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.

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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 - p. 1186 - 1186.

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.
Rapport 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) - 73
Endotoxinen rond stallen. Is een aanvullend toetsingskader nodig?
Erbrink, J.J. ; Heederik, D.J.J. ; Ogink, N.W.M. ; Winkel, A. ; Wouters, I.M. - \ 2017
Tijdschrift Lucht 13 (2017)3. - ISSN 1871-4773 - p. 15 - 18.
In dit artikel beschrijven we een eerste aanzet gegeven tot een kwantitatief microbieel verspreidingsmodel.
Dit moet een onderdeel gaan vormen van een modelketen die leidt tot een risicobeoordelingsmodel
voor de volksgezondheidseffecten van endotoxinen uit de landbouw.
ESBL carriage in pig slaughterhouse workers is associated with occupational exposure
Dohmen, W. ; Gompel, L. Van; Schmitt, H. ; Liakopoulos, A. ; Heres, L. ; Urlings, B.A. ; Mevius, D. ; Bonten, M.J.M. ; Heederik, D.J.J. - \ 2017
Epidemiology and Infection 145 (2017)10. - ISSN 0950-2688 - p. 2003 - 2010.
Antimicrobial resistance - bla - occupational epidemiology - pig abattoir workers - zoonosis
We investigated the prevalence of extended-spectrum β-lactamase (ESBL) carriage in slaughterhouse workers and the association with occupational exposure to slaughter animals and products. Stool samples from 334 employees in a Dutch pig slaughterhouse were obtained. Presence of ESBL was determined by selective plating, microarray analysis, and gene sequencing. Questionnaires were used to collect personal and occupational information. The overall prevalence of ESBL carriage was 4·8% (16/334). All ESBL-producing isolates were Escherichia coli. The ESBL genes detected were bla CTX-M-1 (n = 8), bla CTX-M-15 (n = 3), bla CTX-M-27 (n = 2), bla CTX-M-24 (n = 1), bla CTX-M-55 (n = 1), and bla SHV-12 (n = 1). A higher prevalence of ESBL was seen in workers in jobs with as tasks ‘removal of lungs, heart, liver, tongue’ (33%), and ‘removal of head and spinal cord’ (25%). For further analysis, participants were divided in two groups based on potential exposure to ESBL as related to their job title. One group with an assumed higher exposure to ESBL (e.g. stable work, stabbing, dehairing, removal of organs) and another group with an assumed lower exposure to ESBL (e.g. refrigeration, packaging and expedition). In the ‘higher exposure’ group, ten out of 95 (10·5%) were carrying ESBL vs. six out of 233 (2·6%) in the ‘lower exposure’ group. Human ESBL carriage was significantly associated with job exposure in the slaughterhouse (OR 4·5, CI 1·6–12·6). Results suggest that ESBL carriage in slaughterhouse workers overall is comparable with the Dutch population. Within the slaughterhouse population a difference in carriage exists depending on their position along the slaughter line and tasks involved.
Effect of structural animal health planning on antimicrobial use and animal health variables in conventional dairy farming in the Netherlands
Speksnijder, David C. ; Graveland, Haitske ; Eijck, Ineke A.J.M. ; Schepers, René W.M. ; Heederik, Dick J.J. ; Verheij, Theo J.M. ; Wagenaar, Jaap A. - \ 2017
Journal of Dairy Science 100 (2017)6. - ISSN 0022-0302 - p. 4903 - 4913.
Antimicrobial use - Continuous improvement - Facilitated animal health planning - Implementation

Widespread veterinary use of antimicrobials might contribute to the increasing burden of antimicrobial resistance. Despite many successful efforts to reduce veterinary antimicrobial use in the Netherlands, antimicrobial use on a substantial number of farms has remained relatively high over the past few years. Farm-specific solutions are required to further lower antimicrobial use on these farms. Reducing the burden of animal diseases at the farm level by means of a structured approach to animal health planning could be promising. This intervention study aimed to evaluate the main effects of an animal health planning program developed by an advisory team consisting of a dairy farmer, his veterinarian, and his feed adviser under the guidance of a professional facilitator. During an initial farm visit, the advisory team developed a farm-specific animal health planning program with support from the facilitator. After 1 yr, the effects of this program on animal health, production parameters, and antimicrobial use were evaluated and compared with control farms that did not have a facilitated animal health planning program. Antimicrobial use on intervention farms was significantly reduced between the start and the end of the study period; however, no significant differences in the rate of reduction between the intervention and control groups could be observed (-19% and -14%, respectively). Reduced antimicrobial use did not result in negative effects on animal health and production parameters during the study period in both groups. On intervention farms, a significant positive relationship was found between the percentage of completed action points at farm level and the percentage reduction in antimicrobial use. The level of compliance with action points and the quality of collaboration between farmer and advisers were positively associated with the accomplishment of corresponding objectives. However, the total number of objectives was negatively associated with the level of compliance with action points and tended to be negatively associated with the percentage reduction in antimicrobial use at farm level. Gradually reducing antimicrobial use without adverse effects on animal health and productivity is possible by adjusting management practices in a team effort. Fostering good collaboration among farmer, veterinarian, and feed adviser and focusing on a limited number of objectives have positive effects on the outcomes of the animal health planning program and antimicrobial use.

Risk factors for ESBL-producing Escherichia coli on pig farms : A longitudinal study in the context of reduced use of antimicrobials
Dohmen, Wietske ; Dorado-García, Alejandro ; Bonten, Marc J.M. ; Wagenaar, Jaap A. ; Mevius, Dik ; Heederik, Dick J.J. - \ 2017
PLoS One 12 (2017)3. - ISSN 1932-6203

The presence of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-E. coli) in food animals is a public health concern. This study aimed to determine prevalence of ESBL-E. coli on pig farms and to assess the effect of reducing veterinary antimicrobial use (AMU) and farm management practices on ESBL-E. coli occurrence on pig farms. During 2011-2013, 36 Dutch conventional pig farms participated in a longitudinal study (4 sampling times in 18 months). Rectal swabs were taken from 60 pigs per farm and pooled per 6 pigs within the same age category. Presence of ESBL-E. coli was determined by selective plating and ESBL genes were characterized by microarray, PCR and gene sequencing. An extensive questionnaire on farm characteristics and AMU as Defined Daily Dosages per Animal Year (DDDA/Y) was available for the 6-month periods before each sampling moment. Associations between the presence of ESBL-E. coli-positive pigs and farm management practices were modelled with logistic regression. The number of farms with ESBL-E. coli carrying pigs decreased from 16 to 10 and the prevalence of ESBL-E. coli-positive pooled pig samples halved from 27% to 13%. Overall, the most detected ESBL genes were blaCTX-M-1, blaTEM-52 and blaCTX-M-14. The presence of ESBL-E. coli carrying pigs was not related to total AMU, but it was strongly determined by the presence or absence of cephalosporin use at the farm (OR = 46.4, p = 0.006). Other farm management factors, related with improved biosecurity, were also plausibly related to lower probabilities for ESBL-E. coli-positive farms (e.g. presence of a hygiene lock, pest control delivered by a professional). In conclusion, ESBL-E. coli prevalence decreased in pigs during 2011 and 2013 in the Netherlands. On pig farms, the use of cephalosporins was associated with the presence of ESBL-E. coli carrying pigs.

ESBL prevalentie op vleeskuikenbedrijven 2016
Graveland, H. ; Hordijk, Joost ; Dierikx, C.M. ; Goot, J.A. van der; Heederik, Dick ; Garcia, Alejandro Dorado ; Mevius, D.J. ; Wagenaar, J.A. - \ 2016
Universiteit Utrecht
Quantitative assessment of antimicrobial resistance in livestock during the course of a Nationwide antimicrobial use reduction in the Nethterlands
Dorado-García, Alejandro ; Mevius, D.J. ; Jacobs, José J.H. ; Geijlswijk, I.M. van; Mouton, J.W. ; Wagenaar, J.A. ; Heederik, Dick - \ 2016
Journal of Antimicrobial Chemotherapy 71 (2016)12. - ISSN 0305-7453 - p. 3607 - 3619.
Objectives To quantify associations between antimicrobial use and acquired resistance in indicator Escherichia coli over a period of time which involved sector-wide antimicrobial use reductions in broilers and pigs (years 2004–14), veal calves (2007–14) and dairy cattle (2005–14). Prevalence estimates of resistance were predicted for a hypothetical further decrease in antimicrobial use.

Methods Data reported annually for the resistance surveillance programme in the Netherlands were retrieved. Two multivariate random-effects logistic models per animal sector were used to relate total and class-specific antimicrobial use (as defined daily dosages per animal per year, DDDA/Y) with the probability of E. coli resistance to a panel of 10 antimicrobial agents.

Results Positive dose–response relationships (ORs) were obtained from all models. Specific resistance phenotypes were more often associated with total antimicrobial use than with class-specific use. The most robust associations were found in pigs and veal calves. Resistance to historically widely used antimicrobials (e.g. penicillins, tetracyclines) was, in relative terms, less influenced by drug use changes over time than resistance to newer or less prescribed antimicrobials (e.g. third-/fourth-generation cephalosporins, fluoroquinolones). In pigs and veal calves, prevalence estimates for the most common resistance phenotypes were projected to decline ∼5%–25% during 2014–16 if total antimicrobial use reduction reached 80%; projections for poultry and dairy cows were more modest.

Conclusions Epidemiological evidence indicated that drug use history and co-selection of resistance are key elements for perpetuation of resistance. Data suggest that recent Dutch policies aimed at reducing total use of antimicrobials have decreased E. coli resistance in the pig and veal calf production sectors while the impact on the dairy cattle and poultry sectors is less clear.
Modelling concentrations of antimicrobial drugs : Comparative pharmacokinetics of cephalosporin antimicrobials and accuracy of allometric scaling in food-producing and companion animals
Taverne, Femke J. ; Geijlswijk, Ingeborg M. van; Heederik, Dick J.J. ; Wagenaar, Jaap A. ; Mouton, Johan W. - \ 2016
BMC Veterinary Research 12 (2016)1. - ISSN 1746-6148
Allometric scaling - Antimicrobials - Cephalosporins - Companion animals - Food-producing animals - Mathematical models - Pharmacokinetics

Background: To optimize antimicrobial dosing in different animal species, pharmacokinetic information is necessary. Due to the plethora of cephalosporin antimicrobials and animal species in which they are used, assessment of literature data is unavailable. We assessed the accuracy of allometric scaling by comparing the predicted and the published pharmacokinetic value in an animal pharmacokinetics in all species is unfeasible. In this study we aimed to describe pharmacokinetic data of cephalosporins by reviewing the available literature for food producing and companion animal species. We assessed the accuracy of interspecies extrapolation using allometric scaling techniques to determine pharmacokinetic characteristics of cephalosporins in animal species for which species/humans not included in the allometric modelling. Results: In general, excretion of cephalosporins takes place mainly through renal mechanisms in the unchanged form and volume of distribution is limited in all animal species. Differences in plasma protein binding capacity and elimination half-life are observed but available information was limited. Using allometric scaling, correlations between body weight (BW) and volume of distribution (Vd) and clearance (Cl) were R 2 > 0.97 and R 2 > 0.95 respectively for ceftazidime, ceftiofur, cefquinome and cefepime but not ceftriaxone. The allometric exponent ranged from 0.80 to 1.31 for Vd and 0.83 to 1.24 for Cl. Correlations on half-life ranged from R2 0.07-0.655 (literature) and R2 0.102-0.876 (calculated). Conclusions: Allometric scaling can be applied for interspecies extrapolation of cephalosporin pharmacokinetic parameters Vd and Cl, but not elimination half-life. We hypothesize that the accuracy could be improved by using more refined scaling techniques.

Emissies van endotoxinen uit de veehouderij: emissiemetingen en verspreidingsmodellering = Emissions of endotoxins from animal production: emission measurements and dispersion modelling
Ogink, Nico ; Erbrink, J.J. ; Heederik, D.J.J. ; Winkel, A. ; Wouters, I.M. - \ 2016
Wageningen : Wageningen UR, Livestock Research (Livestock Research rapport 959) - 95 p.
Additionele maatregelen ter vermindering van emissies van bioaerosolen uit stallen: verkenning van opties, kosten en effecten op de gezondheidslast van omwonenden = Additional measures to reduce emissions of bioaerosols from animal houses: exploration of options, costs, and effects on health of neighbouring residents
Winkel, A. ; Wouters, I.M. ; Hagenaars, T.J. ; Heederik, D.J.J. ; Ogink, N.W.M. ; Vermeij, I. - \ 2016
Wageningen : Wageningen UR Livestock Research (Livestock Research rapport 949) - 74 p.
Transmission through air as a possible route of exposure for MRSA
Bos, Marian E.H. ; Verstappen, Koen M. ; Cleef, Brigitte A.G.L. Van; Dohmen, Wietske ; Dorado-García, Alejandro ; Graveland, Haitske ; Duim, Birgitta ; Wagenaar, Jaap A. ; Kluytmans, Jan A.J.W. ; Heederik, Dick J.J. - \ 2016
Journal of Exposure Science and Environmental Epidemiology 26 (2016)3. - ISSN 1559-0631 - p. 263 - 269.
air - exposure - livestock - MRSA - transmission

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is highly prevalent in pigs and veal calves. The environment and air in pig and veal calf barns is often contaminated with LA-MRSA, and can act as a transmission source for humans. This study explores exposure-response relationships between sequence type 398 (ST398) MRSA air exposure level and nasal ST398 MRSA carriage in people working and/or living on farms. Samples and data were used from three longitudinal field studies in pig and veal calf farm populations. Samples consisted of nasal swabs from the human participants and electrostatic dust fall collectors capturing airborne settled dust in barns. In both multivariate and mutually adjusted analyses, a strong association was found between nasal ST398 MRSA carriage in people working in the barns for >20 h per week and MRSA air levels. In people working in the barns <20 h per week there was a strong association between nasal carriage and number of working hours. Exposure to ST398 MRSA in barn air seems to be an important determinant for nasal carriage, especially in the highly exposed group of farmers, next to duration of contact with animals. Intervention measures should therefore probably also target reduction of ST398 MRSA air levels.

Health and health-related quality of life in pig farmers carrying livestock-associated methicillin-resistant Staphylococcus aureus
Cleef, B.A.G.L. van; Benthem, B.H.B. van; Verkade, E.J.M. ; Rijen, M.M.L. van; Kluytmans-van den Bergh, M.F.Q. ; Graveland, H. ; Bosch, T. ; Verstappen, K.M.H.W. ; WAGENAAR, J.A. ; Heederik, D. ; Kluytmans, J.A.J.W. - \ 2016
Epidemiology and Infection (2016). - ISSN 0950-2688 - p. 1774 - 1783.
Infectious disease epidemiology - methicillin-resistant S. aureus (MRSA) - public health - zoonoses

There is limited knowledge about the effect of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) carriage on health-related quality of life (QoL). With this study, we explored whether LA-MRSA causes infections or affects health-related QoL in pig farmers. This prospective cohort study surveyed persons working on 49 farrowing pig farms in The Netherlands for 1 year (2010–2011). On six sampling moments, nasal swabs, environmental samples and questionnaires on activities and infections were collected. At the end of the study year, persons were asked about their QoL using the validated SF-36 and EQ-5D questionnaires. Of 120 persons, 44 (37%) were persistent MRSA carriers. MRSA carriage was not associated with infections, use of antimicrobials, healthcare contact and health-related QoL items in univariate or multivariate analysis, most likely due to the ‘healthy worker effect’. Despite high carriage rates, the impact of LA-MRSA carriage in this population of relatively healthy pig farmers on health and health-related QoL appears limited; more research is needed for confirmation.

Effects of reducing antimicrobial use and applying a cleaning and disinfection program in veal calf farming : Experiences from an intervention study to control livestock-associated MRSA
Dorado-García, Alejandro ; Graveland, Haitske ; Bos, M.E.H. ; Verstappen, K.M. ; Cleef, B.A.G.L. Van; Kluytmans, J.A.J.W. ; Wagenaar, J.A. ; Heederik, D.J.J. - \ 2015
PLoS One 10 (2015)8. - ISSN 1932-6203 - 21 p.

With the ultimate aim of containing the emergence of resistant bacteria, a Dutch policy was set in place in 2010 promoting a reduction of antimicrobial use (AMU) in food-producing animals. In this context, a study evaluated strategies to curb livestock-associated methicillin resistant Staphylococcus aureus (LA-MRSA). Fifty-one veal calf farms were assigned to one of 3 study arms: RAB farms reducing antimicrobials by protocol; RAB-CD farms reducing antimicrobials by protocol and applying a cleaning and disinfection program; and Control farms without interventions. MRSA carriage was tested in week 0 and week 12 of 2 consecutive production cycles in farmers, family members and veal calves. Interventions were validated and a cyclic rise in MRSA-prevalence in animals was shown with a more moderate increase in RAB farms. Prevalence in humans declined parallel over time in the study arms but RAB farms were at the lowest MRSA levels from the beginning of the study. In RAB-CD farms, human and animal prevalence did not differ from Control farms and MRSA air loads were significantly higher than in the other study arms. Mimicking the national trend, an overall AMU decrease (daily dosages per animal per cycle (DDDA/C)) was observed over 4 pre-study and the 2 study cycles; this trend did not have a significant effect on a set of evaluated farm technical parameters. AMU was positively associated with MRSA across study arms (ORs per 10 DDDA/C increase = 1.26 for both humans (p = 0.07) and animals (p = 0.12 in first cycle)). These results suggest that AMU reduction might be a good strategy for curbing MRSA in veal calf farming, however the specific cleaning and disinfecting program in RAB-CD farms was not effective. The drop in MRSA prevalence in people during the study could be attributed to the observed long-term AMU decreasing trend.

Carriage of extended-spectrum β-lactamases in pig farmers is associated with occurrence in pigs
Dohmen, W. ; Bonten, M.J.M. ; Bos, M.E.H. ; Marm, S. van; Scharringa, J. ; Wagenaar, J.A. ; Heederik, D.J.J. - \ 2015
Clinical Microbiology and Infection 21 (2015)10. - ISSN 1198-743X - p. 917 - 923.
Animal reservoirs - Animals - Antimicrobial resistance - CTX-M - Epidemiology - Escherichia coli - Zoonosis

Livestock may serve as a reservoir for extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE). The objectives of this study were to determine the prevalence of carriage with ESBL-PE in pig farmers, family members and employees, and its association with carriage in pigs. Rectal swabs were taken from 2388 pigs (398 pooled samples) on 40 pig farms and faecal samples were obtained from 142 humans living or working on 34 of these farms. Presence of ESBL-PE was determined by selective plating (agar). ESBL genes were analysed by PCR or microarray analysis, and gene sequencing. Genotypes and plasmids were determined by multilocus sequence typing and PCR-based replicon typing for selected isolates. ESBL genes were detected in Escherichia coli from eight humans (6%) (blaCTX-M-1, n = 6; blaTEM-52, n = 1 and blaCTX-M-14, n = 1) on six farms. In 157 pig isolates (107 pooled samples) on 18 farms (45%) ESBL genes were detected (blaCTX-M-1, n = 12; blaTEM-52, n = 6; and blaCTX-M-14, n = 3). Human and pig isolates within the same farm harboured similar ESBL gene types and had identical sequence and plasmid types on two farms (e.g. E. coli ST-453, blaCTX-M-1, IncI1), suggesting clonal transmission. For the remaining farms, sequence types, but not plasmid types, differed. Human ESBL carriage was associated with average number of hours working on the farm per week (OR = 1.04, 95% CI 1.02-1.06) and presence of ESBLs in pigs (OR = 12.5, 95% CI 1.4-111.7). Daily exposure to pigs carrying ESBL-PE is associated with ESBL carriage in humans.

Dose-response relationship between antimicrobial drugs and livestock-associated MRSA in pig farming
Dorado-García, Alejandro ; Dohmen, Wietske ; Bos, M.E.H. ; Verstappen, K.M. ; Houben, Manon ; Wagenaar, J.A. ; Heederik, D.J.J. - \ 2015
Emerging Infectious Diseases 21 (2015)6. - ISSN 1080-6040 - p. 950 - 959.

The farming community can be a vehicle for introduction of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in hospitals. During 2011–2013, an 18-month longitudinal study aimed at reducing the prevalence of LA-MRSA was conducted on 36 pig farms in the Netherlands. Evaluations every 6 months showed a slight decrease in MRSA prevalence in animals and a stable prevalence in farmers and family members. Antimicrobial use, expressed as defined daily dosages per animal per year, decreased 44% during the study period and was associated with declining MRSA prevalence in pigs. MRSA carriage in animals was substantially higher at farms using cephalosporins. Antimicrobial use remained strongly associated with LA-MRSA in humans regardless of the level of animal contact. A risk factor analysis outlined potential future interventions for LA-MRSA control. These results should encourage animal and public health authorities to maintain their efforts in reducing antimicrobial use in livestock and ask for future controlled intervention studies.

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