Regulatory issues surrounding the use of companion animals in clinical investigations,trials, and studies

Laboratory animal veterinarians sometimes encounter animals with rare conditions and may subsequently become involved in the performance of related animal research outside the laboratory, in homes, in veterinary clinics, or in universities to which owners have donated their animals for study. Similarly, veterinarians may monitor animal companion vaccination studies, performed to optimize preventive health care or minimize physiological variability and research confounders associated with a preventive medicine program for dogs and cats utilized for research procedures. These nontraditional uses of dogs, cats, and other companion animals in research have spurred the establishment of regulations to ensure that the animals benefit from clinical veterinary products and techniques. Included and described are the 2002 Public Health Service Policy, the Animal Welfare Act (AWA), the Federal Food, Drug, and Cosmetic Act, and the regulations of the US Department of Agriculture in response to the AWA. The complexities of clinical research with companion animals outside standard biomedical research facilities are discussed.     

Antimicrobial resistance of zoonotic bacteria: current strategies in veterinary medicine

In the European Union, antimicrobials are administered to animals as veterinary drugs. Monitoring of antimicrobial resistance of zoonotic and indicator bacteria were implemented at the European level during the last decade. This methodology can be applied for emerging bacteria observed at a national level to provide data for a risk characterization towards a risk analysis. Tools for monitoring antimicrobial use in veterinary medicine are developed and need to be harmonized at the European level. Development of antimicrobial resistance for veterinary pathogens must be managed to maintain their efficacy in animal health. Engagement of veterinarians and professionals of animal production is on going to preserve efficacy of antimicrobials in human and animal medicine.     

Regulatory initiatives for natural latex allergy: US perspectives

The US Food and Drug Administration (FDA) has regulatory authority over foods, human drugs, cosmetics, medical devices, radiological products, biologics, and veterinary products. Among these products, FDA believes that the use of medical devices, including medical gloves, condoms, catheters, and breathing bags, represents the greatest source of natural latex proteins to exposed individuals. A medical device is defined in the Federal Food Drug and Cosmetic Act (FFDCA) as an instrument, apparatus, implement, machine, etc., that is intended for use in the diagnosis or treatment of disease or is intended to affect the structure or any function of the body of a human or other animal, and that does not achieve any of its principal intended purposes through chemical action in the body. This article provides some brief, general background about FDA's medical device regulatory process and then addresses the issue of natural latex allergy. Finally we discuss the steps the Agency has taken to evaluate the magnitude and nature of the problem, and FDA's efforts to assist manufacturers, health professionals, and others in minimizing exposure and sensitization to natural latex proteins in medical devices.     

The US national antimicrobial resistance monitoring system.

The use of antimicrobial agents in food animals can select for resistant bacterial pathogens that may be transmitted to humans via the commercial meat supply. In the USA, the FDA's Center for Veterinary Medicine regulatory duties require a determination that antimicrobial drugs are safe and effective for use in food animals. In addition, a qualitative assessment of risks to human health from antimicrobial resistance requires development. This risk assessment process is supported by data generated by the FDA's National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria. NARMS data on antimicrobial susceptibility among Salmonella, Campylobacter, Escherichia coli and Enterococcus is collected. Research activities defining the genetic bases of resistance helps to understand the potential public health risks posed by the spread of antimicrobial resistance from food animal antimicrobial use. These activities help insure that antimicrobials are used judiciously to promote human and animal health.     

Determination of Sample Sizes for Demonstrating Efficacy of Radiation Countermeasures

Summary .  In response to the ever increasing threat of radiological and nuclear terrorism, active development of nontoxic new drugs and other countermeasures to protect against and/or mitigate adverse health effects of radiation is ongoing. Although the classical LD₅₀ study used for many decades as a first step in preclinical toxicity testing of new drugs has been largely replaced by experiments that use fewer animals, the need to evaluate the radioprotective efficacy of new drugs necessitates the conduct of traditional LD₅₀ comparative studies ( FDA, 2002 ,  Federal Register   67, 37988–37998). There is, however, no readily available method to determine the number of animals needed for establishing efficacy in these comparative potency studies. This article presents a sample-size formula based on Student's  t  for comparative potency testing. It is motivated by the U.S. Food and Drug Administration's (FDA's) requirements for robust efficacy data in the testing of response modifiers in total body irradiation experiments where human studies are not ethical or feasible. Monte Carlo simulation demonstrated the formula's performance for Student's  t , Wald, and likelihood ratio tests in both logistic and probit models. Importantly, the results showed clear potential for justifying the use of substantially fewer animals than are customarily used in these studies. The present article may thus initiate a dialogue among researchers who use animals for radioprotection survival studies, institutional animal care and use committees, and drug regulatory bodies to reach a consensus on the number of animals needed to achieve statistically robust results for demonstrating efficacy of radioprotective drugs.     

Genetic counseling in the era of molecular diagnostics

Veterinarians with an interest in theriogenology will often be asked by small animal clients for advice concerning hereditary diseases in their breeds. Many new DNA-based tests for analysis of genetic diseases and traits (e.g. coat color) are now available for use by both breeders and veterinarians. With appropriate interpretation, these tests can be invaluable tools in a breeding program. For example, they can be used to produce animals free of specific diseases, to quickly eliminate a disease from an entire breed, or to select for specific traits in breeding stock. Selection strategies that do not take into account maintaining genetic diversity of the breed may be detrimental and reduce the potential for future improvement.     

Data warehouse for assessing animal health,welfare, risk management and –communication

The objective of this paper is to give an overview of existing databases in Denmark and describe some of the most important of these in relation to establishment of the Danish Veterinary and Food Administrations’ veterinary data warehouse. The purpose of the data warehouse and possible use of the data are described. Finally, sharing of data and validity of data is discussed. There are databases in other countries describing animal husbandry and veterinary antimicrobial consumption, but Denmark will be the first country relating all data concerning animal husbandry, -health and -welfare in Danish production animals to each other in a data warehouse. Moreover, creating access to these data for researchers and authorities will hopefully result in easier and more substantial risk based control, risk management and risk communication by the authorities and access to data for researchers for epidemiological studies in animal health and welfare.     

Agricultural (nonbiomedical) animal research outside the laboratory: a review of guidelines for institutional animal care and use committees

Challenges and published guidelines associated with appropriate care and use of farm animals in agricultural research conducted outside the laboratory are briefly reviewed. The Animal Welfare Act (Title 9 of the 2000 Code of Federal Regulations), which regulates the care and use of agricultural animals in biomedical research, does not include livestock and poultry used in agricultural research. Farm animal research funded (and thereby regulated) by the US Public Health Service is further discussed in the National Research Council's 1996 Guide for the Care and Use of Laboratory Animals. However, neither of these guidelines adequately addresses the unique attributes of research and teaching designed to improve production agriculture. That information is contained in the Guide for the Care and Use of Agricultural Animals in Agricultural Research and Teaching (the Ag Guide), published by the Federation of Animal Science Societies in 1999. The Ag Guide provides excellent general recommendations for agricultural animal research. It serves as an invaluable resource for institutional animal care and use committees, which attempt to balance the welfare of farm animals and the needs of those working to improve animal agriculture.     

Invasive animals and wildlife pathogens in the United States: the economic case for more risk assessments and regulation

The United States faces numerous invasions by non-native animal species and wildlife pathogens that pose high risks to the economy, the environment, human health and wildlife health. Nevertheless, the Federal government spends less than $500,000 annually on preventing harmful animal invasions in its “injurious species” listing program under the Lacey Act, which can prohibit imports and interstate commerce in designated taxa. This program is ineffective; numerous costly invasions by intentionally-imported animals have occurred despite the Lacey Act. Additionally, the majority of emerging zoonotic diseases worldwide originate in wildlife and the role the wildlife trade plays in disease emergence is increasing over time. Recent findings demonstrate that conducting risk assessments for the wildlife trade is relatively inexpensive and they can provide net economic benefits for the nation. However, in order to accrue those benefits, dramatic policy improvements are needed centered around developing and funding a proactive, rapid, Federal risk assessment program.     

Human-Directed Empathy and Attitudes Toward Animal Use: A Survey of Spanish Veterinary Students

Veterinary practitioners are thought of as guardians of animal health and wellbeing, and are considered important in the development of policies on animals. Measuring veterinary students’ attitudes toward animals and animal use is needed when assessing the effectiveness of education programs focused on animal welfare and ethics. The present study examined Spanish veterinary students’ attitudes toward different types of animal use, their human-directed empathy, and the relationship between these and various personal variables. The sample comprised 200 students who completed an online questionnaire. Attitudes toward animal use varied significantly, depending on the type of use in question. There was also a relationship between attitudes toward animal use, one component of human-directed empathy, “Empathic Concern,” and a number of personal variables such as gender, career choice, and contact with animal welfare organizations. Concern about the use of animals for research and animal management was lower in students who were in the later years of their studies. Reasons for this and the role of veterinary education are discussed.     

Vitamin A--a pregnancy hazard alert.

Vitamin A is essential to human health, but concerns have arisen recently regarding its potential teratogenicity. Human and animal birth defects have been associated with the use of the vitamin A analogue, isotretinoin, or Accutane, for acne treatment, although the association of such defects with vitamin A itself is unclear. The federal Food and Drug Administration is evaluating the health issues surrounding vitamin A and, together with the manufacturer, has developed restrictions and label warnings to ensure the appropriate use of Accutane. We also have evaluated these issues, with concerns about the possible teratogenicity of high vitamin A intake during pregnancy. Practitioners should be familiar with the possible hazard of excessive dosages of vitamin A and its analogues. Vitamin A daily doses of higher than 8,000 IU for pregnant woman are not necessary for good health and are not recommended. Foods high in beta-carotene can provide the necessary amounts of vitamin A and, in contrast to the synthetic analogues, their use has not been associated with vitamin A toxicity or teratogenicity in humans or animals.     

Cross-cultural Comparison of Medicinal Plants Used to Treat Infections in Northern Thailand

Economic Botany - Drug resistance in pathogenic microorganisms threatens both human and animal health. This has prompted the search for new antimicrobial drugs, including the ones from...     

Fluoroquinolone resistance of Escherichia coli and Salmonella from healthy livestock and poultry in the EU

The potential for transmission of antibiotic-resistant enteric zoonotic bacteria from animals to humans has been a public health concern for several decades. Bacteria carrying antibiotic resistance genes found in the intestinal tract of food animals can contaminate carcasses and may lead to food-borne disease in humans that may not respond to antibiotic treatment. It is consequently important to monitor changes in antimicrobial susceptibility of zoonotic and commensal organism; in this context, there are a number of veterinary monitoring programmes that collect bacteria in food-producing animals at slaughter and determine their susceptibility against antibiotics relevant for human medicine. The data generated are part of the risk analysis for potential food-borne transmission of resistance. There has been much debate about the use of fluoroquinolones in veterinary medicine, and so, this review will consider the fluoroquinolone data from two surveys and compare them to national surveillance programmes. At the outset, it must be pointed out that there is, however, a lack of agreement between several programmes on what is meant by the term 'fluoroquinolone resistance' through use of different definitions of resistance and different resistance breakpoints. An additional aim of this paper is to clarify some of those definitions. Despite the debate about the contribution of antibiotic use in veterinary medicine to the overall resistance development in human pathogens, the data suggest that clinical resistance to fluoroquinolones in Escherichia coli and nontyphoidal Salmonella is generally uncommon, except for a few countries. Ongoing surveillance will continue to monitor the situation and identify whether this situation changes within the respective animal populations. For the benefit of both the epidemiologist and the clinician, it would be strongly advantageous that national monitoring surveys report both percentages of clinical resistance and decreased susceptibility.     

Movement Behaviour of Traditionally Managed Cattle in the Eastern Province of Zambia Captured Using Two-Dimensional Motion Sensors

Two-dimensional motion sensors use electronic accelerometers to record the lying, standing and walking activity of cattle. Movement behaviour data collected automatically using these sensors over prolonged periods of time could be of use to stakeholders making management and disease control decisions in rural sub-Saharan Africa leading to potential improvements in animal health and production. Motion sensors were used in this study with the aim of monitoring and quantifying the movement behaviour of traditionally managed Angoni cattle in Petauke District in the Eastern Province of Zambia. This study was designed to assess whether motion sensors were suitable for use on traditionally managed cattle in two veterinary camps in Petauke District in the Eastern Province of Zambia. In each veterinary camp, twenty cattle were selected for study. Each animal had a motion sensor placed on its hind leg to continuously measure and record its movement behaviour over a two week period. Analysing the sensor data using principal components analysis (PCA) revealed that the majority of variability in behaviour among studied cattle could be attributed to their behaviour at night and in the morning. The behaviour at night was markedly different between veterinary camps; while differences in the morning appeared to reflect varying behaviour across all animals. The study results validate the use of such motion sensors in the chosen setting and highlight the importance of appropriate data summarisation techniques to adequately describe and compare animal movement behaviours if association to other factors, such as location, breed or health status are to be assessed.     

Health management with reduced antibiotic use - the U.S. experience

Since World War II the use of antimicrobial products associated with food animal production has increased. Antimicrobials along with evolving production practices have significantly increased throughput, animal welfare, and improved health. Concerns surrounding the growing significance of emerging and in some cases rapidly disseminating antibiotic (antimicrobial) resistant bacterial pathogens among human and livestock populations has stimulated a reassessment of this application. The negative publicity has led many consumers and activist groups to believe that protein derived from food animals grown in the absence of those drugs is safer than products derived from the conventionally reared. There is a general fear that antimicrobial usage in agriculture threatens the sustainability of human therapeutic agents and the public wellbeing. The issue has gradually emerged from "fringe group paranoia" to mainstream - finally impacting consumer choices. Antimicrobial resistance concerns have stimulated a significant reaction by the US animal agriculture industry. Numerous pig production entities, large and small, have attempted to create additional pork product value by developing niche marketing opportunities. Thus far most of the subtherapeutic in-feed antimicrobial reduction has been voluntary in the US. Two production areas have developed where reduced usage occurs. First is the growth of antibiotic free production (ABF) and second is an increased use of treatment levels which avoids subtherapeutic criticism. The bulk of this article is directed at new production practices, pig health management, disease elimination, and biosecurity efforts that result from early industry attempts at reduced or excluded antimicrobial pig production. Raising antimicrobial (antibiotic) free (ABF) pork from birth is challenging for a variety of reasons. Some of these challenges can be cost effectively dealt with while others are difficult if not impossible to control in modern production environments. Healthy pig production is essential for sustainable ABF operations.     

Health Management with Reduced Antibiotic Use—The U.S. Experience

Since World War II the use of antimicrobial products associated with food animal production has increased. Antimicrobials along with evolving production practices have significantly increased throughput, animal welfare, and improved health. Concerns surrounding the growing significance of emerging and in some cases rapidly disseminating antibiotic (antimicrobial) resistant bacterial pathogens among human and livestock populations has stimulated a reassessment of this application. The negative publicity has led many consumers and activist groups to believe that protein derived from food animals grown in the absence of those drugs is safer than products derived from the conventionally reared. There is a general fear that antimicrobial usage in agriculture threatens the sustainability of human therapeutic agents and the public wellbeing. The issue has gradually emerged from “fringe group paranoia” to mainstream—finally impacting consumer choices.

Antimicrobial resistance concerns have stimulated a significant reaction by the US animal agriculture industry. Numerous pig production entities, large and small, have attempted to create additional pork product value by developing niche marketing opportunities. Thus far most of the subtherapeutic in-feed antimicrobial reduction has been voluntary in the US. Two production areas have developed where reduced usage occurs. First is the growth of antibiotic free production (ABF) and second is an increased use of treatment levels which avoids subtherapeutic criticism. The bulk of this article is directed at new production practices, pig health management, disease elimination, and biosecurity efforts that result from early industry attempts at reduced or excluded antimicrobial pig production. Raising antimicrobial (antibiotic) free (ABF) pork from birth is challenging for a variety of reasons. Some of these challenges can be cost effectively dealt with while others are difficult if not impossible to control in modern production environments. Healthy pig production is essential for sustainable ABF operations.     

Genetics of Antimicrobial Resistance

Antimicrobial resistant strains of bacteria are an increasing threat to animal and human health. Resistance mechanisms to circumvent the toxic action of antimicrobials have been identified and described for all known antimicrobials currently available for clinical use in human and veterinary medicine. Acquired bacterial antibiotic resistance can result from the mutation of normal cellular genes, the acquisition of foreign resistance genes, or a combination of these two mechanisms. The most common resistance mechanisms employed by bacteria include enzymatic degradation or alteration of the antimicrobial, mutation in the antimicrobial target site, decreased cell wall permeability to antimicrobials, and active efflux of the antimicrobial across the cell membrane. The spread of mobile genetic elements such as plasmids, transposons, and integrons has greatly contributed to the rapid dissemination of antimicrobial resistance among several bacterial genera of human and veterinary importance. Antimicrobial resistance genes have been shown to accumulate on mobile elements, leading to a situation where multidrug resistance phenotypes can be transferred to a susceptible recipient via a single genetic event. The increasing prevalence of antimicrobial resistant bacterial pathogens has severe implications for the future treatment and prevention of infectious diseases in both animals and humans. The versatility with which bacteria adapt to their environment and exchange DNA between different genera highlights the need to implement effective antimicrobial stewardship and infection control programs in both human and veterinary medicine.     

Genetics of antimicrobial resistance

Antimicrobial resistant strains of bacteria are an increasing threat to animal and human health. Resistance mechanisms to circumvent the toxic action of antimicrobials have been identified and described for all known antimicrobials currently available for clinical use in human and veterinary medicine. Acquired bacterial antibiotic resistance can result from the mutation of normal cellular genes, the acquisition of foreign resistance genes, or a combination of these two mechanisms. The most common resistance mechanisms employed by bacteria include enzymatic degradation or alteration of the antimicrobial, mutation in the antimicrobial target site, decreased cell wall permeability to antimicrobials, and active efflux of the antimicrobial across the cell membrane. The spread of mobile genetic elements such as plasmids, transposons, and integrons has greatly contributed to the rapid dissemination of antimicrobial resistance among several bacterial genera of human and veterinary importance. Antimicrobial resistance genes have been shown to accumulate on mobile elements, leading to a situation where multidrug resistance phenotypes can be transferred to a susceptible recipient via a single genetic event. The increasing prevalence of antimicrobial resistant bacterial pathogens has severe implications for the future treatment and prevention of infectious diseases in both animals and humans. The versatility with which bacteria adapt to their environment and exchange DNA between different genera highlights the need to implement effective antimicrobial stewardship and infection control programs in both human and veterinary medicine.     

The withdrawal of antimicrobial treatment as a mechanism for defeating resistant microorganisms

Antimicrobial resistance is a major concern in health care and farming settings throughout the world. The level of antimicrobial resistance continues to increase and the requirement for a novel and possibly dramatic change in therapy choices is required. One possible mechanism for overcoming resistance is the actual removal of antimicrobial treatment from the therapeutic armoury. This review examines the potential for success of a policy advocating the reduction of antimicrobial use and additionally the withdrawal of such treatments. Evidence from agriculture suggests that the removal of certain drugs from animal husbandry can result in concomitant falls in certain drug resistances in human patients.     

Research with animals: requirement, responsibility, welfare

Recognition of unacceptable cruelty to animals in pasttimes such as bull-baiting, dates in Britain from the early 19th century. The Society for the Prevention of Cruelty to Animals was founded in 1824. Several bills to curb cruelty were discussed in Parliament, and the Cruel and Improper Treatment of Cattle Act was passed in 1822. Other Acts have followed over the years. Cruelty in the form of painful scientific experiments, including dissection of living, conscious animals, vivisection, was proscribed by the Cruelty to Animals Act 1876. That Act required anyone wishing to experiment with animals to obtain a licence from the Secretary of State. Conditions for issue of licences were strict and remain so to this day. The Act is still valid, and is enforced by the Home Office, with its medical and veterinary Inspectors. The Cruelty to Animals Act 1876 allows experiments on animals under strictly controlled conditions. Experiments must have the clear objective of improving the welfare of man and/or animals. Benefits from experiments carried out under the Act have been enormous, covering every aspect of diagnosis, treatment, and prophylaxis in human and veterinary medicine. Coincidentally, the welfare of laboratory animals has also been greatly improved. There has always been some opposition to the use of animals in biomedical research. The subject is emotive but, by and large, discussion has been rational and within the law. In recent years, however, the morality of using experimental animals has been examined more closely. The possibility of replacing them by alternative methods has been investigated. Where these alternatives are applicable, they are used and further research on them continues. The questioning of animal experiments has emphasized the need to look constantly at animal welfare to ensure humane treatment of all animals, especially those restricted in a laboratory or on a farm. Attention has been drawn in this work to our existing laws protecting animals, but new legislation is being demanded, not only by some lay welfare groups but also by scientists. Hence, it has become very important to discuss various ways of ensuring animal welfare, including by legislation, especially with those knowledgeable in laboratory animal science and animal experiments.(ABSTRACT TRUNCATED AT 400 WORDS)