National Institute for Public Health

Bilthoven, Netherlands

National Institute for Public Health

Bilthoven, Netherlands
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Westdijk J.,National Institute for Public Health | Brugmans D.,National Institute for Public Health | Martin J.,UK National Institute for Biological Standards and Control | Oever A.V.,National Institute for Public Health | And 3 more authors.
Vaccine | Year: 2011

GMP-batches of Sabin-IPV were characterized for their antigenic and immunogenic properties. Antigenic fingerprints of Sabin-IPV reveal that the D-antigen unit is not a fixed amount of antigen but depends on antibody and assay type. Instead of the D-antigen unit we propose standardization of IPV based on a combination of protein amount for dose and D-antigenicity for quality of the vaccine. Although Sabin-IPV type 2 is less immunogenic than regular wild type IPV type 2, the immunogenicity (virus neutralizing titers) per microgram antigen for Sabin-IPV type 2 is in the same order as for wild type serotypes 1 and 3. The latter observations are in line with data from human trials. This suggests that a higher dose of Sabin-IPV type 2 to compensate for the lower rat immunogenicity may not be necessary. © 2011 Elsevier Ltd.

News Article | December 8, 2016

Algorithms used to track 2014 Ebola epidemic could be used to control future outbreaks of infectious diseases New research on the 2014 Ebola epidemic tracks the rate at which infections move from one district to another and how often infections cross the borders between countries. This study, published in PLOS Computational Biology, could be used to analyze breakouts of new infectious diseases - even when little is known about the transmission characteristics of the new infection. The 2014 Ebola epidemic hit some West African districts very hard, while leaving other districts untouched. Yet there is no evidence that the transmission of the Ebola virus differed between those districts, according to Drs Backer and Wallinga at the Dutch National Institute for Public Health (RIVM). By comparing the notification records in all districts of three affected countries (Guinea, Sierra Leone and Liberia), the researchers could trace back how the virus spread through each district and how it traveled from one district to another. Their research shows that each infective infected on average two new cases in the beginning of the epidemic, and that most of the infected individuals (at least 90%) did not leave their district. Some districts were hit harder because infection was introduced earlier and because infections were introduced more often. To extract this information from notification records the researchers developed novel algorithms, which represent an epidemic as a network of local outbreaks that are interconnected through travelers that transport infection from one district to another. The main advantages of this representation are that it avoids making strong assumptions on transmission characteristics, and that it requires few data beyond the number of inhabitants per district and the notification records. In the future, the researchers hope that their algorithms will help to effectively control any new emerging epidemic, even when we don't know much about the transmission characteristics of the new infection. "Monitoring epidemics is crucial if we want to assess the required effectiveness of control measures" says Dr. Backer, the lead author on this paper. "Now we show that when we monitor a local epidemic together with the epidemic in neighboring districts, we can inform decisions on movement bans or even border closures. In this way, our algorithms can help to effectively control emerging infections." In your coverage please use this URL to provide access to the freely available article in PLOS Computational Biology: http://journals. Citation: Backer JA, Wallinga J (2016) Spatiotemporal Analysis of the 2014 Ebola Epidemic in West Africa. PLoS Comput Biol 12(11): e1005210. doi:10.1371/journal.pcbi.1005210 Funding: The authors received no specific funding for this work. Competing Interests: The authors have declared that no competing interests exist.

Elberse K.E.M.,National Institute for Public Health | Tcherniaeva I.,National Institute for Public Health | Berbers G.A.M.,National Institute for Public Health | Schouls L.M.,National Institute for Public Health
Clinical and Vaccine Immunology | Year: 2010

We describe the optimization and application of a multiplex bead-based assay (Luminex) to quantify antibodies against polysaccharides of 13 pneumococcal serotypes. In the optimized multiplex immunoassay (MIA), intravenous immune globulin was introduced as an in-house reference serum, and nonspecific reacting antibodies were adsorbed with the commercial product pneumococcal C polysaccharides Multi. The antibody concentrations were assessed in 188 serum samples obtained pre-and post-booster vaccination at 11 months after administration of a primary series of the pneumococcal seven-valent conjugate vaccine (PCV-7) at 2, 3, and 4 months of age. The results of the MIA were compared with those of the ELISA for the serotypes included in the seven-valent conjugated polysaccharide vaccine and for a non-vaccine serotype, serotype 6A. The geometric mean concentrations of the antibodies determined by MIA were slightly higher than those determined by ELISA. The correlations between the assays were good, with R2 values ranging from 0.84 to 0.91 for all serotypes except serotype 19F, for which R2 was 0.70. The concentrations of antibody against serotype 6A increased after the administration of PCV-7 due to cross-reactivity with serotype 6B. The differences between the results obtained by ELISA and MIA suggest that the internationally established protective threshold of 0.35 μg/ml should be reevaluated for use in the MIA and may need to be amended separately for each serotype. Copyright © 2010, American Society for Microbiology. All Rights Reserved. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

van Passel M.W.J.,Wageningen University | van Passel M.W.J.,National Institute for Public Health | Nijveen H.,Wageningen University | Wahl L.M.,University of Western Ontario
Genetics | Year: 2014

A previous study of prokaryotic genomes identified large reservoirs of putative mobile promoters (PMPs), that is, homologous promoter sequences associated with nonhomologous coding sequences. Here we extend this data set to identify the full complement of mobile promoters in sequenced prokaryotic genomes. The expanded search identifies nearly 40,000 PMP sequences, 90% of which occur in noncoding regions of the genome. To gain further insight from this data set, we develop a birth-death- diversification model for mobile genetic elements subject to sequence diversification; applying the model to PMPs we are able to quantify the relative importance of duplication, loss, horizontal gene transfer (HGT), and diversification to the maintenance of the PMP reservoir. The model predicts low rates of HGT relative to the duplication and loss of PMP copies, rapid dynamics of PMP families, and a pool of PMPs that exist as a single copy in a genome at any given time, despite their mobility. We report evidence of these "singletons" at high frequencies in prokaryotic genomes. We also demonstrate that including selection, either for or against PMPs, was not necessary to describe the observed data. © 2014 by the Genetics Society of America.

Venhuis B.,National Institute for Public Health | Keizers P.,National Institute for Public Health | van Riel A.,University Utrecht | de Kaste D.,National Institute for Public Health
Drug Testing and Analysis | Year: 2014

Food supplements are regularly found to contain pharmacologically active substances. Recently, the food supplement Dexaprine was removed from the Dutch market because it was associated with severe adverse events. Reports to the Dutch Poisons Information Center (DPIC) showed that ingestion of as little as half a tablet caused several cases of nausea, agitation, tachycardia, and palpitations and even one case of cardiac arrest. The remaining tablets of four patients were sent in by different healthcare professionals. Analysis by ultra-performance liquid chromatography quadrupole time of flight mass-spectrometry (UPLC-QTOF-MS) confirmed the presence of synephrine, oxilofrine, deterenol, yohimbine, caffeine, and theophylline. Two more compounds were found which were tentatively identified as β-methyl-β-phenylethylamines. This incident is only the next in a series of similar incidents involving dietary supplements with (undeclared) active substances that are either unsafe or have no known safety profile. © 2014 John Wiley & Sons, Ltd.

Hendriksen M.A.,National Institute for Public Health | Van Raaij J.M.,National Institute for Public Health | Geleijnse J.M.,Wageningen University | Den Hooven C.W.-V.,National Institute for Public Health | And 2 more authors.
Public Health Nutrition | Year: 2014

Objective To monitor the effectiveness of salt-reduction initiatives in processed foods and changes in Dutch iodine policy on Na and iodine intakes in Dutch adults between 2006 and 2010. Design Two cross-sectional studies among adults, conducted in 2006 and 2010, using identical protocols. Participants collected single 24 h urine samples and completed two short questionnaires on food consumption and urine collection procedures. Daily intakes of salt, iodine, K and Na:K were estimated, based on the analysis of Na, K and iodine excreted in urine. Setting Doetinchem, the Netherlands. Subjects Men and women aged 19 to 70 years were recruited through random sampling of the Doetinchem population and among participants of the Doetinchem Cohort Study (2006: n 317, mean age 48·9 years, 43 % men; 2010: n 342, mean age 46·2 years, 45 % men). Results While median iodine intake was lower in 2010 (179 μg/d) compared with 2006 (257 μg/d; P < 0·0001), no difference in median salt intake was observed (8·7 g/d in 2006 v. 8·5 g/d in 2010, P = 0·70). In 2006, median K intake was 2·6 g/d v. 2·8 g/d in 2010 (P < 0·01). In this 4-year period, median Na:K improved from 2·4 in 2006 to 2·2 in 2010 (P < 0·001). Conclusions Despite initiatives to lower salt in processed foods, dietary salt intake in this population remains well above the recommended intake of 6 g/d. Iodine intake is still adequate, although a decline was observed between 2006 and 2010. This reduction is probably due to changes in iodine policy. © 2013 The Authors.

De Jong W.H.,National Institute for Public Health | Van Der Ven L.T.M.,National Institute for Public Health | Sleijffers A.,National Institute for Public Health | Park M.V.D.Z.,National Institute for Public Health | And 3 more authors.
Biomaterials | Year: 2013

Because of its antibacterial activity nanosilver is one of the most commonly used nanomaterials. It is increasingly used in a variety of both medical and consumer products resulting in an increase in human exposure. However, the knowledge on the systemic toxicity of nanosilver is relatively limited. To determine the potential systemic toxicity of silver nanoparticles (Ag-NP) with different sizes (20nm and 100nm) a 28-days repeated dose toxicity study was performed in rats using intravenous administration. The toxic effect of the 20nm Ag-NP was performed using the bench mark dose (BMD) approach.Treatment with a maximum dose of 6mg/kg body weight was well tolerated by the animals. However, both for 20nm and 100nm Ag-NP growth retardation was observed during the treatment. A severe increase in spleen size and weight was present which was due to an increased cell number. Both T and B cell populations showed an increase in absolute cell number, whereas the relative cell numbers remained constant. At histopathological evaluation brown and black pigment indicating Ag-NP accumulation was noted in spleen, liver, and lymph nodes. Ag-NP was also detected incidentally in other organs. Clinical chemistry indicated liver damage (increased alkaline phosphatase, alanine transaminase, and aspartate transaminase) that could not be confirmed by histopathology. Hematology showed a decrease in several red blood cell parameters.The most striking toxic effect was the almost complete suppression of the natural killer (NK) cell activity in the spleen at high doses. Other immune parameters affected were: decreased interferon-γ and interleukin (IL)-10 production by concanavalin-A stimulated spleen cells, increased IL-1β and decreased IL-6, IL-10 and TNF-α production by lipopolysaccharide stimulated spleen cells, increase in serum IgM and IgE, and increase in blood neutrophilic granulocytes. For the spleen weight a critical effect dose of 0.37mg/kg body weight (b.w.) could be established. The lowest critical effect dose (CED) for a 5% change compared to control animals was observed for thymus weight (CED05 0.01mg/kg b.w.) and for functional immune parameters, i.e. decrease in NK cell activity (CED05 0.06mg/kg b.w.) and LPS stimulation of spleen cells (CED05 0.04mg/kg b.w.). These results show that for nanosilver the most sensitive parameters for potential adverse responses were effects on the immune system. © 2013 The Authors.

Schneeberger P.M.,Robert Bosch GmbH | Wintenberger C.,Grenoble University Hospital Center | van der Hoek W.,National Institute for Public Health | Stahl J.P.,Grenoble University Hospital Center
Medecine et Maladies Infectieuses | Year: 2014

Q fever is a zoonosis caused by Coxiella burnetii with a presentation ranging from asymptomatic seroconversion to possibly fatal chronic Q fever. The Netherlands faced an exceptionally large outbreak of Q fever from 2007 to 2010: 4026 human cases were notified, which makes it the largest Q fever outbreak ever reported. This outbreak, because of its size, allowed collecting a wide range of information on the natural history of Q fever, as well as on its transmission and clinical presentation. It also posed unprecedented public healthcare problems, especially for the concomitant management of the epizootic by veterinarian authorities and public health authorities, but also for the management of transmission risk related to blood donation. The need for cost efficient measures emerged rapidly because of the great number of infected individuals or at risk of infection, with a need for guidance on follow-up of acute Q fever patients, screening of pregnant women, or implementation of diagnostic algorithms. The acute outbreak was controlled by drastic veterinarian measures but chronic Q fever will remain a problem for the coming years. © 2014.

Operario D.,Brown University | Kuo C.,Brown University | Sosa-Rubi S.G.,National Institute for Public Health | Galarraga O.,Brown University
Health Psychology | Year: 2013

Objective: This article reviews psychology and behavioral economic approaches to HIV prevention, and examines the integration and application of these approaches in conditional economic incentive (CEI) programs for reducing HIV risk behavior. Methods: We discuss the history of HIV prevention approaches, highlighting the important insights and limitations of psychological theories. We provide an overview of the theoretical tenets of behavioral economics that are relevant to HIV prevention, and utilize CEIs as an illustrative example of how traditional psychological theories and behavioral economics can be combined into new approaches for HIV prevention. Results: Behavioral economic interventions can complement psychological frameworks for reducing HIV risk by introducing unique theoretical understandings about the conditions under which risky decisions are amenable to intervention. Findings from illustrative CEI programs show mixed but generally promising effects of economic interventions on HIV and sexually transmitted infection (STI) prevalence, HIV testing, HIV medication adherence, and drug use. Conclusions: CEI programs can complement psychological interventions for HIV prevention and behavioral risk reduction. To maximize program effectiveness, CEI programs must be designed according to contextual and population-specific factors that may determine intervention applicability and success. © 2013 American Psychological Association.

Schure R.-M.,National Institute for Public Health | Hendrikx L.H.,University of Amsterdam | De Rond L.G.H.,National Institute for Public Health | Ozturk K.,National Institute for Public Health | And 3 more authors.
Clinical and Vaccine Immunology | Year: 2012

Immunization with acellular pertussis vaccine (aP) induces higher specific antibody levels and fewer adverse reactions than does immunization with the whole-cell vaccine (wP). However, antibody levels in infants induced by both types of pertussis vaccines wane already after 1 year. Therefore, long-term T-cell responses upon vaccination might play a role in protection against pertussis. In a cross-sectional study (ISRCTN65428640), we investigated T-helper (Th) cell immune responses in wP- or aP-vaccinated children before and after an aP low-dose or high-dose preschool booster at 4 years of age in The Netherlands. T cells were stimulated with pertussis vaccine antigens. The numbers of gamma interferon-producing cells and Th1, Th2, Th17, and interleukin-10 (IL-10) cytokine concentrations were determined. In addition, pertussis-specific IgE levels were measured in plasma. Children being vaccinated with aP vaccinations at 2, 3, 4, and 11 months of age still showed higher pertussis-specific T-cell responses at 4 years of age than did wP-vaccinated children. These T-cell responses failed to show a typical increase in cytokine production after a fifth aP vaccination but remained high after a low-dose booster and seemed to decline even after a high-dose booster. Importantly, elevated IgE levels were induced after this booster vaccination. In contrast, wP-vaccinated children had only low prebooster T-cell responses, and these children showed a clear postbooster T-cell memory response even after a low-dose booster vaccine. Four high-dose aP vaccinations in infancy induce high T-cell responses still present even 3 years after vaccination and enhanced IgE responses after preschool booster vaccination. Therefore, studies of changes in vaccine dosage, timing of pertussis (booster) vaccinations, and the possible association with local side effects are necessary. Copyright © 2012, American Society for Microbiology. All Rights Reserved.

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