionals. However, 14 countries still lacked specific national guidelines for prevention and control of CPE in mid-2015.

Impact of rapid molecular screening at hospital admission on nosocomial transmission of methicillin-resistant Staphylococcus aureus: cluster randomised trial.

DESIGN: Cluster randomised crossover trial with seven wards randomly allocated to intervention or control arm. SETTING: Medical and surgical wards of a university hospital with active MRSA control programme. PARTICIPANTS: All patients hospitalized >48 h in study wards and screened for MRSA on admission and discharge Intervention: Rapid PCR-based screening test for MRSA compared with control screening test by enrichment culture using chromogenic agar. OBJECTIVE: We determined the benefit of PCR-detection versus culture-based detection of MRSA colonisation upon patient admission on early implementation of isolation precautions and reduction of hospital transmission of MRSA. MAIN OUTCOME: Cumulative rate of MRSA hospital acquisition of in patients screened negative on admission. RANDOMIZATION: The sequential order of inclusion of study wards in each arm was randomised by assigning a number to each ward and using a computer generated list of random numbers. FINDINGS: Of 3704 eligible patients, 67.8% were evaluable for the study. Compared with culture, PCR-screening reduced the median test reporting time from admission from 88 to 11 hours (p<0.001) and the median time from admission to isolation from 96 to 25 hours (p<0.001). MRSA acquisition was detected in 36 patients (3.2%) in the control arm and 34 (3.2%) in the intervention arm. The incidence density rate of hospital acquired MRSA was 2.82 and 2.57/1,000 exposed patient-days in the control and intervention arm, respectively (risk ratio 0.91 (95% confidence interval, 0.60-1.39). Poisson regression model adjusted for colonisation pressure, compliance with hand hygiene and antibiotic use indicated a RR 0.99 (95% CI, 0.69 to 1.44). INTERPRETATION: Universal PCR screening for MRSA on admission to medical and surgical wards in an endemic setting shortened the time to implement isolation precautions but did not reduce nosocomial acquisition of MRSA. TRIAL REGISTRATION: clinicaltrials.gov NCT00846105.