• Host gene expression kinetics during treatment of tuberculosis in HIV-coinfected individuals is independent of HAART therapy.

      Gebremicael, Gebremedhin; Kassa, Desta; Quinten, Edwin; Alemayehu, Yodit; Gebreegziaxier, Atsbeha; Belay, Yohannes; van Baarle, Debbie; Ottenhoff, Tom H M; Cliff, Jacqueline M; Haks, Mariëlle C (2018-07-02)
      Limitations in diagnostic tools to discriminate between active and latent tuberculosis (TB) and for monitoring TB treatment responses are major challenges in TB control, especially in HIV-coinfected individuals.
    • Host genetics of Bordetella pertussis infection in mice: significance of Toll-like receptor 4 in genetic susceptibility and pathobiology.

      Banus, H Alexander; Vandebriel, R J; Ruiter, H de; Dormans, J A M A; Nagelkerke, Nico J D; Mooi, Frits R; Hoebee, Barbara; Kranen, Henk J van; Kimman, Tjeerd G (2006-05-01)
      The susceptibility to and the severity of Bordetella pertussis infections in infants and children varies widely, suggesting that genetic differences between individuals influence the course of infection. We have previously identified three novel loci that influence the severity of whooping cough by using recombinant congenic strains of mice: Bordetella pertussis susceptibility loci 1, 2, and 3 (Bps1, -2, and -3). Because these loci could not account for all genetic differences between mice, we extended our search for additional susceptibility loci. We therefore screened 11 inbred strains of mice for susceptibility to a pertussis infection after intranasal infection. Susceptibility was defined by the number of bacteria in the lungs, being indicative of the effect between the clearance and replication of bacteria. The most resistant (A/J) and the most susceptible (C3H/HeJ) strains were selected for further genetic and phenotypic characterization. The link between bacterial clearance and chromosomal location was investigated with 300 F2 mice, generated by crossing A/J and C3H/HeJ mice. We found a link between the delayed clearance of bacteria from the lung and a large part of chromosome 4 in F2 mice with a maximum log of the odds score of 33.6 at 65.4 Mb, which is the location of Tlr4. C3H/HeJ mice carry a functional mutation in the intracellular domain of Tlr4. This locus accounted for all detectable genetic differences between these strains. Compared to A/J mice, C3H/HeJ mice showed a delayed clearance of bacteria from the lung, a higher relative lung weight, and increased body weight loss. Splenocytes from infected C3H/HeJ mice produced almost no interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) upon ex vivo restimulation with B. pertussis compared to A/J mice and also showed a delayed gamma interferon (IFN-gamma) production. TNF-alpha expression in the lungs 3 days after infection was increased fivefold compared to uninfected controls in A/J mice and was not affected in C3H/HeJ mice. In conclusion, Tlr4 is a major host factor explaining the differences in the course of infection between these inbred strains of mice. Functional Tlr4 is essential for an efficient IL-1-beta, TNF-alpha, and IFN-gamma response; efficient clearance of bacteria from the lung; and reduced lung pathology.
    • Host phylogeny, geographic overlap, and roost sharing shape parasite communities in European bats.

      McKee, CD; Krawczyk, AI; Sandor, AD; Gorfol, T; Foldvari, M; Sprong, H; et. al. (2019-05-10)
    • House dust endotoxin, asthma and allergic sensitization through childhood into adolescence.

      Gehring, Ulrike; Wijga, Alet H; Koppelman, Gerard H; Vonk, Judith M; Smit, Henriëtte A; Brunekreef, Bert (2020-07-08)
      We used data of 854 participants of the prospective Dutch PIAMA birth cohort study with house dust endotoxin measurements at 3 months and/or 5-6 years and data on asthma and/or allergic sensitization from at least one of 11 follow-ups until age 17. We assessed overall and age-specific associations of the prevalence of asthma and sensitization with mattress and living room floor dust concentrations (per gram of dust) and loads (per m2 of sampling surface).
    • House Dust Mite Exposure through Human Milk and Dust: What Matters for Child Allergy Risk?

      Macchiaverni, Patricia; Gehring, Ulrike; Rekima, Akila; Wijga, Alet H; Verhasselt, Valerie (2022-05-17)
      Allergies are major noncommunicable diseases associated with significant morbidity, reduced quality of life, and high healthcare costs. Despite decades of research, it is still unknown if early-life exposure to indoor allergens plays a role in the development of IgE-mediated allergy and asthma. The objective of this study is to contribute to the identification of early-life risk factors for developing allergy. We addressed whether two different sources of house dust mite Der p 1 allergen exposure during early life, i.e., human milk and dust, have different relationships with IgE levels and asthma outcomes in children. We performed longitudinal analyses in 249 mother-child pairs using data from the PIAMA birth cohort. Asthma symptoms and serum total and specific IgE levels in children were available for the first 16 years of life. Der p 1 levels were measured in human milk and dust samples from infant mattresses. We observed that infant exposure to Der p 1 through human milk was associated with an increased risk of having high levels of serum IgE (top tertile > 150 kU/mL) in childhood as compared to infants exposed to human milk with undetectable Der p 1 [adjusted OR (95% CI) 1.83 (1.05-3.20) p = 0.0294]. The Der p 1 content in infant mattress dust was not associated with increased IgE levels in childhood. The risk of asthma and Der p 1 sensitization was neither associated with Der p 1 in human milk nor with Der p 1 in dust. In conclusion, high levels of IgE in childhood were associated with Der p 1 exposure through human milk but not exposure from mattress dust. This observation suggests that human milk is a source of Der p 1 exposure that is relevant to allergy development and fosters the need for research on the determinants of Der p 1 levels in human milk.
    • House Dust Mites: Does a Clean Mattress Mean Der p 1-free Breastmilk?

      Macchiaverni, Patricia; Gehring, Ulrike; Rekima, Akila; Wijga, Alet H; Verhasselt, Valerie (2020-06-10)
    • Household air pollution from, and fuel efficiency of, different coal types following local cooking practices in Xuanwei, China.

      Zhang, Yongliang; Meliefste, Kees; Hu, Wei; Li, Jihua; Xu, Jun; Ning, Baofu; Yang, Kaiyun; Chen, Ying; Liu, Dingyu; Wong, Jason; et al. (2021-08-12)
      The domestic combustion of smoky (bituminous) coal in the Chinese counties of Xuanwei and Fuyuan, are responsible for some of the highest rates of lung cancer in the world. Cancer rates vary between coal producing regions (deposits) in the area, with coals from Laibin exhibiting particularly high risks and smokeless (anthracite) coal exhibiting lower risks. However, little information is available on the specific burning characteristics of coals from throughout the area. We conducted an extensive controlled burning experiment using coal from multiple deposits in either a traditional firepit or ventilated stove, accompanied by a detailed examination of time-weighted and real-time size-aggregated particle concentrations. Smoky coal caused higher particle concentrations of all sizes than smokeless coal, with variations observed by geological source. Virtually all particle emissions were in the PM2.5 fraction (98% - mass based), and 75% and 46% were in the PM1 and PM0.3 fraction respectively. Real-time concentrations of PM1 and PM0.1 peaked after coal was added and declined afterwards. Ventilation reduced particle concentrations by up to 15-fold and increased the coal burning rate by 1.9-fold. These findings may provide valuable insight for reducing exposure and adverse health effects associated with domestic coal combustion.
    • How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology.

      Wittwehr, Clemens; Aladjov, Hristo; Ankley, Gerald; Byrne, Hugh J; de Knecht, Joop; Heinzle, Elmar; Klambauer, Günter; Landesmann, Brigitte; Luijten, Mirjam; MacKay, Cameron; et al. (2017-02)
      Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The adverse outcome pathway (AOP) framework provides a systematic approach for organizing knowledge that may support such inference. Likewise, computational models of biological systems at various scales provide another means and platform to integrate current biological understanding to facilitate inference and extrapolation. We argue that the systematic organization of knowledge into AOP frameworks can inform and help direct the design and development of computational prediction models that can further enhance the utility of mechanistic and in silico data for chemical safety assessment. This concept was explored as part of a workshop on AOP-Informed Predictive Modeling Approaches for Regulatory Toxicology held September 24-25, 2015. Examples of AOP-informed model development and its application to the assessment of chemicals for skin sensitization and multiple modes of endocrine disruption are provided. The role of problem formulation, not only as a critical phase of risk assessment, but also as guide for both AOP and complementary model development is described. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development is made. The contents serve as a vision for how AOPs can be leveraged to facilitate development of computational prediction models needed to support the next generation of chemical safety assessment.
    • How age and infection history shape the antigen-specific CD8 T-cell repertoire: Implications for vaccination strategies in older adults.

      Lanfermeijer, Josien; Borghans, José A M; van Baarle, Debbie (2020-10-20)
      Older adults often show signs of impaired CD8+ T-cell immunity, reflected by weaker responses against new infections and vaccinations, and decreased protection against reinfection. This immune impairment is in part thought to be the consequence of a decrease in both T-cell numbers and repertoire diversity. If this is indeed the case, a strategy to prevent infectious diseases in older adults could be the induction of protective memory responses through vaccination at a younger age. However, this requires that the induced immune responses are maintained until old age. It is therefore important to obtain insights into the long-term maintenance of the antigen-specific T-cell repertoire. Here, we review the literature on the maintenance of antigen-experienced CD8+ T-cell repertoires against acute and chronic infections. We describe the complex interactions that play a role in shaping the memory T-cell repertoire, and the effects of age, infection history, and T-cell avidity. We discuss the implications of these findings for the development of new vaccination strategies to protect older adults.
    • How Can Autonomy Be Maintained and Informal Care Improved for People With Dementia Living in Residential Care Facilities: A Systematic Literature Review.

      Boumans, Jogé; van Boekel, Leonieke C; Baan, Caroline A; Luijkx, Katrien G (2018-09-15)
      For people with dementia living in residential care facilities, maintaining autonomy and receiving informal care are important. The objective of this review is to understand how caregiving approaches and physical environment, including technologies contribute to the maintenance of autonomy and informal care provision for this population.
    • How current risk assessment and risk management methods for drinking water in The Netherlands cover the WHO water safety plan approach.

      van den Berg, H H J L; Friederichs, L; Versteegh, J F M; Smeets, P W M H; de Roda Husman, A M (2019-08-01)
    • How executives' expectations and experiences shape population health management strategies.

      Steenkamer, Betty M; Drewes, Hanneke W; van Vooren, Natascha; Baan, Caroline A; van Oers, Hans; Putters, Kim (2019-10-26)
    • How lay people understand and make sense of personalized disease risk information.

      Damman, Olga C; Bogaerts, Nina M M; van den Haak, Maaike J; Timmermans, Danielle R M (2017-10)
      Disease risk calculators are increasingly web-based, but previous studies have shown that risk information often poses problems for lay users.
    • How ownership rights over microorganisms affect infectious disease control and innovation: A root-cause analysis of barriers to data sharing as experienced by key stakeholders.

      Ribeiro, Carolina Dos S; van Roode, Martine Y; Haringhuizen, George B; Koopmans, Marion P; Claassen, Eric; van de Burgwal, Linda H M (2018)
      Genetic information of pathogens is an essential input for infectious disease control, public health and for research. Efficiency in preventing and responding to global outbreaks relies on timely access to such information. Still, ownership barriers stand in the way of timely sharing of genetic data from pathogens, frustrating efficient public health responses and ultimately the potential use of such resources in innovations. Under a One Health approach, stakeholders, their interests and ownership issues are manifold and need to be investigated. We interviewed key actors from governmental and non-governmental bodies to identify overlapping and conflicting interests, and the overall challenges for sharing pathogen data, to provide essential inputs to the further development of political and practical strategies for improved data sharing practices.
    • How prepared are we for cross-border outbreaks? An exploratory analysis of cross-border response networks for outbreaks of multidrug resistant microorganisms in the Netherlands and Germany.

      Maessen, Jacklien H J; Raab, Jörg; Haverkate, Manon; Smollich, Martin; Ter Waarbeek, Henriëtte L G; Eilers, Renske; Timen, Aura (2019-01-01)
    • How psychological distance of a study sample in discrete choice experiments affects preference measurement: a colorectal cancer screening case study.

      Veldwijk, Jorien; Groothuis-Oudshoorn, Catharina G M; Kihlbom, Ulrik; Langenskiöld, Sophie; Dekker, Evelien; Kallenberg, Frank G J; de Wit, G Ardine; Lambooij, Mattijs S (2019-01-01)
      The purpose of this study was to investigate to what extent the outcomes of a discrete choice experiment (DCE) differ based on respondents' psychological distance to the decision at hand. A DCE questionnaire regarding individuals' preferences for genetic screening for colorectal cancer (CRC) within the Dutch national CRC screening program was created. The DCE contained nine D-efficient designed choice tasks and was distributed among two populations that differ in their psychological distance to the decision at hand: 1) a representative sample of the Dutch general population aged 55-65 years, and 2) a sample of Dutch individuals who attended an information appointment regarding colonoscopies following the detection of blood in their stool sample in the CRC screening program. The DCE consisted of four attributes related to the decision whether to participate in genetic screening for CRC: 1) risk of being genetically predisposed, 2) risk of developing CRC, 3) frequency of follow-up colonoscopies, and 4) survival. Direct attribute ranking, dominant decision-making behavior, and relative importance scores (based on panel MIXL) were compared between the two populations. Attribute level estimates were compared with the Swait and Louviere test. The proportion of respondents who both ranked survival as the most important attribute, and showed dominant decision-making behavior for this attribute, was significantly higher in the screened population compared to the general population. The relative importance scores of the attributes significantly differed between populations. Finally, the Swait and Louviere test also revealed significant differences in attribute level estimates in both the populations. The study outcomes differed between populations depending on their psychological distance to the decision. This study shows the importance of adequate sample selection; therefore, it is advocated to increase attention to study sample selection and reporting in DCE studies.