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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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’.
Veehouderij en gezondheid omwonenden III : Longontsteking in de nabijheid van geiten- en pluimveehouderijen; actualisering van gegevens uit huisartspraktijken 2014-2016
IJzermans, C.J. ; Smit, L.A.M. ; Heederik, D.J.J. ; Hagenaars, T.J. ; Baliatsas, C. ; Dückers, M. ; Huss, A. ; Hogerwerf, L. ; Post, P. ; Boender, G.J. ; Petie, R. - \ 2018
Utrecht : NIVEL - ISBN 9789461225153 - 52
Author Correction: Abundance and diversity of the faecal resistome in slaughter pigs and broilers in nine European countries
Munk, Patrick ; Knudsen, Berith Elkær ; Lukjancenko, Oksana ; Duarte, Ana Sofia Ribeiro ; Gompel, Liese Van; Luiken, Roosmarijn E.C. ; Smit, Lidwien A.M. ; Schmitt, Heike ; Garcia, Alejandro Dorado ; Hansen, Rasmus Borup ; Petersen, Thomas Nordahl ; Bossers, Alex ; Ruppé, Etienne ; Lund, Ole ; Hald, Tine ; Pamp, Sünje Johanna ; Vigre, Håkan ; Heederik, Dick ; Wagenaar, Jaap A. ; Mevius, Dik ; Aarestrup, Frank M. ; Graveland, Haitske ; Essen, Alieda van; Gonzalez-Zorn, Bruno ; Moyano, Gabriel ; Sanders, Pascal ; Chauvin, Claire ; David, Julie ; Battisti, Antonio ; Caprioli, Andrea ; Dewulf, Jeroen ; Blaha, Thomas ; Wadepohl, Katharina ; Brandt, Maximiliane ; Wasyl, Dariusz ; Skarzyńska, Magdalena ; Zajac, Magdalena ; Daskalov, Hristo ; Saatkamp, Helmut W. ; Stärk, Katharina D.C. - \ 2018
Nature Microbiology 3 (2018). - ISSN 2058-5276

In the version of this Article originally published, the surname of author Oksana Lukjancenko was spelt incorrectly as ‘Lukjacenko’. This has now been corrected.

Abundance and diversity of the faecal resistome in slaughter pigs and broilers in nine European countries
Munk, Patrick ; Knudsen, Berith Elkær ; Lukjacenko, Oksana ; Duarte, Ana Sofia Ribeiro ; Gompel, Liese Van; Luiken, Roosmarijn E.C. ; Smit, Lidwien A.M. ; Schmitt, Heike ; Garcia, Alejandro Dorado ; Hansen, Rasmus Borup ; Petersen, Thomas Nordahl ; Bossers, Alex ; Ruppé, Etienne ; Graveland, Haitske ; Essen, Alieda van; Gonzalez-Zorn, Bruno ; Moyano, Gabriel ; Sanders, Pascal ; Chauvin, Claire ; David, Julie ; Battisti, Antonio ; Caprioli, Andrea ; Dewulf, Jeroen ; Blaha, Thomas ; Wadepohl, Katharina ; Brandt, Maximiliane ; Wasyl, Dariusz ; Skarzyńska, Magdalena ; Zajac, Magdalena ; Daskalov, Hristo ; Saatkamp, Helmut W. ; Stärk, Katharina D.C. ; Lund, Ole ; Hald, Tine ; Pamp, Sünje Johanna ; Vigre, Håkan ; Heederik, Dick ; Wagenaar, Jaap A. ; Mevius, Dik ; Aarestrup, Frank M. - \ 2018
Nature Microbiology 3 (2018)8. - ISSN 2058-5276 - p. 898 - 908.

Antimicrobial resistance (AMR) in bacteria and associated human morbidity and mortality is increasing. The use of antimicrobials in livestock selects for AMR that can subsequently be transferred to humans. This flow of AMR between reservoirs demands surveillance in livestock and in humans. We quantified and characterized the acquired resistance gene pools (resistomes) of 181 pig and 178 poultry farms from nine European countries, sequencing more than 5,000 Gb of DNA using shotgun metagenomics. We quantified acquired AMR using the ResFinder database and a second database constructed for this study, consisting of AMR genes identified through screening environmental DNA. The pig and poultry resistomes were very different in abundance and composition. There was a significant country effect on the resistomes, more so in pigs than in poultry. We found higher AMR loads in pigs, whereas poultry resistomes were more diverse. We detected several recently described, critical AMR genes, including mcr-1 and optrA, the abundance of which differed both between host species and between countries. We found that the total acquired AMR level was associated with the overall country-specific antimicrobial usage in livestock and that countries with comparable usage patterns had similar resistomes. However, functionally determined AMR genes were not associated with total drug use.

Associations between pneumonia and residential distance to livestock farms over a five-year period in a large population-based study
Kalkowska, Dominika A. ; Boender, Gert J. ; Smit, Lidwien A.M. ; Baliatsas, Christos ; Yzermans, Joris ; Heederik, Dick J.J. ; Hagenaars, Thomas J. - \ 2018
PLoS ONE 13 (2018)7. - ISSN 1932-6203

In a recent study of electronic health records (EHR) of general practitioners in a livestock-dense area in The Netherlands in 2009, associations were found between residential distance to poultry farms and the occurrence of community-acquired pneumonia (CAP). In addition, in a recent cross-sectional study in 2494 adults in 2014/2015 an association between CAP and proximity to goat farms was observed. Here, we extended the 2009 EHR analyses across a wider period of time (2009–2013), a wider set of health effects, and a wider set of farm types as potential risk sources. A spatial (transmission) kernel model was used to investigate associations between proximity to farms and CAP diagnosis for the period from 2009 to 2013, obtained from EHR of in total 140,059 GP patients. Also, associations between proximity to farms and upper respiratory infections, inflammatory bowel disease, and (as a control disease) lower back pain were analysed. Farm types included as potential risk sources in these analyses were cattle, (dairy) goats, mink, poultry, sheep, and swine. The previously found association between CAP occurrence and proximity to poultry farms was confirmed across the full 5-year study period. In addition, we found an association between increased risk for pneumonia and proximity to (dairy) goat farms, again consistently across all years from 2009 to 2013. No consistent associations were found for any of the other farm types (cattle, mink, sheep and swine), nor for the other health effects considered. On average, the proximity to poultry farms corresponds to approximately 119 extra patients with CAP each year per 100,000 people in the research area, which accounts for approximately 7.2% extra cases. The population attributable risk percentage of CAP cases in the research area attributable to proximity to goat farms is approximately 5.4% over the years 2009–2013. The most probable explanation for the association of CAP with proximity to poultry farms is thought to be that particulate matter and its components are making people more susceptible to respiratory infections. The causes of the association with proximity to goat farms is still unclear. Although the 2007–2010 Q-fever epidemic in the area probably contributed Q-fever related pneumonia cases to the observed additional cases in 2009 and 2010, it cannot explain the association found in later years 2011–2013.

Molecular relatedness of ESBL/AmpC-producing Escherichia coli from humans, animals, food and the enviroment : a pooled analysis
Dorado-Garcia, Alejandro ; Smid, J.H. ; Pelt, Wilfrid Van; Bonten, M.J.M. ; Fluit, A.C. ; Bunt, Gerrita van den; Wagenaar, J.A. ; Hordijk, J. ; Dierikx, C.M. ; Veldman, K.T. ; Koeijer, A.A. de; Dohmen, W. ; Schmitt, H. ; Liakopoulos, A. ; Pacholewicz, Ewa ; Lam, T.J.G.M. ; Velthuis, Annet ; Heuvelink, A. ; Gonggrijp, Maaike ; Duijkeren, E. van; Hoek, A.H.A.M. van; Roda Husman, A.N. de; Blaak, H. ; Havelaar, A.H. ; Mevius, D.J. ; Heederik, D.J.J. - \ 2018
Journal of Antimicrobial Chemotherapy 73 (2018)2. - ISSN 0305-7453 - p. 339 - 347.
Background: In recent years, ESBL/AmpC-producing Escherichia coli ESBL/AmpC-EC) have been isolated with increasing frequency from animals, food, environmental sources and humans. With incomplete and scattered evidence, the contribution to the human carriage burden from these reservoirs remains unclear.
Objectives: To quantify molecular similarities between different reservoirs as a first step towards risk attribution.
Methods: Pooled data on ESBL/AmpC-EC isolates were recovered from 35 studies in the Netherlands comprising.27 000 samples, mostly obtained between 2005 and 2015. Frequency distributions of ESBL/AmpC genes from 5808 isolates and replicons of ESBL/AmpC-carrying plasmids from 812 isolates were compared across 22 reservoirs through proportional similarity indices (PSIs) and principal component analyses (PCAs).
Results: Predominant ESBL/AmpC genes were identified in each reservoir. PCAs and PSIs revealed close human–animal ESBL/AmpC gene similarity between human farming communities and their animals (broilers and pigs) (PSIs from 0.8 to 0.9). Isolates from people in the general population had higher similarities to those from human clinical settings, surface and sewage water and wild birds (0.7–0.8), while similarities to livestock or food reservoirs were lower (0.3–0.6). Based on rarefaction curves, people in the general population had more diversity in ESBL/AmpC genes and plasmid replicon types than those in other reservoirs.
Conclusions: Our ‘One Health’ approach provides an integrated evaluation of the molecular relatedness of ESBL/AmpC-EC from numerous sources. The analysis showed distinguishable ESBL/AmpC-EC transmission cycles in different hosts and failed to demonstrate a close epidemiological linkage of ESBL/AmpC genes and plasmid replicon types between livestock farms and people in the general population.
Samenvatting ESBL-Attributieanalyse (ESBLAT) : Op zoek naar de bronnen van antibioticaresistentie bij de mens
Mevius, Dik ; Heederik, Dick ; Duijkeren, Engeline ; Veldman, Kees ; Essen, Alieda van; Kant, Arie ; Liakopoulos, Apostolos ; Geurts, Yvon ; Pelt, Wilfrid van; Mughini Gras, Lapo ; Schmitt, Heike ; Dierikx, Cindy ; Hoek, Angela van; Evers, Eric ; Roda Husman, Annemaria de; Blaak, Hetty ; Dissel, Jaap van; Smid, Joost ; Dohmen, Wietske ; Dorado-Garcia, Alejandro ; Havelaar, Arie ; Hordijk, Joost ; Wagenaar, Jaap ; Fluit, Ad ; Bunt, Gerrita van den; Bonten, Marc ; Velthuis, Annet ; Heuvelink, Annet ; Buter, Rianne ; Gonggrijp, Maaike ; Santman-Berends, Inge ; Lam, Theo ; Urlings, Bert ; Heres, Lourens ; Bouwknecht, Martijn ; Groot, Jacques de - \ 2018
Netherlands : De Stichting TKI Agri&Food (TKI) - 11 p.
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