Evaluating the efficacy of internal teat sealants at dry-off for the prevention of new intra-mammary infections during the dry-period or clinical mastitis during early lactation in dairy cows: A systematic review update and sequential meta-analysis.

A systematic review and Bayesian sequential pair-wise meta-analyses were conducted to assess the efficacy of internal teat sealants (ITS) administered at dry-off in comparison to no treatment for preventing new intramammary infections (IMI) and clinical mastitis (CM) in dairy cattle. This work updated a previous systematic review and network meta-analysis conducted in 2019 but employed a narrowed scope and eligibility. The updated eligibility included studies that used ITS without concurrent therapy compared to a no treatment control (NTC), a study population of dairy cows or prepartum heifers, controlled trial design, and assessed one of the following outcomes: incidence of new IMI at calving or CM during the first 30 days in milk (DIM). Risk of bias was assessed through the Cochrane Risk of Bias 2.0 tool. Evidence quality was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). There were 141 potentially relevant records identified from the updated search conducted on April 29, 2021, with a publication date restriction of 2018 or later; one study passed full-text screening and was included. Of the 32 studies included in the previous review, 12 studies were relevant after applying the modified eligibility criteria, totaling 13 studies included in this review (12 addressing IMI at calving outcome, 4 addressing CM at 30 DIM outcome). Sequential meta-analysis was conducted for both outcomes in R 3.6.0. Decisions for stopping were assessed at each analysis for intervention effect or futility in finding an effect based on a priori minimum clinically relevant values (ORδ =0.5, 0.75). ITS at dry-off significantly reduced odds of new IMI at calving compared to NTC at the second meta-analysis (OR2 =0.27, 95% CI=0.22-0.34), and onward (OR12 =0.29, 95% CI=0.27-0.32). For CM at 30 DIM, significance was reached at the second meta-analysis (OR2 =0.59, 95% CI=0.47-0.73), and onward (OR3 =0.47, 95% CI=0.42-0.51). Stopping for effect occurred at the second analysis in both outcomes and ORδs, but low-quality evidence and heterogeneity concerns were noted. A continuity-correction to include zero-event CM studies showed significance at the third meta-analysis (OR3 =0.79, 95% CI=0.73-0.86), stopping for effect at the fourth for ORδ = 0.75 (OR4 =0.77, 95% CI=0.72-0.83), and stopping for futility at the second for ORδ = 0.5 (OR2 =0.94, 95% CI=0.75-1.20), but the main CM analysis was considered more appropriate due to the sensitivity analysis' very low-quality evidence assessment. Based on sequential evidence available, sufficient research currently exists for practical use, and cessation of future research until substantial changes to ITS application occur may be appropriate.

Characterisation of burden of illness measures associated with human (Fluoro)quinolone-resistant Campylobacter spp. infections - a scoping review.

Campylobacter spp. are one of the most common causes of bacterial gastroenteritis in Canada and worldwide. Fluoroquinolones are often used to treat complicated human campylobacteriosis and strains of Campylobacter spp. resistant to these drugs are emerging along the food chain. A scoping review was conducted to summarise how human (fluoro)quinolone-resistant (FQR; quinolones including fluoroquinolones) Campylobacter spp. infections are characterised in the literature by describing how burden of illness (BOI) associated with FQR is measured and reported, describing the variability in reporting of study characteristics, and providing a narrative review of literature that compare BOI measures of FQR Campylobacter spp. infections to those with susceptible infections. The review identified 26 studies that yielded many case reports, a lack of recent literature and a lack of Canadian data. Studies reported 26 different BOI measures and the most common were hospitalisation, diarrhoea, fever and duration of illness. There were mixed results as BOI measures reported in literature were inconsistently defined and there were limited comparisons between resistant and susceptible infections. This presents a challenge when attempting to assess the magnitude of the BOI due to FQR Campylobacter spp., highlighting the need for more research in this area.

Evaluation of the health and healthcare system burden due to antimicrobial-resistant Escherichia coli infections in humans: a systematic review and meta-analysis.

BACKGROUND: Assessment of the burden of disease due to antimicrobial-resistant Escherichia coli infections facilitates understanding the scale of the problem and potential impacts, and comparison to other diseases, which allows prioritization of research, surveillance, and funding. Using systematic review and meta-analysis methodology, the objectives were to evaluate whether humans with antimicrobial-resistant E. coli infections experience increases in measures of health or healthcare system burden when compared to susceptible E. coli infections. METHODS: Comprehensive literature searches were performed in four primary and seven grey literature databases. Analytic observational studies of human E. coli infections that assessed the impact of resistance to third/fourth/fifth-generation cephalosporins, resistance to quinolones, and/or multidrug resistance on mortality, treatment failure, length of hospital stay and/or healthcare costs were included. Two researchers independently performed screening, data extraction, and risk of bias assessment. When possible, random effect meta-analyses followed by assessment of the confidence in the cumulative evidence were performed for mortality and length of hospital stay outcomes, and narrative syntheses were performed for treatment failure and healthcare costs. RESULTS: Literature searches identified 14,759 de-duplicated records and 76 articles were included. Based on 30-day and all-cause mortality meta-analyses, regardless of the type of resistance, there was a significant increase in the odds of dying with resistant E. coli infections compared to susceptible infections. A summary mean difference was not presented for total length of hospital stay meta-analyses due to substantial to considerable heterogeneity. Since small numbers of studies contributed to meta-analyses for bacterium-attributable mortality and post-infection length of hospital stay, the summary results should be considered with caution. Studies contributing results for treatment failure and healthcare costs had considerable variability in definitions and reporting. CONCLUSIONS: Overall, resistant E. coli infections were associated with significant 30-day and all-cause mortality burden. More research and/or improved reporting are necessary to facilitate quantitative syntheses of bacterium-attributable mortality, length of hospital stay, and hospital costs. Protocol Registration PROSPERO CRD42018111197.

Seasonality and zoonotic foodborne pathogens in Canada: relationships between climate and Campylobacter, E. coli and Salmonella in meat products.

Infections due to Campylobacter, Escherichia coli and Salmonella pose a significant health burden in Canada, resulting in major costs to the health care system and economic impacts due to lost productivity resulting from illness. Recent literature suggests that climate may play a role in the prevalence of these pathogens along the food chain. This study used integrated surveillance data to examine associations between weather variables, serving as a proxy for climate, in agricultural areas and Campylobacter, generic E. coli and Salmonella contamination on samples of beef, poultry and swine meat products in Canada. Various temperature metrics (average, maximum and variability) were correlated with Campylobacter prevalence along the food chain. The prevalence of E. coli and Salmonella was correlated with both precipitation and temperatures metrics; however, analysis for E. coli was limited to beef and swine meats at retail settings, because prevalence in other combinations approached 100%, which obviated further analysis. Campylobacter contamination in poultry and swine at abattoir and retail settings demonstrated a seasonal trend, with increased prevalence generally from June or July through November, compared to the baseline month of December. Based on these analyses, Campylobacter is the most likely foodborne bacteria studied whose occurrence in meat products is affected by climatic changes in Canada. An exploratory analysis of data at the provincial scale, using Ontario as an example, revealed similar directional relationships between climate and bacterial prevalence.

Avian metapneumovirus subtype C in Wild Waterfowl in Ontario, Canada.

Avian metapneumovirus (aMPV) is an emerging poultry pathogen that has a significant economic impact on poultry production worldwide. The geographic range of the virus continues to expand, and wild birds have been implicated as reservoirs of aMPV that have the potential to spread the virus over long distances. Our objective was to determine the apparent prevalence of aMPV subtype C in wild waterfowl in Ontario, Canada. Wild waterfowl were captured in August and September, 2016 as part of routine migratory waterfowl population monitoring by the Ontario Ministry of Natural Resources and Forestry. Oropharyngeal and cloacal swabs were collected from each bird and placed together for aMPV testing using real-time RT-PCR. A total of 374 live wild birds from 23 lakes were sampled and tested for aMPV. Among all ducks tested, 84 (22%) were positive for aMPV. The proportion of samples that tested positive ranged from 0% in ring-necked ducks (Aythya collaris) and green-winged teal (Anas carolinensis) to 44% (8 of 18) in American black ducks (A. rubripes). Waterfowl positive for aMPV were found at 14 of 23 lakes in the study area and the percent positive at these 14 lakes ranged between 5% and 84%. Although subtype C aMPV has been detected in a variety of wild birds in North America, this is the first report of aMPV in wild ducks in Ontario, Canada. The high apparent prevalence, particularly in mallards and American black ducks (37 and 44%, respectively), suggests that these species may be important reservoirs of aMPV. Given the potential impact of aMPV on domestic poultry and the potential role of wild birds as reservoirs of the virus, further investigation of the geographic distribution, risk factors associated with aMPV carriage in wild waterfowl and potential role of other birds in the epidemiology of aMPV in Canada is warranted.

Risk factors for acquisition of multidrug-resistant Escherichia coli and development of community-acquired urinary tract infections.

We examined risk factors associated with the intestinal acquisition of antimicrobial-resistant extraintestinal pathogenic Escherichia coli (ExPEC) and development of community-acquired urinary tract infection (UTI) in a case-control study of young women across Canada. A total of 399 women were recruited; 164 women had a UTI caused by E. coli resistant to ⩾1 antimicrobial classes and 98 had a UTI caused by E. coli resistant to ⩾3 antimicrobial classes. After adjustment for age, student health service (region of Canada) and either prior antibiotic use or UTI history, consumption of processed or ground chicken, cooked or raw shellfish, street foods and any organic fruit; as well as, contact with chickens, dogs and pet treats; and travel to Asia, were associated with an increased risk of UTI caused by antimicrobial resistant E. coli. A decreased risk of antimicrobial resistant UTI was associated with consumption of apples, nectarines, peppers, fresh herbs, peanuts and cooked beef. Drug-resistant UTI linked to foodborne and environmental exposures may be a significant public health concern and understanding the risk factors for intestinal acquisition of existing or newly emerging lineages of drug-resistant ExPEC is important for epidemiology, antimicrobial stewardship and prevention efforts.

A geographic study of West Nile virus in humans, dead corvids and mosquitoes in Ontario using spatial scan statistics with a survival time application.

Surveillance of West Nile virus (WNv) in Ontario has included passive reporting of human cases and testing of trapped mosquitoes and dead birds found by the public. The dead bird surveillance programme was limited to testing within a public health unit (PHU) until a small number of birds test positive. These dead corvid and mosquito surveillance programmes have not been compared for their ability to provide early warning in geographic areas where human cases occur each year. Spatial scan statistics were applied to time-to-event survival data based on first cases of WNv in found dead corvids, mosquitoes and humans. Clusters identified using raw data were compared to clusters based on model-adjusted survival times to evaluate whether geographic and sociodemographic factors influenced their distribution. Statistically significant (p < .05) space-time clusters of PHUs with faster time to detection were found using each surveillance data stream. During 2002-2004, the corvid surveillance programme outperformed the mosquito programme in terms of time to WNv detection, while the clusters of first-positive mosquito pools were more spatially similar to first human cases. In 2006, a cluster of first-positive dead corvids was located in northern PHUs and preceded a cluster of early human cases that was identified after controlling for the influence of geographic region and sociodemographic profile.

Molecular and Statistical Analysis of Campylobacter spp. and Antimicrobial-Resistant Campylobacter Carriage in Wildlife and Livestock from Ontario Farms.

The objectives of this study were to (i) compare the carriage of Campylobacter and antimicrobial-resistant Campylobacter among livestock and mammalian wildlife on Ontario farms, and (ii) investigate the potential sharing of Campylobacter subtypes between livestock and wildlife. Using data collected from a cross-sectional study of 25 farms in 2010, we assessed associations, using mixed logistic regression models, between Campylobacter and antimicrobial-resistant Campylobacter carriage and the following explanatory variables: animal species (beef, dairy, swine, raccoon, other), farm type (swine, beef, dairy), type of sample (livestock or wildlife) and Campylobacter species (jejuni, coli, other). Models included a random effect to account for clustering by farm where samples were collected. Samples were subtyped using a Campylobacter-specific 40 gene comparative fingerprinting assay. A total of 92 livestock and 107 wildlife faecal samples were collected, and 72% and 27% tested positive for Campylobacter, respectively. Pooled faecal samples from livestock were significantly more likely to test positive for Campylobacter than wildlife samples. Relative to dairy cattle, pig samples were at significantly increased odds of testing positive for Campylobacter. The odds of isolating Campylobacter jejuni from beef cattle samples were significantly greater compared to dairy cattle and raccoon samples. Fifty unique subtypes of Campylobacter were identified, and only one subtype was found in both wildlife and livestock samples. Livestock Campylobacter isolates were significantly more likely to exhibit antimicrobial resistance (AMR) compared to wildlife Campylobacter isolates. Campylobacter jejuni was more likely to exhibit AMR when compared to C. coli. However, C. jejuni isolates were only resistant to tetracycline, and C.  coli isolates exhibited multidrug resistance patterns. Based on differences in prevalence of Campylobacter spp. and resistant Campylobacter between livestock and wildlife samples, and the lack of similarity in molecular subtypes and AMR patterns, we concluded that the sharing of Campylobacter species between livestock and mammalian wildlife was uncommon.

Cluster Analysis of Campylobacter jejuni Genotypes Isolated from Small and Medium-Sized Mammalian Wildlife and Bovine Livestock from Ontario Farms.

Using data collected from a cross-sectional study of 25 farms (eight beef, eight swine and nine dairy) in 2010, we assessed clustering of molecular subtypes of C. jejuni based on a Campylobacter-specific 40 gene comparative genomic fingerprinting assay (CGF40) subtypes, using unweighted pair-group method with arithmetic mean (UPGMA) analysis, and multiple correspondence analysis. Exact logistic regression was used to determine which genes differentiate wildlife and livestock subtypes in our study population. A total of 33 bovine livestock (17 beef and 16 dairy), 26 wildlife (20 raccoon (Procyon lotor), five skunk (Mephitis mephitis) and one mouse (Peromyscus spp.) C. jejuni isolates were subtyped using CGF40. Dendrogram analysis, based on UPGMA, showed distinct branches separating bovine livestock and mammalian wildlife isolates. Furthermore, two-dimensional multiple correspondence analysis was highly concordant with dendrogram analysis showing clear differentiation between livestock and wildlife CGF40 subtypes. Based on multilevel logistic regression models with a random intercept for farm of origin, we found that isolates in general, and raccoons more specifically, were significantly more likely to be part of the wildlife branch. Exact logistic regression conducted gene by gene revealed 15 genes that were predictive of whether an isolate was of wildlife or bovine livestock isolate origin. Both multiple correspondence analysis and exact logistic regression revealed that in most cases, the presence of a particular gene (13 of 15) was associated with an isolate being of livestock rather than wildlife origin. In conclusion, the evidence gained from dendrogram analysis, multiple correspondence analysis and exact logistic regression indicates that mammalian wildlife carry CGF40 subtypes of C. jejuni distinct from those carried by bovine livestock. Future studies focused on source attribution of C. jejuni in human infections will help determine whether wildlife transmit Campylobacter jejuni directly to humans.

Utility of algorithms for the analysis of integrated Salmonella surveillance data.

The objective of this study was to assess the use of statistical algorithms in identifying significant clusters of Salmonella spp. across different sectors of the food chain within an integrated surveillance programme. Three years of weekly Salmonella serotype data from farm animals, meat, and humans were used to create baseline models (first two years) and identify weeks with counts higher than expected using surveillance algorithms in the third (test) year. During the test year, an expert working group identified events of interest reviewing descriptive analyses of same data. The algorithms did not identify Salmonella events presenting as gradual increases or seasonal patterns as identified by the working group. However, the algorithms did identify clusters for further investigation, suggesting they could be a valuable complementary tool within an integrated surveillance system.

Canadian integrated program for antimicrobial resistance surveillance: Retail food highlights, 2003-2012.

BACKGROUND: The Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) is a collaborative, integrated program designed to track antimicrobial resistance (AMR) among enteric bacteria isolated from various livestock commodities along the food-producing continuum ("farm to fork") and in humans. OBJECTIVE: To provide a summary of the prevalence and trends in AMR among select bacteria isolated from raw, fresh chicken, pork, and beef in 2012 at the retail food level and to link these data with other findings from CIPARS. METHODS: Meat samples were collected from randomly selected geographic areas across Canada weighted by population for subsequent isolation of bacteria and interpretation of the associated AMR profiles. Salmonella, Campylobacter and generic Escherichia coli (E. coli) were tested in chicken, and E. coli was tested in beef and pork. Data were analyzed for 2012 and temporal and regional trends were examined between 2003 and 2012 by province/region. RESULTS: Overall, resistance levels to Salmonella in retail chicken varied widely by region and year. For example, ceftiofur resistance to Salmonella in retail chicken was significantly lower in 2012 than in 2004 in Ontario and in Québec; however, among all regions sampled, resistance was significantly higher in 2012 compared to 2006. Across all regions sampled, resistance to Campylobacter in retail chicken was relatively low in 2012 (<16%) with the exception of tetracycline resistance. In 2012, ciprofloxacin resistance to Campylobacter in chicken declined in British Columbia but significantly increased in Ontario, compared to 2011. In 2012, ß-lactam resistance to E. coli in retail beef remained low (≤1%) and was also relatively low comparable to previous years in pork. CONCLUSION: In Canada, as is the case worldwide, there is evidence of resistance to medically important antimicrobials among bacteria from retail meats. Resistance among organisms isolated from poultry, beef, and pork at the retail food level is characterized by wide variation over time and across different regions.

Ciprofloxacin-resistant Campylobacter in broiler chicken in Canada.

This case study outlines the patterns of ciprofloxacin resistance in Campylobacter isolated from retail chicken meat in Canada. Campylobacter is the third most common cause of foodborne enteric illness in Canada; it usually causes a self-limited illness, but in some cases antimicrobials may be indicated. Ciprofloxacin (a fluoroquinolone) is an antimicrobial used to treat a number of infections in humans; other fluoroquinolones are used both therapeutically and prophylactically in livestock animals, including broiler chickens. The Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) has been testing retail chicken meat samples across Canada for the presence of Campylobacter and for resistant strains since 2003. At the end of 2010, CIPARS documented that retail chicken meat samples in Canada contaminated with Campylobacter ranged from 36% in the Maritimes to 42% in British Columbia. Furthermore, levels of ciprofloxacin-resistant Campylobacter varied across the country, with higher percentages in British Columbia (17% in 2010) and Saskatchewan (11%), in comparison with lower percentages in Ontario (5%), Québec (2%, and the Maritimes (4%). In 2011 and 2012, resistance declined in British Columbia and Saskatchewan, but began to rise in Québec and Ontario. Recently, the Canadian poultry industry developed a policy to eliminate the preventive use of third generation cephalosporins and fluoroquinolones in broiler chickens (meat chickens) and broiler breeder chickens (chickens that produce the eggs that will become the broilers). CIPARS will continue to monitor trends in antimicrobial use and resistance following this industry intervention. By following good food preparation and hygiene practices, Canadians can reduce the risks of developing a Campylobacter infection (resistant or susceptible) from retail chicken.