Occupational Health in Animal Care, Use and Research

Table of Contents

Introduction

I. Hazard Identification and Risk Assessment

II. Personnel Training

III. Personal Hygiene

IV. Facilities, Procedures and Monitoring

V. Animal Allergies

VI. Animal Experimentation Involving Hazards

A. Containment

B. Biosafety Levels

C. Animal Biosafety Levels

D. Arthropod Containment Levels

E. Select Agents

VII. Specific Zoonotic Infections of Concern

A. Viral Agents

1. B virus

2. Hantavirus

3. Lymphocytic Choriomeningitis Virus

4. Orf

5. Rabies

D. Rickettsial Agents

1. Cat Scratch Fever

2. Q Fever

C. Bacterial agents

1. Capnocytophagosis and Pasteurellosis

2. Chlamydiosis

3. Helicobacteriosis

4. Leptospirosis

5. Rat Bite Fever

6. Shigellosis

7. Tuberculosis

D. Mycotic

E. Protozoal

1. Toxoplasmosis

2. Cryptosporidiosis

F. Parasitic

VIII. Personal Protection

IX. Medical Surveillance and Preventive Medicine

Conclusion

Introduction

How can we protect the health of laboratory animals unless we protect our own health? Veterinarians, veterinary technicians, animal husbandry personnel and almost any of those persons that work with animals or come into contact with them during the performance of routine duties (hereafter referred to collectively as laboratory animal workers, or LAW) face job-associated risks that are unique to employees of animal care facilities. As the workforce in biomedical research facilities continues to expand as a result of increasing research needs and animal numbers, it is imperative to continue to address occupational health and safety (OHS) issues for LAW in the contemporary laboratory animal environment.

The Occupational Safety and Health Act of 1970 (Public Law 91-596) was implemented to assure, so far as possible, safe and healthful working conditions for every working man and woman and to preserve our human resources.

In this Act, the National Institute of Occupational Safety and Health (NIOSH), as part of the U.S. Department of Health and Human Services, is charged with recommending occupational safety and health standards and describing exposure concentrations that are safe for various periods of employment – including but not limited to concentrations at which no worker will suffer diminished health, functional capacity, or life expectancy as a result of his/her work experience. By means of criteria documents, NIOSH communicates these recommended standards to regulatory agencies (including the Occupational Safety and Health Administration (OSHA) in the U.S. Department of Labor) and to others in the OHS community [78].

Overall, the mission of any OHS program is to maximize employee health and productivity through the targeted delivery of preventive and wellness services, including active oversight and management of employee injury, disease and disability [80]. Each institution, as outlined in the Public Health Service Policy [60], is responsible for conducting their individual OHS program, which must be part of the overall animal care and use program [36,53]. Management sets the tone and pace for safety in every institution; they must understand the importance of an OHS program that fully integrates the aspects of facility design, the animal species involved and the nature of the ongoing research [13,16,18]. The Institutional Animal Care and Use Committee (IACUC) should consider the maintenance of a safe working environment during review of animal protocols and during semi-annual inspections [53].

OHS programs are integral to a sustainable and productive work force in the animal research facility. Due to the unique employment responsibilities in the field of biomedical research, LAW must be made aware of OHS issues related to their jobs. OHS programs must also be consistent with applicable local, state and federal regulations to maintain a safe and healthy work environment [36].

OHS program concerns were the second most common deficiencies identified by the accrediting agency, AAALAC (Association for Assessment and Accreditation of Laboratory Animal Care, International) in the period from 1993-1999 [18,50]. Data analyses have not yet been completed for the years through 2005, yet the expectation is that OHS issues will remain the second most common citation [75]. Deficiencies in any of the components of the OHS program may be documented by AAALAC, but often these deficits merely represent difficulty in coordinating all of the elements for successful LAW health and safety oversight at individual institutions [18]. Therefore, initial and ongoing investments in worker protection strategies and safety knowledge are invaluable.

There are many policies and publications in place to ensure the safety of LAW as well as the animals under their care [29]. The Guide for the Care and Use of Laboratory Animals (abbreviated to the Guide) is the standard reference used by AAALAC for assessment of laboratory animal facilities. The Guide offers recommendations for health and safety oversight to "animal technicians, clinicians, investigators, predoctoral and postdoctoral trainees, research technicians, consultants, maintenance workers, and security personnel" among others that have contact with or duties involving laboratory animals. Interpretation of the Guide requires the use of "professional judgment" in application of "performance"-based standards, including those standards applicable to OHS programs. In addition to the Guide, several other reference texts are available to management professionals and LAW interested in initiating or reviewing an OHS program. The most recognized references include Biosafety in Microbiological and Biomedical Laboratories [PDF] (4th Edition) – (abbreviated to BMBL) [10] and Occupational Health and Safety in the Care and Use of Animals [16]. A more recent publication, Occupational Health and Safety in the Care and Use of Nonhuman Primates [15], specifically addresses the risks associated with exposure to nonhuman primates in biomedical research, including infectious and non-infectious hazards and information on risk management. The information integrated into this chapter primarily will be drawn from the guidance provided by these resources.

The Guide provides suggestions for assessment and evaluation of the following OHS areas, which will be further discussed in corresponding sections below:

1. Hazard identification and risk assessment
2. Personnel training
3. Personal hygiene
4. Facilities, procedures and monitoring
5. Allergies
6. Animal experimentation involving hazards
7. Zoonoses
8. Personal protection
9. Medical evaluations and preventive medicine

Three levels of control are utilized within facilities to limit the occupational exposure of LAW to hazards: Engineering controls, administrative controls, and personal protective equipment (PPE). Engineering controls are uniformly recognized as the most effective means to limit hazard exposures and can include modified or novel equipment (Fig. 1), renovations or physical changes to the facility, and structural design. Administrative controls are efforts from management to perfect employee workflow, alter work schedules or LAW locations, provide guidance and training or generate standard operating procedures. Personal protective equipment offers a barrier between the LAW and environmental and animal exposures and will be discussed further (see Section VIII.)

Figure 1. Engineering controls (down-draft flow hood for cage-changing, chair and floor mat) are implemented to create a more safe working environment in the animal rooms. (Photo credit: R. Ilkhani-Pour and D. Molnar).

I. Hazard Identification and Risk Assessment

Successful development of the OHS program depends on the identification of hazards that are inherent to or intrinsic to LAW interactions with animals. The importance of identified hazards with respect to the risks of occupational injury and illness must be understood [16]. Workplace exposures to hazards are regulated in the United States by OSHA, which enforces the standards described in the Labor Code of Federal Regulations (29 CFR). More specifically, the Occupational Safety and Health Standards can be located in 29 CFR.1910. OSHA is responsible for the continued development and enforcement of workplace safety and health regulations.

Categories of hazards can be separated into chemical, physical, and biological areas, as well as novel research experiments described within approved institutional animal care and use proposals. It is imperative to identify the unique hazards present in each facility; without this, conducting an adequate risk assessment of the LAW in a specific department or program is not possible [18,22].

Chemical safety is an essential component of effective OHS programs [76]. Exposure to chemicals can be encountered daily in the animal facility. For example, LAW may have to protect themselves from routine chemicals like laminar flow hood disinfectants in the animal rooms or acid rinses in cage washing areas or formalin during animal necropsies. Critical information for each chemical is maintained in the Material Safety Data Sheet (MSDS). Often, several versions of the MSDS are available for a chemical, depending upon the manufacturer. These are short technical reports that explain how to use, handle and store chemicals safely. MSDS sheets are required by OSHA to be accessible to all employees, particularly those employers working with a hazardous material. Paper copies normally are maintained in by the department supervisor or within a designated laboratory area, but may also be available electronically on the World Wide Web. It is imperative to never mix any chemicals unless under specific instructions to do so [29]; as well, chemical wastes should be disposed of appropriately.

Physical hazards may be caused by the ergonomics of the assigned tasks and the cumulative injuries of the musculoskeletal system that result from repetitive motions. Musculoskeletal disorders (MSDs) can develop over time and are related to the dose (force) of the activities performed and the exposure (frequency and posturing) of the LAW to the activities [42]. The NIOSH Lifting Equation was revised in 1991 and incorporates biomechanical, physiological and psychophysical components to determine a recommended weight limit (RWL) for certain tasks [81]. Strong evidence of MSDs can be found through review of the risk factors present in the job place, in addition to OSHA 300 Logs (see Section IX) and self-reporting surveys of LAW about their injuries and illnesses [42]. Physical hazards can also include animal bites and scratches, which may be associated with potential exposure to zoonotic pathogens, discussed in Section VII.

The risk assessment (RA) involves the identification and quantification of a particular hazard by health and safety specialists. The RA is the basis for sound comprehensive safety decisions; as well, the RA defines potential exposure and other risks based upon actual job duties. Within the animal facility, the RA is critical for many reasons and guidelines exist for the process [10]. In particular, there is a great deal of variability and individual nuance in the successful performance of job tasks done with animals. Certain routine processes, like cage changes and experimental procedures, are less automated (unlike working with serum or cell cultures). Overall, there are fewer engineering and administrative controls to lower potential risks, and there is a high reliance on PPE and personal behavior, which may be the most difficult job variable to control.

In summary, the hierarchy of risk reduction includes the following:

1. Eliminate the hazard if possible,
2. Incorporate the established engineering controls,
3. Rely further on administrative controls,
4. Sculpt appropriate work practice through education and training,
5. Provide appropriate personal protective equipment (PPE) for LAW. An effective OHS program ensures that risks are reduced to acceptable levels [36].

II. Personnel Training

All animal workers should be educated regarding: zoonoses, chemical safety, microbiologic and physical hazards, unusual conditions that are part of experimental procedures, handling of waste material, personal hygiene and health issues [36,53]. Multiple formats for safety training can be used to keep things fresh and interactive with staff [13]. LAW that are trained proficiently as to their work assignments will contribute to a safer working environment.

Mechanisms need to be in place to inform and educate employees about the OHS program and to encourage their participation [18,50]. Information about the programmatic elements of OHS can be relayed through employee orientation meetings, standard operating procedures (SOPs), signs and themed posters, newsletters, bulletins, email announcements, and periodic gatherings with quizzes and game formats [56].

Training is a critical component needed to help lower hazard risks to LAW; training should be scheduled and continuous. Training issues are at the core of safe handling of hazards in animal work [50].

III. Personal Hygiene

A high standard of cleanliness is expected within the animal facility. The facility should provide areas for LAW to wash and shower to assist with the standards of personal hygiene. Protective garments should be supplied by and laundered at the work site, and should not be worn home by the animal workers. While the request may seem logical, it is imperative that eating, drinking, using tobacco products and applying cosmetics be done in areas other than the animal housing facilities [36].

IV. Facilities, Procedures and Monitoring

It is important that the facilities and various procedures to be performed by LAW adhere to a standard of safety. Problems with uneven or wet floors, broken or aged equipment, narrow hallways, or faulty heating ventilation and air conditioning (HVAC) systems are all possible areas of injury risk to LAW. Specifically, the provision of ergonomically sound operations that reduce physical injury risks will support the health and safety of personnel [36] (Fig. 2). Appropriate animal housing (e.g., shoebox mouse cages, dog runs, squeeze-back nonhuman primate pens) should be maintained to control disposal of contaminated food/bedding/waste materials. The primary enclosures for each species should prevent unwanted animal escapes. The demand for newly constructed facilities that can support infectious disease research in the age of bioterrorism (specifically Biosafety Level (BSL) 3, 3-Agriculture (3-Ag), and 4) (see Section VI.B) continues to grow [17,27].

Figure 2. Specialty items, like raised steps, provide comfort to LAW and enhance the ergonomics of tasks like cage-changing within an isolator. (Photo credit: R. Ilkhani-Pour and D. Molnar).

Assessments should be performed routinely to determine compliance with permissible exposure limits (PELs), as described by OSHA, and relative exposure limits (RELs) as determined by NIOSH.

V. Animal Allergies

Allergic responses are one of the most important health hazards resulting from animal contact. Most major laboratory animal allergens have been identified and characterized [7]. Repeated exposure, particularly through inhalation, to animals or animal products in the workplace can cause asthma and allergies [52]. Up to 40% of LAW experience allergic reactions, and an estimated 10% of LAW eventually develop asthma [16]. The LAW susceptibility to allergens should be evaluated and documented during routine medical screening. Outside of animal allergens, LAW must also be aware of allergies to latex gloves and other medical equipment, fungal spores embedded in bedding materials, and chemicals used for disinfecting or cleaning. These all may contribute to the overall respiratory burden of substances that can induce asthma. To help mitigate allergic reactions, LAW should avoid or limit contact with animal saliva, dander and urine [20]. Methods to limit exposure to allergens have been described, and include engineering (Fig. 3) and administrative controls [43,61,70], along with personal protective measures, like the powered air-purifying respirator units (Fig. 4) [24]. Respirators, that are specifically fitted to the individual LAW, are described further in Section VIII. More information about this topic can be obtained by reviewing the NIH Laboratory Animal Allergy Prevention Program (NIH-LAAPP), which recommends that employees with known allergies to animals wear NIOSH-approved N-95 dust/mite respirators. Prevention of the development of animal allergy should be the aim of all facilities that are engaged in the use of animals in research [16].

Figure 3. Use of a cage dumping station permits a High-Efficiency Particulate Air (HEPA) filter to capture airborne particulates generated by dirty bedding disposal. LAWs using these stations should wear recommended personal protective equipment, as shown. (Photo credit: R. Ilkhani-Pour and D. Molnar).

Figure 4. Facility personnel wearing a powered air-purifying respirator (PAPR) to prevent exposure to aerosols. The use of the PAPR requires fit testing. (Photo credit: N. Figler)

VI. Animal Experimentation Involving Hazards

Standardized operating procedures (SOPs) and animal research facilities should undergo review through an oversight process, potentially by a designated safety committee involving persons knowledgeable in OHS issues.

Review areas include animal care and housing, storage and disbursement of agents, dose preparation and administration, body-fluid and tissue handling, waste and carcass disposal, personal protection, and specialized safety equipment [36]. Institutions should have written policies governing experiments with hazardous agents [36]. Special facilities for animals infected with hazardous agents should be designated (Fig. 5) and separated from other animal housing and support areas. It is recommended to 1) identify the presence of hazards appropriately, 2) limit access to areas with hazardous agents, 3) effectively seal floor drains, 4) control airflow depending on whether negative or positive air pressure is needed for animal or LAW health, and 5) scavenge waste gas.

Figure 5. Biohazard room sign with contact personnel information and a list of required personal protective equipment for room entry. (Photo credit: R. Ilkhani-Pour and D. Molnar).

A. Containment

A large component of managing any categorical risk is containment. The practice of containment aims to reduce or eliminate exposure of laboratory workers and the environment outside the facility to adverse consequences. This is best accomplished by the use of laboratory practice and techniques, safety equipment and facility design. A thorough risk assessment of the work that will be performed using a particular agent will determine the appropriate combination of these three elements [10].

Recommendations for safety practices and containment of specific hazardous biologic agents and materials are available [10], and updates to the BMBL in the form of a 5th Edition are anticipated by the year 2007 [74]. The 5th Edition represents an organized attempt to develop a standard of practice from the government. The recommendations will be advisory, but many of the words are actually used as regulation, and will be based on individual risk assessments. The Centers for Disease Control and Prevention (CDC) and National Institutes of Health (NIH), as well as other sponsoring agencies, will have to agree to the revisions before agreeing to publish the new edition [67]. If agents are to be handled for which the risk level has not been defined, expert personnel at the CDC should be consulted for further information. Within the U.S. Department of Labor, OSHA can enforce the BMBL [68]. Containment strategies are classified through the use of Biosafety Level, Animal Biosafety Level and Arthropod Containment Level practices within individual facilities.

B. Biosafety Levels (BSL)

The BSL recommendations, on a grade scale of BSL-1, -2, -3, -3 Ag (Agriculture) and –4, are made on the basis of the potential hazard of the agent and of the laboratory’s function or activity. Anecdotal evidence suggests that strict adherence to the guidelines does contribute to a healthier and safer work environment. One should view these as the minimal guidance for containment; they should be customized as needed. BSL information deals exclusively with laboratories and general safety recommendations. For a thorough description of the criteria for each BSL, outside of the BMBL, the reader is directed to current reviews [27]. The designation of BSL-3 Ag is for environmental protection from agricultural pathogens, including those that may cause economic or trade problems in animals or crops. BSL-3 Ag criteria include BSL-3 level containment, and also include filtration of both supply and exhaust air, sewage decontamination, personnel exit showers and facility integrity testing [77].

C. Animal Biosafety Levels (ABSL)

The ABSL recommendations are important to follow once animals are introduced into the framework of biosafety levels. In the animal room, the activities of the animals themselves can present additional hazards (e.g., allergens, aerosols, bites, scratches, pathogens) [10]. ABSL-1, -2, -3, and -4 exist and provide increasing levels of protection to personnel and the environment. These are regarded as the minimum standards for activities involving infected laboratory animals [10].

D. Arthropod Containment Levels (ACL)

Guidelines for containment of arthropods have been proposed by the American Society of Tropical Medicine and Hygiene (ASTMH). ACL-1, -2, -3, and -4, characterized by increasingly restrictive levels of containment, have been defined [64,71]. Arthropods that are discussed are limited to those that transmit pathogens to vertebrates, including blood-sucking flies, lice, fleas, ticks, and mites. Thorough descriptions of ACLs are available in Arthropod Containment Guidelines published by ASTMH (www.astmh.org/SIC/files/ACGv31.pdf [PDF]) and also in related publications [71].

E. Select Agents

These agents are defined as though with potential to pose substantial harm to human health. Select agents can be viral, bacterial, rickettsial, fungal or toxic in nature and are thought to pose potential for use by terrorists. Entities that wish to possess, use or transfer select agents must register with the CDC (through the US Dept of Health and Human Services) [www.cdc.gov] or USDA (through APHIS). The CDC regulates the safe transfer and proper containment and disposal of these agents and is the lead agency to address public health planning in this area. Overviews of the recent regulations, as well as information on how to obtain updates, standards, and guidelines for work with select agents have been published [28,37].

VII. Specific Zoonotic Infections of Concern

Within the animal research setting, personnel may be exposed to certain microbial pathogens that can cause disease and are transmitted from animals to humans (zoonotic pathogens). Zoonotic diseases that occur within biomedical and animal research settings have been reviewed [19,25,26,30,31,62,66,83]. The documentation of zoonoses in facility personnel is often confounded because many animal species are healthy carriers of zoonotic pathogens. As well, in humans, there is often a lack of a unique clinical presentation that differs from other flu-like illnesses. For certain zoonoses, even if a particular agent is suspected, there may be ill-defined culture requirements or a lack of appropriate or available diagnostic tests. Random-source and wild animal species, with unknown health histories, pose the greatest risk to personnel working in animal research. For these reasons, persons working with these types of animals should assume that the animals are carriers of potential pathogens and take appropriate precautions.

Through the use of preventive measures within animal facilities, including engineering standards, personal protective equipment, and educational awareness, considerable progress has been made in reducing, if not eliminating, the occurrence of certain zoonotic diseases. Most contemporary laboratory animal species are acquired from quality sources ("purpose-bred") that maintain animals under specific-pathogen-free (SPF) conditions, thereby further reducing the risks of zoonotic pathogen infection and transmission. However, certain known zoonoses remain of concern to animal facility personnel, and emerging zoonotic pathogens must also be considered by those individuals engaged in animal research [16,66].

A. Viral Agents

1. Cercopithecine herpesvirus 1 (B virus; Herpesvirus simiae)

B virus is the most significant infectious occupational health hazard in nonhuman primate research. B virus, an alphaherpesvirus closely related to herpes simplex virus, is carried by Asian and African monkeys in the genus Macaca. The agent has been found principally in rhesus (M. mulatta) and cynomolgus (M. fascicularis), but also has been isolated from bonnet (M. radiata), Japanese (M. fuscata), Taiwan (M. cyclopis), and stumptailed (M. arctoides) macaques [14,84].

Initial infections in macaques are usually asymptomatic; however, lesions may occur in the oral, ocular and genital regions. Lesions consist of fluid-filled vesicles on the dorsum of the tongue, the mucocutaneous border of the lips, the inside of the cheeks, or the genitalia. These blisters rupture, scab over, and eventually heal in seven to fourteen days. Virus is shed from active lesions. As well, conjunctivitis may be observed. Once infection is established, B virus remains latent in the trigeminal and/or lumbosacral sensory ganglia. Systemic disease is rare in macaques [14].

Transmission to humans occurs through exposure to contaminated animals (scratches, bites, splashes to mucosal membranes, contact with infected animal tissues) or contaminated equipment (needle sticks, sharp cage parts). Direct correlation cannot be made between the extent of animal-associated injury and the likelihood of infection [14]. The incubation period from exposure to symptomatic disease ranges from weeks to years (due to reactivation of latent infection). In most cases death has occurred from 2 days to 6 months after infection. The virus propagates within the peripheral nervous tissue (ganglia) and spreads to the spinal cord and eventually the brain [14].

Human cases of B virus are considered rare, despite its prevalence in the host species and the large numbers of macaques used in research [34]. Early stage symptoms include flu-like illness, and headaches. On some occasions, vesicles have formed near skin wounds exposed to contaminated animals or equipment. Progression of the disease involves symptoms attributed to central nervous system infection, including alterations in vision, seizures, and respiratory failure [84].

Detection of the virus in nonhuman primates and humans is performed by serologic testing and virus isolation at the B Virus Research and Resource Laboratory (Georgia State University, Atlanta, GA) or at the Central Public Health Laboratory (London, England). The presence of serum antibodies indicates infection with the virus, but not necessarily shedding of virus. Viral culture is often unreliable because of intermittent shedding of the virus by infected monkeys and the difficulty in recovering virus in tissue culture. Polymerase chain reaction (PCR) and reverse-transcriptase (RT)-PCR also can be used for detection of virus [14,58].

Post-exposure prophylaxis with antiviral therapy has been efficacious in cases when instituted within 72 hours following exposure; however studies of antiviral dosing and time courses have primarily been performed in rabbits [14].

Guidelines for prevention of herpes B virus infection in monkey handlers have been published [14]. Because overt clinical disease is rarely observed in macaques infected with B virus, viral shedding occurs in the absence of observable indicators. All macaque monkeys should be treated as though infected, and their bodily fluids and soiled cages should be handled as if they were contaminated. Macaque monkeys should be used for research purposes only when clearly indicated.

Access to areas where macaques are housed or used should be limited to those who are trained in procedures to avoid risk of infection. Personnel who might contact macaque monkeys or their bodily fluids must wear protective clothing, including long-sleeved gown or laboratory coats, latex gloves, eye goggles or face shields, and surgical masks. Monkey handlers must be trained in proper methods of restraint and in the use of protective clothing. Restraining or handling fully awake macaques is not recommended unless required by the approved scientific protocol. Fully awake macaques should be handled only with arm-length leather gloves and animals can be removed from cages by the use of pole and collar restraint.

The most critical period for the prevention of B virus infection is during the first minutes after the exposure occurs [14]. Bites or scratches from macaques should be immediately and thoroughly scrubbed with a disinfectant soap and water. Any exposure should be reported immediately to appropriate supervisory personnel. The placement of monkey bite, scratch, and needle-stick first aid kits in primate housing facilities has been recommended. Employees working with macaques should receive training in first aid procedures for treatment of wounds potentially contaminated with B virus [14]. Wounds sustained from working with monkeys, or from equipment contaminated with monkey saliva or urine should be scrubbed vigorously for 15 minutes with gauze sponges soaked in disinfectant soap. If eye splashes occur, rinse the eyes immediately with water at an eye wash station or sink for 15 minutes. If water is not available, use ocular irrigating solution. Prompt medical attention should then be sought.

Any wounds sustained from macaque exposure should be cultured for B virus and blood drawn for B virus serologic testing. The patient should be educated about the clinical signs of herpes B virus infection [14]. The wound should be examined every other day for the first week and then weekly through the end of the fourth week. The wound should be assessed for vesicle formation, itching, pain, and numbness. After two to three weeks of observation, a second serum sample should be drawn to determine whether serum antibodies have developed.

If clinical signs develop, the patient should be referred to a physician who is knowledgeable about evaluation and management of B virus infections.

Laboratory evaluation of the monkey associated with the human injury is an important component in treatment of the patient. The monkey should be examined for the presence of lesions, serum samples should be drawn, and viral cultures should be collected from bilateral conjunctiva, buccal mucosa and genitalia. A convalescent serum sample should be collected 3 weeks after injury. A rise in B virus specific antibody suggests active infection at the time of the employee's injury. The monkey colony personnel, veterinary and husbandry staff, and involved physicians should receive the results of the veterinary evaluation.

2. Hantavirus

Hantaviruses comprise a genus in the family Bunyaviridae. Each type of hantavirus, of approximately twenty that have been identified to date, is associated with rodent hosts, including rats, mice and other wild rodents. As hantaviruses continue to be isolated from the estimated 2000 species of Murid rodents, there may be greater numbers of zoonoses characterized in laboratory animal rodents [72]. Hantaviruses have not been reported in personnel working in contemporary animal facilities with commonly used laboratory rats (Rattus norvegicaus) and mice (Mus musculus).

Hantaviruses cause asymptomatic infections in rodent hosts. The virus is shed in the saliva, urine, and feces of persistently infected rodents for months [45]. Transmission occurs though inhalation of infective aerosols, wound contamination, conjunctival exposure and ingestion [31]. Infectious virus also may be present in the blood and organs of infected mice [9]. Rat cell lines have been demonstrated to be a source of infective virus [73].

Hemorrhagic fever with renal syndrome (HFRS) has been documented in numerous animal facility personnel, particularly in Japan, France, the United Kingdom, Singapore, and Belgium [31]. Severity of HRFS is related to the strain of virus involved. Clinical symptoms include acute onset of fever with lower back pain. Hantavirus pulmonary syndrome (HPS), caused by Sin Nombre virus (reservoir: deer mice) is characterized by fever, myalgia, and gastrointestinal distress. HPS has not been associated with rats of the genus Rattus or mice of the genus Mus [72]. The incubation period in humans averages from two to four weeks [12].

Recommendations for management of hantaviruses in laboratory animal facilities have been published [10,72]. In general, potentially infected tissue samples should be handled in BSL-2 facilities in accordance with BSL-3 practices. Experimentally infected rodents that do not excrete the virus can be housed in ABSL-2 facilities and handled using ABSL-2 practices. Biosafety cabinets and other containment devices should be used whenever there is a high potential for generating aerosols. Studies in which virus is inoculated into P. maniculatus or other permissive species should be conducted at ABSL-4.

Prevent exposure to rodents and their tissues by the use of proper personal protective equipment. Treatment of symptoms in humans involves supportive care.

3. Lymphocytic choriomeningitis virus (LCMV)

LCMV is an arenavirus. It exists in the wild mouse population in all areas of the world. Infection has been reported in many potential laboratory animal species including mice, rats, hamsters, guinea pigs, chinchillas, rabbits, dogs, nonhuman primates, swine and chickens. Wild mice are the principal reservoir of infection for susceptible species. Laboratory mice, hamsters, marmosets and tamarins have been implicated in transmission of disease to humans [11,25,26,48].

Disease in infected animals is dependent upon age, strain and dose of virus, and route of inoculation [57]. In adult mice, the disease is self-limiting. However, neonatally infected mice develop persistent, lifelong infections. These animals act as carriers and shed virus particles throughout their lives. Athymic and severe-combined immune deficient mice can harbor silent, chronic infections [21].

Infection may be transmitted by several routes: direct skin or mucous membrane contact with the infective secretions (urine, feces, saliva); ingestion or inhalation of aerosolized virus particles from the animal room or cage; parenteral exposure; contact with contaminated bedding material or infected ectoparasites [16]. In addition, tissue culture cell lines and transmissible tumors can become contaminated and harbor the virus. These can serve as either a means for transmission of the agent into mouse colonies or for infection of laboratory workers. Transmission by aerosolization is a particular hazard for pregnant women; LCMV has been indicated as a teratogen in humans [4]. Flu-like illness due to LCMV infection has occurred in animal technicians, research personnel and veterinarians. Headache, fever and myalgia are often noted and clinical symptoms may progress to aseptic meningitis. The incubation period ranges from one to three weeks [31].

Infection can be detected in mice by virus isolation assays. Contamination of cell and tumor lines can be determined by inoculation of susceptible mice with the tumor or cell line and subsequent detection of antibodies to the virus in infected mice. In humans, serologic detection of rising antibody titers in paired sera is considered diagnostic [12].

Prevention of the disease in humans is fostered by proper hygiene, including the use of latex gloves and subsequent hand washing following rodent handling [26]. ABSL-3 practices and facilities are recommended for activities with a high potential for production of aerosols, for manipulation of quantities of infectious material, or for work with infected animals [10]. Surveillance of rodent colonies for viral contaminants is helpful; infected colonies may be freed of the virus by depopulation and cesarean rederivation [12].

4. Orf (Contagious ecthyma; contagious pustular dermatitis)

Orf disease is caused by a parapoxvirus and occurs worldwide in sheep and goats. Typical lesions in these animal species consist of proliferative, pustules around the lips, gums, nostrils, teats and udders, and urogenital openings [16]. Interdigital and coronet lesions may be associated with laminitis. Disease in goats tends to be more severe than that in sheep [47].

The virus is transmitted, from animal to animal and animal to human, most commonly by direct contact with exudates from lesions and sometimes through fomites [16]. The virus is highly resistant to dessication and can persist in clinically apparent lesions.

In humans, the disease begins as a solitary maculopapular or pustular lesion on the hands, arm or face that progresses to a weeping, proliferative, umbilicated nodule [16]. The incubation period ranges from three to six days. Treatment is typically not undertaken as the disease is self-limiting over three to six weeks.

Personnel working with sheep should wear gloves and possibly other protective clothing. Laboratory sheep and goats may be given pre-emptive vaccinations with live attenuated virus or scarification with a suspension of infective scab material [16,49]. In addition, it is recommended to disallow entry of clinically affected animals into established research herds.

5. Rabies

Rabies is caused by a rhabdovirus and can infect most mammalian species, including laboratory dogs, cats, ferrets, livestock and nonhuman primates. Initial signs of disease in animals vary considerably from agitation and confusion to ataxia and paralysis. Death can occur in animals within two to seven days of illness [47].

Suspect animals should be quarantined for 10 days after any bite injury to humans to observe for behavioral signs suggestive of infection that would warrant euthanasia [39]. Animals that meet criteria for true rabies virus infection should be necropsied and the brain tissues should be analyzed for viral antigen [47].

Transmission is sustained by the bite of a rabid animal or inoculation of infective saliva into mucous membranes or fresh wounds. While no cases of rabies have been reported in animal facility personnel, it is important to monitor for this zoonotic pathogen in facilities that use random-source or conventional animals of unknown health background.

In humans, rabies can cause headaches, fever and malaise that can progress to encephalomyelitis and death due to respiratory paralysis. The incubation period can be as short as ten days, but averages three to eight weeks in length. Detection of viral antibody and viral isolation from affected tissues is necessary for diagnosis. Treatment is usually unrewarding.

Prevention of rabies in high-risk animal personnel is often controlled by preexposure immunization. Immediate and thorough wound disinfection is recommended. Postexposure administration of human rabies immune globulin at the wound site may be beneficial. National standards address prevention of rabies virus for persons in the United States [8,32]. Verification of current rabies vaccination should be mandatory for dogs, cats, and ferrets that enter the existing animal colony if their health history or vaccination status is unknown.

B. Rickettsial Agents

1. Cat Scratch Fever

Bartonella henselae is the etiologic agent of cat scratch fever. Cats and occasionally dogs are the reservoir of this agent. Infection is usually asymptomatic, although reproductive failure in female cats and peliosis hepatis in dogs have been reported.

The cat flea is the principal vector that spreads infection within the animal population; however flea-to-human transmission is unlikely. Infection typically occurs in humans following bites or scratches from healthy young cats and occasionally dogs. This agent is an emerging pathogen among immunosuppressed individuals and warrants appropriate precaution in animal facilities [40].

Most human infections occur between September and February and follow a cat bite or scratch, usually from pet animals [16]. No cases within a laboratory animal setting have been documented. After traumatic inoculation, an erythematous papular lesion develops followed by a vesicle and scab. Although the local lesion resolves within a week, regional lymphadenopathy develops several weeks later. The lymph node may rupture and the patient may exhibit fever, malaise, anorexia, headache, and splenomegaly. More serious complications, although less common, include periocular lymphadenopathy, conjunctivitis, central nervous system involvement, osteolysis, hepatitis, and pneumonia. If the patient is immunocompromised, severe systemic or recurrent infection, including bacillary angiomatosis, can develop [16]. The incubation period ranges from three to fourteen days for development of the primary lesion, and up to fifty days for development of lymphadenopathy.

Definitive diagnosis requires culture of the organism from a lesion. However, it is common to accept a combination of clinical signs, history of contact with cats, histopathological examination of biopsy tissue and failure to isolate other causative agents from cultures as evidence of infection [16].

Personnel handling cats should be instructed in proper restraint techniques and should utilize protective clothing to prevent scratches and bites. Wounds sustained from cats in particular should be thoroughly disinfected.

2. Q Fever

Coxiella burnetii is the etiologic agent of Q fever. Both wild and domestic species act as hosts. Within the animal facility, sheep, goats, and cattle are the most important reservoir hosts [26,87]. Dogs and cats have also been reported to serve as reservoir hosts. Infected animals are generally asymptomatic; however, in cases of severe infection, abortion and reproductive failure may occur.

The organism is shed in the urine, feces, milk, and birth products of domestic sheep, goats, and cattle. Transmission to humans often follows exposure to fetal membranes, birth fluids and stillborn animals. Inhalation of infective tissues may occur during parturition. Ixodid and argasid ticks can serve as reservoirs and vectors of the organism [47].

Acute infection in humans results in flu-like illness, with headaches, fever, and myalgia. Pneumonia accompanied by hilar lymphadenopathy may be observed [3]. Chronic infection may result in granulomatous hepatitis and endocarditis. Infection in pregnant women can lead to spontaneous abortion. The incubation period ranges from two to three weeks.

Diagnosis can be made through detection of increasing antibody titers between acute and convalescent samples. Infection may be treated with the administration of oral tetracycline for two to three weeks.

To prevent exposure to the organism, obtain only male sheep or non-pregnant female sheep for experimental purposes. Sheep may also be purchased from known Q Fever-negative flocks. Employees should wear protective clothing such as surgical masks, disposable gloves, shoe covers, and gowns or laboratory coats when handling sheep and goats. Due to the risk of aerosol transmission, it is helpful to ensure adequate ventilation in ruminant housing areas and keep those animals known to be infected physically separated from humans.

C. Bacterial Agents

1. Capnocytophagosis and Pasteurellosis

Bite and scratch injuries sustained from laboratory animal species represent an important occupational hazard for animal facility personnel. The diverse bacterial flora that inhabits the oral cavities of animals, dogs and cats in particular, may be pathogenic to humans. Two agents of zoonotic importance include Capnocytophaga canimorsus (formerly DF-2) and Pasteurella multocida.

Multiple reports of C. canimorsus transmission to humans from their pet dogs and cats exist; however, no cases have been reported in animal facilities. If humans are exposed to this bacteria, clinical case reports indicate that splenectomy and alcoholism may be strong predisposing factors for overt disease [6].

Clinical symptoms of C. canimorsus infection include cellulitis, fever, and septicemia, that may progress to endocarditis, arthritis, meningitis, and death [38]. The incubation period ranges from one to five days after exposure. The bacteria can be cultured or identified within neutrophils. Treatment includes administration of penicillin G [12].

Animal reservoirs for P. multocida include rabbits, cats, dogs, and pigs. Rabbits often show signs of rhinitis and otitis, but many may be healthy carriers. Cats and dogs have a subclinical infection that is asymptomatic. Pigs can develop atrophic rhinitis if co-infected with other bacterial strains.

Humans are commonly exposed to Pasteurella by bite wounds, but potentially by aerosolization. Cellulitis, erythema and swelling have been reported. Humans may also experience pneumonia, meningitis and fatal congenital complications [2]. Bite and scratch lesions can be cultured for isolation of the bacteria. The incubation period is up to twenty-four hours in length. Treatment with antibiotics is recommended.

Prevention of bites and scratches from multiple species requires appropriate training for handling diverse animals with care and confidence. Gloves and other means of protective equipment should always be worn when handling animals.

2. Chlamydiosis

Many laboratory animal species can serve as hosts for gram-negative Chlamydophila spp., including sheep, goats, dogs, cats, guinea pigs, frogs and poultry. These animal hosts can be asymptomatic carriers, or may exhibit symptoms that are species-specific [31]. Sheep and goats may have pneumonia, enteritis and reproductive complications; dogs may have pneumonia and endocarditis; cats and guinea pigs may experience conjunctivitis and keratitis; frogs may exhibit lethargy, edema, petechiation, and disequilibrium.

Transmission to humans is based on direct contact with animals or their tissues, particularly birth products of ruminants and other mammals. Inhalation of contaminated aerosols is a hazard for those working with poultry.

Disease occurs sporadically in animal facility personnel. Flu-like illness with conjunctivitis, pneumonia and septicemia has been reported. As well, pregnant women are susceptible to febrile illness, congenital infection, and abortion. Following exposure, the incubation period is one to four weeks. The agents can be detected by analysis of paired sera with increasing antibody titers.

Treatment with tetracycline or doxycycline may be beneficial. Prevent direct contact with and inhalation of aerosols through the use of appropriate protective equipment.

3. Helicobacteriosis

Multiple strains of Helicobacter have been isolated from a variety of animal species, including humans. Many of the same identified Helicobacter have been found in gastrointestinal tracts of both animals and humans. Fecal-oral transmission is suspected; however, further studies are necessary to determine whether animals truly serve as a source of the bacteria for zoonotic transmission to humans. Helicobacter pylori can infect humans and cause gastritis, but animal contact has not been implicated as a cause of the infection [26,82].

4. Leptospirosis

Infection is caused by spirochete bacteria of the genus Leptospira, including L. canicola, L. hardjo, L. icterohemorrhagica, L. interrogans serovar ballum, L. pomona, and L. sejroe. Multiple animal species can serve as reservoir hosts, including mice, rats, gerbils, hamsters, dogs, cats, ruminants, swine, and nonhuman primates. Different diseases are seen in the different animal species following infection. In mice, infection is asymptomatic. Dogs may succumb to hepatic and renal disease, with hematuria [65,69]. Ruminants may have reproductive failure, while nonhuman primates may experience abortions and icterohemorrhagic disease [23,59]. To detect the organisms in host species, serology can be performed to assess rising antibody titers. As well, culture and PCR of infective urine can be performed.

Transmission to humans occurs through oral and aerosol exposure to contaminated urine, reproductive tissues, and fetal tissues. Organisms can also infect humans through abrasions in the skin and mucosal membranes.

Disease in humans is variable. Mild flu-like symptoms may progress to severe infection with renal, hepatic, pulmonary or meningeal involvement. Weil’s disease (jaundice) has been documented in animal facility personnel. The incubation period ranges from four to nineteen days. Infection is diagnosed through serology or isolation of leptospires from blood, urine or cerebrospinal fluid.

Treatment involves antimicrobial therapy with penicillin, cephalosporins, tetracyclines or erythromycin [12]. Prevent exposure to contaminated animals through the use of personal protective equipment that covers skin and mucosal surfaces.

5. Rat Bite Fever

The most common etiologic agent of rat bite fever is Streptobacillus moniliformis, a pleomorphic, gram-negative rod. Spirillum minus, a spiral-shaped, gram-negative rod, also has been associated with infections following rat bites but much less frequently [26,86].

Wild and laboratory rats are the principal reservoirs, although the organisms also have been isolated from mice, gerbils, squirrels, weasels, dogs, cats, and nonhuman primates. These agents are considered part of the normal nasopharyngeal flora of rats. Clinical disease in rats and other hosts is rare but has been reported [79,86]. Detection involves isolation of the agents from the oral cavity, nares or conjuctival sacs and identification by culture or PCR. Animal inoculation may be used for isolation of S. minus [12].

In the research setting, human infections are most often associated with rat bites. Transmission can also occur following exposure to infective urine or secretions from the mouth, nares or conjunctival sacs. Although clinical disease occurs infrequently, it must be considered in the treatment of rat bite injuries sustained by LAW. Infection with S. moniliformis can lead to flu-like symptoms, regional lymphadenopathy and arthritis. Infection with S. minus can result in a distinctive rash with red to purple-colored plaques.

The incubation period for S. moniliformis is less than 10 days; however, S. minus has an incubation period of two weeks to three months. Diagnosis requires isolation and culture of the organism from the primary lesion, lymph node, blood or synovial fluid.

Treatment begins with thorough cleansing of the wound. Penicillin or tetracyclines can be administered for seven to ten days [12]. Tetanus prophlyaxis should also be considered following bites from rodents [83]. Transmission of the agents from rodent bites can be prevented through the use of protective equipment like gloves and by thorough disinfection of sustained wounds. As well, LAW should be trained in proper restraint techniques when handling rodents.

6. Shigellosis

Shigella spp, including flexneri, dysenteriae, and sonnei are gram-negative anaerobes. These organisms infect nonhuman and human primates and cause diarrhea, dehydration, and weight loss. Severe infections in monkeys may also lead to gingivitis, air sacculitis, and abortions [5]. The organisms can be cultured from fecal material placed on appropriate microbiological media.

Transmission of the agent to monkeys initially is from humans, with secondary spread to other monkeys and back to humans by the fecal-oral route. Humans infected with the bacteria also develop varying degrees of diarrhea, with fever, nausea and potential autoimmune complications [35]. The incubation period lasts from one to four days. Antimicrobials can be administered based on culture and sensitivity results. Appropriate protective equipment should be worn at all times when working with nonhuman primates (see C. herpesvirus 1 discussion).

7. Tuberculosis

In animals, tuberculosis (TB) is caused by acid-fast rods of the genus Mycobacterium, including M. tuberculosis, M. bovis, M. avium-intracellulare, M. avium subsp paratuberculosis, M. kansasii, M. simiae, M. chelonae, and M. marinum. Many species of animals are susceptible to tuberculosis, including nonhuman primates, dogs, cats, pigs, ruminants, chickens and pigeons. Within the animal research setting, nonhuman primates are the animals most likely to be infected with mycobacteria [16]. These organisms do not occur naturally in monkeys, but are acquired from humans, other animals, or environmental sources. Transmission readily occurs between monkeys with secondary spread back to humans [31].

Susceptibility to tuberculosis varies among all species of nonhuman primates. Macaques are the most susceptible while New World primates are the least. Nonhuman primates usually become infected in their country of origin through contact with infected humans [1,16].

The disease in nonhuman primates can be asymptomatic, but animals may succumb to acute death. Pulmonary disease is a common presentation, although intestinal and cutaneous tuberculosis with draining tracts have been reported. Nodular lesions may form in multiple organs, including vertebrae, brain and spinal cord.

Laboratory nonhuman primates are routinely tested, upon arrival to the facility and thereafter, for exposure to mycobacterial species. In quarantine, monkeys are usually tested every two weeks; however, in established colonies quarterly testing is recommended. Intradermal skin testing (Mantoux testing), using purified protein derivative (PPD) of tuberculin, is performed in captive monkeys. Positive test reactors are re-tested for confirmation and may undergo pulmonary radiography. Animals that are suspected of having tuberculosis are generally euthanized and necropsied to establish a definitive diagnosis. Mycobacterial culture is difficult and may take four to eight weeks for confirmation. Serology and PCR may also be used for detection. False-negative skin testing may occur due to concurrent disease or immunosuppression. Rarely, positive animals may be treated to control the disease [1,16].

Transmission of tuberculosis is primarily by infective aerosols, but fecal-oral routes of transmission have been documented. Individuals working with nonhuman primates have an increased risk for development of a positive tuberculin skin test. In addition, personnel with tuberculosis pose a substantial risk for nonhuman primates. In humans, pulmonary, meningeal, and visceral organs and other body systems may be infected by disease agents. Progressive pulmonary disease may be fatal. Crohn’s disease has been linked to M. avium subsp. paratuberculosis infection [33]. The incubation period ranges from two to ten weeks for development of primary lesions or a positive skin test [12].

Diagnosis can be assisted by skin-testing personnel, PCR, RT-PCR and pulmonary radiography. Treatment of disease in based on established antimicrobial protocols, including combination treatment with isoniazid, rifampin and pyrazinamide [12]. Increasingly, drug-resistant mycobacterial strains are being recognized.

Occupational health programs for personnel working with nonhuman primates should include regular intradermal skin testing of at-risk facility personnel (usually annually or semi-annually), training in the use of personal protective equipment, and education on tuberculosis. Individuals who develop a positive skin test should be referred to a physician for follow-up. They should be reassigned to work tasks other than nonhuman primate areas until it has been determined that they are free of tuberculosis [1,16].

D. Mycotic Agents

Zoonotic fungal infections are relatively uncommon in animal research. The most significant are dermatomycoses caused by Microsporum canis, Tricophyton mentagrophytes. and Trichophyton verrucosum [85]. Potentially, animals obtained from random source dealers may serve as a source for infection, which presents with crusts and ulcerative skin lesions. Transmission to humans is through direct contact with infected animals. Humans develop self-limiting skin lesions, often referred to as "ring worm", which spreads outward circumferentially. Treatment of the disease is accomplished by thorough cleansing with soap and water; fungicides may be applied topically. Prevent transmission through the use of appropriate protective equipment, particularly disposable gloves.

E. Protozoal Agents

1. Toxoplasmosis

Cats are the reservoir host for this parasite, Toxoplasma gondii. Cats are infected following ingestion of infected prey animals and begin to shed oocysts within three weeks. Oocysts take more than twenty-four hours to become infective following shedding. Transmission to humans occurs through ingestion of infective oocysts. While most human infections are subclinical, infected pregnant women are particularly at risk for congenital infections, which may result in severe neurological damage to the fetus. Immunosuppresed individuals are more likely to exhibit clinical symptoms, including lymhadenopathy, fever and pneumonia. Transmission of this pathogen can be greatly diminished, if not eliminated, through management techniques within the facility. Litter boxes should be emptied completely on a daily basis, which will eradicate fecal exposure to infective oocysts. Prevent wild rodent entry into the facility so infection is not introduced to the laboratory cat population.

2. Cyptosporidiosis

Many animal species can serve as reservoirs for Cryptosporidium spp. While infection may be asymptomatic in animal hosts, cats, dogs, ruminants, monkeys, and other species may suffer from intractable diarrhea. Disease can be severe in immunosuppressed animals. Transmission to humans is likely fecal-oral in nature. Humans predominately exposed to livestock have contracted this infection. Disease may be asymptomatic or result in profuse watery diarrhea. The incubation period averages one week in length. Treatment with antimicrobials is often unrewarding, therefore supportive fluid therapy should be administered. Prevent direct contact with contaminated excreta through the use of personal protective equipment.

F. Parasitic Agents

The risk of infection with helminth parasites originating from laboratory animals is insignificant. However, infestations with ectoparasites, e.g. mites, fleas, and ticks, derived from laboratory animals have been reported. Facility personnel may have moderate to severe, yet transient, dermatitis, eczema, pyoderma or painful bites. More substantial consequences may result if personnel are bitten by ectoparasites harboring bacterial, rickettsial, or viral agents of human disease [31]. To control for parasitic infections within laboratory animal colonies, prompt treatment and elimination of infestation of laboratory animals and their enclosures are warranted. Personnel should treat affected lesions with topical or systemic parasiticides and control exposure through the use of protective equipment.

Overall, exposure of LAW to potential zoonoses is most likely to occur in association with laboratory procedures involving the pathogen, vector, or animal handling procedures such as necropsy, injections, handling, and restraint. When working with live animals, it is important to assess whether the pathogen or vector is shed from the infected animal and by what route, if this is known. In the case of handling killed animals, tissues, or fluids, personnel must be appropriately trained in methods to prevent exposure and infection. To assess contemporary exposure rates in animal facilities, a survey of LAW was performed [85]. Of over 1000 individuals surveyed, only 28 cases of infection with zoonotic agents were self-identified from years 2000-2005. The greatest number of exposures happened in veterinarians, followed in decreasing order by husbandry technicians, supervisors and then veterinary technicians. Underreporting of exposures and clinical signs is believed to be problematic. The lack of concern about the potential significance to their health and the perception of punitive consequences for the employees were cited as the main reasons for lack of disclosure in the work environment.

VIII. Personal Protection

Personal protective equipment (PPE) refers to a variety of implements provided to and used by LAW to offer a barrier from environmental and animal exposures. Burden of employee protection falls largely on the individual LAW and if the equipment is defective, the risk of exposure can occur. PPE garbing standards should be established by each individual facility [46].

Usually PPE is designed to protect certain areas of the body that may come into contact with animals, animal waste material and housing materials (e.g., bedding, caging). The body areas that typically are covered include hands (disposable gloves), arms (sleeve covers), eyes (goggles or safety glasses), mouth and nose (facemasks and face shields), head (hair bonnets), and feet (shoe covers). PPE can also be designed to prevent contamination of animals with potential human contaminants, and can include dedicated scrubs, disposable or autoclavable gowns, dedicated shoes and shoe covers. LAW with specific interactions involving nonhuman primates should have additional PPE (eye goggles and arm covers) [36]. Clean protective gear should be provided as often as needed, including in necropsy areas (Fig. 6). It is important to remember that PPE does not prevent contaminations or exposures unless it is worn and removed correctly [29]. The use of PPE is viewed as a "last resort" for hazard management, for use only when potential exposures cannot be eliminated in any other way (i.e. by engineering or administrative controls) [37].

Figure 6. Face shields, safety goggles and optical loupes provided to personnel within the animal necropsy area. (Photo credit: R. Ilkhani-Pour and D. Molnar).

Hearing protection should be used by LAW exposed to prolonged equipment sounds (e.g., cage washers) (Fig. 7) or animal sounds (e.g., barking of dogs and squealing of pigs) that averages 85 decibels (dB) over an 8-hour day. This noise level, above which a hearing conservation program must be instated, is endorsed as the PEL and the REL, by OSHA [54] and NIOSH [51], respectively.

Figure 7. Earmuffs provide hearing protection when exposed to sources of prolonged noise, like cage wash equipment, in the animal facility. (Photo credit: R. Ilkhani-Pour and D. Molnar).

As well, suitable respiratory PPE should be worn in facility areas where aerosol exposures (e.g., airborne particulates or vapors) may occur. The OSHA Respiratory Protection Standard (29 CFR 1910.134) provides guidance to the LAW. The respirator, certified by NIOSH, should be provided by the employer and selected based on the hazards of the workplace. The respirator shall be used in compliance with the conditions of its certification. Fit testing should be done by an industrial or occupational hygienist in circumstances when the LAW requires protection from the work area, whether it for protection against infectious pathogens, dust, particulates, allergens. The employer shall ensure that an employee using a tight-fitting face piece respirator is fit tested prior to initial use of the respirator, whenever a different respirator face piece (size, style, model or make) is used, and at least annually thereafter (29 CFR 1910.134 f(2)). To be clear, N95 testing is not necessary if the respirator is being used outside the animal room as a selection among other facemasks; in that situation, any mask is useful as a general PPE precaution [41]. Surgical masks, which are not able to seal completely to the face, protect the spread of contaminants from the wearer’s respiratory tract to the animals, but are not classified as respirators [41,68].

IX. Medical Evaluations and Preventive Medicine

Medical surveillance continuously monitors for the potential or occurrence of disease in a given population [13]. Medical evaluations, as part of the medical surveillance program for LAW, can fall into distinct categories that may or may not be necessary at every facility. Determining which type(s) of evaluation to perform depends upon the risks assessed at each institution [74]:

1. Preplacement: determines the job RA in animal care and use; establishes baseline health information and identifies pre-existing conditions; provides an opportunity for additional training or accommodations for pre-existing conditions (specific PPE, etc). If the LAW is at low risk, a screening evaluation may be all that is requested; if higher risks are identified, the LAW can be given a detailed medical questionnaire that is reviewed by a medical professional.
2. Periodic: typically where components and the frequency of the exams depend on the potential hazards; seen most frequently for allergies; physical exams are not a routine component unless very high risks are assessed.
3. Episodic: when symptoms occur that may indicate work-related illness; PPE is typically needed, must have a reporting mechanism back to OHS staff.
4. Exit: usually occurs at the cessation of employment; a means to determine health status when exposure to the potential hazard concludes; legal protection exists to institute these examinations.

Medical surveillance issues include immunizations, zoonosis surveillance, allergy monitoring, medical record-keeping, serum banking and scheduled health evaluations [80]. Certain immunizations are recommended for LAW based on risks and exposures, including tetanus, rabies, and others mentioned in the Guide [36]. In particular, work with nonhuman primates requires heightened surveillance measures, including routine tuberculosis testing. Animal allergies pose an added level of risk, as described in Section V. Occupational Medicine physicians are typically incorporated into the Medical Surveillance program and can play an integral part on the team that may include safety officers, industrial hygienists, ergonomists, and other environmental engineers [63].

AAALAC-identified deficiencies are commonly related to issues of medical surveillance [74]. Some of the main concerns include the lack of periodic health system or surveillance follow-up on personnel, limited access by staff to health services, and the absence of complete medical histories for LAW [44]. More specifically, LAW may not be receiving the appropriate vaccinations warranted by their work duties, they may be ill-trained in practices related to the prevention of Q fever (Coxiella burnetii) exposure, and there may be inadequate testing for TB in those LAW interacting with nonhuman primates [44,74].

Documentation of work-related injuries is mandated by OSHA (29 CFR 1904). OSHA utilizes a three-form system for the documentation (recording and reporting) of occupational injuries and illnesses [55]. OSHA 300 Log of Work-Related Injuries and Illnesses, which replaced the OSHA 200 Log, is used to record all injuries or illnesses that are more serious than those requiring standard "first-aid" care. Form 300-A is the Summary of Work-Related Injuries and Illnesses that is placed in the workplace annually for 3 months, from February 1st through April 30th. Form 301 is called the Injury and Illness Report, which his used to record information on how each circumstance surrounding the injury occurred; Form 301 replaced the previous Form 101.

Conclusion

The components of a thorough OHS program for individuals that have contact with animals, referred to as laboratory animal workers, in biomedical research are vast. While numerous regulations and guidelines have been published, through OSHA, NIOSH, CDC and others, performance-based implementation of the practices is essential. Thus, there are many valid ways for a particular institution to fulfill its commitment to provide a healthful and safe environment for an animal care and use workforce. The best model for an OHS program is one that accurately reflects the risks inherent in the research activities and allows for practical methods for controlling the hazards that contribute to those risks [16]. A team approach to management of the OHS program is essential, and should include veterinarians, industrial engineers, safety professionals, physicians and others knowledgeable in health and safety issues.

Resources for all of the major reference texts listed in the introduction are available online electronically. The American Biological Safety Association website offers access to a multitude of information of interest to LAW and OHS programs. Additional guidance essential to the continued success of occupational health and safety practices in the workplace will be forthcoming in the BMBL 5th Edition and potential revisions to the Guide for the Care and Use of Laboratory Animals.