Unit 2

Role of "Agent" in Health and Disease

Characteristics of an infectious agent (parasite or pathogen)

 ability to multiply - generation time of organism

 ability to spread from one animal to another
 ability to evolve quickly to outsmart host defenses
 ability to cause damage (pathogenicity, virulence)

Types of Agents (pathogens)

 Bacteria
 Viruses
 Fungi
 Protozoa
 Parasites

Steps that an Agent must complete to cause disease:

1. attach and enter host

2. evade host defenses/reach target tissue or organ
3. multiply
4. exit and enter another individual (transmission of disease)

Attachment +/or entry into the host body

means of attachment and entry vary, depending on the body site

Sites of attachment/entry
SKIN

 Characteristics of skin
 o difficult to penetrate when intact; easier under following circumstances
 wounds, bites
 softened by moisture
o normally colonized by bacteria, fungi
o keratin, sweat, sebum provide nutrients

MUCUS MEMBRANES

Line the lungs, gastrointestinal (GI) tract, and urogenital tract

Respiratory entry of agents into host

 host defenses

a. nasal turbinates

o temperature lower than required by most pathogens

o baffle
o agents are trapped in mucus and swallowed
o large particles are trapped at this level

b. intermediate level respiratory tract

o coated with a mucociliary blanket

o smaller particles are trapped at this level

c. lower respiratory tract

o alveolar macrophages phagocytize agents

o smallest particles may travel this far

Note that the size of the agent as well as the size of the water droplet or dust particle
upon which it may be carried can determine what level of the lung is exposed to the
agent.
  Agent's means of evading host defenses

a. bacteria/viruses attach to cells by specific receptors to prevent being swept out

o bacteria are able to attach to the cells lining the mucus membranes by
structures called pili or fimbriae
o at the molecular level, adhesins on surface of agent bind to integrins or
other receptors on surface of host cell (ex. S. typhimurium binding to
EGF receptor)

b. agent may interfere with action of cilia/mucus

o Mycoplasma, Bordetella, Haemophilus inhibit ciliary action

o viruses kill epithelial cells

c. agent may interfere with action of alveolar macrophage

o respiratory virus, toxins

Gastro-Intestinal Entry of Agent

 Host defenses
o acid, bile provide hostile environment for agent
o movement of ingesta, constant flushing to prevent attachment
o commensal bacteria (physical barrier)

 Agent's means of evading host defenses/causing disease

o Attachment and adhesion to epithelial cells Enteropathogenic E.
coli, Salmonella and Shigella
 specific structures, receptor sites
 invasive (enteropathogenic E. coli) and noninvasive
 enveloped viruses fuse with cell membrane
 some bacteria enter via specialized epithelial "M" cells over
peyers patches
o Toxin production Bacterial Toxins: Friends or Foes?
 exotoxins
 secreted by bacteria
 acts by damaging host cell surface, causing death of cell
  example -- Clostridium
 endotoxins
 released as agent dies
 enterotoxin - secretory diarrhea
 verotoxin - hemorrhagic diarrhea (EHEC)
o Cause malabsorption of nutrients
 direct damage to epithelial cells
 villus atrophy (cryptosporidia)
 bacterial overgrowth that inhibits absorption

Urogenital (UG) Entry of Agent

 Host defenses
o flow of urine
o long urethra
o vaginal pH

 Agent's means of evading host defenses

o attachment and adhesion
o trauma to UG tract may facilitate entry

Conjunctival Entry of Agent

 Host defense -- tears, flushing and lysozyme

 Agent's means of evading host defenses

o enzymes secreted by agent

 Environment effects -- dry, dusty conditions; flies

Multiplication and Spread of Agent Within Body

Tissue tropism
Some organisms do not normally spread beyond the tissue originally invaded

 skin -- ringworm
 lung -- Bovine Respiratory Syncytial Virus (BRSV)
 intestine -- Rotavirus

These organisms:

1. multiply locally
2. spread rapidly from cell to cell by liquid media (mucus membranes) in
respiratory and GI tracts
3. often held at bay at site of entry by host immune defenses

Other agents have a distant site as target (ex. Salmonella pullorum for adult avian
ovary)

Their location of growth and multiplication depends on specific requirements for

microenvironment within the body

o temperature
o nutrition of disease agent (ex. Brucella - erythritol)
o oxygen tension in tissue
o migration of larval stages of internal parasites (round worm)

Means of travel of the "Agent" -- road

1. bloodstream
2. lymph
3. other routes (i.e. nerves for rabies, pseudorabies, tetanus)

Means of travel of the "agent" -- vehicle

 1. extracellular - free in blood and lymph -- easy target for host immune defences

a. recognized and "eaten" by phagocytes

b. carried to lymph node where specific antibody production is stimulated

c. stimulate immune response in animal -- cytokines, TNF, interferon,

histamine, prostaglandins, acute phase proteins
2. intracellular - hidden from immune system within a host cell

a. Phagocytes (white blood cells) -- must resist digestion -

ex. Listeria, Brucella, Mycobacterium

b. Erythrocytes (red blood cells) -- viruses cannot use

ex. Eperythrozoon, Babesia, Hemobartonella

c. Other host cells, such as epithelial cell of gut

ex. Coccidia, Toxoplasma

Destination

1. determined by "address" receptor on capillary of blood vessels in target organ

2. local extension from site of entry

a. enzymes dissolve and liquefy tissue

(hyaluronidase, streptokinase, fibrinolysin)

EXIT of agent allows spread to other individuals

 Respiratory, salivary route of exit and spread

o agents causing respiratory, systemic disease
(PRV, rabies, foot and mouth disease, etc.)
o increased density of animals, exertion, bawling, coughing, etc.
exacerbate spread

 Fecal route of exit and spread

o proper sanitation can minimize spread
 Venereal route of exit and spread
o testing stock before introducing into herd
o use of artificial insemination (AI)

 Blood as route of exit and spread

o insect control
o sterile needles, syringes, surgical instruments

 Spread without shedding from host

o direct transmission to offspring in utero (vertical transmission)
o eating tissues harboring agent (Trichina, Kuru, BSE)
o environmental contamination by dead animal (Anthrax)
 Unit 3
Role of "Host" in Health and Disease

The host animal has a number of different defense mechanisms by which it deals with
the onslaught of infectious agents. They can be broken into three parts, based on the
specificity of response.

First Line of Defense -- skin & mucus membranes

Temperature -- the surface temperature of skin is lower than the core body
temperature of an animal and is also lower than the temperature required for many
infectious agents to multiply.

Surface layer of cells -- the skin has an outer layer of dry, dead, keratinized cells that
do not provide a hospitable environment for infectious agents. Likewise, many mucus
membranes are covered with a mucus layer that traps infectious agents and physically
prevents them from interacting with the epithelial cells lining the mucus membrane.
This mucus layer in the respiratory tract is swept up from the deeper regions of the
lung to the oropharynx of the animal by cilia on the surface of the epithelial cells
lining the bronchioles and bronchi.

Secretions and excretions -- the anti-microbial action of gastric acid and bile secreted
into the gastrointestinal tract; peristaltic movement of ingesta through the intestinal
tract and flushing and antimicrobial action of urine and tears prevents the attachment
and proliferation of infectious agents in many parts of the body.

Second Line of Defense -- nonspecific immune response (Hoopes and Thwaits,

chapter 5; Mims, chapter 3 -- inflammatory response)

Inflammation -- an increase in blood circulation at site of infection leads to the

classic signs of inflammation -- redness, swelling, heat, pain. This is due to:

o increase in the permeability of blood vessels in the area. This results in a

buildup of the following compounds in the effected tissues:
 complement
 proteins, such as fibrinogen, histamine, kinins
 cytokines (interferon, interleukins, etc.)
 leukocytes (white blood cells-WBC)
 phagocytes -- monocytes (macrophages)
  polymorphs
 lymphocytes -- B & T cells

Inflammation is a two-edged sword for the host animal.

The benefit of the inflammatory reaction is that there is a very quick response to the
disease agent which may stop further progression of the disease. The downside of the
inflammatory reaction is that it is nonspecific and the inflammatory compounds
released are also harmful to the host.

Because of this, inflammation is under tight regulatory control in the body.

Increase in lymph circulation -- this results in:

1. transport of "agent" to local lymph node

2. ingestion by macrophages (phagocyte) in marginal sinus of lymph node
3. presentation of "antigenic units" to lymphocytes
4. beginning of specific immune response
5.

Third Line of Defense -- Specific Immune Response

There are two different parts, or branches to this response. They consist of:

o Cell-mediated immunity (CMI) - T lymphocytes, Natural Killer (NK)

cells
o Humoral immunity (antibody) - B lymphocytes

Humoral Immunity

Role of antigen presenting cell (APC)

o monocyte, macrophage, histiocyte, dendritic cell

o "process" proteins from agent
o present the processed proteins to T "helper" lymphocyte, or B
lymphocyte

Role of B lymphocyte

o circulate and bind some specific antigens or processed proteins from T

helper lymphocytes
o differentiate into "memory" cells
o differentiate into plasma cells -- produce antibody (immunoglobulin)
Immunoglobulin M (IgM)

 produced first by the B lymphocytes

 very large - stays in bloodstream
 activates complement - kills cells (membrane attack complex)
 short lived - isotype switch to IgG, E, A production by B
lymphocytes
 relatively nonspecific - cross reactions
 only immunoglobulin produced by fetus

Immunoglobulin G (IgG)

 takes longer to produce - requires B cell switch

 smaller molecule (monomer) - gets into tissues
 "opsonizes" agent to aid in phagocytosis
 long lived in body - varies with agent
 more specific

Immunoglobulin A (IgA)

 "mucosal" antibody
 also requires B cell switch to produce
 present as a dimer - secreted onto the mucosal surface
 poor at opsinization but binds and neutralizes agent

Immunoglobulin E (IgE)

 produced in allergic and parasitic reactions

 binds to mast cells beneath epithelium
 stimulates degranulation of mast cells

Functions of IgG and IgA

o Neutralize bacterial toxins

o Neutralize viral agent by binding to specific receptor used to enter cell
o Neutralize bacterial agent by binding to "adhesin" - especially IgA
o "Opsinize" bacteria - function of IgG

Cell-mediated Immunity

Role of T lymphocyte (2 types)

CD4 "helper" T lymphocyte

 helps B cells produce immunoglobulins (antibodies)

 activates macrophages
 activates polymorhs
 activates NK (natural killer) cells
 helps CD8 "cytotoxic" T cells

CD8 "cytotoxic" T lymphocyte

 destroys infected host cells

Host Reactions as indirect mechanisms of disease

Immune complexes -- may be deposited onto cell membranes and cause damage
(kidney disease, arthritis)

Anti-host antibody production -- cross-reacting haptans

Cell-mediated immunity -- destroys host cells

Review of Interactions between Agent and Host

Persistent Infection

A. Ways in which agent out-maneuvers the host

1. antigenic variation - influenza virus

2. become "latent" until immunity wanes

a. intracellular bacteria, viruses - herpes
b. stress, hormonal changes, etc. lead to reactivation

3. resistance to or exploitation of host defense

a. live & multiply within phagocyte
b. live & multiply within lymphocyte

AIDS - T lymphocyte
mouse mammary tumor - B lymphocyte

B. Immunosuppression contributes to persistence

1. stress - cortisol inhibits B cell differentiation

 2. Staphylococcal toxins are immunosuppressive
3. other agents also suppress immune system

C. Failure of host defense system

1. Inherited Immunodeficiency

a. BLAD (bovine leukocye adhesion deficiency)

b. Chediak-Higashi Syndrome - failure of intracellular killing - Aleutian mink
disease
c. SCID (severe combined immune deficiency) - mice

2. Acquired Immune Deficiency

a. AIDS - human
b. SIV - monkey
c. FeLV - cat
d. BLV - cattle

3. "Immaturity" of Immune System - Neonate

a. importance of colostrum
b. role of maternal antibodies in blocking active immunity

Role of Host -- Practical Aspects of Immune Function

Classification of Immunity -- Natural vs Acquired

Natural Immunity is the innate or inborne resistance of an animal to certain types of

disease. This does not require antibody (immunoglobulin) production. Natural
immunity could be due to lack of receptors for the infectious agent within the host cell,
or nonspecific immune responses.

Acquired Immunity is an immunity to specific infectious agents that the animal

acquires, either actively or passively. Acquired immunity is usually evaluated by
measuring antibodies in the blood of the animal.

Passive Immunity is the result of passive transfer of antibodies from an immune

individual to a susceptible individual. It provides immediate protection against the
infecting agent, however the protection is short-lived and wanes as antibodies are
catabolized.

1. "Colostrum" is the primary means of transfer of passive immunity to neonatal

animals in domestic species.
2. Transplacental transfer of antibodies occurs in rabbits and primates; there is
limited transplacental transfer in dogs and cats and essentially no transplacental
transfer in domestic livestock.
3. Passive immunity can also be obtained by injecting immune antiserum into the
susceptible animal.

Active Immunity is developed by an animal in response to exposure to an agent, or by

vaccination. Active immunity takes longer to develop (4-5 or 7-10 days), but it is also
longer lived in the animal. Protection can be increased by "boosting" (anamnestic
response).
 Unit 4
Role of Environment in Health and Disease

General Factors

Weather -- optimal conditions for host and pathogen may be similar or very different

 temperature
 humidity
 wet environments
o favor diseases such as foot rot, leptospirosis
o cause proliferation of mosquitoes that carry disease agents such as West
Nile Virus
 dry environments
o favor other diseases such as coccidiomycosis

stress imposed by high or low temperatures, or high humidity may affect immune
function of host

Air Quality & Ventilation

 NH3, H2S, dust, airborne bacteria

 effect on productivity
 effect on immune system
 high NH3 contributes to E. Coli & Aspergillus air sacculitis in poultry

Prevailing Winds

 Eastern Equine Encephalitis (EEE) spread by wind blown mosquitoes

 swine/poultry enterprises located so they are not downwind of other animal
facilities
 Foot & Mouth Disease

Geographic Econiche of agent

 "Texas Fever line" - Boophilus tick territory

 geographic source of feedstuffs, bedding contaminated with agent - blister
beetle poisoning
Social Distance

 increases in wildlife population of an area

o deer population - Tuberculosis in diary cattle
o raccoon population - rabies threat
 increases in livestock population density result in faster transmission of disease
agent
 potential management control point for disease

Husbandry Factors

A number of factors related to the environment and other health parameters of the host
can be controlled by altering the husbandry (scientific control and management) of the
animal. Some of these factors are:

 Nutrition of the host animal(s)

 Housing of the host animal(s)
o use of layer cages removed birds from source (agent) of coccidiosis
o use of slatted floors in swine units removed animals from source of other
infectious agents
 Genetic Selection of the host animal(s)
o increased resistance to disease
o eliminate hereditary diseases such as inherited immunodeficiencies
 Appropriate vaccination/controlled exposure to infectious agents
 Population Density control
 Protection of young and pregnant
o regulation of body temperature in newborn
o farrowing crate, creep areas for young
o minimize stress in pregnant animal
 Control environmental contamination with agent(sanitation)
o decrease dose of agent to host
o hardiness of agent in environment affects methods that can or must be
used
 (anthrax vs. SIV)
 Other husbandry techniques that effect the health status of the host animal
o tail docking - use of elastrator bands can lead to tetanus unless
vaccinated or given toxoid
o syringes & needles - dirty equipment can lead to abscesses, spread of
agent
 o animal handling techniques - roughness can lead to increased stress,
body temperature, bruising

Toxins in the environment

Toxic Plants

"Indiana Plants Poisonous to Livestock & Pets"

Among the most important toxic plants in Indiana are:

o white snakeroot, pokeweed, pigweed

o poison hemlock, spotted waterhemlock
o yew, wild black cherry, Ohio buckeye
o cocklebur, jimson weed, nightshade
o sweet & alsike clover, Johnsongrass

Plant poisonings more common when good forage and feedstuffs are scarce

o early spring and fall on pasture

o winter - stored forages contaminated with toxic plants

Chemical Toxins

The presence of chemicals in the environment of the host animal may cause disease in
the exposed animal(s). Examples of some chemicals toxic to livestock are:

 Insecticides
o Organophosphates
o Carbamates

 Rodenticides
o Warfarin & other anticoagulants
o Strychnine
o Rampage, vitamin D3 type rodenticides

 Metals
o Arsenic
o Lead
o Selenium (in excess)

Biotoxins
Other toxins in the environment of the host animal are produced by other living
organisms. Examples of these biotoxins are the mycotoxins produced by fungi present
in feedstuffs produced or stored under environmental conditions conducive to their
growth. Examples of such mycotoxins are:

Fusarium moniliforme

o present in contaminated corn

o causes neurologic disease (horses),
o pulmonary disease (swine)

Fusarium graminearum

o present in contaminated corn

o produces estrogen-like compound (zearalenone), feed refusal factors
(swine)

Claviceps purpurea

o present in contaminated wheat & rye

o responsible for ergot poisoning
 Unit 5
Principles of Control of Infectious Disease
This unit is divided into three subtopics. Select a topic to get started:

Unit 5
Principles of Control of Infectious Disease
General concepts of prevention, control and eradication
of disease in an animal population

There are 3 concepts of control of infectious disease that will be examined in this unit.
These are Prevention of disease within a group on animals, Control of pre-existing
diseases within a group of animals, and Eradication of disease from an animal
population.

I. Prevention of Disease within a group of animals

A. Quarantine and testing of animals before introducing into the group or, maintaining
a completely closed herd, with no live animal additions (must use artificial
insemination to introduce new genetic material)

B. Vaccination

1. doesn't prevent exposure to disease agent, but will hopefully prevent disease when
exposed

II. Control of Disease within a group of animals -- reduction of disease to

biologically +/or economically feasible levels

A number of sub-populations of animals exists within a diseased herd. They consist

of :

1. infected animals
a. sick
b. "apparently" normal

2. uninfected animals

a. susceptible
b. non-susceptible

The goals of disease control within the herd or flock are threefold:

1. decrease prevalence of existing disease

2. decrease incidence of new infection
3. decrease morbidity and mortality rates

A number of management practices can be used to carry out these goals.

1. To decrease the number of currently infected animals, one must:

o identify the infected animals

o cull them from the herd or flock or
o treat infected animals promptly and effectively

2. To decrease the incidence of new infection, one must reduce the infection
pressure on uninfected, susceptible animals within the herd or flock. This can be
accomplished through a combination of the following environmental management
techniques:

o Sanitation -- maintain a clean environment, feed and water supply. Many

agents are spread from animal to animal by fecal contamination of feed,
water and the environment.
o Provide "controlled" infection pressure
 lower the level of exposure in environment
 expose new additions to limited doses of environmental agents
(add small amounts of fecal material to isolated animals)
o Quarantine new additions; isolate sick animals
o Don't mix animals from different sources
o Separate neonates from dams early in life (assure adequate colostrum
intake)

Another way of decreasing the incidence of new infections in a herd is to decrease

host risk factors. This can be done by:
 o providing adequate colostral immunity
o vaccinating to enhance immunity within herd
o decreasing stress on the animals
o providing proper nutrition

Morbidity and mortality can be decreased by adhering to the above described

environment and host management techniques.

III. Eradication of Disease from Herd/Geographic Area can theoretically be

accomplished by several techniques outlined below.

1. Complete Depopulation -- destruction & disposal of all clinically affected and

exposed animals

This can be either a compulsory program dictated and supervised by governmental

agencies, or it can be voluntarily carried out by a producer who is no longer able to
realize a profit due to the deleterious effects of disease in his animals.

2. Limited depopulation accomplished by testing and removal of animals identified as

carrying the disease "Test-and-Removal"

This method relies on diagnostic tests to detect exposed/carrier animals. No test is 100%
sensitive and specific. That means that either some positive animals will go
undetected or some negative animals will be removed from the herd, or both will
happen.

3. Elimination of disease agent by treatment

An example of this is the elimination of psittacosis (Chlamydiosis) from the pet bird
population. In order for this method to be effective, the drug must be very effective in
killing the agent. The drugs are usually given for long periods of time.

The advantages of completely eradicating a disease from a group of animals are

threefold:

1. There is no disease to decrease productivity

2. There is no need for vaccination (cost)
3. There is no need for treatment (cost)
There are, however, disadvantages that must be weighed against the advantages listed
above. Some of the disadvantages are:

1. The cost of eradication, both in actual value of animals removed, and the value of
their genetic potential, loss of income if depopulation is performed and cost of
treatment if that is the alternative chosen.

2. The need for specific, sensitive tests to detect the agent.

Any successful disease eradication Program Requires Continued Surveillance for

Disease to assure that it does not return .

This surveillance includes within herd surveillance for the presence of the agent, as
well as surveillance within the given geographic region (an example is surveillance
within the United States for foreign animal diseases)
 Vaccination as a Means of Disease Control

A vaccine is composed of material from an infectious agent that induces

immunologically mediated resistance to a disease. The vaccine may contain one or
more adjuvants such as alum, aluminum hydroxide, oils, or other materials that
enhance the immune response.

Vaccines are not used to treat disease, but rather, to prevent disease by establishing
an acquired resistance to the disease causing agent.

The material from the infectious agent may be present in several forms in a vaccine.

Live (attenuated) vaccines contain living organisms that have been rendered less
virulent, but are still capable of multiplication and spread within the body.

Advantages of using attenuated live vaccines are:

o provide strong, long lasting immunity

o fewer inoculating doses are required
o vaccine is often effective by nonparenteral routes (oral, intranasal)
o less chance of hypersensitivity, since the initial antigenic mass is less

Disadvantages of using attenuated live vaccines are:

o it may cause a mild form of the disease

o it may revert to a virulent state
o the attenuated agent may remain in the host/environment
o it may infect the fetus and cause abortion/birth defects
o has a limited shelf life; defined storage conditions
o possibility of contamination with other adventitious agents (canine
vaccine contaminated with Blue Tongue virus) during production

Killed (inactivated) vaccines contain organisms that have been inactivated by

treatment with formalin or other chemicals.

Advantages of using killed vaccines are:

o the vaccine is unlikely to cause disease

o the vaccine usually is far more stable in storage

Disadvantages of using killed vaccines are:

o possibility of incomplete inactivation of the agent

 o immunity is short-lived
o effective only by the parenteral route
o multiple doses are usually required
o hypersensitivity may occur due to greater antigenic mass
o use of adjuvants may cause local reactions

Biosynthetic, genetically engineered vaccines may contain agents that have been
manipulated to remove virulence factors from the agent, rendering them incapable of
causing disease even though they can reproduce; or they may be composed of a
noninfectious, protective subunit immunogen of the agent.

Advantages of using genetically engineered vaccines are:

o safety (unlikely to cause disease or carry other adventitious agents)

o subunit immunogens are usually stable and easy to store
o ability to distinguish the genetically engineered agent from field strains
of the agent serologically

Disadvantages of using genetically engineered vaccines are:

o cost is higher due to high cost of research and development

o short duration of immunity, multiple doses required with subunit
vaccines

A number of factors determine whether vaccination to prevent a given disease is

desirable or even possible.

1. Positive identification of the causative agent(s) of the disease is necessary. In

many diseases, the exact etiology (causation) is unknown and vaccination may
result in immunity to an agent that may not be involved in the current
disease. Proper diagnosis of the disease by a qualified veterinarian and
diagnostic laboratory is essential!!
2. If the causative agent is known, will an immune response to the agent protect
against disease? Sometimes the immune response of the animal to the agent is
what actually causes the disease.
3. Is the risk of vaccinating the animal greater than the risk of disease? There are a
variety of adverse reactions to vaccination, such as toxic or allergic reactions to
vaccine components, establishment of a latent, attenuated infection in the
animal, and infection of the developing fetus resulting in malformation or death.
An "Ideal Vaccine", if there were such a thing, would have the following properties:

1. provide effective resistance to disease (to the host animal and/or to it's fetus or
offspring)
2. provide long-lasting protection
3. be free of adverse side effects
4. be inexpensive
5. be stable, and suitable for use in mass vaccination
6. establish an immune response which is distinguishable from natural infection.
This is especially important if vaccination is used in a disease eradication
program, such as pseudorabies eradication in the swine population.

In order for a vaccine to promote "effective resistance" to disease in an animal, it must:

 induce the right type of immune response in the animal.

Vaccines that stimulate a B cell immune response are effective against agents which
are best neutralized and cleared from the animal by antibodies.

Vaccines that stimulate a T cell immune response are effective against agents that are
cleared from the animal by mechanisms of cell-mediated immunity.

 induce an immune response in the right place.

Production of circulating IgG, and IgM may be effective against agents that cause
systemic infections.

Production of IgA may be most effective in preventing infection with agents that enter
through mucus membranes.

 induce an immune response to the right antigens.

o outer surface protein
o receptor/attachment factor
o toxin ("toxoid" vaccines)

There are a number of ways in which vaccines are administered to animals.

Administration by the parenteral (injection) route, either subcutaneously (SC-under
the skin) or intramuscularly (IM-into the muscle) usually results in development of a
systemic immune response. Administration through intranasal instillation, aerosol, or
in the feed or drinking water will stimulate a local immune response with secretion of
IgA by the mucous membranes. Vaccines should only be given by the route
recommended by the manufacturer!
No vaccine can be expected to be 100% effective in all cases. There are a number of
reasons for vaccination failures, some of which are listed below:

 the animal may have been exposed to the agent prior to vaccination
 the infectious agent may have mutated beyond recognition by the immune
system
 the infectious agent may be present at such a high concentration that it
overwhelms the host immune system
 the host immune system may be suppressed due to stress, poor nutrition or
other concurrent infections (especially viral infections)
 there may be interference with the host immune response due to high levels of
maternal antibody, presence of too many antigens within the vaccine or mixing
and administration of multiple vaccines
 the vaccine may not have been stored, handled or administered properly
 the vaccine may never have been properly tested for efficacy (until recently, the
ability of a vaccine to produce reasonable levels of serum antibodies was
accepted as proof of efficacy, rather than the ability to prevent disease in
challenged animals)
 Use of Drugs to Control Disease

The variety of substances available to treat disease is constantly changing, with new
drugs being introduced and others being removed from the marketplace. Consequently,
we will not discuss specific drugs or substances in terms of recommendations for their
use in treating specific diseases in this course. Any mention of specific drugs will be
done simply as an example to illustrate general principles which must be kept in mind
when using drugs in food animal species.

In chapter 15 of Principles of Veterinary Science, Hoopes and Thwaits discuss a

variety of drug classes, including anesthetics, analgesics, cardiac drugs and so on.
Very few drugs in these classes have been approved for use in food producing animals
and most can only be obtained under veterinary prescription. The majority of drugs
used legally in food producing animals are in the classification of antimicrobials and
antiparasitics, consequently, we will concentrate on these classes of drugs in our
discussions.

When deciding whether to treat or not to treat an animal, always remember the
adage "above all do no harm" and also remember that "there is no such thing as an
absolutely safe and effective drug; safety and efficacy are relative"1

Basic Principles

The primary goal in using an antibiotic or other antimicrobial drug is to treat bacterial
infections, not to prevent them (that is the goal of vaccine use). Antibiotics are
ineffective against viruses.

Antibiotics are sometimes used to prevent a secondary bacterial infection from

developing when an animal is suffering from a viral disease that compromises the
animals ability to fight off bacterial infections.

Antibiotics are sometimes used prophylacticly to treat animals at high risk of

developing a bacterial infection (example: treatment of stressed beef cattle upon
arrival at a feedlot to prevent shipping fever).

Antibiotics have been included at low levels in feed rations for growth promotion
benefits unrelated to treating specific diseases. This use of antibiotics is being hotly
debated world-wide, and guidelines have been proposed by the World Health
Organization (WHO). For the latest information on the guidelines, see an excerpt
from the August 2000 Pig International Electronic Newsletter.
It is likely that use of antibiotics for any reason other than the treatment of specific
diseases for specified periods of time will be prohibited in the future.

Bactericidal antibiotics kill bacteria; bacteriostatic antibiotics simply prevent

bacteria from multiplying (the host immune system kills them).

The liver and kidney are the primary organs for metabolizing and excreting antibiotics
from the animal. Animals with compromised liver and/or kidney function may have
higher tissue levels of antibiotic than a normal animal, and may have violative levels
of antibiotic even after the appropriate drug withdrawal time has elapsed. Metabolism
and excretion of all drugs varies with the species (cats, for example cannot metabolize
aspirin and acetaminophen), age and sex of an animal.

Guidelines for Proper Drug Use

1. Diagnose the problem accurately

o establish a veterinary/ client relationship

o seek confirmatory culture and drug sensitivity of agent

2. Use a drug that is effective against the agent

3. Administer the drug in the proper form by the correct route

Parenteral

Intravenous (IV) gives immediate blood levels but is cleared from the body rapidly

Intramuscular (IM) blood levels reached more slowly than IV, should not inject more
than 5-10 cc/site depending upon the size of the animal.

Subcutaneous (SC) released into blood even more slowly, less painful than IM and
larger volumes can usually be injected per site.

Oral -- rate of absorption depends upon the formulation; can be by addition to feed or
water (palatability is an issue), by pill, paste, drench

Topical -- usually the least rapid rate of absorption, however this can be altered by
mixing with other chemicals

4. Administer the drug at the appropriate dosage, time interval and for the proper
length of time
5. Store drugs under proper conditions

6. Observe expiration dates, contraindications, withdrawal times

Always read and follow the label directions

Some drugs, termed "over-the-counter' or OTC drugs, can be purchased by a lay

person directly from a veterinary supply house, pet store or farm supply store. Drugs
that are approved for OTC sales by the FDA must have "adequate written directions
for safe and effective use by a lay person."

"safe use" refers to:

 Safety to animal
 Safety of food products from the animals
 Safety of persons associated with the animals
 Safety of environment

"effective use" refers to:

 Accurate diagnosis can be made

 Drug can be properly administered
 Course of disease and success or failure of drug can be monitored

Other drugs can only be dispensed under veterinary prescription and are referred to as Rx
drugs. Dispensing of these drugs requires a valid veterinarian-client-patient relationship.

Valid Veterinarian-Client-Patient Relationship

as defined by the American Veterinary Medical Association is: "An appropriate veterinarian-
client-patient relationship will exist when:

(1) the veterinarian has assumed the responsibility for making medical judgements regarding
the health of the animal(s) and the need for medical treatment, and the client (owner or
caretaker) has agreed to follow the instructions of the veterinarian; and when

(2) there is sufficient knowledge of the animal(s) by the veterinarian to initiate at least a general
or preliminary diagnosis of the medical condition of the animal(s). This means that the
veterinarian has recently seen and is personally acquainted with the keeping and care of the
animal(s), and/or by medically appropriate and timely visits to the premises where the animals
are kept; and when
(3) the practicing veterinarian is readily available for follow-up in case of adverse reactions or
failure of the regimen of therapy."

Instances Requiring a Valid Veterinarian-Client-Patient Relationship

1. Dispensing perscription drugs

2. Dispensing "extra-label" prescription drugs via AMDUCA
3. Dispensing medicated feeds regulated under a Veterinary Feed Directive

Drug Safety Issues

Drug Interactions and Incompatibilities --

Whenever more than one drug is administered to an animal, the potential exists for
drug interactions. Sometimes we purposely use multidrug treatment because the drugs
work synergistically, but in other instances, there may be antagonism between the
action of two drugs. An example of this is the administration of a bactericidal drug in
combination with a bacteriostatic drug. Bactericidal drugs are only effective against
bacteria that are moving through the cell cycle (their mode of action is usually
targeted at one or another stage of the cell cycle). The presence of a bacteriostatic
drug will stop the organism from moving through the cell cycle and cancel out the
benefit of the bactericidal drug.

Drug Residues --

There are strict rules and regulations in place which restrict the use of drugs in food
producing animals. These regulations are designed to prevent the carry-over of drugs
into foods for human consumption. Failure to observe these regulations [link
1 || link 2] and the appropriate withdrawal times when using drugs can result in loss of
market and severe penalties including jail time. Cull cows and bob veal calves have
been observed to have a higher prevalence of violative drug residues than other types
of animals. It is very important for the producer to properly identify animals and keep
accurate and complete records of drug use.

Development of Antimicrobial Resistance --

There are two major ways in which bacteria may develop resistance to any particular
antibiotic.
 1. Mutation of chromosomal DNA of the bacterium
2. Acquisition of resistance factors from another bacterium via
transformation or receipt of plasmids containing resistance
factor(s). The continued presence of a large population of
chloramphenicol resistant bacteria in animals after
chloramphenicol had been removed from the market for more
than 10 years is thought to be due to it's resistance factor being
included in a "packet" of tightly linked resistance factors for drugs
that continued to be used in the human and animal population.

The complete prohibition of extra-label use of fluoroquinolones and glycopeptide

classes antimicrobials in food producing animals is due to the concern over rapid
development of a population of bacteria resistant to classes of drugs reserved as
"drugs of last resort" in the human population. Previously approved use
of fluoroquinolones in poultry production are being revoked, due to development of
antimicrobial resistance among campylobacter species, a major foodborne pathogen in
humans.

Drug Use in Food-Producing Livestock

Use of drugs in food producing animals has been a subject of controversy for quite
some time. In addition to concerns about drug residues that may remain in food
products, there is concern over the potential for development of drug resistance, as
discussed above. A good summary of recent information on this subject can be found
in "Livestock Drugs: More Questions Than Answers?" Agricultural Outlook,
September 2001.