Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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    Association of antimicrobial usage with faecal abundance of aph(3’)-III, ermB, sul2 and tetW resistance genes in veal calves in three European countries
    Yang, Dongsheng ; Gompel, Liese Van; Luiken, Roosmarijn E.C. ; Sanders, Pim ; Joosten, Philip ; Heijnsbergen, Eri van; Wouters, Inge M. ; Scherpenisse, Peter ; Chauvin, Claire ; Wadepohl, Katharina ; Greve, Gerdit D. ; Jongerius-Gortemaker, Betty G.M. ; Tersteeg-Zijderveld, Monique H.G. ; Soumet, Christophe ; Skarżyńska, Magdalena ; Juraschek, Katharina ; Fischer, Jennie ; Wasyl, Dariusz ; Wagenaar, Jaap A. ; Dewulf, Jeroen ; Schmitt, Heike ; Mevius, Dik J. ; Heederik, Dick J.J. ; Smit, Lidwien A.M. - \ 2020
    International Journal of Antimicrobial Agents 56 (2020)4. - ISSN 0924-8579
    Antimicrobial resistance - qPCR - Resistance genes - Risk factors - Veal calves

    Background: High antimicrobial use (AMU) and antimicrobial resistance (AMR) in veal calves remain a source of concern. As part of the EFFORT project, the association between AMU and the abundance of faecal antimicrobial resistance genes (ARGs) in veal calves in three European countries was determined. Methods: In 2015, faecal samples of veal calves close to slaughter were collected from farms located in France, Germany and the Netherlands (20 farms in France, 20 farms in the Netherlands and 21 farms in Germany; 25 calves per farm). Standardized questionnaires were used to record AMU and farm characteristics. In total, 405 faecal samples were selected for DNA extraction and quantitative polymerase chain reaction to quantify the abundance (16S normalized concentration) of four ARGs [aph(3’)-III, ermB, sul2 and tetW] encoding for resistance to frequently used antimicrobials in veal calves. Multiple linear mixed models with random effects for country and farm were used to relate ARGs to AMU and farm characteristics. Results: A significant positive association was found between the use of trimethoprim/sulfonamides and the concentration of sul2 in faeces from veal calves. A higher weight of calves on arrival at the farm was negatively associated with aph(3’)-III and ermB. Lower concentrations of aph(3’)-III were found at farms with non-commercial animals present. Furthermore, farms using only water for the cleaning of stables had a significantly lower abundance of faecal ermB and tetW compared with other farms. Conclusion: A positive association was found between the use of trimethoprim/sulfonamides and the abundance of sul2 in faeces in veal calves. Additionally, other relevant risk factors associated with ARGs in veal calves were identified, such as weight on arrival at the farm and cleaning practices.

    Farm dust resistomes and bacterial microbiomes in European poultry and pig farms
    Luiken, Roosmarijn E.C. ; Gompel, Liese Van; Bossers, Alex ; Munk, Patrick ; Joosten, Philip ; Hansen, Rasmus Borup ; Knudsen, Berith E. ; García-Cobos, Silvia ; Dewulf, Jeroen ; Aarestrup, Frank M. ; Wagenaar, Jaap A. ; Smit, Lidwien A.M. ; Mevius, Dik J. ; Heederik, Dick J.J. ; Schmitt, Heike - \ 2020
    Environment International 143 (2020). - ISSN 0160-4120
    Air - Farm - Metagenomics - Microbiome - One health - Resistome

    Background: Livestock farms are a reservoir of antimicrobial resistant bacteria from feces. Airborne dust-bound bacteria can spread across the barn and to the outdoor environment. Therefore, exposure to farm dust may be of concern for animals, farmers and neighboring residents. Although dust is a potential route of transmission, little is known about the resistome and bacterial microbiome of farm dust. Objectives: We describe the resistome and bacterial microbiome of pig and poultry farm dust and their relation with animal feces resistomes and bacterial microbiomes, and on-farm antimicrobial usage (AMU). In addition, the relation between dust and farmers’ stool resistomes was explored. Methods: In the EFFORT-study, resistomes and bacterial microbiomes of indoor farm dust collected on Electrostatic Dust fall Collectors (EDCs), and animal feces of 35 conventional broiler and 44 farrow-to-finish pig farms from nine European countries were determined by shotgun metagenomic analysis. The analysis also included 79 stool samples from farmers working or living at 12 broiler and 19 pig farms and 46 human controls. Relative abundance of and variation in resistome and bacterial composition of farm dust was described and compared to animal feces and farmers’ stool. Results: The farm dust resistome contained a large variety of antimicrobial resistance genes (ARGs); more than the animal fecal resistome. For both poultry and pigs, composition of dust resistomes finds (partly) its origin in animal feces as dust resistomes correlated significantly with fecal resistomes. The dust bacterial microbiome also correlated significantly with the dust resistome composition. A positive association between AMU in animals on the farm and the total abundance of the dust resistome was found. Occupational exposure to pig farm dust or animal feces may contribute to farmers’ resistomes, however no major shifts in farmers resistome towards feces or dust resistomes were found in this study. Conclusion: Poultry and pig farm dust resistomes are rich and abundant and associated with the fecal resistome of the animals and the dust bacterial microbiome.

    Description and determinants of the faecal resistome and microbiome of farmers and slaughterhouse workers : A metagenome-wide cross-sectional study
    Gompel, Liese Van; Luiken, Roosmarijn E.C. ; Hansen, Rasmus B. ; Munk, Patrick ; Bouwknegt, Martijn ; Heres, Lourens ; Greve, Gerdit D. ; Scherpenisse, Peter ; Jongerius-Gortemaker, Betty G.M. ; Tersteeg-Zijderveld, Monique H.G. ; García-Cobos, Silvia ; Dohmen, Wietske ; Dorado-García, Alejandro ; Wagenaar, Jaap A. ; Urlings, Bert A.P. ; Aarestrup, Frank M. ; Mevius, Dik J. ; Heederik, Dick J.J. ; Schmitt, Heike ; Bossers, Alex ; Smit, Lidwien A.M. - \ 2020
    Environment International 143 (2020). - ISSN 0160-4120
    Antimicrobial resistance - Farmers - Microbiome - Occupational exposure - Resistome - Slaughterhouse workers

    Background: By studying the entire human faecal resistome and associated microbiome, the diversity and abundance of faecal antimicrobial resistance genes (ARGs) can be comprehensively characterized. Prior culture-based studies have shown associations between occupational exposure to livestock and carriage of specific antimicrobial resistant bacteria. Using shotgun metagenomics, the present study investigated 194 faecal resistomes and bacteriomes from humans occupationally exposed to ARGs in livestock (i.e. pig and poultry farmers, employees and family members and pig slaughterhouse workers) and a control population (Lifelines cohort) in the Netherlands. In addition, we sought to identify determinants for the human resistome and bacteriome composition by applying a combination of multivariate (NMDS, PERMANOVA, SIMPER and DESeq2 analysis) and multivariable regression analysis techniques. Results: Pig slaughterhouse workers and pig farmers carried higher total ARG abundances in their stools compared to broiler farmers and control subjects. Tetracycline, β-lactam and macrolide resistance gene clusters dominated the resistome of all studied groups. No significant resistome alpha diversity differences were found among the four populations. However, the resistome beta diversity showed a separation of the mean resistome composition of pig and pork exposed workers from broiler farmers and controls, independent of their antimicrobial use. We demonstrated differences in resistome composition between slaughter line positions, pig versus poultry exposed workers, as well as differences between farmers and employees versus family members. In addition, we found a significant correlation between the bacteriome and resistome, and significant differences in the bacteriome composition between and within the studied subpopulations. Finally, an in-depth analysis of pig and poultry farms – of which also farm livestock resistomes were analysed – showed positive associations between the number of on-farm working hours and human faecal AMR loads. Conclusion: We found that the total normalized faecal ARG carriage was larger in persons working in the Dutch pork production chain compared to poultry farmers and controls. Additionally, we showed significant differences in resistome and bacteriome composition of pig and pork exposed workers compared to a control group, as well as within-population (farms, slaughterhouse) compositional differences. The number of on-farm working hours and the farm type (pig or broiler) that persons live or work on are determinants for the human faecal resistome. Overall, our results may suggest direct or indirect livestock contact as a determinant for human ARG carriage. Future studies should further focus on the connection between the human and livestock resistome (i.e. transmission routes) to substantiate the evidence for livestock-associated resistome acquisition.

    The impact of manure and soil texture on antimicrobial resistance gene levels in farmlands and adjacent ditches
    Macedo, Gonçalo ; Hernandez-Leal, Lucia ; Maas, Peter van der; Heederik, Dick ; Mevius, Dik ; Schmitt, Heike - \ 2020
    Science of the Total Environment 737 (2020). - ISSN 0048-9697

    Manure application can spread antimicrobial resistance (AMR) from manure to soil and surface water. This study evaluated the role of the soil texture on the dynamics of antimicrobial resistance genes (ARGs) in soils and surrounding surface waters. Six dairy farms with distinct soil textures (clay, sand, and peat) were sampled at different time points after the application of manure, and three representative ARGs sul1, erm(B), and tet(W) were quantified with qPCR. Manuring initially increased levels of erm(B) by 1.5 ± 0.5 log copies/kg of soil and tet(W) by 0.8 ± 0.4 log copies/kg across soil textures, after which levels gradually declined. In surface waters from clay environments, regardless of the ARG, the gene levels initially increased by 2.6 ± 1.6 log copies/L, after which levels gradually declined. The gene decay in soils was strongly dependent on the type of ARG (erm(B) < tet(W) < sul1; half-lives of 7, 11, and 75 days, respectively), while in water, the decay was primarily dependent on the soil texture adjacent to the sampled surface water (clay < peat < sand; half-lives of 2, 6, and 10 days, respectively). Finally, recovery of ARG levels was predicted after 29–42 days. The results thus showed that there was not a complete restoration of ARGs in soils between rounds of manure application. In conclusion, this study demonstrates that rather than showing similar dynamics of decay, factors such as the type of ARG and soil texture drive the ARG persistence in the environment.

    Veehouderij en Gezondheid Omwonenden III: Longontsteking in de nabijheid van geitenhouderijen in Gelderland, Overijssel en Utrecht
    Smit, Lidwien ; Huss, Anke ; Jacobs, José ; Baliatsas, Christos ; Dückers, Michel ; Boender, Gert Jan ; McCarthy, Catharine ; Hagenaars, Thomas ; IJzermans, Joris ; Heederik, Dick - \ 2019
    Utrecht : Institute for Risk Assessment Sciences (IRAS), Universiteit Utrecht - 39
    Implementation and evaluation of an antimicrobial stewardship programme in companion animal clinics: A stepped-wedge design intervention study
    Hopman, Nonke E.M. ; Portengen, Lützen ; Hulscher, Marlies E.J.L. ; Heederik, Dick J.J. ; Verheij, T.J.M. ; Wagenaar, Jaap A. ; Prins, Jan M. ; Bosje, Tjerk ; Schipper, Louska ; Geijlswijk, Ingeborg M. Van; Broens, Els M. - \ 2019
    PLoS ONE 14 (2019)11. - ISSN 1932-6203

    Background To curb increasing resistance rates, responsible antimicrobial use (AMU) is needed, both in human and veterinary medicine. In human healthcare, antimicrobial stewardship programmes (ASPs) have been implemented worldwide to improve appropriate AMU. No ASPs have been developed for and implemented in companion animal clinics yet. Objectives The objective of the present study was to implement and evaluate the effectiveness of an ASP in 44 Dutch companion animal clinics. The objectives of the ASP were to increase awareness on AMU, to decrease total AMU whenever possible and to shift AMU towards 1st choice antimicrobials, according to Dutch guidelines on veterinary AMU. Methods The study was designed as a prospective, stepped-wedge, intervention study, which was performed from March 2016 until March 2018. The multifaceted intervention was developed using previous qualitative and quantitative research on current prescribing behaviour in Dutch companion animal clinics. The number of Defined Daily Doses for Animal (DDDAs) per clinic (total, 1st, 2nd and 3rd choice AMU) was used to quantify systemic AMU. Monthly AMU data were described using a mixed effect time series model with auto-regression. The effect of the ASP was modelled using a step function and a change in the (linear) time trend. Results A statistically significant decrease of 15% (7%-22%) in total AMU, 15% (5%-24%) in 1st choice AMU and 26% (17%-34%) in 2nd choice AMU was attributed to participation in the ASP, on top of the already ongoing time trends. Use of 3rd choice AMs did not significantly decrease by participation in the ASP. The change in total AMU became more prominent over time, with a 16% (4%-26%) decrease in (linear) time trend per year. Conclusions This study shows that, although AMU in Dutch companion animal clinics was already decreasing and changing, AMU could be further optimised by participation in an antimicrobial stewardship programme.

    Risk of pneumonia among residents living near goat and poultry farms during 2014-2016
    Post, Pim M. ; Hogerwerf, Lenny ; Huss, Anke ; Petie, Ronald ; Boender, Gert Jan ; Baliatsas, Christos ; Lebret, Erik ; Heederik, Dick ; Hagenaars, Thomas J. ; IJzermans, Joris C. ; Smit, Lidwien A.M. - \ 2019
    PLoS ONE 14 (2019)10. - ISSN 1932-6203

    In the Netherlands, an association was found between the prevalence of pneumonia and living near goat and poultry farms in 2007-2013. This association then led to regulatory decisions to restrict the building of new goat farms and to reduce emissions of poultry farms. Confirmation of these results, however, is required because the period of previous analyses overlapped a Q-fever epidemic in 2007-2010. To confirm the association, we performed a population-based study during 2014-2016 based on general practitioner (GP) data. Electronic medical records of 90,183 persons were used to analyze the association between pneumonia and the population living in the proximity (within 500-2000 m distance) of goat and poultry farms. Data were analyzed with three types of logistic regression (with and without GP practice as a random intercept and with stratified analyses per GP practice) and a kernel model to discern the influence of different statistical methods on the outcomes. In all regression analyses involving adults, a statistically significant association between pneumonia and residence within 500 meters of goat farms was found (odds ratio [OR] range over all analyses types: 1.33-1.60), with a decreasing OR for increasing distances. In kernel analyses (including all ages), a population-attributable risk between 6.0 and 7.8% was found for a distance of 2000 meters in 2014-2016. The associations were consistent across all years and robust for mutual adjustment for proximity to other animals and for several other sensitivity analyses. However, associations with proximity to poultry farms are not supported by the present study. As the causes of the elevated pneumonia incidence in persons living close to goat farms remain unknown, further research into potential mechanisms is required for adequate prevention.

    Kringlooplandbouw? Vergeet de dieren niet
    Stegeman, Arjan ; Zwietering, M.H. ; Heederik, D.J.J. - \ 2019
    De Volkskrant (2019).
    Associations between antimicrobial use and the faecal resistome on broiler farms from nine European countries
    Luiken, Roosmarijn E.C. ; Gompel, Liese Van; Munk, Patrick ; Sarrazin, Steven ; Joosten, Philip ; Dorado-García, Alejandro ; Borup Hansen, Rasmus ; Knudsen, Berith E. ; Bossers, Alex ; Wagenaar, Jaap A. ; Aarestrup, Frank M. ; Dewulf, Jeroen ; Mevius, Dik J. ; Heederik, Dick J.J. ; Smit, Lidwien A.M. ; Schmitt, Heike - \ 2019
    Journal of Antimicrobial Chemotherapy 74 (2019)9. - ISSN 0305-7453 - p. 2596 - 2604.

    OBJECTIVES: To determine associations between farm- and flock-level antimicrobial usage (AMU), farm biosecurity status and the abundance of faecal antimicrobial resistance genes (ARGs) on broiler farms. METHODS: In the cross-sectional pan-European EFFORT study, conventional broiler farms were visited and faeces, AMU information and biosecurity records were collected. The resistomes of pooled faecal samples were determined by metagenomic analysis for 176 farms. A meta-analysis approach was used to relate total and class-specific ARGs (expressed as fragments per kb reference per million bacterial fragments, FPKM) to AMU (treatment incidence per DDD, TIDDDvet) per country and subsequently across all countries. In a similar way, the association between biosecurity status (Biocheck.UGent) and the resistome was explored. RESULTS: Sixty-six (38%) flocks did not report group treatments but showed a similar resistome composition and roughly similar ARG levels to antimicrobial-treated flocks. Nevertheless, we found significant positive associations between β-lactam, tetracycline, macrolide and lincosamide, trimethoprim and aminoglycoside antimicrobial flock treatments and ARG clusters conferring resistance to the same class. Similar associations were found with purchased products. In gene-level analysis for β-lactams and macrolides, lincosamides and streptogramins, a significant positive association was found with the most abundant gene clusters blaTEM and erm(B). Little evidence was found for associations with biosecurity. CONCLUSIONS: The faecal microbiome in European broilers contains a high diversity of ARGs, even in the absence of current antimicrobial selection pressure. Despite this, the relative abundance of genes and the composition of the resistome is positively related to AMU in European broiler farms for several antimicrobial classes.

    Attributable sources of community-acquired carriage of Escherichia coli containing β-lactam antibiotic resistance genes: a population-based modelling study
    Mughini-Gras, Lapo ; Dorado-García, Alejandro ; Duijkeren, Engeline van; Bunt, Gerrita van den; Dierikx, Cindy M. ; Bonten, Marc J.M. ; Bootsma, Martin C.J. ; Schmitt, Heike ; Hald, Tine ; Evers, Eric G. ; Koeijer, Aline de; Pelt, Wilfrid van; Franz, Eelco ; Mevius, Dik J. ; Heederik, Dick J.J. - \ 2019
    The Lancet Planetary Health 3 (2019)8. - ISSN 2542-5196 - p. e357 - e369.

    Background: Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC), plasmid-mediated AmpC-producing E coli (pAmpC-EC), and other bacteria are resistant to important β-lactam antibiotics. ESBL-EC and pAmpC-EC are increasingly reported in animals, food, the environment, and community-acquired and health-care-associated human infections. These infections are usually preceded by asymptomatic carriage, for which attributions to animal, food, environmental, and human sources remain unquantified. Methods: In this population-based modelling study, we collected ESBL and pAmpC gene data on the Netherlands population for 2005–17 from published datasets of gene occurrences in E coli isolates from different sources, and from partners of the ESBL Attribution Consortium and the Dutch National Antimicrobial Surveillance System. Using these data, we applied an established source attribution model based on ESBL-EC and pAmpC-EC prevalence and gene data for humans, including high-risk populations (ie, returning travellers, clinical patients, farmers), farm and companion animals, food, surface freshwater, and wild birds, and human exposure data, to quantify the overall and gene-specific attributable sources of community-acquired ESBL-EC and pAmpC-EC intestinal carriage. We also used a simple transmission model to determine the basic reproduction number (R0) in the open community. Findings: We identified 1220 occurrences of ESBL-EC and pAmpC-EC genes in humans, of which 478 were in clinical patients, 454 were from asymptomatic carriers in the open community, 103 were in poultry and pig farmers, and 185 were in people who had travelled out of the region. We also identified 6275 occurrences in non-human sources, including 479 in companion animals, 4026 in farm animals, 66 in wild birds, 1430 from food products, and 274 from surface freshwater. Most community-acquired ESBL-EC and pAmpC-EC carriage was attributed to human-to-human transmission within or between households in the open community (60·1%, 95% credible interval 40·0–73·5), and to secondary transmission from high-risk groups (6·9%, 4·1–9·2). Food accounted for 18·9% (7·0–38·3) of carriage, companion animals for 7·9% (1·4–19·9), farm animals (non-occupational contact) for 3·6% (0·6–9·9), and swimming in freshwater and wild birds (ie, environmental contact) for 2·6% (0·2–8·7). We derived an R0 of 0·63 (95% CI 0·42–0·77) for intracommunity transmission. Interpretation: Although humans are the main source of community-acquired ESBL-EC and pAmpC-EC carriage, the attributable non-human sources underpin the need for longitudinal studies and continuous monitoring, because intracommunity ESBL-EC and pAmpC-EC spread alone is unlikely to be self-maintaining without transmission to and from non-human sources. Funding: 1Health4Food, Dutch Ministry of Economic Affairs, and the EU's Horizon-2020 through One-Health European Joint Programme.

    Endotoxin and particulate matter emitted by livestock farms and respiratory health effects in neighboring residents
    Rooij, Myrna M.T. de; Smit, Lidwien A.M. ; Erbrink, Hans J. ; Hagenaars, Thomas J. ; Hoek, Gerard ; Ogink, Nico W.M. ; Winkel, Albert ; Heederik, Dick J.J. ; Wouters, Inge M. - \ 2019
    Environment International 132 (2019). - ISSN 0160-4120
    Air pollution - Emissions - Endotoxin - Livestock farming - Public health - Spatial modelling

    Background: Living in livestock-dense areas has been associated with health effects, suggesting airborne exposures to livestock farm emissions to be relevant for public health. Livestock farm emissions involve complex mixtures of various gases and particles. Endotoxin, a pro-inflammatory agent of microbial origin, is a constituent of livestock farm emitted particulate matter (PM) that is potentially related to the observed health effects. Quantification of livestock associated endotoxin exposure at residential addresses in relation to health outcomes has not been performed earlier. Objectives: We aimed to assess exposure-response relations for a range of respiratory endpoints and atopic sensitization in relation to livestock farm associated PM10 and endotoxin levels. Methods: Self-reported respiratory symptoms of 12,117 persons participating in a population-based cross-sectional study were analyzed. For 2494 persons, data on lung function (spirometry) and serologically assessed atopic sensitization was additionally available. Annual-average PM10 and endotoxin concentrations at home addresses were predicted by dispersion modelling and land-use regression (LUR) modelling. Exposure-response relations were analyzed with generalized additive models. Results: Health outcomes were generally more strongly associated with exposure to livestock farm emitted endotoxin compared to PM10. An inverse association was observed for dispersion modelled exposure with atopic sensitization (endotoxin: p =.004, PM10: p =.07) and asthma (endotoxin: p =.029, PM10: p =.022). Prevalence of respiratory symptoms decreased with increasing endotoxin concentration at the lower range, while at the higher range prevalence increased with increasing concentration (p <.05). Associations between lung function parameters with exposure to PM10 and endotoxin were not statistically significant (p >.05). Conclusions: Exposure to livestock farm emitted particulate matter is associated with respiratory health effects and atopic sensitization in non-farming residents. Results indicate endotoxin to be a potentially plausible etiologic agent, suggesting non-infectious aspects of microbial emissions from livestock farms to be important with respect to public health.

    Time trends, seasonal differences and determinants of systemic antimicrobial use in companion animal clinics (2012-2015)
    Hopman, Nonke E.M. ; Portengen, Lützen ; Heederik, Dick J.J. ; Wagenaar, Jaap A. ; Geijlswijk, Ingeborg M. Van; Broens, E.M. - \ 2019
    Veterinary Microbiology 235 (2019). - ISSN 0378-1135 - p. 289 - 294.
    Antimicrobial use - Companion animal - Determinant - Seasonality - Time trend - Veterinary medicine

    Any antimicrobial use (AMU) in humans and animals selects for antimicrobial resistance (AMR) and responsible AMU should therefore be promoted both in human and veterinary medicine. Insight into current AMU in companion animal clinics is necessary to be able to optimise antimicrobial (AM) prescribing behaviour. The objective of this study was to describe systemic AMU in 44 Dutch companion animal clinics over a 3-year time period (2012–2015), using retrospectively collected data. The number of Defined Daily Doses for Animals (DDDAs) per month and per clinic were calculated from prescription data for total, 1st, 2nd and 3rd choice AMU (classification according to Dutch policy on veterinary AMU). Time trends, seasonality and the influence of potential determinants (e.g., the number of dogs, cats and rabbits per clinic and other clinic characteristics) were explored using statistical modelling. Overall, the findings show that total AMU decreased over time and a shift in used classes of antimicrobials towards more 1st choice AMs was visible. Mean total AMU decreased from 1.82 DDDA/year in 2012–2013 to 1.56 DDDA/year in 2014-2015. Aminopenicillins, with and without clavulanic acid, accounted for the largest group of antimicrobials used; 38.7% (2012–2013), 40.2% (2013–2014) and 39.3% (2014–2015) of total AMU, respectively. Strong seasonal differences in AMU were found, with highest AMU in July-August and lowest in February-March. The distribution of different animal species per clinic appeared to affect AMU as well. In clinics with a larger proportion of dogs, 2nd choice AMU was significantly higher, whereas in clinics with a larger proportion of rabbits, 2nd choice AMU was significantly lower. Despite the decrease of AMU during the study period, there is still room for improvement left, especially with regard to the antimicrobial classes prescribed. According to Dutch classification of veterinary AMU, 1st choice AMs should be used as empirical therapy. A decrease in 2nd (might select for ESBL-producing bacteria) and 3rd choice AMU (i.e. fluoroquinolones and 3rd generation cephalosporins) should be aimed for.

    Quantifying antimicrobial use in Dutch companion animals
    Hopman, Nonke E.M. ; Dijk, Marloes A.M. Van; Broens, Els M. ; Wagenaar, Jaap A. ; Heederik, Dick J.J. ; Geijlswijk, Ingeborg M. Van - \ 2019
    Frontiers in Veterinary Science 6 (2019)May. - ISSN 2297-1769
    Antibiotic - Antimicrobial - Companion animals - DDDA - Defined daily dose - Prescribing - Veterinary medicine

    Antimicrobial resistance (AMR) is an increasing threat, both in human and in veterinary medicine. To reduce the selection and spread of AMR, antimicrobial use (AMU) should be optimized, also in companion animals. To be able to optimize AMU, a feasible method to quantify AMU and information on current AMU are needed. Therefore, a method to quantify AMU was developed, using the number of Defined Daily Doses Animal (DDDA). This method was used to explore applied antimicrobial classes and to identify differences in prescribing patterns in time and between veterinary clinics. Antimicrobial procurement data of the years 2012-2014 were collected retrospectively from 100 Dutch veterinary clinics providing care for companion animals. The mean number of DDDAs per clinic per year decreased significantly from 2012 to 2014. A shift in used classes of antimicrobials (AMs) was seen as well, with a significant decrease in use of third choice AMs (i.e., fluoroquinolones and third generation cephalosporins). Large differences in total AMU were seen between clinics ranging from 64-fold in 2012 to 20-fold in 2014. Despite the relative low and decreasing AMU in Dutch companion animal clinics during the study, the substantial differences in antimicrobial prescribing practices between clinics suggest that there is still room for quantitative and qualitative optimization of AMU.

    Dynamics of faecal shedding of ESBL- or AmpC-producing Escherichia coli on dairy farms
    Hordijk, Joost ; Fischer, Egil A.J. ; Werven, Tine van; Sietsma, Steven ; Gompel, Liese Van; Timmerman, Arjen J. ; Spaninks, Mirlin P. ; Heederik, Dick J.J. ; Nielen, Mirjam ; Wagenaar, Jaap A. ; Stegeman, Arjan - \ 2019
    Journal of Antimicrobial Chemotherapy 74 (2019)6. - ISSN 0305-7453 - p. 1531 - 1538.

    OBJECTIVES: To explore the dynamics of faecal ESBL/AmpC shedding in dairy cattle and farmers, a study was conducted to examine changes in shedding by individual animals, as well as environmental exposure, and to study the association between antimicrobial use (AMU) and ESBL/AmpC shedding. METHODS: The study comprised a cross-sectional survey of 20 farms and a 1 year follow-up of 10 farms. Faecal samples were cultured by both direct inoculation on MacConkey agar + 1 mg/L cefotaxime (MC+) and enrichment in LB-broth + 1 mg/L cefotaxime with subsequent inoculation on MC+. Dust samples were collected using electrostatic dustfall collectors (EDCs). Human faecal samples were collected by the farmers. Presence of ESBL/AmpC genes was screened for by PCR and sequencing. Using mixed effects logistic regression, ORs were determined and population-attributable fractions (PAFs) calculated subsequently. RESULTS: In Phase 1, 8/20 farms were positive for ESBL/AmpC and, with 2 negative farms, were selected for Phase 2. Transient shedding of dominant allele variants was observed in the animals. EDCs and human faecal samples did not reflect what was observed in the animals. AMU was related to shedding of ESBLs in the next sampling moment [OR 14.6 (95% CI 3.0-80.0)] and the PAF of AMU was 0.36 (95% CI 0.08-0.77). Calves fed with colostrum from cows on dry-off therapy was not a risk factor [OR 1.7 (95% CI 0.7-4.9, P = 0.28)]. CONCLUSIONS: The presence of ESBL/AmpC could only be partly explained by AMU. No link was shown between shedding in cattle and humans or the environment. Interventions should focus on prevention of introduction.

    Risicomodellering veehouderij en gezondheid (RVG) : modellering van regionale endotoxineconcentraties en relaties met gezondheidseffecten
    Heederik, Dick ; Erbrink, Hans ; Farokhi, Azadeh ; Hagenaars, Thomas ; Hoek, Gerard ; Ogink, Nico ; Rooij, Myrna de; Smit, Lidwien ; Winkel, Albert ; Wouters, Inge - \ 2019
    Wageningen : Wageningen University & Research (IRAS UU 2019-01) - 133
    The antimicrobial resistome in relation to antimicrobial use and biosecurity in pig farming, a metagenome-wide association study in nine European countries
    Gompel, Liese Van; Luiken, Roosmarijn E.C. ; Sarrazin, Steven ; Munk, Patrick ; Knudsen, Berith E. ; Hansen, Rasmus B. ; Bossers, Alex ; Aarestrup, Frank M. ; Dewulf, Jeroen ; Wagenaar, Jaap A. ; Mevius, Dik J. ; Schmitt, Heike ; Heederik, Dick J.J. ; Dorado-García, Alejandro ; Smit, Lidwien A.M. - \ 2019
    Journal of Antimicrobial Chemotherapy 74 (2019)4. - ISSN 0305-7453 - p. 865 - 876.

    OBJECTIVES: Previous studies in food-producing animals have shown associations between antimicrobial use (AMU) and resistance (AMR) in specifically isolated bacterial species. Multi-country data are scarce and only describe between-country differences. Here we investigate associations between the pig faecal mobile resistome and characteristics at the farm-level across Europe. METHODS: A cross-sectional study was conducted among 176 conventional pig farms from nine European countries. Twenty-five faecal samples from fattening pigs were pooled per farm and acquired resistomes were determined using shotgun metagenomics and the Resfinder reference database, i.e. the full collection of horizontally acquired AMR genes (ARGs). Normalized fragments resistance genes per kilobase reference per million bacterial fragments (FPKM) were calculated. Specific farm-level data (AMU, biosecurity) were collected. Random-effects meta-analyses were performed by country, relating farm-level data to relative ARG abundances (FPKM). RESULTS: Total AMU during fattening was positively associated with total ARG (total FPKM). Positive associations were particularly observed between widely used macrolides and tetracyclines, and ARGs corresponding to the respective antimicrobial classes. Significant AMU-ARG associations were not found for β-lactams and only few colistin ARGs were found, despite high use of these antimicrobial classes in younger pigs. Increased internal biosecurity was directly related to higher abundances of ARGs mainly encoding macrolide resistance. These effects of biosecurity were independent of AMU in mutually adjusted models. CONCLUSIONS: Using resistome data in association studies is unprecedented and adds accuracy and new insights to previously observed AMU-AMR associations. Major components of the pig resistome are positively and independently associated with on-farm AMU and biosecurity conditions.

    Quantitative and qualitative analysis of antimicrobial usage at farm and flock level on 181 broiler farms in nine European countries
    Joosten, Philip ; Sarrazin, Steven ; Gompel, Liese Van; Luiken, Roosmarijn E.C. ; Mevius, Dik J. ; Wagenaar, Jaap A. ; Heederik, Dick J.J. ; Dewulf, Jeroen - \ 2019
    Journal of Antimicrobial Chemotherapy 74 (2019)3. - ISSN 0305-7453 - p. 798 - 806.

    OBJECTIVES: To control the emerging threat of antimicrobial resistance, international policy appeals for appropriate monitoring of antimicrobial usage (AMU) at supranational, species and farm level. The aim of this study was to quantify AMU in broilers at farm and flock level in nine European countries. METHODS: Antimicrobial treatment data of one flock and purchased antimicrobials over one year were collected at 181 European broiler farms. Afterwards AMU was quantified using treatment incidence (TI) per 100 days based on Defined Daily Dose (DDDvet), Defined Course Dose (DCDvet) or Used Daily Dose (UDDvet) values. Total AMU at flock level was obtained by summing the TIDDDvet of all treatments in the sampled flock (TIDDDvetFl*). RESULTS: The median TIDDDvetFl* was 9.0 (95% CI 5.5-10.8), meaning that broilers were treated with antimicrobials during 9% of their rearing period. TIDDDvetFl* varied considerably within and between countries. However, in every country at least one untreated flock was present. Average TIDDDvetFl* at country level ranged from 3.3 to 36.7. Polymyxins, extended-spectrum aminopenicillins and fluoroquinolones were the most used antimicrobials, accounting for 26%, 26% and 18% of total AMU, respectively. Twenty-six percent of the farms started a treatment on day 1 of production, and 49% of overall AMU was administered within the first week. CONCLUSIONS: Results show that rearing broilers without AMU is feasible. However, a huge variation in AMU in terms of amount, moment of administration and antimicrobial classes was observed. This shows that there is still ground to be covered when it comes to AMU on broiler farms.

    Quantitative and qualitative analysis of antimicrobial usage patterns in 180 selected farrow-to-finish pig farms from nine European countries based on single batch and purchase data
    Sarrazin, Steven ; Joosten, Philip ; Gompel, Liese Van; Luiken, Roosmarijn E.C. ; Mevius, Dik J. ; Wagenaar, Jaap A. ; Heederik, Dick J.J. ; Dewulf, Jeroen - \ 2019
    Journal of Antimicrobial Chemotherapy 74 (2019)3. - ISSN 0305-7453 - p. 807 - 816.

    OBJECTIVES: Farm-level quantification of antimicrobial usage (AMU) in pig farms. METHODS: In a cross-sectional study, AMU data on group treatments administered to a single batch of fattening pigs from birth to slaughter (group treatment data) and antimicrobials purchased during 1 year (purchase data) were collected at 180 pig farms in nine European countries. AMU was quantified using treatment incidence (TI) based on defined (DDDvet) and used (UDDvet) daily doses and defined (DCDvet) and used (UCDvet) course doses. RESULTS: The majority of antimicrobial group treatments were administered to weaners (69.5% of total TIDDDvet) followed by sucklers (22.5% of total TIDDDvet). AMU varied considerably between farms with a median TIDDDvet of 9.2 and 7.1 for a standardized rearing period of 200 days based on group treatment and purchase data, respectively. In general, UDDvet and UCDvet were higher than DDDvet and DCDvet, respectively, suggesting that either the defined doses were set too low or that group treatments were often dosed too high and/or administered for too long. Extended-spectrum penicillins (31.2%) and polymyxins (24.7%) were the active substances most often used in group treatments, with the majority administered through feed or water (82%). Higher AMU at a young age was associated with higher use in older pigs. CONCLUSIONS: Collecting farm-level AMU data of good quality is challenging and results differ based on how data are collected (group treatment data versus purchase data) and reported (defined versus used daily and course doses).

    A systematic knowledge synthesis on the spatial dimensions of Q fever epidemics
    Rooij, Myrna M.T. de; Leuken, Jeroen P.G. van; Swart, Arno ; Kretzschmar, Mirjam E.E. ; Nielen, Mirjam ; Koeijer, Aline A. de; Janse, Ingmar ; Wouters, Inge M. ; Heederik, Dick J.J. - \ 2019
    Zoonoses and Public Health 66 (2019)1. - ISSN 1863-1959 - p. 14 - 25.
    airborne exposure - Coxiella burnetii - epidemiology - Q fever - risk assessment - spatial analysis

    From 2007 through 2010, the Netherlands experienced the largest Q fever epidemic ever reported. This study integrates the outcomes of a multidisciplinary research programme on spatial airborne transmission of Coxiella burnetii and reflects these outcomes in relation to other scientific Q fever studies worldwide. We have identified lessons learned and remaining knowledge gaps. This synthesis was structured according to the four steps of quantitative microbial risk assessment (QMRA): (a) Rapid source identification was improved by newly developed techniques using mathematical disease modelling; (b) source characterization efforts improved knowledge but did not provide accurate C. burnetii emission patterns; (c) ambient air sampling, dispersion and spatial modelling promoted exposure assessment; and (d) risk characterization was enabled by applying refined dose–response analyses. The results may support proper and timely risk assessment and risk management during future outbreaks, provided that accurate and structured data are available and exchanged readily between responsible actors.

    Emissies van endotoxinen uit de veehouderij : eindrapport endotoxine metingen = Emissions of endotoxins from animal production: final report on endotoxin measurements
    Winkel, A. ; Erbrink, J.J. ; Wouters, I.M. ; Huis in ’T Veld, J.W.H. ; Heederik, D.J.J. ; Ogink, N.W.M. - \ 2018
    Wageningen : Wageningen Livestock Research (Wageningen Livestock Research rapport 1092) - 67
    Cijfers over de emissie van endotoxinen uit stallen zijn nodig als input voor een eventueel endotoxinetoetsingskader ter bescherming van de gezondheid van omwonenden van stallen. Daarnaast zijnemissiecijfers nodig in lopend onderzoek waarin concentratiegradiëntkaarten worden gegenereerd en relatiestussen gemodelleerde endotoxineconcentraties en medische gegevens van bewoners worden onderzocht. Intwee eerdere rapportages is een literatuurstudie uitgevoerd (WLR Rapport 773) en is een eerste setemissiecijfers verkregen waarmee ook indicatieve verspreidingsberekeningen voor een aantal fictieve stallenzijn uitgevoerd (WLR Rapport 959). Dit derde deel van het onderzoek richtte zich op verdere onderbouwingen detaillering van de emissiecijfers en de uitgangspunten voor de verspreidingsmodellering vanendotoxinen. In dit rapport is de eerste set emissiecijfers uitgebreid tot een totaal van 60endotoxinemetingen, verricht bij een totaal van 18 stallen voor leghennen, vleeskuikens, vleesvarkens,zeugen, biggen en melkkoeien. Daarnaast bevat dit rapport twee literatuurstudies die inzichten opleverenvoor het juist vormgeven van de modellering van endotoxinen vanuit stallen naar leefomgeving enomwonenden. Met dit alles is eerder ontbrekende kennis ontwikkeld dat in de toekomst kan dienen alscomponenten van een endotoxine toetsingskader en als een basis voor het project ‘Risicomodelleringveehouderij en gezondheid’.---Data on the emission of endotoxins from livestock farms are needed as input for a possible endotoxinassessment framework for the protection of the health of people living in the vicinity of farms. In addition,emission figures are needed in a current research project in which concentration gradient maps aregenerated and relationships between modelled endotoxin concentrations and residents' medical data areexamined. In two previous reports, a literature study was conducted (WLR Report 773) and a first set ofemission figures was obtained which were used in indicative dispersion calculations at a number of fictitiousfarm sites (WLR Report 959). This third part of the research focused on a further substantiation and detailingof the emission figures and the dispersion modelling of endotoxins. In this report, the first set of emissionfigures has been extended to a total of 60 measurements carried out at a total of 18 livestock houses forlaying hens, broilers, fattening pigs, sows, piglets and dairy cows. In addition, this report contains twoliterature studies that provide insights for a valid design of the dispersion modelling of endotoxins fromlivestock farms to the environment and local residents. With all this, previously lacking knowledge has beendeveloped which in future can serve as components of a possible endotoxin assessment framework and asinput for the project ‘Modelling health risks of livestock houses’.
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