• An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment.

      GeurtsvanKessel, Corine H; Okba, Nisreen M A; Igloi, Zsofia; Bogers, Susanne; Embregts, Carmen W E; Laksono, Brigitta M; Leijten, Lonneke; Rokx, Casper; Rijnders, Bart; Rahamat-Langendoen, Janette; et al. (2020-07-06)
    • Evaluation of data from the literature on the transport and survival of Escherichia coli and thermotolerant coliforms in aquifers under saturated conditions.

      Foppen, J W A; Schijven, J F (2006-02-01)
      Escherichia coli and thermotolerant coliforms are of major importance as indicators of fecal contamination of water. Due to its negative surface charge and relatively low die-off or inactivation rate coefficient, E. coli is able to travel long distances underground and is therefore also a useful indicator of fecal contamination of groundwater. In this review, the major processes known to determine the underground transport of E. coli (attachment, straining and inactivation) are evaluated. The single collector contact efficiency (SCCE), eta0, one of two parameters commonly used to assess the importance of attachment, can be quantified for E. coli using classical colloid filtration theory. The sticking efficiency, alpha, the second parameter frequently used in determining attachment, varies widely (from 0.003 to almost 1) and mainly depends on charge differences between the surface of the collector and E. coli. Straining can be quantified from geometrical considerations; it is proposed to employ a so-called straining correction parameter, alpha(str). Sticking efficiencies determined from field experiments were lower than those determined under laboratory conditions. We hypothesize that this is due to preferential flow mechanisms, E. coli population heterogeneity, and/or the presence of organic and inorganic compounds in wastewater possibly affecting bacterial attachment characteristics. Of equal importance is the inactivation or die-off of E. coli that is affected by factors like type of bacterial strain, temperature, predation, antagonism, light, soil type, pH, toxic substances, and dissolved oxygen. Modeling transport of E. coli can be separated into three steps: (1) attachment rate coefficients and straining rate coefficients can be calculated from Darcy flow velocity fields or pore water flow velocity fields, calculated SCCE fields, realistic sticking efficiency values and straining correction parameters, (2) together with the inactivation rate coefficient, total rate coefficient fields can be generated, and (3) used as input for modeling the transport of E. coli in existing contaminant transport codes. Areas of future research are manifold and include the effects of typical wastewater characteristics, including high concentrations of organic compounds, on the transport of E. coli and thermotolerant coliforms, and the upscaling of experiments to represent typical field conditions, possibly including preferential flow mechanisms and the aspect of population heterogeneity of E. coli.
    • Evaluation of Disease Causality of Rare -Borne Infections in Europe.

      Azagi, Tal; Hoornstra, Dieuwertje; Kremer, Kristin; Hovius, Joppe W R; Sprong, Hein (2020-02-24)
      In Europe, Ixodes ricinus ticks transmit pathogens such as Borrelia burgdorferi sensu lato and tick-borne encephalitis virus (TBEV). In addition, there is evidence for transmission to humans from I. ricinus of Anaplasma phagocytophilum, Babesia divergens, Babesia microti, Babesia venatorum, Borrelia miyamotoi, Neoehrlichia mikurensis, Rickettsia helvetica and Rickettsiamonacensis. However, whether infection with these potential tick-borne pathogens results in human disease has not been fully demonstrated for all of these tick-borne microorganisms. To evaluate the available evidence for a causative relation between infection and disease, the current study analyses European case reports published from 2008 to 2018, supplemented with information derived from epidemiological and experimental studies. The evidence for human disease causality in Europe found in this review appeared to be strongest for A. phagocytophilum and B. divergens. Nonetheless, some knowledge gaps still exist. Importantly, comprehensive evidence for pathogenicity is lacking for the remaining tick-borne microorganisms. Such evidence could be gathered best through prospective studies, for example, studies enrolling patients with a fever after a tick bite, the development of specific new serological tools, isolation of these microorganisms from ticks and patients and propagation in vitro, and through experimental studies.
    • Evaluation of neurological effects of cerium dioxide nanoparticles doped with different amounts of zirconium following inhalation exposure in mouse models of Alzheimer's and vascular disease.

      Wahle, Tina; Sofranko, Adriana; Dekkers, Susan; Miller, Mark R; Heusinkveld, Harm J; Albrecht, Catrin; Cassee, Flemming R; Schins, Roel P F (2020-09-01)
      Increasing evidence from toxicological and epidemiological studies indicates that the brain is an important target for ambient (ultrafine) particles. Disturbance of redox-homeostasis and inflammation in the brain are proposed as possible mechanisms that can contribute to neurotoxic and neurodegenerative effects. Whether and how engineered nanoparticles (NPs) may cause neurotoxicity and promote neurodegenerative diseases such as Alzheimer's disease (AD) is largely unstudied. We have assessed the neurological effects of subacute inhalation exposures (4 mg/m3 for 3 h/day, 5 days/week for 4 weeks) to cerium dioxide (CeO2) NPs doped with different amounts of zirconium (Zr, 0%, 27% and 78%), to address the influence of particle redox-activity in the 5xFAD transgenic mouse model of AD. Four weeks post-exposure, effects on behaviour were evaluated and brain tissues were analysed for amyloid-β plaque formation and reactive microglia (Iba-1 staining). Behaviour was also evaluated in concurrently exposed non-transgenic C57BL/6J littermates, as well as in Western diet-fed apolipoprotein E-deficient (ApoE-/-) mice as a model of vascular disease. Markers of inflammation and oxidative stress were evaluated in brain cortex. The brains of the NP-exposed 5xFAD mice revealed no accelerated amyloid-β plaque formation. No significant treatment-related behaviour impairments were observed in the healthy C57BL/6J mice. In the 5xFAD and ApoE-/- models, the NP inhalation exposures did not affect the alternation score in the X-maze indicating absence of spatial working memory deficits. However, following inhalation exposure to the 78% Zr-doped CeO2 NPs changes in forced motor performance (string suspension) and exploratory motor activity (X-maze) were observed in ApoE-/- and 5xFAD mice, respectively. Exposure to the 78% doped NPs also caused increased cortical expression of glial fibrillary acidic protein (GFAP) in the C57BL/6J mice. No significant treatment-related changes neuroinflammation and oxidative stress were observed in the 5xFAD and ApoE-/- mice. Our study findings reveal that subacute inhalation exposure to CeO2 NPs does not accelerate the AD-like phenotype of the 5xFAD model. Further investigation is warranted to unravel whether the redox-activity dependent effects on motor activity as observed in the mouse models of AD and vascular disease result from specific neurotoxic effects of these NPs.
    • Evaluation of receptor and chemical transport models for PM10 source apportionment.

      Belis, CA; Pernigotti, D; Pirovano, G; Favez, O; Jaffrezo, JL; Kuenen, J; Denier van der Gon, H; Reizer, M; Riffault, V; Alleman, LY; et al. (2020-04-23)
    • An evaluation of serological methods to diagnose tick-borne encephalitis from serum and cerebrospinal fluid.

      Reusken, Chantal; Boonstra, Marrit; Rugebregt, Sharona; Scherbeijn, Sandra; Chandler, Felicity; Avšič-Županc, Tatjana; Vapalahti, Olli; Koopmans, Marion; GeurtsvanKessel, Corine H (2019-11-01)
    • Evaluation of the Dutch neonatal screening for congenital adrenal hyperplasia.

      van der Linde, Annelieke A A; Schönbeck, Yvonne; van der Kamp, Hetty J; van den Akker, Erica L T; van Albada, Mirjam E; Boelen, Anita; Finken, Martijn J J; Hannema, Sabine E; Hoorweg-Nijman, Gera; Odink, Roelof J; et al. (2019-02-02)
      In 2002, a nationwide screening for congenital adrenal hyperplasia (CAH) was introduced in the Netherlands. The aim of our study is to evaluate the validity of the neonatal screening for CAH and to assess how many newborns with salt-wasting (SW) CAH have already been clinically diagnosed before the screening result was known. Retrospective, descriptive study. The following data of patients with positive screening results since implementation of the screening programme were collected (1 January 2002 up until 31 December 2013): gestational age, sex, diagnosis, clinical presentation and contribution of screening to the diagnosis. In the evaluated period, 2 235 931 newborns were screened. 479 children had an abnormal screening result, 133 children were diagnosed with CAH (114 SW, 14 simple virilizing (SV)), five non-classic CAH. During this period, no patients with SW CAH were missed by neonatal screening (sensitivity was 100%). After exclusion of 17 cases with missing information on diagnosis, specificity was 99.98% and positive predictive value was 24.7%. Most false positives (30%) were attributable to prematurity. Of patients with SW CAH, 68% (71/104) patients were detected by neonatal screening and 33 (33/104) were clinically diagnosed. Of girls with SW CAH, 38% (14/37) were detected by neonatal screening and 62% (23/37) were clinically diagnosed. The Dutch neonatal screening has an excellent sensitivity and high specificity. Both boys and girls can benefit from neonatal screening.
    • Evaluation of the impact of a hygiene warning label on the packaging of poultry

      Antonise-Kamp, Laura; Friesema, Ingrid H.M.; van der Vossen-Wijmenga, Wieke P.; Beaujean, Desirée J.M.A. (2018-10)
    • An Evaluation of the Loss-on-Ignition Method for Determining the Soil Organic Matter Content of Calcareous Soils

      Hoogsteen, M.J.J.; Lantinga, E.A.; Bakker, E.J.; Tittonell, P.A.; National Institute for Public Health and the Environment, Bilthoven, The Netherlands; Farming Systems Ecology Group, Wageningen University and Research Centre, Wageningen, The Netherlands; Mathematical and Statistical methods, Wageningen University and Research Centre, Wageningen, The Netherlands; Farming Systems Ecology Group, Wageningen University and Research Centre, Wageningen, The Netherlands (2018-05-21)
    • Evaluation of the medical devices benchmark materials in the controlled human patch testing and in the RhE in vitro skin irritation protocol.

      Kandárová, Helena; Bendova, Hana; Letasiova, Silvia; Coleman, Kelly P; De Jong, Wim H; Jírova, Dagmar (2018-02-17)
      Several irritants were used in the in vitro irritation medical device round robin. The objective of this study was to verify their irritation potential using the human patch test (HPT), an in vitro assay, and in vivo data. The irritants were lactic acid (LA), heptanoic acid (HA), sodium dodecyl sulfate (SDS), Genapol® X-80 (GP), and Y-4 polymer. Dilute saline and sesame seed oil (SSO) solutions of each were evaluated using a 4 and 18 h HPT and the EpiDerm™ SIT-MD RhE assay; results were then compared to existing rabbit skin irritation test data. Results from the 4 h HPT were negative in most cases except for GP and SDS, while the 18 h HPT also identified some LA, HA, and GP samples as irritants. EpiDerm™ SIT-MD correctly identified all irritants except GP in SSO due to limited solubility. Data from cutaneous rabbit irritation tests were negative, while all intracutaneous results were strongly or weakly positive except for the most dilute GP solutions. These findings indicate that EpiDerm™ SIT-MD results correlate with those from the rabbit intracutaneous test and confirm that RhE assays are suitable replacements for animals in evaluating the tissue irritation potential of medical devices.
    • Evaluation of the Process of Implementing an Outdoor School Ground Smoking Ban at Secondary Schools.

      Rozema, Andrea D; Mathijssen, Jolanda J P; van Oers, Hans A M; Jansen, Maria W J (2018-11)
      Although outdoor smoking bans at school are becoming important, it remains unclear whether successful implementation is feasible and what conditions promote it. Therefore, this study evaluates the implementation process by identifying important factors.
    • Evaluation of the Recipe Function in Popular Dietary Smartphone Applications, with Emphasize on Features Relevant for Nutrition Assessment in Large-Scale Studies.

      Zhang, Liangzi; Nawijn, Eline; Boshuizen, Hendriek; Ocké, Marga (2019-01-19)
      Nutrient estimations from mixed dishes require detailed information collection and should account for nutrient loss during cooking. This study aims to make an inventory of recipe creating features in popular food diary apps from a research perspective and to evaluate their nutrient calculation. A total of 12 out of 57 screened popular dietary assessment apps included a recipe function and were scored based on a pre-defined criteria list. Energy and nutrient content of three recipes calculated by the apps were compared with a reference procedure, which takes nutrient retention due to cooking into account. The quality of the recipe function varies across selected apps with a mean score of 3.0 (out of 5). More relevant differences (larger than 5% of the Daily Reference Intake) between apps and the reference were observed in micronutrients (49%) than in energy and macronutrients (20%). The primary source of these differences lies in the variation in food composition databases underlying each app. Applying retention factors decreased the micronutrient contents from 0% for calcium in all recipes to more than 45% for vitamins B6, B12, and folate in one recipe. Overall, recipe features and their ability to capture true nutrient intake are limited in current apps.
    • Evaluation of the surveillance system for invasive meningococcal disease (IMD) in the Netherlands, 2004-2016.

      Brandwagt, Diederik A H; van der Ende, Arie; Ruijs, Wilhelmina L M; de Melker, Hester E; Knol, Mirjam J (2019-10-17)
    • Evaluation of the taxonomic and functional variation of freshwater plankton communities induced by trace amounts of the antibiotic ciprofloxacin.

      Lu, Tao; Zhu, Youchao; Ke, Mingjing; Peijnenburg, W J G M; Zhang, Meng; Wang, Tingzhang; Chen, Jun; Qian, Haifeng (2019-02-27)
      Ciprofloxacin (CIP), one of the most frequently detected antibiotics in water systems, has become an aquatic contaminant because of improper disposal and excretion by humans and animals. It is still unknown how trace amounts of CIP affect the aquatic microbial community diversity and function. We therefore investigated the effects of CIP on the structure and function of freshwater microbial communities via 16S/18S rRNA gene sequencing and metatranscriptomic analyses. CIP treatment (7 μg/L) did not significantly alter the physical and chemical condition of the water body as well as the composition of the main species in the community, but slightly increased the relative abundance of cyanobacteria and decreased the relative abundance of eukaryotes. Metatranscriptomic results showed that bacteria enhanced their phosphorus transport and photosynthesis after CIP exposure. The replication, transcription, translation and cell proliferation were all suppressed in eukaryotes, while the bacteria were not affected in any of these aspects. This interesting phenomenon was the exact opposite to both the antibacterial property of CIP and its safety for eukaryotes. We hypothesize that reciprocal and antagonistic interactions in the microcosm both contribute to this result: cyanobacteria may enhance their tolerance to CIP through benefiting from cross-feeding and some secreted substances that withstand bacterial CIP stress would also affect eukaryotic growth. The present study thus indicates that a detailed assessment of the aquatic ecotoxicity of CIP is essential, as the effects of CIP are much more complicated in microbial communities than in monocultures. CIP will continue to be an environmental contaminant due to its wide usage and production and more attention should be given to the negative effects of antibiotics as well as other bioactive pollutants on aquatic environments.
    • An evaluation of the TREC assay with regard to the integration of SCID screening into the Dutch newborn screening program.

      Blom, Maartje; Pico-Knijnenburg, Ingrid; Sijne-van Veen, Marja; Boelen, Anita; Bredius, Robbert G M; van der Burg, Mirjam; Schielen, Peter C J I (2017-07)
      Newborn screening of severe combined immunodeficiency through the detection of T-cell receptor excision circles will provide the opportunity of treating before the occurrence of life-threatening infections. With the EnLite Neonatal TREC assay (PerkinElmer) and end-point PCR, 39 samples (3.0%) of 1295 heel prick cards of the Dutch newborn screening program required a retest after initial analysis. After retest, 21 samples (1.62%) gave TREC levels below cut-off. A significant reduction in TREC levels was observed in heel prick cards stored for three months (n=33) and one year (n=33). Preterm newborns (n=155) showed significantly lower TREC levels and a higher retest-rate than full-term newborns. Peripheral blood spots of 22 confirmed SCID patients and 17 primary immunodeficiency patients showed undetectable or low TREC-levels. These findings suggest that the EnLite Neonatal TREC assay is a suitable method for SCID-screening in the Netherlands, thereby providing guidance in the decisions concerning implementation into the Dutch program.
    • Evaluation of tuberculosis screening of immigrants in the Netherlands.

      van de Berg, Sarah; Erkens, Connie; van Rest, Job; van den Hof, Susan; Kamphorst, Margreet; Keizer, Sytze; de Vries, Gerard (2017-10)
    • Evidence for missing HPV-45 and -59 positives with the SPF-DEIA-LiPA (version 1) platform compared to the type-specific qPCR assays and the impact on vaccine effectiveness estimates.

      van Eer, Kahren; Leussink, Suzan; Severs, Tim T; van Marm-Wattimena, Naomi; Woestenberg, Petra J; Bogaards, Johannes A; King, Audrey J (2020-09-09)
      Human papillomavirus (HPV) epidemiological and vaccine studies require highly sensitive HPV detection systems. The widely used broad-spectrum SPF10-DEIA-LiPA25 (SPF10 method) has reduced sensitivity towards HPV-45 and -59. Therefore, anogenital samples from the PASSYON study were retrospectively analyzed with type-specific (TS) HPV-45 and -59 qPCR assays. The SPF10 method missed 51.1% of HPV-45 and 76.1% of HPV-59 infections, detected by the TS qPCR assays. Viral copy number (VCn) of SPF10 missed HPV-45 and -59 was significantly lower than SPF10 detected HPV-45 and -59 (p<0.0001 for both HPV types). Sanger sequencing showed no phylogenetic distinction between SPF10 missed and detected HPV-59 variants, but variants bearing the A6562G SNP in the SPF10 target region were more likely to be missed (p=0.0392). HPV co-occurrence slightly influenced the detection probability of HPV-45 and -59 with the SPF10 method. Moreover, HPV-59 detection with the SPF10 method was hampered more in non-vaccinated women than vaccinated women, likely due a stronger masking effect by increased HPV co-occurrence in the former group. Consequentially, the SPF10 method led to a strong negative vaccine effectiveness (VE) of -84.6% against HPV-59 while the VE based on TS qPCR was 3.1%. For HPV45, the relative increase in detection in non-vaccinated women compared vaccinated women was more similar, resulting in comparable VE estimates. In conclusion, this study shows that HPV-45 and -59 detection with SPF10 method is dependent on factors including VCn, HPV co-occurrence, and vaccination, thereby showing that knowledge of the limitations of the HPV detection method used is of great importance.
    • Evidence for the Effect of Vaccination on Host-Pathogen Interactions in a Murine Model of Pulmonary Tuberculosis by .

      Zatarain-Barrón, Zyanya Lucia; Ramos-Espinosa, Octavio; Marquina-Castillo, Brenda; Barrios-Payán, Jorge; Cornejo-Granados, Fernanda; Maya-Lucas, Otoniel; López-Leal, Gamaliel; Molina-Romero, Camilo; Anthony, Richard M; Ochoa-Leyva, Adrián; et al. (2020-01-01)
      The global control of Tuberculosis remains elusive, and Bacillus Calmette-Guérin (BCG) -the most widely used vaccine in history-has proven insufficient for reversing this epidemic. Several authors have suggested that the mass presence of vaccinated hosts might have affected the Mycobacterium tuberculosis (MTB) population structure, and this could in turn be reflected in a prevalence of strains with higher ability to circumvent BCG-induced immunity, such as the recent Beijing genotype. The effect of vaccination on vaccine-escape variants has been well-documented in several bacterial pathogens; however the effect of the interaction between MTB strains and vaccinated hosts has never been previously described. In this study we show for the first time the interaction between MTB Beijing-genotype strains and BCG-vaccinated hosts. Using a well-controlled murine model of progressive pulmonary tuberculosis, we vaccinated BALB/c mice with two different sub-strains of BCG (BCG-Phipps and BCG-Vietnam). Following vaccination, the mice were infected with either one of three selected MTB strains. Strains were selected based on lineage, and included two Beijing-family clinical isolates (strains 46 and 48) and a well-characterized laboratory strain (H37Rv). Two months after infection, mice were euthanized and the bacteria extracted from their lungs. We characterized the genomic composite of the bacteria before and after exposure to vaccinated hosts, and also characterized the local response to the bacteria by sequencing the lung transcriptome in animals during the infection. Results from this study show that the interaction within the lungs of the vaccinated hosts results in the selection of higher-virulence bacteria, specifically for the Beijing genotype strains 46 and 48. After exposure to the BCG-induced immune response, strains 46 and 48 acquire genomic mutations associated with several virulence factors. As a result, the bacteria collected from these vaccinated hosts have an increased ability for immune evasion, as shown in both the host transcriptome and the histopathology studies, and replicates far more efficiently compared to bacteria collected from unvaccinated hosts or to the original-stock strain. Further research is warranted to ascertain the pathways associated with the genomic alterations. However, our results highlight novel host-pathogen interactions induced by exposure of MTB to BCG vaccinated hosts.
    • Evidence for transmission of COVID-19 prior to symptom onset.

      Tindale, Lauren C; Stockdale, Jessica E; Coombe, Michelle; Garlock, Emma S; Lau, Wing Yin Venus; Saraswat, Manu; Zhang, Louxin; Chen, Dongxuan; Wallinga, Jacco; Colijn, Caroline (2020-06-22)