Associations of Anti-COVID-19 Measures and Lifestyle Changes During the COVID-19 Pandemic With Sleep Patterns in the Netherlands: A Longitudinal Study.

Although there is scientific evidence for an increased prevalence of sleep disorders during the coronavirus disease 2019 (COVID-19) pandemic, there is still limited information on how lifestyle factors might have affected sleep patterns. Therefore, we followed a large cohort of participants in the Netherlands (n = 5,420) for up to 1 year (September 2020-2021) via monthly Web-based questionnaires to identify lifestyle changes (physical activity, cigarette smoking, alcohol consumption, electronic device use, and social media use) driven by anti-COVID-19 measures and their potential associations with self-reported sleep (latency, duration, and quality). We used the Containment and Health Index (CHI) to assess the stringency of anti-COVID-19 measures and analyzed associations through multilevel ordinal response models. We found that more stringent anti-COVID-19 measures were associated with higher use of electronic devices (per interquartile-range increase in CHI, odds ratio (OR) = 1.47, 95% confidence interval (CI): 1.40, 1.53), less physical activity (OR = 0.94, 95% CI: 0.90, 0.98), lower frequency of alcohol consumption (OR = 0.63, 95% CI: 0.60, 0.66), and longer sleep duration (OR = 1.11, 95% CI: 1.05, 1.16). Lower alcohol consumption frequency and higher use of electronic devices and social media were associated with longer sleep latency. Lower physical activity levels and higher social media and electronic device use were related to poorer sleep quality and shorter sleep duration.

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 NH3 and PM10, 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 NH3 and PM10. 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 NH3 and PM10 were obtained through monitoring stations. Lung function parameters (FEV1, FVC, FEV1/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 NH3 and PM10 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. FEV1 was negatively associated with week-average endotoxin exposure, but less consistent after co-pollutant adjustment. FEV1/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.

Effects of long-term exposure to outdoor air pollution on COVID-19 incidence: A population-based cohort study accounting for SARS-CoV-2 exposure levels in the Netherlands.

Several studies have linked air pollution to COVID-19 morbidity and severity. However, these studies do not account for exposure levels to SARS-CoV-2, nor for different sources of air pollution. We analyzed individual-level data for 8.3 million adults in the Netherlands to assess associations between long-term exposure to ambient air pollution and SARS-CoV-2 infection (i.e., positive test) and COVID-19 hospitalisation risks, accounting for spatiotemporal variation in SARS-CoV-2 exposure levels during the first two major epidemic waves (February 2020-February 2021). We estimated average annual concentrations of PM10, PM2.5 and NO2 at residential addresses, overall and by PM source (road traffic, industry, livestock, other agricultural sources, foreign sources, other Dutch sources), at 1 × 1 km resolution, and weekly SARS-CoV-2 exposure at municipal level. Using generalized additive models, we performed interval-censored survival analyses to assess associations between individuals' average exposure to PM10, PM2.5 and NO2 in the three years before the pandemic (2017-2019) and COVID-19-outcomes, adjusting for SARS-CoV-2 exposure, individual and area-specific confounders. In single-pollutant models, per interquartile (IQR) increase in exposure, PM10 was associated with 7% increased infection risk and 16% increased hospitalisation risk, PM2.5 with 8% increased infection risk and 18% increased hospitalisation risk, and NO2 with 3% increased infection risk and 11% increased hospitalisation risk. Bi-pollutant models suggested that effects were mainly driven by PM. Associations for PM were confirmed when stratifying by urbanization degree, epidemic wave and testing policy. All emission sources of PM, except industry, showed adverse effects on both outcomes. Livestock showed the most detrimental effects per unit exposure, whereas road traffic affected severity (hospitalisation) more than infection risk. This study shows that long-term exposure to air pollution increases both SARS-CoV-2 infection and COVID-19 hospitalisation risks, even after controlling for SARS-CoV-2 exposure levels, and that PM may have differential effects on these COVID-19 outcomes depending on the emission source.

Childhood lower respiratory tract infections linked to residential airborne bacterial and fungal microbiota.

Residential microbial composition likely contributes to the development of lower respiratory tract infections (LRTI) among children, but the association is poorly understood. We aimed to study the relationship between the indoor airborne dust bacterial and fungal microbiota and childhood LRTI in Ibadan, Nigeria. Ninety-eight children under the age of five years hospitalized with LRTI were recruited and matched by age (±3 months), sex, and geographical location to 99 community-based controls without LRTI. Participants' homes were visited and sampled over a 14-day period for airborne house dust using electrostatic dustfall collectors (EDC). In airborne dust samples, the composition of bacterial and fungal communities was characterized by a meta-barcoding approach using amplicons targeting simultaneously the bacterial 16S rRNA gene and the internal-transcribed-spacer (ITS) region-1 of fungi in association with the SILVA and UNITE database respectively. A 100-unit change in house dust bacterial, but not fungal, richness (OR 1.06; 95%CI 1.03-1.10) and a 1-unit change in Shannon diversity (OR 1.92; 95%CI 1.28-3.01) were both independently associated with childhood LRTI after adjusting for other indoor environmental risk factors. Beta-diversity analysis showed that bacterial (PERMANOVA p < 0.001, R2 = 0.036) and fungal (PERMANOVA p < 0.001, R2 = 0.028) community composition differed significantly between homes of cases and controls. Pair-wise differential abundance analysis using both DESEq2 and MaAsLin2 consistently identified the bacterial phyla Deinococcota (Benjamini-Hochberg (BH) adjusted p-value <0.001) and Bacteriodota (BH-adjusted p-value = 0.004) to be negatively associated with LRTI. Within the fungal microbiota, phylum Ascomycota abundance (BH adjusted p-value <0.001) was observed to be directly associated with LRTI, while Basidiomycota abundance (BH adjusted p-value <0.001) was negatively associated with LRTI. Our study suggests that early-life exposure to certain airborne bacterial and fungal communities is associated with LRTI among children under the age of five years.

Residential exposure to livestock farms and lung function in adolescence - The PIAMA birth cohort study.

BACKGROUND: There is a growing interest in the impact of air pollution from livestock farming on respiratory health. Studies in adults suggest adverse effects of livestock farm emissions on lung function, but so far, studies involving children and adolescents are lacking. OBJECTIVES: To study the association of residential proximity to livestock farms and modelled particulate matter ≤10 µm (PM10) from livestock farms with lung function in adolescence. METHODS: We performed a cross-sectional study among 715 participants of the Dutch prospective PIAMA (Prevention and Incidence of Asthma and Mite Allergy) birth cohort study. Relationships of different indicators of residential livestock farming exposure (distance to farms, distance-weighted number of farms, cattle, pigs, poultry, horses and goats within 3 km; modelled atmospheric PM10 concentrations from livestock farms) with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) at age 16 were assessed by linear regression taking into account potential confounders. Associations were expressed per interquartile range increase in exposure. RESULTS: Higher exposure to livestock farming was consistently associated with a lower FEV1, but not with FVC among participants living in less urbanized municipalities (<1500 addresses/km2, N = 402). Shorter distances of homes to livestock farms were associated with a 1.4% (0.2%; 2.7%) lower FEV1. Larger numbers of farms within 3 km and higher concentrations of PM10 from livestock farming were associated with a 1.8% (0.8%, 2.9%) and 0.9% (0.4%,1.5%) lower FEV1, respectively. CONCLUSIONS: Our findings suggest that higher exposure to livestock farming is associated with a lower FEV1 in adolescents. Replication and more research on the etiologic agents involved in these associations and the underlying mechanisms is needed.

Antimicrobial resistance genes aph(3')-III, erm(B), sul2 and tet(W) abundance in animal faeces, meat, production environments and human faeces in Europe.

BACKGROUND: Real-time quantitative PCR (qPCR) is an affordable method to quantify antimicrobial resistance gene (ARG) targets, allowing comparisons of ARG abundance along animal production chains. OBJECTIVES: We present a comparison of ARG abundance across various animal species, production environments and humans in Europe. AMR variation sources were quantified. The correlation of ARG abundance between qPCR data and previously published metagenomic data was assessed. METHODS: A cross-sectional study was conducted in nine European countries, comprising 9572 samples. qPCR was used to quantify abundance of ARGs [aph(3')-III, erm(B), sul2, tet(W)] and 16S rRNA. Variance component analysis was conducted to explore AMR variation sources. Spearman's rank correlation of ARG abundance values was evaluated between pooled qPCR data and earlier published pooled metagenomic data. RESULTS: ARG abundance varied strongly among animal species, environments and humans. This variation was dominated by between-farm variation (pigs) or within-farm variation (broilers, veal calves and turkeys). A decrease in ARG abundance along pig and broiler production chains ('farm to fork') was observed. ARG abundance was higher in farmers than in slaughterhouse workers, and lowest in control subjects. ARG abundance showed a high correlation (Spearman's ρ > 0.7) between qPCR data and metagenomic data of pooled samples. CONCLUSIONS: qPCR analysis is a valuable tool to assess ARG abundance in a large collection of livestock-associated samples. The between-country and between-farm variation of ARG abundance could partially be explained by antimicrobial use and farm biosecurity levels. ARG abundance in human faeces was related to livestock antimicrobial resistance exposure.

Risk factors for the abundance of antimicrobial resistance genes aph(3')-III, erm(B), sul2 and tet(W) in pig and broiler faeces in nine European countries.

OBJECTIVES: The occurrence and zoonotic potential of antimicrobial resistance (AMR) in pigs and broilers has been studied intensively in past decades. Here, we describe AMR levels of European pig and broiler farms and determine the potential risk factors. METHODS: We collected faeces from 181 pig farms and 181 broiler farms in nine European countries. Real-time quantitative PCR (qPCR) was used to quantify the relative abundance of four antimicrobial resistance genes (ARGs) [aph(3')-III, erm(B), sul2 and tet(W)] in these faeces samples. Information on antimicrobial use (AMU) and other farm characteristics was collected through a questionnaire. A mixed model using country and farm as random effects was performed to evaluate the relationship of AMR with AMU and other farm characteristics. The correlation between individual qPCR data and previously published pooled metagenomic data was evaluated. Variance component analysis was conducted to assess the variance contribution of all factors. RESULTS: The highest abundance of ARG was for tet(W) in pig faeces and erm(B) in broiler faeces. In addition to the significant positive association between corresponding ARG and AMU levels, we also found on-farm biosecurity measures were associated with relative ARG abundance in both pigs and broilers. Between-country and between-farm variation can partially be explained by AMU. Different ARG targets may have different sample size requirements to represent the overall farm level precisely. CONCLUSIONS: qPCR is an efficient tool for targeted assessment of AMR in livestock-related samples. The AMR variation between samples was mainly contributed to by between-country, between-farm and within-farm differences, and then by on-farm AMU.

Indoor bacterial and fungal aerosols as predictors of lower respiratory tract infections among under-five children in Ibadan, Nigeria.

BACKGROUND: This study aimed to investigate the association between exposure to diverse indoor microbial aerosols and lower respiratory tract infections (LRTI) among children aged 1 to 59 months in Ibadan, Nigeria. METHODS: One hundred and seventy-eight (178) hospital-based LRTI cases among under-five children were matched for age (± 3 months), sex and geographical location with 180 community-based controls (under-five children without LRTI). Following consent from caregivers of eligible participants, a child's health questionnaire, clinical proforma and standardized home-walkthrough checklist were used to collect data. Participant homes were visited and sampled for indoor microbial exposures using active sampling approach by Anderson sampler. Indoor microbial count (IMC), total bacterial count (TBC), and total fungal count (TFC) were estimated and dichotomized into high (> median) and low (≤ median) exposures. Alpha diversity measures including richness (R), Shannon (H) and Simpson (D) indices were also estimated. Conditional logistic regression models were used to test association between exposure to indoor microbial aerosols and LRTI risk among under-five children. RESULTS: Significantly higher bacterial and fungal diversities were found in homes of cases (R = 3.00; H = 1.04; D = 2.67 and R = 2.56; H = 0.82; D = 2.33) than homes of controls (R = 2.00; H = 0.64; D = 1.80 and R = 1.89; H = 0.55; D = 1.88) p < 0.001, respectively. In the multivariate models, higher categories of exposure to IMC (aOR = 2.67, 95% CI 1.44-4.97), TBC (aOR = 2.51, 95% CI 1.36-4.65), TFC (aOR = 2.75, 95% CI 1.54-4.89), bacterial diversity (aOR = 1.87, 95% CI 1.08-3.24) and fungal diversity (aOR = 3.00, 95% CI 1.55-5.79) were independently associated with LRTI risk among under-five children. CONCLUSIONS: This study suggests an increased risk of LRTI when children under the age of five years are exposed to high levels of indoor microbial aerosols.

Serologic Screening of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Cats and Dogs during First Coronavirus Disease Wave, the Netherlands.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect many animal species, including minks, cats, and dogs. To gain insights into SARS-CoV-2 infections in cats and dogs, we developed and validated a set of serologic assays, including ELISA and virus neutralization. Evaluation of samples from animals before they acquired coronavirus disease and samples from cats roaming SARS-CoV-2-positive mink farms confirmed the suitability of these assays for specific antibody detection. Furthermore, our findings exclude SARS-CoV-2 nucleocapsid protein as an antigen for serologic screening of cat and dog samples. We analyzed 500 serum samples from domestic cats and dogs in the Netherlands during April-May 2020. We showed 0.4% of cats and 0.2% of dogs were seropositive. Although seroprevalence in cats and dogs that had unknown SARS-CoV-2 exposure was low during the first coronavirus disease wave, our data stress the need for development of continuous serosurveillance for SARS-CoV-2 in these 2 animal species.

Occupational and environmental exposure to SARS-CoV-2 in and around infected mink farms.

OBJECTIVE: Unprecedented SARS-CoV-2 infections in farmed minks raised immediate concerns regarding transmission to humans and initiated intensive environmental investigations to assess occupational and environmental exposure. METHODS: Air sampling was performed at infected Dutch mink farms, at farm premises and at nearby residential sites. A range of other environmental samples were collected from minks' housing units, including bedding materials. SARS-CoV-2 RNA was analysed in all samples by quantitative PCR. RESULTS: Inside the farms, considerable levels of SARS-CoV-2 RNA were found in airborne dust, especially in personal inhalable dust samples (approximately 1000-10 000 copies/m3). Most of the settling dust samples tested positive for SARS-CoV-2 RNA (82%, 75 of 92). SARS-CoV-2 RNA was not detected in outdoor air samples, except for those collected near the entrance of the most recently infected farm. Many samples of minks' housing units and surfaces contained SARS-CoV-2 RNA. CONCLUSIONS: Infected mink farms can be highly contaminated with SARS-CoV-2 RNA. This warns of occupational exposure, which was substantiated by considerable SARS-CoV-2 RNA concentrations in personal air samples. Dispersion of SARS-CoV-2 to outdoor air was found to be limited and SARS-CoV-2 RNA was not detected in air samples collected beyond farm premises, implying a negligible risk of environmental exposure to nearby communities. Our occupational and environmental risk assessment is in line with whole genome sequencing analyses showing mink-to-human transmission among farm workers, but no indications of direct zoonotic transmission events to nearby communities.

Association of indoor microbial aerosols with respiratory symptoms among under-five children: a systematic review and meta-analysis.

BACKGROUND: Despite the recognition of the importance of indoor microbial exposures on children's health, the role of different microbial agents in development and aggravation of respiratory symptoms and diseases is only poorly understood. This study aimed to assess whether exposure to microbial aerosols within the indoor environment are associated with respiratory symptoms among children under-5 years of age. METHODS: A systematic literature search was conducted on PubMed, Web of Science, GreenFILE, ScienceDirect, EMBASE and Cochrane library through February 2020. Studies that investigated the exposure-response relationship between components of the indoor microbial communities and respiratory symptoms among under-five children were eligible for inclusion. A random-effect meta-analysis was applied to estimate pooled relative risk (RR) and 95% confidence interval (CI) for study specific high versus low microbial exposures. The potential effect of individual studies on the overall estimate was evaluated using leave-one-out analysis, while heterogeneity was evaluated by I2 statistics using RevMan 5.3. RESULTS: Fifteen studies were eligible for inclusion in a meta-analysis. The pooled risk estimate suggested that increased microbial exposure was associated with an increased risk of respiratory symptoms [pooled relative risk (RR): 1.24 (1.09, 1.41), P = 0.001]. The association was strongest with exposure to a combination of Aspergillus, Penicillium, Cladosporium and Alternaria species [pooled RR: 1.73 (1.30, 2.31), P = 0.0002]. Stratified analysis revealed an increased risk of wheeze [pooled RR: 1.20 (1.05, 1.37), P = 0.007 and allergic rhinitis [RR: 1.18 (0.94, 1.98), P = 0.16] from any microbial exposure. CONCLUSIONS: Microbial exposures are, in general, associated with risk of respiratory symptoms. Future studies are needed to study the indoor microbiome more comprehensively, and to investigate the mechanism of these associations.

Fecal Carriage of Extended-Spectrum-ß-Lactamase/AmpC-Producing Escherichia coli in Horses.

A nationwide study on the occurrence of extended-spectrum ß-lactamase (ESBL)/AmpC in nonhospitalized horses in the Netherlands was performed. Molecular characterization was done, and questionnaires were analyzed to identify factors associated with carriage. In total, 796 horse owners were approached; 281 of these submitted a fecal sample from their horse(s), resulting in 362 samples. All samples were cultured qualitatively in Luria-Bertani (LB) broth and subsequently on MacConkey agar, both supplemented with 1 mg/liter cefotaxime (LB+ and MC+). Positive samples were subsequently cultured quantitatively on MC+. Initial extended-spectrum-ß-lactamase (ESBL)/AmpC screening was performed by PCR, followed by whole-genome sequencing on selected strains. Associations between ESBL/AmpC carriage and questionnaire items were analyzed using a univariate generalized estimating equation (GEE) regression analysis, followed by a multiple GEE model for relevant factors. In total, 39 of 362 samples (11%) were determined to be positive for ESBL/AmpC. blaCTX-M-1-carrying isolates were obtained from 77% of positive samples (n = 30). Other ESBL/AmpC genes observed included blaCTX-M-2, blaCTX-M-14, blaCTX-M-15, blaCTX-M-32, blaSHV-12, blaCMY-2, and blaACT-10 A high association between the presence of blaCTX-M-1 and IncHI1 plasmids was observed (46% of samples; n = 18). Based on core genome analysis (n = 48 isolates), six Escherichia coli clusters were identified, three of which represented 80% of the isolates. A negative association between ESBL/AmpC carriage and horses being in contact with other horses at a different site was observed. The presence of a dog on the premises and housing in a more densely human-populated region were positively associated.IMPORTANCE Extended-spectrum ß-lactamases (ESBLs) are widespread in human and animal populations and in the environment. Many different ESBL variants exist. The dissemination of ESBLs within and between populations and the environment is also largely influenced by genetic mobile elements (e.g., plasmids) that facilitate spread of these ESBLs. In order to identify potential attributable ESBL sources for, e.g., the human population, it is important to identify the different ESBL variants, the bacteria carrying them, and the potential risk factors for ESBL carriage from other potential sources. This nationwide study focuses on ESBL carriage in the open horse population and investigated the molecular characteristics, geographical distribution throughout the Netherlands, and potential risk factors for fecal ESBL carriage in horses. These data can be used for future attribution studies in order to reduce potential transmission of ESBL-producing bacteria between sources.

Clinical and Pathological Findings in SARS-CoV-2 Disease Outbreaks in Farmed Mink (Neovison vison).

SARS-CoV-2, the causative agent of COVID-19, caused respiratory disease outbreaks with increased mortality in 4 mink farms in the Netherlands. The most striking postmortem finding was an acute interstitial pneumonia, which was found in nearly all examined mink that died at the peak of the outbreaks. Acute alveolar damage was a consistent histopathological finding in mink that died with pneumonia. SARS-CoV-2 infections were confirmed by detection of viral RNA in throat swabs and by immunohistochemical detection of viral antigen in nasal conchae, trachea, and lung. Clinically, the outbreaks lasted for about 4 weeks but some animals were still polymerase chain reaction-positive for SARS-CoV-2 in throat swabs after clinical signs had disappeared. This is the first report of the clinical and pathological characteristics of SARS-CoV-2 outbreaks in mink farms.

The antimicrobial resistome in relation to antimicrobial use and biosecurity in pig farming, a metagenome-wide association study in nine European countries.

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 ß-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.

Associations between antimicrobial use and the faecal resistome on broiler farms from nine European countries.

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 ß-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 ß-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.

Patients with overlapping diagnoses of asthma and COPD: is livestock exposure a risk factor for comorbidity and coexisting symptoms and infections?

BACKGROUND: Epidemiological research on health effects of livestock exposure in population subgroups with compromised respiratory health is still limited. The present study explored the association between livestock exposure and comorbid/concurrent conditions in patients with overlapping diagnoses of asthma and COPD. METHODS: Electronic health record data from 23 general practices in the Netherlands were collected from 425 patients diagnosed with both asthma and COPD, living in rural areas with high livestock density ("study area"). Data of 341 patients with the same overlapping diagnoses, living in rural areas with lower livestock density ("control areas") were obtained from 19 general practices. First, the prevalence of comorbid disorders and symptoms/infections were compared between the study and control area. Second, the examined health outcomes were analyzed in relation to measures of individual livestock exposure. RESULTS: Pneumonia was twice as common among patients living in areas with a high livestock density (OR 2.29, 99% CI 0.96-5.47); however, there were generally no statistically significant differences in the investigated outcomes between the study and control area. Significant associations were observed between presence of goats within 1000 m and allergic rhinitis (OR 5.71, 99% CI 1.11-29.3, p < 0.01), number of co-occurring symptoms (IRR 1.69, 99% CI 1.03-2.77, p < 0.01) and anxiety (OR 8.18, 99% 1.5-44.7, p < 0.01). Presence of cattle within 500 m was associated with pneumonia prevalence (OR 2.48, 99% CI 1.05-5.84, p < 0.01). CONCLUSION: Livestock exposure is not associated with comorbid chronic conditions but appears to be a risk factor for symptomatic effects in patients with overlapping diagnoses of asthma and COPD.

Long-term Carriage of Extended-Spectrum ß-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae in the General Population in The Netherlands.

Background: This longitudinal study aimed to investigate (risk factors for) persistence of carriage and molecular characteristics of extended-spectrum and plasmid-encoded AmpC ß-lactamase-producing (ESBL/pAmpC) Escherichia coli and Klebsiella pneumoniae (ESBL-E/K) in adults in the Dutch community. Methods: Following a cross-sectional study (ESBL-E/K prevalence, 4.5%), a subset of ESBL-E/K-positive (n = 76) and -negative (n = 249) individuals volunteered to provide 5 monthly fecal samples and questionnaires. ESBL-E/K was cultured using selective enrichment/culture, and multilocus sequence types (MLSTs) were determined. ESBL/pAmpC-genes were analyzed using polymerase chain reaction (PCR) and sequencing. Plasmids were characterized and subtyped by plasmid MLST. Risk factors for persistent carriage were analyzed using logistic regression. Results: Of the initially ESBL-E/K-positive participants, 25 of 76 (32.9%) remained positive in all subsequent samples; 51 of 76 persons (67.1%) tested ESBL-E/K negative at some time point during follow-up, of which 31 (40.8%) stayed negative throughout the longitudinal study. Carriers often carried the same ESBL gene and plasmid, but sometimes in different ESBL-E/K strains, indicative for horizontal transfer of plasmids. Of the 249 initially ESBL-E/K-negative participants, the majority (n = 218 [87.6%]) tested negative during 8 months of follow-up, whereas 31 of 249 (12.4%) participants acquired an ESBL-E/K. Escherichia coli phylogenetic group B2 and D and travel to ESBL high-prevalence countries were associated with prolonged carriage. Conclusions: ESBL-E/K carriage persisted for >8 months in 32.9% of the initially ESBL-positive individuals, while 12.4% of initially negative individuals acquired ESBL-E/K during the study. A single positive test result provides no accurate prediction for prolonged carriage. Acquisition/loss of ESBL-E/K does not seem to be a random process, but differs between bacterial genotypes.

Residential proximity to livestock farms is associated with a lower prevalence of atopy.

OBJECTIVES: Exposure to farm environments during childhood and adult life seems to reduce the risk of atopic sensitisation. Most studies have been conducted among farmers, but people living in rural areas may have similar protective effects for atopy. This study aims to investigate the association between residential proximity to livestock farms and atopy among non-farming adults living in a rural area in the Netherlands. METHODS: We conducted a cross-sectional study among 2443 adults (20-72 years). Atopy was defined as specific IgE to common allergens and/or total IgE ≥100 IU/mL. Residential proximity to livestock farms was assessed as 1) distance to the nearest pig, poultry, cattle or any farm, 2) number of farms within 500 m and 1000 m, and 3) modelled annual average fine dust emissions from farms within 500 m and 1000 m. Data were analysed with multiple logistic regression and generalised additive models. RESULTS: The prevalence of atopy was 29.8%. Subjects living at short distances from farms (<327 m, first tertile) had a lower odds for atopy compared with subjects living further away (>527 m, third tertile) (OR 0.79, 95% CI 0.63 to 0.98). Significant associations in the same direction were found with distance to the nearest pig or cattle farm. The associations between atopy and livestock farm exposure were somewhat stronger in subjects who grew up on a farm. CONCLUSIONS: Living in close proximity to livestock farms seems to protect against atopy. This study provides evidence that protective effects of early-life and adult farm exposures may extend beyond farming populations.

Endotoxin enhances respiratory effects of phthalates in adults: Results from NHANES 2005-6.

Phthalates have been associated with respiratory symptoms in adults; they may enhance effects of inflammatory compounds. To assess the potential interactions of phthalates and endotoxin on respiratory and allergic symptoms in adults, we used cross-sectional information from the 1091 adults with complete data on urinary phthalates and house dust endotoxin from NHANES 2005-2006. We used multivariable logistic regression to assess whether endotoxin levels modified the association between nine phthalate metabolites and four current allergic symptoms (asthma, wheeze, hay fever, and rhinitis). Endotoxin was classified into tertiles (<10, 10-25, >25EU/mg dust). Urinary phthalate and dust endotoxin levels were not correlated (r < |0.02|). Under low endotoxin conditions, no associations between phthalates and respiratory outcomes were observed. Under medium or high endotoxin conditions, exposure-response relationships were observed between specific phthalates and wheeze and asthma. For wheeze, three phthalates (mono-benzyl phthalate (MBzP), mono(carboxyoctyl) phthalate (MCOP), and di-ethylhexyl phthalate (DEHP) had significant interactions with endotoxin); for asthma, two phthalates (MCOP and mono(carboxyoctyl) phthalate (MCNP)) had significant interactions. Endotoxin did not modify the associations between phthalates and hay fever or rhinitis. These results are consistent with the hypothesis that endotoxin enhances the respiratory toxicity of phthalates; however this cross-sectional study cannot address key temporal issues. The lack of an association between wheeze or asthma and phthalates when endotoxin exposure was low suggests that phthalates alone may not increase these symptoms.

Respiratory health effects of exposure to low levels of airborne endotoxin - a systematic review.

BACKGROUND: Elevated endotoxin levels have been measured in ambient air around livestock farms, which is a cause of concern for neighbouring residents. There is clear evidence that occupational exposure to high concentrations of airborne endotoxin causes respiratory inflammation, respiratory symptoms and lung function decline. However, health effects of exposure to low levels of endotoxin are less well described. The aim of this systematic review is to summarize published associations between exposure to relatively low levels of airborne endotoxin and respiratory health endpoints. METHODS: Studies investigating respiratory effects of measured or modelled exposure to low levels of airborne endotoxin (average < 100 EU/m3) were eligible for inclusion. In total, 1362 articles were identified through a Pubmed database search, of which 31 articles were included in this review. Studies were included up to February 2017. Overview tables and forest plots were created, and study quality was assessed. RESULTS: Twenty-two included studies had a cross-sectional design, others were designed as longitudinal observational (n = 7) or experimental (n = 2) studies. Most studies (n = 23) were conducted in an occupational setting, some involved domestic or experimental exposure. Several studies reported statistically significant effects of exposure to low levels of endotoxin on respiratory symptoms and lung function. However, considerable heterogeneity existed in the outcomes of the included studies and no overall estimate could be provided by meta-analysis to quantify the possible relationship. Instead, a best evidence synthesis was performed among studies examining the exposure-response relationship between endotoxin and respiratory outcomes. Significant exposure-response relationships between endotoxin and symptoms and FEV1 were shown in several studies, with no conflicting findings in the studies included in the best evidence synthesis. Significantly different effects of endotoxin exposure were also seen in vulnerable subgroups (atopics and patients with broncho-obstructive disease) and smokers. CONCLUSIONS: Respiratory health effects of exposure to low levels of airborne endotoxin (< 100 EU/m3) seem plausible. Future studies are needed to investigate ambient exposure to endotoxin and potential respiratory health effects, especially in vulnerable subgroups of the population.