• Waning and boosting: on the dynamics of immune status.

      Diekmann, O; de Graaf, W F; Kretzschmar, M E E; Teunis, P F M (2018-05-15)
      The aim is to describe the distribution of immune status (as captured by antibody level) on the basis of a within-host submodel for continuous waning and occasional boosting. Inspired by Feller's fundamental work and the more recent delay equation formulation of models for the dynamics of physiologically structured populations, we derive, for given force of infection, a linear renewal equation. The solution is obtained by generation expansion, with the generation number corresponding to the number of times the individual became infected. Our main result provides a precise characterization of the stable distribution of immune status.
    • Weather correlates of Campylobacter prevalence in broilers at slaughter under tropical conditions in Sri Lanka.

      Kalupahana, R S; Mughini-Gras, L; Kottawatta, S A; Somarathne, S; Gamage, C; Wagenaar, J A (2018-04-15)
      Campylobacter is the primary agent of human bacterial gastroenteritis worldwide. In contrast to temperate zones, weather effects on Campylobacter prevalence in broilers under tropical conditions are under-researched. We examined the association between weather and Campylobacter prevalence in slaughtered broilers in Sri Lanka, a tropical country with weather variations led by monsoons. Each month (October 2009-July 2011), 20-30 broiler batches referring to two semi-automated slaughterhouses from five Sri Lankan provinces were tested for Campylobacter contamination and analysed in relation to temperature, humidity and rainfall. Overall prevalence was 63.8% (95% CI 59.6-67.9%, n = 542), peaking in September-November. Each 1 °C increase in monthly mean temperature up to 26 °C increased Campylobacter-positive batches by 16.4% (95% CI 0.4-35.1%). For each 10 mm increase in monthly total rainfall up to 300 mm, Campylobacter-positive batches increased significantly by 0.8% (0.1-1.5%) at 1-month lag. For each 1% increase in relative humidity up to 80% at 1- and 2-month lags, Campylobacter-positive batches increased of respectively 4.2% (1.9-6.7%) and 4.0% (1.5-6.5), and decreased by 3.6% (2.6-4.6%) and 4.0% (2.6-5.4%) for unit increases above 80%. These results suggest that even in tropical countries without marked seasons, there are weather effects possibly reflecting Campylobacter potential to colonise its preferred host and/or survive in the environment.
    • Werknemers en kinkhoest: criteria voor vaccinatie

      Meerstadt F; Maas J; Ruijs H; van Vliet H (2018-04)
    • What Is the Optimal Time to Retest Patients With a Urogenital Chlamydia Infection? A Randomized Controlled Trial.

      van der Helm, Jannie J; Koekenbier, Rik H; van Rooijen, Martijn S; Schim van der Loeff, Maarten F; de Vries, Henry J C (2018-02)
      Chlamydia trachomatis is a common, often recurring sexually transmitted infection, with serious adverse outcomes in women. Current guidelines recommend retesting after a chlamydia infection, but the optimum timing is unknown. We assessed the optimal retest interval after urogenital chlamydia treatment.
    • WHO Environmental Noise Guidelines for the European Region: A Systematic Review of Transport Noise Interventions and Their Impacts on Health.

      Brown, Alan Lex; van Kamp, Irene (2017-08-03)
      This paper describes a systematic review (1980-2014) of evidence on effects of transport noise interventions on human health. The sources are road traffic, railways, and air traffic. Health outcomes include sleep disturbance, annoyance, cognitive impairment of children and cardiovascular diseases. A conceptual framework to classify noise interventions and health effects was developed. Evidence was thinly spread across source types, outcomes, and intervention types. Further, diverse intervention study designs, methods of analyses, exposure levels, and changes in exposure do not allow a meta-analysis of the association between changes in noise level and health outcomes, and risk of bias in most studies was high. However, 43 individual transport noise intervention studies were examined (33 road traffic; 7 air traffic; 3 rail) as to whether the intervention was associated with a change in health outcome. Results showed that many of the interventions were associated with changes in health outcomes irrespective of the source type, the outcome or intervention type (source, path or infrastructure). For road traffic sources and the annoyance outcome, the expected effect-size can be estimated from an appropriate exposure-response function, though the change in annoyance in most studies was larger than could be expected based on noise level change.
    • WHO Environmental Noise Guidelines for the European Region: A Systematic Review on Environmental Noise and Cardiovascular and Metabolic Effects: A Summary.

      Kempen, Elise van; Casas, Maribel; Pershagen, Göran; Foraster, Maria (2018-02-22)
      To update the current state of evidence and assess its quality, we conducted a systematic review on the effects of environmental noise exposure on the cardio-metabolic systems as input for the new WHO environmental noise guidelines for the European Region. We identified 600 references relating to studies on effects of noise from road, rail and air traffic, and wind turbines on the cardio-metabolic system, published between January 2000 and August 2015. Only 61 studies, investigating different end points, included information enabling estimation of exposure response relationships. These studies were used for meta-analyses, and assessments of the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). A majority of the studies concerned traffic noise and hypertension, but most were cross-sectional and suffering from a high risk of bias. The most comprehensive evidence was available for road traffic noise and Ischeamic Heart Diseases (IHD). Combining the results of 7 longitudinal studies revealed a Relative Risk (RR) of 1.08 (95% CI: 1.01-1.15) per 10 dB (LDEN) for the association between road traffic noise and the incidence of IHD. We rated the quality of this evidence as high. Only a few studies reported on the association between transportation noise and stroke, diabetes, and/or obesity. The quality of evidence for these associations was rated from moderate to very low, depending on transportation noise source and outcome. For a comprehensive assessment of the impact of noise exposure on the cardiovascular and metabolic system, we need more and better quality evidence, primarily based on longitudinal studies.
    • Whole genome sequence of Mycobacterium kansasii isolates of the genotype 1 from Brazilian patients with pulmonary disease demonstrates considerable heterogeneity.

      Machado, Edson; Vasconcellos, Sidra Ezidio Gonçalves; Cerdeira, Camillo; Gomes, Lia Lima; Junqueira, Ricardo; Carvalho, Luciana Distasio de; Ramos, Jesus Pais; Redner, Paulo; Campos, Carlos Eduardo Dias; Caldas, Paulo Cesar de Souza; Gomes, Ana Paula Chaves Sobral; Goldenberg, Telma; Montes, Fatima Fandinho; Mello, Fernanda Carvalho de Queiroz; Mussi, Vinicius de Oliveira; Lasunskaia, Elena; Soolingen, Dick van; Miranda, Antonio Basílio de; Rigouts, Leen; Jong, Bouke C de; Meehan, Conor J; Catanho, Marcos; Suffys, Philip N (2018-06-25)
      Mycobacterium kansasii is an opportunistic pathogen and one of the most commonly encountered species in individuals with lung disease. We here report the complete genome sequence of 12 clinical isolates of M. kansasii from patients with pulmonary disease in Brazil.
    • Whole-Cell or Acellular Pertussis Primary Immunizations in Infancy Determines Adolescent Cellular Immune Profiles

      van der Lee, Saskia; Hendrikx, Lotte H.; Sanders, Elisabeth A. M.; Berbers, Guy A. M.; Buisman, Anne-Marie (2018-01-24)
    • Whole-cell or acellular pertussis vaccination in infancy determines IgG subclass profiles to DTaP booster vaccination.

      van der Lee, Saskia; Sanders, Elisabeth A M; Berbers, Guy A M; Buisman, Anne-Marie (2018)
      Duration of protection against pertussis is shorter in adolescents who have been immunized with acellular pertussis (aP) in infancy compared with adolescents who received whole-cell pertussis (wP) vaccines in infancy, which is related to immune responses elicited by these priming vaccines. To better understand differences in vaccine induced immunity, we determined pertussis, diphtheria, and tetanus (DTaP) vaccine antigen-specific IgG subclass responses in wP- and aP-primed children before and after two successive DTaP booster vaccinations.
    • Whole-Genome Characterization and Strain Comparison of VT2f-Producing Escherichia coli Causing Hemolytic Uremic Syndrome.

      Grande, Laura; Michelacci, Valeria; Bondì, Roslen; Gigliucci, Federica; Franz, Eelco; Badouei, Mahdi Askari; Schlager, Sabine; Minelli, Fabio; Tozzoli, Rosangela; Caprioli, Alfredo; Morabito, Stefano (2016)
      Verotoxigenic Escherichia coli infections in humans cause disease ranging from uncomplicated intestinal illnesses to bloody diarrhea and systemic sequelae, such as hemolytic uremic syndrome (HUS). Previous research indicated that pigeons may be a reservoir for a population of verotoxigenic E. coli producing the VT2f variant. We used whole-genome sequencing to characterize a set of VT2f-producing E. coli strains from human patients with diarrhea or HUS and from healthy pigeons. We describe a phage conveying the vtx2f genes and provide evidence that the strains causing milder diarrheal disease may be transmitted to humans from pigeons. The strains causing HUS could derive from VT2f phage acquisition by E. coli strains with a virulence genes asset resembling that of typical HUS-associated verotoxigenic E. coli.
    • Whole-Genome Next-Generation Sequencing to Study Within-Host Evolution of Norovirus (NoV) Among Immunocompromised Patients With Chronic NoV Infection.

      van Beek, Janko; de Graaf, Miranda; Smits, Saskia; Schapendonk, Claudia M E; Verjans, Georges M G M; Vennema, Harry; van der Eijk, Annemiek A; Phan, My V T; Cotten, Matthew; Koopmans, Marion (2017-12-19)
      The genus Norovirus comprises large genetic diversity, and new GII.4 variants emerge every 2-3 years. It is unknown in which host these new variants originate. Here we study whether prolonged shedders within the immunocompromised population could be a reservoir for newly emerging strains.
    • Whole-Genome Sequencing and Variant Analysis of Human Papillomavirus 16 Infections.

      van der Weele, Pascal; Meijer, Chris J L M; King, Audrey J (2017-10-01)
      Human papillomavirus (HPV) is a strongly conserved DNA virus, high-risk types of which can cause cervical cancer in persistent infections. The most common type found in HPV-attributable cancer is HPV16, which can be subdivided into four lineages (A to D) with different carcinogenic properties. Studies have shown HPV16 sequence diversity in different geographical areas, but only limited information is available regarding HPV16 diversity within a population, especially at the whole-genome level. We analyzed HPV16 major variant diversity and conservation in persistent infections and performed a single nucleotide polymorphism (SNP) comparison between persistent and clearing infections. Materials were obtained in the Netherlands from a cohort study with longitudinal follow-up for up to 3 years. Our analysis shows a remarkably large variant diversity in the population. Whole-genome sequences were obtained for 57 persistent and 59 clearing HPV16 infections, resulting in 109 unique variants. Interestingly, persistent infections were completely conserved through time. One reinfection event was identified where the initial and follow-up samples clustered differently. Non-A1/A2 variants seemed to clear preferentially (P = 0.02). Our analysis shows that population-wide HPV16 sequence diversity is very large. In persistent infections, the HPV16 sequence was fully conserved. Sequencing can identify HPV16 reinfections, although occurrence is rare. SNP comparison identified no strongly acting effect of the viral genome affecting HPV16 infection clearance or persistence in up to 3 years of follow-up. These findings suggest the progression of an early HPV16 infection could be host related.IMPORTANCE Human papillomavirus 16 (HPV16) is the predominant type found in cervical cancer. Progression of initial infection to cervical cancer has been linked to sequence properties; however, knowledge of variants circulating in European populations, especially with longitudinal follow-up, is limited. By sequencing a number of infections with known follow-up for up to 3 years, we gained initial insights into the genetic diversity of HPV16 and the effects of the viral genome on the persistence of infections. A SNP comparison between sequences obtained from clearing and persistent infections did not identify strongly acting DNA variations responsible for these infection outcomes. In addition, we identified an HPV16 reinfection event where sequencing of initial and follow-up samples showed different HPV16 variants. Based on conventional genotyping, this infection would incorrectly be considered a persistent HPV16 infection. In the context of vaccine efficacy and monitoring studies, such infections could potentially cause reduced reported efficacy or efficiency.
    • Whole-Inactivated Influenza Virus Is a Potent Adjuvant for Influenza Peptides Containing CD8+ T Cell Epitopes

      Soema, Peter C.; Rosendahl Huber, Sietske K.; Willems, Geert-Jan; Jacobi, Ronald; Hendriks, Marion; Soethout, Ernst; Jiskoot, Wim; de Jonge, Jørgen; van Beek, Josine; Kersten, Gideon F. A.; Amorij, Jean-Pierre (2018-03-14)
    • Why are the public so positive about colorectal cancer screening?

      Douma, Linda N; Uiters, Ellen; Timmermans, Danielle R M (2018-10-30)
      Colorectal cancer (CRC) screening is widely recommended. Earlier research showed that the general public are positive about CRC screening, as too the eligible CRC screening population. Among the eligible CRC screening population this positive perception has been shown to be associated with their perceptions of cancer, preventive health screening and their own health. It is unclear whether these concepts are also associated with the positive perception of the general public. Knowing this can provide insight into the context in which public perception concerning CRC screening is established. The aim of our study was to examine which main perceptions are associated with the public perception concerning CRC screening. An online survey was carried out in a Dutch population sample (adults 18+) among 1679 respondents (response rate was 56%). We assessed the public's perceptions concerning cancer, preventive health screening, own health, and the government, and examined their possible association with public opinion concerning CRC screening. The public's positive attitude towards CRC screening is associated with the public's positive attitude towards preventive health screening in general, their perceived seriousness of cancer, their belief of health being important, and their trust in the government regarding national screening programmes. Trust in the government and perceptions regarding the seriousness of cancer, preventive health screening and the importance of one's health seem to be important factors influencing how the public view CRC screening. The public are likely to process information about CRC screening in such a way that it confirms their existing beliefs of cancer being serious and preventive screening being positive. This makes it likely that they will notice information about the possible benefits of CRC screening more than information about its possible downsides, which would also contribute to the positive perception of CRC screening.
    • Why Do Countries Regulate Environmental Health Risks Differently? A Theoretical Perspective

      Clahsen, Sander C. S.; van Kamp, Irene; Hakkert, Betty C.; Vermeire, Theo G.; Piersma, Aldert H.; Lebret, Erik; Centre for Sustainability, Environment and Health; National Institute for Public Health and the Environment-RIVM; Bilthoven The Netherlands; Centre for Sustainability, Environment and Health; National Institute for Public Health and the Environment-RIVM; Bilthoven The Netherlands; Centre for Safety of Substances and Products; National Institute for Public Health and the Environment-RIVM; Bilthoven The Netherlands; Centre for Safety of Substances and Products; National Institute for Public Health and the Environment-RIVM; Bilthoven The Netherlands; Institute for Risk Assessment Sciences; Utrecht University; Utrecht The Netherlands; Institute for Risk Assessment Sciences; Utrecht University; Utrecht The Netherlands (2018-08-15)
    • Wild, insectivorous bats might be carriers of Campylobacter spp.

      Hazeleger, Wilma C; Jacobs-Reitsma, Wilma F; Lina, Peter H C; de Boer, Albert G; Bosch, Thijs; van Hoek, Angela H A M; Beumer, Rijkelt R (2018-01-11)
      The transmission cycles of the foodborne pathogens Campylobacter and Salmonella are not fully elucidated. Knowledge of these cycles may help reduce the transmission of these pathogens to humans.
    • Workplace interventions to improve work ability: A systematic review and meta-analysis of their effectiveness

      Oakman, Jodi; Neupane, Subas; Proper, Karin I; Kinsman, Natasha; Nygård, Clas-Håkan (2017-11-03)
    • Workshop on acceleration of the validation and regulatory acceptance of alternative methods and implementation of testing strategies.

      Piersma, A H; Burgdorf, T; Louekari, K; Desprez, B; Taalman, R; Landsiedel, R; Barroso, J; Rogiers, V; Eskes, C; Oelgeschläger, M; Whelan, M; Braeuning, A; Vinggaard, A M; Kienhuis, A; van Benthem, J; Ezendam, J (2018-03-02)
      This report describes the proceedings of the BfR-RIVM workshop on validation of alternative methods which was held 23 and 24 March 2017 in Berlin, Germany. Stakeholders from governmental agencies, regulatory authorities, universities, industry and the OECD were invited to discuss current problems concerning the regulatory acceptance and implementation of alternative test methods and testing strategies, with the aim to develop feasible solutions. Classical validation of alternative methods usually involves one to one comparison with the gold standard animal study. This approach suffers from the reductionist nature of an alternative test as compared to the animal study as well as from the animal study being considered as the gold standard. Modern approaches combine individual alternatives into testing strategies, for which integrated and defined approaches are emerging at OECD. Furthermore, progress in mechanistic toxicology, e.g. through the adverse outcome pathway approach, and in computational systems toxicology allows integration of alternative test battery results into toxicity predictions that are more fine-tuned to the human situation. The road towards transition to a mechanistically-based human-focused hazard and risk assessment of chemicals requires an open mind towards stepping away from the animal study as the gold standard and defining human biologically based regulatory requirements for human hazard and risk assessment.
    • Worth a thousand words? Visual concept mapping of the quality of life of people with severe mental health problems

      Buitenweg, David C.; Bongers, Ilja L.; van de Mheen, Dike; van Oers, Hans A.M.; Van Nieuwenhuizen, Chijs; Tranzo Scientific Centre for Care and Welfare; Tilburg University; Tilburg the Netherlands; Tranzo Scientific Centre for Care and Welfare; Tilburg University; Tilburg the Netherlands; Tranzo Scientific Centre for Care and Welfare; Tilburg University; Tilburg the Netherlands; Tranzo Scientific Centre for Care and Welfare; Tilburg University; Tilburg the Netherlands; Tranzo Scientific Centre for Care and Welfare; Tilburg University; Tilburg the Netherlands (2018-09)
    • Year-to-year variation in the density of Ixodes ricinus ticks and the prevalence of the rodent-associated human pathogens Borrelia afzelii and B. miyamotoi in different forest types.

      Ruyts, Sanne C; Tack, Wesley; Ampoorter, Evy; Coipan, Elena C; Matthysen, Erik; Heylen, Dieter; Sprong, Hein; Verheyen, Kris (2017-08-26)
      The human pathogens Borrelia afzelii, which causes Lyme borreliosis and B. miyamotoi, which causes relapsing fever, both circulate between Ixodes ricinus ticks and rodents. The spatiotemporal dynamics in the prevalence of these pathogens have not yet been fully elucidated, but probably depend on the spatiotemporal population dynamics of small rodents. We aimed to evaluate the effect of different forest types on the density of infected nymphs in different years and to obtain more knowledge about the spatial and temporal patterns of ticks and tick-borne pathogens. We analysed unfed nymphal ticks from 22 stands of four different forest types in Belgium in 2009, 2010, 2013 and 2014 and found that the density of nymphs in general and the density of nymphs infected with B. afzelii and B. miyamotoi varied yearly, but without temporal variation in the infection prevalence. The yearly variation in density of infected nymphs in our study thus seems to be caused most by the variation in the density of nymphs, which makes it a good predictor of disease risk. The risk for rodent-associated tick-borne diseases also varied between forest types. We stress the need to elucidate the contribution of the host community composition to tick-borne disease risk.