• Een uitbraak met Campylobacter fetus na het eten van rauwmelkse schapenkaas : Hoe traceer je de bron van een uitbraak

      Koppenaal, H; Groenendijk, F; van den Berge, M; Verkade, E; Verduin, K; Zomer, A L; Duim, B; Wagenaar, J A; Tijsma, A S L; Spierenburg, M A H; te Wierik, M J M (2017-10-17)
      Campylobacter fetus is a species of gram-negative bacteria whose primary reservoir is the gastrointestinal tracts of cattle and sheep. Human infections are rare, though often invasive and sometimes fatal. In this paper, we studied an outbreak of six patients with a C. fetus infection and outlined their disease histories. In each case we were able to identify factors that led to a reduced resistance, including pre-existing illnesses and old age. Because of the unusually high number of patients that presented in a time period of only five months, the Community Health Services were commissioned to identify the source of infection. Using whole genome sequencing, we showed that 5 out of 6 patients belonged to the same cluster. This One Health approach resulted in the conclusion that the infection originated from unpasteurized sheep's milk processed into unripened cheese. Finally, various measures were put into place to prevent any further outbreaks.
    • Under-vaccinated groups in Europe and their beliefs, attitudes and reasons for non-vaccination; two systematic reviews.

      Fournet, N; Mollema, L; Ruijs, W L; Harmsen, I A; Keck, F; Durand, J Y; Cunha, M P; Wamsiedel, M; Reis, R; French, J; Smit, E G; Kitching, A; van Steenbergen, J E (2018-01-30)
      Despite effective national immunisation programmes in Europe, some groups remain incompletely or un-vaccinated ('under-vaccinated'), with underserved minorities and certain religious/ideological groups repeatedly being involved in outbreaks of vaccine preventable diseases (VPD). Gaining insight into factors regarding acceptance of vaccination of 'under-vaccinated groups' (UVGs) might give opportunities to communicate with them in a trusty and reliable manner that respects their belief system and that, maybe, increase vaccination uptake. We aimed to identify and describe UVGs in Europe and to describe beliefs, attitudes and reasons for non-vaccination in the identified UVGs.
    • Unifying the functional diversity in natural and cultivated soils using the overall body-mass distribution of nematodes.

      Mulder, Christian; Maas, Rob (2017-11-28)
      Sustainable use of our soils is a key goal for environmental protection. As many ecosystem services are supported belowground at different trophic levels by nematodes, soil nematodes are expected to provide objective metrics for biological quality to integrate physical and chemical soil variables. Trait measurements of body mass carried out at the individual level can in this way be correlated with environmental properties that influence the performance of soil biota.
    • Unraveling the drivers of regional variation in healthcare spending by analyzing prevalent chronic diseases.

      de Vries, Eline F; Heijink, Richard; Struijs, Jeroen N; Baan, Caroline A (2018-05-03)
      To indicate inefficiencies in health systems, previous studies examined regional variation in healthcare spending by analyzing the entire population. As a result, population heterogeneity is taken into account to a limited extent only. Furthermore, it clouds a detailed interpretation which could be used to inform regional budget allocation decisions to improve quality of care of one chronic disease over another. Therefore, we aimed to gain insight into the drivers of regional variation in healthcare spending by studying prevalent chronic diseases.
    • Unveiling the important roles of coexisting contaminants on photochemical transformations of pharmaceuticals: Fibrate drugs as a case study.

      Zhang, Ya-Nan; Zhou, Yangjian; Qu, Jiao; Chen, Jingwen; Zhao, Jianchen; Lu, Ying; Li, Chao; Xie, Qing; Peijnenburg, Willie J G M (2018-09-15)
      Pharmaceuticals are a group of ubiquitous emerging pollutants, many of which have been shown to undergo efficient photolysis in the environment. Photochemically produced reactive intermediates (PPRIs) sensitized by the pharmaceuticals in sunlit natural waters may induce photodegradation of coexisting compounds. In this study, the roles of coexisting contaminants on the phototransformation of pharmaceuticals were unveiled with the fibrate drugs gemfibrozil (GMF), fenofibrate (FNF), and fenofibric acid (FNFA) as model compounds. GMF undergoes initial concentration dependent photodegradation due to the involvement of singlet oxygen (1O2) initiated self-sensitized photolysis, and undergoes pH dependent photodegradation due to dissociation and hydroxyl radical (OH) generation. The decarboxylated intermediates of GMF and coexisting FNFA significantly accelerated the photodegradation of GMF. The promotional effects of the decarboxylated intermediates are attributed to generation of PPRIs, e.g. 1O2, superoxide (O2-), that subsequently react with GMF. Besides, FNFA can also promote the photodegradation of GMF through the electron transfer reaction from ground state GMF to excited state FNFA, leading to the formation of decarboxylated intermediates. The formed intermediates can subsequently also facilitate GMF photodegradation. The results presented here provided valuable novel insights into the effects of coexisting contaminants on the photodegradation of pharmaceuticals in polluted waters.
    • Update on Neonatal Herpes Simplex Epidemiology in the Netherlands: A Health Problem of Increasing Concern?

      van Oeffelen, Louise; Biekram, Manisha; Poeran, Jashvant; Hukkelhoven, Chantal; Galjaard, Sander; van der Meijden, Wim; Op de Coul, Eline (2018-01-18)
      This paper provides an update on the incidence of neonatal herpes, guideline adherence by health care professionals (HCP), and trends in genital herpes simplex virus (HSV) infection during pregnancy in the Netherlands.
    • Updated cost-effectiveness and risk-benefit analysis of two infant rotavirus vaccination strategies in a high-income, low-endemic setting.

      Bruijning-Verhagen, P; van Dongen, J A P; Verberk, J D M; Pijnacker, R; van Gaalen, R D; Klinkenberg, D; de Melker, H E; Mangen, M-J J (2018)
      Since 2013, a biennial rotavirus pattern has emerged in the Netherlands with alternating high and low endemic years and a nearly 50% reduction in rotavirus hospitalization rates overall, while infant rotavirus vaccination has remained below 1% throughout. As the rotavirus vaccination cost-effectiveness and risk-benefit ratio in high-income settings is highly influenced by the total rotavirus disease burden, we re-evaluated two infant vaccination strategies, taking into account this recent change in rotavirus epidemiology.
    • Urban Chikungunya in the Middle East and North Africa: A systematic review.

      Humphrey, John M; Cleton, Natalie B; Reusken, Chantal B E M; Glesby, Marshall J; Koopmans, Marion P G; Abu-Raddad, Laith J (2017-06)
      The epidemiology of Chikungunya virus (CHIKV) in the Middle East and North Africa (MENA) is not well characterized despite increasing recognition of its expanding infection and disease burden in recent years.
    • Urban road traffic noise and noise annoyance-a study on perceived noise control and its value among the elderly.

      Riedel, Natalie; Köckler, Heike; Scheiner, Joachim; van Kamp, Irene; Erbel, Raimund; Loerbroks, Adrian; Claßen, Thomas; Bolte, Gabriele (2018-07-26)
      Noise annoyance may reflect a pro-participatory attitude towards public information and consultation according to the European Environmental Noise Directive. However, noise annoyance is also indicative of a stress response to perceived uncontrollable noise exposure. Using cross-sectional data on a sample of elderly citizens (n = 1772), we investigated whether the value residents ascribed to being able to control noise exposure at home moderated the potential indirect effect of road traffic noise on annoyance through perceived noise control. Our results confirmed the presence of such a moderated mediation, which may justify studying the impact of residents' valuing perceived noise control on participation readiness.
    • The urgency for optimization and harmonization of thyroid hormone analyses and their interpretation in developmental and reproductive toxicology studies.

      Beekhuijzen, Manon; Schneider, Steffen; Barraclough, Narinder; Hallmark, Nina; Hoberman, Alan; Lordi, Sheri; Moxon, Mary; Perks, Deborah; Piersma, Aldert H; Makris, Susan L (2018-05-02)
      In recent years several OECD test guidelines have been updated and some will be updated shortly with the requirement to measure thyroid hormone levels in the blood of mammalian laboratory species. There is, however, an imperative need for clarification and guidance regarding the collection, assessment, and interpretation of thyroid hormone data for regulatory toxicology and risk assessment. Clarification and guidance is needed for 1) timing and methods of blood collection, 2) standardization and validation of the analytical methods, 3) triggers for additional measurements, 4) the need for T4 measurements in postnatal day (PND) 4 pups, and 5) the interpretation of changes in thyroid hormone levels regarding adversity. Discussions on these topics have already been initiated, and involve expert scientists from a number of international multisector organizations. This paper provides an overview of existing issues, current activities and recommendations for moving forward.
    • Urine as Sample Type for Molecular Diagnosis of Natural Yellow Fever Virus Infections.

      Reusken, Chantal B E M; Knoester, Marjolein; GeurtsvanKessel, Corine; Koopmans, Marion; Knapen, Daan G; Bierman, Wouter F W; Pas, Suzan (2017-11)
    • Usability of the international HAVNet hepatitis A virus database for geographical annotation, backtracing and outbreak detection.

      Kroneman, Annelies; de Sousa, Rita; Verhoef, Linda; Koopmans, Marion P G; Vennema, Harry; On Behalf Of The HAVNet Network (2018-09)
      BackgroundHAVNet is an international laboratory network sharing sequences and corresponding metadata on hepatitis A virus in an online database. Aim: We give an overview of the epidemiological and genetic data and assess the usability of the present dataset for geographical annotation, backtracing and outbreak detection. Methods: A descriptive analysis was performed on the timeliness, completeness, epidemiological data and geographic coverage of the dataset. Length and genomic region of the sequences were reviewed as well as the numerical and geographical distribution of the genotypes. The geographical signal in the sequences was assessed based on a short common nt stretch using a 100% identity analysis. Results: The 9,211 reports were heterogeneous for completeness and timeliness, and for length and genomic region of the sequences. Some parts of the world were not represented by the sequences. Geographical differences in prevalence of HAV genotypes described previously could be confirmed with this dataset and for a third (1,075/3,124) of the included sequences, 100% identity of the short common sequence coincided with an identical country of origin. Conclusion: Analysis of a subset of short, shared sequences indicates that a geographical annotation on the level of individual countries is possible with the HAVNet data. If the current incompleteness and heterogeneity of the data can be improved on, HAVNet could become very useful as a worldwide reference set for geographical annotation and for backtracing and outbreak detection.
    • The use of generic failure frequencies in QRA: the quality and use of failure frequencies and how to bring them up-to-date.

      Beerens, H I; Post, J G; Uijt de Haag, P A M (2006-03-31)
      Quantitative Risk Assessment (QRA) is a method which is often used in the chemical industry and, in some countries, also in land-use planning. In QRA calculations the frequency of an accident scenario is most often assessed by a generic failure frequency approach. The credibility and validity of the failure frequencies used in the Netherlands for land-use planning is evaluated by means of an historical review. Furthermore, the possibility is presented how these generic data can be revised and updated.
    • Use of quantum-chemical descriptors to analyse reaction rate constants between organic chemicals and superoxide/hydroperoxyl (O2•-/HO2•).

      Nolte, Tom M; Peijnenburg, Willie J G M (2018-11-13)
      The reaction between superoxide (O2•-) and organic chemicals is of interest in many scientific disciplines including biology and synthetic chemistry, as well as for the evaluation of chemical fate in the environment. Due to limited data and lack of congeneric modelling, the involvement of superoxide in many complex processes cannot be adequately evaluated. In this study, we developed new quantitative structure-property relationship (QSPR) models for the prediction of the aqueous-phase rate constant for the reaction between superoxide and a wide variety of organic chemicals reacting via one-electron oxidation, reduction and hydrogen-transfer. It is shown that the relative importance of these pathways is related to frontier molecular orbital (FMO) interaction and to pH. The class-specific QSPRs developed have good statistics (0.84 ≤ R2 ≤ 0.92). For non-congeneric chemicals it is demonstrated that the reactivity toward superoxide can be described by applying explicit descriptions for competition kinetics and speciation. Therefore, the relationships developed in this study are useful as a starting point to evaluate more complex molecules having, for example, multiple reactive functional groups, labile H bonds, or delocalised cationic charges. However, additional kinetic data and more rigorous computation are needed to evaluate such molecules.
    • Use of Repeated Blood Pressure and Cholesterol Measurements to Improve Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis.

      Paige, Ellie; Barrett, Jessica; Pennells, Lisa; Sweeting, Michael; Willeit, Peter; Di Angelantonio, Emanuele; Gudnason, Vilmundur; Nordestgaard, Børge G; Psaty, Bruce M; Goldbourt, Uri; Best, Lyle G; Assmann, Gerd; Salonen, Jukka T; Nietert, Paul J; Verschuren, W M Monique; Brunner, Eric J; Kronmal, Richard A; Salomaa, Veikko; Bakker, Stephan J L; Dagenais, Gilles R; Sato, Shinichi; Jansson, Jan-Håkan; Willeit, Johann; Onat, Altan; de la Cámara, Agustin Gómez; Roussel, Ronan; Völzke, Henry; Dankner, Rachel; Tipping, Robert W; Meade, Tom W; Donfrancesco, Chiara; Kuller, Lewis H; Peters, Annette; Gallacher, John; Kromhout, Daan; Iso, Hiroyasu; Knuiman, Matthew; Casiglia, Edoardo; Kavousi, Maryam; Palmieri, Luigi; Sundström, Johan; Davis, Barry R; Njølstad, Inger; Couper, David; Danesh, John; Thompson, Simon G; Wood, Angela (2017-10-15)
      The added value of incorporating information from repeated blood pressure and cholesterol measurements to predict cardiovascular disease (CVD) risk has not been rigorously assessed. We used data on 191,445 adults from the Emerging Risk Factors Collaboration (38 cohorts from 17 countries with data encompassing 1962-2014) with more than 1 million measurements of systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol. Over a median 12 years of follow-up, 21,170 CVD events occurred. Risk prediction models using cumulative mean values of repeated measurements and summary measures from longitudinal modeling of the repeated measurements were compared with models using measurements from a single time point. Risk discrimination (C-index) and net reclassification were calculated, and changes in C-indices were meta-analyzed across studies. Compared with the single-time-point model, the cumulative means and longitudinal models increased the C-index by 0.0040 (95% confidence interval (CI): 0.0023, 0.0057) and 0.0023 (95% CI: 0.0005, 0.0042), respectively. Reclassification was also improved in both models; compared with the single-time-point model, overall net reclassification improvements were 0.0369 (95% CI: 0.0303, 0.0436) for the cumulative-means model and 0.0177 (95% CI: 0.0110, 0.0243) for the longitudinal model. In conclusion, incorporating repeated measurements of blood pressure and cholesterol into CVD risk prediction models slightly improves risk prediction.
    • Using volunteered observations to map human exposure to ticks.

      Garcia-Marti, Irene; Zurita-Milla, Raul; Harms, Margriet G; Swart, Arno (2018-10-18)
      Lyme borreliosis (LB) is the most prevalent tick-borne disease in Europe and its incidence has steadily increased over the last two decades. In the Netherlands alone, more than 20,000 citizens are affected by LB each year. Because of this, two Dutch citizen science projects were started to monitor tick bites. Both projects have collected nearly 50,000 geo-located tick bite reports over the period 2006-2016. The number of tick bite reports per area unit is a proxy of tick bite risk. This risk can also be modelled as the result of the interaction of hazard (e.g. tick activity) and human exposure (e.g. outdoor recreational activities). Multiple studies have focused on quantifying tick hazard. However, quantifying human exposure is a harder task. In this work, we make a first step to map human exposure to ticks by combining tick bite reports with a tick hazard model. Our results show human exposure to tick bites in all forested areas of the Netherlands. This information could facilitate the cooperation between public health specialists and forest managers to create better mitigation campaigns for tick-borne diseases, and it could also support the design of improved plans for ecosystem management.
    • V-MRSA-dragerschap en het dagelijks leven van veehouders

      Domsdorf TAPB; Haverkate MR; Eilers R; Timen A (2017-09)
    • Vaccinating children against influenza increases variability in epidemic size.

      Backer, J A; van Boven, M; van der Hoek, W; Wallinga, J (2018-10-10)
      Seasonal influenza causes a high disease burden. Many influenza vaccination programmes target the elderly and persons at high risk of complications. Some countries have recommended or even implemented a paediatric vaccination programme. Such a programme is expected to reduce influenza transmission in the population, offering direct protection to the vaccinated children and indirect protection to the elderly. We study the impact of a child vaccination programme with an age- and risk-structured transmission model, calibrated to data of 11 influenza seasons in the Netherlands. The model tracks the build-up of immunes and susceptibles in each age cohort over time, and it allows for seasonal variation in vaccine match and antigenic drift. Different vaccination strategies are evaluated for three target age groups (2-3, 2-12 and 2-16 year olds) over the full range of vaccination coverages (0-100%). The results show that the paediatric vaccination programme has only a limited impact on the elderly age groups, which account for most influenza morbidity and mortality. This is due to two notable changes in infection dynamics. First, an age shift is observed: influenza infections are reduced in vaccinated children, but are increased in young adults with limited natural immunity after years of vaccination. These young adults assume the role of driving the epidemic. Second, a year with low influenza activity can be followed by a large epidemic due to build-up of susceptibles. This variation of the infection attack rate increases with increasing vaccination coverage. The increased variability in the infection attack rate implies that health care facilities should be prepared for rare but larger peaks in influenza patients. Moreover, vaccinating the group with the highest transmission potential, results in a larger dependency on a secure vaccine supply. These arguments should be taken into account in the decision to introduce mass vaccination of school-aged children against influenza.
    • Vaccine antigens modulate the innate response of monocytes to Al(OH)3.

      Kooijman, Sietske; Brummelman, Jolanda; van Els, Cécile A C M; Marino, Fabio; Heck, Albert J R; van Riet, Elly; Metz, Bernard; Kersten, Gideon F A; Pennings, Jeroen L A; Meiring, Hugo D (2018)
      Aluminum-based adjuvants have widely been used in human vaccines since 1926. In the absence of antigens, aluminum-based adjuvants can initiate the inflammatory preparedness of innate cells, yet the impact of antigens on this response has not been investigated so far. In this study, we address the modulating effect of vaccine antigens on the monocyte-derived innate response by comparing processes initiated by Al(OH)3 and by Infanrix, an Al(OH)3-adjuvanted trivalent combination vaccine (DTaP), containing diphtheria toxoid (D), tetanus toxoid (T) and acellular pertussis (aP) vaccine antigens. A systems-wide analysis of stimulated monocytes was performed in which full proteome analysis was combined with targeted transcriptome analysis and cytokine analysis. This comprehensive study revealed four major differences in the monocyte response, between plain Al(OH)3 and DTaP stimulation conditions: (I) DTaP increased the anti-inflammatory cytokine IL-10, whereas Al(OH)3 did not; (II) Al(OH)3 increased the gene expression of IFNγ, IL-2 and IL-17a in contrast to the limited induction or even downregulation by DTaP; (III) increased expression of type I interferons-induced proteins was not observed upon DTaP stimulation, but was observed upon Al(OH)3 stimulation; (IV) opposing regulation of protein localization pathways was observed for Al(OH)3 and DTaP stimulation, related to the induction of exocytosis by Al(OH)3 alone. This study highlights that vaccine antigens can antagonize Al(OH)3-induced programming of the innate immune responses at the monocyte level.
    • Vaccine preferences and acceptance of older adults.

      Eilers, R; de Melker, H E; Veldwijk, J; Krabbe, P F M (2017-05-15)
      Expanding vaccination programs for the older population might be important as older adults are becoming a larger proportion of the general population. The aim of this study is to determine the relative importance of vaccine and disease specific characteristics and acceptance for Dutch older adults, including pneumococcal disease, herpes zoster, pertussis vaccination, and influenza vaccination.