Antimicrobial resistance and phylogenetic relatedness of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli in peridomestic rats (Rattus norvegicus and Rattus tanezumi) linked to city areas and animal farms in Hong Kong.

Extended-spectrum ß-lactamase-producing Escherichia (E.) coli (ESBL-EC) in the clinical setting have emerged as a major threat to public and animal health. Wildlife, including Rattus spp. may serve as reservoirs and spreaders of ESBL-EC in the environment. Peridomestic rats are well adapted to living in proximity to humans and animals in a variety of urban and agricultural environments and may serve as sentinels to identify variations of ESBL-EC within their different habitats. In this study, a set of 221 rats (Rattus norvegicus, R. tanezumi, R. andamanensis, and Niviventer huang) consisting of 104 rats from city areas, 44 from chicken farms, 52 from pig farms, and 21 from stables of horse-riding schools were screened for ESBL-EC. Overall, a total of 134 ESBL-EC were isolated from the caecal samples of 130 (59%) rats. The predominant blaESBL genes were blaCTX-M-14, blaCTX-M-15, blaCTX-M-55, and blaCTX-M-65. Phylogenetic analysis revealed a total of 62 sequence types (STs) and 17 SNP clusters. E. coli ST10 and ST155 were common to ESBL-EC from city areas and chicken farms, and ST44 were found among ESBL-EC from city areas and pig farms. Extra-intestinal pathogenic E. coli (ExPEC) ST69, ST131 and ST1193 were found exclusively among rats from city areas, and avian pathogenic E. coli (APEC) ST177 was restricted to ESBL-EC originating from chicken farms. Phylogenetic analysis showed that the populations of rodent ESBL-EC from city areas, chicken farms and pig farms were genetically different, suggesting a certain degree of partitioning between the human and animal locations. This study contributes to current understanding of ESBL-EC occurring in rats in ecologically diverse locations.

Antimicrobial resistance in bacteria isolated from peridomestic Rattus species: A scoping literature review.

Rattus spp. may acquire and disseminate antimicrobial resistant bacteria or antimicrobial resistance (AMR) genes. We conducted a scoping review to synthesize available research findings on AMR in Rattus spp. and to describe the size and scope of available literature on AMR epidemiology in Rattus spp. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR). The search focused on scientific peer-reviewed publications focusing on AMR in peridomestic Rattus spp. The review was limited to publications in English available in PubMed, Web of Science and Scopus between 2000 and 2021. The results were summarized descriptively. Thirty-four studies conducted in twenty-one countries were included in this scoping review. Twelve bacterial species with AMR were identified with Escherichia coli and Staphylococcus aureus being the two most commonly reported. The resistant bacteria were isolated from species of peridomestic Rattus spp. in which R. norvegicus and R. rattus were the two most commonly studied. Rats were also found to carry multi-drug resistant (MDR) bacteria including extended-spectrum beta (ß)-lactamase (ESBL), methicillin-resistant Staphylococcus aureus (MRSA), colistin-resistant Enterobacteriaceae (CoRE), and vancomycin-resistant Enterococci (VRE). This scoping review suggests that peridomestic Rattus spp. can carry multiple antimicrobial resistant bacteria, indicating their potential to serve as reservoirs and spreaders of AMR thus posing a threat to human and animal health.

Fertility risk factors in transferring Japanese Black embryos into dairy heifers: An epidemiological study.

The aims of this study were 1) to summarize the current status of Japanese Black (JB) embryo transfer into Holstein heifers, which is carried out on a commercial basis in Japan, and 2) to reveal fertility risk factors, including those from the environment (year and season of transfer), recipient (age, number of transfers, clinical status of the ovaries) and embryo (quality, stage, state, genetic background). We used data from 4467 JB fresh or frozen embryo transfers into Holstein heifers conducted by Zen-noh Embryo Transfer Center during 2016-2018, and the differences in fertility risk due to factors related to the environment, recipient, and embryo were statistically evaluated. Differences in fertility risk due to each variable were observed, leading to significant differences in fertility with respect to year of transfer, embryo quality, embryo state, and embryo breed. These results suggest that the fertility of JB embryos might depend on differences in genetic background. There have been no previous reports of differences in embryo fertility due to the differences among JB's bloodline combinations. In the future, overall reproductive efficiency must be monitored, including the effects of different bloodline combinations on the success of embryo recovery and transfer.

Economic effects of policy options restricting antimicrobial use for high risk cattle placed in U.S. feedlots.

The rising public health threat of antimicrobial resistance, the influence of food service companies, as well as the overall lack of positive image of using medical products in intensive farming are major drivers curbing antimicrobial use. In the future, government policies may affect practices of antimicrobial use in beef production in feedlots, a prominent current user of antimicrobials in animal agriculture, but also the agricultural industry generating the highest cash receipt in the U.S. Our objective was to estimate the cost effect from the following policies in feedlots: 1) using antimicrobials for disease prevention, control, and treatment; 2) using antimicrobials only for treatment of disease; and 3) not using antimicrobials for any reason. We modelled a typical U.S. feedlot, where high risk cattle may be afflicted by diseases requiring antimicrobial therapy, namely respiratory diseases, liver abscesses and lameness. We calculated the net revenue loss under each policy of antimicrobial use restriction. With moderate disease incidence, the median net revenue loss was $66 and $96 per animal entering the feedlot, for not using antimicrobials for disease prevention and control, or not using any antimicrobials, respectively, compared to using antimicrobials for disease prevention, control, and treatment. Losses arose mainly from an increase of fatality and morbidity rates, almost doubling for respiratory diseases in the case of antimicrobial use restrictions. In the case of antimicrobial use prohibition, decreasing the feeder cattle price by 9%, or alternatively, increasing the slaughter cattle price by 6.3%, would offset the net revenue losses for the feedlot operator. If no alternatives to antimicrobial therapy for prevention, control and treatment of current infectious diseases are implemented, policies that economically incentivize adoption of non-antimicrobial prevention and control strategies for infectious diseases would be necessary to maintain animal welfare and the profitability of beef production while simultaneously curbing antimicrobial use.

How do veterinarians influence sales of antimicrobials? A spatial-temporal analysis of the French prescribing-delivery complex in cattle.

BACKGROUND: In animal agriculture, antimicrobials (AM) are used to control infectious diseases whose incidence and severity vary across production systems, but may contribute to select AM resistant bacteria, potentially disseminating in humans. Antimicrobial resistance (AMR) represents a public threat, leading policymakers to implement measures to reduce antimicrobial use (AMU). Investigating AMU patterns at prescriber's level, beyond national AMU trends, enables evaluation of substitutions between AM classes (occurring when one product is replaced by another), or average consumption per production system. Our aim was to identify the influence veterinarians would exert on AMU by quantifying substitution between AM products prescribed and delivered in similar therapeutic indications, in cattle production. METHODS: Monthly sales data on four critically important AM in five French areas (representative of production systems) were analysed from 2008 to 2013. We calculated the animal live weight receiving a treatment course and evaluated substitutions between brand-name and generic products, and between products from different AM classes with similar indications. RESULTS: Substitutions occurred, between products of the same class (macrolides) with similar indications, between generic and brand-name products (fluoroquinolones, ceftiofur, florfenicol) and between innovative and brand-name products (marbofloxacin, ceftiofur). Innovative products reaching the market represented between 2% and 40% of the yearly sales for a given molecule, depending on the active ingredient and the area. The introduction of generic products of fluoroquinolones and ceftiofur led to a moderate adoption of the generic product at the expense of the brand-name one, unlike in human health care where the adoption reaches up to 80%. CONCLUSION: Veterinary prescription remains a strong regulating power of AMU; substitutions only occurred for products with similar indications.

Antimicrobial Policies in United States Beef Production: Choosing the Right Instruments to Reduce Antimicrobial Use and Resistance Under Structural and Market Constraints.

Antimicrobial use (AMU) in animal agriculture contributes to the selection of resistant bacteria, potentially constituting a public health threat. To address antimicrobial resistance, public policies set by governments, as well as intra-sectoral approaches, can be implemented. In this paper, we explore how common policy instruments such as regulations, economic incentives, and voluntary agreements could help reduce AMU in beef production. We first describe the structure of the beef supply chain which directly influences the choice of policy instruments. We describe how externalities and imperfect information affect this system. We then discuss how five policy instruments would each perform to achieve a reduction in AMU. Bovine respiratory disease complex (BRD) represents the major driver of AMU in beef production; consequently, reducing its incidence would decrease significantly the amounts of antimicrobials administered. We consider control options for BRD at different stages of the beef supply chain.

An assessment of the economic costs to the U.S. dairy market of antimicrobial use restrictions.

Antimicrobial resistance is a public threat for humans, generated by the use of antimicrobials in human medicine as well as animal agriculture. Consequently, governments set public policies aim at curbing antimicrobial use (AMU). In dairy production, the occurrence of diseases triggers AMU to limit the costs associated with these afflictions. Therefore, any policies targeting AMU are likely to generate additional costs for farmer, and impact the dairy market. The objective of our research was to assess at the market level the costs associated with potential regulations (a prohibition scenario and tax scenarios) surrounding antimicrobial use in the U.S. dairy sector, comparing to a business as usual scenario. We conducted a two-step analysis, first at the farm and then the market level, to estimate the costs to both farmers and consumers. We found that potential policies restricting AMU would have a minor effect at the market level. In the case of prohibition of AMU, the average milk price would rise from $0.423 to $0.425 per liter. In the short run, the total annual losses would be $152 million. Implementing taxes on AMU would also slightly increase milk price, up to $0.426 in the case of a tax multiplying by five the initial antimicrobial price. Under the prohibition scenario, the quantity of milk produced would decrease by 356 million kilograms, representing 0.4% of the average U.S. milk production over the period 2012-2016. Implementing such policies would lead to a slight increase in costs of production, borne by both consumers and farmers through higher milk prices and lower milk production. As AMU in animal agriculture also fulfills animal welfare and public health objectives, the impacts of restricting AMU should be weighed with these other objectives in policy decisions. Further research is necessary to assess the distributional benefits and costs of AMU policies across farmers, retailers, animal and human health workers, and the public, incorporating multiple dimensions, such as animal welfare and food safety.

Sow removal in commercial herds: Patterns and animal level factors in Finland.

This observational retrospective cohort study provides benchmarking information on recent sow productivity development in Finnish herds. It focuses on parity cycle specific trends in sow removal patterns, and especially on the role of litter performance (size and piglet survival) in sow removal. In addition, the generated models offer a tool for calculating sow removal risks in any period, which could be used in economic and other simulation models. The data used in the study pool information of sows starting the same parity cycle (1 through 8) over the enrollment period of July 1st, 2013 through June 30th, 2014 and followed until the end of the study period (December 31st, 2014), and their performance histories across their entire previous productive life. Out of 71,512 individual sow parity cycle observations from the first to the eighth, 15,128 ended up in removal. Average litter sizes exceeded 13 piglets born in total in all of the most recent farrowings. Yet, even larger litter sizes were favored by the implemented culling policies, as sows having medium and large early life litters had lower risks of removal compared to those with the smallest litters, particularly in younger animals. With regard to piglets born just prior to removal, the smallest litter sizes were associated with the greatest culling risk for sows of that particular parity. In addition, having more than one stillborn piglet in the first and second litter put the sow at higher risk of being removed in all but the last (sixth through eighth) of the studied parity cycles. Investigation of removal patterns revealed a negative linear relationship between parity count and the mean days from farrowing to removal. More specifically, the median (mean) times to removal varied across the parity cycles from 62 (72) in the first to 34 days in both the seventh and eighth (47 and 42, respectively). Moreover, one in every six sows was removed within the first and second parity cycle. The findings especially in the earliest cycles may be a reflection of removal decisions not made according to any clear and pre-determined policy, or of biological issues that prevent farmers from firmly adhering to their policy. Quantitative performance should be linked to overall system functionality and profitability while taking animal welfare into consideration in identifying opportunities to improve herd parity structure and future farm success.

The farm cost of decreasing antimicrobial use in dairy production.

Antimicrobials are used in animal agriculture to cure bacterial infectious diseases. However, antimicrobial use (AMU) inevitably leads to the selection of resistant bacteria, potentially infecting humans. As a global public threat, antimicrobial resistance has led policy makers to implement regulations supervising AMU. The objective of our research was to investigate the farm impact of several potential policies aimed at decreasing AMU. We modeled a dairy herd of 1000 cows with an average level of disease prevalence for the nine most frequent bacterial dairy diseases found in western countries. We calculated the farm net costs of AMU prohibition, as well as cost increases in antimicrobial treatments prices, and an increase in the milk withdrawal period after AMU. Sensitivity analyses were conducted to assess the impact of output and input prices, and disease prevalence. At a mean disease prevalence, the average net costs of not using antimicrobials were $61 per cow per year greater compared to a scenario modeling current farm AMU. The model predicted that the minimum and maximum increased costs associated with AMU prohibition were $46 and $73 per cow per year compared to current AMU. In each scenario, the cost difference increased with disease prevalence. Sensitivity analysis showed that the three stochastic variables which most significantly influenced the cost difference were respectively, cow replacement prices, cow slaughter price, and the milk price. Antimicrobial price increases of a factor of five, or extending the milk withdrawal period by 15 days, resulted in increasing the costs of diseases to a level where the farmer was better off not using antimicrobials. Our results suggest that the farm level costs of AMU prohibition in many cases might be minor, although the consequences of any policy instrument should be carefully evaluated to reach the ultimate goal of decreasing AMU without threatening the sustainability of milk production.

Use of Approximate Bayesian Computation to Assess and Fit Models of Mycobacterium leprae to Predict Outcomes of the Brazilian Control Program.

Hansen's disease (leprosy) elimination has proven difficult in several countries, including Brazil, and there is a need for a mathematical model that can predict control program efficacy. This study applied the Approximate Bayesian Computation algorithm to fit 6 different proposed models to each of the 5 regions of Brazil, then fitted hierarchical models based on the best-fit regional models to the entire country. The best model proposed for most regions was a simple model. Posterior checks found that the model results were more similar to the observed incidence after fitting than before, and that parameters varied slightly by region. Current control programs were predicted to require additional measures to eliminate Hansen's Disease as a public health problem in Brazil.

Sero-prevalence and risk factors associated with African swine fever on pig farms in southwest Nigeria.

BACKGROUND: African swine fever (ASF) is one of the major setbacks to development of the pig industry in Nigeria. It is enzootic in southwest Nigeria. We determined the sero-prevalence and factors associated with ASF among-herd seropositivity in 144 pig farms in six States from southwest Nigeria during the dry and rainy seasons using indirect Enzyme Linked Immunosorbent Assay (ELISA) for ASF IgG antibodies. An interviewer-administered questionnaire was used to collect information on demography, environmental and management factors. We performed descriptive statistics, and univariate and multivariable analyses to determine the among-herd sero-prevalence of ASF and its associated factors. RESULTS: The overall herd sero-prevalence of ASF was 28% (95% Confidence interval (95% CI) 21-36); it was significantly higher (P <0.05) in the dry season (54%; 95% CI 37-70) than the rainy season (18%; 95% CI 11-27). In the univariate analysis, having a quarantine/ isolation unit within 100 m radius of a regular pig pen (OR = 3.3; 95% CI 1.3-8.9), external source of replacement stock (OR = 3.2; 95% CI 1.3-8.3) and dry season (OR = 5.3; 95% CI 2.2-12.7) were risk factors for ASF among-herd seropositivity. In the multivariable logistic regression, there was interaction between season and herd size. Our final model included season, source of replacement stock, herd size and interaction between herd size and season. Herds with an external source of replacement always had higher ASF sero-prevalence compared with herds with an internal source. The herd size effect varied between seasons. CONCLUSIONS: The ASF herd level sero-prevalence in southwest Nigeria was higher in pig herds with an external source of replacement stock and in the dry season. The effect of season of the year the samples were taken on ASF seropositivity was modified by herd size. We encourage strict compliance with biosecurity measures, especially using an internal source of replacement stock and measures that minimize movement on pig farms in southwest Nigeria, in order to enhance ASF free farms.

Mathematical model of plasmid-mediated resistance to ceftiofur in commensal enteric Escherichia coli of cattle.

Antimicrobial use in food animals may contribute to antimicrobial resistance in bacteria of animals and humans. Commensal bacteria of animal intestine may serve as a reservoir of resistance-genes. To understand the dynamics of plasmid-mediated resistance to cephalosporin ceftiofur in enteric commensals of cattle, we developed a deterministic mathematical model of the dynamics of ceftiofur-sensitive and resistant commensal enteric Escherichia coli (E. coli) in the absence of and during parenteral therapy with ceftiofur. The most common treatment scenarios including those using a sustained-release drug formulation were simulated; the model outputs were in agreement with the available experimental data. The model indicated that a low but stable fraction of resistant enteric E. coli could persist in the absence of immediate ceftiofur pressure, being sustained by horizontal and vertical transfers of plasmids carrying resistance-genes, and ingestion of resistant E. coli. During parenteral therapy with ceftiofur, resistant enteric E. coli expanded in absolute number and relative frequency. This expansion was most influenced by parameters of antimicrobial action of ceftiofur against E. coli. After treatment (>5 weeks from start of therapy) the fraction of ceftiofur-resistant cells among enteric E. coli, similar to that in the absence of treatment, was most influenced by the parameters of ecology of enteric E. coli, such as the frequency of transfer of plasmids carrying resistance-genes, the rate of replacement of enteric E. coli by ingested E. coli, and the frequency of ceftiofur resistance in the latter.