• ECDC Round Table Report and ProMed-mail most useful international information sources for the Netherlands Early Warning Committee.

      Bijkerk, Paul; Monnier, Annelie A; Fanoy, Ewout B; Kardamanidis, Katina; Friesema, Ingrid Hm; Knol, Mirjam J (2017-04-06)
      The Netherlands Early Warning Committee (NEWC) aims to identify infectious diseases causing a potential threat to Dutch public health. Threats are assessed and published as (information) alerts for public health experts. To identify threats from abroad, the NEWC screens 10 sources reporting disease outbreaks each week. To identify the sources essential for complete and timely reporting, we retrospectively analysed 178 international alerts published between 31 January 2013 and 30 January 2014. In addition, we asked the four NEWC coordinators about the required time to scan the information sources. We documented the date and source in which the signal was detected. The ECDC Round Table (RT) Report and ProMED-mail were the most complete and timely sources, reporting 140 of 178 (79%) and 121 of 178 (68%) threats respectively. The combination of both sources reported 169 (95%) of all threats in a timely manner. Adding any of the other sources resulted in minor increases in the total threats found, but considerable additional time investment per additional threat. Only three potential relevant threats (2%) would have been missed by only using the ECDC RT Report and ProMed-mail. We concluded that using only the ECDC RT Report and ProMed-mail to identify threats from abroad maintains a sensitive Early Warning System.
    • Echovirus type 6 transmission clusters and the role of environmental surveillance in early warning, the Netherlands, 2007 to 2016.

      Monge, Susana; Benschop, Kimberley; Soetens, Loes; Pijnacker, Roan; Hahné, Susan; Wallinga, Jacco; Duizer, Erwin (2018-11-01)
      BackgroundIn the Netherlands, echovirus type 6 (E6) is identified through clinical and environmental enterovirus surveillance (CEVS and EEVS). AimWe aimed to identify E6 transmission clusters and to assess the role of EEVS in surveillance and early warning of E6. MethodsWe included all E6 strains from CEVS and EEVS from 2007 through 2016. CEVS samples were from patients with enterovirus illness. EEVS samples came from sewage water at pre-specified sampling points. E6 strains were defined by partial VP1 sequence, month and 4-digit postcode. Phylogenetic E6 clusters were detected using pairwise genetic distances. We identified transmission clusters using a combined pairwise distance in time, place and phylogeny dimensions. ResultsE6 was identified in 157 of 3,506 CEVS clinical episodes and 92 of 1,067 EEVS samples. Increased E6 circulation was observed in 2009 and from 2014 onwards. Eight phylogenetic clusters were identified; five included both CEVS and EEVS strains. Among these, identification in EEVS did not consistently precede CEVS. One phylogenetic cluster was dominant until 2014, but genetic diversity increased thereafter. Of 14 identified transmission clusters, six included both EEVS and CEVS; in two of them, EEVS identification preceded CEVS identification. Transmission clusters were consistent with phylogenetic clusters, and with previous outbreak reports. ConclusionAlgorithms using combined time-place-phylogeny data allowed identification of clusters not detected by any of these variables alone. EEVS identified strains circulating in the population, but EEVS samples did not systematically precede clinical case surveillance, limiting EEVS usefulness for early warning in a context where E6 is endemic.
    • Eco-epidemiology of Novel Bartonella Genotypes from Parasitic Flies of Insectivorous Bats.

      Sándor, Attila D; Földvári, Mihály; Krawczyk, Aleksandra I; Sprong, Hein; Corduneanu, Alexandra; Barti, Levente; Görföl, Tamás; Estók, Péter; Kováts, Dávid; Szekeres, Sándor; et al. (2018-04-29)
      Bats are important zoonotic reservoirs for many pathogens worldwide. Although their highly specialized ectoparasites, bat flies (Diptera: Hippoboscoidea), can transmit Bartonella bacteria including human pathogens, their eco-epidemiology is unexplored. Here, we analyzed the prevalence and diversity of Bartonella strains sampled from 10 bat fly species from 14 European bat species. We found high prevalence of Bartonella spp. in most bat fly species with wide geographical distribution. Bat species explained most of the variance in Bartonella distribution with the highest prevalence of infected flies recorded in species living in dense groups exclusively in caves. Bat gender but not bat fly gender was also an important factor with the more mobile male bats giving more opportunity for the ectoparasites to access several host individuals. We detected high diversity of Bartonella strains (18 sequences, 7 genotypes, in 9 bat fly species) comparable with tropical assemblages of bat-bat fly association. Most genotypes are novel (15 out of 18 recorded strains have a similarity of 92-99%, with three sequences having 100% similarity to Bartonella spp. sequences deposited in GenBank) with currently unknown pathogenicity; however, 4 of these sequences are similar (up to 92% sequence similarity) to Bartonella spp. with known zoonotic potential. The high prevalence and diversity of Bartonella spp. suggests a long shared evolution of these bacteria with bat flies and bats providing excellent study targets for the eco-epidemiology of host-vector-pathogen cycles.
    • Ecologische risico's van cytostatica in Nederlandse oppervlaktewateren

      van Dijk, J; Venhuis, B; van Vlaardingen, P; Moermond, C; Marinkovic, M (2019-02-06)
    • Ecosystem quality in LCIA: status quo, harmonization, and suggestions for the way forward

      Woods, John S.; Damiani, Mattia; Fantke, Peter; Henderson, Andrew D.; Johnston, John M.; Bare, Jane; Sala, Serenella; Maia de Souza, Danielle; Pfister, Stephan; Posthuma, Leo; et al. (2017-11-27)
    • Ecotypes of the Mycobacterium tuberculosis complex.

      Smith, Noel H; Kremer, Kristin; Inwald, Jacqueline; Dale, James; Driscoll, Jeffrey R; Gordon, Stephen V; Soolingen, Dick van; Hewinson, R Glyn; Smith, John Maynard (2006-03-21)
      A phylogeny of the Mycobacterium tuberculosis complex has recently shown that the animal-adapted strains are found in a single lineage marked by the deletion of chromosomal region 9 (RD9) [Brosch et al., 2002. A new evolutionary scenario for the Mycobacterium tuberculosis complex. Proc. Natl Acad. Sci. USA 99 (6), 3684-3689]. We have obtained the spoligotype patterns of the RD9 deleted strains used to generate this new evolutionary scenario and we show that the presence of spoligotype spacers 3, 9, 16, 39, and 40-43 is phylogenetically informative in this lineage. We have used the phylogenetically informative spoligotype spacers to screen a database of spoligotype patterns and have identified further members of a group of strains apparently host-adapted to antelopes. The presence of the spoligotype spacers is congruent with the phylogeny generated by chromosomal deletions, suggesting that recombination is rare or absent between strains of this lineage. The phylogenetically informative spacers, in concert with the previously identified single nucleotide mutations and chromosomal deletions, can be used to identify a series of clades in the RD9 deleted lineage each with a separate host preference. Finally, we discuss the application of the ecotype concept to this series of clades and suggest that the M. tuberculosis complex may best be described as a series of host-adapted ecotypes.
    • Editorial for the Special Issue of JPH-Autumn 2017.

      Rushmer, Rosemary; van Oers, Hans; Kothari, Anita (2018-03-01)
    • Editorial to “Use of non-human primate disease models”

      Vermeire, Theo; Badin, Romina Aron; Langermans, Jan; Prescott, Mark J. (2018-09)
    • Editorial: dose-dependent ZnO particle-induced acute phase response in humans warrants re-evaluation of occupational exposure limits for metal oxides.

      Vogel, Ulla; Cassee, Flemming R (2018-02-12)
      Epidemiological studies link inhalation of particles to increased risk of cardiovascular disease. Inhaled particles may induce cardiovascular disease by several different mechanisms including translocation of particles to systemic circulation, activation of airway sensory nerves resulting in autonomic imbalance and particle-induced pulmonary inflammation and acute phase response.The acute phase response is the systemic response to acute and chronic inflammatory states caused by for example bacterial infection, virus infection, trauma and infarction. It is characterized by differential expression of ca. 50 different acute phase proteins including C-reactive protein and Serum amyloid A, which are the most differentially up-regulated acute phase response proteins. Blood levels of these two acute phase proteins are closely associated with risk of cardiovascular disease in epidemiological studies and SAA has been causally related to the formation of plaques in the aorta in animal studies.In a recent paper in Particle and Fibre Toxicology, Christian Monsé et al. provide evidence that inhalation of ZnO nanoparticles induces dose-dependent acute phase response in humans at dose levels well below the current mass-based occupational exposure limits in a number of countries including Germany, The Netherlands, UK, Sweden, Denmark and the US.Given the evidence suggesting a causal relationship between increased levels of serum amyloid A and atherosclerosis, the current results call for a re-evaluation of occupational exposure limits for a number of particle exposures including ZnO taking induction of acute phase response into account. Furthermore, it underscores cardiovascular disease as an occupational disease.
    • Een virtuele zombie-epidemie tijdens Lowlands

      Klinkenberg D; Tieben R; Rijswijk J van; Bhulai S; Luigies R; Wallinga J (2018-03)
    • Effect of 5-year community intervention Hartslag Limburg on cardiovascular risk factors.

      Schuit, Albertine J; Wendel-Vos, Gerrie C W; Verschuren, Wilhelmina M M; Ronckers, Emma T; Ament, Andre; Assema, Patricia van; Ree, Jan van; Ruland, Erik C (2006-03-01)
      BACKGROUND: A widely advocated strategy in public health is community-based health promotion. The aim of this study was to investigate the net effect of a cardiovascular disease prevention program (Hartslag Limburg) on cardiovascular risk factors after 5 years of intervention. DESIGN: Cohort study comparing 5-year mean change in risk factors between the intervention and reference area. The statistical analyses for the study were performed in 2005. SETTING/PARTICIPANTS: In 1998, 3000 subjects (aged 25 to 70) from the intervention area and 895 subjects from a reference area participated in the baseline measurement. Of these, 2414 intervention subjects and 758 reference subjects completed the follow-up measurement in 2003. INTERVENTION: Hartslag Limburg is an integrative community-based cardiovascular disease prevention program promoting a healthy lifestyle. MAIN OUTCOME MEASURES: Body mass index (BMI), waist circumference, blood pressure, serum glucose (nonfasting), and serum total and high-density lipoprotein (HDL) cholesterol. RESULTS: During the 5-year follow-up, risk factors changed unfavorably in the reference group, whereas changes were less pronounced or absent in the intervention group. The adjusted difference in mean change in risk factors between intervention and reference group was significant (p<0.05) for BMI: -0.36 kg/m(2) in men and -0.25 kg/m(2) in women; waist circumference -2.9 cm in men and -2.1 cm in women; systolic blood pressure: -7.8 mmHg in men and -5.5 mmHg in women; total cholesterol 0.11 mmol/L in women and finally serum glucose -0.23 mmol/L in women. CONCLUSIONS: Hartslag Limburg succeeded in reducing-and in some cases, preventing-age- and time-related increase in BMI, waist circumference, blood pressure, and, in women, nonfasting glucose concentration.
    • Effect of a Russian-backbone live-attenuated influenza vaccine with an updated pandemic H1N1 strain on shedding and immunogenicity among children in The Gambia: an open-label, observational, phase 4 study.

      Lindsey, Benjamin B; Jagne, Ya Jankey; Armitage, Edwin P; Singanayagam, Anika; Sallah, Hadijatou J; Drammeh, Sainabou; Senghore, Elina; Mohammed, Nuredin I; Jeffries, David; Höschler, Katja; et al. (2019-08-01)
    • Effect of Adding Sugar to Burley Tobacco on the Emission of Aldehydes in Mainstream Tobacco Smoke

      Cheah, Nuan Ping; Borst, Simon; Hendrickx, Loes; Cremers, Hans; Jansen, Eugene; Opperhuizen, Antoon; Talhout, Reinskje (2018-03-01)
    • Effect of Antibiotic-Mediated Microbiome Modulation on Rotavirus Vaccine Immunogenicity: A Human, Randomized-Control Proof-of-Concept Trial.

      Harris, Vanessa C; Haak, Bastiaan W; Handley, Scott A; Jiang, Baoming; Velasquez, Daniel E; Hykes, Barry L; Droit, Lindsay; Berbers, Guy A M; Kemper, Elles Marleen; van Leeuwen, Ester M M; et al. (2018-08-08)
      Rotavirus vaccines (RVV) protect against childhood gastroenteritis caused by rotavirus (RV) but have decreased effectiveness in low- and middle-income settings. This proof-of-concept, randomized-controlled, open-label trial tested if microbiome modulation can improve RVV immunogenicity. Healthy adults were randomized and administered broad-spectrum (oral vancomycin, ciprofloxacin, metronidazole), narrow-spectrum (vancomycin), or no antibiotics and then vaccinated with RVV, 21 per group per protocol. Baseline anti-RV IgA was high in all subjects. Although antibiotics did not alter absolute anti-RV IgA titers, RVV immunogenicity was boosted at 7 days in the narrow-spectrum group. Further, antibiotics increased fecal shedding of RV while also rapidly altering gut bacterial beta diversity. Beta diversity associated with RVV immunogenicity boosting at day 7 and specific bacterial taxa that distinguish RVV boosters and RV shedders were identified. Despite the negative primary endpoint, this study demonstrates that microbiota modification alters the immune response to RVV and supports further exploration of microbiome manipulation to improve RVV immunogenicity.
    • The effect of body mass index on the risk of surgical site infection.

      Meijs, Anouk P; Koek, Mayke B G; Vos, Margreet C; Geerlings, Suzanne E; Vogely, H Charles; de Greeff, Sabine C (2019-09-01)
    • The effect of capping agents on the toxicity of silver nanoparticles to Danio rerio embryos.

      Abramenko, N; Demidova, T B; Krutyakov, Yu A; Zherebin, P M; Krysanov, E Y; Kustov, L M; Peijnenburg, W (2019-01-29)
      Addition of capping agents like surfactants and polymers during the synthesis of nanoparticles may affect the stability and toxicity of dispersions of nanoparticles. This study revealed the impact of anionic, cationic, and amphoteric surfactants and a cationic polymer on the physical and chemical properties, stability and behavior of silver nanomaterials, as well as on the toxicity of nanosized silver particles with respect to zebrafish embryos. Some of the stabilizers applied were shown to significantly affect embryos of Danio rerio. Colloidal dispersions of stabilized silver nanoparticles were demonstrated to induce a complex mechanism of toxicity with respect to embryos of D. rerio, which is mainly explained by the toxicity of the organic ligand, while other parameters are somewhat inferior. The newly generated data on the toxicity of nanoparticles and their stabilizers with respect to D. rerio embryos reveal the complexity of the toxicity mechanism of nanoparticles impacting living systems.
    • Effect of childhood pneumococcal conjugate vaccination on invasive disease in older adults of 10 European countries: implications for adult vaccination.

      Hanquet, Germaine; Krizova, Pavla; Valentiner-Branth, Palle; Ladhani, Shamez N; Nuorti, J Pekka; Lepoutre, Agnes; Mereckiene, Jolita; Knol, Mirjam; Winje, Brita A; Ciruela, Pilar; et al. (2018-10-24)
      Pneumococcal conjugate vaccines (PCVs) have the potential to prevent pneumococcal disease through direct and indirect protection. This multicentre European study estimated the indirect effects of 5-year childhood PCV10 and/or PCV13 programmes on invasive pneumococcal disease (IPD) in older adults across 13 sites in 10 European countries, to support decision-making on pneumococcal vaccination policies.
    • The effect of chitosan on the bioaccessibility and intestinal permeability of acyclovir.

      Kubbinga, Marlies; Augustijns, Patrick; García, Mauricio A; Heinen, Christian; Wortelboer, Heleen M; Verwei, Miriam; Langguth, Peter (2019-03-01)
      Chitosan is object of pharmaceutical research as a candidate permeability enhancer. However, chitosan was recently shown to reduce the oral bioavailability of acyclovir in humans. The effect of chitosan on two processes determining the oral bioavailability of acyclovir, bioaccessibility and intestinal absorption, was now investigated. Acyclovir's bioaccessibility was studied using the dynamic TNO gastro-Intestinal Model (TIM-1). Four epithelial models were used for permeability experiments: a Caco-2 cell model in absence and presence of mucus and both rat and porcine excised intestinal segments. Study concentrations of acyclovir (0.8 g/l) and chitosan (1.6 g/l and 4 g/l) were in line with those used in the aforementioned human study. No effect of chitosan was measured on the bioaccessibility of acyclovir in the TIM-1 system. The results obtained with the Caco-2 models were not in line with the in vivo data. The tissue segment models (rat and porcine intestine) showed a negative trend of acyclovir's permeation in presence of chitosan. The Ussing type chamber showed to be the most biopredictive, as it did point to an overall statistically significantly reduced absorption of acyclovir. This model thus seems most appropriate for pharmaceutical development purposes, in particular when interactions between excipients and drugs are to become addressed.
    • The Effect of Chronic NO Synthase Inhibition on the Vasoactive and Structural Properties of Thoracic Aorta, NO Synthase Activity, and Oxidative Stress Biomarkers in Young SHR.

      Berenyiova, Andrea; Dovinova, Ima; Kvandova, Miroslava; Kristek, Frantisek; Jansen, Eugene; Majzunova, Miroslava; Cacanyiova, Sona (2018)
      Although the role of nitric oxide (NO) in essential hypertension is still unclear, the effects of long-term NO deficiency have not yet been investigated during the critical juvenile period in spontaneously hypertensive rats (SHR). We aimed to analyze the effects of chronic NO synthase (NOS) inhibition on systolic blood pressure (sBP), vasoactivity, morphological changes and superoxide level in the thoracic aorta (TA), NOS activity in different tissues, and general biomarkers of oxidative stress in plasma of young SHR. Four-week-old SHR were treated with NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day, p.o.) for 4-5 weeks. L-NAME treatment induced a transient sBP increase only, and surprisingly, slightly inhibited endothelium-dependent relaxation of TA. Hereby, the inhibition of NOS activity varied from tissue to tissue, ranging from the lowest in the TA and the kidney to the highest in the brain stem. In spite of an increased sensitivity of adrenergic receptors, the maximal adrenergic contraction of TA was unchanged, which was associated with changes in elastin arrangement and an increase in wall thickness. The production of reactive oxygen species in the TA was increased; however, the level of selected biomarkers of oxidative stress did not change. Our findings proved that the TA of young SHR responded to chronic NO deficiency by the development of adaptive mechanisms on the functional (preserved NO-derived vasorelaxation, unincreased contraction) and molecular (preserved NOS activity) level.
    • Effect of diet with or without exercise on abdominal fat in postmenopausal women - a randomised trial.

      van Gemert, Willemijn A; Peeters, Petra H; May, Anne M; Doornbos, Adriaan J H; Elias, Sjoerd G; van der Palen, Job; Veldhuis, Wouter; Stapper, Maaike; Schuit, Jantine A; Monninkhof, Evelyn M (2019-02-11)
      We assessed the effect of equivalent weight loss with or without exercise on (intra-) abdominal fat in postmenopausal women in the SHAPE-2 study. The SHAPE-2 study is a three-armed randomised controlled trial conducted in 2012-2013 in the Netherlands. Postmenopausal overweight women were randomized to a diet (n = 97), exercise plus diet (n = 98) or control group (n = 48). Both intervention groups aimed for equivalent weight loss (6-7%) following a calorie-restricted diet (diet group) or a partly supervised intensive exercise programme (4 h per week) combined with a small caloric restriction (exercise plus diet group). Outcomes after 16 weeks are amount and distribution of abdominal fat, measured by magnetic resonance imaging (MRI) with the use of the three-point IDEAL Dixon method. The diet and exercise plus diet group lost 6.1 and 6.9% body weight, respectively. Compared to controls, subcutaneous and intra-abdominal fat reduced significantly with both diet (- 12.5% and - 12.0%) and exercise plus diet (- 16.0% and - 14.6%). Direct comparison between both interventions revealed that the reduction in subcutaneous fat was statistically significantly larger in the group that combined exercise with diet: an additional 10.6 cm We conclude that weight loss of 6-7% with diet or with exercise plus diet reduced both subcutaneous and intra-abdominal fat. Only subcutaneous fat statistically significantly reduced to a larger extent when exercise is combined with a small caloric restriction.