• A systematic knowledge synthesis on the spatial dimensions of Q fever epidemics.

      De Rooij, Myrna M T; Van Leuken, Jeroen P G; Swart, Arno; Kretzschmar, Mirjam E E; Nielen, Mirjam; De Koeijer, Aline A; Janse, Ingmar; Wouters, Inge M; Heederik, Dick J J (2019-02-01)
      From 2007 through 2010, the Netherlands experienced the largest Q fever epidemic ever reported. This study integrates the outcomes of a multidisciplinary research programme on spatial airborne transmission of Coxiella burnetii and reflects these outcomes in relation to other scientific Q fever studies worldwide. We have identified lessons learned and remaining knowledge gaps. This synthesis was structured according to the four steps of quantitative microbial risk assessment (QMRA): (a) Rapid source identification was improved by newly developed techniques using mathematical disease modelling; (b) source characterization efforts improved knowledge but did not provide accurate C. burnetii emission patterns; (c) ambient air sampling, dispersion and spatial modelling promoted exposure assessment; and (d) risk characterization was enabled by applying refined dose-response analyses. The results may support proper and timely risk assessment and risk management during future outbreaks, provided that accurate and structured data are available and exchanged readily between responsible actors.
    • A Systematic Review of Social Contact Surveys to Inform Transmission Models of Close-contact Infections.

      Hoang, Thang; Coletti, Pietro; Melegaro, Alessia; Wallinga, Jacco; Grijalva, Carlos G; Edmunds, John W; Beutels, Philippe; Hens, Niel (2019-09-01)
    • Systematic selection of a dose metric for metal-based nanoparticles.

      Verschoor, AJ; Harper, S; Delmaar, CJE; Park, MVDZ; Sips, AJAM; Vijver, MG; Peijnenburg, WJGM (2019-01-17)
    • Systematically Developing a Web-Based Tailored Intervention Promoting HPV-Vaccination Acceptability Among Mothers of Invited Girls Using Intervention Mapping.

      Pot, Mirjam; Ruiter, Robert A C; Paulussen, Theo W G M; Heuvelink, Annerieke; de Melker, Hester E; van Vliet, Hans J A; van Keulen, Hilde M (2018)
      Background: Currently, the eHealth field calls for detailed descriptions of theory-based interventions in order to support improved design of such interventions. This article aims to provide a systematic description of the design rationale behind an interactive web-based tailored intervention promoting HPV-vaccination acceptability. Methods: The 6-step Intervention Mapping (IM) protocol was used to describe the design rationale. After the needs assessment in Step 1, intervention objectives were formulated in Step 2. In Step 3, we translated theoretical methods into practical applications, which were integrated into a coherent intervention in Step 4. In Step 5, we anticipated future implementation and adoption, and finally, an evaluation plan was generated in Step 6. Results: Walking through the various steps of IM resulted in a detailed description of the intervention. The needs assessment indicated HPV-vaccination uptake remaining lower than expected. Mothers play the most important role in decision-making about their daughter's immunization. However, they generally feel ambivalent after they made their decisions, and their decisions are based on rather unstable grounds. Therefore, intervention objectives were to improve HPV-vaccination uptake and informed decision-making, and to decrease decisional conflict among mothers of invited girls. Computer-tailoring was chosen as the main method; virtual assistants were chosen as a practical application to deliver interactive tailored feedback. To maximize compatibility with the needs of the target group, a user-centered design strategy by means of focus groups and online experiments was applied. In these, prototypes were tested and sequentially refined. Finally, efficacy, effectiveness, and acceptability of the intervention were tested in a randomized controlled trial. Results showed a significant positive effect of the intervention on informed decision-making, decisional conflict, and nearly all determinants of HPV-vaccination uptake (P < 0.001). Mothers evaluated the intervention as highly positive. Discussion: Using IM led to an innovative effective intervention for promoting HPV-vaccination acceptability. The intervention maps will aid in interpreting the results of our evaluation studies. Moreover, it will ease the comparison of design rationales across interventions, and may provide leads for the development of other eHealth interventions. This paper adds to the plea for systematic reporting of design rationales constituting the process of developing interventions.
    • The SysteMHC Atlas project.

      Shao, Wenguang; Pedrioli, Patrick G A; Wolski, Witold; Scurtescu, Cristian; Schmid, Emanuel; Vizcaíno, Juan A; Courcelles, Mathieu; Schuster, Heiko; Kowalewski, Daniel; Marino, Fabio; et al. (2018-01-04)
      Mass spectrometry (MS)-based immunopeptidomics investigates the repertoire of peptides presented at the cell surface by major histocompatibility complex (MHC) molecules. The broad clinical relevance of MHC-associated peptides, e.g. in precision medicine, provides a strong rationale for the large-scale generation of immunopeptidomic datasets and recent developments in MS-based peptide analysis technologies now support the generation of the required data. Importantly, the availability of diverse immunopeptidomic datasets has resulted in an increasing need to standardize, store and exchange this type of data to enable better collaborations among researchers, to advance the field more efficiently and to establish quality measures required for the meaningful comparison of datasets. Here we present the SysteMHC Atlas (https://systemhcatlas.org), a public database that aims at collecting, organizing, sharing, visualizing and exploring immunopeptidomic data generated by MS. The Atlas includes raw mass spectrometer output files collected from several laboratories around the globe, a catalog of context-specific datasets of MHC class I and class II peptides, standardized MHC allele-specific peptide spectral libraries consisting of consensus spectra calculated from repeat measurements of the same peptide sequence, and links to other proteomics and immunology databases. The SysteMHC Atlas project was created and will be further expanded using a uniform and open computational pipeline that controls the quality of peptide identifications and peptide annotations. Thus, the SysteMHC Atlas disseminates quality controlled immunopeptidomic information to the public domain and serves as a community resource toward the generation of a high-quality comprehensive map of the human immunopeptidome and the support of consistent measurement of immunopeptidomic sample cohorts.
    • Tall height and obesity are associated with an increased risk of aggressive prostate cancer: results from the EPIC cohort study.

      Perez-Cornago, Aurora; Appleby, Paul N; Pischon, Tobias; Tsilidis, Konstantinos K; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Kaaks, Rudolf; Kühn, Tilman; Boeing, Heiner; et al. (2017-07-13)
      The relationship between body size and prostate cancer risk, and in particular risk by tumour characteristics, is not clear because most studies have not differentiated between high-grade or advanced stage tumours, but rather have assessed risk with a combined category of aggressive disease. We investigated the association of height and adiposity with incidence of and death from prostate cancer in 141,896 men in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
    • Tannic acid promotes ion release of copper oxide nanoparticles: Impacts from solution pH change and complexation reactions.

      Zhao, Jing; Liu, Yang; Pan, Bo; Gao, Guoqian; Liu, Ying; Liu, Siqian; Liang, Ni; Zhou, Dandan; Vijver, Martina G; Peijnenburg, Willie J G M (2017-12-15)
      The increasing number of applications in which copper oxide nanoparticles (CuO NPs) are used, may lead to potential release of CuO NPs into the environment. However, the impact of natural organic matters on the behavior and fate of CuO NPs in aquatic media is still largely unknown. In this study, the dissolution and aggregation of CuO NPs under the exposure of tannic acid (TA) were monitored over a period of 72 h, with a focus on assessing the contributions of solution pH changes and complexation reactions. Results showed that the total amount of Cu2+released from CuO NPs increased in the presence of TA especially at the highest TA concentration of 73.5 μmol/L. Although TA was observed to wrap around the CuO NPs, the aggregation of CuO NPs was not strongly influenced by TA and by the solution pH as investigated in this study. The kinetics of Cu2+release were fitted using the modified pseudo second-order model and the rate of dissolution was assessed to be highest at TA = 14.7 μmol/L. At pH = 4, the increased H+concentration was responsible for increased Cu2+release, whereas the complexation reaction between Cu2+and TA dominated at pH = 7. These findings suggested that the effects of TA on the dissolution of CuO NPs were a combination of solution pH change and complexation reaction, the relative fractions of which also depended on the solution pH. Additionally, the percentage of Cu2+released from the CuO NPs was found to increase upon decreasing concentrations of CuO NPs. Our work helps to further understand how and to which extent natural organic matters affect the behavior and fate of CuO NPs.
    • Tar, nicotine and carbon monoxide yield of UK cigarettes and the risk of non-muscle-invasive and muscle-invasive bladder cancer.

      van Osch, Frits H M; Pauwels, Charlotte G G M; Jochems, Sylvia H J; Fayokun, Ranti; James, Nicholas D; Wallace, D Michael A; Cheng, Kar-Keung; Bryan, Richard T; van Schooten, Frederik J; Zeegers, Maurice P (2017-07-04)
      Cigarette smoking is a major risk factor for bladder cancer (BC); however, the impact of cigarette content remains unclear. This study aims to investigate tar, nicotine and carbon monoxide (TNCO) yields of different filtered cigarettes in relation to BC risk. From the Bladder Cancer Prognosis Programme 575 non-muscle-invasive bladder cancer (NMIBC) cases, 139 muscle-invasive bladder cancer (MIBC) cases and 130 BC-free controls with retrospective data on smoking behaviour and cigarette brand were identified. Independently measured TNCO yields of cigarettes sold in the UK were obtained through the UK Department of Health and merged with the Bladder Cancer Prognosis Programme dataset to estimate the daily intake of TNCO. BC risk increased by TNCO intake category for NMIBC cases (P <0.050 in all multivariate models), but only for the daily intake of tar for MIBC cases (P=0.046) in multivariate models. No difference in risk was observed between smokers of low-tar/low-nicotine and high-tar/high-nicotine cigarettes compared with never smokers, either for NMIBC (P=0.544) or MIBC (P=0.449). High daily intake of TNCO additionally increases the risk of both NMIBC and MIBC compared with low daily intake. However, as there is no difference in BC risk between low-tar/low-nicotine and high-tar/high-nicotine cigarette smokers, it remains unclear whether smoking behaviour or TNCO yield of cigarettes explains this association.
    • Targeted outreach hepatitis B vaccination program in high-risk adults: The fundamental challenge of the last mile.

      Mangen, M-J J; Stibbe, H; Urbanus, A; Siedenburg, E C; Waldhober, Q; de Wit, G A; van Steenbergen, J E (2017-05-31)
      The aim of this study was to evaluate the cost-effectiveness of the on-going decentralised targeted hepatitis B vaccination program for behavioural high-risk groups operated by regional public health services in the Netherlands since 1-November-2002. Target groups for free vaccination are men having sex with men (MSM), commercial sex workers (CSW) and hard drug users (HDU). Heterosexuals with a high partner change rate (HRP) were included until 1-November-2007.
    • Targeting the thioredoxin system as a novel strategy against B cell acute lymphoblastic leukemia.

      Fidyt, Klaudyna; Pastorczak, Agata; Goral, Agnieszka; Szczygiel, Kacper; Fendler, Wojciech; Muchowicz, Angelika; Bartlomiejczyk, Marcin Adam; Madzio, Joanna; Cyran, Julia; Graczyk-Jarzynka, Agnieszka; et al. (2019-03-12)
      B cell precursor acute lymphoblastic leukemia (BCP-ALL) is a genetically heterogeneous blood cancer characterized by abnormal expansion of immature B cells. Although intensive chemotherapy provides high cure rates in a majority of patients, subtypes harboring certain genetic lesions, such as MLL rearrangements or BCR-ABL1 fusion, remain clinically challenging, necessitating a search for other therapeutic approaches. Herein, we aimed to validate antioxidant enzymes of the thioredoxin system as potential therapeutic targets in BCP-ALL. We observed oxidative stress along with aberrant expression of the enzymes associated with the activity of thioredoxin antioxidant system in BCP-ALL cells. Moreover, we found that auranofin and adenanthin, inhibitors of the thioredoxin system antioxidant enzymes, effectively kill BCP-ALL cell lines and pediatric and adult BCP-ALL primary cells, including primary cells co-cultured with bone marrow-derived stem cells. Furthermore, auranofin delayed the progression of leukemia in MLL-rearranged patient-derived xenograft model and prolonged the survival of leukemic NSG mice. Our results unveil the thioredoxin system as a novel target for BCP-ALL therapy, and indicate that further studies assessing the anticancer efficacy of combinations of thioredoxin system inhibitors with conventional anti BCP-ALL drugs should be continued.
    • Tekenencefalitis, een nieuwe ziekte in Nederland?

      Brandwagt D; Spit S; Sprong H; Broek I van den; Broek I van den; Gassner F; Fanoy E (2017-04-24)
    • Tekenencefalitis: een lastige diagnose

      Hira V; Reimerink JHJ (2017-07)
    • Template for the description of cell-based toxicological test methods to allow evaluation and regulatory use of the data.

      Krebs, Alice; Waldmann, Tanja; Wilks, Martin F; Van Vugt-Lussenburg, Barbara M A; Van der Burg, Bart; Terron, Andrea; Steger-Hartmann, Thomas; Ruegg, Joelle; Rovida, Costanza; Pedersen, Emma; et al. (2019-01-01)
    • Temporal and spatial analysis of psittacosis in association with poultry farming in the Netherlands, 2000-2015.

      Hogerwerf, Lenny; Holstege, Manon M C; Benincà, Elisa; Dijkstra, Frederika; van der Hoek, Wim (2017-07-26)
      Human psittacosis is a highly under diagnosed zoonotic disease, commonly linked to psittacine birds. Psittacosis in birds, also known as avian chlamydiosis, is endemic in poultry, but the risk for people living close to poultry farms is unknown. Therefore, our study aimed to explore the temporal and spatial patterns of human psittacosis infections and identify possible associations with poultry farming in the Netherlands.
    • Temporal associations between national outbreaks of meningococcal serogroup W and C disease in the Netherlands and England: an observational cohort study.

      Knol, Mirjam J; Hahné, Susan J M; Lucidarme, Jay; Campbell, Helen; de Melker, Hester E; Gray, Stephen J; Borrow, Ray; Ladhani, Shamez N; Ramsay, Mary E; van der Ende, Arie (2017-10)
      Since 2009, the incidence of meningococcal serogroup W disease has increased rapidly in the UK because of a single strain (the so-called original UK strain) belonging to the hypervirulent sequence type-11 clonal complex (cc11), with a variant outbreak strain (the so-called 2013 strain) emerging in 2013. Subsequently, the Netherlands has had an increase in the incidence of meningococcal serogroup W disease. We assessed the temporal and phylogenetic associations between the serogroup W outbreaks in the Netherlands and England, and the historical serogroup C outbreaks in both countries.
    • Temporal-Spatial Variation in Questing Tick Activity in the Netherlands: The Effect of Climatic and Habitat Factors.

      Hartemink, Nienke; van Vliet, Arnold; Sprong, Hein; Jacobs, Frans; Garcia-Martí, Irene; Zurita-Milla, Raul; Takken, Willem (2019-02-27)
      Longitudinal studies are fundamental in the assessment of the effect of environmental factors on tick population dynamics. In this study, we use data from a 10-year study in 11 different locations in the Netherlands to gauge the effects of climatic and habitat factors on the temporal and spatial variation in questing tick activity. Marked differences in the total number of ticks were found between locations and between years. We investigated which climatic and habitat factors might explain this variation. No effects of climatic factors on the total number of ticks per year were observed, but we found a clear effect of temperature on the onset of tick activity. In addition, we found positive associations between (1) humus layer thickness and densities of all three stages, (2) moss and blackberry abundance and larval densities, and (3) blueberry abundance and densities of larva and nymphs. We conclude that climatic variables do not have a straightforward association with tick density in the Netherlands, but that winter and spring temperatures influence the onset of tick activity. Habitats with apparently similar vegetation types can still differ in tick population densities, indicating that local composition of vegetation and especially of wildlife is likely to contribute considerably to the spatial variation in tick densities.
    • Ten years of HPV vaccination in the Netherlands: current evidence and future challenges in HPV-related disease prevention.

      Qendri, V; Schurink-Van 't Klooster, T M; Bogaards, J A; Berkhof, J (2018-12-01)
      Girls-only vaccination against human papillomavirus (HPV) type 16 and 18 was implemented in the Netherlands in 2009. Despite the evidence of the efficacy against precancerous lesions, cross-protection induced by the vaccine and a greater potential for cancer prevention than cervical cancer only, vaccine coverage in the girls-only program has remained below target levels. Areas covered: In this paper, we review the literature from the Netherlands on the effectiveness and cost-effectiveness of HPV vaccination since vaccine introduction, give an account of the coverage, safety and effectiveness of HPV vaccination as has been reported in the Dutch surveillance program and discuss challenges of the current HPV vaccination program. Expert commentary: Girls-only HPV vaccination may confer a substantial health gain in HPV-related disease prevention. However, vaccine coverage declined remarkably recently possibly related to safety concerns, limiting the benefits from girls' vaccination and increasing the potential additional benefit of sex-neutral HPV vaccination. Considering the emergence of novel vaccination and screening options and the change from cytology- to HPV-based screening in 2017, further research is required to inform decisions on the optimization of an integrated vaccination and screening program.
    • Test sensitivity of a commercial serine protease digestion kit for the detection of Trichinella spiralis and Trichinella pseudospiralis larvae in pig muscle.

      Franssen, F; Johne, A; van der Giessen, J; Nöckler, K; Mayer-Scholl, A (2019-04-01)
      The reference method for Trichinella detection at meat inspection is the magnetic stirrer method (MSM) utilising HCl-pepsin for pooled sample digestion. Due to availability and quality issues with pepsin, alternative digestion methods are being offered, such as the Priocheck Trichinella AAD kit (T-AAD), based on serine endopeptidase digestion. In this study the T-AAD kit was compared to the reference method. Minced pork samples were spiked with T. spiralis muscle larvae (ML) with- and without capsule or T. pseudospiralis ML, and analysed with both tests. Test results of individually spiked test samples were analysed by generalised linear modelling. The T-AAD test kit was comparable to the reference method for the qualitative detection of T. spiralis in pigs, but not quantitatively. Overall, 94% of spiked T. spiralis were recovered using MSM against 75.2% when using T-AAD (p < 0.0001). Using the MSM 80.0% of spiked T. pseudospiralis were recovered against 20% with the T-AAD (p < 0.0001). Based on our experience with the T-AAD kit, we strongly recommend validating the method on site prior to introduction into routine diagnostic laboratories, but this will not alleviate the poor test sensitivity of the T-AAD for the detection of T. pseudospiralis.
    • Testing developmental toxicity in a second species: are the differences due to species or replication error?

      Braakhuis, Hedwig M; Theunissen, Peter T; Slob, Wout; Rorije, Emiel; Piersma, Aldert H (2019-06-19)