Unveiling the landscape of resistance against high priority critically important antimicrobials in food-producing animals across Africa: A scoping review.

The rapid population growth in Africa is associated with an increasing demand for livestock products which in turn can lead to antimicrobial use. Antimicrobial usage in animals contributes to the emergence and selection of resistant bacteria which constitutes a serious public health threat. This study aims to review and summarize the available information on highest priority critically important antimicrobials (HPCIAs) resistance in livestock production in Africa. This work will help to inform future policies for controlling antimicrobial resistance (AMR) in the food production chain. A scoping review was conducted according to the Cochrane handbook and following PRISMA 2020 guidelines for reporting. Primary research studies published after 1999 and reporting resistance of Escherichia coli, Enterococcus spp, Staphylococcus aureus, Salmonella spp, and Campylobacter spp to HPCIAs in poultry, cattle, pigs, goats, and sheep in Africa were searched in four databases. A total of 312 articles were included in the review. The majority of the studies (40.7) were conducted in North African countries. More than 49.0% of included studies involved poultry and 26.2% cattle. Cephalosporins and quinolones were the most studied antimicrobial classes. Of the bacteria investigated in the current review, E. coli (41.7%) and Salmonella spp (24.9%) represented the most commonly studied. High levels of resistance against erythromycin in E. coli were found in poultry (MR 96.1%, IQR 83.3-100.0%), cattle (MR 85.7%, IQR 69.2-100.0%), and pigs (MR 94.0%, IQR 86.2-94.0%). In sheep, a high level of resistance was observed in E. coli against nalidixic acid (MR 87.5%, IQR 81.3-93.8%). In goats, the low level of sensibility was noted in S. aureus against streptomycin (MR 86.8%, IQR 19.4-99.0%). The study provides valuable information on HPCIAs resistance in livestock production in Africa and highlights the need for further research and policies to address the public health risk of AMR. This will likely require an investment in diagnostic infrastructure across the continent. Awareness on the harmful impact of AMR in African countries is a requirement to produce more effective and sustainable measures to curb AMR.

Review state-of-the-art of output-based methodological approaches for substantiating freedom from infection.

A wide variety of control and surveillance programmes that are designed and implemented based on country-specific conditions exists for infectious cattle diseases that are not regulated. This heterogeneity renders difficult the comparison of probabilities of freedom from infection estimated from collected surveillance data. The objectives of this review were to outline the methodological and epidemiological considerations for the estimation of probabilities of freedom from infection from surveillance information and review state-of-the-art methods estimating the probabilities of freedom from infection from heterogeneous surveillance data. Substantiating freedom from infection consists in quantifying the evidence of absence from the absence of evidence. The quantification usually consists in estimating the probability of observing no positive test result, in a given sample, assuming that the infection is present at a chosen (low) prevalence, called the design prevalence. The usual surveillance outputs are the sensitivity of surveillance and the probability of freedom from infection. A variety of factors influencing the choice of a method are presented; disease prevalence context, performance of the tests used, risk factors of infection, structure of the surveillance programme and frequency of testing. The existing methods for estimating the probability of freedom from infection are scenario trees, Bayesian belief networks, simulation methods, Bayesian prevalence estimation methods and the STOC free model. Scenario trees analysis is the current reference method for proving freedom from infection and is widely used in countries that claim freedom. Bayesian belief networks and simulation methods are considered extensions of scenario trees. They can be applied to more complex surveillance schemes and represent complex infection dynamics. Bayesian prevalence estimation methods and the STOC free model allow freedom from infection estimation at the herd-level from longitudinal surveillance data, considering risk factor information and the structure of the population. Comparison of surveillance outputs from heterogeneous surveillance programmes for estimating the probability of freedom from infection is a difficult task. This paper is a 'guide towards substantiating freedom from infection' that describes both all assumptions-limitations and available methods that can be applied in different settings.

Strategies to reduce antimicrobials in livestock and aquaculture, and their impact under field conditions: a structured scoping literature review.

Antimicrobial resistance is a pandemic problem, causing substantial health and economic burdens. Antimicrobials are extensively used in livestock and aquaculture, exacerbating this global threat. Fostering the prudent use of antimicrobials will safeguard animal and human health. A lack of knowledge about alternatives to replace antimicrobials, and their effectiveness under field conditions, hampers changes in farming practices. This work aimed to understand the impact of strategies to reduce antimicrobial usage (AMU) in livestock and aquaculture, under field conditions, using a structured scoping literature review. The Extension for Scoping Reviews of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA-ScR) were followed and the Patient, Intervention, Comparison, Outcome, Time and Setting (PICOTS) framework used. Articles were identified from CAB Abstracts, MEDLINE and Scopus. A total of 7505 unique research articles were identified, 926 of which were eligible for full-text assessment; 203 articles were included in data extraction. Given heterogeneity across articles in the way alternatives to antimicrobials or interventions against their usage were described, there was a need to standardize these by grouping them in categories. There were differences in the impacts of the strategies between and within species; this highlights the absence of a 'one-size-fits-all' solution. Nevertheless, some options seem more promising than others, as their impacts were consistently equivalent or positive when compared with animal performance using antimicrobials. This was particularly the case for bioactive protein and peptides, and feed/water management. The outcomes of this work provide data to inform cost-effectiveness assessments of strategies to reduce AMU.

How is depth of anaesthesia assessed in experimental pigs? A scoping review.

BACKGROUND: Despite the large number of pigs involved in translational studies, no gold standard depth of anaesthesia indicators are available. We undertook a scoping review to investigate and summarize the evidence that sustains or contradicts the use of depth of anaesthesia indicators in this species. METHODS: Medline, Embase and CAB abstract were searched up to September 22nd 2022. No limits were set for time, language and study type. Only original articles of in vivo studies using pigs or minipigs undergoing general anaesthesia were included. The depth of anaesthesia indicators reported in the selected papers were divided in two categories: A, indicators purposely investigated as method to assess depth of anaesthesia; B, indicators reported but not investigated as method to assess depth of anaesthesia. RESULTS: Out of 13792 papers found, 105 were included after the screening process. Category A: 17 depth of anaesthesia indicators were found in 19 papers. Studies were conducted using inhalant anaesthetics as the main anaesthetic agent in the majority of the cases (13/19 = 68.4%), while 3/19 (15.8%) used propofol. The most investigated depth of anaesthesia indicators were bispectral index (8/19 = 42.1%) and spectral edge frequency 95% (5/19 = 26.3%). Contrasting results about the specific usefulness of each depth of anaesthesia indicators were reported. Category B: 23 depth of anaesthesia indicators were found in 92 papers. The most reported depth of anaesthesia indicators were: motor response following a stimulus (37/92 = 40.2%), depth of anaesthesia scores (21/92 = 23.3%), bispectral index (16/92 = 17.8%) and spectral edge frequency 95% (9/92 = 9.8%). CONCLUSION: Results highlight the lack of scientifically valid and reliable indicators to ensure adequate depth of anaesthesia in pigs.

THE IMPLEMENTATION GAP IN EMERGING DISEASE RISK MANAGEMENT IN THE WILDLIFE TRADE.

The wildlife trade has been characterized as one of the biggest risk factors in the emergence of new infectious diseases. In the shadow of COVID-19, there is growing political and scientific urgency to manage this risk. Existing studies and experiences make it clear that something must be done but are less clear on how to get it done. It is a quite different task to accumulate evidence on the presence of pathogens, their locations in the supply chain, and their spillover to new hosts than to identify effective ways to prevent and mitigate emerging disease under real-world conditions. This study sought peer-reviewed evidence on the effectiveness, acceptability, feasibility, and sustainability of risk reduction interventions for zoonotic and nonzoonotic disease emergence in the wildlife trade. An environmental scan triangulated information from a scoping review following a Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for scoping review protocol, two narrative literature reviews, and key informant interviews of 26 international wildlife health experts. Existing literature has been inattentive to program implementation or evaluation studies. There was insufficient evidence to identify effective and sustainable risk management actions. Studies on the effects of social, epidemiologic, and ecologic context on intervention success was lacking, as was research using a complex systems perspective. The lack of systematic program evaluations or implementation studies leaves decision makers with insufficient evidence to select interventions likely to be acceptable, effective, and sustainable within and across the disparate context of the wildlife trade. This necessitates adaptive risk management and innovations in program implementation and evaluation to ensure evidence-based risk management.

Corrigendum: Overview of Cattle Diseases Listed Under Category C, D or E in the Animal Health Law for Which Control Programmes Are in Place Within Europe.

[This corrects the article DOI: 10.3389/fvets.2021.688078.].

Towards risk-based surveillance of African Swine Fever in Switzerland.

African Swine Fever (ASF) has emerged as a disease of great concern to swine producers and government disease control agencies because of its severe consequences to animal health and the pig industry. Early detection of an ASF introduction is considered essential for reducing the impact of the disease. Risk-based surveillance approaches have been used as enhancements to early disease epidemic detection systems in livestock populations. Such approaches may consider the role wildlife plays in hosting and transmitting a disease. In this study, a method is presented to estimate and map the risk of introducing ASF into the domestic pig population through wild boar intermediate hosts. It makes use of data about hunted wild boar, rest areas along motorways connecting ASF affected countries to Switzerland, outdoor piggeries, and forest cover. These data were used to compute relative wild boar abundance as well as to estimate the risk of both disease introduction into the wild boar population and disease transmission to domestic pigs. The way relative wild boar abundance was calculated adds to the current state of the art by considering the effect of beech mast on hunting success and the probability of wild boar occurrence when distributing relative abundance values among individual grid cells. The risk of ASF introduction into the domestic pig population by wild boar was highest near the borders of France, Germany, and Italy. On the north side of the Alps, areas of high risk were located on the unshielded side of the main motorway crossing the Central Plateau, which acts as a barrier for wild boar. Estimating the risk of disease introduction into the domestic pig population without the intermediary of wild boar suggested that dispersing wild boar may play a key role in spreading the risk to areas remote from motorways. The results of this study can be used to focus surveillance efforts for early disease detection on high risk areas. The developed method may also inform policies to control other diseases that are transmitted by a direct contact from wild boar to domestic pigs.

Antimicrobial usage in Swiss fattening pig farms: is there still potential for improvement?

OBJECTIVE: The aim of this study was to analyze antimicrobial usage (AMU) in fattening pig farms that took part in the SuisSano/Safety + Health Programme in Switzerland over the year 2020 and to discuss the potential for further improvement. Usage was examined according to the antimicrobial's class and indication for use, with emphasis on highest priority critically important antimicrobials (HPCIAs). METHODS: Data on AMU from 1411 farms, reported in an electronic treatment journal, was used. AMU was quantified through treatment incidence (TI) based on Swiss Defined Daily Doses (DDDch). Indication of use for each antimicrobial class was analyzed with particular focus on HPCIAs. RESULTS: The total TI of all antimicrobials used in the farms corresponds to 8.9 DDDch per 1000 pig-days at risk, of which HPCIAs represented 2.6 %. A total of 140 farms (9.9 %) partake in HPCIAs usage, with tylosin (73.8 % of total HPCIA TI) and colistin (22.8 % of total HPCIA TI) being the most frequently antimicrobials used. The most common indication for treatment with HPCIAs was gastrointestinal disorders (62.1 % of total HPCIA TI). CONCLUSION AND CLINICAL RELEVANCE: This study shows that the efforts made in recent years to foster prudent use of antimicrobials and, especially HPCIAs in Swiss pig production, have been successful. Indeed, 90.1 % (1271 of 1411) of the farms did not use any HPCIAs over the year 2020. Of the recorded treatments, HPCIA's represented only 2.6 % of the total TIs used in fattening pigs. Since many farms do not use any HPCIAs, knowledge can be obtained from these farms to identify practices which can further reduce or even stop HPCIAs usage. Moreover, information concerning indications for HPCIAs usage provide input concerning where treatment options other than HPCIAs should be explored by both farmers and veterinarians.

Overview of Cattle Diseases Listed Under Category C, D or E in the Animal Health Law for Which Control Programmes Are in Place Within Europe.

The COST action "Standardising output-based surveillance to control non-regulated diseases of cattle in the European Union (SOUND control)," aims to harmonise the results of surveillance and control programmes (CPs) for non-EU regulated cattle diseases to facilitate safe trade and improve overall control of cattle infectious diseases. In this paper we aimed to provide an overview on the diversity of control for these diseases in Europe. A non-EU regulated cattle disease was defined as an infectious disease of cattle with no or limited control at EU level, which is not included in the European Union Animal health law Categories A or B under Commission Implementing Regulation (EU) 2020/2002. A CP was defined as surveillance and/or intervention strategies designed to lower the incidence, prevalence, mortality or prove freedom from a specific disease in a region or country. Passive surveillance, and active surveillance of breeding bulls under Council Directive 88/407/EEC were not considered as CPs. A questionnaire was designed to obtain country-specific information about CPs for each disease. Animal health experts from 33 European countries completed the questionnaire. Overall, there are 23 diseases for which a CP exists in one or more of the countries studied. The diseases for which CPs exist in the highest number of countries are enzootic bovine leukosis, bluetongue, infectious bovine rhinotracheitis, bovine viral diarrhoea and anthrax (CPs reported by between 16 and 31 countries). Every participating country has on average, 6 CPs (min-max: 1-13) in place. Most programmes are implemented at a national level (86%) and are applied to both dairy and non-dairy cattle (75%). Approximately one-third of the CPs are voluntary, and the funding structure is divided between government and private resources. Countries that have eradicated diseases like enzootic bovine leukosis, bluetongue, infectious bovine rhinotracheitis and bovine viral diarrhoea have implemented CPs for other diseases to further improve the health status of cattle in their country. The control of non-EU regulated cattle diseases is very heterogenous in Europe. Therefore, the standardising of the outputs of these programmes to enable comparison represents a challenge.

Existence and Quality of Data on Control Programs for EU Non-regulated Cattle Diseases: Consequences for Estimation and Comparison of the Probability of Freedom From Infection.

Some European countries have successfully implemented country-specific control programs (CPs) for infectious cattle diseases that are not regulated or are regulated only to a limited extent at the European Union (EU) level. Examples of such diseases include bovine viral diarrhea (BVD), infectious bovine rhinotracheitis (IBR), and Johne's disease (JD). The CPs vary between countries in the design and quality of collected data as well as methods used to detect infection and estimate prevalence or probability of freedom from infection. Differences in disease status between countries and non-standardized approaches to assess freedom from infection pose a risk for countries with CPs for non-regulated diseases as infected animals may influence the progress of the disease control or eradication program. The implementation of output-based standards allows estimation and comparison of the probability of freedom for non-regulated cattle diseases in European countries. The aim of the current study was to assess the existence and quality of data that could be used for estimating freedom from infection in European countries. The online data collection tool was sent to 32 countries participating in the SOUND control COST Action and was completed by 24 countries. Data on cattle demographics and data from CPs of IBR and BVD exist in more than 50% of the response countries. However, data describing risk factors and CP of JD was reported as existing in <25% of the countries. The overall quality of data in the sections on demographics and CPs of IBR and BVD were evaluated as "good", but risk factors and JD data were mostly evaluated as "fair." Data quality was considered less good mainly due to two quality criteria: accessibility and accuracy. The results of this study show that the quantity and quality of data about cattle populations and CPs are relatively similar in many surveyed countries. The outcome of this work provides an overview of the current situation in the European countries regarding data on EU non-regulated cattle diseases and will further assist in the development and implementation of output-based standards.

Overview and Evaluation of Existing Guidelines for Rational Antimicrobial Use in Small-Animal Veterinary Practice in Europe.

Antimicrobial stewardship guidelines (ASGs) represent an important tool to help veterinarians optimize their antimicrobial use with the objective of decreasing antimicrobial resistance. The aim of this study was to map and qualitatively assess the ASGs for antimicrobial use in cats and dogs in Europe. Country representatives of the European Network for Optimization of Veterinary Antimicrobial Treatment (ENOVAT) were asked to identify ASGs published in their countries. All collated ASGs updated since January 2010 containing recommendations on antimicrobial therapy for at least three conditions affecting different organ systems in cats and dogs underwent detailed review including AGREE II analysis. Out of forty countries investigated, fifteen ASGs from eleven countries met the inclusion criteria. Several critical principles of antimicrobial use were identified, providing a framework that should assist development of stewardship guidance. The AGREE II analysis highlighted several methodological limitations of the currently available ASGs. This study sheds light on the lack of national ASGs for dogs and cats in multiple European countries and should encourage national bodies to prioritize guideline development in small animals. A greater awareness of the need to use a structured approach to guideline development could improve the quality of ASGs in the future.

Multivariate syndromic surveillance for cattle diseases: Epidemic simulation and algorithm performance evaluation.

Multivariate Syndromic Surveillance (SyS) systems that simultaneously assess and combine information from different data sources are especially useful for strengthening surveillance systems for early detection of infectious disease epidemics. Despite the strong motivation for implementing multivariate SyS and there being numerous methods reported, the number of operational multivariate SyS systems in veterinary medicine is still very small. One possible reason is that assessing the performance of such surveillance systems remains challenging because field epidemic data are often unavailable. The objective of this study is to demonstrate a practical multivariate event detection method (directionally sensitive multivariate control charts) that can be easily applied in livestock disease SyS, using syndrome time series data from the Swiss cattle population as an example. We present a standardized method for simulating multivariate epidemics of different diseases using four diseases as examples: Bovine Virus Diarrhea (BVD), Infectious Bovine Rhinotracheitis (IBR), Bluetongue virus (BTV) and Schmallenberg virus (SV). Two directional multivariate control chart algorithms, Multivariate Exponentially Weighted Moving Average (MEWMA) and Multivariate Cumulative Sum (MCUSUM) were compared. The two algorithms were evaluated using 12 syndrome time series extracted from two Swiss national databases. The two algorithms were able to detect all simulated epidemics around 4.5 months after the start of the epidemic, with a specificity of 95%. However, the results varied depending on the algorithm and the disease. The MEWMA algorithm always detected epidemics earlier than the MCUSUM, and epidemics of IBR and SV were detected earlier than epidemics of BVD and BTV. Our results show that the two directional multivariate control charts are promising methods for combining information from multiple time series for early detection of subtle changes in time series from a population without producing an unreasonable amount of false alarms. The approach that we used for simulating multivariate epidemics is relatively easy to implement and could be used in other situations where real epidemic data are unavailable. We believe that our study results can support the implementation and assessment of multivariate SyS systems in animal health.

Expert opinion on livestock antimicrobial usage indications and patterns in Denmark, Portugal and Switzerland.

We aimed at describing antimicrobial usage patterns throughout livestock production cycles, and comparing them across three countries from Northern, Central and Southern Europe. Given the difficulties to collect such detailed usage data, an expert opinion was deemed the most appropriate study design. This study provides new insights into the time periods and indications for which specific antimicrobial substances are used in different livestock sectors. Veterinary experts (n=67) from different livestock sectors (broilers, pigs, dairy cattle and veal/fattening calves) and countries (Denmark, Portugal and Switzerland) replied to a questionnaire focusing on the time periods in the production cycle when antimicrobial substances were administered, and the respective indications for treatment. Our results showed that for several antimicrobials, between-country and within-country variations exist regarding the temporal distributions of treatments and indications for use. These differences were also true for several critically important antimicrobials, which is a matter of concern. Furthermore, differences between countries were also evident regarding the antimicrobial substances licensed. Based on our results, it is recommended to establish and promote treatment guidelines, invest in the prevention of diseases during critical moments of the production cycle and target undifferentiated use of antimicrobials. Moreover, discrepancies between countries should be further investigated to better understand the factors underlying the identified patterns and to distinguish prudent from non-prudent use. The results can inform decision-making with the aim to foster antimicrobial prudent use in the veterinary setting and, therefore, protect public health from the threat of antimicrobial resistance.

Risk Ranking of Antimicrobial-Resistant Hazards Found in Meat in Switzerland.

Human exposure to bacteria resistant to antimicrobials and transfer of related genes is a complex issue and occurs, among other pathways, via meat consumption. In a context of limited resources, the prioritization of risk management activities is essential. Since the antimicrobial resistance (AMR) situation differs substantially between countries, prioritization should be country specific. The objective of this study was to develop a systematic and transparent framework to rank combinations of bacteria species resistant to selected antimicrobial classes found in meat, based on the risk they represent for public health in Switzerland. A risk assessment model from slaughter to consumption was developed following the Codex Alimentarius guidelines for risk analysis of foodborne AMR. Using data from the Swiss AMR monitoring program, 208 combinations of animal species/bacteria/antimicrobial classes were identified as relevant hazards. Exposure assessment and hazard characterization scores were developed and combined using multicriteria decision analysis. The effect of changing weights of scores was explored with sensitivity analysis. Attributing equal weights to each score, poultry-associated combinations represented the highest risk. In particular, contamination with extended-spectrum ß-lactamase/plasmidic AmpC-producing Escherichia coli in poultry meat ranked high for both exposure and hazard characterization. Tetracycline- or macrolide-resistant Enterococcus spp., as well as fluoroquinolone- or macrolide-resistant Campylobacter jejuni, ranked among combinations with the highest risk. This study provides a basis for prioritizing future activities to mitigate the risk associated with foodborne AMR in Switzerland. A user-friendly version of the model was provided to risk managers; it can easily be adjusted to the constantly evolving knowledge on AMR.