• 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.
    • Underreporting of meningococcal disease incidence in the Netherlands: results from a capture-recapture analysis based on three registration sources with correction for false positive diagnoses.

      Greeff, Sabine C de; Spanjaard, Lodewijk; Dankert, Jacob; Hoebe, Christian J P A; Nagelkerke, Nico J D; Melker, Hester E de (2006-05-10)
      In order to come to a reliable evaluation of the effectiveness of the chosen vaccination policy regarding meningococcal disease, the completeness of registrations on meningococcal disease in the Netherlands was estimated with the capture-recapture method. Data over 1993-1998 were collected from (A) mandatory notifications (n = 2926); (B) hospital registration (n = 3968); (C) laboratory surveillance (n = 3484). As the standard capture-recapture method does not take into account false positive diagnoses, we developed a model to adjust for the lack of specificity of our sources. We estimated that 1363 cases were not registered in any of the three sources in the period of study. The completeness of the three sources was therefore estimated at 49% for source A, 67% for source B and 58% for source C. After adjustment for false positive diagnoses, the completeness of source A, B, and C was estimated as 52%, 70% and 62%, respectively. The capture-recapture methods offer an attractive approach to estimate the completeness of surveillance sources and hence contribute to a more accurate estimate of the disease burden under study. However, the method does not account for higher-order interactions or presence of false positive diagnoses. Being aware of these limitations, the capture-recapture method still elucidates the (in)completeness of sources and gives a rough estimate of this (in)completeness. This makes a more accurate monitoring of disease incidence possible and hence attributes to a more reliable foundation for the design and evaluation of health interventions such as vaccination programs.
    • Understanding conflicting views of endocrine disruptor experts: a pilot study using argumentation analysis

      Clahsen, SCS; van Klaveren, HS; Vermeire, TG; van Kamp, I; Garssen, B; Piersma, AH; Lebret, E (2019-01-28)
    • 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 oseltamivir in Dutch nursing homes during the 2004-2005 influenza season.

      Sande, Marianne A B van der; Ruijs, Wilhelmina L M; Meijer, Adam; Cools, Herman J M; Plas, Simone M van der (2006-11-10)
      To assess the implementation of guidelines for using neuraminidase inhibitors in the control of influenza outbreaks in Dutch nursing homes, data were collected on prophylactic and therapeutic use of anti-viral medication, indications for use and criteria for prescribing, based on experiences during the influenza season 2004-2005 in a retrospective cross-sectional survey among Dutch nursing homes after the 2004-2005 season. Ninety/194 (49%) participating nursing homes reported an outbreak of influenza-like illness; in 57/194 (29%) influenza was laboratory confirmed. In 37/57 homes (65%) oseltamivir had been used as prophylaxis. Prophylactic use was extended to all residents and staff in 6/37 (16%) of homes, but limited in the others. In 9/37 (24%) no staff were issued prophylaxis. Among clinicians with laboratory confirmed influenza, 41/46 (89%) had used oseltamivir therapeutically. Main reasons for not prescribing oseltamivir for prophylaxis and/or therapy were lack of scientific evidence, high costs, and absent or delayed laboratory confirmation. Logistical bottlenecks in diagnosis, cost-effectiveness concerns, and lack of an evidence-base hamper full integration in policy and should be addressed.
    • 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.
    • Use of saliva to monitor meningococcal vaccine responses: proposing a threshold in saliva as surrogate of protection.

      van Ravenhorst, Mariëtte B; van der Klis, Fiona R M; van Rooijen, Debbie M; Sanders, Elisabeth A M; Berbers, Guy A M (2019-01-05)
      Mucosal antibodies against capsular polysaccharides offer protection against acquisition and carriage of encapsulated bacteria like Neisseria meningitidis serogroup C. Measurements of salivary antibodies as replacement for blood testing has important (cost-effective) advantages, particular in studies that assess the impact of large-scale vaccination or in populations in which blood sampling is difficult. This study aimed to estimate a threshold for meningococcal IgG salivary antibody levels to discriminate between unprotected and protected vaccinated individuals. MenA-, MenC-, MenW- and MenY-polysaccharide (PS) specific IgG levels in serum and saliva from participants in a meningococcal vaccination study were measured using the fluorescent-bead-based multiplex immunoassay. Functional antibody titers in serum against the four serogroups were measured with serum bactericidal assay using rabbit complement (rSBA). A threshold for salivary IgG was determined by analysis of ROC curves using a serum rSBA titer ≥128 as correlate of protection. The area under the curve (AUC) was calculated to quantify the accuracy of the salivary test and was considered adequate when ≥0.80. The optimal cut-off was considered adequate when salivary IgG cut-off levels provided specificity of ≥90%. True positive rate (sensitivity), positive predictive value, and negative predictive value were calculated to explore the possible use of salivary antibody levels as a surrogate of protection. The best ROC curve (AUC of 0.95) was obtained for MenC, with an estimated minimum threshold of MenC-PS specific salivary IgG ≥3.54 ng/mL as surrogate of protection. An adequate AUC (> 0.80) was also observed for MenW and MenY with an estimated minimal threshold of 2.00 and 1.82 ng/mL, respectively. When applying these thresholds, all (100%) samples collected 1 month and 1 year after the (booster) meningococcal vaccination, that were defined as protective in the saliva test for MenC, MenW and MenY, corresponded with concomitant serum rSBA titer ≥128 for the respective meningococcal serogroups. The saliva test offers an alternative screening tool to monitor protective vaccine responses up to one year after meningococcal vaccination against MenC, MenW and MenY. Future (large) longitudinal vaccination studies evaluating also clinical protection against IMD or carriage acquisition are required to validate the currently proposed threshold in saliva.
    • The use of the DR CALUX bioassay and indicator polychlorinated biphenyls for screening of elevated levels of dioxins and dioxin-like polychlorinated biphenyls in eel.

      Hoogenboom, Ron; Bovee, Toine; Traag, Win A; Hoogerbrugge, Ronald; Baumann, Bert; Portier, Liza; Weg, Guido van de; Vries, Jaap de (2006-10-01)
      The DR CALUX bioassay is a very suitable screening method for dioxins and dioxin-like-PCBs in feed and food. This was, e. g. demonstrated in a survey in the Netherlands to control the dioxin levels in eel. The DR CALUX assay, but also indicator polychlorinated biphenyls (PCB) were evaluated as a screening method. Based on the limit for polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/F) [at that time 8 pg toxic equivalents (TEQ)/g eel], and the relation between PCDD/F and dioxin-like-PCB, a decision limit of 30 pg TEQ/g eel was used for screening of 153 field samples. Suspected samples (21) and part of the higher contaminated negative samples (35) were analyzed by GC/MS for dioxins, non-ortho, mono-ortho and indicator PCB, revealing 13 samples exceeding the action limit of 30 pg TEQ/g eel. Only one sample slightly exceeded the dioxin level of 8 pg TEQ/g eel. The relatively low sensitivity for mono-ortho PCB was overcome by the use of reference samples, as shown by the correlation of 0.93 between GC/MS and CALUX determined total TEQ levels. The present data show that the DR CALUX assay can be used for screening of total TEQ levels in eel. The use for dioxins only requires a safe, and therefore relatively low, decision limit. The indicator PCB also showed a good correlation with total TEQ levels, mainly due to the large contribution of the mono-ortho PCB at higher concentrations. The relation with dioxins was very poor and as such indicator PCB seem less suitable than the DR CALUX assay for screening for dioxins only. The present study clearly shows that part of the wild eel samples contains high total TEQ levels and will exceed the future European Union limit of 12 pg TEQ/g eel for dioxins and dioxin-like PCB. Especially at high TEQ levels, dioxin-like PCB contribute most to the total TEQ. In practice, wild eel presents only a minor part of the eel consumed.