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THE SAFE HANDLING OF LABORATORY ANIMALS
ST. LOUIS UNIVERSITY
POLICY
Safety ranks equal in importance to all other objectives of the University. Safety is promoted and achieved
through good facilities and equipment, the establishment and enforcement of safety rules, informed and
trained personnel, and the use of appropriate protective equipment. General principles include:
* Each individual is responsible for safety.
* Don't take unnecessary chances.
* Read posted signs and information.
* Obey safety precautions.
* Ask questions, if you are not sure.
* Don't rush.
* Use common sense at all times.
INTRODUCTION
What are the safety and health hazards of working with laboratory animals?
As a rule, the incidence of zoonotic diseases (zoonosis = disease of animals transmissible to man) is rather
low among personnel who care for and use laboratory animals. A complete listing of possible diseases is apt
to produce a distorted impression of the actual danger. Some of the more common and serious diseases will
be highlighted later in this document (see pp 7-16). In general, health and safety matters relate to the species
you work with and the frequency and type of contact.
HAZARDS ASSOCIATED WITH ANIMALS
Rodents and Rabbits
Practically all of the smaller laboratory animals (e.g. mice, rats, rabbits, hamsters, guinea pigs, etc.) are
procured from vendors having animal colonies free of human and animal pathogens (disease causing
organisms). After receipt, these animals are usually maintained pathogen-free through use of proper control
measures (e.g. quarantine and health-monitoring, including laboratory tests). Thus the chance of contracting
an infectious disease from a laboratory bred rodent or rabbit is small. The most significant hazard associated
with these animals is the possibility of developing or exacerbating an allergy (see
discussion of laboratory animal allergies, p 6).
Dogs and Cats
These animals are also obtained from kennels where the animals are bred for research purposes. Therefore,
their health status and vaccination history is known. The most frequent injuries associated with dogs and cats
are bites, scratches and allergies.
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Farm Animals
Farm-type laboratory animals such as cattle, swine, goats, sheep, and poultry, are purchased from varied
sources, usually without complete information on their health and immunization history. This dictates the need
for care in handling these animals and taking appropriate measures such as quarantine and isolation to control
and identify diseases, especially those transmissible to man. The most common laboratory acquired infection
associated with these species is Q-fever. Q-fever is discussed on page 14. Q-fever is most commonly
associated with sheep and is a particular problem when working with pregnant sheep and newborn lambs.
This disease will be discussed in more detail later. Care must be exercised when working with farm animals to
avoid bites, scratches, kicks, and strains.
Non-Human Primates
Monkeys can harbor and transmit a number of serious human
diseases. The most important of these will be discussed later. In addition, monkeys are wild, strong, and
unpredictable. Rooms housing monkeys should always be locked and access restricted.
Feral Animals and Unusual Species
Non-traditional laboratory animals are used frequently. It is not unusual to have in our facilities ferrets,
opossums, muskrats, and various amphibians and reptiles. It is possible for many of these type animals to
harbor and transmit a variety of zoonotic diseases, including rabies. Most such species will be maintained in
an isolated, restricted setting with specific safety instructions, as indicated.
Summary
Thus, not all laboratory animals are free of zoonotic diseases, although most can be used safely if there is
awareness of the potential risks and hazards and adherence to certain procedures. The purpose of this
document is to describe appropriate procedures for working with animals in a safe manner. It describes
procedures for human and animal health maintenance and some of the common zoonotic diseases of animals
used in research at St. Louis University.
PERSONAL HYGIENE
1.
Personnel are advised and encouraged to wear a uniform or a full length laboratory coat in animal
holding rooms. These should not be worn in public areas and never taken home.
2.
It is advisable to wear disposable gloves when handling any animal or related equipment. Sinks, soap,
and hand towels are available in all animal rooms. Remove gloves and wash your hands when leaving
the room.
3.
Whenever, bare hands, arms, neck/face, head become accidentally or unavoidably contaminated with
animal blood, urine, feces, or hair, such contamination should be removed as soon as possible by
washing thoroughly with water and soap. When such contamination enters the mouth or eyes, this
should be removed quickly by flushing with generous amounts of water.
4.
Any person entering a monkey room for any reason must wear a laboratory coat or coveralls,
disposable nose-mouth mask, and disposable plastic gloves.
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5.
Clothing requirements for handling most other animals, including rodents, rabbits, cats, dogs, swine,
sheep, goats, and cattle, are usually less stringent, but at a minimum, persons entering the animal
facilities and/or working with the animals should wear a laboratory coat that is supplied and laundered
by the University.
6.
Do not smoke, eat, or drink in rooms or areas where laboratory animals are housed and/or used.
SAFETY RELATED TO SANITATION
1.
Floors, walls, sinks, and all fixed equipment should be kept uncluttered and clean.
2.
Movable equipment should be properly placed, stable and/or stored.
3.
When pests (insects, wild rodents) are noted, the Comparative Medicine Manager should be notified.
He will arrange for the contract pest exterminator to rid the area of the pests. The unauthorized use of
pesticides can be hazardous to personnel and disruptive to research.
4.
In the SLU facilities, is acceptable to use only the antiseptics, disinfectants, and detergents selected by
Comparative Medicine. They must be used precisely as directed. If used improperly, they can be
ineffective, wasteful, and even hazardous.
5.
Animal carcasses, waste bedding, and other biological wastes are best disposed of by incineration.
Carcasses and other wastes should be carefully sealed in plastic bags and placed in the assigned
refrigerated storage area.
GENERAL SAFETY RULES
*
Wear protective clothing and use animal restraint techniques and equipment as instructed by CM
personnel or the PI.
*
Report immediately all bites, scratches, and kicks, etc. inflicted on you by any animal. Report all
injuries immediately. Any CM supervisor can provide the appropriate report form.
*
Keep your work area uncluttered. Allow sufficient aisle space between cage racks and worktables.
*
Do not smoke, eat or drink in animal use or housing areas.
*
Set damaged or defective cages and racks aside and notify a supervisor so the equipment can be
repaired.
*
Do not overload carts, obscure vision, or exceed weight capacity of transport carriers.
*
Do not use an incorrect transport carrier for the job. Non-nesting cages stacked in tiers could slide
under impact and must be held in place by vertical or horizontal supports.
*
Broken glassware should be swept up with a brush and dustpan, not picked up with your fingers.
*
Do not handle animal species unless and until you have been thoroughly trained. This is for your
safety as well as that of the animal.
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BIOHAZARDOUS PROJECTS
1.
Special containment rooms, designed for projects involving known hazardous agents, are available.
2.
Projects involving hazardous agents or materials will have very strict requirements for clothing and
procedures. Containment procedures are for the protection of personnel and other animals. Specific
standard operating procedures will be posted.
3.
Generally, working with hazardous agents will require full body protection with appropriate clothing and
other safety equipment.
EMERGENCIES
This includes any serious animal bite and/or scratch, and
on-the-job injuries.
When an employee is injured in any way at work, he/she should immediately report the injury to a supervisor.
The supervisor should assist the employee with filling out the Accident Form and send the employee to
Employee Health or the Emergency Room (after normal working hours) for treatment.
If any person is injured to the extent that he cannot be sent to Employee Health or the Emergency Room, the
supervisor should:
1.
Call x2222.
2.
Advise where injured person is located and give person's name.
3.
Describe extent of injury or illness.
4.
Instruct the emergency help to go to the front desk, 1402 S. Grand.
5.
Send someone to the front desk to meet the emergency help.
When a supervisor or other responsible person is not available to assist, an injured employee should call or go
directly to Employee Health or the emergency room. The injured person should notify a fellow employee if he
leaves his work area to obtain medical treatment.
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OCCUPATIONAL HEALTH PROGRAM
This program is for all St. Louis University personnel who are considered to have some risk because of their
involvement with laboratory animals.
It is recognized that the Basic Program is the minimum required for all such personnel. Personnel in the
department of Comparative Medicine are covered by a separate, more comprehensive program.
Certain projects, particularly those involving hazardous agents or certain species, may necessitate more
comprehensive tests, exams, or protective measures. These will be decided upon during the protocol review
process and implemented as appropriate.
1.
Basic program, all personnel at risk
a.
b.
c.
d.
e.
Medical history evaluation.
Tetanus immunization every 10 years.
Tuberculosis screening (PPD) once, upon enrollment in program.
Evaluation of University work related injuries and illnesses (referral to Employee Health).
Written material entitled "The Safe Handling of Laboratory Animals" which includes information
on zoonotic diseases.
2.
Additional procedures, depending on species involvement
a.
Rodents and rabbits -- nothing additional
b.
Carnivore, livestock, feral species -- Basic program +
1)
Rabies prophylactic immunization + biannual booster (projects involving random source
dogs or cats or feral species only).
2)
Q fever surveillance (projects involving sheep, cattle, or goats only).
3)
Toxoplasmosis - awareness (cat projects only).
c.
Non-human primates -- Basic program +
1)
Tuberculosis screening every six months.
2)
Rubeola (measles) vaccination.
3)
Special attention regarding a bite or scratch by a nonhuman primate.
3.
Comparative Medicine personnel receive all of the above.
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ALLERGY TO LABORATORY ANIMALS
The following is excerpted from the book "Occupational Health and Safety in the Care and Use of Research
Animals." Allergies to animals are common. Allergies to laboratory animals (LAA) are a common and
important occupational health problem for persons who care for or work with them.
Allergic reactions to animals are among the most common conditions that adversely affect the health of
workers involved in the care and use of animals in research.
Workers exposed to laboratory animals can be categorized into several risk groups.
Risk of Developing Allergy to Laboratory Animals
Risk Group
Normal
Atopic
Asymptomatic
Symptomatic
Risk of allergic
reactions to
History
laboratory animals
No evidence of
allergic disease
Pre-existing allergic
disease
~10%
Immunoglobulin E
antibodies to
allergenic animal
proteins
Clinical symptoms on
exposure to allergenic
animal proteins
Up to 100%
Up to 73%
100%
Comment
90% of normal group will never develop
symptoms in spite of repeated animal contact
Workers who become sensitized to animal
proteins will eventually develop symptoms on
exposure
Risk of developing allergic symptoms of rhinitis,
asthma, or contact urticaria with continued
exposure is high
33% with chest symptoms; 10% of group might
develop occupational asthma; even minimal
exposure can lead to permanent impairment
MECHANISMS OF ALLERGIC REACTIONS
In the case of laboratory animal allergy, the route of exposure is most often due to airborne allergens.
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Allergic Reactions to Laboratory-Animal Allergens
Disorder
Symptoms
Signs
Contact urticaria
Redness, itchiness of skin, welts, hives
Allergic conjunctivitis
Sneezing, itchiness, clear nasal
drainage, nasal congestion
Allergic rhinitis
Sneezing, itchiness, clear nasal
drainage, nasal congestion
Cough, wheezing, chest tightness,
shortness of breath
Asthma
Anaphylaxis
Generalized itching, hives, throat
tightness, eye or lip swelling, difficulty in
swallowing, hoarseness, shortness of
breath, dizziness, fainting, nausea,
vomiting, abdominal cramps, diarrhea
Raised, circumscribed erythematous
lesions
Conjunctival vascular engorgement,
cheminosis, clear discharge (usually
bilateral)
Pale or edematous nasal mucosa,
clear rhinorrhea
Decreased breath sounds, prolonged
expiratory phase or wheezing,
reversible airflow obstruction, airway
hyper responsiveness
Flushing, urticaria, angioedema,
stridor, wheezing, hypo tension
Virtually all human beings are capable of developing allergic reactions; however, some individuals are more
susceptible. These people (topics) are more likely to develop IgE antibodies to allergens owing to an inherited
tendency.
Persons with atopy often develop allergic diseases, such as allergic rhinitis, asthma, and atopic dermatitis
(eczema) when chronically exposed to allergens.
SPECIFIC ANIMALS THAT CAN PROVOKE ALLERGIC REACTIONS
Rats
Rats are among the most commonly used laboratory animals and are responsible for symptoms in a large
portion of people who have laboratory-animal allergy. The major sources of rat-allergen exposure appear to
be urine and saliva of the animal.
Mice
Mice are another important source of allergen exposure of laboratory workers. The major mouse allergen is a
urinary protein.
Guinea Pigs
Immunochemical studies have identified allergenic components in the dander, fur, saliva, and urine of guinea
pigs.
Rabbits
Rabbits are used widely as laboratory animals and are a recognized cause of allergic symptoms in many
workers. A major glycoprotein allergen has been described that appears to occur in the fur of the animals,
and minor allergenic components found in rabbit saliva and urine have been identified.
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Cats
Domestic cats are kept as pets by many people, and sensitization can occur outside the laboratory
environment. Furthermore, allergy to cats might predispose workers to the development of allergy to
laboratory animals, such as mice and rats (Hollander and other 1996). Thee is a close link between
immunological sensitization and development of asthma in people sensitive to cats (Desjardins and others
1993). Those with pre-existing sensitivity might encounter worsening of their symptoms and possibly develop
asthma during the course of their work exposure.
Dogs
Like exposure to cats, exposure to domestic dogs outside the work environment can lead to sensitization and
is also a risk factor for laboratory animal allergy.
Primates
Sensitization to primates is unusual, despite widespread exposure.
Birds
Exposure to birds can cause rhinitis and asthma symptoms. Birds are also a potential source of
hypersensitivity pneumonitis, a lung condition in which a pneumonia-like illness develops after repeated
exposure to the antigen.
PREVENTIVE MEASURES AND INTERVENTIONS
Screening Programs
Preplacement screening evaluations can be helpful in identifying and alerting persons who might be at risk for
developing laboratory-animal allergy or asthma and educating them to take protective measures.
The presence of pre-existing allergic conditions in a person might increase likelihood of development of
asthma in an occupational setting where there is exposure to laboratory animals. Because most people will
not develop sensitivities beyond pre-existing conditions, this evaluation should not preclude employment.
Clearly people with pre-existing laboratory animal sensitivity should avoid repetitive exposure.
Facility Design
Cage emptying where loose bedding is used results in particularly high levels of allergen exposure. Use of
ventilated hoods or workstations for cage emptying and cage cleaning with filtered, recirculated air can reduce
exposure.
Filter-top cages have been shown to reduce concentrations of airborne allergens, compared with conventional
open-top cages.
Work Practices
Personnel with a history of allergies and particularly those with known sensitivities to animals are at highest
risk and so should be especially sought out for education.
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People with known risks are best assigned to tasks that minimize exposure. Some tasks -- such as simple
feeding, weighing, or necropsy -- produce low levels of exposure, whereas cage cleaning can lead to high
levels of exposure.
Personal Protective Equipment
However, surgical (cloth or paper) disposable masks are probably not effective. The use of gloves, laboratory
coats, shoe covers, and other kinds of protective clothing that are worn only in the animal rooms should be
encouraged. Frequent hand washing is important and showering after work might be of value.
Some commercial dust respirators can exclude up to 98% of mouse urinary allergens.
At a minimum, for symptomatic workers, the use of a dust-mist respirator certified by the National Institute for
Occupational Safety and Health should be required to control symptoms.
1.
Allergens. In: Occupational Health and Safety in the Care and Use of Research Animals. National
Academy Press, Washington DC, 1997, pp51-64.
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ZOONOSES
The term zoonoses is applied to those diseases which are naturally transmitted from animals to man.
A.
It is important to note that the transmission of zoonotic disease in the laboratory-animal environment is
uncommon, despite the number of animal pathogens that have the capacity to cause disease in
humans.
B.
The primary reasons for such a low incidence is that the laboratory-animal industry has had much
success in providing high-quality laboratory animals of defined health status for use in research.
For purposes of this discussion, we will exclude diseases produced by non-infective agents such as toxins and
poisons. Only some of the more important zoonoses are described below. Most discussions of zoonoses are
organized by agent category (e.g. virus, bacteria, etc.). We have arranged our discussion by the category of
species used in the laboratory. Further, we emphasize that we are only highlighting a few common or
important diseases. A more extensive discussion can be found in the NRC book which is available in
Comparative Medicine.
Rats, Mice, Hamsters, Guinea Pigs, and Rabbits
The vast majority of these animals are raised in highly controlled commercial facilities and are free of all
pathogens and, therefore, pose no risk. There are two diseases that need to be mentioned, primarily related
to animals raised in investigator-based breeding colonies.
Lymphocytic Choriomeningitis
Reservoir and Incidence - Lymphocytic choriomeningitis (LCM) virus is a member of the family Arenaviridae,
which consists of single-stranded-RNA viruses with a predilection for rodent reservoirs. Human infection with
LCM associated with laboratory-animal and pet contact has been recorded on numerous occasions.
Mode of Transmission - The LCM virus produces a pantropic infectin under some circumstances and can be
present in blood, cerebrospinal fluid, urine, nasophayngeal secretions, feces, and tissues of infected natural
hosts and possibly humans. Bedding material and other fomites contaminated by LCM-infected animals are
potential sources of infection, as are infected ectoparasites.
Slinical Signs, Susceptibility, and Resistance - Humans develop an influenza-like illness characterized by
fever, myalgia, headache, and malaise after an incubation period of 1-3 weeks.
Diagnosis and Prevention - Prevention of this disease in the laboratory is achieved through the periodic
serological surveillance of new animals that have inadequate disease profiles and of resident animal colonies
at risk and through screening for the presence of LCM in all tumors and cell liens intended for animal passage.
Rat-Bite Fever
Reservoir and Incidence - Rat-bite fever is caused by either Streptobacillus moniliformis or Spirillum minor, two
microorganisms that are present in the upper respiratory tracts and oral cavities of asymptomatic rodents,
especially rats.
Mode of Transmission - Most human cases result from a bite wound inoculated with nasopharyngeal
secretions.
Clinical Signs, Susceptibility, and Resistance - In Strep. moniliformis infections, patients develop chills, fever,
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malaise, headache, and muscle pain and then a maculopapular or petechial rash most evident on the
extremities.
Diagnosis and Prevention - Proper animal-handling techniques are critical to the prevention of rat-bite fever.
Dogs, Cats, and Pigs
As mentioned previously, only purpose-bred dogs and cats are used at Saint Louis University. As such, the
potential risk for acquiring a zoonotic disease is minimal. A few diseases will be discussed. Rabies is
discussed in the feral animal category.
Campylobacteriosis
Reservoir and Incidence - Organisms of the genus Campylobacter have been recognized as a leading cause
of diarrhea in humans and animals in recent years, and numerous cases involving the zoonotic transmission of
the organisms in pet and laboratory animals have been described.
Mode of Transmission - The organism is transmitted by the facal-oral route via contaminated food or water or
direct contact with infected animals.
Clinical Signs, Susceptibility, and Resistance - Campylobacters produce an acute gastrointestinal illness,
which in most cases if brief and self-limiting.
Diagnosis and Prevention - Personnel should rely on the use of protective clothing, personal hygiene, and
sanitation measures to prevent the transmission of the disease.
Fungal Diseases
Dermatomycosis
Reservoir and Incidence - The dermatophytes have a cosmopolitan distribution; some dermatophytes have a
regional geographic concentration. These organisms cause ringworm in humans and animals, which
continues to be common among dogs, cats, and livestock.
Mode of Transmission - The transmission of dermatophyte infection from humans to animals is by direct skinto-skin contact with infected animals or indirect contact with contaminated equipment or materials. Infected
animals can have no, fe, or difficult-to-detect skin lesions that result in transmission to unsuspecting persons.
Clinical Signs, Susceptibility, and Resistance - Dermatophytes that are better adapted to humans produce
focal, flat, spreading annular lesions that are clear in the center and crusted, scaly, and erythematous in the
periphery. Lesions often are on the hands, arms, or other expose areas, but invasive and systemic infections
have been reported in immunocompromised people.
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Diagnosis and Prevention - The definitive diagnosis of dermatomycosis is achieved by fungal culture and
identification, but lesions appearance and scapings, of active lesions cleared in 10% potassium hydroxide and
examined microscopically for fungal filaments can be used for a tentative diagnosis. The use of protective
clothing, disposable gloves, and other appropriate personal-hygiene measures is essential to the reduction of
this zoonosis in a laboratory-animal facility.
Cat-Scratch Fever
Reservoir and Incidence - Bartonella henselae, a newly described rickettsial organism, has been directly
associated with cat-scratch fever and bacillary angiomatois. The organism has been isolated on fleas that fed
on infected cats, and fleas have been shown to be capable of transmitting the organism between cats.
Although cat-scratch fever usually has bee associated with the scratch or bite of a young cat, other animals
have been implicated, including dogs, monkeys and porcupines.
Mode of Transmission - Of patients with the disease, 75% report having been bitten or scratched by a cat, and
over 90% report a history of exposure to a cat.
Clinical Signs, Susceptibility, and Resistance - The disease begins with inoculation of the organism into the
skin of an extremity, usually a hand or forearm. A small erythematous papule appears at the site of
inoculation several days late and is followed by vesicle and scab formation. The lesion resolves within a few
days to a week.
Diagnosis and Prevention - Isolation of the causative organism from the blood, a cutaneous lesion, or biopsy
material is required for a definitive diagnosis of cat-scratch fever. The use of proper cat-handling techniques
and protective clothing should minimize the likelihood of personnel exposure to the organism of cat-scratch
fever.
Toxoplasmosis
Reservoir and Incidence - Toxoplasma gondii is a coccidian parasite with a worldwide distribution among
warm-blooded animals. Wild and domestic felines are the only definitive hosts of this organism; they are
infected by one another or through predation of an intermediate host, and they support all phases of the t.
gondii life cycle in their intestinal tract, although numerous other tissues are also involved in feline
toxoplasmosis.
Mode of Transmission - Infection results from the ingestion of infectious oocysts in food, water, or other
sources contaminated by feline feces.
Clinical Signs, Suceptivility, and Resistance - Toxoplasmosis generally produces an asymptomatic or mild
infection with fever, myalgia, arthralgia, lymphadenopathy, and hepatitis. Toxoplasma infection can have
severe consequences in pregnant women and immonologically impaired people. In a pregnant woman with a
primary infection, rapidly dividing tachysoites can circulate in the bloodstream and produce a transplacental
infectin of the fetus.
Diagnosis and Prevention - Toxoplasmosis can be diagnosed by finding the organism in clinical specimens.
Personnel should practice appropriate personal-hygiene practices and maintain rigorous sanitation of an
animal facility to prevent exposure to toxoplasma. Unless they are known to have antibodies to toxoplasma,
pregnant women should be advised of the risk associated with fetal infection. Cat feces and litter should be
disposed of promptly before sporocysts become infectious, and gloves should be worn in the handling of
potentially infective material.
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Sheep, Goats, and Other Ruminants
There is a much higher likelihood of injury as a result of a kick or muscle strain than acquiring a zoonotic
infection.
Q Fever
Reservoir and Incidence - Q Fever is caused by the rickettsial agent Coxiella bernetii. Infection is widespread
within the domestic-animal cycle, which includes sheep, goats, and cattle. Cats, dogs, and domestic fowl also
can be infected. The prevalence of the infection among sheet is high throughout the United States, and sheep
have been the primary species associated with outbreaks of the disease in laboratory-animal facilities.
However, an outbreak of Q fever with one death in a human cohort exposed to a parturient cat and her litter
and cases of the disease associated with exposure to rabbits indicate that other species should not be
overlooked as possible sources of the infection in the laboratory animal environment.
Mode of Transmission - Humans usually acquire this infection via inhalation of infectious aerosols, although
transmission by ingestion has been recorded. The organism is shed in urine, feces, milk, and especially birth
products of domestic ungulates, which generally are asymptomatic. The organism is resistant to desiccation
and persists in the environment for long periods, contributing to the widespread dissemination of infectious
aerosols. The importance of those factors was evident in outbreaks of the disease associated with the use of
pregnant sheet in research facilities in the United States when personnel became infected along the routes of
sheep transport and in the vicinity of sheep surgery from contact with soiled linens.
Slinical Signs, Susceptibility, and Resistance - The disease in humans varies widely in duration and severity,
and asymptomatic infection if possible. The disease often has a sudden onset with fever, chills, retro bulbar
headache, weakness, malaise, and profuse sweating. Acute pericarditis and acute or chronic granulomatous
hepatitis also have been reported. Persons with valvular heart disease should not work with C. burnetii.
Diagnosis and Prevention - Serological methods available for the detection of a rise in specific antibody
between acute and convalescent samples include microagglutination, immunofluorescent, complement fixation
(CF) and ELISA tests. Recommendations for the control of Q fever in a research facility are available and
should be applied rigorously in surgical, laboratory, and housing areas used for sheep. Physical barriers or
air-handling systems, the appropriate use and disposal of protective clothing, and the use of disinfectants in
the sanitation and waste-management programs minimize the risk of exposure.
Orf Disease (Contagious Ecthyma and Contagious Pustular Dermatitis)
Reservoir and Incidence - Orf disease is a poxvirus infection that is endemic in many sheep flocks and
goatherds throughout the United States and worldwide.
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