• Quality assurance of colonoscopy within the Dutch national colorectal cancer screening program.

      Bronzwaer, Maxime E S; Depla, Annekatrien C T M; van Lelyveld, Niels; Spanier, Marcel B W; Oosterhout, Yvonne H; van Leerdam, Monique E; Spaander, Manon C W; Dekker, Evelien; van Haastert, M; Keller, J J; Koch, A D; Koornstra, J J; van Kouwen, M C A; Masclee, A; Mundt, M W; de Ridder, R J; van der Sluys-Veer, A; van Wieren, M (2018-09-18)
      Colorectal cancer (CRC) screening is capable of reducing CRC-related morbidity and mortality. Colonoscopy is the reference standard to detect CRC, also providing the opportunity to detect and resect its precursor lesions; colorectal polyps. Therefore, colonoscopy is either used as a primary screening tool or as a subsequent procedure after a positive triage test in screening programs based on non-invasive stool testing or sigmoidoscopy. However, in both settings, colonoscopy is not fully protective for the occurrence of post-colonoscopy CRCs (PCCRCs). Because the majority of PCCRCs are the result of colonoscopy-related factors, a high-quality procedure is of paramount importance to assure optimal effectiveness of CRC screening programs. For this reason, at the start of the Dutch fecal immunochemical test (FIT)-based screening program, quality criteria for endoscopists performing colonoscopies in FIT-positive screenees, as well as for endoscopy centers, were defined. In conjunction, an accreditation and auditing system was designed and implemented. In this report we describe the quality assurance process for endoscopists participating in the Dutch national CRC Screening Program, including a detailed description of the evidence-based quality criteria. We believe that our experience might serve as an example for colonoscopy quality assurance programs in other CRC screening programs.
    • Quality evaluation of human and environmental toxicity studies performed with nanomaterials – the GUIDEnano approach

      Fernández-Cruz, M. L.; Hernández-Moreno, D.; Catalán, J.; Cross, R. K.; Stockmann-Juvala, H.; Cabellos, J.; Lopes, Viviana R.; Matzke, M.; Ferraz, N.; Izquierdo, J. J.; Navas, J. M.; Park, M.; Svendsen, C.; Janer, G.; National Institute for Agricultural and Food Research and Technology; National Institute for Agricultural and Food Research and Technology; Work Environment; College of Life and Environmental Sciences; Work Environment; Leitat Technological Center; Nanotechnology and Functional Materials; NERC Centre for Ecology and Hydrology; Nanotechnology and Functional Materials; National Institute for Agricultural and Food Research and Technology; National Institute for Agricultural and Food Research and Technology; National Institute for Public Health and the Environment; NERC Centre for Ecology and Hydrology; Leitat Technological Center (2018)
      The GUIDEnano quality tool establishes objective criteria to score the quality of eco/toxicity studies performed with nanomaterials.
    • Quantification of Salmonella Survival and Infection in an In vitro Model of the Human Intestinal Tract as Proxy for Foodborne Pathogens.

      Wijnands, Lucas M; Teunis, Peter F M; Kuijpers, Angelina F A; Delfgou-Van Asch, Ellen H M; Pielaat, Annemarie (2017)
      Different techniques are available for assessing differences in virulence of bacterial foodborne pathogens. The use of animal models or human volunteers is not expedient for various reasons; the use of epidemiological data is often hampered by lack of crucial data. In this paper, we describe a static, sequential gastrointestinal tract (GIT) model system in which foodborne pathogens are exposed to simulated gastric and intestinal contents of the human digestive tract, including the interaction of pathogens with the intestinal epithelium. The system can be employed with any foodborne bacterial pathogens. Five strains of Salmonella Heidelberg and one strain of Salmonella Typhimurium were used to assess the robustness of the system. Four S. Heidelberg strains originated from an outbreak, the fifth S. Heidelberg strain and the S. Typhimurium strain originated from routine meat inspections. Data from plate counts, collected for determining the numbers of surviving bacteria in each stage, were used to quantify both the experimental uncertainty and biological variability of pathogen survival throughout the system. For this, a hierarchical Bayesian framework using Markov chain Monte Carlo (MCMC) was employed. The model system is able to distinguish serovars/strains for in vitro infectivity when accounting for within strain biological variability and experimental uncertainty.
    • Quantifying biomass production for assessing ecosystem services of riverine landscapes

      Koopman, K.R.; Straatsma, M.W.; Augustijn, D.C.M.; Breure, A.M.; Lenders, H.J.R.; Stax, S.J.; Leuven, R.S.E.W. (2018-05)
    • Quantifying the impact of mass vaccination programmes on notified cases in the Netherlands.

      van Wijhe, M; Tulen, A D; Korthals Altes, H; McDonald, S A; de Melker, H E; Postma, M J; Wallinga, J (2018-03-14)
      Vaccination programmes are considered a main contributor to the decline of infectious diseases over the 20th century. In recent years, the national vaccination coverage in the Netherlands has been declining, highlighting the need for continuous monitoring and evaluation of vaccination programmes. Our aim was to quantify the impact of long-standing vaccination programmes on notified cases in the Netherlands. We collected and digitised previously unavailable monthly case notifications of diphtheria, poliomyelitis, mumps and rubella in the Netherlands over the period 1919-2015. Poisson regression models accounting for seasonality, multi-year cycles, secular trends and auto-correlation were fit to pre-vaccination periods. Cases averted were calculated as the difference between observed and expected cases based on model projections. In the first 13 years of mass vaccinations, case notifications declined rapidly with 82.4% (95% credible interval (CI): 74.9-87.6) of notified cases of diphtheria averted, 92.9% (95% CI 85.0-97.2) cases of poliomyelitis, and 79.1% (95% CI 67.1-87.4) cases of mumps. Vaccination of 11-year-old girls against rubella averted 49.9% (95% CI 9.3-73.5) of cases, while universal vaccination averted 68.1% (95% CI 19.4-87.3) of cases. These findings show that vaccination programmes have contributed substantially to the reduction of infectious diseases in the Netherlands.
    • Quantifying the impact of social groups and vaccination on inequalities in infectious diseases using a mathematical model.

      Munday, James D; van Hoek, Albert Jan; Edmunds, W John; Atkins, Katherine E (2018-09-26)
      Social and cultural disparities in infectious disease burden are caused by systematic differences between communities. Some differences have a direct and proportional impact on disease burden, such as health-seeking behaviour and severity of infection. Other differences-such as contact rates and susceptibility-affect the risk of transmission, where the impact on disease burden is indirect and remains unclear. Furthermore, the concomitant impact of vaccination on such inequalities is not well understood.
    • Quantitative Assessment of the Health Risk for Livestock When Animal Viruses Are Applied in Human Oncolytic Therapy: A Case Study for Seneca Valley Virus.

      Schijven, Jack; Brizee, Sabrina; Teunis, Peter; de Vos, Clazien; Eblé, Phaedra; Rutjes, Saskia (2018-11-05)
      Some viruses cause tumor regression and can be used to treat cancer patients; these viruses are called oncolytic viruses. To assess whether oncolytic viruses from animal origin excreted by patients pose a health risk for livestock, a quantitative risk assessment (QRA) was performed to estimate the risk for the Dutch pig industry after environmental release of Seneca Valley virus (SVV). The QRA assumed SVV excretion in stool by one cancer patient on Day 1 in the Netherlands, discharge of SVV with treated wastewater into the river Meuse, downstream intake of river water for drinking water production, and consumption of this drinking water by pigs. Dose-response curves for SVV infection and clinical disease in pigs were constructed from experimental data. In the worst scenario (four log
    • A quantitative comparison of anti-Müllerian hormone measurement and its shifting boundaries between two assays.

      de Kat, A C; Broekmans, F J M; van Westing, A C; Lentjes, E; Verschuren, W M M; van der Schouw, Y T (2017-07)
      Anti-Müllerian hormone (AMH), a quantitative marker of ovarian reserve, is used for both clinical and research purposes in the field of reproductive medicine. Numerous AMH assays have been developed. Among other factors, the lack of large-scale comparisons of the various assays hinders the universal interpretation of AMH levels. Moreover, little is known of the practical performance of highly sensitive assays compared with conventional assays with regard to the very low AMH levels found in women nearing menopause. This study aimed to compare the measurements of the Gen II (Beckman Coulter) assay with those of the highly sensitive picoAMH (AnshLabs) assay.
    • Quantitative human health risk assessment along the lifecycle of nano-scale copper-based wood preservatives.

      Hristozov, Danail; Pizzol, Lisa; Basei, Gianpietro; Zabeo, Alex; Mackevica, Aiga; Hansen, Steffen Foss; Gosens, Ilse; Cassee, Flemming R; de Jong, Wim; Koivisto, Antti Joonas; Neubauer, Nicole; Sanchez Jimenez, Araceli; Semenzin, Elena; Subramanian, Vrishali; Fransman, Wouter; Jensen, Keld Alstrup; Wohlleben, Wendel; Stone, Vicki; Marcomini, Antonio (2018-06-12)
      The use of nano-scale copper oxide (CuO) and basic copper carbonate (Cu2(OH)2CO3) in both ionic and micronized wood preservatives has raised concerns about the potential of these substances to cause adverse humans health effects. To address these concerns, we performed quantitative (probabilistic) human health risk assessment (HHRA) along the lifecycles of these formulations used in antibacterial and antifungal wood coatings and impregnations by means of the EU FP7 SUN project's Decision Support System (SUNDS, www.sunds.gd). The results from the risk analysis revealed inhalation risks from CuO in exposure scenarios involving workers handling dry powders and performing sanding operations as well as potential ingestion risks for children exposed to nano Cu2(OH)2CO3 in a scenario involving hand-to-mouth transfer of the substance released from impregnated wood. There are, however, substantial uncertainties in these results, so some of the identified risks may stem from the safety margin of extrapolation to fill data gaps and might be resolved by additional testing. Our stochastic approach successfully communicated the contribution of different sources of uncertainty in the risk assessment. The main source of uncertainty was the extrapolation from short to long-term exposure, which was necessary due to the lack of (sub)chronic in vivo studies with CuO and Cu2(OH)2CO3. Considerable uncertainties also stemmed from the use of default inter- and intra-species extrapolation factors.
    • A quantitative risk assessment for human Taenia solium exposure from home slaughtered pigs in European countries.

      Meester, Marina; Swart, Arno; Deng, Huifang; van Roon, Annika; Trevisan, Chiara; Dorny, Pierre; Gabriël, Sarah; Vieira-Pinto, Madalena; Johansen, Maria Vang; van der Giessen, Joke (2019-02-12)
      Taenia solium, a zoonotic tapeworm, is responsible for about a third of all preventable epilepsy human cases in endemic regions. In Europe, adequate biosecurity of pig housing and meat inspection practices have decreased the incidence of T. solium taeniosis and cysticercosis. Pigs slaughtered at home may have been raised in suboptimal biosecurity conditions and slaughtered without meat inspection. As a result, consumption of undercooked pork from home slaughtered pigs could pose a risk for exposure to T. solium. The aim of this study was to quantify the risk of human T. solium exposure from meat of home slaughtered pigs, in comparison to controlled slaughtered pigs, in European countries. A quantitative microbial risk assessment model (QMRA) was developed and porcine cysticercosis prevalence data, the percentage of home slaughtered pigs, meat inspection sensitivity, the cyst distribution in pork and pork consumption in five European countries, Bulgaria, Germany, Poland, Romania and Spain, were included as variables in the model. This was combined with literature about cooking habits to estimate the number of infected pork portions eaten per year in a country. The results of the model showed a 13.83 times higher prevalence of contaminated pork portions from home slaughtered pigs than controlled slaughtered pigs. This difference is brought about by the higher prevalence of cysticercosis in pigs that are home raised and slaughtered. Meat inspection did not affect the higher exposure from pork that is home slaughtered. Cooking meat effectively lowered the risk of exposure to T. solium-infected pork. This QMRA showed that there is still a risk of obtaining an infection with T. solium due to consumption of pork, especially when pigs are reared and slaughtered at home, using data of five European countries that reported porcine cysticercosis cases. We propose systematic reporting of cysticercosis cases in slaughterhouses, and in addition molecularly confirming suspected cases to gain more insight into the presence of T. solium in pigs and the risk for humans in Europe. When more data become available, this QMRA model could be used to evaluate human exposure to T. solium in Europe and beyond.
    • Quantitative structure-activity relationships for green algae growth inhibition by polymer particles.

      Nolte, Tom M; Peijnenburg, Willie J G M; Hendriks, A Jan; van de Meent, Dik (2017-07)
      After use and disposal of chemical products, many types of polymer particles end up in the aquatic environment with potential toxic effects to primary producers like green algae. In this study, we have developed Quantitative Structure-Activity Relationships (QSARs) for a set of highly structural diverse polymers which are capable to estimate green algae growth inhibition (EC50). The model (N = 43, R2 = 0.73, RMSE = 0.28) is a regression-based decision tree using one structural descriptor for each of three polymer classes separated based on charge. The QSAR is applicable to linear homo polymers as well as copolymers and does not require information on the size of the polymer particle or underlying core material. Highly branched polymers, non-nitrogen cationic polymers and polymeric surfactants are not included in the model and thus cannot be evaluated. The model works best for cationic and non-ionic polymers for which cellular adsorption, disruption of the cell wall and photosynthesis inhibition were the mechanisms of action. For anionic polymers, specific properties of the polymer and test characteristics need to be known for detailed assessment. The data and QSAR results for anionic polymers, when combined with molecular dynamics simulations indicated that nutrient depletion is likely the dominant mode of toxicity. Nutrient depletion in turn, is determined by the non-linear interplay between polymer charge density and backbone flexibility.
    • Radiation Protection for Interventional Fluoroscopy: Results of a Survey Among Dutch Hospitals.

      Bijwaard, Harmen; Valk, Doreth; de Waard-Schalkx, Ischa (2018-06)
      A survey was conducted among 20 Dutch hospitals about radiation protection for interventional fluoroscopy. This was a follow-up of a previous study in 2007 that led to several recommendations for radiation protection for interventional fluoroscopy. The results indicate that most recommendations have been followed. However, radiation-induced complications from interventional procedures are still often not recorded in the appropriate register. Furthermore, even though professionals with appropriate training in radiation protection are usually involved in interventional procedures, this often is not the case when these procedures are carried out outside the radiology department. Although this involvement is not required by Dutch law, it is recommended to have radiation protection professionals present more often at interventional procedures. Further improvements in radiation protection for interventional fluoroscopy may come from a comparison of dose-reducing practices among hospitals, the introduction of diagnostic reference levels for interventional procedures, and a more thorough form of screening and follow-up of patients.

      Smetsers, R C G M; Blaauboer, R O; Dekkers, F; Slaper, H (2018-09-01)
      Radon and thoron progenies in Dutch dwellings cause ~400 cases of lung cancer per year. Some 30% of the risk is due to thoron progeny, which demonstrates that the influence of thoron progeny is much larger than previously anticipated. This was concluded from a national survey in 2500 Dutch dwellings, built since 1930. Radon concentrations (15.6 ± 0.3 Bq m-3 on average) are correlated to type of dwelling, year of construction, ventilation system, location (soil type) and smoking behaviour of inhabitants. The survey data support the establishment of a comparatively low national reference level for radon in dwellings in the Netherlands of 100 Bq m-3, in line with recommendations by WHO and ICRP. Some 24 thousand of the 6.2 million dwellings in the Netherlands (built since 1930) are expected to exceed this level. Around 80% of these are located in the relatively small group of naturally ventilated single-family houses in two designated geographical areas. Radon concentrations above 200 Bq m-3 are rare in the Netherlands and simple and inexpensive measures will be sufficient to reduce enhanced radon concentrations to values below the national reference level. Thoron progeny concentrations (0.64 Bq m-3, on average) show correlations with year of construction and smoking behaviour. In 75 additional dwellings, a pilot study was conducted to determine the relationship between the exhalation of thoron from walls and the concentration of thoron progeny in the room. Thoron exhalation values exceeding the median value of 2.2 × 10-2 Bq m-2 s-1 by a factor 10 or more were found frequently, but enhanced concentrations of thoron progeny were measured only occasionally. Under very unfavourable conditions, however, for instance if phosphogypsum is applied as finishing material on all walls and ceilings in the house, strongly elevated thoron progeny concentrations may occur. This survey yielded a maximum recording of 13.3 Bq m-3. There is no reason to expect that such levels are specific to the Netherlands, indicating that in other regions with low radon levels, thoron may be a more important contributor to the population dose as well.
    • Random effect modelling of patient-related risk factors in orthopaedic procedures: results from the Dutch nosocomial infection surveillance network 'PREZIES'.

      Muilwijk, J; Walenkamp, G H I M; Voss, Andreas; Wille, Jan C; Hof, Susan van den (2006-03-01)
      In the Dutch surveillance for surgical site infections (SSIs), data from 70277 orthopaedic procedures with 1895 SSIs were collected between 1996 and 2003. The aims of this study were: (1) to analyse the trends in SSIs associated with Gram-positive and Gram-negative bacteria; (2) to estimate patient-related risk factors for deep and superficial SSIs after all orthopaedic procedures, with special attention to primary total hip arthroplasty (THA); and (3) to analyse inherent differences in infection risk between hospitals. A random effect model was used to estimate the odds ratios of patient-related risk factors for developing an SSI, and to describe the distribution of the most widespread bacterial species responsible for SSIs among hospitals. Gram-positive organisms, mainly staphylococci, were the main cause of both deep (84.0%) and superficial SSIs (69.1%) after orthopaedic procedures. The percentage of SSIs after THA caused by coagulase-negative staphylococci decreased over the surveillance period, while the contribution of Staphylococcus aureus increased. Temporary elevations in the incidence of the most widespread pathogen species were observed within hospitals. Patient-related factors such as the National Nosocomial Infections Surveillance System risk index or age had little effect on the predictive power of the random effect models. This study underlines the usefulness of a random effect model, which adjusts risk estimates for random variation between hospitals, in a multicentre study on risk factors for SSIs.
    • Rapid Assessment of Stakeholder Concerns about Public Health. An Introduction to a Fast and Inexpensive Approach Applied on Health Concerns about Intensive Animal Production Systems.

      Kraaij-Dirkzwager, Marleen; van der Ree, Joost; Lebret, Erik (2017-12-11)
      To effectively manage environmental health risks, stakeholders often need to act collectively. Stakeholders vary in their desire to act due to many factors, such as knowledge, risk perception, interests, and worldviews. Understanding their perceptions of the issues at stake is crucial to support the risk governance process. Even though concern assessment is a pivotal element of risk governance, few tools for rapid assessment are reported in the literature. We tested a rapid and relatively cheap approach, taking the Dutch debate on Intensive Animal Production Systems (IAPS) and health as an example. Dutch policy-oriented publications on IAPS and health and ten semi-structured in-depth interviews with a variety of stakeholders were analyzed to identify stakeholders and concerns involved in the Dutch debate about IAPS and health. Concerns were mapped and a stakeholder network was derived. Three classes of concerns were recognized in the discussions about IAPS and health: concerns related to health risks, concerns regarding the activity causing the risks (IAPS), and concerns about the process to control the risks. The notions of 'trust' and 'scientific uncertainty' appeared as important themes in the discussions. Argumentation based on concerns directly related to health risks, the activity causing the risk (IAPS), and its risk management can easily become muddled up in a societal debate, limiting the development of effective action perspectives. Acknowledging these multiple stakeholder concerns can clarify the positions taken by stakeholders and allow for more and other action perspectives to develop.
    • Real-time detection of noroviruses in surface water by use of a broadly reactive nucleic acid sequence-based amplification assay.

      Rutjes, Saskia A; Berg, Harold H J L van den; Lodder, Willemijn J; Roda Husman, Ana Maria de (2006-08-01)
      Noroviruses are the most common agents causing outbreaks of viral gastroenteritis. Outbreaks originating from contaminated drinking water and from recreational waters have been described. Due to a lack of cell culture systems, noroviruses are detected mostly by molecular methods. Molecular detection assays for viruses in water are often repressed by inhibitory factors present in the environment, like humic acids and heavy metals. To study the effect of environmental inhibitors on the performance of nucleic acid sequence-based amplification (NASBA), we developed a real-time norovirus NASBA targeting part of the RNA-dependent RNA polymerase (RdRp) gene. Specificity of the assay was studied with 33 divergent clones that contained part of the targeted RdRp gene of noroviruses from 15 different genogroups. Viral RNA originated from commercial oysters, surface waters, and sewage treatment plants in The Netherlands. Ninety-seven percent of the clones derived from human noroviruses were detected by real-time NASBA. Two clones containing animal noroviruses were not detected by NASBA. We compared the norovirus detection by real-time NASBA with that by conventional reverse transcriptase PCR (RT-PCR) with large-volume river water samples and found that inhibitory factors of RT-PCR had little or no effect on the performance of the norovirus NASBA. This consequently resulted in a higher sensitivity of the NASBA assay than of the RT-PCR. We show that by combining an efficient RNA extraction method with real-time NASBA the sensitivity of norovirus detection in water samples increased at least 100 times, which consequently has implications for the outcome of the infectious risk assessment.
    • Real-time Estimation of Epidemiologic Parameters from Contact Tracing Data During an Emerging Infectious Disease Outbreak.

      Soetens, Loes; Klinkenberg, Don; Swaan, Corien; Hahné, Susan; Wallinga, Jacco (2018-03)
      Contact tracing can provide accurate information on relevant parameters of an ongoing emerging infectious disease outbreak. This is crucial to investigators seeking to control such an outbreak. However, crude contact tracing data are difficult to interpret and methods for analyzing these data are scarce. We present a method to estimate and visualize key outbreak parameters from contact tracing information in real time by taking into account data censoring.
    • Recommendation on test readiness criteria for new approach methods in toxicology: Exemplified for developmental neurotoxicity.

      Bal-Price, Anna; Hogberg, Helena T; Crofton, Kevin M; Daneshian, Mardas; FitzGerald, Rex E; Fritsche, Ellen; Heinonen, Tuula; Hougaard Bennekou, Susanne; Klima, Stefanie; Piersma, Aldert H; Sachana, Magdalini; Shafer, Timothy J; Terron, Andrea; Monnet-Tschudi, Florianne; Viviani, Barbara; Waldmann, Tanja; Westerink, Remco H S; Wilks, Martin F; Witters, Hilda; Zurich, Marie-Gabrielle; Leist, Marcel (2018-02-23)
      Multiple non-animal-based test methods have never been formally validated. In order to use such new approach methods (NAMs) in a regulatory context, criteria to define their readiness are necessary. The field of developmental neurotoxicity (DNT) testing is used to exemplify the application of readiness criteria. The costs and number of untested chemicals are overwhelming for in vivo DNT testing. Thus, there is a need for inexpensive, high-throughput NAMs, to obtain initial information on potential hazards, and to allow prioritization for further testing. A background on the regulatory and scientific status of DNT testing is provided showing different types of test readiness levels, depending on the intended use of data from NAMs. Readiness criteria, compiled during a stakeholder workshop, uniting scientists from academia, industry and regulatory authorities are presented. An important step beyond the listing of criteria, was the suggestion for a preliminary scoring scheme. On this basis a (semi)-quantitative analysis process was assembled on test readiness of 17 NAMs with respect to various uses (e.g. prioritization/screening, risk assessment). The scoring results suggest that several assays are currently at high readiness levels. Therefore, suggestions are made on how DNT NAMs may be assembled into an integrated approach to testing and assessment (IATA). In parallel, the testing state in these assays was compiled for more than 1000 compounds. Finally, a vision is presented on how further NAM development may be guided by knowledge of signaling pathways necessary for brain development, DNT pathophysiology, and relevant adverse outcome pathways (AOP).
    • Recommendations for enterovirus diagnostics and characterisation within and beyond Europe.

      Harvala, Heli; Broberg, Eeva; Benschop, Kimberley; Berginc, Natasa; Ladhani, Shamez; Susi, Petri; Christiansen, Claus; McKenna, James; Allen, David; Makiello, Phoebe; McAllister, Georgina; Carmen, Mirabelli; Zakikhany, Katherina; Dyrdak, Robert; Nielsen, Xiaohui; Madsen, Tina; Paul, Joel; Moore, Catherine; von Eije, Karin; Piralla, Antonio; Carlier, Mieke; Vanoverschelde, Laura; Poelman, Randy; Anton, Andrés; López-Labrador, F Xavier; Pellegrinelli, Laura; Keeren, Kathrin; Maier, Melanie; Cassidy, Hayley; Derdas, Stavros; Savolainen-Kopra, Carita; Diedrich, Sabine; Nordbø, Svein; Buesa, Javier; Bailly, Jean-Luc; Baldanti, Fausto; MacAdam, Andrew; Mirand, Audrey; Dudman, Susanne; Schuffenecker, Isabelle; Kadambari, Seilesh; Neyts, Johan; Griffiths, Michael J; Richter, Jan; Margaretto, Cristina; Govind, Sheila; Morley, Ursula; Adams, Ortwin; Krokstad, Sidsel; Dean, Jonathan; Pons-Salort, Margarita; Prochazka, Birgit; Cabrerizo, Maria; Majumdar, Manasi; Nebbia, Gaia; Wiewel, Maryse; Cottrell, Simon; Coyle, Peter; Martin, Javier; Moore, Catrin; Midgley, Sofie; Horby, Peter; Wolthers, Katja; Simmonds, Peter; Niesters, Hubert; Fischer, Thea K (2018-02-06)
      Enteroviruses (EV) can cause severe neurological and respiratory infections, and occasionally lead to devastating outbreaks as previously demonstrated with EV-A71 and EV-D68 in Europe. However, these infections are still often underdiagnosed and EV typing data is not currently collected at European level. In order to improve EV diagnostics, collate data on severe EV infections and monitor the circulation of EV types, we have established European non-polio enterovirus network (ENPEN). First task of this cross-border network has been to ensure prompt and adequate diagnosis of these infections in Europe, and hence we present recommendations for non-polio EV detection and typing based on the consensus view of this multidisciplinary team including experts from over 20 European countries. We recommend that respiratory and stool samples in addition to cerebrospinal fluid (CSF) and blood samples are submitted for EV testing from patients with suspected neurological infections. This is vital since viruses like EV-D68 are rarely detectable in CSF or stool samples. Furthermore, reverse transcriptase PCR (RT-PCR) targeting the 5'noncoding regions (5'NCR) should be used for diagnosis of EVs due to their sensitivity, specificity and short turnaround time. Sequencing of the VP1 capsid protein gene is recommended for EV typing; EV typing cannot be based on the 5'NCR sequences due to frequent recombination events and should not rely on virus isolation. Effective and standardized laboratory diagnostics and characterisation of circulating virus strains are the first step towards effective and continuous surveillance activities, which in turn will be used to provide better estimation on EV disease burden.