Select agent regulations

In recent years, there has been an increase in research with biological agents, particularly those that pose a potential for use by terrorists. In this environment, laws have been enacted and regulations developed to ensure the appropriate use of specified "select agents and toxins" for legitimate research. Within this regulatory environment, it has been necessary for institutions and investigators to adapt to an entirely new set of requirements to begin or continue to work with these pathogens. Registration and approval for use of select agents and toxins, security and safety requirements, and daunting record-keeping requirements are only some of the regulatory challenges that researchers face in working with these agents. A brief overview of recent regulations is presented, as well as where to obtain additional information on regulations, standards, and guidelines related to work with select agents and toxins.     

Rodent quarantine programs: purpose, principles, and practice

In animal research, validity and reproducibility of data are critically influenced by the microbial status of the experimental animals. One of the most crucial aspects of assuring quality in animal research is providing research personnel with confidence that experimental results will not be invalidated due to interference caused by infectious disease. An effective quarantine program is essential to providing this assurance. Quarantine programs are generally instituted to prevent the introduction of rodent pathogens into established specific-pathogen-free colonies in a facility. Therefore, programs should be designed to isolate newly acquired rodents until their health status can be determined and to maximize the probability that microorganisms of interest will be detected before the animals are introduced into (and thus, could potentially contaminate) established colonies. Important principles that are critical to designing an effective quarantine program will be discussed here, as will the practical implementation of these principles. Although quarantine programs may be costly in terms of time and effort, these costs must be balanced against the potential costs of disease outbreaks that could invalidate long-term studies, alter normal biological baselines, and cause the loss or necessitate re-derivation of rare or valuable strains of rodents. Reducing the incidence of quarantine failures through appropriate program design and implementation helps to maintain the confidence of research personnel in the value of quarantine programs and in our competence as specialists in laboratory animal management and as partners in the research process.     

Lurking in the shadows: emerging rodent infectious diseases

Rodent parvoviruses, Helicobacter spp., murine norovirus, and several other previously unknown infectious agents have emerged in laboratory rodents relatively recently. These agents have been discovered serendipitously or through active investigation of atypical serology results, cell culture contamination, unexpected histopathology, or previously unrecognized clinical disease syndromes. The potential research impact of these agents is not fully known. Infected rodents have demonstrated immunomodulation, tumor suppression, clinical disease (particularly in immunodeficient rodents), and histopathology. Perturbations of organismal and cellular physiology also likely occur. These agents posed unique challenges to laboratory animal resource programs once discovered; it was necessary to develop specific diagnostic assays and an understanding of their epidemiology and transmission routes before attempting eradication, and then evaluate eradication methods for efficacy. Even then management approaches varied significantly, from apathy to total exclusion, and such inconsistency has hindered the sharing and transfer of rodents among institutions, particularly for genetically modified rodent models that may not be readily available. As additional infectious agents are discovered in laboratory rodents in coming years, much of what researchers have learned from experiences with the recently identified pathogens will be applicable. This article provides an overview of the discovery, detection, and research impact of infectious agents recently identified in laboratory rodents. We also discuss emerging syndromes for which there is a suspected infectious etiology, and the unique challenges of managing newly emerging infectious agents.     

Epidemiology and disease control in everyday beef practice

It is important for food animal veterinarians to understand the interaction among animals, pathogens, and the environment, in order to implement herd-specific biosecurity plans. Animal factors such as the number of immunologically protected individuals influence the number of individuals that a potential pathogen is able to infect, as well as the speed of spread through a population. Pathogens differ in their virulence and contagiousness. In addition, pathogens have various methods of transmission that impact how they interact with a host population. A cattle population's environment includes its housing type, animal density, air quality, and exposure to mud or dust and other health antagonists such as parasites and stress; these environmental factors influence the innate immunity of a herd by their impact on immunosuppression. In addition, a herd's environment also dictates the "animal flow" or contact and mixing patterns of potentially infectious and susceptible animals. Biosecurity is the attempt to keep infectious agents away from a herd, state, or country, and to control the spread of infectious agents within a herd. Infectious agents (bacteria, viruses, or parasites) alone are seldom able to cause disease in cattle without contributing factors from other infectious agents and/or the cattle's environment. Therefore to develop biosecurity plans for infectious disease in cattle, veterinarians must consider the pathogen, as well as environmental and animal factors.     

The Impact of the National Institute for Pharmaceutical Technology and Education on Academic Research

Surveys of institutional representatives of member institutions and faculty members engaged in the National Institute for Pharmaceutical Technology and Education (NIPTE) revealed that NIPTE is having a positive impact on academic research in the area of pharmaceutical technology by aligning research directions with FDA needs, by providing funding that may not be available elsewhere, and by creating a collegial and collaborative relationship among researchers in this area from various institutions. NIPTE is contributing to the viability of pharmaceutics and pharmaceutical engineering research in academic settings. Some responders cite the fluctuations in funding and relative low levels of funding received as a problem in maintaining programs, but most perceived a positive impact.     

Issues related to the use of animals in biocontainment research facilities

The expansion and improvement of high-containment animal facilities has been driven by terrorism, economics, the emergence of new pathogens, and the re-emergence of other pathogens in new areas. Working with highly infectious viral agents requires a team of trained scientists, laboratory technicians, veterinarians, animal care staff, biological safety officers, engineers, and physical plant staff to ensure safety, biocontainment, and the animals' well being, while providing essential scientific data. The challenges of working with infectious disease agents in high levels of containment, and some solutions to these challenges, are described from an animal care point of view.     

Emerging and Reemerging Infectious Diseases: Biocomplexity as an Interdisciplinary Paradigm

Understanding factors responsible for reemergence of diseases believed to have been controlled and outbreaks of previously unknown infectious diseases is one of the most difficult scientific problems facing society today. Significant knowledge gaps exist for even the most studied emerging infectious diseases. Coupled with failures in the response to the resurgence of infectious diseases, this lack of information is embedded in a simplistic view of pathogens and disconnected from a social and ecological context, and assumes a linear response of pathogens to environmental change. In fact, the natural reservoirs and transmission rates of most emerging infectious diseases primarily are affected by environmental factors, such as seasonality or meteorological events, typically producing nonlinear responses that are inherently unpredictable. A more realistic view of emerging infectious diseases requires a holistic perspective that incorporates social as well as physical, chemical, and biological dimensions of our planet’s systems. The notion of biocomplexity captures this depth and richness, and most importantly, the interactions of human and natural systems. This article provides a brief review and a synthesis of interdisciplinary approaches and insights employing the biocomplexity paradigm and offers a social–ecological approach for addressing and garnering an improved understanding of emerging infectious diseases. Drawing on findings from studies of cholera and other examples of emerging waterborne, zoonotic, and vectorborne diseases, a “blueprint” for the proposed interdisciplinary research framework is offered which integrates biological processes from the molecular level to that of communities and regional systems, incorporating public health infrastructure and climate aspects.     

Pathogenicity of biological control agents for livestock ectoparasites: a simulation analysis

The management of arthropod ectoparasites of livestock currently relies largely on the use of neurotoxic chemicals. However, concerns over the development of resistance, as well as operator and environmental contamination, have stimulated research into alternative approaches to their control, including the use of biological pathogens. The search for suitable pathogens often focuses on identifying the most highly virulent agents for application. However, practical issues such as the ability of a pathogen to penetrate to the skin through hair or wool, tolerance of high skin surface temperatures and high residual activity may mean that the most virulent pathogens are not necessarily the most appropriate for commercial application. Here, a simulation model is constructed and used to highlight a range of key features which characterize suitable pathogens for such application. Sensitivity analysis shows that even a relatively low probability of infection following contact between infectious and susceptible individuals may give acceptable control, providing it is counterbalanced by higher survival of both infected and infectious parasite hosts in order to allow the rate of transmission to exceed the threshold required to suppress parasite population growth. The model highlights the need for studies attempting to identify sustainable biocontrol agents to explore the use of pathogens which have a range of the characteristics that contribute to overall pathogenicity, but which are also most compatible with practical application systems.     

Plant-mediated interactions: Considerations for agent selection in weed biological control programs

Plant-mediated indirect interactions among herbivores (arthropods and pathogens) are common and extensively reported in the ecological literature. However, they are not well-documented with respect to weed biological control. Such interactions between biological control agents can have net positive or negative impacts on total weed suppression depending on the strength of the interaction(s), the relative importance of the agent indirectly impacted, and the combined weed suppression that results. A better understanding of plant-mediated interactions may improve decision-making about which agents to introduce in classical biological control programs for greatest impact on invasive weeds. This paper reviews the subject, including examples from the biological control literature; outlines the need for research on indirect effects of herbivores on other herbivores; discusses how such knowledge may strengthen classical biological control programs for invasive weeds; and provides recommendations for the kind of studies that should be done and how information about plant-mediated interactions could be integrated into agent evaluation protocols, to assist in decision-making about agents for importation and release.     

Recommendations for control of pathogens and infectious diseases in fish research facilities

Concerns about infectious diseases in fish used for research have risen along with the dramatic increase in the use of fish as models in biomedical research. In addition to acute diseases causing severe morbidity and mortality, underlying chronic conditions that cause low-grade or subclinical infections may confound research results. Here we present recommendations and strategies to avoid or minimize the impacts of infectious agents in fishes maintained in the research setting. There are distinct differences in strategies for control of pathogens in fish used for research compared to fishes reared as pets or in aquaculture. Also, much can be learned from strategies and protocols for control of diseases in rodents used in research, but there are differences. This is due, in part, the unique aquatic environment that is modified by the source and quality of the water provided and the design of facilities. The process of control of pathogens and infectious diseases in fish research facilities is relatively new, and will be an evolving process over time. Nevertheless, the goal of documenting, detecting, and excluding pathogens in fish is just as important as in mammalian research models.     

The biological threat to U.S. water supplies: Toward a national water security policy

In addition to providing potable drinking water, U.S. water systems are critical to the maintenance of many vital public services, such as fire suppression and power generation. Disruption of these systems would produce severe public health and safety risks, as well as considerable economic losses. Thus, water systems have been designated as critical to national security by the U.S. government. Previous outbreaks of waterborne disease have demonstrated the vulnerability of both the water supply and the public's health to biological contamination of drinking water. Such experiences suggest that a biological attack, or even a credible threat of an attack, on water infrastructure could seriously jeopardize the public's health, its confidence, and the economic vitality of a community. Despite these recognized vulnerabilities, protecting water supplies from a deliberate biological attack has not been sufficiently addressed. Action in this area has suffered from a lack of scientific understanding of the true vulnerability of water supplies to intentional contamination with bioweapons, insufficient tools for detecting biological agents, and a lack of funds to implement security improvements. Much of what is needed to address the vulnerability of the national water supply falls outside the influence of individual utilities. This includes developing a national research agenda to appropriately identify and characterize waterborne threats and making funds available to implement security improvements.     

Occupational medicine programs for animal research facilities

Occupational medicine is a key component of a comprehensive occupational health and safety program in support of laboratory animal research and production facilities. The mission of the department is to maximize employee health and productivity utilizing a population health management approach, which includes measurement and analysis of health benefits utilization. The department works in close cooperation with other institutional health and safety professionals to identify potential risks from exposure to physical, chemical, and biological hazards in the workplace. As soon as exposures are identified, the department is responsible for formulating and providing appropriate medical surveillance programs. Occupational medicine is also responsible for targeted delivery of preventive and wellness services; management of injury, disease, and disability; maintenance of medical information; and other clinic services required by the institution. Recommendations are provided for the organization and content of occupational medicine programs for animal research facilities.     

The science,art and business of successful bioherbicides

In this article, the critical issues in the production of successful bioherbicides have been defined in an effort to stimulate discussion on the underlying science, art of formulation and fermentation and the business of producing and marketing of bioherbicides. To a large extent the science of bioherbicides has focussed on epidemiology, although the enormous potential of molecular technology to improve the efficacy of these agents is being investigated. Some of this potential is coming to fruition in terms of development of tools for the identification and tracking of biological controls, although the genetic modification of biological control agents is still in its infancy. On the other hand, knowledge in the areas of formulation and fermentation is often proprietary in nature. This makes it critical for researchers to work in collaboration with other researchers or industry in these areas. The importance of the appropriate involvement of industry and commercialization partners early in the development process should not be underestimated. Although ad hoc research into biological control should not be discouraged, researchers should be encouraged to think carefully before they postulate on the potential of a bioherbicide based purely on preliminary isolation and pathogenicity testing. As much of the research is specific to a single pathogen/host system, the way ahead in bioherbicide research would appear to be the development of consortia or research nodes in which scientists and business people with backgrounds in the discovery, development and commercialization of biopesticides work collaboratively on a number of projects. There has been movement towards this type of model in countries such as Canada, USA and New Zealand although other countries lag behind. Interestingly, all five of the recently registered bioherbicides in the U.S. and Canada were developed and registered by small-business enterprises or a subsidiary of enterprises with no prior record in pesticide development.The constraints to bioherbicides are not in the science, art or business: it is in bringing all of these aspects together in an accessible way and the sharing of intellectual property in an equitable fashion. A new model for the commercialization of bioherbicides should build on currently established research networks, but need to have a stronger link to industry (especially small–medium enterprises) and requires funding for infrastructure and personnel. This funding needs to come from the public sector. Industry is interested in engaging this type of research, but they need to be reassured that the approach is feasible, economic and realistic and that the resources required are available.     

Risk Assessment of Potential Bio-Terrorism Agents for Laboratory Workers

In the wake of recent national and global events, biological weapons have become an increasingly urgent issue. Preparedness and defense are now the topic of numerous conferences and funding opportunities. Due to this increasing activity researchers must now focus more intently on their own safety and security. Bio-safety measures are analyzed by means of risk assessments. In this paper we will explore qualitative risk assessments and the risks associated with six specific pathogens and toxins that are potential bio-terrorism agents: Bacillus anthracis, Yersinia pestis, Francisella tularemia, Smallpox virus, and the two toxins, ricin and botulinum.     

Pathogen survival in the external environment and the evolution of virulence

Recent studies have provided evolutionary explanations for much of the variation in mortality among human infectious diseases. One gap in this knowledge concerns respiratory tract pathogens transmitted from person to person by direct contact or through environmental contamination. The sit-and-wait hypothesis predicts that virulence should be positively correlated with durability in the external environment because high durability reduces the dependence of transmission on host mobility. Reviewing the epidemiological and medical literature, we confirm this prediction for respiratory tract pathogens of humans. Our results clearly distinguish a high-virulence high-survival group of variola (smallpox) virus, Mycobacterium tuberculosis, Cornynebacterium diphtheriae, Bordetella pertussis, Streptococcus pneumoniae, and influenza virus (where all pathogens have a mean percent mortality > or = 0.01% and mean survival time >10 days) from a low-virulence low-survival group containing ten other pathogens. The correlation between virulence and durability explains three to four times of magnitude of difference in mean percent mortality and mean survival time, using both across-species and phylogenetically controlled analyses. Our findings bear on several areas of active research and public health policy: (1) many pathogens used in the biological control of insects are potential sit-and-wait pathogens as they combine three attributes that are advantageous for pest control: high virulence, long durability after application, and host specificity; (2) emerging pathogens such as the 'hospital superbug' methicillin-resistant Staphylococcus aureus (MRSA) and potential bioweapons pathogens such as smallpox virus and anthrax that are particularly dangerous can be discerned by quantifying their durability; (3) hospital settings and the AIDS pandemic may provide footholds for emerging sit-and-wait pathogens; and (4) studies on food-borne and insect pathogens point to future research considering the potential evolutionary trade-offs and genetic linkages between virulence and durability.     

An evaluation of the status of living collections for plant,environmental, and microbial research

While living collections are critical for biological research, support for these foundational infrastructure elements is inconsistent, which makes quality control, regulatory compliance, and reproducibility difficult. In recent years, the Ecological Society of America has hosted several National Science Foundation–sponsored workshops to explore and enhance the sustainability of biological research infrastructure. At the same time, the United States Culture Collection Network has brought together managers of living collections to foster collaboration and information exchange within a specific living collections community. To assess the sustainability of collections, a survey was distributed to collection scientists whose responses provide a benchmark for evaluating the resiliency of these collections. Among the key observations were that plant collections have larger staffing requirements and that living microbe collections were the most vulnerable to retirements or other disruptions. Many higher plant and vertebrate collections have institutional support and several have endowments. Other collections depend on competitive grant support in an era of intense competition for these resources. Opportunities for synergy among living collections depend upon complementing the natural strong engagement with the research communities that depend on these collections with enhanced information sharing, communication, and collective action to keep them sustainable for the future. External efforts by funding agencies and publishers could reinforce the advantages of having professional management of research resources across every discipline.     

基于荧光检测的新型细胞传感器

主要介绍了一类基于荧光检测的新型细胞传感器,这类传感器利用免疫细胞表面分子特异性识别、结合抗原的特性和生物(或化学)发光技术,通过检测荧光信号在数分钟内达到检测病原体或其他抗原的目的.这类传感器的发光原理主要是利用钙离子敏感型化学荧光探针发光,如Fluo-4等,或钙离子敏感型发光蛋白发光,如水母发光蛋白、绿色荧光蛋白等.现在已经应用的主要是B细胞传感器和肥大细胞传感器.这类传感器具有灵敏度高、检测准确、反应速度快的优点.同时又存在交叉反应、细胞不易保存等不足之处.这类传感器在疾病诊断、环境监测、生物战剂检测等领域具有较大的应用前景.     

Chemo-biological suppression of root-infecting zoosporic pathogens in recirculating hydroponic systems

Zoosporic root-infecting pathogens are the most destructive organisms in enclosed environment agricultural systems which recycle irrigation water. Numerous strategies have been proposed for reducing or eliminating these pathogens from recycled irrigation water. These strategies include the following: filtration, sedimentation, chlorination, ozonation, heat, ultraviolet light, application of antimicrobial chemicals, suppressive potting substrates, and biological control agents. The latter strategy has been the focus of numerous investigations but consistency in performance in disease abatement following their application has not been realized. This has been attributed, in part, to the inability of these potential biocontrol bacteria to maintain a critical threshold population necessary for sustained biocontrol activity. That threshold population has been estimated at not less than 10⁶ CFU g^?1 of soil or root. Recently, we demonstrated that amending recycled irrigation water with specific carbon substrates (i.e., N-Serve® or Truban®) resulted in the selective enhancement of the indigenous fluorescent pseudomonad populations to levels at or above the presumed threshold levels necessary for disease control. In our current study, we verified the ubiquity of that response in different cultural systems involving two different host plants (i.e., cucumber and pepper) and, most significantly, we document, for the first time, significant and sustained disease abatement. Additionally, we demonstrated that nitrapyrin, the active ingredients in N-Serve® and Truban®, exerted direct antifungal activity whereas the inert ingredients had an indirect role in disease suppression. Specifically, the inert ingredients were responsible for the increase in the fluorescent pseudomonad population. Amending the recirculating nutrient solution with a representative fluorescent pseudomonad isolate verified and substantiated their role in disease control. Cumulatively, our results support the hypothesis that it is possible to modify the environment to make it more conducive to the multiplication and survival of indigenous biocontrol bacteria. The resident microflora in many, if not most, habitats already contain prospective biological control members who, if enhanced, could function as antagonists to other microorganisms in the same habitat.     

Programs for invasive research in North American zoos and aquariums

Zoo-based research in North America is an emerging field, which has progressed from an ad hoc approach in a small number of zoos to a coordinated, integrated network of scientists with recognized research programs in approximately one half of the accredited institutions in North America. The disciplines most active in these programs--veterinary medicine and pathology, nutrition, reproductive biology, contraception, and behavior--are now becoming coordinated in zoos through Scientific Advisory Groups. Zoos with research programs generally establish either an institutional animal care and use committee or another committee to evaluate research proposals. In addition to scientific merit and experimental design, zoos evaluate proposals based on factors such as priority by conservation program/identified need; direct effect on species conservation, species type, and appropriateness; availability and location of animals; operational requirements/logistics; communication between institutions; and available funding. Euthanasia is considered only in rare circumstances. Zoo-based research has evolved into an integral component in animal management and conservation programs by providing practical information that is used to improve animal care, well-being, health, and reproduction. However, the degree to which zoos participate in invasive research varies considerably among institutions, due not only to resource limitations but also to how the term "invasive" is defined and accepted at each institution. A more standardized approach among zoological institutions for examining and approving research projects that are supported by zoo-based conservation programs would greatly facilitate the wildlife research efforts of North American zoos.     

基于禽流感发生风险的生态安全评价研究进展

禽流感是危害公共健康、社会经济和政治稳定重要的传染性疾病。近年来,禽流感引发的区域生态安全(公共卫生安全和生物安全)问题日益受到学界关注。为此,有必要从禽流感发生风险的角度来开展区域生态安全评价。根据1996—2017年发表的禽流感发生风险与生态安全评价英文文献,运用Citespace软件综合分析了禽流感与生态安全评价的最新研究进展。在阐述禽流感发生风险与生态安全评价关系基础上,结合生态安全评价理论框架,从数据来源、适用范围、优缺点等方面分别对禽流感发生风险评估方法以及基于禽流感发生风险的生态安全评价方法进行对比与总结。综述表明:禽流感发生风险对生物物种安全和公共卫生安全的威胁已经严重影响到区域生态安全,其引发的公共卫生危机和生物多样性减少是生态安全评价研究的重要内容,从禽流感发生风险视角评价区域生态安全具有其必要性和紧迫性,并迫切需要加强相关模型方法及其应用研究。目前,禽流感研究主要以病毒学、流行病学为主,与生态安全领域结合研究较为缺乏,在生态安全评价中有关禽流感发生风险内容的研究基本被忽视。既可为深入揭示禽流感发生与传播的动力学机制与防控和监测禽流感提供科学依据,亦可为未来开展基于禽流感发生风险的区域生态安全评价研究提供方法借鉴。