• Staphylococcus aureus Carriage in a New Zealand Primary School: A Cohort Study.

      Scott, Pippa; Priest, Patricia C; Chambers, Stephen T; Heijne, Janneke Cm; Murdoch, David R (2017-09-22)
      Asymptomatic carriage of Staphylococcus aureus is a source of transmission between healthy individuals. Seventy children at a primary school were swabbed 7 times to identify patterns of S. aureus carriage. S. aureus carriage prevalence was 53-65% at each round, and 45% carried at every round. High carriage prevalence may indicate that school-aged children are important contributors to S. aureus transmission.
    • Statement on advancing the assessment of chemical mixtures and their risks for human health and the environment.

      Drakvik, Elina; Altenburger, Rolf; Aoki, Yasunobu; Backhaus, Thomas; Bahadori, Tina; Barouki, Robert; Brack, Werner; Cronin, Mark T D; Demeneix, Barbara; Hougaard Bennekou, Susanne; et al. (2019-11-05)
    • Status, quality and specific needs of Zika virus (ZIKV) diagnostic capacity and capability in National Reference Laboratories for arboviruses in 30 EU/EEA countries, May 2016.

      Mögling, Ramona; Zeller, Hervé; Revez, Joana; Koopmans, Marion; Reusken, Chantal (2017-09-07)
      With international travel, Zika virus (ZIKV) is introduced to Europe regularly. A country's ability to robustly detect ZIKV introduction and local transmission is important to minimise the risk for a ZIKV outbreak. Therefore, sufficient expertise and diagnostic capacity and capability are required in European laboratories. To assess the capacity, quality, operational specifics (guidelines and algorithms), technical and interpretation issues and other possible difficulties that were related to ZIKV diagnostics in European countries, a questionnaire was conducted among national reference laboratories in 30 countries in the European Union/European Economic Area (EU/EEA) in May 2016. While the coverage and capacity of ZIKV diagnostics in the EU/EEA national reference laboratories were found to be adequate, the assessment of the quality and needs indicated several crucial points of improvement that will need support at national and EU/EEA level to improve ZIKV preparedness, response and EU/EEA ZIKV surveillance activities.
    • A Stepwise Approach to a National Hepatitis C Screening Strategy in Malaysia to Meet the WHO 2030 Targets: Proposed Strategy, Coverage, and Costs.

      Hiebert, Lindsey; Hecht, Robert; Soe-Lin, Shan; Mohamed, Rosmawati; Shabaruddin, Fatiha H; Syed Mansor, Syed Mukhtar; Dahlui, Maznah; Azzeri, Amirah; McDonald, Scott A (2019-03-25)
      In Malaysia, more than 330 000 individuals are estimated to be chronically infected with hepatitis C virus (HCV), but less than 2% have been treated to date. To estimate the required coverage and costs of a national screening strategy to inform the launch of an HCV elimination program. We designed an HCV screening strategy based on a "stepwise" approach. This approach relied on targeting of people who inject drugs in the early years, with delayed onset of widespread general population screening. Annual coverage requirements and associated costs were estimated to ensure that the World Health Organization elimination treatment targets were met. In total, 6 million individuals would have to be screened between 2018 and 2030. Targeting of people who inject drugs in the early years would limit annual screening coverage to less than 1 million individuals from 2018 to 2026. General population screening would have to be launched by 2026. Total costs were estimated at MYR 222 million ($58 million). Proportional to coverage targets, 60% of program costs would fall from 2026 to 2030.
    • The Sterilizing Effect of Ertapenem-Clavulanate in a Hollow-Fiber Model of Tuberculosis and Implications on Clinical Dosing.

      van Rijn, Sander P; Srivastava, Shashikant; Wessels, Mireille A; van Soolingen, Dick; Alffenaar, Jan-Willem C; Gumbo, Tawanda (2017-09)
      Carbapenems are now being explored for treatment of multidrug-resistant tuberculosis (MDR-TB), especially in conjunction with clavulanate. Clinical use is constrained by the need for multiple parenteral doses per day and the lack of knowledge of the optimal dose for sterilizing effect. Our objective was to identify the ertapenem exposure associated with optimal sterilizing effect and then design a once-a-day dose for clinical use. We utilized the hollow-fiber system model of tuberculosis in a 28-day exposure-response study of 8 different ertapenem doses in combination with clavulanate. The systems were sampled at predetermined time points to verify the concentration-time profile and identify the total bacterial burden. Inhibitory sigmoid maximum-effect (Emax) modeling was used to identify the relationship between total bacterial burden and the drug exposure and to identify optimal exposures. Contrary to the literature, ertapenem-clavulanate combination demonstrated good microbial kill and sterilizing effect. In a dose fractionation hollow-fiber study, efficacy was linked to percentage of the 24-h dosing interval of ertapenem concentration persisting above MIC (%TMIC). We performed 10,000 MDR-TB patient computer-aided clinical trial simulations, based on Monte Carlo methods, to identify the doses and schedule that would achieve or exceed a %TMIC of ≥40%. We identified an intravenous dosage of 2 g once per day as achieving the target in 96% of patients. An ertapenem susceptibility breakpoint MIC of 2 mg/liter was identified for that dose. An ertapenem dosage of 2 g once daily is the most suitable to be tested in a phase II study of sterilizing effect in MDR-TB patients.
    • The stimulant higenamine in weight loss and sports supplements.

      Cohen, Pieter A; Travis, John C; Keizers, Peter H J; Boyer, Frederick E; Venhuis, Bastiaan J (2018-09-06)
      Higenamine is a stimulant with cardiovascular properties recently prohibited in sport by the World Anti-Doping Agency (WADA). Higenamine is also a natural constituent of several traditional botanical remedies and is listed as an ingredient in weight loss and sports supplements sold over-the-counter in the United States.
    • STIs in sex partners notified for chlamydia exposure: implications for expedited partner therapy.

      van Aar, Fleur; van Benthem, Birgit H B; van den Broek, Ingrid V F; Götz, Hannelore M (2018-01-11)
      Expedited partner therapy (EPT) may reduce chlamydia reinfection rates. However, the disadvantages of EPT for chlamydia include missing the opportunity to test for other STIs and unnecessary use of antibiotics among non-infected partners. As part of a larger study that investigated the feasibility of EPT in the Netherlands, we explored the frequency of STI among a potential EPT target population of chlamydia-notified heterosexual men and women attending STI clinics for testing.
    • A stochastic simulation model to study respondent-driven recruitment.

      Stein, Mart L; Buskens, Vincent; van der Heijden, Peter G M; van Steenbergen, Jim E; Wong, Albert; Bootsma, Martin C J; Kretzschmar, Mirjam E E (2018-01-01)
      Respondent-driven detection is a chain recruitment method used to sample contact persons of infected persons in order to enhance case finding. It starts with initial individuals, so-called seeds, who are invited for participation. Afterwards, seeds receive a fixed number of coupons to invite individuals with whom they had contact during a specific time period. Recruitees are then asked to do the same, resulting in successive waves of contact persons who are connected in one recruitment tree. However, often the majority of participants fail to invite others, or invitees do not accept an invitation, and recruitment stops after several waves. A mathematical model can help to analyse how various factors influence peer recruitment and to understand under which circumstances sustainable recruitment is possible. We implemented a stochastic simulation model, where parameters were suggested by empirical data from an online survey, to determine the thresholds for obtaining large recruitment trees and the number of waves needed to reach a steady state in the sample composition for individual characteristics. We also examined the relationship between mean and variance of the number of invitations sent out by participants and the probability of obtaining a large recruitment tree. Our main finding is that a situation where participants send out any number of coupons between one and the maximum number is more effective in reaching large recruitment trees, compared to a situation where the majority of participants does not send out any invitations and a smaller group sends out the maximum number of invitations. The presented model is a helpful tool that can assist public health professionals in preparing research and contact tracing using online respondent-driven detection. In particular, it can provide information on the required minimum number of successfully sent invitations to reach large recruitment trees, a certain sample composition or certain number of waves.
    • Strategies for achieving viral hepatitis C micro-elimination in the Netherlands.

      Kracht, P A M; Arends, J E; van Erpecum, K J; Urbanus, A; Willemse, J A; Hoepelman, A I M; Croes, E A (2018)
      The Netherlands is striving to achieve national elimination of the hepatitis C virus (HCV) as one of the first countries worldwide. The favorable HCV epidemiology with both low prevalence and incidence, together with access to care and treatment, present excellent conditions to further build on towards this objective. The Dutch national plan on viral hepatitis, introduced in 2016, defines targets in the HCV healthcare cascade and provides a structural framework for the development of elimination activities. Since many different stakeholders are involved in HCV care in the Netherlands, focus has been placed on micro-elimination initiatives as a pragmatic and efficient approach. These numerous micro-eliminations projects have brought the Netherlands closer to HCV elimination. In the near future, efforts specifically have to be made in order to optimize case-finding strategies and to successfully accomplish the nationwide implementation of the registration and monitoring system of viral hepatitis mono-infections, before this final goal can be reached. The upcoming years will then elucidate if the Dutch' hands on approach has resulted in sufficient progress against HCV and if the Netherlands will lead the way towards nationwide HCV elimination.
    • Strategies of employees in the construction industry to increase their sustainable employability.

      Tonnon, Susanne C; van der Veen, Rozan; de Kruif, Anja Th C M; Robroek, Suzan J W; van der Ploeg, Hidde P; Proper, Karin I; van der Beek, Allard J (2018-01-19)
      The aging work force makes sustainable employability (SE) of workers a priority. However, it is unknown to what extent employees use implemented SE measures.
    • Strengths and weaknesses of the FAIRMODE benchmarking methodology for the evaluation of air quality models

      Monteiro, A.; Durka, P.; Flandorfer, C.; Georgieva, E.; Guerreiro, C.; Kushta, J.; Malherbe, L.; Maiheu, B.; Miranda, A. I.; Santos, G.; et al. (2018-02-28)
    • Strong correlation between the rates of intrinsically antibiotic-resistant species and the rates of acquired resistance in Gram-negative species causing bacteraemia, EU/EEA, 2016.

      Jarlier, Vincent; Diaz Högberg, Liselotte; Heuer, Ole E; Campos, José; Eckmanns, Tim; Giske, Christian G; Grundmann, Hajo; Johnson, Alan P; Kahlmeter, Gunnar; Monen, Jos; et al. (2019-01-01)
      BackgroundAntibiotic resistance, either intrinsic or acquired, is a major obstacle for treating bacterial infections.AimOur objective was to compare the country-specific species distribution of the four Gram-negative species Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter species and the proportions of selected acquired resistance traits within these species.MethodWe used data reported for 2016 to the European Antimicrobial Resistance Surveillance Network (EARS-Net) by 30 countries in the European Union and European Economic Area.ResultsThe country-specific species distribution varied considerably. While E. coli accounted for 31.9% to 81.0% (median: 69.0%) of all reported isolates, the two most common intrinsically resistant species P. aeruginosa and Acinetobacter spp. combined (PSEACI) accounted for 5.5% to 39.2% of isolates (median: 10.1%). Similarly, large national differences were noted for the percentages of acquired non-susceptibility to third-generation cephalosporins, carbapenems and fluoroquinolones. There was a strong positive rank correlation between the country-specific percentages of PSEACI and the percentages of non-susceptibility to the above antibiotics in all four species (rho > 0.75 for 10 of the 11 pairs of variables tested).ConclusionCountries with the highest proportion of P. aeruginosa and Acinetobacter spp. were also those where the rates of acquired non-susceptibility in all four studied species were highest. The differences are probably related to national differences in antibiotic consumption and infection prevention and control routines.
    • Structure elucidation of sildenafil analogues in herbal products.

      Blok-Tip, L; Zomer, B; Bakker, F; Hartog, K D; Hamzink, M; Hove, J ten; Vredenbregt, M; Kaste, D de (2004-08-01)
      The structure of unknown compounds present in herbal products was elucidated using liquid chromatography-electrospray ionization-mass spectrometry, direct-infusion electrospray ionization-mass spectrometry, and nuclear magnetic resonance. Compounds 1-3 were identified as sildenafil analogues, 1 bearing an N-ethylpiperazine moiety instead of an N-methylpiperazine, and an acetyl group instead of the sulfonyl group, named acetildenafil, 2 bearing an N-ethylpiperazine moiety instead of an N-methylpiperazine (homosildenafil), and 3 bearing an N-hydroxylethylpiperazine moiety instead of an N-methylpiperazine, named hydroxyhomosildenafil. When analysing products marketed for penile erectile dysfunction or marketed as aphrodisiacs, attention should be given to the possible presence of these components.
    • Structure of general-population antibody titer distributions to influenza A virus.

      Nhat, Nguyen Thi Duy; Todd, Stacy; de Bruin, Erwin; Thao, Tran Thi Nhu; Vy, Nguyen Ha Thao; Quan, Tran Minh; Vinh, Dao Nguyen; van Beek, Janko; Anh, Pham Hong; Lam, Ha Minh; et al. (2017-07-20)
      Seroepidemiological studies aim to understand population-level exposure and immunity to infectious diseases. Their results are normally presented as binary outcomes describing the presence or absence of pathogen-specific antibody, despite the fact that many assays measure continuous quantities. A population's natural distribution of antibody titers to an endemic infectious disease may include information on multiple serological states - naiveté, recent infection, non-recent infection, childhood infection - depending on the disease in question and the acquisition and waning patterns of immunity. In this study, we investigate 20,152 general-population serum samples from southern Vietnam collected between 2009 and 2013 from which we report antibody titers to the influenza virus HA1 protein using a continuous titer measurement from a protein microarray assay. We describe the distributions of antibody titers to subtypes 2009 H1N1 and H3N2. Using a model selection approach to fit mixture distributions, we show that 2009 H1N1 antibody titers fall into four titer subgroups and that H3N2 titers fall into three subgroups. For H1N1, our interpretation is that the two highest-titer subgroups correspond to recent and historical infection, which is consistent with 2009 pandemic attack rates. Similar interpretations are available for H3N2, but right-censoring of titers makes these interpretations difficult to validate.
    • Studies into the mechanism of measles-associated immune suppression during a measles outbreak in the Netherlands.

      Laksono, Brigitta M; de Vries, Rory D; Verburgh, R Joyce; Visser, Eline G; de Jong, Alwin; Fraaij, Pieter L A; Ruijs, Wilhemina L M; Nieuwenhuijse, David F; van den Ham, Henk-Jan; Koopmans, Marion P G; et al. (2018-11-23)
      Measles causes a transient immune suppression, leading to increased susceptibility to opportunistic infections. In experimentally infected non-human primates (NHPs) measles virus (MV) infects and depletes pre-existing memory lymphocytes, causing immune amnesia. A measles outbreak in the Dutch Orthodox Protestant community provided a unique opportunity to study the pathogenesis of measles immune suppression in unvaccinated children. In peripheral blood mononuclear cells (PBMC) of prodromal measles patients, we detected MV-infected memory CD4
    • Study protocol of a cluster randomised controlled trial investigating the effectiveness of a tailored energy balance programme for recent retirees.

      Werkman, Andrea; Schuit, Albertine J; Kwak, Lydia; Kremers, Stef P J; Visscher, Tommy L S; Kok, Frans J; Schouten, Evert G (2006)
      BACKGROUND: People in transitional life stages, such as occupational retirement, are likely to gain weight and accumulate abdominal fat mass caused by changes in physical activity and diet. Hence, retirees are an important target group for weight gain prevention programmes, as described in the present paper. METHODS/DESIGN: A systematic and stepwise approach (Intervention Mapping) is used to develop a low-intensity energy balance intervention programme for recent retirees. This one-year, low-intensity multifaceted programme aims to prevent accumulation of abdominal fat mass and general weight gain by increasing awareness of energy balance and influencing related behaviours of participants' preference. These behaviours are physical activity, fibre intake, portion size and fat consumption. The effectiveness of the intervention programme is tested in a cluster randomised controlled trial. Measurements of anthropometry, physical activity, energy intake, and related psychosocial determinants are performed at baseline and repeated at 6 months for intermediate effect, at 12 months to evaluate short-term intervention effects and at 24 months to test the sustainability of the effects. DISCUSSION: This intervention programme is unique in its focus on retirees and energy balance. It aims at increasing awareness and takes into account personal preferences of the users by offering several options for behaviour change. Moreover, the intervention programme is evaluated at short-term and long-term and includes consecutive outcome measures (determinants, behaviour and body composition).
    • Study protocol of the iMPaCT project: a longitudinal cohort study assessing psychological determinants, sexual behaviour and chlamydia (re)infections in heterosexual STI clinic visitors.

      van Wees, Daphne A; Heijne, Janneke C M; Heijman, Titia; Kampman, Karlijn C J G; Westra, Karin; de Vries, Anne; Kretzschmar, Mirjam E E; den Daas, Chantal (2018-11-13)
      Chlamydia trachomatis (chlamydia), the most commonly reported sexually transmitted infection (STI) in the Netherlands, can lead to severe reproductive complications. Reasons for the sustained chlamydia prevalence in young individuals, even in countries with chlamydia screening programs, might be the asymptomatic nature of chlamydia infections, and high reinfection rates after treatment. When individuals are unaware of their infection, preventive behaviour or health-care seeking behaviour mostly depends on psychological determinants, such as risk perception. Furthermore, behaviour change after a diagnosis might be vital to reduce reinfection rates. This makes the incorporation of psychological determinants and behaviour change in mathematical models estimating the impact of interventions on chlamydia transmission especially important. Therefore, quantitative real-life data to inform these models is needed. A longitudinal cohort study will be conducted to explore the link between psychological and behavioural determinants and chlamydia (re)infection among heterosexual STI clinic visitors aged 18-24 years. Participants will be recruited at the STI clinics of the public health services of Amsterdam, Hollands Noorden, Kennemerland, and Twente. Participants are enrolled for a year, and questionnaires are administrated at four time points: baseline (before an STI consultation), three-week, six-month and at one-year follow-up. To be able to link psychological and behavioural determinants to (re)infections, participants will be tested for chlamydia at enrolment and at six-month follow-up. Data from the longitudinal cohort study will be used to develop mathematical models for curable STI incorporating these determinants to be able to better estimate the impact of interventions. This study will provide insights into the link between psychological and behavioural determinants, including short-term and long-term changes after diagnosis, and chlamydia (re)infections. Our mathematical model, informed by data from the longitudinal cohort study, will be able to estimate the impact of interventions on chlamydia prevalence, and identify and prioritise successful interventions for the future. These interventions could be implemented at STI clinics tailored to psychological and behavioural characteristics of individuals. Dutch Trial Register NTR-6307 . Retrospectively registered 11-nov-2016.
    • Subacute effects of the brominated flame retardants hexabromocyclododecane and tetrabromobisphenol A on hepatic cytochrome P450 levels in rats.

      Germer, Silke; Piersma, Aldert H; Ven, Leo T M van der; Kamyschnikow, Andreas; Fery, Yvonne; Schmitz, Hans-Joachim; Schrenk, Dieter (2006-02-01)
      The brominated flame retardants tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCD) are found in the environment, e.g., in sediments and organisms, in food items, human blood samples and mother's milk. In this study, the effects of both compounds on rat hepatic cytochrome P450 (CYP) levels and activities were investigated. Juvenile/young male and female Wistar rats were treated orally with various doses via the feed (TBBPA) or by gavage (HBCD). After 28 days of treatment the animals were sacrificed and hepatic mRNA and microsomes were isolated. HBCD treatment led to a significant induction of CYP2B1 mRNA, CYP2B1/2B2 protein and 7-pentoxyresorufin O-depentylase (PROD) activity suggesting a phenobarbital-type of induction. Furthermore, a significant increase in CYP3A1/3A3 mRNA, CYP3A1 protein, and luciferin benzylether debenzylase (LBD) activity was found, being more pronounced in females than in males. The effect on CYP3A1/3A3 mRNA was significant in female rats at a daily dose of 3.0mg/kg body weight and above. HBCD exhibited no effects on CYP1A2 mRNA, CYP1A1/1A2 protein, or microsomal 7-ethoxyresorufin O-deethylase (EROD) activity suggesting lack of activation of the aryl hydrocarbon receptor. No significant effects on any of the parameters measured were obtained with TBBPA. Our findings suggest that oral exposure to HBCD induces drug-metabolising enzymes in rats probably via the CAR/PXR signalling pathway. Induction of CYPs and co-regulated enzymes of phase II of drug metabolism may affect homeostasis of endogenous substrates including steroid and thyroid hormones.
    • Subjectively different but objectively the same? Three profiles of QoL in people with severe mental health problems.

      Buitenweg, David C; Bongers, Ilja L; van de Mheen, Dike; van Oers, Hans A M; van Nieuwenhuizen, Chijs (2018-11)
      Quality of life (QoL) is a broad outcome that is often used to assess the impact of treatment and care interventions in mental health services. QoL, however, is known to be influenced by individual values and preferences. To investigate this heterogeneity on the individual level, this study aimed to distinguish classes with distinct QoL profiles in a broad group of people with severe mental health problems and to identify the QoL domains that are most strongly related to the classes.
    • Subjects' Perception in Quantifying Printed and Digital Photos of Food Portions.

      Nichelle, Pryscila G; Almeida, Claudia C B; Camey, Suzi A; Garmus, Lenine M; Elias, Vanessa C M; Marchioni, Dirce M; da Silva, Danielle G; Ocke, Marga C; Slimani, Nadia; Fisberg, Regina M; et al. (2019-02-27)
      Although digital photos have the potential to improve the precision of reported portions in dietary assessment, there are few studies investigating its accuracy in comparison to printed photos. The aim of this study was to evaluate the perception of adults in quantifying food portion sizes using printed and digital photos, displayed on computer-screens and tablets. In total, 1165 evaluations were performed for 60 photos of portion sizes in Brazil. Each participant (