• V-MRSA-dragerschap en het dagelijks leven van veehouders

      Domsdorf TAPB; Haverkate MR; Eilers R; Timen A (2017-09)
    • Vaccinatieprogramma's in Nederland ; Impact op het aantal ziektegevallen.

      Tulen, Anna D; van Wijhe, Maarten; Korthals Altes, Hester; McDonald, Scott A; de Melker, Hester E; Postma, Maarten J; Wallinga, Jacco (2018-09-20)
      To quantify the impact of long-standing vaccination programmes on notified cases in the Netherlands. Estimates based on model projections of historical morbidity data. We collected and digitised previously unavailable monthly case notifications of diphtheria, poliomyelitis, mumps and rubella in the Netherlands over the period 1919-2015. Poisson regression models accounting for seasonality, multi-year cycles, secular trends and auto-correlation were fit to pre-vaccination periods. Cases averted were calculated as the difference between observed and expected cases based on model projections. In the first 13 years of mass vaccinations, case notifications declined rapidly with 18,900 (95%-CI: 12,000-28,600) notified cases of diphtheria averted, 5100 (95%-CI: 2200-13,500) cases of poliomyelitis, and 1800 (95%-CI: 1000-3200) cases of mumps. Vaccination of 11-year-old girls against rubella averted 13700 (95%-CI: 1400-38,300) cases, while universal rubella vaccination averted 700 (95%-CI: 80-2300) cases.
    • Vaccinaties in het eerste levensjaar en gerapporteerde allergische aandoeningen bij kinderen van 8-12 jaar

      Bernsen, R M D; Jongste, Johan C de; Koes, B W; Aardoom, H A; Wouden, J C van der (RIVM, 2006-06-01)
      Evidence for the relationship between the diphtheria tetanus pertussis (DTP) vaccination and allergic disorders is inconclusive, because the available studies that constitute the evidence are liable to confounding by indication. Further the Haemophilus influenzae type b (Hib) vaccination was added recently to most existing vaccination programmes and therefore no conclusive data on the relationship with allergic disorders are yet available. Objective of the study was to assess the relationship between vaccinations in the first year of life and reported allergic disorders at primary school age. We conducted a cross sectional study in 1875 children attending Orthodox Reformed (Protestant) primary schools in the Netherlands. The parents returned questionnaires with data on vaccination status, allergic symptoms and lifetime allergic disorders (asthma, hay fever, eczema and food allergy), and possible confounders. In the diphtheria tetanus pertussis (inactivated) poliomyelitis (DTP-IPV) vaccinated group Hib vaccinated and Hib unvaccinated children were compared as to allergic disorders. No clinically or statistically significant differences in the prevalence of asthma, hay fever, eczema and food allergy appeared between vaccinated and unvaccinated groups. The DTP-IPV vaccination and the Hib-vaccination, administered in the first year of life, do not increase the risk of allergic disorders in 8-12 years-old, Dutch children.
    • Vaccinating children against influenza increases variability in epidemic size.

      Backer, J A; van Boven, M; van der Hoek, W; Wallinga, J (2018-10-10)
      Seasonal influenza causes a high disease burden. Many influenza vaccination programmes target the elderly and persons at high risk of complications. Some countries have recommended or even implemented a paediatric vaccination programme. Such a programme is expected to reduce influenza transmission in the population, offering direct protection to the vaccinated children and indirect protection to the elderly. We study the impact of a child vaccination programme with an age- and risk-structured transmission model, calibrated to data of 11 influenza seasons in the Netherlands. The model tracks the build-up of immunes and susceptibles in each age cohort over time, and it allows for seasonal variation in vaccine match and antigenic drift. Different vaccination strategies are evaluated for three target age groups (2-3, 2-12 and 2-16 year olds) over the full range of vaccination coverages (0-100%). The results show that the paediatric vaccination programme has only a limited impact on the elderly age groups, which account for most influenza morbidity and mortality. This is due to two notable changes in infection dynamics. First, an age shift is observed: influenza infections are reduced in vaccinated children, but are increased in young adults with limited natural immunity after years of vaccination. These young adults assume the role of driving the epidemic. Second, a year with low influenza activity can be followed by a large epidemic due to build-up of susceptibles. This variation of the infection attack rate increases with increasing vaccination coverage. The increased variability in the infection attack rate implies that health care facilities should be prepared for rare but larger peaks in influenza patients. Moreover, vaccinating the group with the highest transmission potential, results in a larger dependency on a secure vaccine supply. These arguments should be taken into account in the decision to introduce mass vaccination of school-aged children against influenza.
    • Vaccine antigens modulate the innate response of monocytes to Al(OH)3.

      Kooijman, Sietske; Brummelman, Jolanda; van Els, Cécile A C M; Marino, Fabio; Heck, Albert J R; van Riet, Elly; Metz, Bernard; Kersten, Gideon F A; Pennings, Jeroen L A; Meiring, Hugo D (2018)
      Aluminum-based adjuvants have widely been used in human vaccines since 1926. In the absence of antigens, aluminum-based adjuvants can initiate the inflammatory preparedness of innate cells, yet the impact of antigens on this response has not been investigated so far. In this study, we address the modulating effect of vaccine antigens on the monocyte-derived innate response by comparing processes initiated by Al(OH)3 and by Infanrix, an Al(OH)3-adjuvanted trivalent combination vaccine (DTaP), containing diphtheria toxoid (D), tetanus toxoid (T) and acellular pertussis (aP) vaccine antigens. A systems-wide analysis of stimulated monocytes was performed in which full proteome analysis was combined with targeted transcriptome analysis and cytokine analysis. This comprehensive study revealed four major differences in the monocyte response, between plain Al(OH)3 and DTaP stimulation conditions: (I) DTaP increased the anti-inflammatory cytokine IL-10, whereas Al(OH)3 did not; (II) Al(OH)3 increased the gene expression of IFNγ, IL-2 and IL-17a in contrast to the limited induction or even downregulation by DTaP; (III) increased expression of type I interferons-induced proteins was not observed upon DTaP stimulation, but was observed upon Al(OH)3 stimulation; (IV) opposing regulation of protein localization pathways was observed for Al(OH)3 and DTaP stimulation, related to the induction of exocytosis by Al(OH)3 alone. This study highlights that vaccine antigens can antagonize Al(OH)3-induced programming of the innate immune responses at the monocyte level.
    • Vaccine preferences and acceptance of older adults.

      Eilers, R; de Melker, H E; Veldwijk, J; Krabbe, P F M (2017-05-15)
      Expanding vaccination programs for the older population might be important as older adults are becoming a larger proportion of the general population. The aim of this study is to determine the relative importance of vaccine and disease specific characteristics and acceptance for Dutch older adults, including pneumococcal disease, herpes zoster, pertussis vaccination, and influenza vaccination.
    • Validation by interlaboratory trials of EN ISO 10272 - Microbiology of the food chain - Horizontal method for detection and enumeration of Campylobacter spp. - Part 1: Detection method.

      Biesta-Peters, Elisabeth G; Jongenburger, Ida; de Boer, Enne; Jacobs-Reitsma, Wilma F (2018-06-19)
      During the last decade Campylobacter has been the most commonly reported gastrointestinal bacterial infection in humans in the European Union. The use of a sensitive detection method based on enrichment of Campylobacter spp. is often needed when examining foods. However, as background flora developed resistance to third generation β-lactams used in selective culture media, the ISO method was adapted. It now consists of three different procedures (A, B, and C) depending on the expected concentration and condition of Campylobacter and the background microflora. As the diagnostic sensitivity of the detection test varies between laboratories, this justifies the validation of the method in an interlaboratory study. The matrices selected for testing in the collaborative trials were frozen spinach (procedure A, Bolton enrichment broth), minced meat (procedure A, Bolton enrichment broth), raw milk (procedure B, Preston enrichment broth), chicken skin (procedure B, Preston enrichment broth), and broiler caecal material (procedure C, direct plating on mCCD agar). Each matrix was artificially inoculated with a different Campylobacter strain at a low and high contamination level, and with sterile diluent for 'blanks'. Seventeen laboratories participated in the interlaboratory study. The sensitivity and specificity of the methods for the five selected matrices were determined, as well as the level of detection (LOD50). Calculated LOD50 values ranged from 0.84 cfu/test portion in frozen spinach and 2.2 cfu/test portion in minced meat to 14 cfu/test portion in chicken skin and 57 cfu/test portion in raw milk, all based on test portions of 10 g. The test portion size for broiler caecal material was a 10 μl-loop, yielding a LOD50 of 6.1 cfu/test portion. The validation data were incorporated in the newly published ISO standard EN ISO 10272-1:2017 - Microbiology of the food chain - Horizontal method for detection and enumeration of Campylobacter - Part 1: Detection method.
    • Validation by interlaboratory trials of EN ISO 10272 - Microbiology of the food chain - Horizontal method for detection and enumeration of Campylobacter spp. - Part 2: Colony-count technique.

      Jacobs-Reitsma, Wilma F; Jongenburger, Ida; de Boer, Enne; Biesta-Peters, Elisabeth G (2018-06-18)
      The validation in an interlaboratory study of the International Standards Organization standard method for the enumeration of Campylobacter in foods (ISO 10272-2) was performed after preparation of the revised Standard based on scientifically sound and validated methods of analysis. The matrices selected for testing in the collaborative trial were frozen spinach, minced meat, raw milk, chicken skin, and broiler caecal material. Each matrix was artificially inoculated with a different Campylobacter strain. Fifteen laboratories participated in the interlaboratory study. As a general indication of repeatability limit (r), the following overall values can be used when testing chicken skin samples: As a general indication of reproducibility limit (R), the following overall values can be used when testing chicken skin samples: The validation data for all matrices were incorporated in the newly published ISO standard EN ISO 10272-2:2017 - Microbiology of the food chain - Horizontal method for detection and enumeration of Campylobacter - Part 2: colony-count technique.
    • Validation of EN ISO 6579-1 - Microbiology of the food chain - Horizontal method for the detection, enumeration and serotyping of Salmonella - Part 1 detection of Salmonella spp.

      Mooijman, Kirsten A; Pielaat, Annemarie; Kuijpers, Angelina F A (2018-05-12)
      The European and International Standard method for the detection of Salmonella spp. in samples from the primary production stage, EN ISO 6579:2002/Amd.1:2007, was validated by an interlaboratory study in the frame of Mandate M/381, ordered by the European Commission and accepted by the European Standardisation Organisation (CEN). In addition to this study, results from two interlaboratory studies organised earlier by the European Union Reference Laboratory (EURL) for Salmonella were used for determination of the performance characteristics. Parallel to the performance evaluation for the Mandate, the revision of EN ISO 6579:2002 started. Part of this revision was the incorporation of the standardised method for detection of Salmonella in samples from the primary production stage (EN ISO 6579:2002/Amd.1:2007) and its performance characteristics in the new part 1 of EN ISO 6579. The 2002 version of EN ISO 6579 already contained performance characteristics for the detection of Salmonella in food samples, but LOD50 values (contamination level at which 50% of the samples are found positive) were not yet included. To be in line with the performance characteristics determined for detection of Salmonella spp. in samples from the primary production stage, LOD50 values for detection of Salmonella in food samples were calculated from the raw data of the validation studies performed in 2000. In this paper, the performance characteristics of EN ISO 6579-1:2017 are determined based not only on the results of the interlaboratory study carried out in 2013 under the Mandate, but also on several other interlaboratory studies. These performance characteristics consist of specificity, sensitivity and LOD50.
    • Validation of ISO method 15216 part 1 - Quantification of hepatitis A virus and norovirus in food matrices.

      Lowther, J A; Bosch, A; Butot, S; Ollivier, J; Mäde, D; Rutjes, S A; Hardouin, G; Lombard, B; In't Veld, P; Leclercq, A (2017-11-21)
      Hepatitis A virus (HAV) and norovirus are important agents of food-borne human viral illness, with common vehicles including bivalve molluscan shellfish, soft fruit and various vegetables. Outbreaks of viral illness due to contamination of the surfaces of foods, or food preparation surfaces by for example infected food handlers are also common. Virus analysis of food matrices can contribute towards risk management for these hazards and a two-part technical specification for determination of Hepatitis A virus and norovirus in food matrices (ISO/TS 15216:2013) was published jointly by the European Committee for Standardisation and the International Organization for Standardization in 2013. As part of the European Mandate No. M381 to validate 15 standards in the field of food microbiology, an international validation study involving 18 laboratories from 11 countries in Europe was conducted between 2012 and 2014. This study aimed to generate method characteristics including limit of detection, limit of quantification, repeatability and reproducibility for ISO 15216 - Part 1, the method for quantification, in seven food matrices. The organization and results of this study, including observations that led to improvements in the standard method are presented here. After its conclusion, the method characteristics generated were added to the revised international standard, ISO 15216-1:2017, published in March 2017.
    • Validation of the exposure assessment for veterinary medicinal products.

      Montforts, Mark H M M (2006-04-01)
      Under the EU Directive 2004/28/EC, an environmental risk assessment of new veterinary medicinal products is required. Given the nature of risk assessment for new applications, there is a need to model exposure concentrations. Critical evaluations are essential to ensure that the use of models by regulators does not result in the propagation of misleading information. The empirical validations of soil exposure models, previously discussed in this journal, indicate that it is impossible to analyse the contribution of every model parameter to the variability in the predictions. In particular, the prediction of the slurry concentration is challenged by uncertainties concerning dilution, mixing and dissipation of residues. Surface water and groundwater models generated highly deviating results compared to the field results, questioning the usefulness of the available screening models. Animal husbandry, slurry handling and environmental conditions throughout Europe are considered in order to define realistic worst case scenarios, to be used in conjunction with distribution models for the environmental risk assessment of veterinary medicinal products at registration. Given the variability in manure management practice throughout Europe, a deterministic approach for the manure-to-soil model was selected. Both worst case and best case scenario were developed. Several modelling assumptions applied in the surface water exposure model for fish nursery effluent were validated against newly available data. Since the available data give no proof that a settling tank contributes to the removal of pesticides from waste water, it is recommended for risk assessment purposes to consider the contribution of the settling tank to removal of pesticides and medicines to be negligible. Surface water dilution factors may be considered to be rather small, a factor of 2, for low flow situations.
    • Validation redefined.

      Piersma, Aldert H; van Benthem, Jan; Ezendam, Janine; Kienhuis, Anne S (2018-02)
    • Variability and cost implications of three generations of the Roche LightCycler® 480.

      Dullaert-de Boer, Maria; Akkerman, Onno W; Vermeer, Marloes; Hess, Dorine L J; Kerstjens, Huib A M; Anthony, Richard M; van der Werf, Tjip S; van Soolingen, Dick; van der Zanden, Adri G M (2018-01-12)
      Real time PCR has become a dominant method for the highly sensitive detection of pathogens in clinical material. Real time PCR can generate a fluorescence signal by using fluorescence labelled probes, allowing us to detect and semi quantify the amount of amplified DNA. Here we test the variability of the detection system and cost implications of three different versions of the LightCycler® 480 (LC480), focusing on the intensity of fluorescence and Cq in monoplex and multiplex rtPCRs. For gastro-intestinal pathogens there was no correlation between the intensity of fluorescence and the Cq value in the different LC480 types. For probes with the dyes FAMTM, HEXTM, Cy5 and Red610 a higher fluorescence intensity was seen in LC480 type II and III compared to LC480 type I. After lowering the probe concentration for the Cy5 dye three-fold (from 0.3μM to 0.1μM) the Cq value remains the same and the intensity of fluorescence decreases. For the LC480 type II and III the difference in fluorescence intensity was much more extreme. The concentration of the different labelled probes can be lowered at least six-fold in LC480 type II and III cyclers while maintaining a fluorescence intensity as high as achieved in the LC480 type I with undiluted probe. In conclusion, the strength of the fluorescence signal of the LightCycler® 480 type III is superior to that of LightCycler® 480 types I and II, allowing the use of lower probe concentrations for all dyes, particularly for the dyes Red610 and Cy5. This results in a two thirds reduction in PCR probe costs. Switching to these newer machines for real-time PCR can reduce dye labelled probe consumption and thus reduce costs significantly.
    • Variability in market uptake of psychotropic medications in Europe reflects cultural diversity.

      Hoebert, J M; Mantel-Teeuwisse, A K; Leufkens, H G M; van Dijk, L (2017-11-06)
      In the last 20-30 years, many international studies have found substantial differences in the use of (older) psychotropic medication between European countries. The majority mentioned an important role for attitudes and beliefs towards psychotropic medication. So far, no studies have looked into the effects of cultural diversity on the use of new medications entering the market. As national cultures relate deeply to held values regarding, for example, what is seen as effective versus ineffective or safe versus dangerous, (cultural) diversity in decision making around the role of new medications in clinical practice may already be expected from the first day after market authorization.
    • Variable host-pathogen compatibility in Mycobacterium tuberculosis.

      Gagneux, Sebastien; DeRiemer, Kathryn; Van, Tran; Kato-Maeda, Midori; Jong, Bouke C de; Narayanan, Sujatha; Nicol, Mark; Niemann, Stefan; Kremer, Kristin; Gutierrez, M Cristina; Hilty, Markus; Hopewell, Philip C; Small, Peter M (2006-02-21)
      Mycobacterium tuberculosis remains a major cause of morbidity and mortality worldwide. Studies have reported human pathogens to have geographically structured population genetics, some of which have been linked to ancient human migrations. However, no study has addressed the potential evolutionary consequences of such longstanding human-pathogen associations. Here, we demonstrate that the global population structure of M. tuberculosis is defined by six phylogeographical lineages, each associated with specific, sympatric human populations. In an urban cosmopolitan environment, mycobacterial lineages were much more likely to spread in sympatric than in allopatric patient populations. Tuberculosis cases that did occur in allopatric hosts disproportionately involved high-risk individuals with impaired host resistance. These observations suggest that mycobacterial lineages are adapted to particular human populations. If confirmed, our findings have important implications for tuberculosis control and vaccine development.
    • Variation in loss of immunity shapes influenza epidemics and the impact of vaccination.

      Woolthuis, Rutger G; Wallinga, Jacco; van Boven, Michiel (2017-09-19)
      Protective antibody immunity against the influenza A virus wanes in 2-7 years due to antigenic drift of the virus' surface proteins. The duration of immune protection is highly variable because antigenic evolution of the virus is irregular. Currently, the variable nature of the duration of immunity has had little attention in analyses of the impact of vaccination, including cost-effectiveness studies.
    • Varicella vaccination elicits a humoral and cellular response in children with rheumatic diseases using immune suppressive treatment.

      Groot, Noortje; Pileggi, Gecilmara; Sandoval, Cleonice B; Grein, Ingrid; Berbers, Guy; Ferriani, Virginia Paes Leme; Wulffraat, Nico; de Roock, Sytze (2017-05-15)
      To assess humoral and cellular responses to live-attenuated varicella zoster virus (VZV) vaccination of patients with juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM) or juvenile scleroderma (JScle) compared to those of healthy controls (HC).
    • VDJdb: a curated database of T-cell receptor sequences with known antigen specificity.

      Shugay, Mikhail; Bagaev, Dmitriy V; Zvyagin, Ivan V; Vroomans, Renske M; Crawford, Jeremy Chase; Dolton, Garry; Komech, Ekaterina A; Sycheva, Anastasiya L; Koneva, Anna E; Egorov, Evgeniy S; Eliseev, Alexey V; Van Dyk, Ewald; Dash, Pradyot; Attaf, Meriem; Rius, Cristina; Ladell, Kristin; McLaren, James E; Matthews, Katherine K; Clemens, E Bridie; Douek, Daniel C; Luciani, Fabio; van Baarle, Debbie; Kedzierska, Katherine; Kesmir, Can; Thomas, Paul G; Price, David A; Sewell, Andrew K; Chudakov, Dmitriy M (2018-01-04)
      The ability to decode antigen specificities encapsulated in the sequences of rearranged T-cell receptor (TCR) genes is critical for our understanding of the adaptive immune system and promises significant advances in the field of translational medicine. Recent developments in high-throughput sequencing methods (immune repertoire sequencing technology, or RepSeq) and single-cell RNA sequencing technology have allowed us to obtain huge numbers of TCR sequences from donor samples and link them to T-cell phenotypes. However, our ability to annotate these TCR sequences still lags behind, owing to the enormous diversity of the TCR repertoire and the scarcity of available data on T-cell specificities. In this paper, we present VDJdb, a database that stores and aggregates the results of published T-cell specificity assays and provides a universal platform that couples antigen specificities with TCR sequences. We demonstrate that VDJdb is a versatile instrument for the annotation of TCR repertoire data, enabling a concatenated view of antigen-specific TCR sequence motifs. VDJdb can be accessed at https://vdjdb.cdr3.net and https://github.com/antigenomics/vdjdb-db.
    • Verschillen zorgkosten tussen zorggroepen?: Vergelijking van zorggroepen voor mensen met diabetes

      Mohnen, S M; Molema, C C M; Steenbeek, W; van den Berg, M J; de Bruin, S R; Baan, C A; Struijs, J N (2017)
      Is the simple mean of the costs per diabetes patient a suitable tool with which to compare care groups? Do the total costs of care per diabetes patient really give the best insight into care group performance?