• The 2015-2016 influenza epidemic in Beijing, China: Unlike elsewhere, circulation of influenza A(H3N2) with moderate vaccine effectiveness.

      Zhang, Li; Pan, Yang; Hackert, Volker; van der Hoek, Wim; Meijer, Adam; Krafft, Thomas; Yang, Peng; Wang, Quanyi (2018)
      While the 2015-2016 influenza season in the northern hemisphere was dominated by A(H1N1)pdm09 and B/Victoria viruses, in Beijing, China, there was also significant circulation of influenza A(H3N2) virus. In this report we estimate vaccine effectiveness (VE) against influenza A(H3N2) and other circulating viruses, and describe further characteristics of the 2015-2016 influenza season in Beijing.
    • 2015/16 I-MOVE/I-MOVE+ multicentre case-control study in Europe: Moderate vaccine effectiveness estimates against influenza A(H1N1)pdm09 and low estimates against lineage-mismatched influenza B among children.

      Kissling, Esther; Valenciano, Marta; Pozo, Francisco; Vilcu, Ana-Maria; Reuss, Annicka; Rizzo, Caterina; Larrauri, Amparo; Horváth, Judit Krisztina; Brytting, Mia; Domegan, Lisa; Korczyńska, Monika; Meijer, Adam; Machado, Ausenda; Ivanciuc, Alina; Višekruna Vučina, Vesna; van der Werf, Sylvie; Schweiger, Brunhilde; Bella, Antonino; Gherasim, Alin; Ferenczi, Annamária; Zakikhany, Katherina; O Donnell, Joan; Paradowska-Stankiewicz, Iwona; Dijkstra, Frederika; Guiomar, Raquel; Lazar, Mihaela; Kurečić Filipović, Sanja; Johansen, Kari; Moren, Alain (2017-11-10)
      During the 2015/16 influenza season in Europe, the cocirculating influenza viruses were A(H1N1)pdm09 and B/Victoria, which was antigenically distinct from the B/Yamagata component in the trivalent influenza vaccine.
    • 2015/16 seasonal vaccine effectiveness against hospitalisation with influenza A(H1N1)pdm09 and B among elderly people in Europe: results from the I-MOVE+ project.

      Rondy, Marc; Larrauri, Amparo; Casado, Itziar; Alfonsi, Valeria; Pitigoi, Daniela; Launay, Odile; Syrjänen, Ritva K; Gefenaite, Giedre; Machado, Ausenda; Vučina, Vesna Višekruna; Horváth, Judith Krisztina; Paradowska-Stankiewicz, Iwona; Marbus, Sierk D; Gherasim, Alin; Díaz-González, Jorge Alberto; Rizzo, Caterina; Ivanciuc, Alina E; Galtier, Florence; Ikonen, Niina; Mickiene, Aukse; Gomez, Veronica; Kurečić Filipović, Sanja; Ferenczi, Annamária; Korcinska, Monika R; van Gageldonk-Lafeber, Rianne; Valenciano, Marta (2017-07-27)
      We conducted a multicentre test-negative case-control study in 27 hospitals of 11 European countries to measure 2015/16 influenza vaccine effectiveness (IVE) against hospitalised influenza A(H1N1)pdm09 and B among people aged ≥ 65 years. Patients swabbed within 7 days after onset of symptoms compatible with severe acute respiratory infection were included. Information on demographics, vaccination and underlying conditions was collected. Using logistic regression, we measured IVE adjusted for potential confounders. We included 355 influenza A(H1N1)pdm09 cases, 110 influenza B cases, and 1,274 controls. Adjusted IVE against influenza A(H1N1)pdm09 was 42% (95% confidence interval (CI): 22 to 57). It was 59% (95% CI: 23 to 78), 48% (95% CI: 5 to 71), 43% (95% CI: 8 to 65) and 39% (95% CI: 7 to 60) in patients with diabetes mellitus, cancer, lung and heart disease, respectively. Adjusted IVE against influenza B was 52% (95% CI: 24 to 70). It was 62% (95% CI: 5 to 85), 60% (95% CI: 18 to 80) and 36% (95% CI: -23 to 67) in patients with diabetes mellitus, lung and heart disease, respectively. 2015/16 IVE estimates against hospitalised influenza in elderly people was moderate against influenza A(H1N1)pdm09 and B, including among those with diabetes mellitus, cancer, lung or heart diseases.
    • The 2017 Dutch Physical Activity Guidelines.

      Weggemans, Rianne M; Backx, Frank J G; Borghouts, Lars; Chinapaw, Mai; Hopman, Maria T E; Koster, Annemarie; Kremers, Stef; van Loon, Luc J C; May, Anne; Mosterd, Arend; van der Ploeg, Hidde P; Takken, Tim; Visser, Marjolein; Wendel-Vos, G C Wanda; de Geus, Eco J C (2018-06-25)
      The objective of this study was to derive evidence-based physical activity guidelines for the general Dutch population.
    • A 28-day oral dose toxicity study enhanced to detect endocrine effects of hexabromocyclododecane in Wistar rats.

      Ven, Leo T M van der; Verhoef, Aart; Kuil, Ton van de; Slob, Wout; Leonards, Pim E G; Visser, Theo J; Hamers, Timo; Herlin, Maria; Håkansson, Helen; Olausson, Hanna; Piersma, Aldert H; Vos, Josephus G (2006-12-01)
      A 28-day repeated dose study in rats (OECD407) enhanced for endocrine and immune parameters was performed with hexabromocyclododecane (HBCD). Rats were exposed by daily gavage to HBCD dissolved in corn oil in 8 dose groups with doses ranging between 0 and 200 mg/kg bw per day (mkd). Evaluation consisted of dose-response analysis with calculation of a benchmark dose at the lower 95% one-sided confidence bound (BMDL) at predefined critical effect sizes (CESs) of 10-20%. The most remarkable findings were dose-related effects on the thyroid hormone axis, that is, decreased total thyroxin (TT4, BMDL 55.5 mkd at CES--10%), increased pituitary weight (29 mkd at 10%) and increased immunostaining of TSH in the pituitary, increased thyroid weight (1.6 mkd at 10%), and thyroid follicle cell activation. These effects were restricted to females. Female rats also showed increased absolute liver weights (22.9 mkd at 20%) and induction of T4-glucuronyl transferase (4.1 mkd at 10%), suggesting that aberrant metabolization of T4 triggers feedback activation of the thyroid hormone system. These effects were accompanied by possibly secondary effects, including increased cholesterol (7.4 mkd at 10%), increased tibial bone mineral density (> 49 mkd at 10%), both in females, and decreased splenocyte counts (0.3-6.3 mkd at 20%; only evaluated in males). Overall, female rats appeared to be more sensitive to HBCD than male rats, and an overall BMDL is proposed at 1.6 mkd, based on a 10% increase of the thyroid weight, which was the most sensitive parameter in the sequence of events.
    • A multi-model approach to monitor emissions of CO<sub>2</sub> and CO from an urban–industrial complex

      Super, Ingrid; Denier van der Gon, Hugo A. C.; van der Molen, Michiel K.; Sterk, Hendrika A. M.; Hensen, Arjan; Peters, Wouter (2017-11-09)
      Monitoring urban–industrial emissions is often challenging because observations are scarce and regional atmospheric transport models are too coarse to represent the high spatiotemporal variability in the resulting concentrations. In this paper we apply a new combination of an Eulerian model (Weather Research and Forecast, WRF, with chemistry) and a Gaussian plume model (Operational Priority Substances – OPS). The modelled mixing ratios are compared to observed CO2 and CO mole fractions at four sites along a transect from an urban–industrial complex (Rotterdam, the Netherlands) towards rural conditions for October–December 2014. Urban plumes are well-mixed at our semi-urban location, making this location suited for an integrated emission estimate over the whole study area. The signals at our urban measurement site (with average enhancements of 11 ppm CO2 and 40 ppb CO over the baseline) are highly variable due to the presence of distinct source areas dominated by road traffic/residential heating emissions or industrial activities. This causes different emission signatures that are translated into a large variability in observed ΔCO : ΔCO2 ratios, which can be used to identify dominant source types. We find that WRF-Chem is able to represent synoptic variability in CO2 and CO (e.g. the median CO2 mixing ratio is 9.7 ppm, observed, against 8.8 ppm, modelled), but it fails to reproduce the hourly variability of daytime urban plumes at the urban site (R2 up to 0.05). For the urban site, adding a plume model to the model framework is beneficial to adequately represent plume transport especially from stack emissions. The explained variance in hourly, daytime CO2 enhancements from point source emissions increases from 30 % with WRF-Chem to 52 % with WRF-Chem in combination with the most detailed OPS simulation. The simulated variability in ΔCO :  ΔCO2 ratios decreases drastically from 1.5 to 0.6 ppb ppm−1, which agrees better with the observed standard deviation of 0.4 ppb ppm−1. This is partly due to improved wind fields (increase in R2 of 0.10) but also due to improved point source representation (increase in R2 of 0.05) and dilution (increase in R2 of 0.07). Based on our analysis we conclude that a plume model with detailed and accurate dispersion parameters adds substantially to top–down monitoring of greenhouse gas emissions in urban environments with large point source contributions within a  ∼  10 km radius from the observation sites.
    • Acarological Risk of Borrelia burgdorferi Sensu Lato Infections Across Space and Time in The Netherlands.

      Takken, Willem; van Vliet, Arnold J H; Verhulst, Niels O; Jacobs, Frans H H; Gassner, Fedor; Hartemink, Nienke; Mulder, Sara; Sprong, Hein (2017)
      A longitudinal investigation on tick populations and their Borrelia infections in the Netherlands was undertaken between 2006 and 2011 with the aim to assess spatial and temporal patterns of the acarological risk in forested sites across the country and to assess variations in Borrelia genospecies diversity. Ticks were collected monthly in 11 sites and nymphs were examined for Borrelia infections. Tick populations expressed strong seasonal variations, with consistent and significant differences in mean tick densities between sites. Borrelia infections were present in all study sites, with a site-specific mean prevalence per month ranging from 7% to 26%. Prevalence was location-dependent and was not associated with tick densities. Mean Borrelia prevalence was lowest in January (4%), gradually increasing to reach a maximum (24%) in August. Borrelia afzelii represented 70% of all infections, with Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia valaisiana represented with 4%, 8%, and 10%, respectively. The density of infected nymphs and the proportional distribution of the four Borrelia genospecies, were significantly different between sites. The results show a consistent and significant spatial and temporal difference in acarological risk across the Netherlands.
    • The Acceptability of Pre-Exposure Prophylaxis: Beliefs of Health-Care Professionals Working in Sexually Transmitted Infections Clinics and HIV Treatment Centers.

      Bil, Janneke P; Hoornenborg, Elske; Prins, Maria; Hogewoning, Arjan; Dias Goncalves Lima, Fernando; de Vries, Henry J C; Davidovich, Udi (2018)
      Pre-exposure prophylaxis (PrEP) is highly effective for preventing HIV infections, but is not yet implemented in the Netherlands. As the attitudes of health-care professionals toward PrEP can influence future PrEP implementation, we studied PrEP knowledge and beliefs and their association with PrEP acceptability among professionals in clinics for sexually transmitted infection (STI professionals) and HIV treatment centers (HIV specialists). In addition, we examined preferred regimens, attitudes toward providing PrEP to key populations and to reimbursement of PrEP costs.
    • Accessibility of standardized information of a national colorectal cancer screening program for low health literate screening invitees: A mixed method study.

      Fransen, Mirjam P; Dekker, Evelien; Timmermans, Daniëlle R M; Uiters, Ellen; Essink-Bot, Marie-Louise (2017-02)
      To explore the accessibility of standardized printed information materials of the national Dutch colorectal cancer screening program among low health literate screening invitees and to assess the effect of the information on their knowledge about colorectal cancer and the screening program.
    • Achieving successful community engagement: a rapid realist review

      De Weger, E.; Van Vooren, N.; Luijkx, K. G.; Baan, C. A.; Drewes, H. W. (2018-04-13)
    • Acquisition of C1 inhibitor by Bordetella pertussis virulence associated gene 8 results in C2 and C4 consumption away from the bacterial surface.

      Hovingh, Elise S; van den Broek, Bryan; Kuipers, Betsy; Pinelli, Elena; Rooijakkers, Suzan H M; Jongerius, Ilse (2017-07)
      Whooping cough, or pertussis, is a contagious disease of the respiratory tract that is re-emerging worldwide despite high vaccination coverage. The causative agent of this disease is the Gram-negative Bordetella pertussis. Knowledge on complement evasion strategies of this pathogen is limited. However, this is of great importance for future vaccine development as it has become apparent that a novel pertussis vaccine is needed. Here, we unravel the effect of Virulence associated gene 8 (Vag8) of B. pertussis on the human complement system at the molecular level. We show that both recombinant and endogenously secreted Vag8 inhibit complement deposition on the bacterial surface at the level of C4b. We reveal that Vag8 binding to human C1-inhibitor (C1-inh) interferes with the binding of C1-inh to C1s, C1r and MASP-2, resulting in the release of active proteases that subsequently cleave C2 and C4 away from the bacterial surface. We demonstrate that the depletion of these complement components in the bacterial surrounding and subsequent decreased deposition on B. pertussis leads to less complement-mediated bacterial killing. Vag8 is the first protein described that specifically prevents C1s, C1r and MASP-2 binding to C1-inh and thereby mediates complement consumption away from the bacterial surface. Unravelling the mechanism of this unique complement evasion strategy of B. pertussis is one of the first steps towards understanding the interactions between the first line of defense complement and B. pertussis.
    • Acquisition of wild-type HIV-1 infection in a patient on pre-exposure prophylaxis with high intracellular concentrations of tenofovir diphosphate: a case report.

      Hoornenborg, Elske; Prins, Maria; Achterbergh, Roel C A; Woittiez, Lycke R; Cornelissen, Marion; Jurriaans, Suzanne; Kootstra, Neeltje A; Anderson, Peter L; Reiss, Peter; de Vries, Henry J C; Prins, Jan M; de Bree, Godelieve J (2017-11)
      Pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate is highly effective against acquisition of HIV infection, and only two cases of infection with a multidrug-resistant virus have been reported under adequate long-term adherence, as evidenced by tenofovir diphosphate concentrations in dried blood spots. We report a case of wild-type HIV-1 infection despite consistent use of emtricitabine and tenofovir disoproxil fumarate.
    • Active case finding and treatment adherence in risk groups in the tuberculosis pre-elimination era.

      Gupta, R K; Lipman, M; Story, A; Hayward, A; de Vries, G; van Hest, R; Erkens, C; Rangaka, M X; Abubakar, I (2018-05-01)
      Vulnerable populations, including homeless persons, high-risk drug and alcohol users, prison inmates and other marginalised populations, contribute a disproportionate burden of tuberculosis (TB) cases in low-incidence settings. Drivers of this disease burden include an increased risk of both TB transmission in congregate settings, and progression from infection to active disease. Late diagnosis and poor treatment completion further propagate the epidemic and fuel the acquisition of drug resistance. These groups are therefore a major priority for TB control programmes in low-incidence settings. Targeted strategies include active case finding (ACF) initiatives and interventions to improve treatment completion, both of which should be tailored to local populations. ACF usually deploys mobile X-ray unit screening, which allows sensitive, high-throughput screening with immediate availability of results. Such initiatives have been found to be effective and cost-effective, and associated with reductions in proxy measures of transmission in hard-to-reach groups. The addition of point-of-care molecular diagnostics and automated X-ray readers may further streamline the screening pathway. There is little evidence to support interventions to improve adherence among these risk groups. Such approaches include enhanced case management and directly observed treatment, while video-observed therapy (currently under evaluation) appears to be a promising tool for the future. Integrating outreach services to include both case detection and case-management interventions that share a resource infrastructure may allow cost-effectiveness to be maximised. Integrating screening and treatment for other diseases that are prevalent among targeted risk groups into TB outreach interventions may further improve cost-effectiveness. This article reviews the existing literature, and highlights priorities for further research.
    • Active commuting through natural environments is associated with better mental health: Results from the PHENOTYPE project.

      Zijlema, Wilma L; Avila-Palencia, Ione; Triguero-Mas, Margarita; Gidlow, Christopher; Maas, Jolanda; Kruize, Hanneke; Andrusaityte, Sandra; Grazuleviciene, Regina; Nieuwenhuijsen, Mark J (2018-12)
      Commuting routes with natural features could promote walking or cycling for commuting. Commuting through natural environments (NE) could have mental health benefits as exposure to NE can reduce stress and improve mental health, but there is little evidence. This study evaluates the association between NE and commuting, whether active or not, and the association between commuting (through NE), whether active or not, and mental health. We also evaluate the moderating effect of NE quality on the association between NE commuting and mental health.
    • Acute illness from Campylobacter jejuni may require high doses while infection occurs at low doses.

      Teunis, Peter F M; Bonačić Marinović, Axel; Tribble, David R; Porter, Chad K; Swart, Arno (2018-02-08)
      Data from a set of different studies on the infectivity and pathogenicity of Campylobacter jejuni were analyzed with a multilevel model, allowing for effects of host species (nonhuman primates and humans) and different strains of the pathogen. All challenge studies involved high doses of the pathogen, resulting in all exposed subjects to become infected. In only one study a dose response effect (increasing trend with dose) for infection was observed. High susceptibility to infection with C. jejuni was found in a joint analysis of outbreaks and challenge studies. For that reason four outbreaks, associated with raw milk consumption, were also included in the present study. The high doses used for inoculation did not cause all infected subjects to develop acute enteric symptoms. The observed outcomes are consistent with a dose response effect for acute symptoms among infected subjects: a conditional illness dose response relation. Nonhuman primates and human volunteers did not appear to have different susceptibilities for developing enteric symptoms, but exposure in outbreaks (raw milk) did lead to a higher probability of symptomatic campylobacteriosis.
    • Acute Otitis Media During Infancy: Parent-reported Incidence and Modifiable Risk Factors.

      Prins-van Ginkel, Annemarijn C; Bruijning-Verhagen, Patricia C J; Uiterwaal, Cuno S P M; van der Ent, Cornelis K; Smit, Henriette A; de Hoog, Marieke L A (2017-03)
      Age at exposure to acute otitis media (AOM) risk factors such as day care attendance, lack of breastfeeding and tobacco smoke is little studied but important for targeting AOM prevention strategies. Moreover, studies are typically restricted to clinically diagnosed AOM, while a significant subset can occur outside the health care system, depending on the country setting. This study aims to determine risk factor exposure and effect of its timing within the first year of life on parent-reported AOM symptom episodes.
    • Adaptation of Bordetella pertussis to the respiratory tract.

      van Beek, Lucille L F; de Gouw, Daan D; Eleveld, Marc M J; Bootsma, Hester H J; de Jonge, Marien M I; Mooi, Frits F R; Zomer, Aldert A; Diavatopoulos, Dimitri D A (2018-03-08)
      There is a lack of insight into the basic mechanisms by which Bordetella pertussis adapts to the local host environment during infection. We analysed B. pertussis gene expression in the upper and lower airways of mice and compared this to SO4-induced in vitro Bvg-regulated gene transcription. Approximately 30% of all genes were found to be differentially expressed between in vitro vs. in vivo conditions. This included several novel potential vaccine antigens that were exclusively expressed in vivo. Significant differences in expression profile and metabolic pathways were identified between the upper versus the lower airways, suggesting distinct antigenic profiles. We found high expression of several Bvg-repressed genes during infection and mouse vaccination experiments using purified protein fractions from both Bvg- and Bvg+ cultures demonstrated protection against intranasal B. pertussis challenge. This study provides novel insights into the in vivo adaptation of B. pertussis and may facilitate the improvement of pertussis vaccines.
    • Added Value of Serum Hormone Measurements in Risk Prediction Models for Breast Cancer for Women Not Using Exogenous Hormones: Results from the EPIC Cohort.

      Hüsing, Anika; Fortner, Renée T; Kühn, Tilman; Overvad, Kim; Tjønneland, Anne; Olsen, Anja; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Fournier, Agnes; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vassiliki; Orfanos, Philippos; Masala, Giovanna; Pala, Valeria; Tumino, Rosario; Fasanelli, Francesca; Panico, Salvatore; Bueno de Mesquita, H Bas; Peeters, Petra H; van Gills, Carla H; Quirós, J Ramón; Agudo, Antonio; Sánchez, Maria-Jose; Chirlaque, Maria-Dolores; Barricarte, Aurelio; Amiano, Pilar; Khaw, Kay-Tee; Travis, Ruth C; Dossus, Laure; Li, Kuanrong; Ferrari, Pietro; Merritt, Melissa A; Tzoulaki, Ioanna; Riboli, Elio; Kaaks, Rudolf (2017-08-01)
      Purpose: Circulating hormone concentrations are associated with breast cancer risk, with well-established associations for postmenopausal women. Biomarkers may represent minimally invasive measures to improve risk prediction models.Experimental Design: We evaluated improvements in discrimination gained by adding serum biomarker concentrations to risk estimates derived from risk prediction models developed by Gail and colleagues and Pfeiffer and colleagues using a nested case-control study within the EPIC cohort, including 1,217 breast cancer cases and 1,976 matched controls. Participants were pre- or postmenopausal at blood collection. Circulating sex steroids, prolactin, insulin-like growth factor (IGF) I, IGF-binding protein 3, and sex hormone-binding globulin (SHBG) were evaluated using backward elimination separately in women pre- and postmenopausal at blood collection. Improvement in discrimination was evaluated as the change in concordance statistic (C-statistic) from a modified Gail or Pfeiffer risk score alone versus models, including the biomarkers and risk score. Internal validation with bootstrapping (1,000-fold) was used to adjust for overfitting.Results: Among women postmenopausal at blood collection, estradiol, testosterone, and SHBG were selected into the prediction models. For breast cancer overall, model discrimination after including biomarkers was 5.3 percentage points higher than the modified Gail model alone, and 3.4 percentage points higher than the Pfeiffer model alone, after accounting for overfitting. Discrimination was more markedly improved for estrogen receptor-positive disease (percentage point change in C-statistic: 7.2, Gail; 4.8, Pfeiffer). We observed no improvement in discrimination among women premenopausal at blood collection.Conclusions: Integration of hormone measurements in clinical risk prediction models may represent a strategy to improve breast cancer risk stratification. Clin Cancer Res; 23(15); 4181-9. ©2017 AACR.
    • Adherence to the WCRF/AICR Dietary Recommendations for Cancer Prevention and Risk of Cancer in Elderly from Europe and the United States: A Meta-Analysis within the CHANCES Project.

      Jankovic, Nicole; Geelen, Anouk; Winkels, Renate M; Mwungura, Blaise; Fedirko, Veronika; Jenab, Mazda; Illner, Anne K; Brenner, Hermann; Ordóñez-Mena, José M; Kiefte de Jong, Jessica C; Franco, Oscar H; Orfanos, Philippos; Trichopoulou, Antonia; Boffetta, Paolo; Agudo, Antonio; Peeters, Petra H; Tjønneland, Anne; Hallmans, Göran; Bueno-de-Mesquita, H Bas; Park, Yikyung; Feskens, Edith J; de Groot, Lisette C; Kampman, Ellen (2017)
      It is unknown whether dietary recommendations for cancer prevention are applicable to the elderly. We analyzed WCRF/AICR recommendations in cohorts of European and U.S. adults ages 60 years and above.
    • Adhering to a national surgical care bundle reduces the risk of surgical site infections.

      Koek, Mayke B G; Hopmans, Titia E M; Soetens, Loes C; Wille, Jan C; Geerlings, Suzanne E; Vos, Margreet C; van Benthem, Birgit H B; de Greeff, Sabine C (2017)
      In 2008, a bundle of care to prevent Surgical Site Infections (SSIs) was introduced in the Netherlands. The bundle consisted of four elements: antibiotic prophylaxis according to local guidelines, no hair removal, normothermia and 'hygiene discipline' in the operating room (i.e. number of door movements). Dutch hospitals were advised to implement the bundle and to measure the outcome. This study's goal was to assess how effective the bundle was in reducing SSI risk.