Longitudinal Study of Dynamic Epidemiology of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli in Pigs and Humans Living and/or Working on Pig Farms

Extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales have been increasingly isolated from pigs, highlighting their potential for transmission to humans living and/or working within pig farms. As longitudinal data on the prevalence and the molecular characteristics of such isolates from the high-risk farming population remain scarce, we performed a long-term study on 39 Dutch pig farms. Fecal samples from pigs, farmers, family members, and employees were collected during four sampling occasions with a 6-month period. The presence of ESBL-producing Enterobacterales and their molecular characteristics (ESBL gene, plasmid, and sequence types) were determined by standard methods. Data on personal and farm characteristics were collected using questionnaires. ESBL-producing Escherichia coli was present in pigs at least once for 18 of 39 farms and in 17 of 146 farmers, family members, and/or employees. Among these 417 E. coli isolates, bla CTX-M-1 was the most frequently observed ESBL gene in pigs ( n  = 261) and humans ( n  = 25). Despite the great variety in plasmid (sub)types and E. coli sequence types (STs), we observed genetic similarity between human- and pig-derived isolates in (i) ESBL gene, plasmid (sub)type, and ST, suggesting potential clonal transmission in seven farms, and (ii) only ESBL gene and plasmid (sub)type, highlighting the possibility of horizontal transfer in four farms. Five pig farmers carried ESBL producers repeatedly, of whom two carried an identical combination of gene, plasmid (sub)type, and ST over time. Human ESBL carriage was associated with both presence of ESBL producers in pigs and average number of hours working on the pig farm per week, while prolonged human carriage was observed only incidentally. IMPORTANCE Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli represents a public health hazard due to reduced therapeutic options for the treatment of infections. Although direct contact with pigs is considered a risk factor for human ESBL-producing E. coli carriage through occupational exposure, nationwide data regarding the occurrence of such isolates among pigs and humans living and/or working on farms remain scarce. Therefore, we determined (i) the longitudinal dynamics in prevalence and molecular characteristics of ESBL-producing E. coli in Dutch pig farmers and their pigs over time and (ii) the potential transmission events between these reservoirs based on genetic relatedness and epidemiological associations in longitudinal data. Our data suggesting the possibility of clonal and horizontal dissemination of ESBL-producing Escherichia coli between pigs and pig farmers can be used to inform targeted intervention strategies to decrease the within-farm human exposure to ESBL-producing E. coli

Quantifying Antimicrobial Use in Dutch Companion Animals

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

Short-term residential exposure to endotoxin emitted from livestock farms in relation to lung function in non-farming residents

BACKGROUND: Evidence on the public health relevance of exposure to livestock farm emissions is increasing. Research mostly focused on chemical air pollution, less on microbial exposure, while endotoxins are suggested relevant bacterial components in farm emissions. Acute respiratory health effects of short-term exposure to livestock-related air pollution has been shown for NH 3 and PM 10, but has not yet been studied for endotoxin. We aimed to assess associations between lung function and short-term exposure to livestock farming emitted endotoxin in co-pollutant models with NH 3 and PM 10. METHODS: In 2014/2015, spirometry was conducted in 2308 non-farming residents living in a rural area in the Netherlands. Residential exposure to livestock farming emitted endotoxin during the week prior to spirometry was estimated by dispersion modelling. The model was applied to geo-located individual barns within 10 km of each home address using provincial farm data and local hourly meteorological conditions. Regional week-average measured concentrations of NH 3 and PM 10 were obtained through monitoring stations. Lung function parameters (FEV 1, FVC, FEV 1/FVC, MMEF) were expressed in %-predicted value based on GLI-2012. Exposure-response analyses were performed by linear regression modelling. RESULTS: Week-average endotoxin exposure was negatively associated with FVC, independently from regional NH 3 and PM 10 exposure. A 1.1% decline in FVC was estimated for an increase of endotoxin exposure from 10th to 90th percentile. Stratified analyses showed a larger decline (3.2%) for participants with current asthma and/or COPD. FEV 1 was negatively associated with week-average endotoxin exposure, but less consistent after co-pollutant adjustment. FEV 1/FVC and MMEF were not associated with week-average endotoxin exposure. CONCLUSIONS: Lower lung function in non-farming residents was observed in relation to short-term residential exposure to livestock farming emitted endotoxin. This study indicates the probable relevance of exposure to microbial emissions from livestock farms considering public health besides chemical air pollution, necessitating future research incorporating both

Seasonality of antimicrobial use in Dutch food-producing animals

Due to globally increasing antimicrobial resistance (AMR), it is pivotal to understand factors contributing to antimicrobial use (AMU) to enable development and implementation of AMR-reducing interventions. Therefore, we explored seasonal variations of systemic AMU in food-producing animals in the Netherlands. Dutch surveillance data from January 2013 to December 2018 from cattle, pig, and broiler farms were used. AMU was expressed as the number of Defined Daily Dosages Animal per month (DDDA/animal-month) per farm by animal sector, antimicrobial line (first, second, and third), antimicrobial class, and farm type. Seasonality of AMU was analyzed using Generalized Additive Models (GAMs) with DDDA/animal-month as outcome variable, and year and month as independent variables. Year and month were modelled as smooth terms represented with penalized regression splines.Significant seasonality of AMU was found in the cattle and pig sectors, but not in broilers. Significant seasonality of AMU was found mainly for first-line antimicrobials. In the cattle sector, a significant increase during winter was found for the use of amphenicols (an increase of 23.8%) and long-acting macrolides (an increase of 3.4%). In the pig sector, seasonality of AMU was found for pleuromutilins (p < 0.001) with an increase of 20% in October-November. The seasonality of pleuromutilins was stronger in sows/piglets (an increase of 47%) than in fattening pigs (16% increase). Only in fattening pigs, the use of amphenicols showed a significant seasonality with an increase of 11% during winter (P < 0.001). AMU in cattle and pig sectors shows seasonal variations likely caused by seasonality of diseases. In broilers, no AMU seasonality was observed, possibly due to the controlled environment in Dutch farms. In the context of the one health concept, future studies are necessary to explore whether this seasonality is present in other populations and whether it has implications for antimicrobial resistance in humans through the food chain

Occupational endotoxin exposure in association with atopic sensitization and respiratory health in adults:Results of a 5-year follow-up

<div><p>The objective of the present longitudinal study was to investigate the effects of occupational endotoxin exposure on respiratory health and atopic sensitization in adults. Health outcomes and personal endotoxin exposure estimates were determined for 234 farmers and agricultural workers both at baseline and 5 years later. A questionnaire was used to assess respiratory symptoms, spirometry tests were performed and total and specific IgE levels were measured in serum.</p><p>A twofold increase in personal endotoxin exposure was associated with less hay fever (OR 0.68, 95%CI 0.54-0.87) and grass IgE positivity (OR 0.81, 95%CI 0.68-0.97) at both time points (“persistent” versus “never”). Although not statistically significant, a consistent protective pattern was observed for an increased loss of hay fever symptoms (OR 2.19, 95%CI 0.96-4.99) and grass IgE positivity (OR 1.24, 95%CI 0.76-2.02), and for less new-onset of hay fever (OR 0.87, 95%CI 0.65-1.17), grass IgE positivity (OR 0.83, 95%CI 0.61-1.12) and atopic sensitization (OR 0.75, 95%CI 0.55-1.02). Endotoxin exposure was not associated with changes in lung function.</p><p>We showed that occupational endotoxin exposure is associated with a long-term protective effect on hay fever and grass IgE positivity. Results on longitudinal changes in hay fever, atopy and grass IgE positivity in adulthood were consistent with a protective effect of endotoxin exposure, but results need to be confirmed in larger cohorts. An effect of endotoxin exposure on lung function decline was not found.</p></div

Quantifying topical antimicrobial use before and during participation in an antimicrobial stewardship programme in Dutch companion animal clinics

The emergence of bacterial strains resistant to topical antimicrobials in both human and veterinary medicine has raised concerns over retaining the efficacy of these preparations. Yet, little information is available regarding the use of topical antimicrobials in either sector for planning targeted interventions. This study aims to quantify the use of topical antimicrobials in 44 Dutch companion animal clinics before and during their participation in an antimicrobial stewardship programme (ASP), to explore the effect of the intervention on topical antimicrobial use (AMU). Hence, prescription and clinic animal population data, collected from July 2012 until June 2018 were used. Specifically, the period from July 2012 until June 2015 was defined as pre-intervention period, whereas clinics started to participate in the ASP from March 2016 onwards. As quantification metric, the Defined Daily Dose for Animals (DDDA) was used and a mixed effect times series model with auto-regression was applied to monthly topical AMU data. The intervention effect was modelled using a step function with a change in (linear) time trend and clinic characteristics, as potential determinants of topical AMU, were assessed using a multivariable regression model. A seasonal pattern was identified, in the pre-intervention period, where topical AMU was highest in July-August and lowest in February-March. In addition, total topical AMU appeared to significantly decrease over time in the pre-intervention period and the proportion of dogs in the clinic was positively associated with topical AMU. The intervention effect was significant only for second line and for skin product AMU. This study demonstrates that during participation in an ASP, second line and skin product AMU decreased in Dutch companion animal clinics. Additionally, this study demonstrates the existence of a seasonal effect and a decrease in topical AMU over time already before introduction of a targeted intervention

Associations between proximity to livestock farms, primary health care visits and self-reported symptoms

BACKGROUND: Living in a neighbourhood with a high density of livestock farms has been associated with adverse respiratory health effects, but less is known about healthcare utilisation. This study aimed at investigating the associations between livestock exposure and primary health care visits and self-reported symptoms. In addition, we examined the potentially confounding effect of distance from home to general practice. METHODS: Contact data between 2006 and 2009 were obtained from electronic medical records of 54,777 persons registered within 16 general practices in an area with a high density of livestock farms in the Netherlands. Data on self-reported symptoms were used from a cross-sectional sample of 531 patients in 2010. Livestock presence in a 500 m radius from home was computed using Geographic Information System data. RESULTS: In general, livestock exposure was associated with fewer contacts and self-reported symptoms for respiratory and other conditions. The number of poultry within 500 m was positively associated with the number of contacts. A longer distance to general practice was associated with fewer contacts, but did not confound associations. CONCLUSIONS: People living close to livestock farms less often see their general practitioner and report symptoms

Respiratory symptoms and occupation: a cross-sectional study of the general population

BACKGROUND: This study focused on respiratory symptoms due to occupational exposures in a contemporary general population cohort. Subjects were from the Dutch Monitoring Project on Risk Factors for Chronic Diseases (MORGEN). The composition of this population enabled estimation of respiratory risks due to occupation from the recent past for both men and women. METHODS: The study subjects (aged 20–59) were all inhabitants of Doetinchem, a small industrial town, and came from a survey of a random sample of 1104 persons conducted in 1993. A total of 274 cases with respiratory symptoms (subdivided in asthma and bronchitis symptoms) and 274 controls without symptoms were matched for age and sex. Relations between industry and occupation and respiratory symptoms were explored and adjusted for smoking habits and social economic status. RESULTS: Employment in the 'construction' (OR = 3.38; 95%CI 1.02 – 11.27), 'metal' (OR = 3.17; 95%CI 0. 98 – 10.28), 'rubber, plastics and synthetics' (OR = 6.52; 95%CI 1.26 – 53.80), and 'printing' industry (OR = 3.96; 95%CI 0.85 – 18.48) were positively associated with chronic bronchitis symptoms. In addition, the 'metal' industry was found to be weakly associated with asthma symptoms (OR = 2.59; 95%CI 0.87 – 7.69). Duration of employment within these industries was also positively associated with respiratory symptoms. CONCLUSION: Respiratory symptoms in the general population are traceable to employment in particular industries even in a contemporary cohort with relatively young individuals