Institutional Oversight of Occupational Health and Safety for Research Programs Involving Biohazards
Research with hazardous biologic materials (biohazards) is essential to the progress of medicine and science. The field of microbiology has rapidly advanced over the years, partially due to the development of new scientific methods such as recombinant DNA technology, synthetic biology,
viral vectors, and the use of genetically modified animals. This research poses a potential risk to personnel as well as the public and the environment. Institutions must have appropriate oversight and take appropriate steps to mitigate the risks of working with these biologic hazards. This
article will review responsibilities for institutional oversight of occupational health and safety for research involving biologic hazards.
The occupational health and safety program is an integral component of a comprehensive animal care and use program. It is important to mitigate the risk of exposures of animal care and research personnel to allergens and physical, chemical, radiologic, and biologic hazards during the
conduct of various tasks. This need is especially true in infectious disease and biocontainment research. One aspect of the program is the provision of personal protective equipment (PPE). Commercially available PPE should be carefully evaluated based on their material composition and performance
according to manufacturer data. To help institutions and end users by providing them guidance on choosing appropriate PPE, we here discuss the regulatory framework, device standards, and materials engineering for various PPE, including gloves, shoe covers, head caps, gowns, aprons, masks,
hearing and eye protection devices, and respirators. Ultimately, the choice of appropriate PPE is based on the risk assessment, which should include consideration for personnel comfort, correct device fitting, and the containment level for the hazard used.
Viral vector research presents unique occupational health and safety challenges to institutions due to the rapid development of both in vivo and in vitro gene-editing technologies. Risks to human and animal health make it incumbent on institutions to appropriately evaluate viral vector
usage in research on the basis of available information and governmental regulations and guidelines. Here we review the factors related to risk assessment regarding viral vector usage in animals and the relevant regulatory documents associated with this research, and we highlight the most
commonly used viral vectors in research today. This review is particularly focused on the background, use in research and associated health and environmental risks related to adenoviral, adeno-associated viral, lentiviral, and herpesviral vectors.
Animal models are vital in understanding the transmission and pathogenesis of infectious organisms and the host immune response to infection. In addition, animal models are essential in vaccine and therapeutic drug development and testing. Prior to selecting an animal model to use when
studying an infectious agent, the scientific team must determine that sufficient in vitro and ex vivo data are available to justify performing research in an animal model, that ethical considerations are addressed, and that the data generated from animal work will add useful information to
the body of scientific knowledge. Once it is established that an animal should be used, the questions become 'Which animal model is most suitable?' and 'Which experimental design issues should be considered?' The answers to these questions take into account numerous factors, including scientific, practical, welfare, and regulatory considerations, which are the focus of this article.
Arthropod-borne viruses (arboviruses) have continued to emerge in recent years, posing a significant health threat to millions of people worldwide. The majority of arboviruses that are pathogenic to humans are transmitted by mosquitoes and ticks, but other types of arthropod vectors
can also be involved in the transmission of these viruses. To alleviate the health burdens associated with arbovirus infections, it is necessary to focus today's research on disease control and therapeutic strategies. Animal models for arboviruses are valuable experimental tools that can shed
light on the pathophysiology of infection and will enable the evaluation of future treatments and vaccine candidates. Ideally an animal model will closely mimic the disease manifestations observed in humans. In this review, we outline the currently available animal models for several viruses vectored by mosquitoes, ticks, and midges, for which there are no standardly available vaccines or therapeutics.
Zika virus has garnered great attention over the last several years, as outbreaks of the disease have emerged throughout the Western Hemisphere. Until quite recently Zika virus was considered a fairly benign virus, with limited clinical severity in both people and animals. The size
and scope of the outbreak in the Western Hemisphere has allowed for the identification of severe clinical disease that is associated with Zika virus infection, most notably microcephaly among newborns, and an association with Guillian–Barré syndrome in adults. This recent association
with severe clinical disease, of which further analysis strongly suggested causation by Zika virus, has resulted in a massive increase in the amount of both basic and applied research of this virus. Both small and large animal models are being used to uncover the pathogenesis of this emerging
disease and to develop vaccine and therapeutic strategies. Here we review the animal-model–based Zika virus research that has been performed to date.
Ebola virus is a highly pathogenic member of the family Filoviridae that causes a severe hemorrhagic disease in humans and NHP. The 2013–2016 West African outbreak has increased interest in the development and refinement of animal models of Ebola virus disease. These models
are used to test countermeasures and vaccines, gain scientific insights into the mechanisms of disease progression and transmission, and study key correlates of immunology. Ebola virus is classified as a BSL4 pathogen and Category A agent, for which the United States government requires preparedness
in case of bioterrorism. Rodents, such as Syrian golden hamsters (Mesocricetus auratus), mice (Mus musculus), and guinea pigs (Cavia porcellus), are the most common research species. However, NHP, especially macaques, are favored for Ebola virus disease research due to
similarities with humans regarding the pathogenesis, clinical presentation, laboratory findings, and causes of fatality. To satisfy the regulatory requirements for approval of countermeasures against high-consequence pathogens, the FDA instituted the Animal Rule, which permits efficacy studies
in animal models in place of human clinical data when such studies are not feasible or ethical. This review provides a comprehensive summary of various animal models and their use in Ebola virus disease research.
The use of zebrafish (Danio rerio) as an animal model for experimental studies of stress has increased rapidly over the years. Although many physiologic and behavioral characteristics associated with stress have been defined in zebrafish, the effects of stress on hematologic
parameters have not been described. The purpose of our study was to induce a rise in endogenous cortisol through various acute and chronic stressors and compare the effects of these stressors on peripheral WBC populations. Acutely stressed fish underwent dorsal or full-body exposure to air
for 3 min, repeated every 30 min over the course of 90 min. Chronically stressed fish underwent exposure to stressors twice daily over a period of 5 d. After the last stressful event, fish were euthanized, and whole blood and plasma were obtained. A drop of whole blood was used to create a
blood smear, which was subsequently stained with a modified Wright–Giemsa stain and a 50-WBC differential count determined. Plasma cortisol levels were determined by using a commercially available ELISA. Endogenous cortisol concentrations were significantly higher in both stressed groups
as compared with control fish. Acutely stressed fish demonstrated significant lymphopenia, monocytosis, and neutrophilia, compared with unstressed, control fish. Chronic stress induced lymphopenia and monocytosis but no significant changes in relative neutrophil populations in zebrafish. The
changes in both stressed groups most likely are due to increases in endogenous cortisol concentrations and represent the first description of a stress leukogram in zebrafish.
Recent human studies indicate a possible correlation between the administration of antibiotics during early life and the risk of later obesity, potentially due to antibiotic-induced alteration of the gastrointestinal microbiome. In humans, the risk of obesity increases with multiple
courses of antibiotics and when fetuses or infants are treated with broad-spectrum and macrolide antibiotics. In addition, the obesity risk in humans seems higher for males than females. We used a retrospective, case-control, matched-pair study design to evaluate health records for 99 control-matched
pairs of rhesus macaques (Macaca mulatta) from an outdoor breeding colony. We hypothesized that NHP treated with antibiotics prior to 6 mo of age would have steeper growth curves than those who were not. However, in contrast to prior research with humans and mice, growth curves did
not differ between antibiotic-treated and control animals. Differences between humans and NHP may have influenced this outcome, including the relative standardization of NHP environmental factors and diet compared with those of human populations, types of infections encountered in infancy
and choice of antibiotic treatment, and the different relative maturity at 6 mo of age in the 2 species. The results provide support for current standard medical practice in NHP and highlight a difference between macaques and humans that may influence future obesity research using macaques.
Determining the basis for this difference might improve our understanding of the risks of earlylife antibiotic treatment and suggest mitigation strategies for treating infant illnesses without risking obesity.
Endometriosis is the presence of endometrium outside of the uterus. Although endometriosis occurs in both pelvic and extrapelvic locations, extrapelvic locations are less common. The development of abdominal wall or incisional endometriosis in women is associated with gynecologic surgeries
and is often misdiagnosed. Because they naturally develop endometriosis similar to women, Old World NHP, including rhesus macaques, provide excellent opportunities for studying endometriosis. Here, we describe a case of abdominal wall endometriosis in a rhesus macaque that had undergone cesarean
section. Microscopically, the tissue consisted of pseudocolumnar epithelium-lined glands within a decidualized stroma, which dissected through the abdominal wall musculature and into the adjacent subcutaneous tissue. The stroma was strongly positive for vimentin and CD10 but was rarely, weakly
positive for estrogen receptors and negative for progesterone. Close examination of extrapelvic endometriosis in rhesus macaques and other NHP may promote increased understanding of endometriosis in women.