Transmission rates of veterinary and clinically important antibiotic resistant Escherichia coli: A meta- ANALYSIS.

The transmission rate per hour between hosts is a key parameter for simulating transmission dynamics of antibiotic-resistant bacteria, and might differ for antibiotic resistance genes, animal species, and antibiotic usage. We conducted a Bayesian meta-analysis of resistant Escherichia coli (E. coli) transmission in broilers and piglets to obtain insight in factors determining the transmission rate, infectious period, and reproduction ratio. We included blaCTX-M-1, blaCTX-M-2, blaOXA-162, catA1, mcr-1, and fluoroquinolone resistant E. coli. The Maximum a Posteriori (MAP) transmission rate in broilers without antibiotic treatment ranged from 0.4∙10-3 to 2.5∙10-3 depending on type of broiler (SPF vs conventional) and inoculation strains. For piglets, the MAP in groups without antibiotic treatment were between 0.7∙10-3 and 0.8∙10-3, increasing to 0.9∙10-3 in the group with antibiotic treatment. In groups without antibiotic treatment, the transmission rate of resistant E. coli in broilers was almost twice the transmission rate in piglets. Amoxicillin increased the transmission rate of E. coli carrying blaCTX-M-2 by three-fold. The MAP infectious period of resistant E. coli in piglets with and without antibiotics is between 971 and 1065 hours (40 - 43 days). The MAP infectious period of resistant E. coli in broiler without antibiotics is between 475 and 2306 hours (20 - 96 days). The MAP infectious period of resistant E. coli in broiler with antibiotics is between 2702 and 3462 hours (113 - 144 days) which means a lifelong colonization. The MAP basic reproduction ratio in piglets of infection with resistant E. coli when using antibiotics is 27.70, which is higher than MAP in piglets without antibiotics between 15.65 and 18.19. The MAP basic reproduction ratio in broilers ranges between 3.46 and 92.38. We consider three possible explanations for our finding that in the absence of antibiotics the transmission rate is higher among broilers than among piglets: i) due to the gut microbiome of animals, ii) fitness costs of bacteria, and iii) differences in experimental set-up between the studies. Regarding infectious period and reproduction ratio, the effect of the resistance gene, antibiotic treatment, and animal species are inconclusive due to limited data.

Comparing the transmission of carbapenemase-producing and extended-spectrum beta-lactamase-producing Escherichia coli between broiler chickens.

The emergence of carbapenemase-producing Enterobacteriaceae (CPE) is a threat to public health, because of their resistance to clinically important carbapenem antibiotics. The emergence of CPE in meat-producing animals is particularly worrying because consumption of meat contaminated with resistant bacteria comparable to CPE, such as extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, contributed to colonization in humans worldwide. Currently, no data on the transmission of CPE in livestock is available. We performed a transmission experiment to quantify the transmission of CPE between broilers to fill this knowledge gap and to compare the transmission rates of CPE and other antibiotic-resistant E. coli. A total of 180 Ross 308 broiler chickens were distributed over 12 pens on the day of hatch (day 0). On day 5, half of the 10 remaining chickens in each pen were orally inoculated with 5·102 colony-forming units of CPE, ESBL, or chloramphenicol-resistant E. coli (catA1). To evaluate the effect of antibiotic treatment, amoxicillin was given twice daily in drinking water in 6 of the 12 pens from days 2-6. Cloacal swabs of all animals were taken to determine the number of infectious broilers. We used a Bayesian hierarchical model to quantify the transmission of the E. coli strains. E. coli can survive in the environment and serve as a reservoir. Therefore, the susceptible-infectious transmission model was adapted to account for the transmission of resistant bacteria from the environment. In addition, the caecal microbiome was analyzed on day 5 and at the end of the experiment on day 14 to assess the relationship between the caecal microbiome and the transmission rates. The transmission rates of CPE were 52 - 68 per cent lower compared to ESBL and catA1, but it is not clear if these differences were caused by differences between the resistance genes or by other differences between the E. coli strains. Differences between the groups in transmission rates and microbiome diversity did not correspond to each other, indicating that differences in transmission rates were probably not caused by major differences in the community structure in the caecal microbiome. Amoxicillin treatment from day 2-6 increased the transmission rate more than three-fold in all inoculums. It also increased alpha-diversity compared to untreated animals on day 5, but not on day 14, suggesting only a temporary effect. Future research could incorporate more complex transmission models with different species of resistant bacteria into the Bayesian hierarchical model.

Rapid risk assessment tool (RRAT) to prioritize emerging and re-emerging livestock diseases for risk management.

Increasing globalization and international trade contribute to rapid expansion of animal and human diseases. Hence, preparedness is warranted to prevent outbreaks of emerging and re-emerging diseases or detect outbreaks in an early stage. We developed a rapid risk assessment tool (RRAT) to inform risk managers on the incursion risk of multiple livestock diseases, about the main sources for incursion and the change of risk over time. RRAT was built as a relational database to link data on disease outbreaks worldwide, on introduction routes and on disease-specific parameters. The tool was parameterized to assess the incursion risk of 10 livestock diseases for the Netherlands by three introduction routes: legal trade in live animals, legal trade of animal products, and animal products illegally carried by air travelers. RRAT calculates a semi-quantitative risk score for the incursion risk of each disease, the results of which allow for prioritization. Results based on the years 2016-2018 indicated that the legal introduction routes had the highest incursion risk for bovine tuberculosis, whereas the illegal route posed the highest risk for classical swine fever. The overall incursion risk via the illegal route was lower than via the legal routes. The incursion risk of African swine fever increased over the period considered, whereas the risk of equine infectious anemia decreased. The variation in the incursion risk over time illustrates the need to update the risk estimates on a regular basis. RRAT has been designed such that the risk assessment can be automatically updated when new data becomes available. For diseases with high-risk scores, model results can be analyzed in more detail to see which countries and trade flows contribute most to the risk, the results of which can be used to design risk-based surveillance. RRAT thus provides a multitude of information to evaluate the incursion risk of livestock diseases at different levels of detail. To give risk managers access to all results of RRAT, an online visualization tool was built.

Quantitative Risk Assessment for the Introduction of Carbapenem-Resistant Enterobacteriaceae (CPE) into Dutch Livestock Farms.

Early detection of emerging carbapenem-resistant Enterobacteriaceae (CPE) in food-producing animals is essential to control the spread of CPE. We assessed the risk of CPE introduction from imported livestock, livestock feed, companion animals, hospital patients, and returning travelers into livestock farms in The Netherlands, including (1) broiler, (2) broiler breeder, (3) fattening pig, (4) breeding pig, (5) farrow-to-finish pig, and (6) veal calf farms. The expected annual number of introductions was calculated from the number of farms exposed to each CPE source and the probability that at least one animal in an exposed farm is colonized. The total number of farms with CPE colonization was estimated to be the highest for fattening pig farms, whereas the probability of introduction for an individual farm was the highest for broiler farms. Livestock feed and imported livestock are the most likely sources of CPE introduction into Dutch livestock farms. Sensitivity analysis indicated that the number of fattening pig farms determined the number of high introductions in fattening pigs from feed, and that uncertainty on CPE prevalence impacted the absolute risk estimate for all farm types. The results of this study can be used to inform risk-based surveillance for CPE in livestock farms.

Assessing the introduction risk of vector-borne animal diseases for the Netherlands using MINTRISK: A Model for INTegrated RISK assessment.

To evaluate and compare the risk of emerging vector-borne diseases (VBDs), a Model for INTegrated RISK assessment, MINTRISK, was developed to assess the introduction risk of VBDs for new regions in an objective, transparent and repeatable manner. MINTRISK is a web-based calculation tool, that provides semi-quantitative risk scores that can be used for prioritization purposes. Input into MINTRISK is entered by answering questions regarding entry, transmission, establishment, spread, persistence and impact of a selected VBD. Answers can be chosen from qualitative answer categories with accompanying quantitative explanation to ensure consistent answering. The quantitative information is subsequently used as input for the model calculations to estimate the risk for each individual step in the model and for the summarizing output values (rate of introduction; epidemic size; overall risk). The risk assessor can indicate his uncertainty on each answer, and this is accounted for by Monte Carlo simulation. MINTRISK was used to assess the risk of four VBDs (African horse sickness, epizootic haemorrhagic disease, Rift Valley fever, and West Nile fever) for the Netherlands with the aim to prioritise these diseases for preparedness. Results indicated that the overall risk estimate was very high for all evaluated diseases but epizootic haemorrhagic disease. Uncertainty intervals were, however, wide limiting the options for ranking of the diseases. Risk profiles of the VBDs differed. Whereas all diseases were estimated to have a very high economic impact once introduced, the estimated introduction rates differed from low for Rift Valley fever and epizootic haemorrhagic disease to moderate for African horse sickness and very high for West Nile fever. Entry of infected mosquitoes on board of aircraft was deemed the most likely route of introduction for West Nile fever into the Netherlands, followed by entry of infected migratory birds.

Quantitative risk assessment of the introduction of low pathogenic avian influenza H5 and H7 strains into Poland via legal import of live poultry.

Low pathogenic avian influenza (LPAI) caused by H5 and H7 viruses is considered a threatening disease for poultry production due to the possibility of prolonged undetected virus circulation in a poultry flock and its potential to mutate to highly pathogenic avian influenza (HPAI). The occurrence of HPAI may have devastating impact on the poultry industry and has serious economic consequences. The possibility of LPAI virus (LPAIV) being introduced into Poland via import of live poultry from EU countries was considered. The main aim of the study was to quantitatively assess the probability of LPAIV H5 and H7 introduction into Poland (PLPAI) via this pathway, to evaluate the relative contribution of exporting countries and species of poultry to this probability and to present the spatial distribution of the introduction probability in Poland. To this end, a stochastic multilevel binomial risk model, taking into account uncertainty and variability of input parameter values, was developed. The results of this model indicate that the mean annual probability of LPAIV H5 or H7 introduction into Poland is 0.088 [95 % uncertainty interval: 0.0575, 0.128], which corresponds to, on average, one outbreak every 11 years. The countries contributing most to this probability are Germany, Czech Republic and Denmark. Importations of ducks, chickens and turkeys contribute most to PLPAI, whereas importations of geese and guinea fowl represent a minor risk. The probability of LPAIV introduction is not equally distributed across Poland with the majority of counties having a high probability of LPAIV introduction being located in the Western part of the country. The results of this study can be used to support decision makers on targeted prevention or risk-based surveillance strategies for LPAI.

Cross-Validation of Generic Risk Assessment Tools for Animal Disease Incursion Based on a Case Study for African Swine Fever.

In recent years, several generic risk assessment (RA) tools have been developed that can be applied to assess the incursion risk of multiple infectious animal diseases allowing for a rapid response to a variety of newly emerging or re-emerging diseases. Although these tools were originally developed for different purposes, they can be used to answer similar or even identical risk questions. To explore the opportunities for cross-validation, seven generic RA tools were used to assess the incursion risk of African swine fever (ASF) to the Netherlands and Finland for the 2017 situation and for two hypothetical scenarios in which ASF cases were reported in wild boar and/or domestic pigs in Germany. The generic tools ranged from qualitative risk assessment tools to stochastic spatial risk models but were all parameterized using the same global databases for disease occurrence and trade in live animals and animal products. A comparison of absolute results was not possible, because output parameters represented different endpoints, varied from qualitative probability levels to quantitative numbers, and were expressed in different units. Therefore, relative risks across countries and scenarios were calculated for each tool, for the three pathways most in common (trade in live animals, trade in animal products, and wild boar movements) and compared. For the 2017 situation, all tools evaluated the risk to the Netherlands to be higher than Finland for the live animal trade pathway, the risk to Finland the same or higher as the Netherlands for the wild boar pathway, while the tools were inconclusive on the animal products pathway. All tools agreed that the hypothetical presence of ASF in Germany increased the risk to the Netherlands, but not to Finland. The ultimate aim of generic RA tools is to provide risk-based evidence to support risk managers in making informed decisions to mitigate the incursion risk of infectious animal diseases. The case study illustrated that conclusions on the ASF risk were similar across the generic RA tools, despite differences observed in calculated risks. Hence, it was concluded that the cross-validation contributed to the credibility of their results.

Health effects of feeding genetically modified (GM) crops to livestock animals: A review.

A large share of genetically modified (GM) crops grown worldwide is processed into livestock feed. Feed safety of GM crops is primarily based on compositional equivalence with near-isogenic cultivars and experimental trials in rodents. However, feeding studies in target animals add to the evaluation of GM crops with respect to animal health. This review aimed to evaluate the possible health effects of feeding GM crops to livestock by reviewing scientific publications on experimental studies in ruminants, pigs, and poultry in which at least one of the following health parameters was investigated: body condition score, organ weight, haematology, serum biochemistry, histopathology, clinical examination, immune response, or gastrointestinal microbiota. In most experiments, either Bt (Bacillus thuringiensis) maize, Roundup Ready (RR) soybean, or both were fed to livestock animals. Significant differences (P<0.05) in health parameters were most often observed when animals were fed Bt maize, although most effects measured were unlikely to be of biological significance and were within normal biological ranges. Health effects of RR soybean were only observed in one experimental study with broilers. Based on this literature review, we conclude that there is no clear evidence that feed composed of first generation GM crops has adverse effects on animal health.

Quantitative analysis of the probability of introducing equine encephalosis virus (EEV) into The Netherlands.

Equine encephalosis is a midge-borne viral disease of equines caused by equine encephalosis virus (EEV, Orbivirus, Reoviridae), and closely related to African horse sickness virus (AHSV). EEV and AHSV share common vectors and show similar transmission patterns. Until now EEV has caused outbreaks in Africa and Israel. This study aimed to provide insight in the probability of an EEV outbreak in The Netherlands caused by infected vectors or hosts, the contribution of potential source areas (risk regions) to this probability, and the effectiveness of preventive measures (sanitary regimes). A stochastic risk model constructed for risk assessment of AHSV introduction was adapted to EEV. Source areas were categorized in risk regions (high, low, and very low risk) based on EEV history and the presence of competent vectors. Two possible EEV introduction pathways were considered: importation of infected equines and importation of infected vectors along with their vertebrate hosts. The probability of EEV introduction (PEEV) was calculated by combining the probability of EEV release by either pathway and the probability of EEV establishment. The median current annual probability of EEV introduction by an infected equine was estimated at 0.012 (90% uncertainty interval 0.002-0.020), and by an infected vector at 4.0 10(-5) (90% uncertainty interval 5.3 10(-6)-2.0 10(-4)). Equines from high risk regions contributed most to the probability of EEV introduction with 74% on the EEV introduction by equines, whereas low and very low risk regions contributed 18% and 8%, respectively. International movements of horses participating in equestrian events contributed most to the probability of EEV introduction by equines from high risk regions (86%), but also contributed substantially for low and very low risk regions with 47% and 56%. The probability of introducing EEV into The Netherlands is much higher than the probability of introducing AHSV with equines from high risk countries contributing most. The introduction by an infected equine is the most likely pathway. Control measures before exportation of equines showed to have a strong mitigating effect on the probability of EEV introduction. The risk of EEV outbreaks should be taken into account when altering these import regulations.

Risk-based testing of imported animals: A case study for bovine tuberculosis in The Netherlands.

In intra-EU trade, the health status of animals is warranted by issuing a health certificate after clinical inspection in the exporting country. This certificate cannot provide guarantee of absence of infection, especially not for diseases with a long incubation period and no overt clinical signs such as bovine tuberculosis (bTB). The Netherlands are officially free from bTB since 1999. However, frequent reintroductions occurred in the past 15 years through importation of infected cattle. Additional testing (AT) of imported cattle could enhance the probability of detecting an imported bTB infection in an early stage. The goal of this study was to evaluate the effectiveness of risk-based AT for bTB in cattle imported into The Netherlands. A generic stochastic import risk model was developed that simulates introduction of infection into an importing country through importation of live animals. Main output parameters are the number of infected animals that is imported (Ninf), the number of infected animals that is detected by testing (Ndet), and the economic losses incurred by importing infected animals (loss). The model was parameterized for bTB. Model calculations were optimized to either maximize Ndet or to minimize loss. Model results indicate that the risk of bTB introduction into The Netherlands is very high. For the current situation in which Dutch health checks on imported cattle are limited to a clinical inspection of a random sample of 5-10% of imported animals, the calculated annual Ninf=99 (median value). Random AT of 8% of all imported cattle results in Ndet=7 (median value), while the median Ndet=75 if the sampling strategy for AT is optimized to maximize Ndet. However, in the latter scenario, loss is more than twice as large as in the current situation, because only calves are tested for which cost of detection is higher than the expected gain of preventing a possible outbreak. When optimizing the sampling strategy for AT to minimize loss, only breeding and production cattle are selected for AT resulting in Ndet=1 (median value). Loss is; however, reduced by 75% if compared to the current situation. We conclude that the effectiveness of AT can greatly be improved by risk-based sampling. The optimal sampling strategy for risk-based AT for bTB is highly dependent on the objective of AT. If economic losses are to be contained, AT should focus on breeding and production cattle originating from high-risk countries.

Probability of exporting infected carcasses from vaccinated pigs following a foot-and-mouth disease epidemic.

Emergency vaccination is an effective control strategy for foot-and-mouth disease (FMD) epidemics in densely populated livestock areas, but results in a six-month waiting period before exports can be resumed, incurring severe economic consequences for pig exporting countries. In the European Union, a one-month waiting period has been discussed based on negative test results in a final screening. The objective of this study was to analyze the risk of exporting FMD-infected pig carcasses from a vaccinated area: (1) directly after final screening and (2) after a six-month waiting period. A risk model has been developed to estimate the probability that a processed carcass was derived from an FMD-infected pig (P(carc)). Key variables were herd prevalence (P(H)), within-herd prevalence (P(A)), and the probability of detection at slaughter (P(SL)). P(H) and P(A) were estimated using Bayesian inference under the assumption that, despite all negative test results, > or =1 infected pigs were present. Model calculations indicated that P(carc) was on average 2.0 x 10(-5) directly after final screening, and 1.7 x 10(-5) after a six-month waiting period. Therefore, the additional waiting time did not substantially reduce P(carc). The estimated values were worst-case scenarios because only viraemic pigs pose a risk for disease transmission, while seropositive pigs do not. The risk of exporting FMD via pig carcasses from a vaccinated area can further be reduced by heat treatment of pork and/or by excluding high-risk pork products from export.

The BSE risk of processing meat and bone meal in nonruminant feed: a quantitative assessment for the Netherlands.

The total ban on use of meat and bone meal (MBM) in livestock feed has been very successful in reducing bovine spongiform encephalopathy (BSE) spread, but also implies a waste of high-quality proteins resulting in economic and ecological loss. Now that the BSE epidemic is fading out, a partial lifting of the MBM ban might be considered. The objective of this study was to assess the BSE risk for the Netherlands if MBM derived from animals fit for human consumption, i.e., category 3 MBM, would be used in nonruminant feed. A stochastic simulation model was constructed that calculates (1) the probability that infectivity of undetected BSE-infected cows ends up with calves and (2) the quantity of infectivity (Q(inf)) consumed by calves in case of such an incident. Three pathways were considered via which infectivity can reach cattle: (1) cross-contamination in the feed mill, (2) cross-contamination on the primary farm, and (3) pasture contamination. Model calculations indicate that the overall probability that infectivity ends up with calves is 3.2%. In most such incidents the Q(inf) is extremely small (median = 6.5 x 10(-12) ID(50); mean = 1.8 x 10(-4) ID(50)), corresponding to an average probability of 1.3 x 10(-4) that an incident results in >or=1 new BSE infections. Cross-contamination in the feed mill is the most risky pathway. Combining model results with Dutch BSE prevalence estimates for the coming years, it can be concluded that the BSE risk of using category 3 MBM derived from Dutch cattle in nonruminant feed is very low.

Sensitivity analysis to evaluate the impact of uncertain factors in a scenario tree model for classical swine fever introduction.

Introduction of classical swine fever virus (CSFV) is a continuing threat to the pig production sector in the European Union. A scenario tree model was developed to obtain more insight into the main risk factors determining the probability of CSFV introduction (P(CSFV)). As this model contains many uncertain input parameters, sensitivity analysis was used to indicate which of these parameters influence model results most. Group screening combined with the statistical techniques of design of experiments and meta-modeling was applied to detect the most important uncertain input parameters among a total of 257 parameters. The response variable chosen was the annual P(CSFV) into the Netherlands. Only 128 scenario calculations were needed to specify the final meta-model. A consecutive one-at-a-time sensitivity analysis was performed with the main effects of this meta-model to explore their impact on the ranking of risk factors contributing most to the annual P(CSFV). The results indicated that model outcome is most sensitive to the uncertain input parameters concerning the expected number of classical swine fever epidemics in Germany, Belgium, and the United Kingdom and the probability that CSFV survives in an empty livestock truck traveling over a distance of 0-900 km.

Scenario tree modeling to analyze the probability of classical swine fever virus introduction into member states of the European Union.

The introduction of classical swine fever virus (CSFV) into a country free of disease without vaccination may have huge consequences in terms of both disease spread and economic losses. More quantitative insight into the main factors determining the probability of CSFV introduction (PCSFV) is needed to optimally use resources for the prevention of CSFV introduction. For this purpose a spreadsheet model was constructed that calculates the annual PCSFV into member states of the European Union (EU). The scenario pathway approach was used as most probabilities in the model are very small. Probability distributions were used to take into account inherent variability of input parameters. The model contained pathways of CSFV introduction including the import of pigs and pork products, returning livestock trucks, and contacts with wild boar. All EU member states were included as possible sources of CSFV. Default results for the Netherlands showed a mean overall annual PCSFV of approximately 0.06, indicating that the Netherlands can expect CSFV introduction on average once every 18 years from the pathways and countries included in the model. Almost 65% of this probability could be attributed to the pathway of returning livestock trucks. The most likely sources of CSFV introduction were Germany, Belgium, and the United Kingdom. Although the calculated probabilities were rather low when compared with expert estimates and recent history, the most likely causes of CSFV introduction indicated by the model were considered to be realistic. It was therefore concluded that the model is a useful tool to structure and analyze information for decision making concerning the prevention of CSFV introduction.