Parechovirus A Circulation and Testing Capacities in Europe, 2015-2021.

Parechovirus infections usually affect neonates and young children; manifestations vary from asymptomatic to life-threatening. We describe laboratory capacity in Europe for assessing parechovirus circulation, seasonality, and epidemiology. We used retrospective anonymized data collected from parechovirus infection case-patients identified in Europe during January 2015-December 2021. Of 21 laboratories from 18 countries that participated in the study, 16 (76%) laboratories with parechovirus detection capacity reported 1,845 positive samples; 12/16 (75%) with typing capability successfully identified 517 samples. Parechovirus A3 was the most common type (n = 278), followed by A1 (153), A6 (50), A4 (13), A5 (22), and A14 (1). Clinical data from 1,269 participants highlighted correlation of types A3, A4, and A5 with severe disease in neonates. We observed a wide capacity in Europe to detect, type, and analyze parechovirus data. To enhance surveillance and response for PeV outbreaks, sharing typing protocols and data on parechovirus-positive cases should be encouraged.

Seasonality of respiratory syncytial virus and its association with meteorological factors in 13 European countries, week 40 2010 to week 39 2019.

BackgroundRespiratory syncytial virus (RSV) is the predominant cause of clinical pneumonia among infants and young children, often peaking during the winter months in temperate regions.AimTo describe RSV seasonality in 13 European countries and examine its association with meteorological factors.MethodsWe included weekly RSV seasonality data from 13 European countries between week 40 2010 and week 39 2019. Using local weighted regression method, we modelled weekly RSV activity with meteorological factors using data from the 2010/11 to the 2017/18 season. We predicted the weekly RSV activity of the 2018/19 season across 41 European countries and validated our prediction using empirical data.ResultsAll countries had annual wintertime RSV seasons with a longitudinal gradient in RSV onset (Pearson's correlation coefficient, r = 0.71, 95% CI: 0.60 to 0.80). The RSV season started 3.8 weeks later (95% CI: -0.5 to 8.0) in countries in the eastern vs western parts of Europe, and the duration ranged from 8-18 weeks across seasons and countries. Lower temperature and higher relative humidity were associated with higher RSV activity, with a 14-day lag time. Through external validation, the prediction error in RSV season onset was -2.4 ± 3.2 weeks. Similar longitudinal gradients in RSV onset were predicted by our model for the 2018/19 season (r = 0.45, 95% CI: 0.16 to 0.66).ConclusionMeteorological factors, such as temperature and relative humidity, could be used for early warning of RSV season onset. Our findings may inform healthcare services planning and optimisation of RSV immunisation strategies in Europe.

Molecular Epidemiology and Evolutionary Trajectory of Emerging Echovirus 30, Europe.

In 2018, an upsurge in echovirus 30 (E30) infections was reported in Europe. We conducted a large-scale epidemiologic and evolutionary study of 1,329 E30 strains collected in 22 countries in Europe during 2016-2018. Most E30 cases affected persons 0-4 years of age (29%) and 25-34 years of age (27%). Sequences were divided into 6 genetic clades (G1-G6). Most (53%) sequences belonged to G1, followed by G6 (23%), G2 (17%), G4 (4%), G3 (0.3%), and G5 (0.2%). Each clade encompassed unique individual recombinant forms; G1 and G4 displayed >2 unique recombinant forms. Rapid turnover of new clades and recombinant forms occurred over time. Clades G1 and G6 dominated in 2018, suggesting the E30 upsurge was caused by emergence of 2 distinct clades circulating in Europe. Investigation into the mechanisms behind the rapid turnover of E30 is crucial for clarifying the epidemiology and evolution of these enterovirus infections.

Recommendations for respiratory syncytial virus surveillance at the national level.

Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infections and hospitalisations among young children and is globally responsible for many deaths in young children, especially in infants aged <6 months. Furthermore, RSV is a common cause of severe respiratory disease and hospitalisation among older adults. The development of new candidate vaccines and monoclonal antibodies highlights the need for reliable surveillance of RSV. In the European Union (EU), no up-to-date general recommendations on RSV surveillance are currently available. Based on outcomes of a workshop with 29 European experts in the field of RSV virology, epidemiology and public health, we provide recommendations for developing a feasible and sustainable national surveillance strategy for RSV that will enable harmonisation and data comparison at the European level. We discuss three surveillance components: active sentinel community surveillance, active sentinel hospital surveillance and passive laboratory surveillance, using the EU acute respiratory infection and World Health Organization (WHO) extended severe acute respiratory infection case definitions. Furthermore, we recommend the use of quantitative reverse transcriptase PCR-based assays as the standard detection method for RSV and virus genetic characterisation, if possible, to monitor genetic evolution. These guidelines provide a basis for good quality, feasible and affordable surveillance of RSV. Harmonisation of surveillance standards at the European and global level will contribute to the wider availability of national level RSV surveillance data for regional and global analysis, and for estimation of RSV burden and the impact of future immunisation programmes.

Variable Sensitivity of SARS-CoV-2 Molecular Detection in European Expert Laboratories: External Quality Assessment, June and July 2020.

During the ongoing coronavirus disease 2019 (COVID-19) outbreak, robust detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key element for clinical management and to interrupt transmission chains. We organized an external quality assessment (EQA) of molecular detection of SARS-CoV-2 for European expert laboratories. An EQA panel composed of 12 samples, containing either SARS-CoV-2 at different concentrations to evaluate sensitivity or other respiratory viruses to evaluate specificity of SARS-CoV-2 testing, was distributed to 68 laboratories in 35 countries. Specificity samples included seasonal human coronaviruses hCoV-229E, hCoV-NL63, and hCoV-OC43, as well as Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and human influenza viruses A and B. Sensitivity results differed among laboratories, particularly for low-concentration SARS-CoV-2 samples. Results indicated that performance was mostly independent of the selection of specific extraction or PCR methods.

COVID-19 research priorities for non-pharmaceutical public health and social measures.

Europe is in the midst of a COVID-19 epidemic and a number of non-pharmaceutical public health and social measures have been implemented, in order to contain the transmission of severe acute respiratory syndrome coronavirus 2. These measures are fundamental elements of the public health approach to controlling transmission but have proven not to be sufficiently effective. Therefore, the European Centre for Disease Prevention and Control has conducted an assessment of research gaps that can help inform policy decisions regarding the COVID-19 response. We have identified research gaps in the area of non-pharmaceutical measures, physical distancing, contact tracing, transmission, communication, mental health, seasonality and environment/climate, surveillance and behavioural aspects of COVID-19. This prioritisation exercise is a step towards the global efforts of developing a coherent research road map in coping with the current epidemic but also developing preparedness measures for the next unexpected epidemic.

Meta-analysis of the clinical performance of commercial SARS-CoV-2 nucleic acid and antibody tests up to 22 August 2020.

BackgroundReliable testing for SARS-CoV-2 is key for the management of the COVID-19 pandemic.AimWe estimate diagnostic accuracy for nucleic acid and antibody tests 5 months into the COVID-19 pandemic, and compare with manufacturer-reported accuracy.MethodsWe reviewed the clinical performance of SARS-CoV-2 nucleic acid and antibody tests based on 93,757 test results from 151 published studies and 20,205 new test results from 12 countries in the European Union and European Economic Area (EU/EEA).ResultsPooling the results and considering only results with 95% confidence interval width ≤ 5%, we found four nucleic acid tests, including one point-of-care test and three antibody tests, with a clinical sensitivity ≥ 95% for at least one target population (hospitalised, mild or asymptomatic, or unknown). Nine nucleic acid tests and 25 antibody tests, 12 of them point-of-care tests, had a clinical specificity of ≥ 98%. Three antibody tests achieved both thresholds. Evidence for nucleic acid point-of-care tests remains scarce at present, and sensitivity varied substantially. Study heterogeneity was low for eight of 14 sensitivity and 68 of 84 specificity results with confidence interval width ≤ 5%, and lower for nucleic acid tests than antibody tests. Manufacturer-reported clinical performance was significantly higher than independently assessed in 11 of 32 and four of 34 cases, respectively, for sensitivity and specificity, indicating a need for improvement in this area.ConclusionContinuous monitoring of clinical performance within more clearly defined target populations is needed.

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.

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020.

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.

Laboratory readiness and response for novel coronavirus (2019-nCoV) in expert laboratories in 30 EU/EEA countries, January 2020.

Timely detection of novel coronavirus (2019-nCoV) infection cases is crucial to interrupt the spread of this virus. We assessed the required expertise and capacity for molecular detection of 2019-nCoV in specialised laboratories in 30 European Union/European Economic Area (EU/EEA) countries. Thirty-eight laboratories in 24 EU/EEA countries had diagnostic tests available by 29 January 2020. A coverage of all EU/EEA countries was expected by mid-February. Availability of primers/probes, positive controls and personnel were main implementation barriers.

First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020.

In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters' index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases.

Current practices for respiratory syncytial virus surveillance across the EU/EEA Member States, 2017.

BackgroundRespiratory syncytial virus (RSV) is a major contributor to lower respiratory tract infections worldwide and several vaccine candidates are currently in development. Following vaccine introduction, reliable RSV surveillance should enable monitoring of vaccination impact. Data on the RSV disease burden in the European Union and European Economic Area (EU/EEA) are sparse.AimThe aim of this study was to gather knowledge on current practices of national RSV surveillance in the EU/EEA.MethodsNational Coordinators and National Focal Points for Influenza (epidemiologists and virologists) from the EU/EEA countries (n = 31) were invited to participate in an online survey in August and September 2017. The questionnaire covered questions on epidemiological and laboratory aspects of RSV surveillance.ResultsAll EU/EEA countries except Liechtenstein replied to the survey. Eighteen countries reported to have a sentinel surveillance system, 26 countries a non-sentinel surveillance system and three countries to have neither. RSV data collection was mostly done within the context of influenza surveillance. A wide range of diagnostic and characterisation assays was used for the detection of RSV.DiscussionThe majority of EU/EEA countries have some surveillance for RSV in place. The prevailing integration of RSV surveillance into the existing influenza sentinel surveillance system may lead to under-reporting of RSV. The documented variations in existing RSV surveillance systems and their outputs indicate that there is scope for developing guidelines on establishing comparable methods and outcomes for RSV surveillance across the EU/EEA, to ensure the availability of a consistent evidence base for assessing future vaccination programmes.

Piloting a surveillance system for HIV drug resistance in the European Union.

BackgroundA steady increase in HIV drug resistance (HIVDR) has been demonstrated globally in individuals initiating first-line antiretroviral therapy (ART). To support effective use of ART and prevent spread of HIVDR, monitoring is essential.AimWe piloted a surveillance system for transmitted HIVDR to assess the feasibility of implementation at the European level.MethodAll 31 countries in the European Union and European Economic Area were invited to retrospectively submit data on individuals newly diagnosed with HIV in 2015 who were tested for antiviral susceptibility before ART, either as case-based or as aggregate data. We used the Stanford HIV database algorithm to translate genetic sequences into levels of drug resistance.ResultsNine countries participated, with six reporting case-based data on 1,680 individuals and four reporting aggregated data on 1,402 cases. Sequence data were available for 1,417 cases: 14.5% of individuals (n = 244) showed resistance to at least one antiretroviral drug. In case-based surveillance, the highest levels of transmitted HIVDR were observed for non-nucleoside reverse-transcriptase inhibitors (NNRTIs) with resistance detected in 8.6% (n = 145), followed by resistance to nucleoside reverse-transcriptase inhibitors (NRTI) (5.1%; n = 85) and protease inhibitors (2.0%; n = 34).ConclusionWe conclude that standard reporting of HIVDR data was feasible in the participating countries. Legal barriers for data sharing, consensus on definitions and standardisation of interpretation algorithms should be clarified in the process of enhancing European-wide HIV surveillance with drug resistance information.

Upsurge in echovirus 30 detections in five EU/EEA countries, April to September, 2018.

An upsurge in Echovirus 30 (E30) infections, associated with meningitis/meningoencephalitis, has been observed in Denmark, Germany, the Netherlands, Norway and Sweden in the period April to September 2018, compared with 2015-2017. In total, 658 E30 infections among 4,537 enterovirus infections were detected in 15 countries between January and September 2018 and affected mainly newborns and 26-45 year-olds. National public health institutes are reminded to remain vigilant and inform clinicians of the ongoing epidemic.

Seasonality and geographical spread of respiratory syncytial virus epidemics in 15 European countries, 2010 to 2016.

Respiratory syncytial virus (RSV) is considered the most common pathogen causing severe lower respiratory tract infections among infants and young children. We describe the seasonality and geographical spread of RSV infection in 15 countries of the European Union and European Economic Area. We performed a retrospective descriptive study of weekly laboratory-confirmed RSV detections between weeks 40/2010 and 20/2016, in patients investigated for influenza-like illness, acute respiratory infection or following the clinician's judgment. Six countries reported 4,230 sentinel RSV laboratory diagnoses from primary care and 14 countries reported 156,188 non-sentinel laboratory diagnoses from primary care or hospitals. The median length of the RSV season based on sentinel and non-sentinel surveillance was 16 (range: 9-24) and 18 (range: 8-24) weeks, respectively. The median peak weeks for sentinel and non-sentinel detections were week 4 (range: 48 to 11) and week 4.5 (range: 49 to 17), respectively. RSV detections peaked later (r = 0.56; p = 0.0360) and seasons lasted longer with increasing latitude (r = 0.57; p = 0.0329). Our data demonstrated regular seasonality with moderate correlation between timing of the epidemic and increasing latitude of the country. This study supports the use of RSV diagnostics within influenza or other surveillance systems to monitor RSV seasonality and geographical spread.

Surveillance and laboratory detection for non-polio enteroviruses in the European Union/European Economic Area, 2016.

Enteroviruses (EVs) cause severe outbreaks of respiratory and neurological disease as illustrated by EV-D68 and EV-A71 outbreaks, respectively. We have mapped European laboratory capacity for identification and characterisation of non-polio EVs to improve preparedness to respond to (re)-emerging EVs linked to severe disease. An online questionnaire on non-polio EV surveillance and laboratory detection was submitted to all 30 European Union (EU)/European Economic Area (EEA) countries. Twenty-nine countries responded; 26 conducted laboratory-based non-polio EV surveillance, and 24 included neurological infections in their surveillance. Eleven countries have established specific surveillance for EV-D68 via sentinel influenza surveillance (n = 7), typing EV-positive respiratory samples (n = 10) and/or acute flaccid paralysis surveillance (n = 5). Of 26 countries performing non-polio EV characterisation/typing, 10 further characterised culture-positive EV isolates, whereas the remainder typed PCR-positive but culture-negative samples. Although 19 countries have introduced sequence-based EV typing, seven still rely entirely on virus isolation. Based on 2015 data, six countries typed over 300 specimens mostly by sequencing, whereas 11 countries characterised under 50 EV-positive samples. EV surveillance activity varied between EU/EEA countries, and did not always specifically target patients with neurological and/or respiratory infections. Introduction of sequence-based typing methods is needed throughout the EU/EEA to enhance laboratory capacity for the detection of EVs.

Assessment of HIV molecular surveillance capacity in the European Union, 2016.

IntroductionExpanding access to HIV antiretroviral treatment is expected to decrease HIV incidence and acquired immunodeficiency syndrome (AIDS) mortality. However, this may also result in increased HIV drug resistance (DR). Better monitoring and surveillance of HIV DR is required to inform treatment regimens and maintain the long term effectiveness of antiretroviral drugs. As there is currently no formal European Union (EU)-wide collection of HIV DR data, this study aimed to assess the current HIV molecular surveillance capacity in EU/European Economic Area (EEA) countries in order to inform the planning of HIV DR monitoring at EU level. Methods: Thirty EU/EEA countries were invited to participate in a survey on HIV molecular surveillance capacity, which also included laboratory aspects. Results: Among 21 responding countries, 13 reported using HIV sequence data (subtype and/or DR) for surveillance purposes at national level. Of those, nine stated that clinical, epidemiological and sequence data were routinely linked for analysis. Discussion/conclusion: We identified similarities between existing HIV molecular surveillance systems, but also found important challenges including human resources, data ownership and legal issues that would need to be addressed.Information on capacities should allow better planning of the phased introduction of HIV DR surveillance at EU/EEA level.

Predominance of influenza A(H1N1)pdm09 virus genetic subclade 6B.1 and influenza B/Victoria lineage viruses at the start of the 2015/16 influenza season in Europe.

Influenza A(H1N1)pdm09 viruses predominated in the European influenza 2015/16 season. Most analysed viruses clustered in a new genetic subclade 6B.1, antigenically similar to the northern hemisphere vaccine component A/California/7/2009. The predominant influenza B lineage was Victoria compared with Yamagata in the previous season. It remains to be evaluated at the end of the season if these changes affected the effectiveness of the vaccine for the 2015/16 season.