Animal Population Management
Animals must be carefully
managed and maintained when being used for research to prevent disease
and death. Illness and poor husbandry can introduce unplanned and
unwanted variables that may invalidate test results,
unpredictably altering the animal's response to the experimental
variables.
There are numerous
classification systems used to describe animals in a research
facility.
The pathogen status or
ecological classification of an animal is a description of the
micro-organisms present prior to the start of an experiment. Many
experiments introduce bacteria or viruses into animals, changing their
microbial make up. These animals' pathogen status, however,
continues to be classified by their initial microbial population.
Conventional animals
are raised under standard conditions. They have the
"normal" micro-organisms that are present in any healthy
animal. Dogs and cats at a boarding kennel are conventional
animals. These are the least expensive animals for research.
Specific pathogen free
(SPF) animals are conventional animals that
have been tested for designated disease-causing pathogens by serology, bacterial culture or
histopathology, and the tests show no evidence of infection. Cats
that have been tested for feline leukemia virus (FeLV) and mice tested
for mouse hepatitis virus (MHV) are SPF. They may contain,
however, a variety of other micro-organisms which have not been
identified.
Gnotobiotic (noe-toe-bye-ah'-tic)
or defined-flora animals have no pathogenic micro-organisms, and the
nonpathogenic microbes present are identified. We know the
organisms present--often bacteria and protozoa that are needed for
hindgut fermentation. To prevent contamination by other microbes,
these animals are maintained in sterile flexible film isolators.
Axenic animals are
germ-free. There are no detectable viruses, bacteria, fungi,
parasites or protozoa present. These animals are removed
from their dam by caesarian section (caesarean-derived), and are raised
and maintained in a sterile isolator. Many transgenic and most
immunodeficient rodents are axenic.
Dogs and cats are also
classified based on their origin. Purpose-bred animals are
raised specifically for research. The animals have been
selectively bred for health and temperament and are generally SPF for
pathogens such as FeLV and canine heartworm.
Random source animals are obtained from anywhere except a purpose
breeder, generally from animal shelters and pounds. These animals
have unknown history and pedigree.
Larger animals, such as
cats, dogs, primates and farm animals, can be classified by the amount
of conditioning or processing that they have
received. Unconditioned animals have been held at
least five days by the supplier and have not been vaccinated, dewormed or
tested or treated for disease-causing organisms. Conditioned
animals have been held by the supplier for two or more weeks and have
been vaccinated and treated for bacterial and parasitic infections.
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Animal Selection and
Handling:
Animals are
usually obtained from commercial animal breeders and dealers. In
New York, only purpose-bred dogs and cats are available from dealers.
To prevent the inadvertent use of pets in experiments, it is
illegal to purchase pound animals for research. Primates may be wild-caught and
imported or bred at primate centers in the United States. Animals
may be donated for use in research if the donator bred and raised the
animal.
When selecting an animal,
it is important to evaluate the source, to ensure that the supplier is
able to provide the required animal.
Most dealers perform a number
of tests and treatments on their animals, and
health reports should be
provided. The requirements of the experiment determine the
pathogen and genetic status of the animals needed.
Transport of animals is
regulated by the Animal Welfare Act. Post-transport stabilization
for twenty-four hours after receipt is essential to allow stress-induced
immune depression to return to normal.
Newly-arrived animals
should be quarantined to prevent the potential transmission of disease
from these animals to resident animals. Quarantined animals should
be housed separately from other animals and monitored for health and
disease. In-house conditioning (acclimation), including exposure
to experimental conditions and procedures, should be utilized to
ensure the health and well-being of the new animals.
Health monitoring should
continue throughout an animal's tenure at a research facility to prevent
and treat disease and to guarantee the validity of experimental
data. Genetic monitoring is used to ensure that exact strains are
maintained. Constant environmental monitoring of temperature and
humidity is essential.
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Animal Identification
and Record-Keeping:
Everything done
with and to an animal must be recorded completely and correctly,
including identification of the animal being used.
Permanent identification
is required for all animals the size of guinea pigs or larger.
There are a variety of methods that can be used. Some animals can
be identified by description (the white cat with a black patch on its
left flank) or by the cage that they are in. Collars and bands can
be placed on dogs and cats, primates, birds, sheep and cattle.
Tattoos can be used on any animal, from neonatal (newborn) mice to
horses. Freeze branding can be used on larger farm animals.
Ear tags are available
for most animals and ear notching (punching) can be used. A
uniform number code is used for notching rodent ears. Tags and ear
notches may be torn or removed, making identification difficult.
Neonatal mice and rats
rarely are identified by amputating a toe (toe clip); this
method, however, requires IACUC approval.
Nontoxic dyes, markers and crayons can be used as temporary
identification methods.
A subcutaneous
transponder (microchip) is a miniature radio transmitter that is
inserted under an animal's skin. It transmits a specific
identifying code to the receiver and can be used to identify
animals. Some transponders can also monitor physiologic factors
such as body temperature. This systems are expensive, but are
extremely accurate and are more durable than ear notching or tagging.
A research facility requires a lot of paperwork.
Administrative records include:
Animal records must also
be maintained. These include clinical and breeding records,
medical profiles and acquisition and disposition documentation.
All records must be
maintained at least three years. If records are supporting
documentation for product development, they must be kept at least seven
years.
Budget:
The budget process is an
essential part of experimental design. Cost accounting is the
determination of the cost of services in order to project budget
requirements. Both direct expenses (for animals, supplies and
staff) and indirect expenses (for power, depreciation, etc.) must be
calculated. Many research facilities charge a per diem fee
for animals housed on site. This is the cost charged to the
researcher of maintaining one animal for one day. It includes the
activities of the animal care personnel, husbandry supplies, veterinary
care, laundry and uniforms, and facility maintenance and overhead.
Generally, smaller animals have a lower per diem than larger dogs, pigs
and cattle. Transgenic and immunodeficient rodents have a higher
per diem than outbred or SPF mice and rats.
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Health and Disease:
Disease is dis-ease: an alteration of the normal anatomy and
physiology of an animal. Typically, more than one body system is
involved, resulting in a sick animal.
Laboratory animal personnel are responsible for keeping the animals
in their care healthy. This includes monitoring animals during
quarantine, conditioning, maintenance and experiment. Every animal
must be observed every day. Any indications of discomfort or
disease in an animal should be documented on the animal's record and
reported to the supervisor immediately.
Stress is
an animal's physiological and emotional response to stimuli.
Almost any change in an animal's environment is accompanied by signs of
stress. It is important to keep the need for a stable environment
in mind to minimize stress-induced nonexperimental variables.
Transportation, routine handling, isolation or overcrowding, a change in
the caretaker or food, or differences in the frequency of food or cage
cleaning can all be stressful and may lead to disease.
Stress and disease can
introduce unplanned and nonexperimental variables into a study. In
this situation, it is difficult to determine if an observed change is
due to the experiment variable or disease. In order to minimize
stress, disease, and invalidated research, it is essential to use high
quality animals, ensure proper quarantine and conditioning, strict
adherence to the facility's Standard Operating Procedures, and careful
observation and prompt reporting of any abnormalities.
The etiology of a
disease is the organism or problem that causes it to occur. Many
animals can harbor a variety of micro-organisms, and yet not be
ill. When a number of factors coincide, however, disease may
result. Inadequate control of environmental factors, such as
noise, humidity and airborne contaminants, is an important contributing
factor to the development of disease. It is essential that
animals receive pure high quality food and water. The genetics of
an animal may result in inherited diseases or creation of a new disease
state due to genetic mutation. Pathogenic microbes and parasites
are common causes of disease, especially in an animal that is stressed
and / or in substandard housing. Our inadvertent mistakes can
cause iatrogenic disease: it's our fault, for example, that the
rabbit has a broken back, because we did not restrain it
adequately. Some diseases are idiopathic: we just
don't know why the animal has developed cancer or osteoarthritis
or other degenerative diseases.
Diseases can be
transmitted by a variety of mechanisms. Disease caused by viruses,
bacteria, fungi or parasites is infectious. Diseases that
occur due to genetics, trauma or similar causes are noninfectious.
If an animal has an infectious disease that can be transmitted to
another animal, the disease is contagious. Contagious
disease can be transmitted by direct contact with the infected animal,
through fomites (inanimate objects, such as cages and brushes, that were
contaminated during use on an infected animal), by vectors
(blood-sucking arthropod parasites that transfer infected blood to an
uninfected animal) and through aerosols. Transmission from animal
to animal within a cage or room is horizontal disease
transmission. Passage of the pathogen from the dam to her
offspring before birth is called vertical transmission.
Animal diseases that are contagious to people are called zoonoses.
It is essential that
animal care personnel know what an healthy ("normal") animal
looks like and how it acts. The signs of a disease are the
objective characteristics that you determine: the body
temperature, vocalizations when touching a painful area, refusal to eat
or drink. (Animals do not have symptoms: these are
subjective assessments of how you feel...and animals are unable to
express these thoughts.)
Common signs of disease
in animals include:
- Alopecia (thinning or loss of
hair)
- Anorexia (lack of appetite and
refusing to eat)
- Coughing or sneezing (C/S)
- Dyspnea (difficulty breathing)
- Lethargy (weak and inactive)
- Depression (uninterested in
surroundings)
- Pruritis (itching)
- Rough hair coat and hunched posture
- Vomiting and diarrhea (V/D)
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Animals are frequently
characterized by their response to their surroundings and general
attitude. Animals that are lethargic, anorectic and depressed are LAD.
Bright, alert and responsive animals are BAR. Some animals
are QAR (quiet, alert and responsive).
Often, a disease will be
inapparent or subclinical: no signs will be detected. The
animal's immune system may eliminate the pathogen, so clinical disease
will never occur, or, if the animal is stressed, the animal may lose the
battle of the microbe and become ill.
Chronic diseases develop
slowly. Tuberculosis (TB) and feline leukemia are slow-onset
diseases, but cause very serious illness or even death. An acute
disease develops rapidly: a pimple or mosquito bite is acute, but often much
less serious.
Identification and
Treatment of Disease:
Prevention is the
first, most effective and most important method of controlling
disease. The ideal animal in the ideal animal facility will never
become ill. However, stress, disease and accidents can occur, and
the results must be addressed.
Diagnosis is the
identification of a disease. To make a diagnosis, a veterinarian
will evaluate the clinical signs, laboratory tests and necropsy
(autopsy) results.
It is important to be
able to describe the severity and incidence of a disease. There
are several terms that aid in this description. Morbidity
is the number of animals with a disease. Some diseases, such as
canine distemper, have a low morbidity: few dogs are infected. Mortality
is the number of animals that die from the disease: all dogs that are
infected with rabies virus die from that disease. An enzootic
(like an endemic in people) is a situation where a few cases of the
disease occur sporadically, such as rabies
in bats. An epizootic (like an epidemic) occurs when
there is an outbreak of large numbers of animals with the disease, such
as rabies in
raccoons (New York has more cases of rabies per year than any other
state in the United States--not a very desirable statistic!).
If prevention is not
effective and disease is diagnosed in a colony of animals, there are
three primary options:
- Cull (euthanize) the animals and start
over
- Treat the individual animal
- Treat the entire colony of animals
If an animal is ill due
to a very virulent and/or highly infectious organism, it may be most
effective to eliminate the infected animal(s) and begin again, before
the infection spread to other animal cages, rooms or facilities.
When an animal is extremely valuable, due either to its initial cost or
its role in an experiment, it may be treated individually. It is
often advisable to isolate sick animals and treat all of the
animals, sick and healthy, so that the rest of the colony is protected
from becoming ill.
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Reading
Recommendations: Guide- Chapter
2 and Chapter
4 and the in-text links