• H7N9 influenza split vaccine with SWE oil-in-water adjuvant greatly enhances cross-reactive humoral immunity and protection against severe pneumonia in ferrets.

      de Jonge, Jørgen; van Dijken, Harry; de Heij, Femke; Spijkers, Sanne; Mouthaan, Justin; de Jong, Rineke; Roholl, Paul; Adami, Eduardo Alfredo; Akamatsu, Milena Apetito; Ho, Paulo Lee; et al. (2020-01-01)
    • Habit formation of preventive behaviours during the COVID-19 pandemic: a longitudinal study of physical distancing and hand washing.

      Zhang, Chao; Adriaanse, Marieke A; Potgieter, Renske; Tummers, Lars; de Wit, John; Broersen, Jan; de Bruin, Marijn; Aarts, Henk (2022-08-20)
    • Haem iron intake and risk of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

      Ward, Heather A; Whitman, Julia; Muller, David C; Johansson, Mattias; Jakszyn, Paula; Weiderpass, Elisabete; Palli, Domenico; Fanidi, Anouar; Vermeulen, Roel; Tjønneland, Anne; et al. (2018-10-18)
      Epidemiological studies suggest that haem iron, which is found predominantly in red meat and increases endogenous formation of carcinogenic N-nitroso compounds, may be positively associated with lung cancer. The objective was to examine the relationship between haem iron intake and lung cancer risk using detailed smoking history data and serum cotinine to control for potential confounding.
    • Haem is crucial for medium-dependent metronidazole resistance in clinical isolates of Clostridioides difficile.

      Boekhoud, Ilse M; Sidorov, Igor; Nooij, Sam; Harmanus, Céline; Bos-Sanders, Ingrid M J G; Viprey, Virginie; Spittal, William; Clark, Emma; Davies, Kerrie; Freeman, Jane; et al. (2021-04-20)
    • Haemophilus is overrepresented in the nasopharynx of infants hospitalized with RSV infection and associated with increased viral load and enhanced mucosal CXCL8 responses.

      Ederveen, Thomas H A; Ferwerda, Gerben; Ahout, Inge M; Vissers, Marloes; de Groot, Ronald; Boekhorst, Jos; Timmerman, Harro M; Huynen, Martijn A; van Hijum, Sacha A F T; de Jonge, Marien I (2018-01-11)
      While almost all infants are infected with respiratory syncytial virus (RSV) before the age of 2 years, only a small percentage develops severe disease. Previous studies suggest that the nasopharyngeal microbiome affects disease development. We therefore studied the effect of the nasopharyngeal microbiome on viral load and mucosal cytokine responses, two important factors influencing the pathophysiology of RSV disease. To determine the relation between (i) the microbiome of the upper respiratory tract, (ii) viral load, and (iii) host mucosal inflammation during an RSV infection, nasopharyngeal microbiota profiles of RSV infected infants (< 6 months) with different levels of disease severity and age-matched healthy controls were determined by 16S rRNA marker gene sequencing. The viral load was measured using qPCR. Nasopharyngeal CCL5, CXCL10, MMP9, IL6, and CXCL8 levels were determined with ELISA.
    • Half a Century of Wilson & Jungner: Reflections on the Governance of Population Screening.

      Sturdy, Steve; Miller, Fiona; Hogarth, Stuart; Armstrong, Natalie; Chakraborty, Pranesh; Cressman, Celine; Dobrow, Mark; Flitcroft, Kathy; Grossman, David; Harris, Russell; et al. (2020-01-01)
      Background: In their landmark report on the "Principles and Practice of Screening for Disease" (1968), Wilson and Jungner noted that the practice of screening is just as important for securing beneficial outcomes and avoiding harms as the formulation of principles. Many jurisdictions have since established various kinds of "screening governance organizations" to provide oversight of screening practice. Yet to date there has been relatively little reflection on the nature and organization of screening governance itself, or on how different governance arrangements affect the way screening is implemented and perceived and the balance of benefits and harms it delivers. Methods: An international expert policy workshop convened by Sturdy, Miller and Hogarth. Results: While effective governance is essential to promote beneficial screening practices and avoid attendant harms, screening governance organizations face enduring challenges. These challenges are social and ethical as much as technical. Evidence-based adjudication of the benefits and harms of population screening must take account of factors that inform the production and interpretation of evidence, including the divergent professional, financial and personal commitments of stakeholders. Similarly, when planning and overseeing organized screening programs, screening governance organizations must persuade or compel multiple stakeholders to work together to a common end. Screening governance organizations in different jurisdictions vary widely in how they are constituted, how they relate to other interested organizations and actors, and what powers and authority they wield. Yet we know little about how these differences affect the way screening is implemented, and with what consequences. Conclusions: Systematic research into how screening governance is organized in different jurisdictions would facilitate policy learning to address enduring challenges. Even without such research, informal exchange and sharing of experiences between screening governance organizations can deliver invaluable insights into the social as well as the technical aspects of governance.
    • The half-life of maternal transplacental antibodies against diphtheria, tetanus, and pertussis in infants: an individual participant data meta-analysis.

      Oguti, Blanché; Ali, Asad; Andrews, Nick; Barug, Daan; Anh Dang, Duc; Halperin, Scott A; Thu Hoang, Ha Thi; Holder, Beth; Kampmann, Beate; Kazi, Abdul M; et al. (2021-12-21)
      De-identified data from infants born to women taking part in 10 studies, in 9 countries (UK, Belgium, Thailand, Vietnam, Canada, Pakistan, USA, Guatemala and the Netherlands) were combined in an individual participant data meta-analysis. Blood samples were taken at two timepoints before any DTP-containing vaccines were received by the infant: at birth and at 2-months of age. Decay rates for each antigen were log2-transformed and a mixed effects model was applied. Half-lives were calculated by taking the reciprocal of the absolute value of the mean decay rates.
    • The hallmarks of CMV-specific CD8 T-cell differentiation.

      van den Berg, Sara P H; Pardieck, Iris N; Lanfermeijer, Josien; Sauce, Delphine; Klenerman, Paul; van Baarle, Debbie; Arens, Ramon (2019-04-13)
      Upon cytomegalovirus (CMV) infection, large T-cell responses are elicited that remain high or even increase over time, a phenomenon named memory T-cell inflation. Besides, the maintained robust T-cell response, CMV-specific T cells seem to have a distinctive phenotype, characterized by an advanced differentiation state. Here, we will review this "special" differentiation status by discussing the cellular phenotype based on the expression of CD45 isoforms, costimulatory, inhibitory and natural killer receptors, adhesion and lymphocyte homing molecules, transcription factors, cytokines and cytotoxic molecules. In addition, we focus on whether the differentiation state of CMV-specific CD8 T cells is unique in comparison with other chronic viruses and we will discuss the possible impact of factors such as antigen exposure and aging on the advanced differentiation status of CMV-specific CD8 T cells.
    • Hand hygiene compliance and its drivers in long-term care facilities; observations and a survey.

      Haenen, Anja; de Greeff, Sabine; Voss, Andreas; Liefers, Janine; Hulscher, Marlies; Huis, Anita (2022-03-18)
    • Hand rub consumption and hand hygiene compliance are not indicators of pathogen transmission in intensive care units.

      Eckmanns, T; Schwab, F; Bessert, J; Wettstein, R; Behnke, M; Grundmann, Hajo; Rüden, H; Gastmeier, P (2006-08-01)
      The objective of this study was to investigate whether nosocomial infection (NI) rates, hand hygiene compliance rates and the amount of alcohol-based hand rub used for hand disinfection are useful indicators of pathogen transmission in intensive care units (ICUs), and whether they could be helpful in identifying infection control problems. All isolates of 10 of the most frequent pathogens from patients who were hospitalized in an ICU for >48 h were genotyped to identify transmission episodes in five ICUs. The incidence of transmission was correlated with hand hygiene compliance, hand rub consumption and NI rates. The incidence of transmission episodes varied between 2.8 and 6.8 in the five ICUs. The NI rate was 8.6-22.5 per 1000 patient-days, hand hygiene compliance was 30-47% and hand rub consumption was 57-102 L per 1000 patient-days. There was no correlation between the incidence of transmission episodes and hand rub consumption or hand hygiene compliance. The correlation between transmission rates and NI rates was 0.4 (P = 0.5), and with the exclusion of one ICU, it was 1 (P < 0.01). The incidence of NI is a relatively good indicator for the identification of pathogen transmissions, but hand rub consumption and hand hygiene compliance, at least with the relatively low level of compliance found in this study, are not indicators of pathogen transmission.
    • Hangijzer: autobanden op grasvelden

      de Vries, M; Kraaij-Dirkzwager, M (2019-05-10)
    • Hangijzer: Vaccinatie tegen HPV

      Timmermans, D (2019-05-10)
    • 'Happy the man, who, studying nature's laws, Thro' known effects can trace the secret cause.' Do we have enough pieces to solve the pyrazinamide puzzle?

      Anthony, R M; den Hertog, A L; van Soolingen, D (2018-03-08)
      A low pH was assumed to be required for the activity of pyrazinoic acid (the active form of pyrazinamide) against Mycobacterium tuberculosis, but recently activity has been demonstrated at neutral pH. Renewed interest in pyrazinamide has led to an increasing number of potential targets and the suspicion that pyrazinamide is a 'dirty drug'. However, it is our opinion that the recent demonstration that pyrazinoic acid is active against PanD provides an alternative explanation for the secret of pyrazinamide's unusual activity. In this article we propose that PanD is the primary target of pyrazinoic acid but expression of pyrazinoic acid susceptibility requires an intact stress response. As the mycobacterial stress response requires the interaction of a number of genes, disruption of any could result in an inability to enter the susceptible phenotype. We believe this model can explain most of the recent observations of the seemingly diverse spectrum of activity of pyrazinamide.
    • Harmonization of Human Biomonitoring Studies in Europe: Characteristics of the HBM4EU-Aligned Studies Participants.

      Gilles, Liese; Govarts, Eva; Rodriguez Martin, Laura; Andersson, Anna-Maria; Appenzeller, Brice M R; Barbone, Fabio; Castaño, Argelia; Coertjens, Dries; Den Hond, Elly; Dzhedzheia, Vazha; et al. (2022-06-01)
      Human biomonitoring has become a pivotal tool for supporting chemicals' policies. It provides information on real-life human exposures and is increasingly used to prioritize chemicals of health concern and to evaluate the success of chemical policies. Europe has launched the ambitious REACH program in 2007 to improve the protection of human health and the environment. In October 2020 the EU commission published its new chemicals strategy for sustainability towards a toxic-free environment. The European Parliament called upon the commission to collect human biomonitoring data to support chemical's risk assessment and risk management. This manuscript describes the organization of the first HBM4EU-aligned studies that obtain comparable human biomonitoring (HBM) data of European citizens to monitor their internal exposure to environmental chemicals. The HBM4EU-aligned studies build on existing HBM capacity in Europe by aligning national or regional HBM studies. The HBM4EU-aligned studies focus on three age groups: children, teenagers, and adults. The participants are recruited between 2014 and 2021 in 11 to 12 primary sampling units that are geographically distributed across Europe. Urine samples are collected in all age groups, and blood samples are collected in children and teenagers. Auxiliary information on socio-demographics, lifestyle, health status, environment, and diet is collected using questionnaires. In total, biological samples from 3137 children aged 6-12 years are collected for the analysis of biomarkers for phthalates, HEXAMOLL® DINCH, and flame retardants. Samples from 2950 teenagers aged 12-18 years are collected for the analysis of biomarkers for phthalates, Hexamoll® DINCH, and per- and polyfluoroalkyl substances (PFASs), and samples from 3522 adults aged 20-39 years are collected for the analysis of cadmium, bisphenols, and metabolites of polyaromatic hydrocarbons (PAHs). The children's group consists of 50.4% boys and 49.5% girls, of which 44.1% live in cities, 29.0% live in towns/suburbs, and 26.8% live in rural areas. The teenagers' group includes 50.6% girls and 49.4% boys, with 37.7% of residents in cities, 31.2% in towns/suburbs, and 30.2% in rural areas. The adult group consists of 52.6% women and 47.4% men, 71.9% live in cities, 14.2% in towns/suburbs, and only 13.4% live in rural areas. The study population approaches the characteristics of the general European population based on age-matched EUROSTAT EU-28, 2017 data; however, individuals who obtained no to lower educational level (ISCED 0-2) are underrepresented. The data on internal human exposure to priority chemicals from this unique cohort will provide a baseline for Europe's strategy towards a non-toxic environment and challenges and recommendations to improve the sampling frame for future EU-wide HBM surveys are discussed.
    • Harmonization of PCR-based detection of intestinal pathogens: experiences from the Dutch external quality assessment scheme on molecular diagnosis of protozoa in stool samples.

      Schuurs, Theo A; Koelewijn, Rob; Brienen, Eric A T; Kortbeek, Titia; Mank, Theo G; Mulder, Bert; Stelma, Foekje F; van Lieshout, Lisette; van Hellemond, Jaap J (2018-02-16)
      Real-time PCR methods are increasingly used in routine patient care settings not only to determine the presence or absence of pathogens in patient materials, but also to obtain semiquantitative results to estimate the pathogen load. However, it is so far unknown how well these methods are harmonized among different laboratories.
    • Harmonized methodology to assess chronic dietary exposure to residues from compounds used as pesticide and veterinary drug.

      Arcella, Davide; Boobis, Alan; Cressey, Peter; Erdely, Holly; Fattori, Vittorio; Leblanc, Jean-Charles; Lipp, Markus; Reuss, Rainer; Scheid, Stefan; Tritscher, Angelika; et al. (2019-03-28)
      Risk assessments for pesticide and veterinary drug residues in food are performed respectively by the Joint FAO/WHO Expert Meeting on Pesticide Residues (JMPR) and the Joint FAO/WHO Expert Committee on Food Additives (JECFA). The models used by the two Committees to assess chronic dietary exposure are based on different data and assumptions which may be confusing, particularly for risk managers, when the same compound is used to treat plants and animals. This publication details the results of combined chronic dietary exposure assessments for eight compounds used both as pesticide and veterinary drugs. It compares the results from models in use by JMPR and JECFA with those from national estimates performed by 17 countries. Results show that the JECFA model is better reflecting less than lifetime dietary exposure by considering consumption of children and high consumers. The JMPR model is a suitable model for estimating average chronic (lifetime) exposure to residues present in widely and regularly consumed staple commodities. However, it is suitable neither for estimating children's exposure nor more generally for assessing less than lifetime dietary exposure. In order to select the appropriate exposure model related to the occurrence of adverse effects i.e. effects occurring over less-than-lifetime or effects occurring only over lifetime, this paper proposes criteria to match the toxicological profile of the compound and the appropriate exposure scenarios. These approaches will continue to be harmonized to ensure the most scientifically sound basis for the risk assessment for pesticides and veterinary drug residues and consequently for other chemicals in food.
    • Harmonizing across environmental nanomaterial testing media for increased comparability of nanomaterial datasets.

      Geitner, NK; Hendren, CO; Cornelis, G; Kaegi, R; Lead, JR; Lowry, GV; Lynch, I; Quik, KT (2020-11-23)
    • Harvesting the wisdom of the crowd: using online ratings to explore care experiences in regions.

      Hendrikx, Roy J P; Spreeuwenberg, Marieke D; Drewes, Hanneke W; Struijs, Jeroen N; Ruwaard, Dirk; Baan, Caroline A (2018-10-20)
      Regional population health management (PHM) initiatives need an understanding of regional patient experiences to improve their services. Websites that gather patient ratings have become common and could be a helpful tool in this effort. Therefore, this study explores whether unsolicited online ratings can provide insight into (differences in) patient's experiences at a (regional) population level.
    • Hazard classification of chemicals inducing haemolytic anaemia: An EU regulatory perspective.

      Muller, Andre; Jacobsen, Helene; Healy, Edel; McMickan, Sinead; Istace, Fréderique; Blaude, Marie-Noëlle; Howden, Peter; Fleig, Helmut; Schulte, Agnes (2006-08-01)
      Haemolytic anaemia is often induced following prolonged exposure to chemical substances. Currently, under EU Council Directive 67/548/EEC, substances which induce such effects are classified as dangerous and assigned the risk phrase R48 'Danger of serious damage to health by prolonged exposure.' Whilst the general classification criteria for this endpoint are outlined in Annex VI of this Directive, they do not provide specific information to assess haemolytic anaemia. This review produced by the EU Working Group on Haemolytic Anaemia provides a toxicological assessment of haemolytic anaemia and proposes criteria that can be used in the assessment for classification of substances which induce such effects. An overview of the primary and secondary effects of haemolytic anaemia which can occur in rodent repeated dose toxicity studies is given. A detailed analysis of the toxicological significance of such effects is then performed and correlated with the general classification criteria used for this endpoint. This review intends to give guidance when carrying out an assessment for classification for this endpoint and to allow for better transparency in the decision-making process on when to classify based on the presence of haemolytic anaemia in repeated dose toxicity studies. The extended classification criteria for haemolytic anaemia outlined in this review were accepted by the EU Commission Working Group on the Classification and Labelling of Dangerous Substances in September 2004.
    • HCV micro-elimination in individuals with HIV in the Netherlands 4 years after universal access to direct-acting antivirals: a retrospective cohort study.

      Smit, Colette; Boyd, Anders; Rijnders, Bart J A; van de Laar, Thijs J W; Leyten, Eliane M; Bierman, Wouter F; Brinkman, Kees; Claassen, Mark A A; den Hollander, Jan; Boerekamps, Anne; et al. (2020-12-22)