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       Trpanosomiasis
       Drug Resistance
       Foot Rot
       Interferon
       Recombinnat Vaccine
       Cestod Infestation
       Round Worm Infection
       Myasis
       ELISA
       Colic
       Diarrhea
       Tick Infestation
       Mnge
       Hook Worm
       Kidney Worm
       Candidiasis
       Chlamydiosis
       Colibacilosis molecular Diagnosis
       Food Posoning



                                          Antibiotics
                                             Penicillin
The penicillins are a large and commonly used class of β-lactam antibiotics that share many
features, including chemistry, mechanism of action, pharmacologic properties, clinical effects,
and immunologic characteristics.
                                           Classification
Several subclassifications of the penicillins, based mainly on differences in antibacterial spectra, are

recognized.

Narrow-spectrum β-Lactamase-sensitive Penicillins:
This group includes naturally occurring penicillin G (benzylpenicillin) in its various pharmaceutical

forms and     a few    biosynthetic acid-stable   penicillins intended    for oral   use   (penicillin V [

phenoxymethyl-penicillin] and phenethicillin). Penicillins in this class are active against many gram-

positive and a limited number of gram-negative bacteria, but they are susceptible to β-lactamase

(penicillinase) hydrolysis.

Narrow-spectrum β-Lactamase-resistant Penicillins:
This group, through substitution on the penicillin nucleus (6-aminopenicillanic acid [6-APA]), is

refractory to a greater or lesser degree to the effects of various β-lactamase enzymes produced by

resistant gram-positive organisms, particularly Staphylococcus aureus . However, penicillins in this

class are not as active against many gram-positive bacteria as penicillin G and are inactive against

almost all gram-negative bacteria. Acid-stable members of this group (that are used PO) include

isoxazolyl penicillins, such as oxacillin, cloxacillin, dicloxacillin, and flucloxacillin. Methicillin and

nafcillin are available as parenteral preparations. Temocillin is a semisynthetic penicillin that is β-

lactamase    stable   but   also   active    against   nearly   all   isolates   of   gram-negative     bacteria

except Pseudomonas spp .

Broad-spectrum β-Lactamase-sensitive Penicillins:

Penicillins in this class are derived semisynthetically and are active against many gram-positive and

gram-negative bacteria. However, they are readily destroyed by the β-lactamases (produced by

many bacteria). Many members of the group are acid stable and are administered either PO or

parenterally. Of those used in veterinary medicine, aminopenicillins, eg, ampicillin and amoxicillin,

are the best known. Several ampicillin precursors that are more completely absorbed from the GI

tract also belong to this class (eg, hetacillin, pivampicillin, talampicillin). Mecillinam is less active than

ampicillin against gram-positive bacteria but is highly active against many intestinal organisms

(except Proteus spp) that do not produce β-lactamases.

Broad-spectrum β-Lactamase-sensitive Penicillins with Extended Spectra:

Several semisynthetic broad-spectrum penicillins are also active against Pseudomonas aeruginosa ,

certain Proteus spp , and even strains of Klebsiella , Shigella , and Enterobacterspp in certain cases.

Examples of this class include carboxypenicillins (carbenicillin, its acid-stable indanyl ester, and

ticarcillin), ureido-penicillins (azlocillin and mezlocillin), and piperazine penicillins (piperacillin).

β-Lactamase-protected Broad-spectrum Penicillins (Potentiated Penicillins):

Several naturally occurring and semisynthetic compounds can inhibit many of the β-lactamase

enzymes produced by penicillin-resistant bacteria. When used in combination with broad-spectrum

penicillins, there is a notable synergistic effect because the active penicillin is protected from

enzymatic hydrolysis—and thus is fully active against a wide variety of previously resistant bacteria.

Examples of this chemotherapeutic approach include clavulanate-potentiated amoxicillin and ticarcillin

as well as sulbactam-potentiated ampicillin.

Carbapenems:

Imipenem is one of the most active drugs against a wide variety of bacteria. It is derived from a

compound produced by Streptomyces cattleya . Aztreonam is a related (monobactam) compound.

The penicillins are somewhat unstable, being sensitive to heat, light, extremes in pH, heavy metals,
and oxidizing and reducing agents. Also, they often deteriorate in aqueous solution and thus require

reconstitution with a diluent just before injection. Penicillins are poorly soluble, weak organic acids

that are administered parenterally either as suspensions in water or oil, or as water-soluble salts. For

example, sodium or potassium salts of penicillin G are highly water soluble and are absorbed rapidly

from injection sites, whereas organic salts in microsuspension such as procaine penicillin G or

benzathine penicillin G are gradually absorbed over 1-3 (or even more) days, respectively. The

trihydrate forms of the semisynthetic penicillins have greater aqueous solubility than the parent

compounds and are usually preferred for both parenteral and oral use.

General Properties
Penicillins contain a β-lactam nucleus that when cleaved by a β-lactamase enzyme (penicillinase)

produces penicilloic acid derivatives that are inactive but which may act as the antigenic determinants

for penicillin hypersensitivity. Modification of the 6-aminopenicillanic acid nucleus, either by

biosynthetic or semisynthetic means, has produced the array of penicillins used clinically. These differ

in their antibacterial spectra, pharmacokinetic characteristics, and susceptibility to microbial enzymatic

degradation.


Mode of Action:

Penicillins impair the development of bacterial cell walls by interfering with transpeptidase enzymes

responsible for the formation of the cross-links between peptidoglycan strands. These enzymes are

associated with a group of proteins in both gram-positive and gram-negative bacteria called the

penicillin-binding proteins (PBP). During bacterial cell growth, while the peptidoglycan structure is

being formed, autolysins continuously cleave the lattice to provide acceptor sites for new strands.

Normal bacterial growth depends on a balance between cell wall deposition and autolysis. When a

penicillin interacts with PBP and inhibits the synthetic enzymes, defective cell walls are formed, which
lead to abnormal elongation of cells, formation of spheroplasts, or osmotic lysis. The effect of the

penicillins is generally bactericidal. At concentrations lower than minimal inhibitory concentrations

(MIC [at so-called minimal antibiotic concentrations]), β-lactam antibiotics do exert residual effects

on bacterial structure and function that, in turn, promote phagocytosis.

β-Lactam antibiotics have little influence on formed bacterial cell walls, and even susceptible

organisms must be actively multiplying or growing. Penicillins are most active during the logarithmic

phase of bacterial growth. They also tend to be somewhat more active in a slightly acidic

environment (pH 5.5-6.5), perhaps because of enhanced membrane penetration.

Efficacy of the β-lactams is related to the time that plasma or tissue drug concentrations exceed the
MIC of the infecting organism. Generally, concentrations should remain above the MIC for about two-

thirds of the dosing interval.
Bacterial Resistance:

Only microorganisms that have cell walls are susceptible to the action of penicillins and other β-lactam

antibiotics. Within this range of bacteria, resistance to penicillins is well recognized and takes a

number of forms.

β-Lactamase (Penicillinase) Resistance:

The most important mechanism of bacterial resistance to penicillins and the other β-lactam antibiotics

is enzymatic inactivation. There are at least 6 major types of β-lactamase enzymes that can cleave

the β-lactam ring, which renders the drug inactive. β-Lactamases are produced by gram-positive

organisms ( Staphylococcus aureus , S epidermidis ), and 5 of the 6 types of β-lactamases are

produced by gram-negative organisms. Some of these enzymes are active exclusively against

penicillins, others are principally active against cephalosporins, and several types hydrolyze both

equally. The type and concentration of β-lactamases are also bacterial species-specific. Gram-positive

β-lactaases are generally excreted into the external environment as exoenzymes, produced in large

quantity, plasmid-mediated (single determinant), usually inducible (rarely constitutive), unable to

initiate self-transmission (rely principally on transduction), and active primarily against penicillins.

Staphylococcal strains are the main gram-positive bacteria in which β-lactamase resistance develops,

often very quickly. Gram-negative β-lactamases are generally heterogenous (wide range), retained

within the periplasmic space, produced in small quantity, often constitutive (less often inducible),

able to initiate self-transmission (conjugation mechanisms), and active against both penicillins and

cephalosporins. Gram-negative bacteria capable of resistance as a result of β-lactamase production

include Escherichia , Haemophilus , Klebsiella , Pasteurella , Proteus , Pseudomonas ,

and Salmonella spp ; resistance may take longer to develop in some of these strains.

β-Lactamase-induced       resistance        is     widespread.     Of    veterinary     isolates,   ~50-60%
of Staphylococcus spp strains and 40-70% of E coli strains are resistant to penicillin G; 15-40%

of E coli strains from farm animals may also be resistant to ampicillin.

Antibacterial Spectra:
Penicillin G and its oral congeners (eg, penicillin V) are active against both aerobic and anaerobic

gram-positive bacteria and, with a few exceptions ( Haemophilus and Neisseriaspp and strains

of Bacteroides other   than B fragilis ),    are   inactive   against   gram-negative   organisms   at   usual

concentrations. Organisms usually sensitive in vitro to penicillin G include streptococci, penicillin-

sensitive

staphylococci, Corynebacterium pyogenes , Clostridium spp , Erysipelothrix rhusiopathiae , Actinomyce

s ovis , Leptospira canicola , Bacillus anthracis ,Fusiformis nodosus , and Nocardia spp .

The semisynthetic β-lactamase-resistant penicillins, such as oxacillin, cloxacillin, floxacillin, and
nafcillin, have spectra similar to those noted above (although often at higher MIC) but also include

many of the β-lactamase-producing strains of staphylococci (especially S aureus and S epidermidis ).

A large number of gram-positive and gram-negative bacteria (but not β-lactamase-producing strains)

are sensitive to the semisynthetic broad-spectrum penicillins (ampicillin and amoxicillin). Susceptible

genera

include Staphylococcus , Streptococcus , Corynebacterium , Clostridium , Escherichia , Klebsiella , Shi

gella , Salmonella , Proteus ,   and Pasteurella .    While   bacterial   resistance     is    widespread,   the

combination of β-lactamase inhibitors and broad-spectrum penicillins markedly enhances the

spectrum and efficacy against both gram-positive and gram-negative pathogens. Clavulanate-

potentiated amoxicillin is an excellent example of such a synergistic association.

The anti- Pseudomonas and other extended-spectrum penicillins are active against most of the usual

penicillin-sensitive bacteria. They often have a degree of β-lactamase resistance and are usually

active against one or more characteristic penicillin-resistant organisms. Yet, as a class, they remain

susceptible to destruction by β-lactamases. Examples include the use of carbenicillin, ticarcillin, and

piperacillin against Pseudomonas aeruginosa and several Proteus strains, and the use of piperacillin

against Pseudomonas aeruginosa ,                     several Shigella and Proteus strains,                   and

some Citrobacter and Enterobacter spp . Streptococcus faecalis is         often    resistant    to   these   new

extended-spectrum penicillins. Imipenem is relatively resistant to β-lactamase destruction. Its

spectrum includes a wide variety of aerobic and anaerobic microorganisms, including most strains

of Pseudomonas ,       streptococci,     enterococci,       staphylococci,        and Listeria .     Anaerobes,

including Bacteroides fragilis , are highly susceptible.

The pharmacokinetics of the many penicillins differ substantially. The general guidelines below

emphasize singularly significant aspects.
Therapeutic Indications and Dose Rate:
The penicillins are commonly used to treat or prevent local and systemic infections caused by
susceptible bacteria. There are several acute infectious disease syndromes that are specifically
responsive. Penicillins are also used topically in the eye and ear as well as on the skin;
intramammary administration to treat or prevent bovine mastitis is widespread.
Dose Rates of Penicillins

 Penicillin                                                 Dosage, Route, and Frequency
 Sodium penicillin G                                        10,000-20,000 IU/kg, IV or IM, qid
 Potassium penicillin G                                     25,000 IU/kg, PO, qid
 Procaine penicillin G                                      10,000-30,000 IU/kg, IM or SC, sid-
                                                            bid
 Benzathine penicillin G                                    10,000-40,000 IU/kg, IM (horses) or
                                                      SC (cattle), every 48-72 hr
 Penicillin V                                         15,000 IU/kg or 8-10 mg/kg, PO, tid
 Cloxacillin                                          10 mg/kg, IM or PO, qid
 Ampicillin                                           5-10 mg/kg, IV, IM, or SC, bid-tid
                                                      10-25 mg/kg, PO, bid-qid
 Amoxicillin                                          4-7 mg/kg, IM, sid-bid 11 mg/kg, PO,
                                                      bid (dogs) or sid-bid (cats)
 Sodium carbenicillin                                 10-20 mg/kg, IV or IM, bid- tid
 Potassium clavulanate:amoxicillin (1:4)              10-20 mg/kg (amoxicillin) and 2.5-5
                                                      mg/kg (clavulanate), PO, bid
 Probenecid (prolongs blood levels of penicillins     1-2 mg/1,000 IU penicillin G (dogs),
 that have short plasma half-lives or that are        PO, qid
 costly)
 Amoxicillin-clavulanic acid                          10-20 mg/kg, PO, bid- tid
 Imepenem                                             1-7 mg/kg, IV or IM, tid- qid
 Ticarcillin                                          15-110 mg/kg, IM or IV, every 4-8 hr

Side Effects and Toxicity:
Organ toxicity is rare. Hypersensitivity reactions do occur (particularly in cattle) and include
skin reactions, angioedema, drug fever, serum sickness, vasculitis, eosinophilia, and
anaphylaxis. Cross-sensitivity between penicillins is well recognized. Intrathecal
administration may result in convulsions. Guinea pigs, chinchillas, birds, snakes, and turtles
are sensitive to procaine penicillin. The use of broad-spectrum penicillins may lead to
superinfection, and GI disturbances may occur after PO administration of ampicillin.
Potassium penicillin G should be administered IV with some caution, especially if
hyperkalemia is present. The sodium salt of penicillin G may also contribute to the sodium
load in congestive heart failure.
Interactions:
Penicillins are displaced from plasma-protein binding sites and tubular secretion is delayed
when drugs such as salicylates, phenylbutazone, sulfonamides, and other weak acids are
administered concurrently. Gut-active penicillins potentiate the action of anticoagulants by
depressing vitamin K production by gut flora. Absorption of ampicillin is impaired by the
presence of food. Carbenicillin and ticarcillin interact chemically with the aminoglycosides and
should not be mixed in vitro. Ampicillin and penicillin G are incompatible with many other
drugs and solutions and should not be mixed.
Effects on Laboratory Tests:
Laboratory determinations may be altered, depending on the penicillin used. Alkaline
phosphatase, AST, ALT, and eosinophil count may be increased. A false positive Coombs‘ test
may also result after penicillin therapy. A positive test for urine glucose and protein is also
possible. Procaine is detectable in the urine of horses for several days after the administration of
procaine penicillin; the pre-race withdrawal time may be up to 6 days.
Drug Withdrawal and Milk Discard Times:
Regulatory requirements for withdrawal times for food animals and milk discard times vary
among countries. These must be followed carefully to prevent food residues and consequent
public health implications

                     Cephalosporins and Cephamycins
The early cephalosporins differed mainly with respect to pharmacokinetic characteristics; the
newer generations have much broader ranges of activity, and the modern classification of the
group is based mainly on antibacterial spectra.
First-generation Cephalosporins:
 This group includes cephalothin, cephaloridine, cephapirin, cefazolin, cephalexin, cephradine,
 and cefadroxil. Cephalosporins in this group are usually quite active against many gram-
 positive bacteria but are only moderately active against gram-negative organisms. They are
 relatively susceptible to β-lactamases (cephalosporinases) and are not as effective against
 anaerobes as are the penicillins.
Second-generation Cephalosporins:
 This group includes cefamandole, cefoxitin (a cephamycin), cefotiam, cefachlor, cefuroxime,
 and ceforanide. These agents are generally active against both gram-positive and gram-negative
 bacteria. Moreover, they are relatively resistant to β-lactamase. They are ineffective against
 enterococci, Pseudomonas aeruginosa , Actinobacter spp , and many obligate anaerobes.
Third-generation Cephalosporins:
 This group includes ceftiofur, ceftriaxone, cefsulodin, cefotaxime, cefoperazone, moxalactam
 (not a true cephalosporin), and several others. Typically, these have only moderate activity
 against gram-positive bacteria but are active against a wide variety of gram-negative bacteria,
 including in certain instances Pseudomonas spp , Proteus vulgaris , Enterobacter spp , and
 Citrobacter spp . They are usually highly resistant to β-lactamase enzymes. Third-generation
 cephalosporins are often able to penetrate the blood-brain barrier and are frequently indicated in
 bacterial meningitis caused by susceptible pathogens. Ceftiofur has been specifically approved
 for use in cattle with bronchopneumonia, especially if caused by Pasteurella haemolytica or P
 multocida .
Fourth-generation Cephalosporins:
 A fourth generation of cephalosporins includes new drugs such as cefpodoxime and cefixime.
 The spectrum of third- and fourth-generation cepaholosporins varies and should be confirmed
 before using a drug for a targeted organism.
General Porperties
he physical and chemical properties of the cephalosporins are similar to those of the penicillins,
although the cephalosporins are somewhat more stable to pH and temperature changes.
Cephalosporins are weak acids derived from 7-aminocephalosporanic acid. They are used either
as the free base form for PO administration (if acid stable) or as sodium salts in aqueous solution
for parenteral delivery (sodium salt of cephalothin contains 2.4 mEq sodium/g). Cephalosporins
also contain a β-lactam nucleus that is susceptible to β-lactamase (cephalosporinase) hydrolysis.
These β-lactamases may or may not also attack penicillins. Modifications of the 7-
aminocephalosporanic acid nucleus and substitutions on the sidechains by semisynthetic means
have produced differences among cephalosporins in antibacterial spectra, β-lactamase
sensitivities, and pharmacokinetics.
Mode of Action:
 This is similar to that of the penicillins. Cephalosporins also bind to penicillin-binding proteins
 located beneath the cell wall and thereby interfere with the action of transpeptidase and other
 cell-wall enzymes. A residual antibacterial effect is also evident with the cephalosporins. As a
 group, these antibiotics are most stable and effective at a pH of 6-7.                              =
Antibacterial Spectra:
The first-generation cephalosporins are generally effective against most gram-positive aerobic
cocci and several of the gram-negative bacteria, including E coli and Proteus , Klebsiella ,
Salmonella , Shigella , and Enterobacter spp . Cephalosporinase-producing organisms are not
susceptible. The second-generation cephalosporins have greater activity against gram-negative
organisms but are somewhat less active against gram-positive species. This trend continues with
the third-generation cephalosporins, which may even be active against P aeruginosa . The newest
members of this group are also highly resistant to β-lactamase. Ceftiofur is a third-generation
cephalosporin, but unlike other members of this class, it has a gram-negative spectrum that is
more similar to first-generation cephalosporins. However, unlike first-generation cephalosporins,
efficacy against Staphylococcus spp is not predictable. The cephalosporins may be effective
against anaerobic bacteria except Bacteroides fragilis , which is susceptible only to certain
cephalosporins.
Indications and Dose Rate:
The cost of cephalosporins has limited their use in veterinary medicine. However, first-
generation cephalosporins have proved useful, particularly for infections involving
Staphylococcus spp (eg, oral cephalexin for dermatitis) and for surgical prophylaxis (eg,
cefazolin). Ceftiofur is approved for use in bovine respiratory disease principally caused by
Pasteurella spp and in urinary tract infections in dogs. Use of ceftiofur for treatment of soft-tissue
infections in dogs is not recommended because proper dosages and safety have not been
documented. Cephalosporins are particularly useful for treating infections of soft tissue and bone
due to bacteria that are resistant to other commonly used antibiotics. Because of their favorable
pharmacokinetic characteristics and effectiveness, they are often administered IV, 1 hr before
surgery. Because of their ability to penetrate tissues and fluids so readily (the CSF being an
exception for most), they are often effective in the management of osteomyelitis, prostatitis, and
arthritis. Oral cephalosporins are also usually effective in the management of urinary tract
infections, except those due to Pseudomonas aeruginosa . Cephapirin benzathine is used for dry-
cow therapy, and cephapirin sodium is used in treatment of mastitis.

Dose Rates of Cephalosporins*

         Cephalosporin               Dosage, Route, and Frequency
         Cephalothin                 20-35 mg/kg, IM or IV, tid- qid
         Cephapirin                  30 mg/kg, IM or IV, every 4-6 hr
         Cefazolin                   20-25 mg/kg, IM or IV, tid- qid
         Cephalexin                  10-30 mg/kg, PO, tid- qid
         Cefadroxil                  22 mg/kg, PO, bid
        Ceftiofur                  1.1 mg/kg, IM, sid

Side Effects and Toxicity:
The cephalosporins are relatively nontoxic, although cephaloridine may be nephrotoxic in
some species. IM injections can be painful, and repeated IV administration may lead to
local phlebitis. Nausea, vomiting, and diarrhea may occasionally be seen. Hypersensitivity
reactions of several forms have been seen, particularly in animals with a history of acute
penicillin allergy. Superinfection may arise with the use of cephalosporins, and
Pseudomonas or Candida spp are likely opportunistic pathogens.
Interactions:
In vitro incompatibilities are quite common for cephalosporin and cephamycin preparations.
Potential pharmacokinetic interactions are similar to those of the penicillin group.
Aminoglycosides may enhance cephaloridine nephrotoxicity, but there is some doubt about this
particular interaction. Furosemide and ethacrynic acid, however, do appear to potentiate the
nephrotoxic action of cephaloridine.
Drug Withdrawal and Milk Discard Times:
Although prolonged tissue residues for most cephalosporins are not anticipated, withdrawal
times are not available for most of the cephalosporins because they are not approved for use in
food animals in most countries


                                   Aminoglycosides
Narrow-spectrum Aminoglycosides:
Included in this group are streptomycin and dihydrostreptomycin, which are mainly active
against aerobic, gram-negative bacteria.
Expanded-spectrum Aminoglycosides:
Neomycin, framycetin (neomycin B), paromomycin (aminosidine), and kanamycin have
broader spectra than streptomycin that often include several gram-positive as well as many
gram-negative aerobic bacteria. Gentamicin, tobramycin, amikacin, sisomicin, and netilmicin
are aminoglycosides with extended spectra that include Pseudomonas aeruginosa .
Miscellaneous Aminoglycoside Antibiotics:
The chemical structure of apramycin differs somewhat from that of the typical aminoglycosides
but is similar enough to be included in this class. The structure of spectinomycin is unusual, but
it is fairly comparable to other aminocyclitols with regard to its mechanism of action and
antibacterial spectrum.
                                        General Properties
Chemically, the aminoglycoside antibiotics are characterized by an aminocyclitol group, with
aminosugars attached to the aminocyclitol ring in glycosidic linkage. Because of minor
differences in the position of substitutions on the molecules, there may be several forms of a
single aminoglycoside. For example, gentamicin is a complex of gentamicins C1 and C2, and
neomycin is a mixture of neomycins B, C, and fradiomycin. The amino groups contribute to the
basic nature of this class of antibiotics, and the hydroxyl groups on the sugar moieties to high
aqueous solubility and poor lipid solubility. If these hydroxyl groups are removed (eg,
tobramycin), antibiotic activity is markedly increased. Differences in the substitutions on the
basic ring structures within the various aminoglycosides account for the relatively minor
differences in antimicrobial spectra, patterns of resistance, and toxicities. Aminoglycosides are
typically quite stable. When the water solubility of an aminoglycoside is marginal, it is usually
the sulfate salt that is used for PO or parenteral administration.
Mode of Action:
 Aminoglycosides are more effective against rapidly multiplying organisms, and they affect and
 ultimately destroy bacteria by several mechanisms. They need only a short contact with
 bacteria to kill them. Their main site of action is the membrane-associated bacterial ribosome
 through which they interfere with protein synthesis. To reach the ribosome, they must first
 cross the bacterial cell wall and then the cell membrane. Because of the polarity of these
 compounds, a specialized transport process is required. The first concentration-dependent step
 requires binding of the aminoglycoside to anionic components in the cell membrane. The
 subsequent steps are energy-dependent and involve the transport of the polar, highly charged
 aminoglycoside across the cytoplasmic membrane, followed by interaction with the ribosomes.
 The driving force for this transfer is probably the membrane potential. These processes are
 much more efficient if the energy used is aerobically generated.
Several features of these mechanisms are of clinical significance: 1) The antibacterial activity
of the aminoglycosides depends on an effective concentration of antibiotic outside the cell. 2)
Anaerobic bacteria and induced mutants are generally resistant because they lack appropriate
transport systems. 3) With low oxygen tension, as in hypoxic tissues, transfer into bacteria is
diminished. 4) Divalent cations, eg, calcium and magnesium, can interfere with transport into
bacteria because they can combine with the specific anionic sites and exclude the cationic
aminoglycosides. 5) Transport of aminoglycosides across bacterial cell membranes is
facilitated by an alkaline pH; a low pH may increase membrane resistance >100-fold. 6)
Changes in osmolality also can alter the uptake of aminoglycosides. 7) Some aminoglycosides
are transported more efficiently than others, and thus tend to have greater antibacterial activity.
8) Synergism is common when aminoglycosides and β-lactam antibiotics (penicillins and
cephalosporins) are used in combination. The cell-wall injury induced by the β-lactam
compounds allows increased uptake of the aminoglycoside by the bacteria because of easier
accessibility to the bacterial cell membrane.
The intracellular site of action of the aminoglycosides is the ribosome, which has binding sites
at both the 30 S and 50 S subunits, although they bind particularly to the former. There is some
variation between aminoglycosides with respect to their affinity and degree of binding. A
number of steps in protein synthesis appear to be affected, but this too varies among
aminoglycosides. Spectinomycin lacks the ability to produce misreading of the mRNA and
often is not bactericidal, in contrast to the other members. At low concentrations, all
aminoglycosides may be only bacteriostatic.
A cell-membrane effect is also seen. The functional integrity of the bacterial cell membrane is
lost during the late phase of the transport process, and high concentrations of aminoglycosides
may cause nonspecific membrane toxicity, even to the point of bacterial cell lysis.
Efficacy of aminoglycosides is enhanced if peak plasma or tissue drug concentrations exceed
MIC by 4-8 times. Once-daily dosing has been used to enhance both efficacy and safety.
Antibacterial Spectra:
Streptomycin and dihydrostreptomycin have relatively narrow spectra, and bacterial resistance
is becoming prevalent. However, some staphylococci and a number of gram-negative bacilli
are still susceptible, among which are strains of Actinomyces bovis , Pasteurella spp , E coli ,
Salmonella spp , Campylobacter fetus , Leptospira spp , and Brucella spp . Mycobacterium
tuberculosis is also sensitive to streptomycin.
Neomycin, framycetin, and kanamycin have broader spectra than streptomycin, and their
clinical use is most often directed against gram-negative species such as E coli and Salmonella
, Klebsiella , Enterobacter , Proteus , and Acinetobacter spp . The aminoglycosides with
broader spectra that include P aeruginosa (gentamicin, tobramycin, amikacin, sisomicin, and
netilmicin) are often highly effective against a wide variety of aerobic bacteria. Anaerobic
bacteria and fungi are not appreciably affected; streptococci are usually only moderately
sensitive or quite resistant.
Despite their potential to cause nephrotoxicity, the aminoglycosides are commonly used to
control local and systemic infections caused by susceptible aerobic bacteria (generally gram-
negative) because of their effectiveness. Examples include septicemia; tracheobronchitis;
pneumonia; osteoarthritis; and infections of the urinary tract, GI tract, and skin and wounds.
Several aminoglycosides are used topically in the ears and eyes. Intrauterine infusion to treat
endometritis is also frequent. Occasionally, aminoglycosides are infused into the udder to treat
mastitis.
While a nomogram based on creatinine clearance values or the creatinine clearance values
themselves could be used to calculate appropriate dosage modifications in renal insufficiency,
such an approach is rarely practical, and generally is unnecessary with once-daily dosing. The
ideal is to monitor both plasma aminoglycoside concentrations and renal function during
therapy. As a precaution, the following general guidelines may be followed in cases of renal
failure in which plasma creatinine values are increased
The treatment interval should be increased in neonates (especially puppies and foals), in renal
failure, and in obese animals. Doses may be increased in animals with edema, hydrothorax, or
ascites, provided their renal function is unimpaired.
Side Effects and Toxicity:
Ototoxicity, neuromuscular blockade, and nephrotoxicity are reported most frequently; these
effects may vary with the aminoglycoside and dose or interval used, but all members of the
group are potentially toxic. Nephrotoxicity is of major concern and may result in renal failure
due to acute tubular necrosis with secondary interstitial damage. Aminoglycosides
accumulate in proximal tubular epithelial cells, where they are sequestered in lysosomes and
interact with ribosomes, mitochondria, and other intracellular constituents to cause cell injury.
Persistence of aminoglycosides in plasma and thus urine is likely to predispose the tubular
cells to toxicity, and the risk may by reduced by allowing plasma drug concentrations to drop
below recommended levels (generally 1-2 mg/mL) before the next dose. Nonoliguric renal
failure is the usual observation; it is generally reversible, although recovery may be
prolonged. Any failure in glomerular filtration results in excessively high concentrations of
aminoglycoside, which in turn result in further renal damage. Renal function should be
monitored during therapy. Polyuria, decreased urine osmolality, enzymuria, proteinuria,
cylindruria, and increased fractional sodium excretion are indicative of aminoglycoside
nephrotoxicity. Later, BUN and creatinine concentrations may be increased. Early changes or
evidence of nephrotoxicity can be detected in 3-5 days, with more overt signs in 7-10 days.
Several factors predispose to aminoglycoside nephrotoxicosis, including age (with young
[especially the newborn foal] and old animals being sensitive), compromised renal function,
total dose, duration of treatment, dehydration and hypovolemia, aciduria, acidosis, severe
sepsis or endotoxemia, concurrent administration of furosemide, and exposure to other
potential nephrotoxins (eg, methoxyflurane, amphotericin B, cis-platinum, and perhaps some
cephalosporins). In renal insufficiency, generally the interval between doses is prolonged
(rather than reducing the dose) to minimize toxicity.
The risk of aminoglycoside-induced nephrotoxicity can be reduced by maintaining patient
hydration and an alkaline urine pH, dosing once daily, and avoiding nephroactive drugs (eg,
NSAID, diuretics).
Aminoglycosides can result in ototoxicity, which manifests as auditory or vestibular
dysfunction. Vestibular injury leads to nystagmus, incoordination, and loss of the righting
reflex. The lesion is often irreversible, although physiologic adaptation can occur. Cats are
particularly sensitive to the toxic vestibular effects. Hearing impairment is produced by
permanent damage and loss of the hair cells in the organ of Corti. High-frequency hearing is
impaired first, and deafness may not be complete, depending on the dosage used. Such an
impediment could be of enormous importance (eg, in guide dogs), and aminoglycosides
should not be administered to such animals except under extenuating circumstances.
Aminoglycosides should not be instilled into the ear unless the tympanic membrane is intact,
because diffusion of the drug into the inner ear could cause damage. Several risk factors may
predispose to vestibular and cochlear damage by aminoglycosides (in addition to those for
nephrotoxicity), including preexisting acoustical or vestibular impairment and previous
treatment with potentially ototoxic drugs or loop-acting diuretics (eg, furosemide, ethacrynic
acid). The ototoxic potential is highest for gentamicin, sisomicin, and neomycin, and lowest
for netilmicin.
All aminoglycosides, when administered in doses that result in high plasma levels, have been
associated with muscle weakness and respiratory arrest attributable to neuromuscular
blockade. The effect is more pronounced when aminoglycosides are used with other drugs
that cause neuromuscular blockade and with gas anesthetics. Neomycin, kanamycin,
amikacin, gentamicin, and tobramycin are listed in order of most to least potent for these
neuromuscular effects. The effect is due to the chelation of calcium and competitive
inhibition of the prejunctional release of acetylcholine in most instances (there are some
differences among aminoglycosides). The blockade is antagonized by calcium gluconate and
somewhat less consistently by neostigmine.
Other forms of toxicity and side effects include CNS disturbances and even convulsions,
collapse after rapid IV administration, superinfection when used topically or PO, a
malabsorption syndrome due to allocation of intestinal villous function when used PO in
neonates, occasional hypersensitivity reactions, contact dermatitis, cardiovascular depression,
and inhibition of some WBC functions (eg, neutrophil migration and chemotaxis and even
bactericidal activity at high concentrations).
Interactions:
Enhanced nephrotoxicity may become evident with concurrent administration of
aminoglycosides and other potentially nephrotoxic agents. Neuromuscular blockade is more
likely when aminoglycosides are administered at the same time as skeletal muscle relaxants
and gas anesthetics. Aminoglycoside ototoxicity is enhanced by the loop-acting diuretics,
especially furosemide. Cardiovascular depression may be aggravated by aminoglycosides
when administered to animals under halothane anesthesia. High concentrations of carbenicillin,
ticarcillin, and piperacillin inactivate aminoglycosides both in vitro and in vivo in the presence
of renal failure.
Effects on Laboratory Tests:
BUN, serum creatinine, serum transaminases, and alkaline phosphatase values may be
increased. Proteinuria is a significant laboratory finding.
Drug Withdrawal and Milk Discard Times:
Regulatory requirements for withdrawal times for food animals and milk discard times vary
among countries. These must be followed carefully to prevent food residues and consequent
public health implications. The selection of times listed serve only as general guidelines

                                        Quinolones
Quinolone carboxylic acid derivatives are synthetic antimicrobial agents. Nalidixic acid and its
congener oxolinic acid have been used for treatment of urinary tract infections for years, while
flumequine has been used successfully in several countries to control intestinal infections in
livestock. Many broad-spectrum antimicrobial agents have been produced by modification of
the various 4-quinolone ring structures.
Classes of Quinolones:

     Quinolone carboxylic     Enrofloxacin, norfloxacin, ciprofloxacin, orbifloxacin,
     acids:                   pefloxacin, danofloxacin, difloxacin, marbofloxacin,
                              rosoxacin, acrosoxacin, oxolinic acid
     Naphthydridine           Enoxacin, nalidixic acid
     carboxylic acids:
     Cinnoline carboxylic     Cinoxacin
     acids:
     Pyridopyrimidine         Pipemidic acid, piromidic acid
     carboxylic acids:
     Quinolizine carboxylic Ofloxacin, flumequine
     acids:

                                     General Properties
Within the diversity of their various ring structures, the quinolones have a number of common
functional groups that are essential for their antimicrobial activity. In addition, various
modifications have produced compounds with differing physical, chemical, pharmacokinetic,
and antimicrobial properties. For example, substitution at position 6 with a fluorine moiety
markedly enhances activity against both gram-negative and gram-positive bacteria, as well as
mycoplasmas and chlamydiae. These so-called fluoroquinolones, which are generally the most
efficacious within each class, include enrofloxacin, norfloxacin, ciprofloxacin, orbifloxacin,
ofloxacin, danofloxacin, flumequine, difloxacin, marbofloxacin, and other newer drugs. In
addition, substitution with a piperazine ring at position 7 significantly increases tissue and
bacterial penetration with consequent enhancement of activity; substitution with an oxygen atom
at position 8 improves activity against gram-positive and anaerobic organisms without affecting
the bactericidal profile.
The quinolones are amphoteric and, with a few exceptions, generally exhibit poor water
solubility between pH 6 and 8. In concentrated acidic urine, such as may be found in dogs and
cats, some quinolones form needle-shaped crystals. Liquid formulations of various quinolones
for PO or parenteral administration usually contain freely soluble salts in stable aqueous
solutions. Solid formulations (eg, tablets, capsules, or boluses) contain the active ingredient
either in its betaine form or, occasionally, as the hydrochloride salt.
Mode of Action:
 The quinolones inhibit the bacterial enzyme DNA-gyrase (topoisomerase), which is
 responsible for the supercoiling of DNA so that the DNA can twist in a number of
 chromosomal domains and seal around an RNA core. To do this, the chromosome also must be
 transiently nicked before sealing. When DNA-gyrase is inhibited by quinolones, a reduction in
 the supercoiling occurs with a consequent disruption of the spatial arrangement of DNA. The
 exposed nicks induce exonucleases that degrade chromosomal DNA into small fragments.
 Mammalian topoisomerases with nicking activity exist, but these enzymes are fundamentally
 different from bacterial gyrase and are not susceptible to quinolone inhibition. The quinolones
 are usually bactericidal; susceptible organisms lose viability within 20 min of exposure to
 optimal concentrations of the newer fluoroquinolones. Typically, clearing of cytoplasm at the
 periphery of the affected bacterium occurs and is followed by lysis. Affected bacteria are then
 recognizable only as ghosts.
Quinolones are known to produce a postantibiotic effect in a number of bacteria (eg,
Escherichia coli , Klebsiella pneumoniae , Pseudomonas aeruginosa ). The effect generally
lasts 4-8 hr after exposure.
Ideal bactericidal concentrations of the quinolones are often 0.1-10 µg/mL; efficacy tends to
diminish at higher concentrations. This unusual biphasic effect is thought to be due to
suppression of RNA synthesis at higher quinolone concentrations. Efficacy of the fluorinated
quinolones depends on concentrations in plasma that exceed the MIC of the infecting organism
by 4- to 10- fold.
The fluoroquinolones often have significant antibacterial activity at extraordinarily low
concentrations. The MIC (µg/mL) for enrofloxacin against some common veterinary
pathogens are <0.01-0.5 for E coli , <0.03-0.5 for Klebsiella spp , 0.003-0.5 for Salmonella spp
, 0.25-2 for P aeruginosa , <0.008-0.12 for Mannheimia (Pasteurella) haemolytica , 0.03-1 for
Staphylococcus aureus , 0.06-4 for Streptococcus spp , and 0.01-1 for Mycoplasma spp .
Bacterial Resistance:
Although resistance develops quite rapidly to nalidixic acid and some older quinolones, only
low-frequency chromosomal mutational resistance to the newer quinolones has been
recognized, and it is not regarded as a significant problem. Resistance is due to modification of
the target gyrase enzyme. Plasmid-mediated resistance is rare. Fortunately, the virulence of
refractory mutants diminishes substantially, and these bacterial populations tend to disappear
because of growth deficiencies. Cross-resistance does occur between some closely related
quinolones.
Antimicrobial Spectrum:
The fluoroquinolones are active against a wide range of gram-negative and a number of gram-
positive aerobes. They are highly effective against all intestinal bacterial pathogens, as well as
several intracellular pathogens, eg, Brucella spp . These newer quinolones also have significant
activity against Mycoplasma and Chlamydia spp . Obligate anaerobes tend to be resistant to
most quinolones, as are most enterococcal group D Streptococcus spp ( S faecalis and S faecium
).
The older quinolones (eg, nalidixic acid and oxolinic acid) and the nonfluorinated quinolones
(eg, cinoxacin) tend to have only a moderately extended gram-negative spectrum.
A synergistic effect of quinolones with the β-lactams, aminoglycosides, clindamycin, and
metronidazole has been demonstrated in vitro.
Therapeutic Indications & Dose Rate:
Quinolones are indicated for the treatment of local and systemic infections caused by susceptible
microorganisms, particularly against deep-seated infections and intracellular pathogens.
Therapeutic success has been obtained in respiratory, intestinal, urinary, and skin infections, as
well as in bacterial prostatitis, meningoencephalitis, osteomyelitis, and arthritis.
Side Effects and Toxicity:
Although side effects with the older quinolones (nalidixic and oxolinic acids) were relatively
common, the newer ones seem to be well tolerated. Quinolones tends to be neurotoxic, and
convulsions can occur at high doses. Vomiting and diarrhea rarely develop with
fluoroquinolones. Dermal reactions and photosensitization have been described in humans, but
the occurrence seems low. Hemolytic anemia has also been seen. Administering large doses of
quinolones for any length of time during pregnancy has resulted in embryonic loss and maternal
toxicity. Because high prolonged dosages in growing dogs have produced cartilaginous erosions
leading to permanent lameness, excessive use of quinolones should be avoided in immature
animals. Quinolone administration in horses has not yet been extensively studied, but there is
some indication that damage to the cartilage in weightbearing joints may be seen. Otherwise,
the safety of quinolones (especially enrofloxacin) has been established in laboratory animals,
calves, pigs, dogs, cats, and poultry.
Interactions:
The likelihood of interactions has not yet been clearly established. Antacids probably interfere
with the GI absorption of the quinolones. It also seems that nitrofurantoin impairs the efficacy
of quinolones if used concurrently for urinary tract infections. Quinolones do inhibit the
biotransformation of theophylline, leading to prolonged and potentially toxic plasma levels.
Effects on Laboratory Tests:
AST, ALT, alkaline phosphatase, and BUN may be increased. Urinalysis may reveal needle-
shaped crystals.


                                        Tetracyclin
The tetracyclines are broad-spectrum antibiotics with similar antimicrobial features, but they
differ somewhat from one another in terms of their spectra and pharmacokinetic disposition.
                                            Classes
There are 3 naturally occurring tetracyclines (oxytetracycline, chlortetracycline, and
demethylchlortetracycline) and several that are derived semisynthetically (tetracycline,
rolitetracycline, methacycline, minocycline, doxycycline, lymec ycline, etc). Elimination times
permit a further classification into short-acting (tetracycline, oxytetracycline, chlortetracycline),
intermediate-acting (demethylchlortetracycline and methacycline), and long-acting (doxycycline
and minocycline).
                                     General Properties
All of the tetracycline derivatives are crystalline, yellowish, amphoteric substances that, in
aqueous solution, form salts with both acids and bases. They characteristically fluoresce when
exposed to ultraviolet light. The most common salt form is the hydrochloride, except for
doxycycline, which is available as doxycycline hyclate. The tetracyclines are stable as dry
powders but not in aqueous solution, particularly at higher pH ranges (7-8.5). Preparations for
parenteral administration must be carefully formulated, often in propylene glycol or polyvinyl
pyrrolidone with additional dispersing agents, to provide stable solutions. Tetracyclines form
poorly soluble chelates with bivalent and trivalent cations, particularly calcium, magnesium,
aluminum, and iron. Doxycycline and minocycline exhibit the greatest liposolubility and better
penetration of bacteria such as Staphylococcus aureus than does the group as a whole.
Mode of Action:
 The exact site involved in the antimicrobial activity of tetracyclines has not been clarified, but
 these antibiotics bind reversibly to bacterial 30 S ribosomes and inhibit protein synthesis,
 perhaps by several mechanisms. Mainly, the binding of aminoacyl-tRNA to the acceptor site on
 the mRNA-ribosome complex seems to be impaired. This effect also is evident in mammalian
 cells, although microbial cells are selectively more susceptible because of the greater
 concentrations that are seen. Tetracyclines enter microorganisms in part by diffusion and in part
 by an energy-dependent, carrier-mediated system that is responsible for the high levels achieved
 in susceptible bacteria. The tetracyclines are generally bacteriostatic, and a responsive host-
 defense system is essential for their successful use. At high concentrations, as may be attained
 in urine, they become bactericidal because the organisms seem to lose the functional integrity of
 the cytoplasmic membrane. Tetracyclines are more effective against multiplying
 microorganisms and tend to be more active at a pH of 6-6.5.
Bacterial Resistance:
 Microbial resistance to tetracyclines is based almost exclusively on decreased penetration of the
 drug into previously susceptible organisms. Two forms are recognized: 1) impaired uptake into
 bacteria, seen in mutant strains that do not have the necessary transport system, and 2) plasmid-
 mediated resistance, which confers the property of either diminished uptake or active efflux of
 tetracycline from the bacterial cell. The genomes for these capabilities may be transferred either
 by transduction (as in Staphylococcus aureus ) or by conjugation (as in many enterobacteria).
 Resistance develops slowly in a multistep fashion but is widespread because of the extensive
 use of low levels of tetracyclines.
Antimicrobial Spectra:
All tetracyclines are about equally active and typically have about the same broad spectrum,
which comprises both aerobic and anaerobic gram-positive and gram-negative bacteria,
mycoplasmas, rickettsiae, chlamydiae, and even some protozoa (amebae). Strains of
Pseudomonas aeruginosa , Proteus , Serratia , Klebsiella , and Corynebacterium spp frequently
are resistant, as are many pathogenic E coli isolates. Even though there is general cross-
resistance among tetracyclines, doxycycline and minocycline usually are more effective against
staphylococci.
The tetracyclines are used to treat both systemic and local infections. General organ infections
include bronchopneumonia, bacterial enteritis, urinary tract infections, cholangitis, metritis,
mastitis, prostatitis, and pyodermatitis. Specific conditions include infectious
keratoconjunctivitis in cattle, chlamydiosis, heartwater, anaplasmosis, actinomycosis,
actinobacillosis, nocardiosis (especially minocycline), ehrlichiosis (especially doxycycline),
eperythrozoonosis, and haemobartonellosis. Minocycline and doxycycline are often effective to a
somewhat lesser degree against resistant strains of Staphylococcus aureus .
In addition to antimicrobial chemotherapy, the tetracyclines are used for other purposes. As
additives in animal feeds, they serve as growth promoters. Because of the affinity of tetracyclines
for bones, teeth, and necrotic tissue, they can be used to delineate tumors by fluorescence.
Demethylchlortetracycline has been used to inhibit the action of antidiuretic hormone in cases of
excessive water retention and to ―stretch‖ flexor digital tendons in neonatal foals.
Dose Rates of Tetracyclines

     Tetracycline       Species                           Dosage, Route, and Frequency
     Tetracycline       Cats, dogs                        7 mg/kg, IM or IV, bid
                                                          20 mg/kg, PO, tid
     Oxytetracycline    Cats, dogs                        7 mg/kg, IM or IV, bid
                                                          20 mg/kg, PO, tid
                        Cattle, sheep, pigs               5-10 mg/kg, IM or IV, sid
                        Calves, foals, lambs, piglets     10-20 mg/kg, PO, bid-tid
                        Horses                            5 mg/kg, IV, sid-bid
     Doxycycline        Dogs                              5-10 mg/kg, PO, sid
                                                          5 mg/kg, IV, sid
    Side Effects and Toxicity:
    Because several diverse effects may result from the administration of the tetracyclines,
    caution should be exercised. Superinfection by nonsusceptible pathogens such as
    fungi, yeasts, and resistant bacteria is always a possibility when broad-spectrum
    antibiotics are used. This may lead to GI disturbances after either PO or parenteral
    administration or to ―persistent infection‖ when they are applied topically (eg, in the
    ear). Severe and even fatal diarrhea can occur in horses receiving tetracyclines,
    especially if the animals are severely stressed or critically ill.
     High doses administered PO to ruminants seriously disrupt microfloral activity in the
     ruminoreticulum, eventually producing stasis. Elimination of the gut flora in monogastric
     animals reduces the synthesis and availability of the B vitamins and vitamin K from the
     large intestine. With prolonged therapy, vitamin supplementation is a useful precaution.
     Tetracyclines chelate calcium in teeth and bones; they become incorporated into these
     structures, inhibit calcification (eg, hypoplastic dental enamel), and cause yellowish
     then brownish discoloration. At extremely high concentrations, the healing processes
in fractured bones is impaired.
Rapid IV injection of a tetracycline can result in hypotension and sudden collapse.
This appears to be related to the ability of the tetracyclines to chelate ionized calcium,
although a depressant effect by the propylene glycol carrier itself may also be
involved. This effect can be avoided by slow infusion of the drug (>5 min) or by
pretreatment with IV calcium gluconate.
The IV administration of undiluted propylene-glycol-based preparations leads to
intravascular hemolysis, which results in hemoglobinuria, and possibly other reactions
such as hypotension, ataxia, and CNS depression.
Because tetracyclines interfere with protein synthesis even in host cells and therefore
tend to be catabolic, an increase in BUN can be expected. The combined use of
glucocorticoids and tetracyclines often leads to a significant weight loss, particularly in
anorectic animals.
Hepatotoxic effects due to large doses of tetracyclines have been reported in pregnant
women and in other animals. The mortality rate is high.
The tetracyclines are also potentially nephrotoxic and are contraindicated (except for
doxycycline) in renal insufficiency. Fatal renal failure has been reported in septicemic
and endotoxemic cattle given high doses of oxytetracycline. The administration of
expired tetracycline products may lead to acute tubular nephrosis.
Swelling, necrosis, and yellow discoloration at the injection site almost inevitably are
seen. Phototoxic dermatitis may be seen in human patients treated with
demethylchlortetracycline and other analogs, but this reaction is rare in other animals.
Hypersensitivity reactions do occur; for example, cats may show a ―drug fever‖
reaction, often accompanied by vomiting, diarrhea, depression, inappetence, and
eosinophilia.
The tetracyclines can inhibit WBC chemotaxis and phagocytosis when present in high
concentrations at sites of infection. This clearly hinders normal host defense
mechanisms. The addition of glucocorticoids to the therapeutic regimen would impair
immunocompetence even further.
Interactions:
The absorption of tetracyclines from the GI tract is decreased by milk and milk
products (less so for doxycycline and minocycline), antacids, kaolin, and iron
preparations. Tetracyclines gradually lose activity when diluted in infusion fluids and
exposed to ultraviolet light. Vitamins of the B-complex group, especially riboflavin,
hasten this loss of activity in infusion fluids. Tetracyclines also bind to the calcium
ions in Ringer‘s solution.
Methoxyflurane anesthesia combined with tetracycline therapy may be nephrotoxic.
Microsomal enzyme inducers such as phenobarbital and phenytoin shorten the plasma
half-lives of minocycline and doxycycline. Except for minocycline and doxycycline,
the presence of food can substantially delay the absorption of tetracyclines from the GI
tract. The tetracyclines are less active in alkaline urine, and urine acidification can
increase their antimicrobial efficacy.
Effects on Laboratory Tests:
    Tetracyclines may increase amylase, BUN, sulfobromophthalein (BSP®), eosinophil
    count, AST, and ALT. Tetracyclines used in combination with diuretics are often
    associated with a marked rise in the BUN. Cholesterol, glucose, potassium, and
    prothrombin time may be decreased. A false-positive urine glucose test is also
    possible.
    Drug Withdrawal and Milk Discard Times:
    Regulatory requirements for withdrawal times for food animals and milk discard times
    vary among countries. These must be followed carefully to prevent food residues and
    consequent public health implications.

                      Chloramphenicol and Congeners
hloramphenicol is a highly effective and well-tolerated broad-spectrum antibiotic. However, it
does have several features that demand careful use in companion animals and that have led to
prohibition of its use in food-producing animals in several countries, including the USA and
Canada.
                                             Classes
Chloramphenicol is a unique antimicrobial agent; however, because of its tendency to cause
blood dyscrasias in humans, 2 related drugs have been developed. Thiamphenicol is less
effective but safer than chloramphenicol; florfenicol, a thiamphenicol derivative, is significantly
more active in vitro than chloramphenicol against many pathogenic strains of bacteria.
Florfenicol is approved for use in cattle.
                                        General Properties
Chloramphenicol is a relatively simple neutral nitrobenzene derivative with a bitter taste. It is
highly lipid soluble and is used either as the free base or in ester forms (eg, the neutral-tasting
palmitate for administration PO and the water-soluble sodium succinate for parenteral injection).
Chloramphenicol is a relatively stable compound and is unaffected by boiling, provided that a
pH of 9 is not exceeded. The nitrophenol group of chloramphenicol is replaced by a methyl
sulfonyl group for thiamphenicol and florfenicol; florfenicol also contains a fluorine molecule.
These structural changes improve efficacy, reduce toxicity, and for florfenicol, the fluorine
molecule reduces bacterial destruction.
Mode of Action:
The antimicrobial mechanism seems to be the same for all of the macrolides. They interfere
with protein synthesis by reversibly binding to the 50 S subunit of the ribosome. They appear to
bind at the donor site, thus preventing the translocation necessary to keep the peptide chain
growing. The effect is essentially confined to rapidly dividing bacteria and mycoplasmas.
Macrolides are regarded as being bacteriostatic, but at high concentrations, erythromycin is
bactericidal. Macrolides are significantly more active at higher pH ranges (7.8-8).
Bacterial Resistance:
Resistance to macrolides in gram-positive organisms results from alterations in ribosomal
structure and loss of macrolide affinity. The resistance may be intrinsic or plasmid-mediated
and constitutive or inducible; it may develop rapidly (erythromycin) or slowly (tylosin). Cross-
resistance between macrolides has been reported. Gram-negative organisms are probably
resistant because macrolides cannot penetrate their cell walls. There are a few exceptions, and
gram-negative forms without cell walls are usually sensitive.
Antimicrobial Spectra:
Macrolides are active against most aerobic and anaerobic gram-positive bacteria, although there
is considerable variation as to potency and activity. In general, macrolides are not active against
gram-negative bacteria, but some strains of Pasteurella , Haemophilus , and Neisseria spp may
be sensitive. An exception is tilmicosin, the spectrum of which is characterized as broad and
includes Mannheimia (Pasteurella) haemolytica and P multocida . Bacteroides fragilis strains
are moderately susceptible to macrolides. Macrolides are active against atypical mycobacteria,
Mycobacterium , Mycoplasma , Chlamydia , and Rickettsia spp but not against protozoa or
fungi. In vitro synergism is seen with cefamandole (against Bacteroides fragilis ), ampicillin
(against Nocardia asteroides ), and rifampin (against Rhodococcus equi ).
Therapeutic Indications & Dose Rate
Chloramphenicol is used to treat both systemic and local infections. Chronic respiratory
infections, bacterial meningoencephalitis, brain abscesses, ophthalmitis and intraocular
infections, pododermatitis, dermal infections, and otitis externa are types of bacterial infections
that are often responsive to chloramphenicol. Salmonellosis and Bacteroides sepsis are fairly
specific indications. Urinary tract infections are often successfully treated with chloramphenicol,
notwithstanding the fairly low concentration of active antibiotic present in the urine.
Hematogenous delivery of chloramphenicol to the site of infection may play a role in these cases.
Florfenicol is approved for use in treatment of bovine respiratory disease.
Dose Rates of Chloramphenicol and Florfenicol

     Drug                   Species    Dosage, Route, and Frequency
     Chloramphenicol        Cats       45-60 mg/kg, PO, IV, or IM, bid
                            Dogs       45-60 mg/kg, PO, IV, or IM, tid- qid
                            Horses     50 mg/kg, PO, tid- qid, or IV, every 2-4 hr
     Florfenicol            Cattle     20 mg/kg, IM, repeated in 48 hr




                                        Macrolides
The macrolide antibiotics typically have a large lactone ring in their structure and are much more
effective against gram-positive than gram-negative bacteria. They are also active against
mycoplasmas and some rickettsiae.
Macrolides fall into 3 classes, depending on the size of the lactone ring. None of the 12-
membered ring group is used clinically. Erythromycin and the closely related oleandomycin and
troleandomycin belong to the 14-membered ring group. Of the 16-membered ring group,
spiramycin, josamycin, and tylosin are used clinically.
General Properies:
A macrolide is actually a complex mixture of closely related antibiotics that differ from one
another with respect to the chemical substitutions on the various carbon atoms in the structure,
and in the aminosugars and neutral sugars. For example, erythromycin is mostly erythromycin A,
but B, C, D, and E forms may also be included in the preparation. The macrolide antibiotics are
colorless, crystalline substances. They contain a dimethylamino group, which makes them basic.
Although they are poorly water soluble, they do dissolve in more polar organic solvents.
Macrolides are often inactivated in basic (pH >10) as well as acidic environments (pH <4 for
erythromycin). The multiple functional groups make it possible for them to undergo a large
number of chemical reactions. More stable ester forms are commonly used in pharmaceutical
preparations—eg, acetylates, estolates, lactobionate, succinates, propionates, and stearates.
Mode of Action:
 The antimicrobial mechanism seems to be the same for all of the macrolides. They interfere
 with protein synthesis by reversibly binding to the 50 S subunit of the ribosome. They appear to
 bind at the donor site, thus preventing the translocation necessary to keep the peptide chain
 growing. The effect is essentially confined to rapidly dividing bacteria and mycoplasmas.
 Macrolides are regarded as being bacteriostatic, but at high concentrations, erythromycin is
 bactericidal. Macrolides are significantly more active at higher pH ranges (7.8-8).
Bacterial Resistance:
 Resistance to macrolides in gram-positive organisms results from alterations in ribosomal
 structure and loss of macrolide affinity. The resistance may be intrinsic or plasmid-mediated
 and constitutive or inducible; it may develop rapidly (erythromycin) or slowly (tylosin). Cross-
 resistance between macrolides has been reported. Gram-negative organisms are probably
 resistant because macrolides cannot penetrate their cell walls. There are a few exceptions, and
 gram-negative forms without cell walls are usually sensitive.
Antimicrobial Spectra:
 Macrolides are active against most aerobic and anaerobic gram-positive bacteria, although there
 is considerable variation as to potency and activity. In general, macrolides are not active against
 gram-negative bacteria, but some strains of Pasteurella , Haemophilus , and Neisseria spp may
 be sensitive. An exception is tilmicosin, the spectrum of which is characterized as broad and
 includes Mannheimia (Pasteurella) haemolytica and P multocida . Bacteroides fragilis strains
 are moderately susceptible to macrolides. Macrolides are active against atypical mycobacteria,
 Mycobacterium , Mycoplasma , Chlamydia , and Rickettsia spp but not against protozoa or
 fungi. In vitro synergism is seen with cefamandole (against Bacteroides fragilis ), ampicillin
 (against Nocardia asteroides ), and rifampin (against Rhodococcus equi ).
Therapeutic Indications & Dose Rate:
The macrolides are used to treat both systemic and local infections. They are often regarded as
alternatives to penicillins for the treatment of streptococcal and staphylococcal infections.
General indications include upper respiratory tract infections, bronchopneumonia, bacterial
enteritis, metritis, pyodermatitis, urinary tract infections, arthritis, and others. Formulations for
treating mastitis are also available and often have the advantage of a short withholding time for
milk. Tilmicosin is approved for use in the treatment of bovine respiratory diseases associated
with Mannheimia (Pasteurella) haemolytica.
Dose Rates of Macrolides

     Macrolide           Species     Dosage, Route, and Frequency
     Erythromycin        Cattle      8-15 mg/kg, IM, sid-bid
                         Cats        15 mg/kg, PO, tid
                         Foals       25 mg/kg, IM, tid
     Tylosin             Cattle      10-20 mg/kg, IM, sid-bid
                         Pigs        10 mg/kg, IM, sid-bid 7-10 mg/kg, PO, tid
                         Cats        10 mg/kg, IM, bid
     Tilmicosin          Cattle      10 mg/kg, SC, once

Side Effects and Toxicity:
Toxicity and side effects are uncommon for most macrolides (except tilmicosin), although pain
and swelling may develop at injection sites. Hypersensitivity reactions have occasionally been
seen. Erythromycin estolate may be hepatotoxic and cause cholestasis; it may also induce
vomiting and diarrhea, particularly when high doses are administered. Horses are sensitive to
macrolide-induced GI disturbances that can be serious and even fatal. In pigs, tylosin may cause
edema of the rectal mucosa, mild anal protrusion with diarrhea, and anal erythema and pruritus.
After 5 mg/kg/day, dogs had a greater tendency to develop ventricular tachycardia and
fibrillation during acute myocardial ischemia. Tilmicosin is characterized by cardiac toxicity
(tachycardia and decreased contractility). It is contraindicated in swine and should not be used in
an extra-label manner. Cattle have died after IV injection of tilmicosin
Interactions:
Macrolide antibiotics probably should not be used with chloramphenicol or the lincosamides
because they may compete for the same 50 S ribosomal binding site, although the in vivo
significance of this potential interaction is unclear. Activity of macrolides is depressed in acidic
environments. Macrolide preparations for parenteral administration are incompatible with many
other pharmaceutical preparations. Erythromycin and troleandomycin are microsomal enzyme
inhibitors that depress the metabolism of some drugs.
Effects on Laboratory Tests:
Alkaline phosphatase, bilirubin, sulfobromophthalein (BSP®), total WBC count, eosinophil
count, AST, and ALT may increase. Cholesterol levels may decrease.
Drug Withdrawal and Milk Discard Times:
Regulatory requirements for withdrawal times and milk discard times vary among countries.
These should be followed carefully to prevent food residues and consequent public health
implications. Tilmicosin is characterized by a 28-day withdrawal time and should not be used in
any species other than adult cattle (but not in dairy cows >20 mo old).

                                       Lincosamide
Lincosamides are derivatives of an amino acid and a sulfur-containing octose. They are
monobasic and more stable in salt forms (hydrochlorides and phosphates).
Mode of Action:
Lincomycin and clindamycin bind exclusively to the 50 S subunit of bacterial ribosomes and
suppress protein synthesis. Lincosamides, macrolides, and chloramphenicol, although not
structurally related, seem to act at this same site. The lincosamides are bacteriostatic or
bactericidal depending on the concentration. Activity is enhanced at an alkaline pH.
Bacterial Resistance:
Resistance to lincosamides appears slowly, perhaps as a result of chromosomal mutation.
Plasmid-mediated resistance has been found in strains of Bacteroides fragilis . Resistance
appears to be due to an alteration in the 50 S ribosomal subunit. Cross-resistance with other
antibiotics has been shown in vitro but not in vivo with erythromycin.
Antimicrobial Spectra:
 Lincomycin has a limited spectrum against aerobic pathogens but a fairly broad spectrum
 against anaerobes. Clindamycin is a more active analog with somewhat different
 pharmacokinetic patterns. Many gram-positive cocci are inhibited by lincosamides, but most
 gram-negative organisms are resistant, as are most mycoplasmas. Bacteroides spp and other
 anaerobes are usually susceptible. Clostridium difficile strains appear to be regularly resistant.
Indications & Dose RateThe lincosamides are indicated for infections caused by susceptible
gram-positive organisms, particularly streptococci and staphylococci, and for those caused by
anaerobic pathogens.
Dose Rates of Lincosamides

     Lincosamide               Species              Dosage, Route, and Frequency
     Lincomycin            Cattle           10 mg/kg, IM, bid
                           Pigs             10 mg/kg, IM, bid
                                            7 mg/kg, in-feed
                           Dogs             20 mg/kg, PO, sid
                           Cats             10 mg/kg, IM, bid
                                            25 mg/kg, PO, bid
     Clindamycin           Dogs, cats       5-10 mg/kg, PO, bid

Side Effects and Toxicity:
No serious organ toxicity has been reported, but GI disturbances do occur. Clindamycin-
induced pseudomembranous enterocolitis (caused by toxigenic Clostridium difficile ) is a
serious adverse reaction seen in humans. Lincosamides are contraindicated in horses
because severe and even fatal colitis may develop. Skeletal muscle paralysis may be seen
at high concentrations. Hypersensitivity reactions occasionally are seen. Lincosamides
should not be used in neonates because of their limited ability to metabolize drugs.
Interactions:
Lincosamides have additive neuromuscular effects with anesthetic agents and skeletal muscle
relaxants. Kaolin-pectin prevents their absorption from the GI tract. They should not be
combined with bactericidal agents or with the macrolides.
Effects on Laboratory Tests:
Alkaline phosphatase, AST, and ALT may be increased.
Drug Withdrawal Times:
 In several countries, there is a 2-day withdrawal time for pigs.


                                     Antifungals
opical infections caused by a large variety of fungi may become established on the skin and
adnexa or mucous membranes (buccal, GI, ruminal, vaginal). The external auditory canal and
cornea may also be invaded by yeasts and fungi that are opportunistic pathogens. Locally active
antifungal drugs are used to treat such topical infections.
A number of serious systemic fungal diseases are well recognized in several parts of the world.
Antifungal agents have greatly reduced earlier mortality rates due to systemic mycoses in
humans. A relatively narrow selection of drugs is used in these cases.
                         Polyene Macrolide Antibiotics
A number of polyene antifungal antibiotics has been isolated from various strains of
Actinomyces , but only amphotericin B, nystatin, and pimaricin (natamycin) are used in
veterinary medicine. The polyenes are poorly soluble in water and the common organic solvents.
They are reasonably soluble in highly polar solvents such as dimethylformamide and dimethyl
sulfoxide. In combination with bile salts, such as sodium deoxycholate, amphotericin B is readily
soluble (micellar suspension) in 5% glucose. This colloidal preparation is used for IV infusion.
The polyenes are quite unstable in aqueous, acidic, or alkaline media but in the dry state, in the
absence of heat and light, they remain stable for indefinite periods. They should be administered
parenterally (diluted in 5% dextrose) as freshly prepared aqueous suspensions (stable for 1 wk if
refrigerated).
Mode of Action:
 The polyenes bind to sterol components in the phospholipid-sterol membranes of fungal cells to
 form complexes that induce physical changes in the membrane. The number of conjugated
 bonds and the molecular size of a particular polyene macrolide influence its avidity for different
 sterols in fungal cell membranes. Amphotericin B, because of its greater affinity, binds to
 ergosterol, the major sterol in fungal membranes, rather than to the cholesterol in host cells. The
 disruption of membrane function results in potassium ion efflux from the fungal cell and
 hydrogen ion influx, producing internal acidification and a halt in enzymatic functions. Sugars
 and amino acids also eventually leak from an arrested cell. Fungistatic effects are most often
 evident at usual polyene concentrations. High drug concentrations and pH values between 6.0
 and 7.3 in the surrounding medium may lead to fungicidal rather than fungistatic action. In
 addition to these direct effects on susceptible yeasts and fungi, evidence suggests that
 amphotericin B may also act as an immunopotentiator (both humoral and cell-mediated), thus
 enhancing the host‘s ability to overcome mycotic infections.
Fungal Resistance:
 Resistance to the polyene antifungal macrolides is rare both clinically and in vitro. Resistance
 develops slowly and does not reach high levels, even after prolonged treatment.
Antifungal Spectra:
 The polyene antibiotics have broad antifungal activity against organisms ranging from yeasts to
 filamentous fungi and from saprophytic to pathogenic fungi, but there are great differences
 between the sensitivities of the various species and strains of fungi. In vitro sensitivities (both
 resistant and highly susceptible) do not always correlate well with the clinical response, which
 suggests that host factors may also play a role. Many algae and some protozoa ( Leishmania ,
 Trypanosoma , Trichomonas , and Entamoeba spp ) are sensitive to the polyenes, but these
 compounds have no significant activity against bacteria, actinomycetes, viruses, or animal cells.
 Amphotericin B is effective against yeasts (eg, Candida spp , Rhodotorula spp , Cryptococcus
 neoformans ), dimorphic fungi (eg, Histoplasma capsulatum , Blastomyces dermatitidis ,
 Coccidioides immitis ), dermatophytes (eg, Trichophyton , Microsporum , and Epidermophyton
 spp ), and molds. The drug also has been used successfully to treat disseminated sporotrichosis,
 pythiosis, and zygomycosis, although it may not always be effective. The polyenes are not
 effective against dermatophytes. Nystatin is mainly used for the treatment of mucocutaneous
candidiasis, but it is effective against other yeasts and fungi. The antimicrobial activity of
pimaricin is similar to that of nystatin, though it is mainly used for the local treatment of
candidiasis, trichomoniasis, and mycotic keratitis.
Indications & Dose Rate:
Amphotericin B is used principally in the treatment of systemic mycotic infections. Despite its
ability to cause nephrotoxicity (see below), amphotericin B remains a commonly used
antifungal agent because of its effectiveness. Nystatin is primarily indicated for the treatment
of mucocutaneous (skin, oropharynx, vagina) or intestinal candidiasis; pimaricin is mainly used
in therapeutic management of mycotic keratitis.
Dose Rates of Polyene Macrolide Antibiotics

      Polyene Macrolide                   Dosage, Route, and Frequency
      Amphotericin B (0.1 mg/mL in 5% 0.1-1 mg/kg, given IV slowly, 3 times/wk Total
      dextrose)                       dose: 4-11 mg/kg
      Nystatin                            50,000-150,000 U, PO, tid (dogs)
      Pimaricin (5% ophthalmic            1 drop, instilled into the eye, every 1-2 hr
      solution)

Side Effects and Toxicity:
Oral administration of nystatin can lead to anorexia and GI disturbances. The IV infusion of
amphotericin B is potentially harmful, but the main concern is nephrotoxicity. Within 15 min of
IV administration, renal arterial vasoconstriction occurs and lasts for 4-6 hr. This leads to
diminished renal blood flow and glomerular filtration. Because amphotericin B binds to the
cholesterol component in the membranes of the distal renal tubules, a change in permeability
occurs in these cells, leading to polyuria, polydipsia, concentration defects, and acidification
abnormalities. The net result is a distal renal tubular acidosis syndrome. The metabolic acidosis
leads to bone buffering, the excessive release of calcium into the circulation, and ultimately,
nephrocalcinosis due to calcium precipitation in the acidic environment of the distal tubules.
Almost every animal treated with amphotericin B suffers some degree of renal impairment,
which may become permanent depending on the total cumulative dose. The administration of
amphotericin B can lead to a number of other adverse effects, including anorexia, nausea,
vomiting, hypersensitivity reactions, drug fever, normocytic normochromic anemia, cardiac
arrhythmias and even arrest, hepatic dysfunction, CNS signs, and thrombophlebitis at the
injection site.
The incidence of serious adverse effects of amphotericin B therapy can be reduced.
Pretreatment with antiemetic and antihistaminic agents prevents the nausea, vomiting, and
hypersensitivity reactions. Giving corticosteroids IV also limits severe hypersensitivity
reactions. Mannitol (1 g/kg, IV) with each dose of amphotericin B, and sodium bicarbonate (2
mEq/kg, IV or PO, daily) may help prevent acidification defects, metabolic acidosis, and
azotemia; however, clinical evidence of efficacy has not been proved. Saralasin (6-12
µg/kg/min, IV) and dopamine (7 µg/kg/min, IV) infusions have prevented oliguria and azotemia
induced by amphotericin B in dogs. Administering IV fluids or furosemide before amphotericin
B prevents pronounced decreases in renal blood flow and glomerular filtration rate. Newer
preparations in which amphotericin B is mixed with lipid or liposomal vehicles are safer
(particularly liposomes) and have maintained efficacy.
Interactions:
Amphotericin B may be combined with other antimicrobial agents with synergistic results. This
often allows both the total dose of amphotericin B and the length of therapy to be decreased.
Examples include combinations of 5-flucytosine and amphotericin B for the treatment of
cryptococcal meningitis, minocycline and amphotericin B for coccidioidomycosis, and
imidazole and amphotericin B for several systemic mycotic infections. Rifampin may also
potentiate the antifungal activity of amphotericin B.
Drugs that should be avoided during amphotericin B therapy include aminoglycosides
(nephrotoxicity), digitalis drugs (increased toxicity), curarizing agents (neuromuscular
blockade), mineralocorticoids (hypokalemia), thiazide diuretics (hypokalemia, hyponatremia),
antineoplastic drugs (cytotoxicity), and cyclosporine (nephrotoxicity).
Effects on Laboratory Tests:
Plasma bilirubin, CK, AST, ALT, BUN, and eosinophil count increase. Plasma potassium and
platelet count decrease. Urine protein increases.

                                         Imidazoles
Imidazoles may have antibacterial, antifungal, antiprotozoal, and anthelmintic activity. Several
distinct phenylimidazoles are therapeutically useful antifungal agents with wide spectra against
yeasts and filamentous fungi responsible for either superficial or systemic infections. The
anthelmintic thiabendazole is also an imidazole with antifungal properties. Clotrimazole,
miconazole, econazole, ketoconazole, itraconazole, and fluconazole are the most clinically
important members of this group.
Imidazoles generally are poorly soluble in water but can be dissolved in organic solvents, such as
chloroform, propylene glycol, and polyethoxylated castor oil (preparation for IV use but
dangerous in dogs). An exception is fluconazole. Imidazoles are weak dibasic agents. Alterations
in side-chain structure determine antifungal activity as well as the degree of toxicity.
Mode of Action:
 Imidazoles alter the cell membrane permeability of susceptible yeasts and fungi by blocking
 the synthesis of ergosterol (demethylation of lanosterol is inhibited), the primary cell sterol of
 fungi. Other enzyme systems are also impaired, such as those required for fatty acid synthesis.
 Because of the drug-induced changes of oxidative and peroxidative enzyme activities, toxic
 concentrations of hydrogen peroxide develop intracellularly. The overall effect is cell
 membrane and internal organelle disruption and cell death. The cholesterol in host cells is not
 affected by the imidazoles, although some drugs impair synthesis of selected steroids and
 drug-metabolizing enzymes in the host.
Fungal Resistance:
 Sensitivity to the imidazoles varies greatly between various strains of yeasts and fungi, but
 neither natural nor acquired resistance appears to be prevalent.
Antimicrobial Spectra:
The antifungal imidazoles also have some antibacterial action but are rarely used for this
purpose. Miconazole has a wide antifungal spectrum against most fungi and yeasts of veterinary
interest. Sensitive organisms include Blastomyces dermatitidis , Paracoccidioides brasiliensis ,
Histoplasma capsulatum , Candida spp , Coccidioides immitis , Cryptococcus neoformans , and
Aspergillus fumigatus . Some Aspergillus and Madurella spp are only marginally sensitive.
Ketoconazole has an antifungal spectrum similar to that of miconazole, but it is more effective
against C immitis and some other yeasts and fungi. Itraconazole and fluconazole are the most
active of the antifungal imidazoles. Their spectrum includes dimorphic fungal organisms and
dermatophytes. They are also effective against some cases of aspergillosis (60-70%) and
cutaneous sporotrichosis. Clotrimazole and econazole are used for superficial mycoses
(dermatophytosis and candidiasis); econazole also has been used for oculomycosis.
Thiabendazole is effective against Aspergillus and Penicillium spp , but its use has largely been
replaced by the more effective imidazoles.
Indications and Dose Rate:
The imidazoles are used to treat systemic fungal diseases, dermatomycoses that have not
responded to griseofulvin or topical therapy, Malassezia in dogs, aspergillosis, and sporotrichosis
in animals that cannot tolerate or do not respond to sodium iodide. For serious infections,
combination with amphotericin B is strongly recommended. Among the imidazoles, fluconazole
is most indicated for tissues that are tough to penetrate. Both itraconzaole and fluconazole are
generally preferred to other imidazoles for treatment of systemic fungal infections, including
aspergillosis and sporotrichosis. Topically applied imidazoles (clotrimazole, miconazole,
econazole) are used for local dermatophytosis. Thiabendazole is included in some otic
preparations for treatment of yeast infections.
Enilconazole is an imidazole that can be applied topically for the treatment of dermatophytosis
and aspergillosis. It has been used safely in cats, dogs, cattle, horses, and chickens and is
prepared as a 0.2% solution for the treatment of fungal skin infections. When infused into the
nasal turbinates of dogs with aspergillosis, enilconazole treated and prevented the recurrence of
fungal disease. When applied topically to dog and cat hairs enilconazole inhibits fungal growth
in 2 rather than 4-8 treatments, as is necessary with other topically administered antifungal
agents.
Dose Rates of Imidazoles

     Imidazole                Dosage, Route, and Frequency
     Enilconazole             10 mg/kg in 5-10 mL, bid for 7-14 days
     Fluconazole              5-10 mg/kg, PO, sid-bid
     Itraconazole             5-10 mg/kg, PO, sid-bid
     Ketoconazole             5-20 mg/kg, PO, bid (dogs)
     Thiabendazole            44 mg/kg, PO, sid, or 22 mg/kg, PO, bid

Side Effects and Toxicity:
The imidazoles given PO result in few side effects, but nausea, vomiting, and hepatic
dysfunction can develop, particularly with ketoconazole. Altered testosterone and cortisol
metabolism, as well as blunted adrenal responsiveness to ACTH, have been reported,
particularly with ketoconazole. Reproductive disorders related to ketoconazole
administration may be seen in dogs. The other antifungal imidazoles are now used
topically only.
Interactions:
The imidazoles may be used concurrently with amphotericin B or 5-flucytosine to potentiate its
antifungal activity. The absorption of the imidazoles, except for that of fluconazole, is inhibited
by concurrent administration of cimetidine, ranitidine, anticholinergic agents, or gastric
antacids. Rifampin decreases the serum levels of active ketoconazole because of microsomal
enzyme induction. The risk of hepatotoxicity is increased if ketoconazole and griseofulvin are
administered together. Ketoconazole inhibits the metabolism of some drugs and, if administered
concurrently, their concentrations may be higher than anticipated.
Effects on Laboratory Tests:
AST, ALT, plasma bilirubin, and plasma cholesterol increase. Adrenal responsiveness is
altered.
                                        Flucytosine
Flucytosine (5-fluorocytosine) is a fluorinated pyrimidine related to fluorouracil that was initially
developed as an antineoplastic agent. It should be stored in airtight containers protected from
light. Solutions for infusion are unstable and should be stored at 15-20°C. Usually, it is given PO
in capsules.
Mode of Action:
 Flucytosine is converted by cytosine deaminase in fungal cells to fluorouracil, which then
 interferes with RNA and protein synthesis. Fluorouracil is metabolized to 5-fluorodeoxyuridylic
 acid, an inhibitor of thymidylate synthetase. DNA synthesis is then also halted. Mammalian
 cells do not convert large amounts of flucytosine to fluorouracil and, thus, are not affected at
 usual dosage levels.
Fungal Resistance:
 Resistance to flucytosine can develop rapidly even during the course of treatment; this has
 restricted its use as the sole treatment for mycotic infections. The mechanisms of resistance are
 not completely understood.
Antifungal Spectrum:
 The following are the main organisms usually sensitive to flucytosine: Cryptococcus
 neoformans , Candida albicans , other Candida spp , Torulopsis glabrata , Sporothrix schenckii ,
 Aspergillus spp , and agents of chromoblastomycosis ( Phialophora , Cladosporium ). The other
 fungi responsible for systemic mycoses and dermatophytes are resistant to flucytosine.
Indications and Dose Rate:
Griseofulvin is used for dermatophyte infections in dogs, cats, calves, horses, and other domestic
and exotic animal species. Most dermatophytes are sensitive, but certain species present greater
therapeutic challenges than others. Several may require higher dose rates for satisfactory control.
Dose Rates of Griseofulvin

     Species      Dosage, Route, and Frequency
     Dogs, cats Microsized: 10-30 (up to 130) mg/kg, PO, sid or divided bid-tid;
                Ultramicrosized: 5-10 (up to 50) mg/kg, PO, sid
     Horses,      5-10 mg/kg, PO, sid for 3-6 wk, or longer if required
     cattle
Side Effects and Toxicity:
Flucytosine is often well tolerated over long periods, but toxic effects may be seen when serum
levels are high (>100 µg/mL). These include GI signs (nausea, vomiting, diarrhea) and
reversible hepatic and hematologic effects (increased liver enzymes, anemia, neutropenia,
thrombocytopenia). In dogs, erythemic and alopecic dermatitis may be seen but subsides when
the drug is discontinued.
Interactions:
There is synergistic antifungal activity between amphotericin B and ketoconazole, and the
combination may retard the emergence of strains resistant to flucytosine. The renal effects of
amphotericin B prolong elimination of flucytosine. If flucytosine is used together with
immunosuppressive drugs, severe depression of bone marrow function is possible.
Effects on Laboratory Tests:
Alkaline phosphatase, AST, ALT, and other liver leakage enzymes increase. RBC, WBC, and
platelet counts decrease.
                                       Griseofulvin
Griseofulvin is a systemic antifungal agent that is effective against the common dermatophytes.
It is practically insoluble in water and only slightly soluble in most organic solvents. Particle
sizes of griseofulvin vary from 2.7 µm (ultramicrosized) to 10 µm (microsized).
Mode of Action:
 Dermatophytes concentrate griseofulvin by an energy-dependent process. The drug then
 disrupts the mitotic spindle by interacting with the polymerized microtubules in susceptible
 dermatophytes. This leads to the production of multinucleate fungal cells. The inhibition of
 nucleic acid synthesis and the formation of hyphal cell wall material may also be involved. The
 result is distortion, irregular swelling, and spiral curling of the hyphae. Griseofulvin is
 fungistatic rather than fungicidal, except in young active cells.
Fungal Resistance:
 Dermatophytes can be made resistant to griseofulvin in vitro.
Antifungal Spectrum:
 Griseofulvin is active against Microsporum , Epidermophyton , and Trichophyton spp . It has no
 effect on bacteria, including Actinomyces and Nocardia spp , other fungi, or yeasts.
 Therapeutic Indictions and Dose Rate:
Griseofulvin is used for dermatophyte infections in dogs, cats, calves, horses, and other domestic
and exotic animal species. Most dermatophytes are sensitive, but certain species present greater
therapeutic challenges than others. Several may require higher dose rates for satisfactory control.
Dose Rates of Griseofulvin

     Species     Dosage, Route, and Frequency
     Dogs, cats Microsized: 10-30 (up to 130) mg/kg, PO, sid or divided bid-tid;
                Ultramicrosized: 5-10 (up to 50) mg/kg, PO, sid
     Horses,     5-10 mg/kg, PO, sid for 3-6 wk, or longer if required
     cattle
Side Effects and Toxicity:
Side effects induced by griseofulvin are rare. Nausea, vomiting, and diarrhea have been seen.
Hepatotoxicity has also been reported. Animals with impaired liver function should not be
given griseofulvin because its biotransformation will be reduced and toxic levels may be
reached. Idiosyncratic toxicity in cats has been reported. Griseofulvin is contraindicated in
pregnant animals (especially mares and queens) because it is teratogenic.
Interactions:
Lipids increase the GI absorption of griseofulvin. Barbiturates decrease its absorption and
antifungal activity. Griseofulvin is a microsomal enzyme inducer and promotes the
biotransformation of many concurrently administered drugs. The combined use of ketoconazole
and griseofulvin may lead to hepatotoxicity.
Effects on Laboratory Tests:
Alkaline phosphatase, AST, and ALT increase. Proteinuria may be detected.


                                            Iodide
Sodium and potassium iodide have both been used to treat selected bacterial, actinomycete, and
fungal infections, although sodium iodide is preferred. The in vivo effects of iodides against
fungal cells are not well understood. Iodide is readily absorbed from the GI tract and distributes
freely into the extracellular fluid and glandular secretions. Iodide concentrates in the thyroid
gland (50 times corresponding plasma level) and to a much lesser degree in salivary, lacrimal,
and tracheobronchial glands. Longterm use at high levels leads to accumulation in the body and
to iodinism. Clinical signs of iodinism include lacrimation, salivation, increased respiratory
secretions, coughing, inappetence, dry scaly skin, and tachycardia. Cardiomyopathy has been
reported in cats. Host defense systems, such as decreased immunoglobulin production and
reduced phagocytic ability of leukocytes, are also impaired. Iodinism may also lead to abortion
and infertility.
Sodium iodide has been used successfully to treat cutaneous and cutaneous/lymphadenitis forms
of sporotrichosis; attempts to control various other mycotic infections with iodides often have
had equivocal results.
The dosage for sodium iodide (20% solution) is 44 mg/kg, PO, sid for dogs, and 22 mg/kg, PO,
sid for cats. The dose for horses is 125 mL of 20% sodium iodide solution, IV, sid for 3 days,
then 30 g, PO, sid for 30 days after clinical remission. The dosage rate for treating actinomycosis
and actinobacillosis in cattle is 66 mg/kg, by slow IV, repeated weekly. Potassium iodide should
never be injected IV.
                             Topical Antifungal Agents
A large number of agents that have antifungal activity are applied topically, either on the skin, in
the ear or eye, or on mucous membranes (buccal, nasal, vaginal) to control superficial mycotic
infections. Concurrent systemic therapy with griseofulvin is often helpful for therapeutic
management of dermatophyte infections. The hair should be clipped from affected areas and the
nails trimmed to fully expose the lesions before antifungal preparations are applied. Bathing the
animal may also be helpful. Isolation or restricted movement of infected animals is wise,
especially when dealing with zoonotic fungi.
Preparations may be used in the form of solutions, lotions, sprays, powders, creams, or ointments
for dermal application, or in the form of irrigant solutions, ointments, tablets, or suppositories for
intravaginal use. The concentration of the active principle in these preparations varies and
depends on the activity of the specific agent.
The clinical response to local antifungal agents is unpredictable. Resistance to many of the
available drugs is common. Spread of infection and reinfection add to the difficulty of
controlling superficial infections. Perseverance is often an essential element of therapy.
Some topical antifungal agents that have been used with success in various conditions and
species include iodine preparations (tincture of iodine, potassium iodide, iodophors), copper
preparations (copper sulfate, copper naphthenate, cuprimyxin), sulfur preparations
(monosulfiram, benzoyl disulfide), phenols (phenol, thymol), fatty acids and salts (propionates,
undecylenates), organic acids (benzoic acid, salicylic acids), dyes (crystal [gentian] violet,
carbolfuchsin), hydroxyquinolines (iodochlorhydroxyquin), nitrofurans (nitrofuroxine,
nitrofurfurylmethyl ether), imidazoles (miconazole, ticonazole, clotrimazole, econazole,
thiabendazole), polyene antibiotics (amphotericin B, nystatin, pimaricin, candicidin,
hachimycin), allylamines (naftifene, terbinafine), thiocarbamates (tolnaftate), and miscellaneous
agents (tolnaftate, acrisorcin, haloprogin, ciclopirox, olamine, dichlorophen, hexetidine,
chlorphenesin, tiacetin, polynoxylin, amorolfine).
Amorolfine is a topical antifungal agent used to treat onychomycosis and dermatophytosis. It is
prepared as a cream or nail lacquer. Amorolfine is a morpholine derivative that appears to act by
interfering with the synthesis of sterols essential for the functioning of fungal cell membranes. In
vitro, activity has been shown against some yeasts and dimorphic, dematiaceous, and
filamentous fungi ( Blastomyces dermatitidis , Candida spp , Histoplasma capsulatum ,
Sporothrix schenckii , and Aspergillus spp ). Despite its in vitro activity, amorolfine is inactive
when given systemically and thus is limited to topical use in the treatment of superficial
infections. Its role in the treatment of fungal infection in animals is not clear.
Terbinafine is an allylamine antifungal agent available as a topical cream or as tablets. It
decreases synthesis of ergosterol by inhibiting squalene epoxidase and is used in the treatment of
dermatophytes (eg, Trichophyton , Microsporum , and Aspergillus spp ). Terbinafine is also
active against yeasts (eg, Blastomyces dermatitidis , Cryptococcus neoformans , Sporothrix
schenckii , Histoplasma capsulatum , Candida , and Pityrosporum spp ). The use of this drug in
animals is limited due to the lack of efficacy and safety studies, and it is used only occasionally
in dogs and cats.
Because of its ability to inhibit chitin synthesis, lufenuron has been used to treat
dermatophytosis and selected uterine fungal infections in mares.



                                   Antiviral Agents
The conventional approach to the control of viral diseases is to develop effective vaccines, but
this is not always possible. The objective of antiviral activity is to eradicate the virus while
minimally impacting the host and to prevent further viral invasion. However, because of their
method of replication, viruses present a greater therapeutic challenge than do bacteria.
Viruses comprise a core genome of nucleic acid surrounded by a protein shell or capsid. Some
viruses are further surrounded by a lipoprotein membrane or envelope. Viruses cannot replicate
independently and, as such, are obligate intracellular parasites. The host‘s pathways of energy
generation, protein synthesis, and DNA or RNA replication provide the means of viral
replication. Viral replication occurs in 5 sequential steps: host cell penetration, disassembly,
control of host protein and nucleic acid synthesis such that viral components are made, assembly
of viral proteins, and release of the virus.
Drugs that target viral processes must penetrate host cells; in doing so, they are likely to
negatively impact normal pathways of the host. Antiviral drugs are characterized by a narrow
therapeutic margin. Therapy is further complicated by viral latency, ie, the ability of the virus to
incorporate its genome in the host genome, with clinical infection becoming evident without
reexposure to the organism. In vitro susceptibility testing must depend on cell cultures, which are
expensive. More importantly, in vitro inhibitory tests do not necessarily correlate with
therapeutic efficacy of antiviral drugs. Part of the discrepancy between in vitro and in vivo
testing occurs because some drugs require activation (metabolism) to be effective.
Only a few agents have been found to be reasonably safe and effective against a limited number
of viral diseases, and most of these have been developed in humans. Few have been studied in
animals, and widespread clinical use of antiviral drugs is not common in veterinary medicine.
Only a selection of the more promising agents and their purported attributes are briefly
discussed.
Most antiviral drugs interfere with viral nucleic acid synthesis or regulation. Such drugs
generally are nucleic acid analogs that interfere with RNA and DNA production. Other
mechanisms of action include interference with viral cell binding or interruption of virus
uncoating. Some viruses contain unique metabolic pathways that serve as a target of drug
therapy. Drugs that simply inhibit single steps in the viral replication cycle are virustatic and
only temporarily halt viral replication. Thus, optimal activity of some drugs depends on an
adequate host immune response. Some antiviral drugs may enhance the immune system of the
host.

Pyrimidine Nucleosides
A variety of pyrimidine nucleosides (both halogenated and nonhalogenated) effectively inhibit
the replication of herpes simplex viruses with limited host-cell toxicity. The exact mechanism of
action of these compounds appears to reflect substitution of pyrimidine for thymidine, causing
defective DNA molecules. Idoxuridine (IDU) is effective for the treatment of herpesvirus
infection of the superficial layers of the cornea (herpesvirus keratitis) and of the skin, but is
toxic when administered systemically.
Trifluridine, also an analog of deoxythymidine, is currently the agent of choice for the treatment
of herpesvirus keratitis in humans. The other antiviral pyrimidine nucleosides have not been
used clinically to any notable extent.
Ribavirin:
Ribavirin is a synthetic triazole nucleoside (an analog of guanosine) with a broad spectrum of
activity against many RNA and DNA viruses, both in vitro and in vivo. Susceptible viruses
include adenoviruses, herpesviruses, orthomyxoviruses, paramyxoviruses, poxviruses,
picornaviruses, rhabdoviruses, rotaviruses, and retroviruses. Viral resistance to ribavirin is rare.
The action of ribavirin involves specific inhibition of viral-associated enzymes, inhibition of the
capping of viral mRNA, and inhibition of viral polypeptide synthesis. It is well absorbed,
widely distributed in the body, eliminated by renal and biliary routes as both parent drug and
metabolites, and has a plasma half-life of 24 hr in humans. It does not have a wide margin of
safety in domestic animals. Toxicity is manifest by anorexia, weight loss, bone marrow
depression and anemia, and GI disturbances. It has been successfully administered by topical,
parenteral, oral, and aerosol routes. Efficacy depends on the site of infection, method of
treatment, age of the animal, and the infecting dose of virus. Results of human influenza studies
with ribavirin have been equivocal.
 Certain purine nucleosides have proved to be effective antivirals and are used as systemic
 agents. Two of these antiviral drugs deserve special mention. Vidarabine, or araA, is used
 topically for ocular herpes and systemically for herpetic encephalitis as well as for neonatal
 herpesviral infections. This drug is an adenosine derivative that is phosphorylated by cellular
 enzymes to a triphosphate compound that inhibits many viral and human DNA polymerases
 and thus DNA synthesis. Herpesviral enzymes are ~20-fold more susceptible to the drug
 compared with host DNA. Vidarabine is administered IV in large volumes of fluid and is
 rapidly inactivated. It may produce bone marrow suppression and CNS side effects when high
 blood levels are reached.
Purine Nucleosides:
Acyclovir (acycloguanosine) represents a new generation of antiviral agents, mainly because of
its unique mechanism of action. This purine nucleoside is phosphorylated more efficiently by
virus-induced thymidine kinase compared with host thymidine kinase. Once in the triphosphate
form, it is a better substrate and inhibitor of viral, compared with host, DNA polymerase.
Binding to DNA polymerase is irreversible. Once incorporated into viral DNA, the DNA chain
is terminated. Acyclovir is relatively safe (probenecid renders the drug safer) and is useful
against a variety of infections caused by DNA viruses, especially the herpesvirus family.
However, resistance is increasing. Acyclovir is unable to eliminate latent infections. It is
available as an ophthalmic ointment, a topical ointment and cream, an IV preparation, and
various oral formulations. The prodrug deoxyacyclovir is more readily absorbed from the GI
tract than acyclovir. Another similar antiviral purine nucleoside analog is ganciclovir, a
synthetic guanine that is effective against human cytomegalovirus. Its mechanism of action is
similar to that of acyclovir.
Zidovudine:
 Zidovudine (azidothymidine, AZT) is a thymidine analog. Within the virus-infected cell, the
 3¢-azido group is used by retroviral reverse transcriptase and incorporated into DNA
 transcription, preventing viral replication. The shared mechanism of action is inhibition of
 RNA-dependent DNA polymerase (reverse transcriptase). This enzyme is responsible for
 conversion of the viral RNA genome into double-stranded DNA before it is integrated into the
 cell genome. Because these actions occur early in replication, the drugs tend to be effective
 for acute infections but are relatively ineffective for chronically infected cells. Cellular α-
 DNA polymerases are inhibited only at concentrations 100-fold greater than those necessary
 to inhibit reverse transcriptase, thus rendering this drug relatively safe to host cells. Cellular γ-
 DNA polymerase, however, is inhibited at lower concentrations.
AZT is effective against a variety of retroviruses at low concentrations. Resistance to AZT is
associated with point mutations resulting in amino acid substitutions in the reverse
transcriptase. Prolonged use of AZT can facilitate viral resistance. The risk of resistance also
appears to correlate with CD4 cell count and the state of infection. Viral susceptibility to AZT
 may return after the drug has been discontinued for a period of time. Little information
 regarding the disposition of AZT is available in animals. Granulocytopenia and anemia are the
 major adverse effects of AZT in human patients. The risk of toxicity increases in human
 patients with low (CD4) lymphocyte counts, high doses, and prolonged therapy. Granulocyte
 colony-stimulating factor is indicated for management of granulocytopenia. CNS side effects
 are more likely as therapy is begun. The risk of myelosuppression is increased by drugs that
 inhibit glucuronidation or renal excretion and may be increased in cats. Studies in cats
 regarding the efficacy of AZT (10-20 mg/kg, bid for 42 days) for feline leukemia virus
 infection indicated that AZT prevents retroviral infection if administered immediately after
 viral exposure and may reduce replication if administered to previously infected animals.
 Serum-neutralizing antibodies developed in some of the infected cats, and the cats became
 resistant to subsequent viral challenge. There was no altered progression of disease in cats
 when treatment was withheld until 28 days after infection, although the level of viremia was
 much lower than in untreated cats. AZT appeared to be nontoxic in uninfected cats, although 3
 of 12 infected kittens became anorectic and icteric and were vomiting after 40 days of
 treatment. AZT may cause Heinz body anemia. CBC should be performed on cats receiving
 AZT.
Amantadine:
Amantadine, and its derivative rimantadine, are synthetic antiviral agents that appear to act on an
early step of viral replication after attachment of virus to cell receptors. The effect seems to lead
to inhibition or delay of the uncoating process that precedes primary transcription. Amantadine
may also interfere with the early stages of viral mRNA transcription. Amantadine at usual
concentrations inhibits replication of different strains of influenza A virus, influenza C virus,
Sendai virus, and pseudorabies virus. It is almost completely absorbed from the GI tract, and
~90% of a dose administered PO is excreted unchanged in the urine over several days (human
data). The main clinical use has been to prevent infection with various strains of influenza A
viruses. However, in humans, it also has been found to produce some therapeutic benefit if taken
within 48 hr after the onset of illness. Amantadine and its derivatives may be given by the PO,
intranasal, SC, IP, or aerosol routes. It produces few side effects, most of which are related to the
CNS; stimulation of the CNS is evident at very high doses.


                                    Anthelmentics
Many highly effective and selective anthelmintics are available, but such compounds must be
used correctly and judiciously to obtain a favorable clinical response, accomplish good control,
and minimize selection for anthelmintic resistance. It is impossible to list all claims and
precautions regarding all drugs in all countries; the label should always be read before using any
drug. Additional information is found under relevant disease headings. Any modification of the
recommended dose rate must be discouraged, as this is likely to result in lowered efficacy and
possibly increased pressure for development of resistance.
Modern anthelmintics generally have a wide margin of safety, considerable activity against
immature (larval) and mature stages of helminths, and a broad spectrum of activity. Nonetheless,
the usefulness of any anthelmintic is limited by the intrinsic efficacy of the drug itself, its
mechanism of action, its pharmacokinetic properties, characteristics of the host animal (eg,
operation of the esophageal groove reflex), and characteristics of the parasite (eg, its location in
the body, its degree of hypobiosis, or whether it has developed anthelmintic resistance). The
―ideal‖ anthelmintic should have a broad spectrum of activity against mature and immature
parasites (including hypobiotic larvae), be easy to administer, inhibit reinfection for extended
periods of time, have a wide margin of safety and be compatible with other compounds, not
require long withholding periods because of residue(s), and be cost effective.
There are several classes of anthelmintics, eg, benzimidazoles and probenzimidazoles,
salicylanilides and substituted phenols, imidazothiazoles, organophosphates, and macrocyclic
lactones. Because of their broad spectrum, high efficacy against all parasitic stages, and their
persistent activity, macrocyclic lactones now dominate the treatment and control of nematodes.
Although it may be thought that chemotherapeutic control of helminth infections is currently
satisfactory, parasite resistance against all important anthelmintics is a significant problem in
some animal hosts.
Anthelmintics must be selectively toxic to the parasite. This is usually achieved either by
inhibiting metabolic processes that are vital to the parasite but not vital to or absent in the host,
or by inherent pharmacokinetic properties of the compound that cause the parasite to be exposed
to higher concentrations of the anthelmintic than are the host cells. While the precise mode of
action of many anthelmintics is not fully understood, the sites of action and biochemical
mechanisms of many of them are generally known. Parasitic helminths must maintain an
appropriate feeding site, and nematodes and trematodes must actively ingest and move food
through their digestive tracts to maintain an appropriate energy state; this and reproductive
processes require proper neuromuscular coordination. Parasites must also maintain homeostasis
despite host immune reactions. The pharmacologic basis of the treatment for helminths generally
involves interference with the integrity of parasite cells, neuromuscular coordination, or
protective mechanisms against host immunity, which lead to starvation, paralysis, and expulsion
of the parasite.
Cellular Integrity:
 There are several classes of anthelmintics that impair cell structure, integrity, or metabolism: 1)
 inhibitors of tubulin polymerization—benzimidazoles and probenzimidazoles (which are
 metabolized in vivo to active benzimidazoles and thus act in the same manner); 2) uncouplers of
 oxidative phosphorylation— salicylanilides and substituted phenols; and 3) inhibitors of
 enzymes in the glycolytic pathway—clorsulon.
The benzimidazoles inhibit tubulin polymerization; it is believed that the other observed effects,
including inhibition of cellular transport and energy metabolism, are consequences of the
depolymerization of microtubules. Inhibition of these secondary events appears to play an
essential role in the lethal effect on worms. Benzimidazoles progressively deplete energy
reserves and inhibit excretion of waste products and protective factors from parasite cells;
therefore, an important factor in their efficacy is prolongation of contact time between drug and
parasite. Cross-resistance can exist among all members of this group because they act on the
same receptor protein, β-tubulin, which is altered in resistant organisms such that none of the
benzimidazoles can bind to the receptor with high affinity.
Uncoupling of oxidative phosphorylation processes has been demonstrated for the
salicylanilides and substituted phenols, which are mainly fasciolicides. These compounds act as
protonophores, allowing hydrogen ions to leak through the inner mitochondrial membrane.
Although isolated nematode mitochondria are susceptible, many fasciolicides are ineffective
against nematodes in vivo, apparently due to a lack of drug uptake. Exceptions are the
hematophagous nematodes, eg, Haemonchus and Bunostomum .
Clorsulon is rapidly absorbed into the bloodstream. When Fasciola hepatica ingest it (in plasma
and bound to RBC), they are killed because glycolysis is inhibited and cellular energy
production is disrupted.
Neuromuscular Coordination:
Interference with this process may occur by inhibiting the breakdown or by mimicking or
enhancing the action of neurotransmitters. The result is paralysis of the parasite. Either spastic
or flaccid paralysis of an intestinal helminth allows it to be expelled by the normal peristaltic
action of the host. Specific categories include: 1) cholinesterase inhibitors—organophosphates
such as coumaphos, crufomate, dichlorvos, haloxon, naftalofos, trichlorfon; 2) cholinergic
agonists—imidazothiazoles (levamisole, tetramisole) and pyrimidines (morantel, oxantel,
pyrantel); 3) muscle hyperpolarization—piperazine; and 4) potentiation of inhibitory
transmitters—macrocyclic lactones (ivermectin, abamectin, doramectin, moxidectin,
milbemycin oxime, eprinomectin, selamectin).
Organophosphates inhibit many enzymes, especially acetylcholinesterase, by phosphorylating
their esterification sites. This blocks cholinergic nerve transmission in the parasite, which
results in spastic paralysis. The cholinesterases of host and parasite and those of different
species of parasites vary in their susceptibility to organophosphates.
The imidazothiazoles are nicotinic anthelmintics that act as agonists at nicotinic acetylcholine
receptors of nematodes. Their anthelmintic activity is mainly attributed to their ganglion-
stimulant (cholinomimetic) activity, whereby they stimulate ganglion-like structures in somatic
muscle cells of nematodes. This stimulation first results in sustained muscle contractions,
followed by a neuromuscular depolarizing blockade resulting in paralysis. Hexamethonium, a
ganglionic blocker, inhibits the action of levamisole.
Piperazine acts to block neuromuscular transmission in the parasite by hyperpolarizing the
nerve membrane, which leads to flaccid paralysis. It also blocks succinate production by the
worm. The parasites, paralyzed and depleted of energy, are expelled by peristalsis.
The macrocyclic lactones act by binding to glutamate-gated chloride channel receptors in
nematode and arthropod nerve cells. This causes the channel to open, allowing an influx of
chloride ions. Different chloride channel subunits may show variable sensitivity to macrocyclic
lactones and different sites of expression, which could account for the paralytic effects of
macrocyclic lactones on different neuromuscular systems at different concentrations. The
macrocyclic lactones paralyze the pharynx, the body wall, and the uterine muscles of
nematodes. Paralysis (flaccid) of body wall muscle may be critical for rapid expulsion, even
though paralysis of pharyngeal muscle is more sensitive. As the macrocyclic lactone
concentration decreases, motility may be regained, but paralysis of the pharynx and resultant
inhibition of feeding may endure longer than body muscle paralysis and contribute to worm
deaths. In filarial nematodes living in the tissues, females move very little and nutrients are
absorbed through the cuticle. A major effect of macrocyclic lactones on adult worms of these
species is probably paralysis of uterine muscles, resulting in disruption of reproduction. None of
the macrocyclic lactones are active against cestodes or trematodes, presumably because these
parasites do not have a receptor at a glutamate-gated chloride channel.
                                    Benzimidazoles
The benzimidazoles are a large chemical family used to treat nematode and trematode infections
in domestic animals. However, with the widespread development of resistance and the
availability of more efficient and easier to administer compounds, their use is rapidly decreasing.
They are characterized by a broad spectrum of activity against roundworms (nematodes), an
ovicidal effect, and a wide safety margin. Those of interest are mebendazole, flubendazole,
fenbendazole, oxfendazole, oxibendazole, albendazole, albendazole sulfoxide, thiabendazole,
thiophanate, febantel, netobimin, and triclabendazole. Netobimin, albendazole, and
triclabendazole are also active against liver flukes; however, unlike all the other benzimidazoles,
triclabendazole has no activity against roundworms.
Because most benzimidazoles are sparingly soluble in water, they are given PO as a suspension,
paste, or bolus. Differences in the rate and extent of absorption from the GI tract depend on such
factors as species, dosage, formulation, solubility, and operation of the esophageal groove reflex.
The most effective of the group are those with the longest half-life, such as oxfendazole,
fenbendazole, albendazole, and their prodrugs, because they are not rapidly metabolized to
inactive products. Effective concentrations are maintained for an extended period in the plasma
and gut, which increases efficacy against immature and arrested larvae and adult nematodes,
including lungworms.
They are more effective in ruminants and horses, in which their rate of passage is slowed by the
rumen or cecum. Because the nature of their antiparasitic action depends on prolongation of
contact time, repeated (2-3 times) PO administration of a full dose at 12-hr intervals increases
their efficacy, even against benzimidazole-resistant worms. In addition, a reduced feed intake,
which reduces the flow rate of digesta, increases the availability of benzimidazoles.
In the case of oxfendazole, and probably other benzimidazoles, the major route of exposure is
biliary metabolites, followed by enterohepatic recycling of the drug after absorption from the
small and large intestine. Worms in the mucosa of the small intestine may be exposed to more
recycled anthelmintic than to drug contained in the passing ingesta in the GI tract.
Ruminants:
 In ruminants, PO treatment with the benzimidazoles removes most of the major adult GI
 parasites and many of the larval stages. The relative rates of oxidation in the liver and reduction
 in the GI tract vary between cattle and sheep, with the metabolism and excretion of
 benzimidazole compounds being more extensive in cattle than in sheep. Consequently, the
 systemic anthelmintic activity of most benzimidazoles is greater in sheep than in cattle, and
 dose rates in cattle are often higher than those in sheep. Albendazole, fenbendazole,
 oxfendazole, and febantel are active against inhibited fourth-stage larvae of Ostertagia spp ;
 however, inconsistent efficacy has been reported. Efficacy against Dictyocaulus viviparus has
 also been noted for these insoluble benzimidazoles. Oxfendazole, albendazole, and febantel are
 minimally teratogenic in sheep, whereas fenbendazole, mebendazole, and oxibendazole are not.
 An oxfendazole pulse-release bolus for intraruminal use has been developed for cattle—5
 therapeutic doses of oxfendazole (750 or 1,250 mg/tablet) are released approximately each 3 wk
 in the rumen. A sustained-release fenbendazole bolus is also available in some countries; it
 contains 12 g fenbendazole and has a release profile of 140 days. An albendazole slow-release
 capsule has been marketed for small ruminants. This device contains 3.85 g of albendazole and
 delivers a daily dose of 36.7 mg for 105 days. It is an efficient device for controlling
 benzimidazole-susceptible nematodes. It may also prevent infection with benzimidazole-
 resistant larvae, but does not reduce existing infections.
In cattle and sheep, triclabendazole at 10 mg/kg, PO, is highly effective against immature
Fasciola hepatica in the liver parenchyma and against the mature stage in the bile ducts.
Albendazole and netobimin at 20 mg/kg are active against mature F hepatica ; the other
benzimidazoles and probenzimidazoles used for nematode control have only a marginal efficacy
against liver flukes. Because of the lack of efficacy against the immature stages, most
benzimidazoles are not indicated for treatment of acute fascioliosis.
Horses:
In horses, the benzimidazoles are characterized by effective removal (90-100%) of almost all
mature strongyles, but third- and fourth-stage larvae are more difficult to eliminate. High levels
and repeated administration may be necessary for extraintestinal migrating stages of large
strongyles and for small-strongyle larvae embedded or encysted in the wall of the intestine.
However, widespread resistance to benzimidazoles in cyathostome nematodes of horses limits
their usage. Repeated doses are thought to be advantageous because the lethal effect of
benzimidazoles is a slow process—hence, their recent incorporation into feed supplements.
Ascarid removal in horses varies with various members of the benzimidazole group. Activity
against Strongyloides westeri varies also, but Oxyuris equi is usually removed by any of the
benzimidazoles at the recommended dose.
Dogs and Cats:
In dogs and cats, mebendazole, fenbendazole, febantel, and flubendazole are used for treatment
of roundworms, hookworms, and tapeworms. However, treatment must be given bid for 3 days.
Fenbendazole has been used in a divided dose regimen in bitches against tissue-dwelling larvae
of Toxocara canis and Ancylostoma caninum ; daily administration of 50 mg/kg to bitches from
day 40 of pregnancy through day 14 after parturition resulted in pups free of both parasites,
although this has limited application in practice.
Birds:
Mebendazole, flubendazole, and fenbendazole can be used effectively against nematodes of the
GI and respiratory tracts of birds.


                                    Imidazothiazoles
The anthelmintic activity of tetramisole, a racemic mixture, resides in the l-isomer, levamisole. It
is commonly used in cattle, sheep, pigs, goats, and poultry to treat nematode infections; it has no
activity against flukes and tapeworms. It is normally administered PO or SC, and efficacy is
generally considered equivalent with either route. Topical preparations for cattle have been
developed.
Levamisole acts on the roundworm nervous system and is not ovicidal. Its broad spectrum of
activity, ease of use (being water soluble), reasonable safety margin, and lack of teratogenic
effects have allowed it to be used successfully. Because of its mechanism of action, the peak
blood concentration is more relevant to its antiparasitic activity than the duration of
concentration. Levamisole resistance appears to be associated with a loss of cholinergic
receptors. Levamisole has immunostimulant effects at dosage rates higher than those used for
anthelmintic activity, and it has been used in humans and to a limited extent in other animals in
several diseases.
Ruminants:
 In ruminants, levamisole is highly effective against the common adult GI nematodes and
lungworms and many larval stages. It lacks efficacy against arrested larvae, such as those of
Ostertagia ostertagi . Levamisole slow-release boluses are available in some countries and
contain 22.05 mg levamisole. They release 2.5 mg during the first 24 hr and the remainder over
a 90-day period.
Birds:
In poultry, levamisole is mainly used to remove ascarid infections.
                               Tetrahydropyrimidines
Pyrantel was first introduced as a broad-spectrum anthelmintic against GI nematodes of sheep
and has also been used in cattle, horses, dogs, and pigs. It is available as a citrate, tartrate,
embonate, or pamoate salt.
Aqueous solutions are subject to isomerization on exposure to light, with a resultant loss in
potency; therefore, suspensions should be kept out of direct sunlight. It is not recommended for
use in severely debilitated animals because of its levamisole-type pharmacologic action.
Pyrantel is used PO as a suspension, paste, drench, or tablets. Both pyrantel and morantel are
effective against adult gut worms and larval stages that dwell in the lumen or on the mucosal
surface.
Ruminants:
 Pyrantel tartrate is effective as a broad-spectrum anthelmintic in ruminants; however, its activity
 is mainly limited to the adult GI nematodes.
Horses:
 Pyrantel is effective against adult ascarids, large and small strongyles, pinworms, and at double
 the recommended dose, the ileocecal tapeworm Anoplocephala perfoliata .
Dogs and Cats:
Pyrantel pamoate is effective against the common GI nematodes, except for whipworms.
Oxantel, a phenol analog of pyrantel, is combined with pyrantel in some anthelmintic
preparations for dogs (and humans) to increase activity against whipworms.
                                   Organophosphates
A number of organophosphates have been used as anthelmintics; however, due to their relative
toxicity, limited efficacy against immature stages, narrow margin of safety, and contamination of
the environment through fecal excretion, their use is declining. Dichlorvos is used as an
anthelmintic in horses, pigs, dogs, and cats; trichlorfon in horses and dogs; and coumaphos,
crufomate, haloxon, and naftalofos in ruminants.
Because of its high volatility, dichlorvos is a particularly versatile organophosphate that can be
incorporated as a plasticizer in vinyl resin pellets; it is released slowly from the inert pellets as
they pass through the GI tract, providing a therapeutic concentration along the tract. This
controlled release governs the concentration available to the host as well as to the parasites and
thereby increases the safety margin. When passed in the feces, the pellets still contain ~45-50%
of the original drug. Dichlorvos is rapidly absorbed and metabolized in the body.
Ruminants:
 Haloxon and naftalofos have been the primary organophosphates used in cattle and sheep.
 However, their use is becoming limited because of their contraindications.
Horses:
Trichlorfon (metrifonate) is still used in horses because of its high degree of activity against
bots, ascarids, and oxyurids.


                                              Mastitis
Mastitis is a major problem in dairy industry throughout the world. Price of dairy animal is based in its
milk production. If one teat is lost, it loses 25-30% production. In cow front teats produce more milk
(60%) than rear teats (40%) and vice versa in case of buffalo. If cow loses its front left or front right teat
then there will be a huge loss. This disease causes huge economic losses to farmers in terms of
production and price of milk. Udder health has effect on animal health also. So loss of udder means the
loss of animal. The dairy products of mastitic milk will have low quality and short half life. These will
become rancid early.
According to National Mastitis Council (NMC), USA: “Mastitis is an inflammation of mammary glands
that happens in response to the injury for purpose of neutralizing infectious agent to prepare way for
healing and turned to normal function.”
In Pakistan every 3rd or 4th cow or buffalo (20-25 %) is mastitic. Overall there is an incidence of 20-25% in
cow and 14-15 % in buffalo. Prevalence of clinical and subclinical mastitis in cow is 7.08 % and 48.7 %
respectively. In buffalo prevalence of clinical and subclinical mastitis is 3.7 % and 23.9 % respectively.
Normal somatic cell count in milk is 200,000 and in mastitis it goes to several thousands. If more than
200,000 cells then consider mastitis. There are two methods: individual Somatic cell count and bulk
somatic cell count (recently named as milkscan). Fossometer is another one and it is mostly used.
Increased number of somatic cells shows severity of infection. Somatic cell count in buffalo is 50,000 to
375,000. Bacterial count varies from 100,000 to 10,00,000 in cows. Mastitic milk has 90 % neutrophils
and 10% somatic cells. If 40 % neutrophils, there will be mild mastitis. In case of 90 % neutrophils; there
will be severe mastitis.
Major pathogens: Staphylococcus aureus, streptococcus aglectai, E.coli
Minor pathogens: Mycoplasma, Klebsella.
                                        Effect of Mastitis on Milk
       Mastitis affects the quality of milk and there is increase in the number of bacteria. Common
        sources of bacteria are inadequate cleaning of milking utensils, hands not properly washed, skin
        of udder not properly cleaned and contamination of the teat skin. There is a direct relationship
        between skin and mastitis. If dirty skin then more chances of mastitis. By providing hygienic
        conditions mastitis can be controlled and quality of milk and its byproducts can be improved.
       Increased somatic cell count and increased neutrophils and macrophages also deteriorate the
        quality of milk. Increased somatic cell count claims mastitis. So there is direct relationship
        between mastitis and somatic cell count. But in late lactation and newly parturating animals,
        somatic cell also increases.
       Whenever there is rise in somatic cell count, casein content falls down (which is very important
        protein). Similarly leakage of certain proteins from serum like albumin, immunoglobulin and
        transferring into milk also occurs.
       Na and K ions also increase.
       Calcium level decreases with fall in level of casein because it has binding capacity with casein.
       Normal pH of milk is 6.6 but it may raise upto 6-9 or more in the milk collected from subclinically
        mastitic animal and even more in clinically mastitic animals.
       There is release of proteolytic enzyme from blood like plasmin. Plasmin is excessive in blood but
        low in milk. It cannot be destroyed at 140 oC. If it is high in milk then deteriorate the quality of
        milk. Milk heated at 140 oC for 1.5 minute destroys the Plasmin and some other enzyme like
        lipase which attack triglycerides to convert them into FFA, which produce offensive smell in milk
        and rancid flavour is developed in milk.
       Watery milk shows chronic type of inflammation. If watery secretion present in first few streaks
        (about 10 streaks) then normal but if more than it then chronic mastitis.
       Plaques present in milk show severe infection. If present at start of milking then shows infection
        due to S. aureus. If at the end of milking then indicates animal having TB. These plaques are
        normally present in milk in 1-2 days of lactation and in last 2-3 days of lactation.

                     Changes in Cow Milk Associated with High Somatic Cell Count
             Constituents             Normal Milk               Milk with high
             Solid non fat                       8.9                       8.8
             Fat                                 3.5                       3.2
             Lactose                             4.9                       4.4
             Total Protein                      3.61                      3.56
             Total Casein                        2.8                       2.3
             Whey protein                        0.8                       1.3
             Serum albumin                      0.02                      0.07
             Lactoferrin                        0.02                      0.10
             Immunoglobulins                    0.10                      0.60
             Sodium                            0.057                     0.105
             Chloride                          0.091                     0.147
             Potassium                         0.173                     0.157
             Calcium                            0.12                      0.04

                                             Types of Mastitis
Latent Mastitis:
Pathological organism present in milk but no swelling of udder and normal cell count.
Sub Clinical Mastitis:
Bacteria and somatic cells present in milk and change in composition of milk but no gross lesion.
Clinical Mastitis:
It is divided into three categories depending upon severity:
          (a): Acute: There are obvious symptoms of inflammation present on udder, change in colour and
          composition of milk and increased temperature.
          (b): Subacute: No obvious change in udder but clots and plaques present in the milk.
          (d): Chronic: Every acute infection develops into chronic infection if not treated. In this phase
          major changes are fibrosis of udder, very tough hard mass of fiber, the quarter may be
          atrophied which may persist for rest of life. There may be fibrotic mass particularly in teat canal.
Aseptic/non Specific Mastitis:
It is due to trauma or injury to the udder.

                                     Pathogens Involved in Mastitis
Contagious Pathogens:
        They spread from quarter to quarter through contamination by hands, flies, wounds etc. They
always require host e.g. Staph aureus, Mycoplasma, Pasteurella. They have very limited life in
environment. In Pakistan mastitis caused by Staph aureus and Streptococcus agalectia is 70-80 % of
mastitis and rest of it is caused by environment (E.coli).
Environmental opportunist:
The primary source is the environment in which the cow/buffalo lives. They spread by direct contact of
the teats to the bedding or mud, dirt and manure. Examples are Coliform species like E.coli, Klebsella),
Streptococcus uberis, streptococcus agalactae, streptococcus faecalis etc.
Opportunist Pathogens:
This group of mastitis pathogens includes around 30 different species fo the genus Staphylococcus
(other than Staph aureus) and Corynebacterium bovis. They are normally present on the tet skin and
streak canal. Therefore they are in an opportunistic position to colonize the teat canal and penetrate the
udder.
Endogenous Pathogens:
Etiological agents of systemic diseases with mammary gland involvement like Leptospira,
Mycobacterium bovis etc.

                                        Etiology of Mastitis
        Due to various endogenous pathogens. Staph aureus is the most common bacteria. 70-80
% cows are infected by this. Streptococcus has been controlled 100 % and Staph aureus 10 %.
E.coli major (-ve) mastitis causing bacteria. Americans are facing environmental mastitis.

                                              Staph aureus
         Staph means clusters and coccus means spheres. In blood agar culture they are in the form of
clusters of spheres. Staph aureus is the most common causative agent of mastitis.
         Milk in udder, teat tips, rectum, eyes, teat orifice, udder, vagina, naries of animal, gut of flies,
even milker‘s hand, throat and naries are different sources of Staph aureus. Similarly the contaminated
milking machine cups are good source of Staph aureus. Infected animals serve as reservoir for infection.
         Pseudocapsules, α and ß toxins (produced during infection), Protein A (a part of cell wal),
Clumping factor C, and fibronectin binding protein are virulence factors of Staph aureus.
Pseudocapsule provides protection to S. aureus and makes it inaccessible to neutrophils, so no
phagocytosis. α toxin causes cytotoxicity of neutrophils so killing defense cells of the body. ß toxin
causes the hemolysis. Protein A, part of cell wall, is very good character and make the bacteria safe from
the attack of host defense mechanism. Protein A binds IgG at the Fc region (neutrophils attachment
region) instead of the Fab (specific antigen attachment of region) and interferes with antibody
presentation region to neutrophils. Correct attachment of IgG to the S. aureus cell wall is required in order
to attract neutrophils to the bacteria and trigger phagocytosis and bacterial killing. Clumping factor C is
required to attach the bacteria with host cells or gland cells or the protein surface of mammary gland.
Most common factor is A1. Fibronectin binding protein is also a source of attachment of bacteria to host
cell and after adhesion start multiplication and multiplication develops infection.
         S. aureus is transmitted through contact at the time of milking when milking man moves from
infected to healthy animal. The quarters of udder are separated. One quarter if affected cannot affect the
other quarter. Only the way of infection of other quarter is contamination by milker‘s hand.
         S. aureus causes fibrosis and scar formation and it is defensive mechanism but antibiotics cannot
reach the udder due to scar formation.
In acute mastitis quarter may be swollen, temperature of animal 103-104 oF, and rarely quarter become
gangrenous and cold to touch. This condition is called as blue bag.

                                        Streptococcus agalectia
         It is the second most important pathogen. Broad zone hemolytic colonies, narrow zone hemolytic
colonies, and non hemolytic colonies on blood agar. Non hemolytic is non pathogenic.
         It is transmitted through contamination. It is controllable by using antibiotics particularly
penicillin is drug of choice. This bacterium affects the lower part of udder i.e. duct system of mammary
gland. It can also affect the tissue of udder as it blocks the duct channels due to which milk stays in udder
and causes scaring, involution, low production, and clotting and accumulation of milk
         Toxin produced by it may cause severe inflammation of udder and as a result of this there is less
milk production. It rarely affects generalized health but may cause infection in humans and can enter in
fetal body and affect in 0-7 days of pregnancy (pneumonia, meningitis, hypotension, abdominal
distension, fever, and jaundice).In late stages meningitis and non specific bacteremia may lead to
immunological disorder in fetus and mostly abortion occurs. Mortality rate is 5-15 %. In America
antibiotics are used to control it in pregnant women.

                                              Coliform Bacteria
        Coliforms bacteria can be engulfed by neutrophils due to O, K, and H antigen, recognized by
phagocytes. Primary virulence factor is lipopolysaccharide present in cell wall of G –ve bacteria (causes
endogenous toxins production from LPS which destroys the vessels and cause endotoxic shock.
E.coli has three sorts of antigen: somatic antigen present on cell wall i.e. ‗O‘ Ag (thermostable and
lipopolysaccharide), K Ag (capsular), and H antigen (flageller Ag). This organism does not require
adhesion. It multiplies and survives in milk. It particularly requires iron. So infection occurs in lactation
phase due to availability of iron. In dry period iron binding protein increases and the availability of iron is
decreased. In case of this organism infection is sudden.
        LPS is present in cell wall of G –ve bacteria and that causes endogenous toxin production and
endotoxemia and bacteremia occur. LPS cause severe damage to blood vessels and endotoxic shock.
Severe inflammation and there is sudden appearance of clinical signs and sometimes skin of udder may be
ruptured and fluid may ooze out.

                                            Sources of Mastitis
    a. Hands of milker. Staph aureus is present on skin, naries of human if no proper bath. He will shift
       from one herd to other.
    b. Lack of proper management i.e. proper teat dipping is not carried out, no antiseptic solution is
       used and no sanitation measures are taken.
    c. Trauma during sitting posture or due to kicking udder or teats may be injured; leading to
       mastitis.
    d. Folded thumb milking particularly in villages damages the teat and causes adhesion and
       increases the chances of mastitis.
    e. In old animals teat canal is fragile and immune system is weak. So more chances of infection.

                                         Pathogenesis of Mastitis
There are three phases of mastitis:
1. Invasive/invasion Phase:
It depends upon no. of bacteria. When bacteria enter, they multiply and increase in population. So
certain no. of bacteria is required for invasion. This determines the infection rate. More no. of bacteria,
severity increases. Any damage to teat canal provides opportunity to bacteria to invade and multiply.
Loose sphincter will also provide the opportunity of entrance and adhesion to bacteria.
2. Infection Phase:
      Whenever bacteria enter, the infection depends upon the nature of bacteria. If highly
         pathogenic, then sever infection.
      Some bacteria are susceptible to antibiotics and some are resistant. Staph aureus if capsulated it
         resists and more chances of infection.
      If less immunoglobulins present in udder or teat canal then more chances of infection.
      Pre existing leukocytes if more in no. less chances of infection. They cause phagocytosis of
         bacteria.
        Stages of lactation also affect the severity of infection e.g. in lactating phase milk flow does not
         allow bacteria to attach. Similarly during lactation, treatment is difficult because antibiotics may
         flow in milk. Dry period is the best time to treat mastitis because antibiotics will stay for longer
         time in udder. The best time for infection is also the dry period; bacteria once entered, remain
         there and cause infection.
3. Inflammation Phase:
         Inflammation depends upon the pathogenecity of bacteria and the production of endotoxins,
particularly the endotoxins of S. aureus (α and ß) and E.coli that cause damage to the capillaries of
udder and cause the release of fluid in s/c parenchyma tissue. In E.coli there is huge number of
endotoxins and huge damage and inflammation. But in S. aureus endotoxins cause less damage to the
vessels. They cause chronic mastitis and more fibrosis. Their ultimate target is to damage milk alveoli.
                                      Clinical Findings of Mastitis
There is change in udder size; size increases in acute cases while in chronic cases it decreases due to
fibrosis and atrophy. Udder and teat will be small in size. Consistency of udder is soft in acute and hard
in chronic due to fibrosis. In case of endogenous spread (like E.coli) systemic reaction may occur and
cause temperature, anorexia, depression and whenever increase in fever animal is off feed. In acute
mastitis udder is soft and hot. In S. aureus infection there is rise in temperature in early stages. In case
of streptococcus no rise in temperature while in case of E.coli high temperature.
                                          Diagnosis of Mastitis
Direct Microscopic Method:
Put 0.1 ml of milk sample on slide, dry it and stain it with Newman Lampert’s Stain and then count
somatic cells with the help of microscope in certain area. Multiply the cell counted with a working factor
of microscope, it will give the number of cells per ml of milk. Normal milk contains 100,000 SCC/ml.
The Coulter Counter:
It allows the rapid and accurate determination of the number of particles above a certain size in a
suspension. Before determining the number of cells, the milk is treated as follows:
Cells are stabilized to make them resistant to further treatments; the milk to be examined is diluted with
an electrolyte; the fat globules are dispersed to a diameter well below the Coulter Counter threshold.
The treated milk is passed through a 100 micrometer aperture located between two electrodes of the
Coulter Counter. When a particle passes through the aperture, a small quantity of highly conductive
liquid in the circuit is displaced by a particle of lower conductivity. The increased resistance raises the
voltage, producing a voltage pulse proportional to the volume of the particle.
Fossometer:
It is an automatic microscopic method for counting cells in liquids. Cells are stained with ethidium
bromide and are then excited with a high energy lamp, causing them to emit light energy which is
detected electronically, the results being displayed are printed out for each successive sample. From the
sample 0.2 ml is taken and transferred to a glass container on a rotary table where it is mixed with
preheated buffer and dye and stirred well. Part of the mixture is then transferred to the periphery of a
rotating disc, which serves as an object plane for the microscope. The film is illuminated by a xenon arc
lamp, the light passes through lenses and a blue filter. Each cell produces an electrical pulse, which is fed
to an amplifier. The printout of the count needs to be multiplied by 1000 to give number of cells per ml.
NAGase Assay:
NAGase (N-acetyl glucosamide) is a lysosomal enzyme. Its level increases due to mastitis which can be
detected for the diagnosis of mastitis. Kits to detect is available
Indirect Method:
(a): California Mastitis Test:
         A reagent is used in California test which is alkaline in nature. Whenever mastitis occurs, there
will be destruction of leukocytes due to phagocytosis. As a result DNA content increases in milk which is
acidic in nature and causes the increase in the acidity of milk. Any alkaline reagent if added, it will
neutralize the milk. The reagent added in California mastits has alkyl aryl sulfoxide which will cause the
precipitation or gel formation in milk.
(b): Surf Field Mastitis Test:
          A test discovered by Prof. Dr. Ghulam Muhammad, Department of Clinical Medicine and
Surgery, Faculty of Veterinary Science, University of Agriculture, Faisalabad. Make 3 % surf field solution:
add 6 teaspoons of surf in half litre water, mix it, filter the solution and heat it. Take milk and add equal
volume of 3% solution, swirl this mixture for half minute and then examine for precipitation or gel
formation.
Mild precipitation                +
Flakes                            ++
Mild gel                          +++
Strong gel                        ++++
The test solution is stable for 6 months at room temperature. The solution should be shaken well before
use.
(c): Strip Cup Method:
          It is the simplest method. Take few streaks in cups with black background and observe the flakes
or any other abnormality.
(d): Ground Test:
Take few streaks on ground. If the absorbance of streak is quick in ground then animal is –ve for
mastitis but if the absorbance is slow then milk is mastitic. Late absorbance is due to pus as mastitic milk
is pus containing milk.
Measuring Electrical Conductivity of Milk:
The concentration of sodium and chloride increases in milk as a result of mastitis. These ionic changes
together with increase in milk pH a decrease of milk fat lead to increased electrical conductivity of milk.
Electrical conductivity measuring can be converted into computer readable signal. Therefore, this
method is easily applicable to on line automatic monitoring of udder health and can be installed in
milking machines. The method however, is not very specific for mastitis.
                                         Treatment of Mastitis
We have to target three things:
(a): Specific treatment according to the cause
(b): Symptomatic treatment
(c): Supportive treatment
First of all determine the nature of mastitis and on the basis of nature of mastitis and its etiological
agent select antibiotics.
Antibiotics can be administered through intramuscular or intramammary rout. Whenever given through
intramuscular rout the best drugs to be given are Macrolides (erythromycin, tylosin), oxytetracyclin,
cephlosporin, chlorofluracin, and quinolines (norfloxacin). Tribrissen (Sulpha and trimethoprim) is also
good. The best approach is to give antibiotics through intramammary rout. Intramammary tubes are
also available like tetradelta, Ritriprim Injector, and Ampiclox.
For subsiding inflammation you may use steroids in acute inflammation otherwise NSAIDS (diclofanic
Na, cubixin, ketoprufin, loxin, proxican).
Vitamin AD3E or lysovit ay be used to increase immunity. To enhance immunity immune enhancer trace
elements like zink, copper, ad iodine are may also be used.
Biotechnological products like Interleuken-1, Interleuken-2, and lysostaphin are also used.
Udder Toilet
It refers to infusing larger quantity of weak antiseptic solution into quarter and withdrawing it. For this
purpose acriflavin solution (1:10000 boiled in water) is generally used. Remove milk from the udder and
infuse the solution, remain there for 5 minutes and then remove out with the help of syringe. Cure has
been 60-70%.
Permanent Dry/Block of Affected Quarter
If quarter do not respond to antibiotic, infuse tincture iodine into that quarter; it will cause irritation and
block that quarter permanently. 50 ml of chlorhexadene (nolvaseen) can also be used.
Basic Remedies:
Garlic, lemon , ginger, red chilies, black pepper, black zera, dried ginger….dry for 5 days. Mix them in
flour, sprinkle water and wrap in newspaper. Give for 5 days.
250 ml lemon and 500 gram sugar may also be given.
250 gram garlic and 1000 ml milk is cooked and given to animal for 2-3 days.
Homeopathic Treatment
For fibrosis inject fibronil 5 ml
Belladona, Bryonia alba, SSC 30 c
                                            Control of Mastitis
Two main objectives of control:
    1. Prevention of new infection in the herd
    2. Duration of existing infection should be reduced.
There are five different plans to control mastitis which were devised by NMC (National Mastitis Council),
USA in 1990.
             a. Post milking teat dipping
             b. Pre milking teat dipping
             c. Dry cow therapy
             d. Prompt treatment of clinical cases
             e. Culling of chronic mastitic animals from the herd
Post Milking Teat Dipping:
Organism is present in environment and teat skin. In order to avoid it we go for post milking dipping.
After milking teat sphincter remain open for 30 minutes to 2 hours. It is ideal time for entry of organism
to teat canal. Teat cups are available having antiseptic in it like iodofores (0.1-1 % iodine). Dip the teats
one by one for 2-3 seconds. Quarernary ammonium compounds, chlorhexidine, and sodium
hypochlorite.
Pre Milking Teat Dipping:
Dip the teats before milking with the same solution as for post milking. Dry the teats after pre dipping by
towel or tissue.
Dry Cow Therapy:
The rate of new udder infections increases dramatically shortly after drying off and remains elevated
during the first 3 weeks of mammary involution. During the first few days after drying off, the cow or
buffalo goes through a period of stress that may predispose her to infections. For example, bacterial
numbers in teat skin increase as a result of terminating germicidal udder washing and teat dipping; milk
flow through the teat canal that flashes out bacteria is terminated and intramammary pressure is
elevated due to accumulation of milk which causes teat canal dilation and enhancement of bacterial
penetration. Up to 40% of all new intramammary infections are established during the first two weeks of
the dry period and without dry cow therapy, 10 to 15% of the quarters will become infected during the
dry period. Dry cow treatment is aimed at preventing new infection from occurring during this period of
increased susceptibility as well as curing existing infection and is beneficial against both contagious and
environmental pathogens. Advantages of dry cow treatment include the following:
The cure rate is higher than during lactation
Higher concentrations of drugs can be used
New infections during the dry period are reduced except first 3 weeks after drying off
Clinical mastitis at freshening is reduced
Drug residues in milk are avoided
Prompt Treatment of Clinical Cases:
Despite implementation of effective mastitis control measures, clinical cases still occur. These cases
should be treated promptly to maximize the chances of recovery. Treatment of clinical cases involves
intramammary and parenteral administration of antibiotics. Extreme care must be taken whenever
anything is being infused into a cow/buffalo's udder. Careless treatment procedures can result in udder
infections resistant to treatment. Approach treatment in the same way a surgeon approaches surgery.
Wash hands with soap and water
Wash teats and udder in sanitizing solution
Thoroughly dry teats and udder with single service individual paper towels
Dip teats in an effective germicidal teat dip
Allow 30 seconds of contact time before wiping off teat dip with an individual towel
Thoroughly scrub the teat end with a cotton swab soaked in alcohol. If all four quarters are being
treated, start by cleaning the teat farthest from you and work toward the closest teat.
Preferably use commercial antibiotic products in single dose containers designed with partial insertion
arrangement (e.g. Ampiclox LC intramammary suspension, Smithkline Beecham) formulated for dry cow
therapy in single dose containers. Do not allow the sterile cannula to touch anything prior to infusion
After infusion, remove cannula, squeeze teat end with one hand, massage antibiotic up into the quarter
with the other hand Dip teats in an effective germicidal teat dip after treatment.
One can also prepare infusion solutions and infused with the help of plastic part of IV catheter (Branula
# 18 or 20).
Managemental control:
      Segregation of healthy and infected animals and milking of healthy animals ahead of infected
      Cull chronically infected animals
      Purchase mastitis-free animals: Purchase only Surf Field Mastitis test -ive animals. Keep them
         segregated for about 2 weeks. Retest with Surf test before adding to already existing herd.
      Mastitis control in heifers: The gradual building up of a separate heifer herd, clean at the outset,
         is of great importance. The occasional appearance of mastitis in first-calving heifers is said to be
         due to the habit of female calves sucking one another's teats. This problem should be addressed
         through appropriate managemental practices. The milk on which calves are fed should be
         boiled,
      Proper treatment of teat and udder wounds
      Fly control
      General cleanliness of farm
      Proper disposal of mastitic milk of clinical cases
      Prepartum milking of animals which develop mastitis close to calving: Many dairy animals which
         have subclinical infections during the dry period often develop severe swelling of the udder and
         teat a few weeks or days before calving. If such is the case, one should start milking the diseased
         quarter(s) before parturition. Appropriate treatment should also be given.
      Proper nutrition: The feed should be balanced in terms of energy, protein contents, as well as
         vitamins and minerals. Soils of different regions of Pakistan have been reported to be deficient
         in minerals including copper, zinc, phosphous, cobalt, and iron.

Vaccination
Plane Staph aureus bactrin                                Dr. Shakoor
Polyvalent plain bactrin                                  Dr. Athar
Oil based polyvalent vaccine                               Dr. Asif Yousif
Oil based montinide adjuvant                               Dr. Irfan Yousef
Bivalent Aluminium hydroxide adjuvant vaccine              Dr. Tanveer
Mastivac (commercial vaccine)
They provide protection for 6 months.
Dr. Irfan used Montinide adjuvant, ability to provide     protection for one year. So people are going for
this.


                                           Babeisiasis
It is found in equine, bovine, and humans. It is transmitted by ticks. There is high morbidity and high
mortality. It causes huge economic losses in term of low productivity and mortality.
B. bovis (in cattle and buffalo) and B. bigemina (buffalo and cattle but mostly in buffalo) are main
culprits other are B. divergens, B. major, B. jakimovi, B. ovata (in cat). This diseases is present in tropical
and tick populated areas. Mosquitoes, flies and contaminated instruments also transmit the disease.
B. bovis is transmitted by larval stage of tick. B. bigemina is transmitted by nymph stage of tick
(Boophilus tick). Incubation period varies from species to species.
B. bovis: 1 % of total RBC infected and animal show clinical signs.
B, bigemnia: 10 % of total RBCs infected (more dangerous damage) then animal shows signs; Damage
occurs in less time.
Clinical Findings:
Elevated temperature, jaundice, anemia, more removal of RBCs from spleen, hemoglobinurea is more
pronounced in this case. Hemoglobin is free and come in urine via filtration through kidney. Hematuria
(fresh blood, settlement of RBCs). Hburea (destructed RBCs do not settle). Abortion, low milk
production, photosensitization. Animal shows nervous signs due to hypoxic injury to brain. Most
problematic condition is DLC (disseminated intravascular coagulopathy). This is coagulation defects,
sometime thromboembolism also develop so you have to give anti coagulants like heparin or sodium
citrate (mostly heparin).
Postmortem Lesions:
Intravascular hemolysis, congestion and edematous lungs, petechial hemorrhages on heart, brown to
red colour fluid present in bladder.
Differential Diagnosis:
Hemoglobinurea: due to phosphorus deficiency and no temperature and seasonal (winter), metabolic
disorder, no presence of parasites.
Anaplasmosis: less acute, replaces are more commo and hemoglobinuria is more common
Leptospirosis: Respond to antibiotics
Hematuria: fever is absent, intac red blood cells in the urine will deposit as a sediment if the sample is
left undisturbed for 1-2 hours or if the urine sample is centrifuged.
Diagnosis:
History, clinical examination, Blood examination, PCR, ELISA, CFT, DNA probing.
Treatment:
Imidocarb dipropionate (immizole) s/c 1-3 mg/kg b. wt.
It is dangerous so you have to keep emergency measures, allergic reaction may occur. So steroids are
used and preferable to use steroid 5-10 minute before injecting immizole.
High dose of immizole can remove parasites but high dose can not be given. You can use it as
prophylactic measure. If injected once it provides protection for 36 days.
Diaminazine (Diaceturate) or example Pronil by Selmor: 3-5 mg/Kg I/M
Cold therapy to lower temperature otherwise at high temperature these drugs can not work.
Supportive therapy: Fluid, blood transfusion (heparanized blood @ 7 ml per Kg), vitamins mainly B-
complex.
Control:
Control ticks, mosquitoes, and flies. Avoid contaminated instruments.
Premonition: it is a type of artificial immunity may be established by means of inoculation o fyoung
cattle with infected blod, which also results in a mild form o babeisiasis.
By keeping pet birds they are good pickers of ticks.
Dipping by Acricides
Burning of shed
By blocking cracks and crevices
Vaccination

                                              Anthrax
Anthrax is originated from Greek word means coal. Other names are spleenic fever, woolsorter’s
disease. Locally it called as golle or sut. It is an acute, contagious and septicemic disease. Highly fatal and
affecting a wide range of mammalian species including human beings.
Before the availability of an effective vaccine, anthrax was one of the most important causes of death in
livestock throughout the world. The results of national epidemiological survey of important diseases of
livestock in Pakistan has indicated that anthrax is one of the leading causes of death among sheep, goat
cattle in hilly and desert areas.
Host range:
Anthrax occurs in all vertebrates but it is more common in cattle and sheep and less frequent in horses
and goats. Humans occupy an intermediate position. Dogs and cats are relatively resistant.
Causative Agent:
Anthrax is caused by a bacterium known as Bacillus anthracis. The organism is G +ve, non motile,
aerobic, facultative anaerobe and spore forming. There are two forms of this organism: vegetative and
spore forming. Vegetative form occurs inside the body of affected animals and is responsible for
producing clinical signs and pathological lesions. The spore formation occurs outside the body of host
and is the result of exposure of vegetative form to oxygen.
When disease is septicemic (usually in herbivores); blood secretion, excretion (urine and feaces) and
tissues of affected animals are filled with vegetative form of B. anthracis. If carcass is not opened, the
vegetative form of organism will die within few hours.
Transmission:
      Mostly animals are infected while grazing in areas that have previously experienced anthrax.
      The spores are also transmitted through the consumption of contaminated water, hay, and
         fodder.
      Eating of bone meal and blood meal of infected animals also cause transmission.
      Eating of dry fodder or spiky grass produces lesions in gastrointestinal mucosa, and the chances
         of infection are increased.
      Flies are also a source of transmission.
Pathogenesis:
Upon ingestion of spores, infection occurs through intact mucous membrane, through defects in
epithelium around erupting teeth or through scratches from tough and fibrous food materials. Organism
is resistant to phagocytosis due to Poly D glutamic acid in capsule. It proliferates in regional draining
lymph nodes passing through lymphatic vessels into blood stream, causing septicemia. Bacillus anthracis
produces lethal lesions that cause edema and tissue damage. Death occurs due to shock, acute renal
failure and anorexia.
Clinical Findings:
Its incubation period is 1-2 weeks, some says 7 weeks. Most common sign of disease is sudden death.
There are three forms of disease:
Peracute: It is most common at the beginning of out break. Animals are found dead without signs.
Course of disease is only two hours. Signs may be fever, dyspnia, congestion of mucosa and muscle
tremor and animal dies after convulsion. After death there is discharge of blood from natural orifices
(mouth, nostrils, anus, vulva etc.).
Acute: Course of disease is 48 hours. There is severe depression, increased body temperature upto 107
o
  F, rapid and deep respiration, and congested mucosal lining.
Pathogenic signs are congestion of mucous membrane, hemorrhage from natural orifices, increased
heart rate, animal off feed, ruminal stasis, abortion in pregnant cows, blood stained or deep yellow milk,
diarrhea, dysentery, and local edema of tongue
Chronic: Chronic infection is characterized by localized, subcutaneous, edematous swelling that can be
quite extensive. Areas most frequently involved are ventral neck, thorax, and shoulders.
Diagnosis:
It is based on the history of the occurrence of disease in an area, then clinical signs, necropsy findings.
Sudden death in an animal without prior symptoms should lead to suspicion of anthrax and bloody fluid
exuding from the nose and mouth or anus of living or dead animal is particularly suggestive of anthrax.
Postmortem is not allowed. But if by mistake the carcass is opened, septicemic lesions are seen. Blood is
dark, thickened, and hemolysed and fails to clot readily. Dark clotted blood in spleen. Spleen is enlarged,
soft and hemorrhagic. The apparent petechial hemorrhages may be visible throughout the organs.
Intestinal mucosa is dark red and edematous with areas of necrosis. The carcass undergoes rapid
purification. Small hemorrhages are detectable in mucosa of serous membranes and subcutaneous
tissues. There is accumulation of blood stained fluid in serous cavities and gelatinous fluid in loose
connective tissue.
To prepare blood smear, blood is obtained from ear by giving incision. Blood film should be dried and
fixed by heat or immersion for one minute in absolute methanol and stained with polychrome
methylene blue. Then it is washed after thirty seconds into hypochlorite solution. After drying the slide,
it is examined under microscope for reddish purple capsular material and deep blue Bacilli. This reaction
is termed as M- Fadyean reaction.
Treatment:
Because it is rapid in onset and with large mortality rate (90%), this is insufficient to initiate treatment
before death. If anthrax is suspected, segregation of animal should be done. Early supportive and
antimicrobial therapy is useful and Bacillus anthracis is highly susceptible to a wide range of antibiotics
including benzylpenicillin @ 20,000-40,000 IU / Kg, tetracycline, and ciprofloxacin (inj. Ciprocin).
First dose of antibiotic should be administered intravenously and then intramuscularly for 5 days.
Prognosis is not favourable and no time to treat the animal.
Differential Diagnosis:
In cattle and buffalo differentiate it from acute fatal blot, per acute babesiasis, gross tetany, black
quarter, acute poisoning, and enteritis. Anthrax should be considered in differential diagnosis when an
animal dies after having observed apparently good health during the preceding 24 hours.
Control Strategy for Anthrax:
Control measure aim is to break the cycle of infection. The important thing is to correct the disposal of
carcasses. When a cow or buffalo dies inside a shed, paddle or barn, its carcass should be received for
burial incineration. Plug all the natural orifices properly before disposing carcass. Burial should be away
from water supply and pasture. The pit should be at least 180 cm deep. The top layer after burying
should be covered with unslacked lime. The burial place should be away from pasture and water supply.
Decontaminate the area, bedding, unconsumed feed, and room. Dip the equipments in 4 %
formaldehyde solution for 12 hours.
Vaccination:
VRI has developed anthrax spore vaccine. It is a suspension of live, attenuated spores of non-capsulated
Bacillus anthracis in glycerin saline. It imparts solid immunity for one year. Packing contains 300 ml. Its
shelf life is one year. Its dosage in cattle and buffalo is 1 ml s/c. vaccination should not be done in area
where disease does not occur. During vaccination one should not be exposed to vaccine by needle prick.


            Hemorrhagic Septicemia/Pasteurellosis
Hemorrhagic septicemia is one of the most important diseases of cattle and buffalo in Pakistan and
causes heavy losses in Livestock. It is considered number one killer of buffalo. HS is caused by two
serotypes of G –ve, non motile, coccobacillus bacteria named as Pasteurella multocida.
Disease is associated with humid weather; increase incidence of disease is reported in wet season. It is
evident that out breaks do occur in all times of the year but those occurring during wet season spread
rapidly because of the longer survival of organism in the moist conditions. The disease is spread by
direct or indirect contact. The source of infection is infected animals or carriers. The causative agent
does not survive for more than 2-3 weeks in soil or pastures.
Signs & Symptoms:
Majority of cases are acute or peracute in nature with death occurring from 6-24 hours in cattle and
buffalo after the appearance of signs. Signs include dullness, reluctant to move, high body temperature,
serous nasal discharge, salivation, edematous swelling (starts in throat region and then spread to
parotid region and to the neck). Mucous membranes are congested, difficult respiration and animal dies
within few hours. Recovery in buffalo is very rare than cattle.
Diagnosis:
Field or clinical diagnosis is usually based on history, clinical signs, pathological lesion observed on
postmortem, previous occurrence of HS in the herd, endemicity of the area, species affected, and
vaccination history. For lab diagnosis best smear and cultures are blood (from heart), liver, lungs and
spleen. Staining can be done with Giemsa stain and methylene blue stain. Pasteurella grows on common
laboratory media like blood agar. Haemagglutination test detecting somatic Ag or mouse protection
tests, which detect capsular antigen, are more reliable.
Treatment:
It is caused by G –ve bacteria. So antibiotics affected for G –ve. In acute HS endotoxins is the main cause
of pathological changes so non steroidal anti-inflammatory (dichlophanic Na) and steroids are given
which have beneficial effects for stoppage of endotoxins.
We should administer bacteriostatic antibiotics like chlorotetracyclin, oxyclor P.
Detoxifying agents: Novococc Forte (100 ml) it is given in diluted form through IV. If direct then give s/c
at different places.
Non steroids and steroids anti-inflammatory drugs , dichlophanic Na,
Vaccination program:
Vaccination is available in Pakistan prepared by Niab and VRI. Dose rate of Niab Vaccine is 1 ml per 60 Kg
body weight twice a year while dose rate of VRI vaccine is 3-4 ml per animal once a year.


                                          Brucellosis
It has zoonotic importance. B. abortis (in bovine and babeline), B. canis, B. ovis (sheep), B. suis (swine),
B. malletansis (in goat). B. malletanis can also cause abortion in bovine and babeline.
In human it causes undulant fever, orchitis, with the history of severe backache and headache. If
orchitis, it will change the whole spermeogram (concentration, mortality, mass etc.).
                                         Sources of Brucellosis
     o Skin lesion
     o Aborted fetus
     o Direct contact with organism
     o Contaminated food
     o Raw milk
     o Dogs/cats
     o Birds
     o Ocular route
For eradication of brucellosis control of stray dogs, cats and birds is necessary. Man working on one
farm should avoid going to other farm.
If observe sudden enlargement and vaginal discharge, check the opening of cervix. If cervix is intact, go
for antibiotic treatment by glass speculum or hand. Once cervix is open it means environment bacteria is
there, now best is to facilitate the abortion to check the post partum infection.
                                              Pathogenesis
When organism enter the body, it localizes in udder and supra mammary lymph nodes. Abortion due to
Brucella occurs in last trimester or late second trimester (in fifth or sixth month of pregnancy) because
at that time placentomes start secreting erithritol which is attractive for this organism and provides
environment to multiply. So the organism comes from udder and supramammary lymph nodes to the
placentomes and detaches the attachment of villi from caruncles and abortion occurs within 48-72
hours. All infectious causes affect usually placentomes and fetus.
                                        Diagnosis of Brucellosis
3-5% of abortion is normal figure at herd level. When outbreak comes abortion in 5-6 animals, after few
days in other 5-6 animals; it shows the problem. It becomes dangerous when there is sudden abortion.
Isolation:
For this purpose freshly aborted fetus is best one with placenta. If placenta is not shed yet, then fetus
sample. If that fetus is contaminated, there should not be dirty particles or spoiled fetus could not be
sent to lab. Preferably fresh fetus should be sent. Whole fetus is kept in plastic bag and sent to lab as
early as possible preferably within 24 hours. It depends upon the season also. Suppose extreme summer
season, it is better to add bag with ice cubes. If there is need to preserve, go for refrigeration. In lab go
for isolation from stomach, lungs, fetal villi and placentome.
Serological test:
MRT (milk ring test), RBPT (rose bangal plate test), ELISA (enzyme linked immunosorbent essay), SAT
(serum agglutination test). First two are for screening, ELISA and CFT are for confirmation. Suppose 10%
aborted; first go for confirmation, reaming for screening.
First separate the aborted one. There should be no direct contact. For non aborted animal go for
screening test if positive go for antibiotic treatment. One should secure the boundary of farm. Penciling
and streptomycin is ideal one.
Animals with thick secretion or mucus at the vulvular lips should be separated. Use the speculum test
for cervix opening. If it is opened ten you will facilitate abortion. Give prostaglandins or estrogen for
early parturition. In other where the opening is intact, go for treatment. Broad spectrum antibiotic,
multivitamin are given to avoid abortion.
Serum sample and raw milk can also be used. Screening test for the farm should be carried out after
every three month.
There are some non infectious causes. Additionally sampling of fetus and placenta, also send the sample
of food and water. 5g of fodder cover in plastic bag and send to lab for examination of mycotoxin,
aflatoxin and even for the nutritive value.
                                      Control and Eradication
First is vaccination. Some prefer from 6 month, most of the people agree female heifer at 1 year.
Brucella strain 19 is used for vaccination.
Then slaughter the positive animals.
In males Brucella is isolated from primary and accessory sex glands. Semen sample could be used for this
purpose. Treatment of bull is required. In male there will be undulant fever and orchitis. If there is
orchitis, it will affect the spermeogram. In human beings, a person who is working in livestock having
and has a history of sever headache, backache and orchitis, he should be checked for Brucella infection.
Control:
     o Problem come when outbreak.
     o First separate aborted animal from the normal.
     o Then go for treatment.
     o Then you have to care for vaginal discharge.
     o Then secure the boundaries of the farm.
     o Then observe strictly the hygienic measurement at entry.
     o There should be proper dispose of aborted material.
     o Keep away cat, stray dos, birds.
     o The herdman should not move from farm to farm.
     o In control, person should be educated about the plan.
     o Enter new animals after screening.
                                                Treatment
Best treatment is penicillin and streptomycin. These are drug of choice.


                                          Glanders
It is chronic respiratory disease (lower respiratory tract). Most of the time old horses are more
susceptible although affect all age groups. Horse, cat, dog and human affected so zoonotic in
nature.
This disease can affect workers and lab workers (more at risk) than horse owners as cultures are
more pathogenic. So lab workers are more prone to this infection. Vets are infected with this as
working for long time.
This is very dangerous disease difficult to handle and no recovery. This disease is characterized
by nasal discharge, coughing, sneezing and congestion of L.N.
Etiology:
Burkholderia (Pseudomonas) mallei. It is non motile, intracellular, G -ve bacteria. This
bacterium also lives in monocytes and macrophages (non spore forming). That is why difficult to
treat. Use drugs which penetrate cells. This bacterium is also used as biological weapon. It‘s
cultured at mass level and then in powder form or liquid form spray on water and food sources of
enemy. Germany used this weapon.
Anthrax was also used as biological weapon in USA. Mass cultivation of bacteria is done in
laboratories.
Epidemiology:
It is more prevalent in Asia particularly South Asia and Africa. Since 1945 it has been eradicated
from USA.
Transmission:
Transmission occurs through direct or indirect contact by any injury or abrasion. Animal sheds
bacteria by breathing, eating food, drinking water. Common mangers are main source of
spreading of this disease in our area.
Pathophysiology:
Enter through injury or respiratory tract, multiply in trachea, then shift to blood through jugular
vein; septicemia can happen from lymphatic, then affect L.N of whole body. Initially there is
swelling and at the end abscess formation and suppuration.
Clinically:
There are two forms
(1): Acute: rarely sudden septicemia, high fever, and death occur quickly. Sudden death due to
sever septicemia.
(2): Chronic: most common form
There are two forms:
(a): Pulmonary Form:
Lesion present in respiratory tract; lower as well as upper respiratory tract, lungs, trachea, and
alveoli affected. There are signs of pneumonia.
Nasal discharge of purulent nature, passage is chocked so there is chocking, high fever, nodules
form in the lungs, ulceration of nasal mucosa, nodules in nasal septum and turbinate bone,
bleeding from nose. Nodules vary from 1-2 cm in diameter.
(b): Cutaneous or Farcy Form:
Lesion present on skin. There is abscess formation; nodules swollen and converted into abscess.
These nodules are more visible particularly in inner surface of thigh and in the form of chain.
These nodules can form on any part of body and whenever drainage, pus give dark honey like
appearance.
Animal may recover but remain carrier so it is very hurdle to control this disease.
Diagnosis:
It is based on clinical picture. You may perform mallein test. Mallein is purified protein derived
for B. mallei. It is used to detect antibodies in serum.it is delayed type hypersensitivity reaction.
Inject 0.2 ml mallein through insulin syringe on right palpebral border of lower eyelid through
intra dermal rout. (When you inject intra dermal, there will be formation of bead but if given
through s/c there will be bell formation).
Wait for 48-72 hours (upto 96 hours) for the presence of any swelling or inflammation.
Blepharospasm will occur due to swelling (animal can not open its eye due to swelling). If no
blepharospasm test is negative; positive in case of blepharospasm.
Treatment:
Not recommended internationally. Dr. Saqib used combination of sulphonamide and
enrofloxacin. Tribrissen 48 % dose rate of double dose first week. \
20 ml tribrissen and 15 ml enrofloxacine 1st week
0 ml tribrissen and 7 ml enrofloxacin 2nd week
Same through I/V 3rd week
It was noted that animal was recovered. Police horses were recovered and became –ve for this
disease but still there are chances that animal may get infection but these animals are negative for
last 7 years.
Control:
Carrier animals should be removed and vaccine is available
                Difference Between Strangle and Glanders
                    Strangles                                          Glanders
Upper respiratory tract                             Lower respiratory tract
G +ve                                               G –ve
Serous to mucopurulent discharge                    No such discharge
Penicillin is drug of choice                        Sefradin is drug of choice
M protein                                           No M protein



                                         Leptospirosis
It has zoonotic importance. It is caused by Leptospira interrogans and L. biflexa. Different strains as L.
Hardjo in cattle, L. pamma and L. canicola in humans. It causes abortion, still birth and leads to infertility.
It changes all reproductive parameters.
                                                   Spread
Through carrier animals. It may be rodents and non rodents as rabbits, fox, and cattle. Occurrence is
high in wild animals. Disease also spreads through contaminated food and water. Disease is high in
tropical areas. All secretes in urine. Bacteria can live in water for years specially in stagnant water. Flood
after heavy rains is also a source of spread.
                                      Pathogenesis and Symptoms
Entry of organism is through skin lesions, through mucosa, direct ingestion of contaminated food and
water. After ingestion bacteremia develops and antibodies are produced. Then organism is localized in
different organs specially in kidney, stomach, lungs, uterus, and in pregnant animals cross the placental
barrier.
In kidney it causes nephritis and hemolysis. If hemolysis occurs, it will lead to hemoglobin urea and then
renal failure.
In uterus there will be placentitis and cotylodinitis, and it will lead to abortion.
In liver there are two types of diseases which appear after damaging liver as an-icteric form and icteric
form. An-icteric form is 90-95 % while icteric form is 5-10 % where symptoms of jaundice appear. In
cattle there is spontaneous abortion (without showing symptoms) from forth month of gestation and
there will be Leptospiral mastitis. There will be appearance of udder like flabby bag. There will be
sudden drop in milk production. It is milk drop syndrome. Milk will be like colostrums. Even there will be
presence of blood in milk.
In human beings symptoms are:
     o Persistent headache (usually in frontal region and usually does not response to treatment).
     o Renal manifestation that leads to protein urea, Hb urea, even renal failure and hemolysis.
     o Pulmonary manifestation leads to cough, pulmonary dysfunction, and pulmonary arrest.
     o Jaundice
                                    Factor for Persistence of Disease
    o   Carriers as rodents and non rodents
    o   Drainage congestion specially after heavy rain; stagnant water, contaminated lakes
    o   If salinity in soil, organism can survive for years.
    o   Soil temperature (50 cm in soil) if remains nearly 22 oC, it provides suitable environment.
    o   Seasonal variation as high occurrence in rainy season
    o   Age and sex: slightly more in male, in younger animals of upto 3-8 years and in between 20-30
        years in human.
                                        High Risk Group
The persons working in rice fields, sugarcane field and pineapple garden and person responsible for
preparing water channel because chances for skin lesion are more. Same for the animals. Animals kept
in area where there is stagnant water and outbreak. Fisherman is rich source. Driver using stagnant
water for washing of cars so they are at high risk.
                                                Diagnosis
For isolation placenta and fetus in case of aborted fetus. From fetus particularly abomasum part.
Placenta is leathery in brucellosis but specific lesions are absent in leptospirosis. If due to Aspergillus,
there will be white lesions. Kidney, lung, liver, and stomach can also be used for sample
Screening test> MAT (microscopic agglutination test)
                                               Treatment
It is responsive to the broad-spectrum antibiotics. Separate the infected animals.
                                                 Control
    o   Person working in filed should use gloves and gum boots.
    o   Use of ointment before going to field. Ointment should have antibiotics and corticosteroids.
    o   There should be proper water channel for drainage.
    o   There should be control of rodents.
                                               Vaccination
                       Cattle: Leptavoid, prepared in UK. It is bivalent or trivalent


                          Rinderpest/Cattle Plague
It is a transboundary disease (the disease which spread in a large area without any discrimination
of boundaries of countries). Pakistan was declared free from rinderpest in 2003. Before this, it
was reported in Sindh. Vaccination of RP is not allowed in Pakistan.
Family of virus is Morbillivirus (Paramyxoviridae), many strains having similar genetic make
up. Animals of all the ages can be affected. Large animals, sheep, goat, camels are affected.
Pathogenesis:
Virus is inhaled in infected droplets and it penetrates through the epithelium of upper respiratory
tract, multiplies in tonsils and regional lymph nodes, from these sites virus enters the blood in
mono nuclear cells and disseminated throughout the body because virus have high affinity for
lymphoid tissues and alimentary mucosa. So it replicates in monocytes, lymphocytes and
epithelial cells. Destruction of leukocytes results in leukopenia. Local necrotic stomatitis and
enteritis result after proliferation in epithelial cells in alimentary tract and death occurs due to
severe dehydration. In less acute cases death occurs due to activated latent parasitic or bacterial
infection because the animal is immunosuppressd due to destruction of lymphoid organs by
virus.
Clinical signs:
Incubation period is 6-9 days and temperature may raise upto 105-107 oF. There are chances of
absence of mucosal lesion. There is anorexia, decrease in milk yield and lacrimation.
In mucosal phase inflammation of buccal mucosa, nasal mucosa, conjuctiva, hyperemia of
vaginal mucosa, swelling of genitalia and lacrimation becomes purulent. Blephropasm (spasm of
eyelids), blood stained salivation, purulent salivation, halitosis (fowl odour from breathing of
animal). Serous nasal discharge that later becomes purulent. Grayish raised necrotic lesions first
appear inside the lower lip, adjacent gums, lower surface of the tongue, and mucosa at
commissures. Later they become general including dorsum of tongue. Small lesions unite and
become large which cause the sloughing. After sloughing of necrotic material red areas are left
that form shallow ulcers. Severe diarrhea, sometimes dysentery. Skin becomes moist and red and
later it is covered with scab.
After period of 3-5 days temperature decreases, dyspnea, cough, diarrhea, dehydration and
abdominal pain may be observed. Pregnant animas may abort and discharge infective virus in
fetus and vaginal secretions for 24 hours.
Necropsy Findings:
Carcass will be dehydrated, emaciated, soiled with feacal material. Small necrotic areas found on
oral mucosa; ulcers can be seen. These lesions extend to pharynx, upper esophagus, and
abomasums; payer‘s patches become swollen and hemorrhagic. Necrotic zones of hemorrhage
running transversely across the colon mucosa produce characteristic strips called zebra strips.
Mucopurulent exudates in respiratory tract.
Tissues for Sampling:
Fixed sections of lymph nodes, tonsils, alimentary tract, fresh spleen and blood.
Treatment:
No treatment is given in this disease but left over and surroundings of animal are burnt.
Control:
Slaughter the infected animals. Proper cleaning and disinfection of premises. Adopt proper
quarantine measures. Vaccination is not recommended in diseased animals.
Vaccine:
Universal vaccine is used; Tissue culture Rinder pest vaccine. It gives life long immunity. It is
cultured on calf kidney cells. It should be used within 2-3 hours otherwise it will be destroyed.
Attenuated vaccine: virus is passaged in goats, rabbits, chicken eggs.
Vaccination failure occurs due to lack of cold chain in Pakistan.


                                         Tetanus
Tetanus is derived from word Stiffness of the muscles. Striated muscles get stiff in this disease
particularly. Clinically recognize animal with stiff belly, legs, whole body, erected ears, erected
penis in males and difficulty in urination and defecation. There is pressure on bladder due to
stiffness of belly due to which small volumes of urine comes. Tetanus is more common in area
where animals are not vaccinated. Owner should be well informed that animal should be
vaccinated.
Etiology:
Cl. Tetani, it is Bacillus G+ve, spore forming, anaerobic bacteria. It can survive many years in
spore form in soil. This organism is commonly found in soil, in tongue of animal. Whenever
organism enters into the body, this causes and locates the anaerobic condition, mostly under scar
and in dead tissue or pus, start multiplying, firstly convert from spore to vegetative form which is
pathogenic. This bacterium requires any injury or break into skin. Infection mostly occurs due to
mishandling during parturition, retention of placenta, mastitis, pus in uterus, and unhygienic
measures during pulling out of placenta. This organism can get enter through uterus and tetanus
occurs in pregnant animals. Mostly tetanus occurs in animals feeding on rough and tough fodder,
rice straw etc. Animal gets injury and the organism invade through it.
Soil dung contains rich no. of organism which is a source of it. This bacterium can survive many
years in spore form; even in glaciers for one year.
Clinically other predisposing factors:
     1. Most common cause is malhandling during shoeing. Hoof has nail portion where less
         supply of blood and more anaerobic condition particularly in wall. Similarly castration,
         branding, tattooing can lead to tetanus.
     2. Blunt wound or any abrasion can lead to this disease.
     3. Bacteria attack the locality by producing toxins.
There are three types of toxins:
             o Tetnospasminogen
             o Tetnolysin
             o Tetno non spasminogen
Tetnospasminogen is main toxin which causes stiffness. Toxin comes in circulation and blocks
the neurotransmitter, glycine and GABA which are required for proper functioning of nerves. It
also blocks cholinesterase which converts acetylecholin into acetyl coA and choline and body
becomes stiff. Animal can not relax itself as the body remains stiff due to blockage of
cholinesterase. If there is no breakage of this enzyme, body remains stiff. It starts producing
impulses. There are two types of paralysis; spastic paralysis and flaccid paralysis. Spastic
paralysis is moor pronounced. In this disease we have to block the attachment of toxin with
neurotransmitter. At one stage we can not reverse the situation. ATS is given through spinal cord
to stop the attachment of toxin with neurotransmitter.
Tetnolysin causes the lysis of the cells of surrounding area wherever bacteria requires by
producing necrosis and anaerobic condition. It ensures more production of toxin by due
anaerobic environment. When there is more production of bacteria, there will be more spasm
Tetno non spasminogen attacks on peripheral nerves and causes flaccid paralysis. This bacterium
affects different species having different strains.
It can affect animals, humans, dogs and cats. Cold blooded animals like fishes are resistant to it.
Among equines mules resists tetanus very well. Horse is more sensitive and can not resist
tetanus. 80 % cause of death in equines. It is very difficult to treat horse with tetanus. There is a
lot of diversity in this disease.
Clinical picture in some animals very sharp. Very rapid onset of stiffness within hours and in
some slow onset and take 5-6days. Fast clinical picture showing animals are very difficult to
treat and very less chances of survival.
In animals the stiffness firstly starts from jaw but in humans and monkeys the body start
becoming stiff and the jaws becomes stiff at last.
Clinical picture:
Erected ears, tail, stiffed fore and hind limbs give woody appearance, tucked up abdomen,
frequent urination, chest muscles become stiff and flared nostrils. Difficult breathing, stiffness of
masseter muscles, animal can not eat but can drink. Movement of viscera slows down due to
which udder remains full.
Due to stiffness of abdomen animal can not pass the dung. Prolapse of third eye lid is first
clinical sign in horse but last in case of donkeys and mules. Prolapse of third eyelid occurs due to
spasm of muscles of third eyelid.
There is frequent urination, at start but later difficult urination due to spasm of muscles and then
constipation and difficult defecation.
It is disease of third world due to lack of awareness and unhygienic conditions. Organism present
in soil and normal inhabitant of intestine of horses and humans. It is also present in feces of other
species. Number one affected species is horse. More than 80 % cases of horses are fatal. There is
50 % mortality in all equine species. In cattle there is 80 % mortality. In small ruminants and
young calves mortality is 100 %. The most basic wound is punctured wound. No. one
predisposing         cause       of        this      disease         is      punctured         wound.
In humans and monkeys the pattern of signs and symptoms little bit different. Lock jaw occurs at
the end in their case but in other animals lock jaw appear first. Horse becomes hypersensitive to
light, sound and touch. If sound or light, it may increase spasm of muscle and more stiffness
occurs. Hypersensitivity or excitability occurs due to more attachment of tetnospasmin to the
nerves (nerve endings), ganglion and side plates of the spinal cord.
Diagnosis:
In this disease only way to diagnose is clinical picture i.e. lock jaw, third eyelid prolapse, erected
ears, stiffed appearance. The animal gives saw horse appearance. There is tucked up belly.
Differential Diagnosis:
It should be differentiated from any neurological disorder like rabies (there is history of dog
bite), strychnine poisoning (there could be history of taking in strychnine, it can be checked in
feces), milk fever (history of parturition and response to Ca therapy), Mg tetany (sudden
recovery and respond to Mg therapy)
Treatment:
Organism is sensitive to oxygen burst. First of all cover the hypersensitivity to lower the spasm.
Plug the ears, place animals in dark room or otherwise close the eyes by putting cloth. Provide
soft bedding, like wheat straw, rice straw, sand as animal may fall.
We have to locate the wound as organism is in scar. Incubation period of organism is 7-21 days.
If on shoe then remove the shoe and dip the foot in 5 % CuSO4 or 10 % formalin solution and
provide more oxygen by removing nail, shoe and dip in formaldehyde to kill the organism. Dip
2-3 times in a day for 15 days. It will destroy the vegetative form but spore form is resistant.
Provide oxygen to destroy vegetative form.
H2O2 can be used which remove debris. Provide more oxygen. If scar is present on wound,
remove it, make wound fresh and wash it with H2O2. The antibiotics can not reach the shoe as it
has the least supply. So locally kill bacteria.
Neutralize the toxins of bacteria. There are two strategies:
(1): Give ATS which contains antibodies.
ATS stands for anti tetanus serum. These are preformed antibodies. Antigen is given again and
again to the same animals. Antibodies will be formed in that animal which will be collected.
If toxin is treated with formalin to make vaccine, it will be toxoid. In Bactrian bacteria is taken.
Formalin kills the pathogenecity but antigenecity remains there.
Give 30,000 IU of ATS I/V or I/M. Give through intrathecal 40000 IU at atlanto-occipital joint.
This joint is 4-5 inch from the pole of animal. Inject by spinal needle of 4-6 inch.
40000 IU is equal to 12-18 ml; so remove CSF by using spinal needle equal to ATS and inject
equal of ATS along with 1 ml of dexamethasone or prednisilone or panacord. It will lower the
intracranial pressure.
If you will inject large amount accidentally, there will be more volume, and ultimately there will
be pressure on nerve.
Anaphylaxis may develop or serum sickness may occur by injecting ATS after 6-7 days. To
check whether animal is sensitive, inject 0.2 ml of ATS through I/M and wait for 30 minutes (as
there is no emergency). If swelling occurs do not give ATS. But in this case we have to give
because we have no other option.
Other precaution is do not use ATS in case of pregnancy but in humans can use. It causes
abortion mares. So vaccinate the animal.
Under dose is highly lethal. So first dose is lodging dose with more drug
(2): To kill bacteria:
Penicillin is drug of choice (9 million I.U.)
Procaine 40 lac (2inj) and benzyle penicillin 10 lacs (3 inj). Benzyle penicillin repeats after 8
hours.
To relax stiffness, give diazepam 6-8 ml in adult three times daily for 7-10 days.
(3): Nursing:
Animal can drink so your can give ORS, glucose for energy, vitamins for proper working, and
porridge (wheat)
In treatment of this disease 80-90 % share is of nursing and 10 % is of medicine.
Usually death occurs due to respiratory distress caused by the stiffness of the intercostal muscles.
Slings are used to prevent animal from falling, lung collapse and developing bed sore. Slings
keep animal in standing position.
Control:
Tetavac (1 ml); vaccine for tetanus
Plan for horse farm:
The foal born from non vaccinated mare, vaccinate it at 3, 4 month of age and booster after 1
month.
If born from vaccinated dam then start vaccination at age of 6 month, booster after 1 month, then
repeat after 1 year and then at 3 year of age and then 5 year.
Unvaccinated horse then vaccinate immediately and then booster after 1 month and then repeat
after every year.


                                            Rabies
Disease of warm blooded animals but cold blooded animals are carrier for this.
Etiology:
Lysa virus belongs to Rhabdoviridae
Transmission:
Rabid dog is the main cause of spread. Bite of rabid dog (saliva is rich source and if entered
through any wound or even bite wound) monocyte carry it to neuromuscular junction → Spinal
cord → brain. It travels 10 cm along axon per hour
Clinical Findings:
There are three phases
Predominal Phase:
It lasts for 1-3 days. Most of the time remains unnoticed specially in trained dogs. Changes in the
behaviour, animal excited, love to live isolated, dilated pupil, decreased corneal reflex and start
disobeying owner. Temperature 104-105 oF.
Furious Phase:
Some sort of aggression. Animal is over excited and try to bite each and everything and run
behind every moving object. There is excessive salivation, tremors, convulsion, muscle
incoordination. In lass 8-10 days animal wanders aimlessly.
Paralytic or Dumb Phase:
This can come very quickly and sometimes skipping the furious phase. Animal has paralysis,
irritation in nerves and aggression and with the passage of time do not respond to any stimulus.
Duration varies from 2-10 days.
Decrease response and paralysis of ascending order. Start from hind legs (dragging hind legs)
and then travels to fore quarter and then paralysis of head and neck and then death of animal.
Centripetal paralysis
Hydrophobia developed due to paralysis of jaw muscles. Animal can not drink and eat.
Zoonosis:
Rabid dog whenever bites human being transfer this virus. It is transmitted by straying dogs
specially. Out of 6 bites, 1 bite may lead to rabies but you can not take risk so give post exposure
vaccination.
Diagnosis:
Detect niegri bodies (intracytoplasmic) in brain. Blue bodies present in neurons when stained
with Giemsa stain. This virus could be present in saliva, milk, secretion of animals.
If the milk is boiled from rabid buffalo then no chances of rabies and if there is no injury in the
oral cavity then it may destroyed by HCl produced in stomach.
This is very sensitive to sunlight 13 minutes), temperature, ordinary disinfectant
Emergency Measures:
Wash wound immediately with carbolic acid soap or with quaternary NH4 compound.
Post exposure vaccine rabicine
                0 day     14 day 21 day
                2ml         1 ml     1ml s/c
                4 ml        3 ml      3 ml (buffalo)
Antisera can be used within 7 days bit if available
Advise antisera along with vaccine. Vaccine has antigenesity but no pathogenecity.
Observe affected dog for 6 month even after post exposure vaccine.
If you suspect that dog is rabid then keep it isolated for 15 days and clinical picture will tell us.
Vaccinate the animal at third month. Vampire bats are reservoir of this virus. (North America)
whenever bite animal or human being
Pre Exposure:
First month, 3rd month, 4th month, 10th month and then repeat after every year. Control the stray
dog population to control the rabies.


                 Hepatic Fascioiasis/ Liver Fluke Disease
F. hepatica and F. gigantica are responsible for it. It is caused by ingestion of metacercariae.
Intermediate host is snail (Lymnaeid snail).
Life Cycle:
Adult liver flukes live in bile duct where they lay eggs which are excreted in feaces. Hatching
occurs in moist condition only after first larval stage, the meracidium, has formed and when
ambient temperature rises above 5-6 oC. Meracidium invades the tissue of intermediate host snail
within 24-30 hours. After asexual multiplication fluke leaves snail as cercariae. They attach to
herbs and transform into metacercariae by secreting a tough cyst wall i.e. protective. After
ingestion by final host each metacercariae releases an immature fluke which crosses the
intestinal wall and migrates across the peritoneal cavity to the liver. F. hepatica migrates
thorough hepatic parenchyma for about 4-5 weeks and after entering the bile duct start laying
eggs about 10-12 weeks after infestation. Adult sheep and cattle may remain carrier.
Pathogenesis:
Acute hepatic fascioliosis cussed by the passage of young liver fluke through liver parenchyma.
Clinical signs occur 5-6 weeks of infestation of large no. of metacercariae. Environment
becomes favorable for Cl. novyi and develops infection known as infectious necrotic hepatitis
also termed as black disease in sheep and goats. It provides suitable environment for Bacillray
hemoglobinurea in cattle.
Chronic hepatic fascioliosis develops only after the adult flukes establish in the bile duct causing
colengitis, biliary obstruction, fibrosis, leakage of plasma protein (albumin), hypoalbumenemia,
loss of whole blood due to sucking activity of flukes and leads to anemia. Chronic infection
limits the growth rate.
Clinical Findings:
Acute Fascioliasis: Sudden death and if signs observed animal is dull, weak, anorexic, pallor and
edema of mucosa and conjuctiva and animal feels pain when pressure excreted on liver. Death
occurs with passage of blood stained discharges from mouth and anus and most death within 2-3
weeks.
Subacute Fascioliasis: Submandibular edema (bottle jaw), weight loss, pallor mucosa.
Chronic Fascioliasis: Submandibular edema (bottle haw), weight loss, pallor mucosa. In case of
sheep there is shedding of wool. Duration of disease may be 2-3 months. In case of cattle there is
loss in milk production, edema and chronic diarrhea.
Clinical Pathology:
Development of anemia, increased serum glutamate dehydrogenase concentration increases, eggs
in feacal material, hypoalbumenemia.
Differential Diagnosis:
In acute fascioliosis: hemoncosis, anthrax, enterotoxemia.
Chronic: Cu or cobalt deficiency, other internal parasitism, johne‘s disease.
Treatment:
Triclabendazole: (oral) Sheep (10 mg/Kg), cattle (12 mg/Kg).
Albendazole: sheep (7.5 mg/Kg), cattle (10 mg/Kg).
Oxychlozanide: (10-15 mg/Kg for sheep/cattle).
Levamisol: (5.5-11 mg/Kg)


                                       Actinobacillosis
It is a disease of soft tissues, lymph node, and skin of oral or nasal region. Mostly infection is on the
tongue especially pharyngeal lymph nodes are involved. Tongue becomes hard painful so also called as
wooden tongue.
Etiology:
Actinobacillus lignieressi is involved. It is normal inhabitant of nasal mucosa and oral cavity. In any
trauma of mucous membrane, this organism enters the body of animal through nasal or oral mucosa.
Rough fodder feeding lead to trauma of oral cavity.
Pathogenesis:
Organism enters the mucous membrane and multiplies there. It is localized infection and may be
multiplied and cause destruction of mucous cells and lymphocytes. So there is accumulation of pus.
When abscess mature this pus comes out through several openings.
When tongue is involved, it becomes hard and shrunken. Ultimately tortion of tongue may occur. Animal
will feel pain during mastication and prehention.
Clinical findings:
Severe inflammation of tongue, hyper salivation, anorexia, gentle chewing of tongue, hard swollen
tongue particularly at the base. Neck may be swollen. Nodule and ulcer formation on lateral side of
tongue. Nodules are replaced by fibrosis of tongue so it will be shrunken and immobilized leading to
permanent disorder. Parotid and submaxillary LN will be swollen particularly in sheep goat. LN rupture
and pus comes out. This pus does not have smell. For small ruminants tongue involvement is not must.
LN of lower jaw, face and nose are swollen. Diameter of lesion is 8 cm (too large than tennis ball).
In small ruminants LN of cranial and cervical regions are swollen and have pus of yellow green color
containing small granules. Removal of pus from LN may lead to fibrosis, making tissue hard.
Clinical Pathology:
Pus containing sulfur granules.
Post mortem:
No need to slaughter only take pus and nodule.
Treatment:
Decide those antibodies which should penetrate otherwise use iodine. NaI or KI will kill pus.
KI
Oral rout 10g daily for 10 days in large animals. 2-3g/day till iodism develop. There may be coughing,
anorexia, dandruff, exudation, dry and scaly skin, and alopecia; it is iodism.
NaI:
1 g/12 Kg of body weight as 10 % solution I/V. It can not be given I/M, S/C or orally because it is highly
irritant and causes sloughing. Make sure needle is in the vessel. In pregnant NaI may cause abortion.
Give therapy after 24-48 hours of disappearing signs.
NI should be given in 2 doses. Repeat same dose after 10-14 days. If this condition persists it could be
given for 4-5 days.
Antibiotics:
Sulfonamide can be given for 3-5 days. Penicillin and streptomycin (5g streptomycin + 40 lac pencillin)
may be given which may help in quick response. Inject 5 gram streptomycin directly into the abscess. It
may help in quick of animals.


                                        Actinomycosis
Actinomyces bovis is involved. Main difference in actinomycosis and actinobacillosis is of tissue. It
affects hard tissue. Pus formation on the bone of mandible but can develop on any other part. Lead to
formation of hard mass.
Same treatment as of actinobacillosis. Pus has focal smell. Problem is with mastication. It is rare but
bacillosis is common.


                                          Tuberculosis
It is progressive disease in which emaciation of body occurs. Previously this disease was diagnosed in
1890 due to Tubercle bacilli but now named as Mycobacterium bovis. It can affect almost all species but
sheep and horses are resistant to this infection.
Etiology:
It is caused by Mycobacterium tuberculosis. There are three strains of this organism:
       Avian in birds
       Bovine in cattle/buffalo
       Human in human beings
Predisposing Factor:
Main factor is close contact in closed area. Large number of animals in small areas, more chances of
infection.
Debilitating Factor:
Factors which cause emaciation are poor feeding, poor housing, lack of ventilation.
Sources of Disease:
Exhaled air, secretion of infected animals i.e. sputum, urine, semen, uterine discharges, and milk,
discharges from open peripheral LN. Reingestion of sputum and excreted in feaces. Wild animals e.g.
deer are the reservoir.
Mode of Transmission:
      Through inhalation and ingestion.
      During grazing, animal may ingest sputum of infected animal.
      Under natural conditions animal having T.B drinks water from the pond of stagnant water and
          goes away. That water remains contaminated for 80 days. Then other animals drink from that
          water and get infection. In running water there is no such problem.
      Drinking infected milk; it is more common in calves. Swelling of retropharyngeal lymph nodes by
          suckling infected milk and due to this swelling calves are not able to swallow.
      Intrauterine infections occur through coitus either from infected female or male. Zebu cattle are
          more resistant particularly Sahiwal cow than Fresian.
Zoonosis:
Milk man and men taking raw milk are more prone to this infection. 5-10 % cases have been reported in
human beings but in human the condition is not as severe as in animals. Taking boiled and pasteurized
milk has reduced it.
Pathogenesis:
Animal inhales, organism in reaches lungs where necrotic fossi are formed within 8 days. Then
calcification of lesions occurs (monocytes, granulocytes, plasma cells and they make a tubercle at
primary site). About 90-95 % dissemination occurs through this tubercle present in the respiratory tract.
If organism ingested then there are no lesions at entry point, but there is ulceration of tonsils and
intestinal mucosa. In calves there is particularly swelling of retropharyngeal lymph nodes.
If infection occurs through intestine then first lesions are formed on liver and this primary complex leads
to millenary lesions on various organs of the body. It is typical sign of chronic T.B.
Clinical Signs:
There is progressive emaciation, weakness, anorexia, and fluctuating temperature. Initially cough is low
(once or twice a day) but with time loudness increases, nasal discharge. Cough is more in morning and
cold. Coughing can be induced by palpating pharynx. Digestive tract involves rarely but if involved there
is diarrhea, ingestion, swelling of L.N., lower jaw becomes immoveable. In case of reproductive tract
involvement abortion may occur. In udder flakes present in last of milking streams in early phase but in
later stages milk becomes thin, watery and may have yellow flakes.
Diagnosis:
Single Intradermal Tuberculin Test:
Tuberculin is purified protein derivative of Mycobacterium bovis. It is more potent and specific. 0.1 ml of
tuberculin is injected to each animal of herd in cervical fold of skin in centre of neck or anal and caudal
region. If animal is positive for T.B then there will be diffused swelling at injection site after 48 hours.
Short Thermal Test:
Inject 4 ml of tuberculin s/c in neck of animal having temperature 102.5 oF. Check temperature after 2,
4, 6, and 8 hours. If increase in temperature after 2 hours of infection then animal is positive. After 2
hours temperature may reach upto 104.5 F and it remains upto 6 hours.
Store Mount Test:
Same as Short Thermal Test. Inject 0.1-0.2 ml of tuberculin and at the same place inject second dose
after 7 days. If increase in thickness of skin upto 5 cm within 24 hours then animal is positive.
Comparative Tuberculin Test:
For comparison with Johne’s Disease which is number one killer in bovines. Inject avian tuberculin at
upper side of neck and inject bovine tuberculin 12 cm apart at lower side of first injection at neck.
Where is more swelling after 4-48 hours that is positive.
Avian tuberculin is used because it is antigenically similar to Jhone’s Disease. The Johne’s organism i.e.
Mycobacterium paratuberculosis and it is present intracellularly and does not give good response to
antibiotics.
Treatment:
No specific treatment available because very much expensive and time consuming. So people prefer to
slaughter. There are chances of reoccurrence of this disease as the organism is intracellular. Huge
quantity of antibiotics are required and for long term.
Control:
Mainly it is based on the culling of infected animals. The animals which give +ve test for tuberculin; start
program to slaughter or cull the animals by burning or buried. In slaughtering you have to keep in mind
if calcified lesions more pronounced on pleura, peritoneum, and liver extensive in nature; this animal
should be burned or buried.
Test policy of herd should be adopted in all area until you achieve an incidence below 0.5 %. If incidence
is higher than 0.5 % then test each and every animal every year until incidence becomes 0.5 %. This
incidence is not disease incidence but it is positive reactor percentage.


                                        Enterotoxaemia
Toxemia originating from intestine. Cl. perfringens present in intestine. It is G +ve anaerobic bacteria.
Enterotoxemia vaccination 1 cc for lamb, 5 cc for sheep. Now a days multivalent vaccine is used
internationally. Acute diarrhea and sudden death. This disease mostly occurs in highly fed animals and
mostly this disease is seen in lambs and calved fed on high lactating animals.
This bacteria is normally expelled from intestine when peristaltic movements occur but if highly fed
peristaltic movements become slow and bacteria get chance to stay and anaerobic conditions will favour
to grow and multiply. Toxins are released. Mostly affect capillaries, permeability is increased. If does not
cause bacteremia, it will only cause toxemia. Only toxins came in blood and cause diarrhea and pulpy
kidney disease.
Control:
Avoid excessive feeding. In winter give oil (20-100 ml). Vegetable oil in adult animals after every 15 days.
(Solution of pollution is dilution)
Treatment:
Ringer lactate D, dextrose
Give fluid and diuretics (manitol is best diuretic because it has no effect on kidney) for 2-3 days.
Penicillin 5 g orally.


                                      Black Leg Disease
This disease is also called chlostridial myonecrosis, black quarter and quarter ill. It is an important
disease of cattle and sheep. It affects skeletal muscles. This condition starts when tissue damage occurs.
It is acute bacterial, emphysematous, myonecrotic, highly fatal disease. Wide range of ruminants are
susceptible to this condition but cattle and sheep are more susceptible of age of 6 months – 2 yeas but
cattle below this age and above 6 years are also susceptible. This disease is more in summer and fall.
Epidemiology:
It is widely distributed all over the world occurring in all the countries mostly in hilly areas, sandy
regions, more prevalent and this is one of the most important causes of cattle mortality in sandy and
hilly regions. According to epidemiological survey it is an economically important disease of livestock.
When pasture or grazing grounds once become affected, the disease will reappear regularly in
susceptible animals year after year.
Etiology:
This disease is caused by Cl. Chouvei which is G +ve, spore forming, anaerobic bacillus and spores are
highly resistant to environmental influence and disinfectants. Other clostridial microorganism such as C.
septicum, C. novyi and C. perferingens. The spores of these organism are highly resistant to environment
influences and disinfection.
Transmission:
First entry is through alimentary mucosa after ingestion of contaminated feed or eruption of teeth.
Bacteria are found in spleen, liver and elementary tract of normal animals. Contamination of soil and
pasture occurs from infected feacal material or decomposition of carcasses of animals. Black quarter
develops when spores proliferate after the trauma or anoxia like conditions.
Pathogenesis:
Spores are ingested though soil contaminated forage and localized in muscles, they remain latent for
indefinite period. Latent spores are not virulent and must be activated to become pathogenic organism.
Black quarter tissue damage creates a focal anaerobic environment in which spores become activated
and transform into vegetative bacterial cells that proliferate locally in the host tissue. Pathogenesis is
similar to the other chlosrtidial disease. No. of toxins are produced like α toxins (necrotizing leukocidin),
ß toxin (doxyribonuclease enzyme), γ toxin (hyluronidase), and delta toxin (hemolysin). These toxins are
liberated by Cl. chouvei into tissue and resulting in muscle necrosis and septicemia occurs. Exotoxins
also cause hemolysis of RBCs and release Hb which produces muscle lesions with dark red appearance.
The characteristic rancid odour is due to formation of butyric acid as an end product of Chlostridial
fermentation and finally toxemia is the cause of the death of the animal.
Clinical signs:
         In small ruminants in black leg lesions occur in limb musculature and results in stiffness of gait.
Animal is disinclined to move because of severe lameness in one or more limbs. Subcut edema and
gaseous creptation develops. They develop just before the death of animal. Discoloration of the skin
occurs but skin necrosis and gangrene develop in the later stages. In cases where infection occurs
through the wounds of the skin or lesions are present on the head there will be severe local swelling due
to edema, bleeding from nose, high fever, anorexia, depression and in later stages death due to
toxemia. In sheep and goat death is due to development of cardiomyositis. In cattle there will be high
fever, gaseous swelling under skin mainly on hind quarter and shoulder. There is stiffness or limping of
one leg. Gaseous swelling may develop in other parts of the body as well like neck, chest and flanks. At
the beginning swellings are hot, painful and limited later they become larger, cold and painless. Skin
over the swellings becomes dry, hard to dark in colour and on palpation crepitation is felt.
Other symptoms include less appetite, cessation of rumination, rapid breathing, depression and death
of animal within 24-48 hours. Affected animal may die without showing signs.
Diagnosis:
         Diagnosis is on the basis of age, season, swelling on specific area. Make smear, gram staining
and observe clostridium.
Postmartem Findings:
Putrefacion develops rapidly except in affected muscles, so that extreme bloat is present shortly after
death. In affected muscles, gas formation continues in the cadaver, leads to marked tympany and causes
the legs on the upper side to exte d stratignt out. Bloody froth often exudates from the mouth, nostrils,
and anus. The skin over the swellings is usually normal but is found to be infiltrated with discoloured
bloody serum and gaas. This emanates an odor that is usually described as sweet sour or like that of
rancid butter. The muscles are swollen emphysematous, dark black and friable. Swelling is due to
distension with gas that presses the bundle part, prevents collapse when they are cut and gives to them
a dry spongy texture. Similar swelling are found rarely in the masseter muscles, the toungue, pharynx,
diaphragm, pleura, lungs and even in the walls of stomach or intestine.
On opening the abdominal cavity one may find serum, hemorrhage, fibrinous exudates on the
peritoneum and and enteritis. The spleen is usually normal but it may be swollen and hemorrhagic.
Kidneys and liver are pale and friable.
In visceral black quarter, a few or no skeletal muscle lesions are seen on necropsy. The most startling
lesions in this form of BQ are serofibrinous to fibrinous pericarditis and peuritis, epcardium is roughened
and granular with petechial to echmotic to paintbrush hemorrhages on the surface and within the heart
wall. The lungs adjacent to the heart may be similarly affected so that a localized serofibrinous pleuritis
is present.
Treatment:
Treatment must be in time within 24-48 hours. For specific treatment, provide oxytetracyclin (without
xylocain or lignocain) 10 mg/kg body weight intravenously for several days. For supportive treatment
give multivitamins like biodil injection in cattle 20 ml with 48 hours interval. Solon- M injection
(prednisilon + antihistamin) may be given 5 10 ml. It is anti-inflammatory, analgesic and antipyretic.
Prevention and control:
Dead animals are potential source of it. Sodead animals should be burned. Vaccine prepared by
Veterinary Research Institute is alum precipitated formalized vaccine prepared from Cl. Chouvei. It is
given in first week of April. First injection conquers immunity for 6 months but if boost injection is given
after 15 days of first infection then it will provide immunity for one year. Dose rate is 5 ml for 275 Kg
body weight. Allergic reaction can develop by vaccien so for it adrenalin (2-5 ml s/c) and prednisilone (4-
10 ml I/M in non pregnant animals).


                                  Foot & Mouth Disease
It is an infectious viral disease of cloven footed animals characterized by high fever and vesicle
formation in oral cavit and on feet and teats. This disease is known throughout the world due to
economic loses. It is causing more losses in cattle as compared to buffalos. In terms of economic loses it
is one of the most important diseases of livestock by drastic fall in meat and milk production. Death in
adult animal is rare; more in young animals and affected females become infertile for long periods. Pure
exotic breeds and cross bred animals that have been recovered form FMD start panting and become
useless for farmers in case of transport or other work.
After recovery the production of animal decreases.
There are four types of virus causing FMD. Type A, type C, type Asia 1, and type O have been identified
in Pakistan; the antigenic difference among various types and sub types is the main problem in the
control of the disease. So regular typing and sub typing of virus should be done and field strains should
be added into vaccine. Mostly cattle and exotic breeds are susceptible. Mouth lesions are more severe
in cattle and foot lesions are more severe in buffalo. In 1992 study showed that cattle are more
susceptible. Disease is not fatal but cause economic losses.

                    Some Factors due to Which FMD is not Controlled in Pakistan
    o   In Pakistan numerous natural and socio-economic problems made the control of FMD very
        difficult.
    o   Occurrence of different serotypes, subtypes and frequent mutation is one of the major
        problems in control of FMD. Apart from 7 serotypes there are several subtypes that are
        ontogenetically and immunologically different and do not provide cross protection. About 80-88
        subtypes have been identified.
    o    New antigenic subtypes are constantly emerging. Animals which are immune against one
         subtype remain susceptible to the emerging subtype.
    o Quality of vaccine: in our area trivalent (A, O, Asia 1) vaccine is given having three serotypes but
         most of the times FMD contains newly emerging strains which lead to failure of vaccine.
    o Lack of comprehensive vaccination program.
    o FMD virus is quite resistant even to commonly used disinfectants.
    o There is lack of quarantine measures in case of entry and exit of animal at farm. (isolate
         diseased from healthy one)
    o Nomadic animals move from one geographical area to another area carrying infection.
    o Some non susceptible animals like birds, dogs, and cats are potential agencies of spread. These
         species are not infected with FMD. Virus passes unchanged from GIT of birds so birds play
         important in dissemination of virus from one area to another. Similarly dogs and cats fed on
         died animals of FMD also becomes the source of spread.
    o Carrier animals (recovered from FMD, non diseased vaccinated and non vaccinated) and these
         animals carries the virus in nasopharyngeal region. About 50 % of recovered animals act as FMD
         carriers. So it is more beneficial to keep recovered animals separate from healthy animals.
    o Lack of communication between farmers and veterinarian.
    o Non certification of freedom from disease before introducing them to the farm.
    o Nosocomial spread (from hospital, veterinarian and para veterinary staff) by syringes, crush,
         thermometer etc.
    o Common grazing and watering and common and not properly disinfected utensils.
    o Socio economic factor: farmers can not afford the vaccination
    o Farming with multiple animal species.
    o Lack of effective reporting system.
Etiological Agent:
Picornaviridae, genus Aphthovirus. There are 7 types A, O, E, Asia l, SAT 1, SAT 2, and SAT 3.
One of the important characteristic of FMD is that the virus is produced in large amount in infected
animal and present in all secretions and excretions of animals including urine, feaces, and exhaled air;
that is why it is contagious disease. Virus is also present in the products from infected animals e.g. meat,
milk, hides etc.
Transmission:
Direct contact with effected animals
Movement of contaminated animalproducts
Trough artificial insemination
Contaminated feed and water
Spread through wind
Pathogenesis:
The primary site of infection and replication is usually the mucosa of pharynx although the virus can
enter through skin abrasions or the GIT. Virus is distributed through the lymphatic system to sites of
replication in the epithelium of the mouth, muzzle, feet and teats and also to areas of damaged skin
(e.g. the knees and hocks of pigs kept on concrete). Vesicles develop at these sites and rupture, usually
within 48 hours. Viremia persists for three days.
Signs:
High rise in body temperature that generally do not respond to antibiotics, heavy stringy salivation,
occurrence of vesicles and ulcers in the mouth, on feet and teats of the animals, reduction in feed intake
and milk production, teat infection may lead to mastitis, lameness due to lesions on feet, high death
rate in young animals, deformities in hooves, 50 % weight loss.
Diagnosis:
FMD viral antigenic serotype is identified in tissue and body fluid. ELISA. For lab test epithelium of
ruptured or non ruptured vesicle on feet is best sample (at least 1 g). Vesicles of buccal mucosa and
udder, blood sample, and esophageal pharyngeal fluid (OP fluid) are also used.
Treatment:
As it is a viral infection so no specific treatment but purpose is to shorten the disease.
      Isolate the sick animal with separate feeding and watering utensils.
      Wash the mouth of animal with 2 % alum solution or 1:1000 dilution of potassium per magnate.
      Ointment for vesicle:

Alum: 1 tea spoon
Potassium chlorate: 1 tea spoon                       smear on vesicle (mouth) three times a day
Boric acid: 1 tea spoon
Xylocain injection with 2 % adrenalin: 15 ml

     Antibiotics:
Tribacteril (trimethoprin + sulphadiazine) 20ml I/M for four days in adult buffalo and cattle.
     Dipyrone (antipyretic) 25 ml (I/M). Cold water therapy for fever.
     2 % solution of CuSO4, wash feet lesions and then smear with piodine or tincture iodine.
     Multivitamins (AD3E) 15 ml (I/M)
     Soft diet (leafy) should be given.
     Protect lesion from flies to avoid maggots because maggots can produce in lesions.
     Ethnoveterinary practice:
Hot bread (roti) with butter is offered which will rupture the vesicles.
Walk on hot sand or floor.
Water from tanneries is app the lied on vesicles. It will dry the vesicles.
Vaccination:
Vaccinate animals thrice a year (in February, March and August – September 5-10 ml s/c)



                               Bacillary Haemoglobinuria
Its causative organism is Chlostridium haemolyticum it provides hemolytic toxin (lysis of blood). These
are spore forming, G +ve, anaerobic bacteria. In infected animal, organism is found in liver of healthy
animal. Whenever animal ingest organism it is lodged in liver. Association of this disease is with poorly
drained pasture or more irrigated pasture because of presence of liver fluke or snails and in summer and
in autumn.
Pathogenesis:
Organism is ingested through contaminated feed. It enters into animal, lodges in liver,. Liver fluke
invasion: infarct areas due to necrosis of liver tissue or portal vein thrombus or due to Fusebacterium
necrobacillosis or due to cysticercus. These infarct areas are site for proliferation of Clhlostridium. They
produce hemolytic toxin and go into blood and cause systemic toxemia and also cause vascular damage.
Clinical signs:
There is fever (106 oF) but in terminal stages sub normal temperature, off feed, anorexia, week and
anemic animal, jaundice, abortion. Blood in urine (haemoglobinuria); dark red colour urine.
Treatment:
First specific/immediate treatment: antitoxic serum, penicillin, tetracycline (6-10 mg/Kg), 20,000-40,000
IU/Kg in large animals. By this treatment haemoglobinuria disappear within 12 hours.
In supportive treatment: blood transfusion, fluid therapy, haemopiotic drugs (iron or copper), liver tonic
(hepamer).
Control:
Vaccination: 4-6 week before expected season, pasture management.
Differential Diagnosis:
Hematuria (intact blood in urine). This condition develops in kidney infection or in trauma of
urinogenital tract. In this case RBCs will settle down at bottom.
Lysed blood mostly in parturient hemoglobinuria, babisiasis, theleriasis. But in parturient
haemoglobinuria: no toxemia, deficiency of phosphorus, oxidants are more in amount in feed, fever
does not occur, non responsive to antibiotics.
In babesiasis and theleriasis parasite present is seen in blood smear, staining with Giemsa stain. If red
water haematuria due to phosphorus deficiency then urine colour will be chocolate coloured. In
haemoglobinuria temperature remains increased. If phosphorus deficiency then wall of RBC will become
fragile as phosphorus is required for the formation of cell wall. When it breaks down the RBCs will be
lysed and come to urine.
Theleria and babesia: dark yellow colour. When parasites are present in RBC then animal suffer fever
and when RBCs burst, fever falls down. So intermittent fever and they are not treated with antibiotics.
Animal will not respond to antibiotics.


                                            Strangles
Strangles is derived from strangulation. In this there will be swelling of retropharyhngeal L.N.
which cause pressure on pharynx and ultimately animal feels dyspnea.
In few cases you have to perform esophagotomy or tracheotomy to relief from suffocation. This
disease is mostly of young equines but can affect equines of all ages.
Clinically characterized by serous discharge, initially flue like, and then after 3-5 days
mucopurulent. It mostly occurs as secondary bacterial infection of influenza.
Etiology:
Streptococcus equi is G+ve have M protein in cell wall due to which this organism can hide itself
from phagocytes as there is no presentation to antibodies and then no immunity work.
Wherever Ag enters body, first line against antigen is neutrophils, then macrophages. Such
chemotactic agents are produced such as interleukens which attracts B and T cells.
B cells when activated convert into plasma cells. T cells convert to cytotoxic, helper and memory
cells.
T cells cytotoxic engulf Ags. T helper cell releases chemotactic. T memory cells remember Ag
and when 2nd attack comes, memory cells come in action. So that‘s why booster vaccine is given.
If there is M protein this organism will not be detected and no engulfment by neutrophils. It will
help to adhere the epithelium of respiratory tract particularly upper respiratory and there will be
involvement of larynx, pharynx and guttural pouches. Organism will multiply in respiratory tract
and then travel to lymph nodes (retropharyngeal, submandibular L.N). This organism is very
sensitive to penicillin. The wall degrades.
Pathogenesis:
Enters through nasopharyngeal or oral mucosa, it will cause pharyngitis, rhinitis and in guttural
pouches it will cause sinusitis, particularly perpura hemorrhagica (superficial bleeding in small
vessels). It travels to retropharyngeal and submadibular L.N and then spread to whole body
through lymphatic system. There will be accumulation of pus and abscess formation. If abscess
ruptures, there will be creamy pus from the opening of this abscess. If opening is external then
this pus will contaminate environment and will become source for other animals. It can also
drain interiorly in trachea, larynx and lungs, and may lead to aspiratory pneumonia.
This organism survives in environment for 4-8 weeks. Severe outbreak; very rapid spread. The
animal with nasal discharge must be isolated daily to avoid spread.
Clinical findings:
Nasal discharge, temperature 103-105 oF, dyspnea, soft coughing will convert to productive
cough, off feed, emaciated, difficult swallowing. Nasal discharge initially serous then after 3-6
days becomes mucopurulent. Neck is stretched out. L.N painful on palpation. This disease may
end up spontaneously but in chronic cases 10-15 days. Incubation period varies from 3-21 days
depending upon type.
Complications:
Aspiratory pneumonia
Guttural pouch emphsymia
Bacterial strangles (L.N. of whole body swell)
Perpura hemorrhagica
Myocarditis leading to heart attack
Hepatic abscess may lead to dysfunction of liver.
Mortality is 1 % but if complication may increase upto 10 %.
Morbidity could be 100 % and if no complication then recovers within 4-6 days.
Bastard strangles: When there is abscess formation on different sites on skin. Theses pus
contains St. equi. If drain out, affect environment. If drain in, lead to many complications.
Transmission:
Through direct or indirect transmission; if there is contamination of food, fodder, utensils etc.
organism becomes implanted in guttural pouches and affect when there is stress. Due to
implantation in guttural pouches animal becomes carrier.
Diagnosis:
Culturing of organism; take swab from nasal discharge and culture on blood agar and stain with
Geimsa stain.
This organism may become carrier if some granules remain in guttural pouch, on L.N and can
not be recognized easily. In this way it becomes difficult to control. Animal of 1-2 years old is
more prone to this disease.
Treatment:
It is self limiting disease. Provide rest to the animal for 3-5 days. Separate the infected animals
from other animals. Do not give antibiotic in initial phases but in later phases when you feel
complications. Place animal at comfortable place and prevention from cold.
Try to observe the animal. Make three plans; animal with good mood, light mood or depressed
mood.
St. equi is highly sensitive to antibiotics. Penicillin is drug of choice.
There are two forms of disease; mild and complicated. There will be lacremation from nose and
eye from same direction.
We have to devise two strategies. If mild, there is no need to give antibiotics. Give NSAID,
meloxicam, diclophanic Na, loxin. Segregate the infected animals if possible. In case of
complications some owners prefer tracheotomy.
Next strategy is purely based on treatment of abscess. First mature it. You can use
liniment/iodine or hot therapy to mature it. Then provide an opening for drainage of pus either by
setoning. Apply two openings. From one opening insert swab and from other opening remove it.
Mature abscess can drain internally so you must be very careful about it. Wash with KMNO4 and
then bandage soaked with Tr. Iodine put in it. You can fill MgSO4 in it. Do not give antibiotics
because it delays the maturation of abscess; but after the drainage you can give antibiotics.
Steam of Tr. Benzoin Co: (10 liter of water and 100 ml of Tr. Benzoin Co); give for 15-30
minute.
Provide soft diet as green fodder; avoid horny stuff as wheat straw, hay etc.
Prevention and Control:
Prevention is difficult due to carrier animals. This carrier animal may present for long time and
shed organism in tears, nasal secretion and even during breathing. So identify and cull it. But it is
difficult to identify carriers.
Vaccination:
There are two types of vaccines; bactrin and toxoid. If both; bactrin toxoid. In bactrin vaccine we
use M protein fractions or extracts. But problem is that you can not recognize M protein fractions
so prevention is 50 %. Provide vaccine in highly infectious areas.


                          Parturient Paresis or Milk Fever
Usually it develops due to deficiency of Ca in serum. Whenever there is less Ca there is loss of normal
body tone and muscles become flaccid. It happens in high producing animals. Hypocalcemia, general
weakness, collapse, depression of consciousness.
Factors:
Inability to absorb Ca from intestine or unavailability of ionized calcium ions in serum e.g. in severe
inflammation of intestine and sometimes calcium is bind to some other elements.
Excessive secretion of Ca in colostrum so excessive loss of Ca from body.
Malabsorption, malnutrition, deficiency of thyroid hormone which helps in Ca reabsorption from bone.
When calcium level decreases in serum PTH becomes active and provides Ca by reabsorption of Ca from
bones.
If calcitonin level is increased in body then it binds ionic Ca and makes it unavailable for body for normal
functioning.
Aminoglycosides like kenamycin etc. bind the Ca when given I/v rout. EDTA and oxytetracyclin also bind
the Ca. So we can not use these drugs during pregnancy, parturition and lactation.
Sheep and goat are also prone to milk fever. In sheep it is due to prolonged starvation, rarely lambing
related milk fever but in cattle related to pregnancy.
20-30 % of cows are prone to it and usually 5-10 years old cows having 3rd, 4th, 5th, 6th, or 7th calving.
Incidence at first calving is less. There are three phases of milk fever in cattle:
     o Prior to parturition (animal may fall on ground)
     o During parturition
     o After parturition
Maximum care right after 48 hours and occasionally occurs after 6-8 weeks. Suddenly animal may fall.
Most of time during pregnancy estrogen level is increased due to which loss of appetite; animal does not
take feed properly due to which Ca deficiency occurs and leads to milk fever. Burseem fodder cause
increase in estrogen level and leads to starvation.
Pathogenesis:
Ca level falls in serum which is required from normal body tone, it will cause decreased heart rate, high
pulse rate, flaccid paralysis, hypothermia due to decrease heart rate, and periphery becomes cool and
leads to uterine prolapse and dystokia. Sometimes Mg level falls but in some cases it shoots up and
muscular tetany will be seen. Ca and phosphorus ratio is disturbed. Ca low and phosphorus high, it is
milk fever. Sometimes Ca and P simultaneously low in serum it is more dangerous.
Clinical Findings:
Mild/Prodormal/subclinical stage:
Animal is in standing position, brief state of excitement, muscle tremors (head and neck), animal can not
move and eat, slight shaking of head, tongue protrudes out, teeth grinding, temperature normal or
slightly high, animal ataxic, anorexia. Agalactia (no milk production), ruminal stasis, normal temperature,
respiration, and heart rate.
All this happens due to loss of Ca and loss of body tone. It may remain for several hours and at this time
animal response very well to the calcium therapy. So early diagnosis is important.
Sternal Recumbancy Stage:
Unable to stand, cow is drowsy, turned head towards the flank. No tetany, flaccid muscles, muzzle dry,
skin and periphery cooled, rectal temperature 99-101.5 oF, increased heart rate but intensity very low,
pulse also weak, ruminal stasis, constipation, tympany, and blot.
Lateral Recombancy Stage:
Complete flaccidity, cow can not resume sternal recumbancy, can not move, heart sounds inaudible,
heart rate is increased upto 120 beats/min, pulse almost can not be palpated, can not raise the jugular
vein by putting pressure. This stage can not be retrieved. Drenching pneumonia is common complication
of this stage.
Clinical Pathology:
The Ca level falls from 8 mg to 5 mg/dl of blood and in severe cases upto 2 mg/dl that is critical level.
Calcium and Mg ratio also varies. Normal level of Mg is 1-2 mg but it may increase upto 4-5 mg/Kg.
Normal Ca to Mg ratio is 6:1 but in this condition it is 2:1. in mild cases it is 5:2.
Phosphorus level may remain normal or may change. Normally it is 1.5 mg/dl and increase upto 4.5
mg/dl. Consider these values for diagnosis. Treat animal as soon as possible within 48 hours.
Treatment:
Usually 400-800 ml 25 % calcium borogluconate is given in large animals,
Calcivet.
Melfone-C
While giving Ca note all parameters, high doses may cause Ca toxicity and low dose causes relapse of Ca.
to avoid heart attack give Ca in different doses.
Calcium borogluconate 20-25 ml I/V, 100 ml s/c in small animals.
If slight high dose, immediate death may occur. Ca should be given in combination with 5 % dextrose.
Absorption of Ca in tissue is increased due to dextrose because it emulsifies the Ca. To avoid
reoccurrence give 20-30 ml of vitamin D (AD3E).
Increased absorption of calcium from intestine.
Other multivitamis through I/V like B complex. If aspiratory pneumonia, then give calcium through s/c or
intraperitonial route. If you give I/V it will lead to edema, pulmonary hypertension.
Never inject Ca in summer season in direct sunlight it increases heart rate and chances of heart attack in
animal, so bring animal in shade and give.
Facts:
70-75 % case recovered by calcium therapy, therapy fails in under doing false diagnosis. Low PTH, Ca
therapy you can diagnosis by level of Ca in serum. 100 % animals recovered in first stage. 30 % in second
stage. 26 % in third stage.
Control:
Avoid excessive Ca therapy before parturition. As Ca level increases, calcitonin increases and parathyroid
hormones decreases and whenever pregnancy, high negative pressure and Ca fall in serum and release
in milk so Ca not reabsorbed from bone to serum.
In milk fever diet rich in estrogen level also cause change in Ca level.
You can use testosterone derivatives, they have anabolic action, it not only increas3e appetite of animal
but also decrease estrogen level and improve the calcium metabolism.
Dietary phosphorus can also exert negative pressure on parathyroid hormone. In this disease if animal
getting low P then ratio becomes 6:1 and then there are 30% chances of milk fever.
If Ca P ratio is 1:3.3 then no chances of milk fever during pregnancy it will create negative pressure on
PTH less chances of milk fever but bad impact is osteoporosis of bones in animals and it is more
common in older animals. To avoid this you can give 5 % of monosodium phosphate (add it in
concentrate as control measure) because our soil is deficient in phosphorus. P deficiency also leads to
post parturient hemoglobinurea.
Managemental Practices:
Avoid excessive Ca feeding in parturition.
Ca is 100-150 g/day can be given in diet, avoid over feeding and also avoid stress during parturition
CaCl2 can be used by and after 24 hours of parturition this can minimize chances of milk fever (150 g
cacl2 given 1-2 hour before, 1-2 hours during and 1-2 after parturition and after 10-15 hours of
parturition to avoid jerk of negative pressure. CaCl2 has bitter/bad taste. So you have to give through
stomach tube.
Vitamin D3 should be given it helps in absorbance of calcium, vit. D changes to 2,5 dihydropolycalciferol
and in kidney 1,25 dihydropolycalciferol and liver converts to precursor which reabsorbs calcium.
Vitamin D2 @ dose of 200000 IU/oral 4-5 day prior to parturition. Vitamin D3 10-12 days prior to
parturition.
Avoid vitamin D3 therapy during lactation or dry period because it absorbs more calcium. So lead to
decrease calcium.
Vitamin AD3E injection 50 ml (20 ml, 15 ml, 15 ml) for three days.
Vitamin D3 2-3 million, 8-10 million units can be given one week prior to parturition.
Vitamin D2 used for one or two week can cause excessive calcification. So D3 should be used.
We can give PTH hormone but therapy not feasible because we can not give so much parathyroid
hormone (costly)
NH4Cl 20-100g, increased acidity in stomach/rumen having basic environment but Ca require acidic
environment for absorption. So it will keep in absorption of Ca.


                          Lung Worm Infestation in Cattle
                                     (Bovine Verminous Bronchitis)
This disease has different local names as Parasitic bronchitis, Husk/Hoose in America, bovine infectious
bronchitis.
Dictyocaulus viviparus causes it.
Transmission:
When cattle ingest third stage larvae by grazing. The third stage larvae migrate to intestinal wall to reach
mesenteric lymph nodes. From here they pass via the lymphatics to venous blood stream and through
heart to lungs in alveoli. They migrate up the bronchioles to their predilection site in the larger air
passages and start to lay eggs 3-4 weeks after infestation.
There are four phases:
Penetration Phase: Ingestion to arrival of larvae in lung, 1-7 days.
Prepatent Phase: Larvae in lung, 7-25 days.
Patent Phase: Mature worms in lung, 25-55
Postpatent: Lung worm disappear from lungs, 55-70 days.
Signs:
Coughing, dyspnea, rapid shallow abdominal breathing, 60-100 breaths/min, slight nasal discharge,
breathing through mouth, temperature raise 104-105 oF
Treatment:
Ivermectin, albendazole: 7.5 mg/Kg, oxfandozole: 4.5 mg/Kg, levamisole: 7.5 mg/kg, antihistaminic drugs
like NSAIDS, loxin.
Diagnosis:
Baermann technique (funnel like worms in bottom after one night).


                                           Salmonellosis
Salmonella doblin is its etiological agent. Usually it is a disease of animals which are sent out for grazing.
Drinking on infected water or grazing on infected pasture will cause this disease.
There is high rise in temperature above 40 oC. There is severe diarrhea and dysentery. Abortion may
occur within or after 10 days. After entry into body it localizes in liver, spleen, and lungs. After 6-8 days it
will be shifted to placentome and it will damage the placentome. It will produce endotoxins, every cell
will produce prostaglandin, and there will be irritation in uterus and abortion.
                                                  Diagnosis
Isolation from all the parts of fetus and placenta.
                                                   Control
Separate the infected animal. Avoid grazing with infected animals. Vaccination Salmonella doblin strain
61
(In mummification there is no infectious cause but in maceration there is infectious cause).


                                Paratuberculosis/Johne’s Disease
It is chronic infection of intestine caused by Mycobacterium paratuberculosis.
Transmission:
       Nursing of calf by infected dam.
       Contaminated feed.
       Oral feacal route.
       Also transmitted from dam to fetus also present in genitalia.
Clinical Findings:
Most important is infection occurs under thirty days of age and incubation period is very long so clinical
signs appear at 3-5 years of age.
Stage one is silent stage in which no clinical signs and it occurs in younger animals.
In subclinical stage animal becomes carrier and potential source of infection. It is at adult stage.
In clinical stage chronic diarrhea with presence of air bubbles and no odour, feed intake is normal, all
other parameters normal but more thirst. In advanced clinical stage there is emaciation, dehydration
and ultimately death.
Diagnosis:
Blood test, ELISA, faecal examination.
There is a tuberclin like test in which Mycobecterium is injected in the neck of animal. If swelling occurs
after 48-72 hours, test is positive.
Treatment:
No treatment is recommended. But streptomycin (50 mg/kg b. wt.) can be given.
Losses:
Low milk production, low feed efficiency, more chances of infertility and mastitis, pr mature culling
                                                 Rabies
Rabies ('rage' or 'madness' in latin; lyssa. Hydrophobia in man) is a specific viral fatal encephalomyelitis
affecting all warm-blooded animals (but principally carnivores) and characterized by the derangement of
the nervous system causing interference with the consciousness, nervous irritability and paralysis.
Rabies is one of the most important fatal zoonoses. With 35,000 human deaths notified annually, rabies
occupied the 12th rank in 1995 in the World Health Organization's list of the fatal infectious and
parasitic diseases.
Rabies virus is a bullet shaped single-stranded RNA virus, having negative sense and nonsegmented
genome. The genomic RNA encodes five structural proteins. One of them (matrix protein) is associated
with inner side of the viral envelope, while another (glycoprotein) forms the spike like projections on the
surface of the virion. The remaining three proteins (transcriptase, nucleoprotein, and phosphoprotein)
are associated with genomic A. All isolates of rabies virus including those responsible for bat transmitted
paralytic rabies, belong to a single serotype. All warm-blooded animals with the possible exception of
opossums are susceptible to rabies. However, of all animals, dog is the principal species affected. Dogs,
foxes, wolves, raccoons, mongooses, coyotes, skunks and vampire bats (Desmodus rotundus murinus)
all can serve as reservoirs of rabies virus.
Transmission:
The natural and the most common method of transmission is through bite of an infected animal.
Transmission can also occur through contamination of skin wounds by fresh saliva of an infected animal.
The saliva of an affected animal has been shown to be virulent several days (as long as fourteen days)
before the appearance of symptoms. The danger of infection is greatest when the bite is inflicted
directly through the skin, especially if near the head. The danger is rather less when the bite is through
clothing or through a thick coat of hair or wool. These frequently remove the saliva and virus from the
teeth before the skin is actually wounded. In some cases the virus is carried away by bleeding of the
wound or destroyed by immediate disinfection of the wound. It is believed that probably somewhat less
than one-half of the animals bitten by rabid dogs contract the disease, and that of the total number of
the human beings bitten by the rabid dogs, about 16% develop rabies, and die. Of human beings bitten
in the face by rabid dogs, the mortality is 80%. Even apparently healthy dogs have been reported as
intermittent salivary excretors of rabies virus. Air-borne transmission and transmission through
ingestion, transplacental transmission as well as via drinking water has been suspected (Khan et al.,
1986).
Pathophysiology:
Incubation period may vary from one week to several months and may be influenced by the site of
infection and the virus dose and strain. After inoculation, a region of glycoprotein attaches to the plasma
membrane of cells; a putative binding site is the nicotinic acetylcholine receptor. Usually the virus is
amplified in the cells of the skeletal muscles near the site of inoculation for 1 to 4 days. When the
concentration of the virus is quite sufficient (presenting a possible explanation of the above mentioned
1 to 4 days stay at the site of bite), it enters the nervous system through sensory and motor terminals,
which is the first step of its journey to the brain. In the peripheral nerves, the virus spreads by
retrograde axoplasmic flow at 8 to 20 mm/day until it reaches the spinal cord, when the first specific
symptoms of the disease (pain or paresthesia at the wound site) may appear. Afterwards, as the virus
quickly disseminates through the central nervous system, progressive encephalitis develops, until the
virus spreads throughout the body along the peripheral nerves, including those in the salivary glands.
where it is shed in the saliva, which is the principal route of transmission. Experimental evidence also
supports the possibility of virus dissemination to salivary glands by way of bloodstream (Khan et al.,
1997).
Clinical Signs:
The clinical signs of rabies are variable as embodied in the maxim `Atypical is typical for rabies'. Cattle
and buffaloes generally have the furious form of rabies. The most striking signs are fits of bellowing,
general straining and tenesmus, but they rarely bite. Many cattle will strain more or less constantly as if
to defaecate. Usually air is aspirated into the rectum when there is relaxation between the straining
periods. Animals with furious form of rabies may show belligerence toward objects in their environment
or may run frantically through fences and stall doors. Such behavior may be produced by mild
tactile or auditory stimulation. Rabid cows or buffaloes would charge at innocuous objects, and resist
restraint. Salivation is seen in many but not in all cases, depending on whether or not pharyngeal
paralysis develops. Animal may display hypersexuality and paraparesis. As the disease enters the
paralytic stage, the first signs are the weakness in the hind legs a followed by paralysis that takes over
the muscles of locomotion. A frequent sign is knuckling over the hind fetlocks. Two to three days after
appearance of the clinical signs, affected buffaloes were found to frequently immerse their heads in
water trough. Later on they started rubbing the poll region, head, neck and shoulder on the wall
resulting in abrasions of the skin. Next day the buffalo started charging human beings and birds and
moved continuously in the pen. These signs have not been reported in cattle. The total course of the
disease in buffalo is usually 5 days. In both cattle and buffalo, death usually occurs after a period of
paralysis and prostration.
Pre exposure Immunization:
One ml dose of Rabisin TM (An inactivated aluminium hydroxide)
                    Species                               Minimum age                         Booster
                                                 Born of non-        Born of
                                                vaccinated dam    vaccinated
                                                                     dam
  Carnivores (dog, cat, lion etc.)            4    weeks (but 11 weeks         Annually or triennially depending
                                              preferably at 16                 upon the level of risk of exposure
                                              weeks)
  Herbivores (buffalo, cattle, sheep, goat,   4 months          9 months
  camel, horse, donkey etc.)



                                                 Listeriosis
Its causative agent is Listeria monocytogenes.
Susceptibility:
Mostly sheep but also in other ruminants. It has 16 serotypes on the basis of flageller or somatic Ag.
Virulent strain multiply in macrophages and monocytes and produce Lesteriolysin O (major virulent
factor) and can grow on wide range of pH i.e. from 4.5 to 9.6.
Organism is susceptible to almost all common disinfectants. It is wide spread in nature.
Primarily the disease of ruminants, there may be development of encephalitis, pregnant animal may
abort, spinal myelitus, septicemic disease, ophthelmitis, gastroenteritis and rare chances of
development of mastitis.
Sources of Infection:
Organism is common in environment and infection is not limited jut to the animals, but mammals, birds,
insects, fish. Organism can be isolated from animal fecal material, soil water trough, animal feed, walls
and floor of farm, animal itself can be source of Listeria.
Most of its complication is due to presence of this organism in silage. It is commonly present in silage
but do not multiply in properly fermented silage whose pH is below 4.5.
Transmission:
Lambs can ingest contaminated feed, or it may be congenital disease is due to naval infection.
Encephalitis form of disease results from the infection of the nerves after some injury to the buccal
mucosa from feed or infection of the tooth cavities and browsing.
Spinal myelitus occurs due to involvement of spinal nerves; there are certain risk factors that help in
multiplication of microorganism. Weak the host resistance mechanism. Poor nutrition of the animal
Sudden change of weather.
Spinal mellitus: weakness of hind limb, paralysis of forelimb, constriction of pupil, iris swelling, and
corneal ulceration of mostly found dead. If survive, green colour feaces. Animal is weak lethargy.
Differential Diagnosis:
Encephalitis, middle ear disease, polioencephalomaletia, , nervous ketosis on cattle, gid , pregnancy
toxemia in sheep if enteritis problem then differentiate from salmonellosis..
Zoonosis:
Listeriosos is a feed born disease in humans e.g. milk products and raw milk contaminated with Listeria
through feacal material or valerians aim treating dystokia may get dermatitis. Conjunctivitis may occur
in humans.
Pathogenesis:
Ingestion of microorganism… penetration in musosa of intestine…. Inapparent infection with prolong
faecal excretion of microorganism to a subclinical bacteremia which clears with the development of
immunity, bacteremia is subclinical and microorganism is excreted in milk. Splenic Listeriosis with or
without menegitis occurs in new born ruminants and pregnant sheep and goats. Listeria monocytogenes
is a facultative intracellular pathogen that can infect cells including intestinal cells by direct endocytosis.
It can survive in macrophages and monocytes. Bacterial superoxide dismutase protects against
bactericidal activity of phagocytes and listereolysin O damages the lysosomal membrane allowing the
microorganism to grow in cytoplasm. In pregnant animals, invasion of placenta and fetus occur within 24
hours of onset of bacteremia, edema and necrosis of placenta leads to abortion, 5-10 days post infection
or newly born young ones they may suffer from fetal septicemia. Encephalitis occurs due to acute
inflammation of brain stem and is unilateral. Portal of entry is ascending infection is on the nerves
(cranial and trigeminal nerves). Spinal myelitus mastitis.
Necropsy finding:
Microabscesses in intestine
Clinical pathology:
CFT, agglutination test.
Clinical signs:
Flock depressed, fever (104-107), in coordination, head deviation (tilting), walking in circles, unilateral
facial hypelgesia (pain sensitivity decreased), facial paralysis, dropping of ears, lips paralysis, third eye lid
paralysis (ptoris), panopthalmitis (pus in anterior chamber of one or both eyes), prehention and
mastication become slow, drooling of saliva, food hanging from mouth.
Duration of disease in cattle is 2-3 weeds while in sheep and goat is 2-4 days. If Listerial abortion in last
trimester, retention of placenta, fever 107 0F, abortion assert soon after commencement of silage
feeding, retained placenta, blood stained vaginal discharge for several days.
Septicemic Listeriosis::
Depression, weakness, fever, diarrhea, death within 12 hours. In case of mastitis single or both quarters
are involved, somatic cell count increased but milk remains normal.
Treatment:
Chlorotetracyclin 10 mg per Kg body weight.
Penicillin 44000 IU/Kg b. wt I/M for 7 days or may continue upto 14 days.
Fluid therapy. Atropine, corticosteroid.
                                 Dermatomycosis / Ring worm
Its causative agent: Trichophyton and Microsporum canis
T. verrucosum (sub specie: album and discoides) T. mentagrophyte, T. megninii
In sheep T. verrucosum and M.canis
In goat T. verrucosum
Most common where animals are kept indoor and congested. Direct contact with infected animals or
infected objects like bedding. Young animals are more susceptible, incidence is more in winter, healing
spontaneously in spring but humidity is main factor.
Zoonosis:
Human acquires ring worm infection from equine and cattle.
Pathogenesis:
Ring worm fungus attack keratinized tissue, stratum corneum, and hair fibers. There will be breaking of
hairs; alopecia develops. Exudation from infected epithelial layer starts. Epithelial debris and fungal
hyphae produce crust that is characteristics of this disease. Warm and humid environment is favourable
for mycillial group and alkaline pH of skin. Ring worm fungus is strict aerobes and dies under the crust.
Living on the peripheral site active but die in centre. Due to this mode of growth it produces centrifugal
progression (because animal requires oxygen for growth) and characteristic ring form of lesion.
Secondary bacterial infection to hair follicle is common.
Clinical Findings:
Crust is heavy and grayish white, raised above skin. Lesions are circular and 3 cm in diameter. In early
stages surface below crust is moist. In older lesions the scab becomes detached and alopecia develops.
Lesions are commonly on neck, head but general distribution over whole body particularly in calves.
Itching does not occur. In sheep lesions are mostly present on head and very rare on wooly and fleece
areas and disappear in 4-5 weeks. But disease may persist in flocks for some months. Lesions are normal
patches covered with grey crust. Similar lesions are seen in goat.
Clinical Pathology:
Skin scrapping: first defat with alcohol or ether. Then put a drop of 20 % potassium hydroxide or sodium
hydroxide, warm it and make slide, observe polyhedral rounded, irregular spores in the form of chains
or hair follicles.
Differential diagnosis:
Mycotic dermatitis, sarcoptic mange.
Treatment:
Crusts are removed by soft brushing and burnt.
Apply weak solution of iodine, quaternary NH4 compound.
Bourdeoux mixture (CuSO4 + lime + water), it is basically used in paint.
10 % solution of NaI 1g/14 Kg.
Greseofulvin.
Aminoglycosides if bacterial infection.
Control:
Isolation and treatment of infected animals.
Disinfectant: 5 % formalin, 5 % Na hypochlorite.
2 % formaldehyde + 1 % Caustic soda are used for walls.

                                             Mycotoxins
Important one is Aspergillus. Filaments and spTrores are present in roughages and concentrate.
Vegetative from causes mycosis. It usually develops when immune status is weak. Lungs, udder,
intestine are affected. Mycotoxins of importance in veterinary is aflatoxin. Other toxins are
Deoxynivelenol, T-2 toxin, and ochratoxins. Molds also present in silage.
Symptoms of aflatoxin are weak, anorexic, depression, rough coat, and low production. In chronic case
jaundice like signs.
Treatment:
No such treatment but toxin binders are used. Universal antidote i.e. activated charcoal is given.
Purgative is given along with it. Charcoal 1g per Kg b. wt. orally.
Other proportions aluminosilicate, clay, bentonite, xeolite, complex indigestible carbohydrate like
cellulose, polysaccharide.
Supportive therapy as blood therapy, liver tonic.
Above was to avoid absorption from rumen. If absorbed, give antitoxins. Aflatoxin not more than 20 ppb
in lactating feed. Aflatoxin no more than 0.5 ppb in milk.



                                          Bunostomiasis
It is Hook worm disease.
Transmission:
Through skin, warm and humid environment is favourable.
Signs:
Anemia, diarrhea, and anasarca (subcutaneous edema).
Clinical Pathology:
Eggs in feaces, hypoproteinemia.
Necropsy Findings:
Red worms attached to mucosa of small intestine nearby ingesta often blood stained.
Clinical Findings:
Diarrhea, paleness, weakness, anasarca along belly or under jaws, death under 2-3 days. Blood suckers
cause severe anemia. 100 worms may cause illness, may cause death if no. is 2000.
Loss of blood, mild intermittent diarrhea, mild irritation.


                          Hepatic Fascioiasis/ Liver Fluke Disease
F. hepatica and F. gigantica are responsible for it. It is caused by ingestion of metacercariae.
Intermediate host is snail (Lymnaeid snail).
Life Cycle:
Adult liver flukes live in bile duct where they lay eggs which are excreted in feaces. Hatching occurs in
moist condition only after first larval stage, the meracidium, has formed and when ambient temperature
rises above 5-6 oC. Meracidium invades the tissue of intermediate host snail within 24-30 hours. After
asexual multiplication fluke leaves snail as cercariae. They attach to herbs and transform into
metacercariae by secreting a tough cyst wall i.e. protective. After ingestion by final host each
metacercariae releases an immature fluke which crosses the intestinal wall and migrates across the
peritoneal cavity to the liver. F. hepatica migrates thorough hepatic parenchyma for about 4-5 weeks
and after entering the bile duct start laying eggs about 10-12 weeks after infestation. Adult sheep and
cattle may remain carrier.
Pathogenesis:
Acute hepatic fascioliosis cussed by the passage of young liver fluke through liver parenchyma. Clinical
signs occur 5-6 weeks of infestation of large no. of metacercariae. Environment becomes favorable for
Cl. novyi and develops infection known as infectious necrotic hepatitis also termed as black disease in
sheep and goats. It provides suitable environment for Bacillray hemoglobinurea in cattle.
Chronic hepatic fascioliosis develops only after the adult flukes establish in the bile duct causing
colengitis, biliary obstruction, fibrosis, leakage of plasma protein (albumin), hypoalbumenemia, loss of
whole blood due to sucking activity of flukes and leads to anemia. Chronic infection limits the growth
rate.
Clinical Findings:
Acute Fascioliasis: Sudden death and if signs observed animal is dull, weak, anorexic, pallor and edema
of mucosa and conjuctiva and animal feels pain when pressure excreted on liver. Death occurs with
passage of blood stained discharges from mouth and anus and most death within 2-3 weeks.
Subacute Fascioliasis: Submandibular edema (bottle jaw), weight loss, pallor mucosa.
Chronic Fascioliasis: Submandibular edema (bottle haw), weight loss, pallor mucosa. In case of sheep
there is shedding of wool. Duration of disease may be 2-3 months. In case of cattle there is loss in milk
production, edema and chronic diarrhea.
Clinical Pathology:
Development of anemia, increased serum glutamate dehydrogenase concentration increases, eggs in
feacal material, hypoalbumenemia.
Differential Diagnosis:
In acute fascioliosis: hemoncosis, anthrax, enterotoxemia.
Chronic: Cu or cobalt deficiency, other internal parasitism, johne’s disease.
Treatment:
Triclabendazole: (oral) Sheep (10 mg/Kg), cattle (12 mg/Kg).
Albendazole: sheep (7.5 mg/Kg), cattle (10 mg/Kg).
Oxychlozanide: (10-15 mg/Kg for sheep/cattle).
Levamisol: (5.5-11 mg/Kg)


                                        Coccidiosis
It is caused by genus Emeria, species Emeria tenella, E. acervulina, E. necatrix, E. mites, E.
maxima, E. praecox, E. brunette. They are species specific and site specific but sometime
overlapping.
Coccidiosis is a subclinical to clinical, mild to sever disease characterized by anorexia, enteritis
leading to mucoid to blood containing diarrhea, dropping of wings, hemorrhagic intestinal and
caecal lesions which lead to death.
Pathogenecity:
E. tenella and E. necatrix are the most pathogenic (sever hemorrhagic enteritis) and have
moderate mortality. E. brunette and E. maxima are moderate pathogenic with moderate
mortality. E. acervulina and E. mites are moderate but no mortality. E. praecox causes lesions in
villi.
Sporulation and Survival of Organism out Side the Host:
Factors leading to this are moist environment, oxygen, and 25-28 oC temperature.
Sporulation takes place within 1-2 days under optimum conditions on the ground. Sporulated
oocyst becomes resistant to low temperature and dry conditions and most of bacterial
disinfectants. They can survive for months but unsporulated oocyst died soon. NH4 destroys the
oocyst present in litter. Other favorable condition is humidity and rainy season which extends the
survival of oocysts.
Epidemiology:
Chicken is susceptible species. Transmission between flock occurs by mechanical way as oocyst
remains on cloth and hands of workers. Mixing of infected and healthy birds. Presence of
scavengers. Oocyst remains viable in the intestine of animal. With flock contaminated water and
feed. Vertical transmission does not occur.
Factors Influencing Susceptibility of Infection:
    o Extremes of the weather
    o Litter if moist and warm
    o Pathogenecity of species involved
    o Dose of oocyst
    o Previous exposure to the infection
    o Nutritional status of flock (deficient in vitamin A, E and K)
    o When with other disease like Mark‘s disease, Reovirus or mycotoxins
    o This disease is more sever in broiler than in layers
    o Overcrowding increases the chances
Clinical Signs:
Appear 2-4 days post infection when tissue is damaged.
Schizonts appear in intestine, lead to morbidity and mortality. Anorexia and malabsorption
leading to diarrhea, weakness and loss of weight causes low grading of the birds. Death occurs
due to loss of blood. The susceptible age for caecal coccidiosis is 3-8 weeks of age and for
intestinal coccidiosis 12-20 weeks. Coccidiosis affects on microflora of intestine, increases
invasiveness of E. coli and salmonella, decreases the number of Lactobacilli and Enterococci,
and increases the chances of proliferation of Cl. perfringens.
Pathogenesis:
It depends upon the life cycle of coccidia. Oocysts are thick walled mass of nucleated protoplasm
contain four sporocysts. Each sporocyst contains two banana shape sporozoites. Mode of
infection is ingestion of sporolated cyst. Infective dose is 10,000 oocysts for the development of
infection and 100,000 oocysts leads to sever hemorrhagic enteritis and death of bird.
Ingestion, mechanical action and enzymatic degradation of gizzard on oocyst cause the release of
sporozoites which are carried to intestine and caeca along with digestive content. These
sporozoites are divided into two ways:
    o Asexual stages
    o Sexual stages
Asexual multiplication occurs by division of nucleolus present in sporozoite. When parasites
released they enter in epithelium and lamina propria of intestine. Parasites within cell grows up
and rounds up, called trophozoite; growth continues which ultimately leads to bulging of cells.
Multiply asexually and called as schizonts. They are released into intestine called merozoites.
Merozoites are layered together like sections of an orange. These merozoites are first generation
merozoites. These lead to hemorrhage, blood in feces on 5-7 day post infection and causes
rupture of lamina propria. Some merozoites divide asexually and differentiate into male and
female gametocytes; they reproduce through the sexual life cycle. One male gametocyte
fertilizes with one female gametocyte to form zygote (thick walled) and called oocyst. It breaks
the cells of intestine and liberates and come in droppings. Oocyst is infectious stage of
coccidiosis. From one ingested oocyst, 100,000 oocysts come in the one dropping. Cycle
requires 4-7 days depending upon the species of coccidia.
Postmortem Lesions:
Depends upon the type of coccidia ingested
E. acervulina:
Lesions in duodenal loop, jejunum, sometime posterior part of small intestine. These are whitish
patches, small, rounded, elongated or in the form of ladder. Produced due to sexual cycle of
agent. Congestion and hemorrhages in specific area and due to asexual life cycle. Lamina propria
is not damaged by this.
E. brunetti:
Lesion site: Lower small intestine, below the yolk sac diverticulum and then rectum and
proximal area of caecum. It will lead to coagulative necrosis leading to formation of brownish
cast in intestine. There are pinpoint congested areas above ileu-ceacal junction. Lesions lead to
infection of clostridium group and cause necrotic enteritis.
E. maxima:
Site is middle of intestine leading to hemorrhagic enteritis. Pinpoint hemorrhages on serosal
surface. Thickening of walls and ballooning of intestine. Contents of intestine brown, orange,
pink or reddish brown in colour
E. necatrix:
Site is entire length of GIT mostly mid gut. In this situation you will find bright red hemorrhages
on serosal surface of intestine, ballooning and thickening of wall of intestine. Intestinal contents
mixed with blood. Pathognomonic lesions are formation of whitish yellow plaques containing
schizonts i.e. colonies of protozoa within cell.
E. praecox:
Site is duodenum, upper third of GIT, hemorrhages petechial on mucosal surface, intestinal
contents watery or mucoid in nature.
E. tenella:
Site: Caecal and adjacent area of GIT lead to the swelling and enlargement of caeca upto three
times, sever hemorrhages and lumen filled with blood. Mucosa is ulcerated.
E. mitis:
There are no specific lesions, only redness of mucosa.
Histopathology of Intestine:
Schizonts or oocyst in epithelial cells of intestine, submucosal glands enlarged, necrosis of
intestinal cells, hemorrhages of intestine, inflammatory response represented by white blood
cells proliferation. There is infiltration of eosinophils, monocytes, and plasma cells in mucosa
and submucosa.
Diagnosis:
Lesions and site of lesion shows species involved. In field entire mucosal surface is examined
from lower part of gizzard upto rectum. Search for whitish plaques or petechial hemorrhages on
serosa.
Opening of gut and examining of mucosa for thickening, presence of blood, cast and cheesy
coagulation necrosis.
In lab you can go for microscopic examination at 10X and 40X objectives. Look for schizonts,
merozoites and gametocytes. Sample is collected from duodenal loop below entrance of bile
duct, mid gut near yolk sac diverticulum, lower part of intestine just above union of caecal sac,
and middle portion of the caeca.
Prevention and Control:
Hygiene:
Disinfection of farm with formalin 5%, 5% solution of CuSO4, 5% solution of KI or KOH
Foot dip should present at entry of farm.
Management:
Young flock kept away from adult birds, litter should not be wet, add CaO2 for dryness of litter
@ 5-7 Kg per 100 ft2 of floor.
Heavily infected litter should be removed. Try to add litter gradually.
Chemotherapeutic Control:
Quinolones: non toxic but drug resistance develops rapidly.
Methyl buquinolate
Pyrinodol: clopidol is extremely safe. Broad spectrum but resistance develops rapidly
Carbanilamide
Thiamine analogue e.g. amprolium
Nitrofurans: furazolidone (limited spectrum)
Ionophorous antibiotics: Salinomycine, monensin, they are safe and affect sporozoit and
resistance develop slowly.
Due to chemotherapy residues will find in meat and eggs. So should stop giving medication and
give withdrawal period 2-3 days before marketing.
Rotation of drug; one drug for 6 months to one year is given and then stop and change it by
other. In rainy season use strong medicine and in less severe cases use less effective medicine.
Medicine Failure:
     Low dose taken by bird as birds are anorexic
     Narrow spectrum of drug effective against one species but not against other
     Drug resistance
Treatment in Outbreaks:
Hygiene and management; restrict the entry to farm
Chemotherapy as sulfonamide inhibits second generation of schizonts but at the same time
develops resistance and affect kidneys. Effective against intestinal coccidiosis but not for caecal
coccidiosis.
Sulfaquinoxalin (3 days medication, 2 days withdrawal, and 3days medication)
Sulfadimethoxine
Amprolium for caecal coccidiosis @ 125 ppm in water for 7 days
Supplement of vitamin E, A, D and K
Antibiotics oxytetracycline, streptomycin, and penicillin for secondary bacterial infection
Amino acids and electrolytes should be given
Diet should contain low protein level upto 5-10% of feed. It helps in reduction of mortality due
to coccidiosis.
                       Mycoplasma gallisepticum
Mycoplasma gallisepticum causes chronic respiratory disease (CRD) in chicken and infectious
sinusitis in turkeys (may be single or both sinus). CRD is characterized by coughing, sneezing,
nasal discharge. Chicken and turkeys are more susceptible but may also affect pheasant, pigeons,
peafowl and quail.
Etiology:
Mycoplasma gallisepticum. It is associated with ND, IB, ILT, E. coli, and pasturellosis. It is very
sensitive organism and can live out of host for a few days. Organism is normally present in bird
and carrier birds show infection due to stress as change in temperature or vaccination or other
concurrent problem. Birds remain carrier.
Epidemiology:
Age at which this disease is seen is 4-6 weeks. Transmission is between flock, within flock, or
through vertical transmission. It does not occur between the flock, because organism do not
survive outside the host but sometimes fomites are affected by feaces of affected bird or when
diseased birds cough lead to aerosol transmission.
35% eggs laid by infected hens are infected in vertical transmission. It gradually decreases upto
1% or less. But after 3-4 weeks eggs are free from organism. Vertical transmission occurs
through blood, direct contact of follicles with air sacs, contamination of eggs with feces, or from
infected semen or if oviduct infected. Certain factors which increases susceptibility of infection
are
     Temperature: most common in winter/cold weather
     Acute change in weather, hot temperature with humidity
     Poor ventilation especially during brooding time
     Vaccination stress specifically live virus infection
     Concurrent infection like ND, ILT, IB, Coryza
     Onset of production in pullets
     Poor litter with increased NH3 concentration
     Overcrowding
     Presence of toxins in the feed
Clinical Signs:
Incubation period is variable. In natural infection it is uncertain but experimentally 4-20 days. It
is very slowly developing disease and takes weeks or months for developing diseases. Signs
include coughing, sneezing, nasal discharge and swelling of infraorbital sinus. In chicken leading
to anorexia and poor body weight, much poor carcass may be condemned and prominent keel
bone. In laying birds decreased egg production. In males infected semen. Course of disease may
be week or go upto months. Morbidity is high and mortality is low.
In turkey there is swelling of one or both infraorbital sinuses. If air sacs or lungs are involved
then death may be due to air sacculitis and pneumonia.
Pathogenesis:
Organism get entry from respiratory tract and go to blood causing septicemia, go to respiratory
epithelium. It causes irritation and damage the lining of trachea and air sacs. Damage of cilia and
epithelium is exposed to other microorganisms. Mycoplasmosis does not cause sever damage;
recognized only when it becomes complicated by ND, IB, ILT etc and lead to fibrinous or
purulent inflammation of air sacs, liver, heart, peritoneum. During septicemic form hemorrhages
found and swelling of organs. In acute phase you find septicemic form.
Postmortem Lesions:
There is poor quality carcass. There is catarrhal inflammation of nasal passage, trachea and
bronchi. Air sacs thickened and opaque and contain hyperplastic lymphoid follicles. In chronic
case air sacs may contain mucoid to caseous exudate. Air sacculitis, fibrinous perihepatitis,
adhesive pericarditis may occur but not pathognomonic. These are confused with chlamydial
infection. In turkeys restricted to sinusits but in chronic cases there may be air sacculitis,
fibrinous pneumonia, tracheitis, and salpingitis (inflammation of oviduct).
Histopathology:
There is thickening of mucous membrane and infiltration of mononuclear cells, focal areas of
lymphoid, hyperplasia of the mucous glands, pneumonic lungs with lympho-follicualr changes
and granulomatous lesions.
Diagnosis:
Slow onset of clinical signs, lesions, decrease appetite and decrease weight gain.
Serological test as HIT, positive plate or tube agglutination test, ELISA, and PCR.
But birds recently vaccinated give false positive results
Isolation and identification by taking exudate from sinus
In chicken pulmonary lesions can be confused with collibacillosis and chlamydial infection. In
turkey fibrinous pneumonia can be confused with avian influenza.
Control:
Immunization, activated and non activated vaccines are available but do not give satisfactory
results.
Depopulation of contaminated area, remove the birds from that area for a month and wash and
decontaminate the area.
Purchase day old mycoplasma free bird
Avoid entry of wild bird
Strict isolation and good management
Chicks vaccinated against ND and IB
Minimize factors which increase the occurrence of disease.
Medication of eggs hatched for infected flock but it decreases hatchability of eggs
Egg dipping in cold solution of antibiotic e.g. erythromycin and dose is 400-1000 ppm and
solution should be at temperature of 2-4 oC for 15-20 min and then remove them and set them in
incubator. This reduces the no. of pathogens present in egg but also decreases hatchability upto
8-12%.
Medication of breeder flock. Streptomycin in @ 200 mg per Kg I/M.
Tylosin mixed in feed.
How to Deal in Outbreak:
Antibiotic treatment is effective for mycoplasma but not for E. coli. Medication should be for 7
days. Drug of choice is tetracycline. It is safe in young birds upto 2 weeks of age.
Chlortetracycline can be given in feed 200 g per ton of feed in day old chicks upto 3 weeks of
age and in young birds after 3 weeks dose is 1000 g per ton of feed. Tylosin is poorly absorbed
in GIT so given as injection @ 6-10 mg/Kg s/c or 2-3 g/4 liter of water. Streptomycin is effective
in initial stages it is given @ 60 mg/Kg body weight. Erythromycin can be given but M.
gallisepticum is resistant to it.
                                 Avian influenza
It is a viral disease which ranges from asymptomatic to low egg production, respiratory signs, or
severe fatal disease. In some cases asymptomatic. Then only low egg production then respiratory
signs or it may be fatal. So have many clinical pictures.
                                          Etiology
It belongs to Orthomyxoviridae family. Only influenza virus A produces infection in chick (as
well as in mammals); B, C, D not in chicken but in other species. Avian influenza virus is RNA
virus having 8 single stranded RNA segments. They can assort themselves independently during
replication and many combinations may occur. There is high degree of mutation.
                                   Antigenic Types
On the surface of virus there are glycoproteins, Haemagglutinin HA and neuraminidase N, which
are embedded in capsid. There are 16 different types of hemagglutinin and nine different types of
neuraminidase. There may be 144 different possible combinations and all these are antigenically
different. In reality not 144 as some die, some are non pathogenic, and some may be pathogenic
for poultry. H determines the major antigen and N is minor. For protection you have to vaccinate
with all strains. In Pakistan H7, H5, H9 are present. All the strains are not prevalent at a time.
In Pakistan pathogenic strains are H5N1, H7N3, and H9N2. These are highly pathogenic in
Pakistan. Sometimes one type is active other all inactive. Sometimes two strains are active. In
1994-95 H7N3 was active and killed more than 3 million birds in hilly areas of Pakistan. Later
this became less pathogenic. In 2003, outbreak of H5N1, highly pathogenic caused 100 %
mortality but H9N2 is moderate. Antigenic drift is point mutation but shift is a major change.
Antigenic shift causes change of antigenic structure.
Name is written as: Type/host/geographical site/reference number/year/(H_N_)
A/chicken/Pakistan/447/1995/H7N3 ►It is complete name.
A/chicken/Pakistan/1369/1995/H7N3
Virus is killed by ordinary disinfectants. (IBD virus can survive for months and can not be
destroyed by ordinary disinfectants).
                                       Pathogenecity
Pathogenecity is the potential of virus to produce a disease; it may be non pathogenic, mild
pathogenic or severe pathogenic. So avian influenza may be highly pathogenic (HPAI) mild
pathogenic, and moderately pathogenic. But at this time there are two classifications as highly
pathogenic and non highly pathogenic.
Whenever virus is isolated and inoculated in 10 day old chicken embryo in allontoic cavity and
after three days collect virus which kills chicken. Check its type. Then dilute it (1:10) and inject
in 4-6 week old 8 chicks (0.2 ml I/V). If this incoulum kills 6-8 chicks in 10 days, it is highly
pathogenic; if it kills 2-3 chicks, then non highly pathogenic. Then go for molecular level
classification of virus. HA needs an enzyme to be brokdown and for its replication so highly
pathogenic virus replication is different from non pathogenic. HA Cleavage: HA →H1, H2;
process is caused by proteases. Trypsin is a strong protease present in respiratory tract and
digestive tract can break the virus.
Highly pathogenic virus can be splitted by any protease but non highly pathogenic needs trypsin.
Non HPAI virus has amino acid arginin at cleavage site and also a protective sheath. So it needs
trypsin to be cleaved. But in HPAI virus there are a no. of amino acids and the protective sheath
is not present. So any protease may attack at cleavage site. So if do not kill any chick but on
molecular level it is splitted by any protease then it will be highly pathogenic. In field conditions
classification is different. It may virulent, highly virulent or mild virulent. Highly virulent causes
100 % mortality (severe disease), moderately virulent virus causes 5-97% mortality, mildly
virulent causes less than 5% mortality. Non virulent has no disease.
If moderately virulent virus affect with any concurrent disease, it will be highly virulent e.g. AI +
ND leads to very sever problem. H9 is moderately pathogenic but if in the phase of farmer
vaccinate bird with live ND then it becomes highly pathogenic. (Sometimes AI attacks and
passes away without signs)
One virus may be virulent and non virulent at various times. H5 and H7 are very dangerous
strains.




                                       Clinical Signs
Incubation period is 3-14 days. In moderately pathogenic usually respiratory signs may be mild
or severe depending upon the age, type and production status of bird or presence of any other
disease. There is sneezing, coughing, nasal and lacrimal discharge, decrease in feed intake and
decreased egg production. Broodiness is increased in laying birds. Morbidity is high but
mortality is generally less than 5 %; it may go up in case of concurrent infection.
In case of highly pathogenic there is fulminant disease which occurs suddenly and severely. (100
% mortality in 3 days even observed in 2007). Some birds dead but may not be showing disease
signs. Respiratory problem is not very severe as in moderate but there are nervous signs like
tremors, shivering of body, paralysis, torticollis, opisthotonos, unable to stand and sit, and
imbalance). Overall activity of bird is decreased. Animal is weak and lethargic with decreased
vocalization. There is also drop in egg production even upto 100% in 5-6 days.
                                            Lesions
Mild Pathogenic:
There is sinusitis. It may be catarrhal, mucopurrulent, fibrinous. There is congestion in trachea.
Trachea may have exudates. Birds also show air sacculitis and egg peritonitis, enteritis (catarrhal
or mucopurrulent). Yolk is present very where in reproductive tract. Salpingitis (swelling of
oviduct) may occur. Ovary may be regressed, small ova are present.
Highly Pathogenic:
In per acute cases there are no lesions. But later on edema of face and head can be seen. There
are petechial hemorrhages on shanks, feet, claws, and foot pad. Even echymotic lesions are also
seen. There are hemorrhagic lesions on comb and wattle. When open the birds, there are
hemorrhages on proventriculus, intestine, heart, liver, kidney, and muscles. There are ulcers in
intestine. There are necrotic spots on liver and spleen. Kidneys are swollen and urates are
deposited. There are heamorhages on oviduct. Payer patches in intestine are necrosed. Lungs
show pneumonia, congestion, and edema. Actually no organ left without hemorrhages even on
comb and wattle. (Only in avian influenza hemorrhages are present on comb and wattle). (Fowl
cholera causes minor swelling of wattle). Bird dies within 3-8 days. 70-100% mortality can be
observed.
                                           Diagnosis
By clinical picture and isolation of virus. Test for H type is performed as ELISA. ND and AI
have similar signs. So confirm by haemagglutination Inhibition Test. Both cause agglutination of
RBCs. So take virus + ND antiserum + RBCs; if no hemagglutination, it is ND. Take virus + AI
antiserum + RBCs; if no hemagglutination, it is AI.


                               New Castle Disease
It is the most important disease. This disease first appeared in 1926 in Java, Indonesia and
Newcastle-upon-tyne (UK). It is also called Ranikhet as appeared in Ranikhet (India) in 1926-27.
It is found in all kinds of poultry birds including chicken, pigeon, turkeys etc. It is a viral disease
of birds characterized by respiratory and nervous signs and variable severity and mortality
depending upon the agent and host. Variation in mortality is high as 0-100% depending upon the
virulence of virus. Similarly there is also variation in virulence of virus as from low to highly
virulent. This disease is also immunosuppressive.
                                            Etiology
It belongs to family Paramyxoviridae, subclass Paramyxovirinae and genus Rebula virus among
which there is one group Avian paramyxovirus which varies from APMV1-APMV9. ND virus
causing disease in chicken is APMV1. APMV2, APMV3, APMV6 and APMV7 also lead to
mild respiratory disease in chicken. ND virus has many strains which vary in pathogenecity on
the basis of which these are:
    1. Lentogenic ND virus: Pathogenesis is mild and used as vaccine e.g. B1, Lesota
    2. Mesogenic ND Virus: Moderate in pathogenecity e.g. Komorov, Mukteshwar. It can
        cause disease and kill young birds.
    3. Velogenic ND Virus: It is highly pathogenic virus. Mortality is upto 100%. There are two
        categories:
            a. Viscerotropic Velogenic NDV: respiratory problem, lesions in intestine
            b. Neurotropic valogenic NDV: nervous signs more
Only lentogenic and mesogenic strains are used for vaccine. Vaccine of VRI contains
mukteshwar strain. VVND (very virulent ND) is caused by viscerotropic and neurotropic strains.
                                        Prevalence
Disease is present worldwide even in pet birds, caged birds, and game birds. Most of the birds
have asymptomatic ND.
                                      Transmission
Horizontal transmission is by contact from one to other. Virus is secreted in nasal and ocular
discharge. Water vapours contain virus and other birds inhale. It is also excreted in fecal
material. Common feeder and waterer also spread virus. Virus is taken by strong wind.
Modes of Horizontal Transmission:
    o Movement of birds e.g. flying birds spread virus, even live chicken.
    o Movement f other animals like dog, cat; animal transport mechanically
    o Movement of equipments, utensils, poultry products, dead poultry, people (workers).
       (Egg trays are major source).
    o Air borne spread by wind to near by farm or shed not go beyond 500 meter.
    o Ingestion of contaminated feed and water
    o Poor quality or contaminated vaccines
There is no vertical transmission.

                                  Incubation Period
Incubation period varies from 2-15 days. It may vary but on an average 5-6 days. It is due to
different pathotypes/serotypes and chick immunity (varies with age). In case of velogenic it is 5-
6 days incubation period.
                                      Clinical Signs
Clinical signs vary with the pathogenecity of causative agent (different pathotypes).
Lentogenic NDV:
Adult bird:
There are no symptoms and no mortality. Clinically there may be mild drop in egg production,
mild respiratory signs (coughing, sneezing for 1-2 days then finishes). In some cases flock
produces soft shelled/deformed eggs. (In case IB there is wrinkled egg production) (Soft eggs
may also be due to calcium deficiency). In case of the presence of other diseases as coccidiosis,
mycoplasma, IB birds may show clinical signs.
Young Birds:
No sings to mild respiratory sings (gasping, sneezing, coughing, nasal discharge, and
lacrimation). The signs may be severe if chick is under stress or already suffering from some
other disease. Lentogenic strain is used as live vaccine.
Mesogenic strain:
Adult Birds:
There are no signs in healthy birds. In stress or with concurrent disease there may be respiratory
signs, drop in egg production, nervous signs (paralysis, twisting of neck etc.), soft shelled eggs.
There is no mortality. These viruses are also used in vaccine in older groups more than 8 weeks
of age.
Young Birds:
There are severe respiratory signs, nervous signs (prostration, paralysis, torticollis, and
opisthotonos) and marked decrease in egg production. Mortality is 50 % (0-50%).
Velogenic Strain:
Whether it is young or adult birds the disease is severe and appears suddenly. There are
respiratory signs (coughing, sneezing, ocular discharge etc.), nervous signs (opisthotonos,
torticollis, paralysis of wings/legs, prostration), swelling around the head, face, and eye, greenish
diarrhea (as bird is off feed and gall bladder is full). Mortality can be upto 100% in young birds
and 70-80% in adults. It is severe form of disease known as N.D. If we give Lesota vaccine in
case of ND attack, 35-100% flock will die within 5-6 days.
                                            Lesions
In lentogenic or mesogenic signs are minimum. There are air sacculitis, congestion of trachea,
conjunctivitis and proventriculus hemorrhages. Lesions become severe if suffering from other
diseases. If vaccination is carried out at 2-5 weeks in broiler birds and birds are suffering from
mycoplasma, Ecoli infection, they may show air sacculitis and it may leads to 5-20% mortality.
In velogenic there is congestion, tracheitis, air sacculitis; the very important lesion is ulcer in
intestine which are commonly oval to button shaped and covered with exudates and are visible
from outside. Yellowish exudates is due to bile color, if we remove the yellow exudates then the
below surface is red raw. The number of ulcers varies from 1- 10. These develop in area where
lymphoid tissue is present. There are hemorrhages on mucosa of proventriculus. Ceacal tonsils
are congested, necrotic, and hemorrhagic. In the beginning of ceaca, the raised areas present that
are lymphoid area, near it the signs are seen. Apart from these changes, the ova in hen are free
and flaccid and found in abdominal cavity. These ova may have hemorrhages, partially or
completely black. Muscles are congested, darker in appearance.
                                          Diagnosis
Tentative diagnosis is based on clinical signs. 90% cases can be confidently said as ND. But
these signs are also present in Avian influenza. Lesions are not pathognomonic. In Ghomboro
there are also lesions on proventriculus. So isolate and identify the virus for confirmation. Take
spleen, kidney, intestine, trachea (place of sample), do homogenization with PBS or normal
saline, add some antibiotic and inject it into 9-10 days old chick embryo. After 2-4 days embryo
will die; at the death collect the amniotic fluid.
Amniotic fluid + N.D antiserum + RBC; if agglutination does not occur, it means N.D virus is
present. If agglutination occurs then it is not ND virus.
Also confirm the pathotype of ND virus for this there are different tests as MDT (mean death
time), ICPT (intracerebral pathogenecity test), IVPT (intravenous pathogenecity test).
MDT: Inject fluid in embryo, candle after every 6-8 hours. Note after how much time embryo is
killed.
Lentogenic ≥ 90 hours
Mesogenic < 90 ≥ 60 hours
Velogenic ≤ 6o hours
                                         Prevention
Bio security and vaccination
Live (B1, Lasota) and killed vaccine (Mukteshwar). Live vaccine by eye drop orally, and spray
method. Killed vaccine by S/C or I/M
                                     ND in Pakistan
Disease is highly prevalent. Sporadic cases occur in every season everywhere. In every 2-3 years
there is epidemic of it. Biosecurity and vaccination is the way to prevent.
1 week: Live
2-3 week: Live or killed
6 week: Live or killed
Check haemagglutination inhibition titer in all birds. Use the killed vaccine in breeder flock as it
has long lasting effect.
                                         Treatment
Check secondary bacterial infection; if present, give antibiotics. If no bacterial infection, give
normal diet. Vitamin E is immunostimulant, give this. Give dry feed. During disease vaccination
is not recommended.
                                   Fowl Typhoid
It is caused by Salmonella gallinarum. It is an acute form leading to septicemia in growers and
adult birds and characterized by profuse bright sulfur yellow diarrhea, sleepiness and anemia of
comb or wattles which lead to pale color of comb and wattle.
S. gallinarum is gram negative, non motile, non spore forming, and do not produce toxins, can
not survive outside host. Direct sunlight can kill bacteria within one minute and if 60 oC
temperature then in 10 minutes. If your refrigerate salmonella infected carcass, it remains viable
for 16 months, in feces for 30 days, and in litter for 60-70 days. It can be easily destroyed by
phenol, KMNO4 and formalin
Epidemiology:
Turkeys, chicken, duck, pigeon, peafowl, sparrows and wild birds all are susceptible. There is
vertical Transmission and 80-90% eggs are infected. Droppings also infected so there is lateral
and horizontal transmission.
Clinical signs:
Incubation period is 4-6 days. There is perfuse sulfur colored diarrhea and it contains urates. This
type of diarrhea goes unnoticed. There is elevation of temperature upto 107 oC after two days of
the onset of diarrhea, increased thirst, uneasiness, muscular weakness. Comb in acute case
congested but in chronic cases pale and shriveled. After 7 days post infection diarrhea becomes
mucoid yellow and pasted in feathers of vent. Mortality from 4-50% but morbidity high. Arthritis
may occur. Course of disease in acute case is 48 hours, in subacute 5-6 days and in chronic cases
irregular.
Hematology shows anemia and leukocytosis upto 2-3 times than normal (due to increased
heterohylls).
Pathogenesis:
Organ enters through digestive system, then enters from lining of endothelium to blood, transient
septicemia, then localize in spleen and liver, and reticuloendothelial cells and multiply there,
then again bacteremic phase and lasts for weeks and formation of proliferative lesions. Infected
bird die within 5-9 days in susceptible birds and recovered birds become carrier.
Postmortem Lesions:
In peracute case no lesion. In acute case certain lesions which occur due to anemia as congested
skeletal muscles. Carcass has jaundice appearance with brownish appearance of serous
membrane. Feathers pasted with yellowish green feaces. Liver enlarged, dark red, friable,
congested and on exposure to air for short time its color is changed from greenish brown to
bronze color. This characteristic change is due to unexcreted bile from liver and it is
pathognomonic lesion.
Spleen is swollen and has white necrotic focci. There is catarrhal enteritis and nodules which are
yellowish, flat and irregular specially seen in duodenum and upper portion of ileum. If cut
nodules, leave ulcers covered with white yellowish mucoid exudate.
In chronic case carcass is emaciated and enemic. Heart has white nodules, pin head size to pea
size nodules and lead to myocarditis and pericarditis. In intestine there are irregular lumpy
greyish nodules. In ovary inflamed follicles and broken egg yolk present in peritoneal cavity.
Ova my be misshapened, degenerated and discolored. Lungs are edematous, congested and have
peculiar yellowish brown colour.
Diagnosis:
It is based on clinical signs, isolation and identification of organism from liver, spleen, and bone
marrow, lung heart, gizzard, yolk sac and serological test.
Differential diagnosis:
Fowl cholera - streaks of hemorrhages on the surface of liver not in fowl cholera.


                                            Surra
Causative Agent:
It is caused by T. evansi. It is transmitted by Tabanus fly. It can also affect cattle, sheep, and
buffalo. It is mild disease in cattle, sheep, and buffalo but in equine it is major disease.
Infect healthy animal and they become carrier for long period of time. They transfer this to
healthy animals. It is transmitted by fly or contaminated syringes.
Parasite enters blood orally, multiplies (inter-cellular parasite), and causes inflammatory changes
and anemia. Trypanosome affects bovines, humans, dogs, cats but in equine species more
prevalent. T evansi and T. equinim are transmitted by Tabaus fly. Others are transmitted by
Tsetse fly. But T. equiperdum does not require vector because it is venereal infection. Its
transmission from male to female and vice versa is through coitus. Disease caused by T. evansi is
known as Surra. Disease caused by T. equiperdum is called Dourine. Surra is more common in
African countries. In Africa it is called Murrina.
Immune mechanism varies with specie to specie. Trypanosome can change its body coat i.e.
glycoprotein. It has sets of amino acids which suddenly change according to immunity of body
and this character helps it to remain viable. It is of acute nature of disease particularly in horses
but it is of chronic nature in camel. T. equiperudm (Dourine) is common in horses, mules, and
donkeys but camel is resistant. Mortality is 100 % if animal is not treated. It could be 0 % if
treated timely. Morbidity varies form 20-70 %.
Clinical Findings:
There is intermittent fever (characteristic feature of parasitic or protozoal infection), progressive
anemia, edema of body parts, drowsiness, laziness, decreased appetite, and emaciation. Animal
would be having weak body condition. Edema is visible in testes of male and udder of mare.
Petechial hemorrhages on sclera. Whenever this parasite enters brain, nervous signs like ataxia,
in- coordinated body movements, convulsions, paraplegia, and paralysis appear. Death can occur
within few days to few months depending upon host capacity to fight. Edema may present in
limbs particularly forelimbs.
There are three forms: acute, subacute and chronic. Acute and subacute are common in equine.
Chronic form is more common in camels. There would be decreased milk production, exercise
intolerance, abortion; signs present throughout the year until untreated.
This organism remains in blood for many years in symbiosis without any descriptive clinical
picture but if stress then this parasite can cause infection. Symbiosis depends upon stress free
environment.
Diagnosis:
Make smear of fresh blood and see under microscope; flagellar structure in between cells and
have whip like movement.
Indirect: ELISA, CFT (best for this)
Treatment:
It is very difficult to treat because it can survive in cerebrospinal fluid.
Cymelarsin 0.3-0.6 mg per Kg. it is drug of choice.
Diaminazine (Pronil) 7 mg/Kg
Surramin 10 mg/Kg
Diaminazine and Surramin are not much effective as these can not cross blood brain barrier.
Cymelarsin can cross blood brain barrier. So it is drug of choice.
Antipyretic, fluid therapy (ringer lactate D), liquid diet.
Vitamin A, vitamin D.
Panamine G (amino acid, glucose, vitamins, fatty acid) (I/V)
Control:
Control fly


                                        Dourine
It is venereal disease transmitted by coitus. It is famous in Asia, Africa and South America. In
America it is called Mal de coit.
Etiology:
It is caused by T. equiperdum which belong to T. brucei. Mortality or morbidity is 50-75 %. In
endemic area infection is 50-75 %.
Transmission:
It is transmitted by coitus. It is present in male discharges particularly in semen and mucous
secretions. This parasite is inhabitant of vagina, urethra. Animal may be strong carrier. This
organism grows in genital organs and also comes to circulation. There is swelling of penis,
vulva, and vagina. It also affects the brain, incoordination and paralysis.
Clinical Findings:
Initially no clinical finding.
In genital form: Mucopurulent urethral discharge in female, edema of vulva, profused discharge,
and edema may extend to abdomen, udder and chest.
In cutaneous form there is sub cutaneous inflammation, urticarrial swelling develops on body
and neck and disappear within few hours or days. This is not consistent feature but they may be
present.
In third stage there is progressive anemia, weakness and nervous signs.
Diagnosis:
Direct by smear, indirect by CFT and ELISA.
Treatment:
Diaminizne 7mg/Kg
Surramine 10mg/Kg for 2-3 days.

Control:
Cull the animal
Better management.


                                           Nagana
Trypanosoma vivax causes disease in cattle and buffalo but also in horse. Disease is known as
Nagana in Africa. These disease spread by import but primary territory for it is African territory.
Clinical signs are anemia, jaundice and weakness.


                  Infectious Bursal Disease (IBD)
It also called Avian nephrosis or Ghomboro disease. This disease was first appeared in 1962 in
Ghomboro district of Delaware state of USA. IBD also taken as severe form of IB because sever
nephrosis is observed. It was first thought to be the variant of IB, later on it was declared as
independent virus. In 1972 it was told that it is immunosuppressive disease. Any disease can
attack at flock after IBD (ALLEN). Very virulent strains have been reported in various countries
of Asia, South America, and Africa.
IBD can be defined as it is a highly contagious disease of young chicks characterized by
inflammation followed by atrophy of bursa fabricious, nephrosis, variable degree of
immunosuppression and high mortality.
                                         Occurrence
Prime time for occurrence is 3-6 weeks of age of chick. But it may occur as long as bursa
fabricious is there i.e. 1-6 weeks.
                                            Etiology
It is caused by virus of Birnaviridae family; avibirnavirus which is double stranded RNA virus
(having 2 segments). It can easily be grown in chicken embryo. There are two serotypes of IBD
virus; type 1 is highly virulent and highly pathogenic. Type 2 is non virulent and non pathogenic.
Type1 leads to clinical disease.
The most important characteristic of virus is that it is highly resistant to most of the disinfectants
and environmental factors; even it can survive at 50 oC and 0.5 % phenol solution can not kill it.
More than 70 oC temperature can kill it but it is not completely eradicated. Formalin and iodine
originated disinfectants can kill this virus. It can persist for months in poultry litter, feed,
waterer, and contaminated houses.
                          Distribution & Transmission
It is worldwide distributed disease. It can spread rapidly by contaminated fomites and infected
and contaminated birds. There is no vertical transmission and no carrier stage of poultry.
                                     Susceptible Host
3-6 weeks of age of chicken (clinical disease appear at this stage). Before 3 weeks there is sub
clinical IBD. It can hit the flock as long as functional bursa is present in bird. In layer flock IBD
is clinically more severe in White leghorn as compared to broiler. There are no clinical signs in
turkey.
                                   Incubation Period
Incubation period is 2-3 days.
                                    Clinical Findings
Vent picking (sometimes electrolyte deficiency leads to this problem so give NaCl and you may
also give green fodder or put piece of red color cloth to make birds allentoic from picking).
There is white chalky watery diarrhea, anorexia, depression, ruffled feathers, trembling and
mortality. Bird sits on hock joint (in E.coli problem birds also sit but here it is weak and
dehydrated but in IBD it looks healthy). Bird also shows high fever because of viremia. In winter
bird feels more cold weather. Morbidity is 100 % and mortality is 20-30 %, mortality starts 3
days post infection and remains upto 7-8 days.
                                      Gross Lesions
Discoloration of pectoral muscles, deep hemorrhages in pectoral and thigh muscles, nephritis
(severely swollen kidneys), urates present in ureter, bursa is swollen and edematous,
hemorrhagic and later on atrophied. There are sequential changes in bursa (course of disease is 7-
8 days); after 3 days bursa size increases due to edema, then it go on increasing upto 5 th day post
infection that is double of day 3rd. There will be cheesy material in bursal folds which are
hemorrhagic. After that size decreases and at day 8 the size of bursa is of 1/3rd of that of original
size.

                                Microscopic Changes
Day 1-3 there is necrosis and degeneration of lymphocytes. Lymphocytes are replaced by
heterophills. Pyknotic nuclei are present. Fibroblast proliferation takes place. Sometimes
apoptotic bodies are present. In kidney there are pyknotic changes in tubules and then
karyorrhexis (fragment formation). Urinary space increases in bowman capsule.
                                 Immunosuppression
If chicks are infected at 1st week of age, there is sever immunosuppression. At 3-4 weeks of age
immunosuppression is moderate but these chicks are susceptible to ND, ID, and adenovirus
infection. Passive immunity is of more importance. If parent flock is vaccinated then it can
protect the progeny upto 2-3 weeks of age. If parent flock is not immunized then chicks should
be vaccinated at hatch.
                                Differential Diagnosis
From IB, ND and coccidiosis.
                                 Preventive Measures
There are three types of vaccines. Intermediate, intermediate + and killed. First two are live
vaccines. In Broiler two vaccines of IBD; first shot of intermediate vaccine at 8-10 day of age
and second shot of intermediate plus (hot) at 16-18 or 20 day. Hot strain can also cause disease
which occurs when there is sub-clinical disease. If chances of disease are more then killed
vaccine can be used. It is where the continuous threat of the disease is present.
Sub clinical disease may act as the vaccine. Give any immunostimulant e.g. dry milk (contains
casein) and increase energy. Anti coccidial can be given. In case of IBD do not give
sulfonamides. Toltrazuril (tolox or Kepox) or amprollium can be given which does not damage
kidney. Casein is good for the growth of Emeria so we have to give for 2-3 days. Check for the
root cause of mortality. Priming for killed vaccine is done by live vaccine 2 days at least before.
                         Schedule of Vaccine in Broiler
4-5 day        ND + IB         eye drop
8-10 day       IBD             eye drop or drinking water
16-18 day      HPS            S/C or I/M
20 day         IBD            drinking water
23 day         ND Lesota      drinking water
32 day         ND Lesota      drinking water



                                        Botulism
Botulism is and intoxication (infection of perform toxin) not an infection. It is caused by the
ingestion of toxin in food
Etiology:
Cl. botulinum is anaerobic spore forming. clostridium spores are lethal in vdgetation form.
Strain of Cl. Botulinum: there are seven types A, B c1, E, F, and G. Most susceptible type is
Type A. it is found in neutral and alkaline soil. Type D is found in alkalinesoil while type B & E
are found in damp soil. Type G is found in acidic soil.
Sources: the usual source of the toxin is decaying carcasses or vegetable materials such as
decayng grass, hay,grain, spoiled silage, and cane food.
Toxificatious Botulism
this name is given to the disease in which C. botulinum grows in tissues of a living animal and
produces toxins there. The toxins are liberated during the Shaker foal syndrome.
Pathogenesis:
Toxin is the neurotoxic.
Prefoemed toxin → Blood → Neuromuscular junction → block of ACH → flaccid Paralysis
There will be paralysis of hind quarter
Chances of hind quarter → fore quarter → neck → movement of eye ball and head and medriasis
is frequent.
Diagnosis:
 History.
Treatment:
We give drug which counteract the blockage of ACH Guanidine HCl (11 mg/Kg).
Antiserum is also given
Control:
Dietary deficiency should be fulfilled, and carcass should be disposed off.decaying grass and
spoiled silage should not be offered.


                                 Compylobacteriosis
Gastrointestinal campylobacteriosis, caused by Campylobacter jejuni or C coli , is associated
with diarrhea in various animal hosts, including dogs, cats, calves, sheep, ferrets, mink, several
species of laboratory animals, zoo animals, and humans. In humans, it is a leading cause of
diarrhea. C jejuni and C coli are also recovered from feces of asymptomatic carriers. (See also
bovine genital campylobacteriosis, Bovine Genital Campylobacteriosis: Introduction). Animals,
including dogs and cats (especially those recently purchased from shelters), and wild animals
maintained in captivity can serve as sources of human infection. The agents also are isolated
frequently from the feces of chickens, turkeys, pigs, and other species. The organism commonly
contaminates poultry meat, which serves as one of the major vehicles of spread of C jejuni to
humans.
The disease is found worldwide; its prevalence appears to be increasing as proper culture
techniques for C jejuni and C coli are refined and updated. Clinical manifestations may be more
severe in younger animals. In studies using monoclonal and polyclonal antibodies,
Campylobacter spp (including C jejuni ) have been associated with proliferative ileitis in
hamsters and proliferative colitis in ferrets. A cause and effect relationship has not been proved
experimentally, however. Proliferative bowel disease in these animals is now known to be
caused by Lawsonia intracellularis .
Etiology:
 Campylobacter is a gram-negative, microaerophilic, slender, curved, motile bacterium with a
 polar flagellum. C jejuni is routinely associated with diarrheal disease; however, C coli ,
 distinguished from C jejuni on the basis of hippurate hydrolysis, is occasionally isolated from
 diarrheic animals and is routinely recovered from asymptomatic pigs. Other intestinal, catalase-
 negative campylobacters, C upsaliensis and C helveticus , have been isolated from diarrheic
 dogs and cats as well as asymptomatic dogs and cats. Campylobacter was once associated with
 swine dysentery ( Swine Dysentery), but this is now recognized as being caused by Treponema
 hyodysenteriae . Most believe that Campylobacter spp do not produce porcine proliferative
 enteritis ( Porcine Proliferative Enteritis), even though a new organism, C hyoilei , isolated
 from swine in Australia, has been associated with porcine proliferative enteritis. Its role in this
 disease, however, is not clearly established. C mucosalis and C hyointestinalis have also been
 isolated from swine but are not considered enteric pathogens.
Because of slow growth and microaerobic requirements, standard culture methods require
selective media that incorporate various antibiotics to suppress competing fecal microflora. C
jejuni and C coli grow well at 42°C in an atmosphere of 5-10% carbon dioxide and an equal
amount of oxygen. Cultures are incubated 48-72 hr; colonies are round, raised, translucent, and
sometimes mucoid. The organism can be identified by a series of biochemical tests readily
available in any diagnostic laboratory. Recently, PCR assays have been used to identify
Campylobacter spp . Identification is important to distinguish campylobacters from the growing
number of novel enterohepatic helicobacters being isolated from a variety of animals.
Transmission and Epidemiology:
As with most intestinal pathogens, fecal-oral spread and food- or waterborne transmission
appear to be the principal avenues of infection. One suspected source of infection for pets, as
well as mink and ferrets raised for commercial purposes, is ingestion of undercooked poultry
and other raw meat products. Asymptomatic carriers can shed the organism in their feces for
prolonged periods and contaminate food, water, milk, and fresh processed meats (including
pork, beef, and poultry products). The organism can survive in vitro at 41°F (5°C) for 2 mo and
can survive in feces, milk, water, and urine. Wild birds also may be important sources of water
contamination. Unpasteurized milk has been cited as a principal source of infection in several
human outbreaks. Strain identification to study the epizootiology of C jejuni and C coli , in
addition to Penner serotyping, is now done using molecular techniques such as restriction
fragment length polymorphism and ribotyping.
Clinical Findings:
The diarrhea appears to be most severe in young animals. Typical signs in dogs include mucus-
laden, watery, and/or bile-streaked diarrhea (with or without blood) that lasts 3-7 days; reduced
appetite; and occasional vomiting. Fever and leukocytosis may also be present. In certain cases,
intermittent diarrhea may persist >2 wk; in some, it may be present for months. Gnotobiotic
puppies inoculated with C jejuni developed malaise, loose feces, and tenesmus within 3 days of
inoculation.
In calves, signs vary from mild to moderate. The diarrhea is thick and mucoid with occasionally
visible blood flecks; body temperature may be normal. Diarrhea with mucus and blood also has
been observed in primates, ferrets, mink, and cats. Organisms with ultrastructure similar to that
of Campylobacter spp have been seen in hyperplastic ileal epithelial mucosa of hamsters with
proliferative ileitis; C jejuni has been isolated from these lesions but has failed to reproduce the
syndrome. Organisms with Campylobacter -like morphology also have been associated with
proliferative colitis in ferrets and with hyperplastic intestinal lesions in guinea pigs and rats.
Campylobacter -like organisms have been described in young rabbits with acute typhlitis. It is
now known that these organisms are Lawsonia intracellularis , an organism closely related to
Desulfovibrio spp
Lesions:
In 3-day-old chickens infected with C jejuni , the organisms were detected within epithelial
cells and mononuclear cells of the lamina propria; the jejunum and ileum were the most
severely affected. Congested and edematous colons were found in dogs 43 hr after inoculation;
microscopically, epithelial height, brush border, and numbers of goblet cells in the colon and
cecum were all reduced. Hyperplastic epithelial glands resulted in a thickened mucosa.
Histologic changes in calves primarily involve the jejunum but also can involve the ileum and
colon. The lesions vary from mild changes to severe hemorrhagic enteritis. The mesenteric
lymph nodes are edematous. Experimentally, some strains of C jejuni produce a hepatitis in
mice, and the organism has been isolated from inflamed livers of dogs. A cytotoxin, referred to
as cytolethal distending toxin, has been identified in C jejuni ; however, its role in production of
intestinal disease is not known. In vitro, the cytotoxin causes distention of cell lines and cell
cycle arrest in the G2M1 phase of the cell cycle.
Diagnosis:
The standard method for diagnosis is microaerobic culture of feces at 42°C; a special medium is
commercially available. Diagnosis is also possible by using darkfield or phase-contrast
microscopy, by which fresh fecal samples are examined for the characteristic darting motility of
C jejuni . This method is especially useful during the acute stage of diarrhea when large
numbers of organisms are more likely to be shed in the feces. Various techniques can detect
serum antibodies to various antigens of Campylobacter spp . Heat-stable or heat-labile antigen
schemes are used routinely to serotype various strains. Serial serum samples to demonstrate
rising antibody titers are helpful in diagnosis. Intestinal viruses and other intestinal bacterial
pathogens must be ruled out as primary or copathogens in animals with Campylobacter -
associated diarrhea.
Treatment and Control:
Isolation of C jejuni or C coli from diarrheic feces is not, in itself, an indication for antibiotic
therapy. Because C jejuni and C coli are not routinely cited as potential intestinal pathogens in
animals (except for diarrhea in young cats and dogs and in several species of primates), efficacy
of antibiotic therapy has been reported infrequently. In certain cases in which animals are
severely affected or are a zoonotic threat, antibiotic treatment may be indicated. In general, C
jejuni and C coli isolates from animals are similar to isolates obtained from human populations.
Erythromycin, the drug of choice for Campylobacter diarrhea in humans, is also effective in
other animals, although erythromycin-resistant strains of Campylobacter spp have been
recovered from swine. Gentamicin, furazolidone, and doxycycline also can be used. Ampicillin
is relatively inactive against most strains of Campylobacter , and most strains are also resistant
to penicillin. Tetracycline and kanamycin resistance in certain C jejuni strains is reported to be
plasmid-mediated and transmissible within C jejuni serotypes. Efficacy of sulfadimethoxine and
sulfa combinations is variable. Before therapy is instituted, isolation and sensitivity tests should
be done. Some animals continue to shed the organism despite antibiotic therapy. Quinolone
antibiotics may be useful in eliminating C jejuni and C coli in asymptomatic carriers, but drug
resistance may develop.
                                 Clostridium Botulinum
Botulism is a rapidly fatal motor paralysis caused by ingestion of the toxin of Clostridium
botulinum . The organism proliferates in decomposing animal tissue and sometimes in plant
material.
Etiology:
Botulism is an intoxication, not an infection, and results from ingestion of toxin in food. There
are 7 types of C botulinum , differentiated on the antigenic specificity of the toxins: A, B, C 1,
D, E, F, and G. Types A, B, and E are most important in botulism in people; C 1 in most animal
species, notably wild ducks, pheasants, chickens, mink, cattle, and horses; and D in cattle.
Only 2 outbreaks, both in humans, are known to have been caused by type F. Type G, which
was isolated from soil in Argentina, is not known to have been involved in any outbreak of
botulism either in humans or other animals. The usual source of the toxin is decaying carcasses
or vegetable materials such as decaying grass, hay, grain, or spoiled silage. Toxins of all types
have the same pharmacologic action. Like tetanus toxin, botulinum toxin is a zinc-binding
metalloprotease that cleaves specific proteins in synaptic vesicles.
The incidence of botulism in animals is not known with accuracy, but it is relatively low in
cattle and horses, probably more frequent in chickens, and high in wild waterfowl. Probably
10,000-50,000 birds are lost in most years, with losses reaching 1 million or more during the
great outbreaks in the western USA. Most affected birds are ducks, although loons,
mergansers, geese, and gulls also are susceptible. (See also botulism in poultry, Botulism:
Introduction.) Dogs, cats, and pigs are comparatively resistant to all types of botulinum toxin
when administered orally.
Most botulism in cattle occurs in South Africa, where a combination of extensive agriculture,
phosphorus deficiency in soil, and C botulinum type D in animals creates conditions ideal for
the disease. The phosphorus-deficient cattle chew any bones with accompanying bits of flesh
that they find on the range; if these came from an animal that had been carrying type D strains
of C botulinum , intoxication is likely to result. A gram or so of dried flesh from such a carcass
may contain enough toxin to kill a mature cow. Any animal eating such material also ingests
spores, which germinate in the intestine and, after death of the host, invade the musculature,
which in turn becomes toxic for other cattle. Type C strains also cause botulism in cattle in a
similar fashion. This type of botulism in cattle is rare in the USA, although a few cases have
been reported from Texas under the name of loin disease, and a few cases have occurred in
Montana. Hay or silage contaminated with toxin-containing carcasses of birds or mammals and
poultry litter fed to cattle have also been sources of type C or type D toxin for cattle. Botulism
in sheep has been encountered in Australia, associated not with phosphorus deficiency as in
cattle, but with protein and carbohydrate deficiency, which results in sheep eating carcasses of
rabbits and other small animals found on the range. Botulism in horses often results from
forage contaminated with type C or D toxin.
Toxicoinfectious botulism is the name given the disease in which C botulinum grows in
tissues of a living animal and produces toxins there. The toxins are liberated from the lesions
and cause typical botulism. This has been suggested as a means of producing the shaker foal
syndrome. Gastric ulcers, foci of necrosis in the liver, abscesses in the navel and lungs,
wounds of the skin and muscle, and necrotic lesions of the GI tract are predisposing sites for
development of toxicoinfectious botulism. This disease of foals and adult horses appears to
resemble ―wound botulism‖ in humans. Type B toxin is often implicated in botulism in horses
and foals in the eastern USA.
Botulism in mink usually is caused by type C strains that have produced toxin in chopped raw
meat or fish. Type A and E strains are occasionally involved. Botulism has not been reported in
cats but occurs sporadically in dogs. Type C toxin is usually responsible, but there have been
reports in which type D was incriminated.
Clinical Findings and Lesions:
The signs of botulism are caused by muscle paralysis and include progressive motor paralysis,
disturbed vision, difficulty in chewing and swallowing, and generalized progressive weakness.
Death is usually due to respiratory or cardiac paralysis. The toxin prevents release of
acetylcholine at motor endplates. Passage of impulses down the motor nerves and contractility
of muscles are not greatly hindered; only the passage of impulses from nerves to motor
endplates is affected. No characteristic lesions develop, and pathologic changes may be
ascribed to the general paralytic action of toxin, particularly in the muscles of the respiratory
system, rather than to the specific effect of toxin on any particular organ.
Epidemics have occurred in dairy herds in which up to 65% of adult cows developed clinical
botulism and died 6-72 hr after the onset of recumbency. Major clinical findings included
drooling, inability to urinate, dysphagia, and sternal recumbency that progressed to lateral
recumbency just before death. Skin sensation is usually normal, and withdrawal reflexes of the
limbs are weak. Initially, clinical signs resemble second-stage milk fever ( Parturient Paresis
in Cows), but the cows do not respond to calcium therapy.
In the shaker foal syndrome, foals are usually <4 wk old. They may be found dead without
premonitory signs; most often, they exhibit signs of progressive symmetric motor paralysis.
Stilted gait, muscular tremors, and the inability to stand for >4-5 min are salient features. Other
clinical signs include dysphagia, constipation, mydriasis, and frequent urination. As the disease
progresses, dyspnea with extension of the head and neck, tachycardia, and respiratory arrest
occur. Death occurs most often 24-72 hr after the onset of clinical signs. The most consistent
necropsy findings are pulmonary edema and congestion and excessive pericardial fluid, which
contains free-floating strands of fibrin.
Diagnosis:
Although sporadic cases of botulism often are suspected because of the characteristic motor
paralysis, it is sometimes difficult to establish the diagnosis by demonstrating the toxin in
animal tissues or sera or in the suspect feed. Commonly, the diagnosis is made by eliminating
other causes of motor paralysis. Filtrates of the stomach and intestinal contents should be
tested for toxicity in mice, but a negative answer is unreliable. Primary supportive evidence is
provided by feeding suspect material to susceptible animals. In peracute cases, the toxin may
be detectable in the blood by mouse inoculation tests but usually is not detectable in the
average field case in farm animals. Use of ELISA methodology for detection of the toxin
makes it feasible to test large numbers of samples, increasing the chances of diagnosis
confirmation. In toxicoinfectious botulism, the organism may be cultured from tissues of
affected animals.
Control:
Any dietary deficiencies should be corrected and carcasses disposed of, if possible. Decaying
grass or spoiled silage should be removed from the diet. Immunization of cattle with types C
and D toxoid has proved successful in South Africa and Australia. Toxoid is also effective in
immunizing mink and has been used in pheasants.
Botulinum antitoxin has been used for treatment with varying degrees of success, depending on
the type of toxin involved and the species of host. Treatment of ducks and mink with type C
antitoxin is often successful; however, such treatment is rarely used in cattle. Treatment with
guanidine hydrochloride, 11 mg/kg body wt, has been reported to overcome some of the
paralysis caused by the toxin; however, its use has not been extensive enough to determine its
value.
                                           Ticks Control
    Ticks are economically important in cattle and livestock species. These are vectors for parasites
      like babeisia, theileria, anaplasma, rickettsia; virus like Crimean Congo Hemorrhagic Fever;
      bacteria like pasterurella, brucella, listeria, staphylococcus. Ticks are also blood suckers. Ticks
      belonging to genus Ixodes and Ornithodorus are associated with tick paralysis because of toxin
      is released from ticks. Important species of ticks are Boophilus, Hyaoloma, Rhipicephalous,
      Amblyomma.
    Ticks show a variety of host contact pattern during their life cycle.
    One host tick: Boophilus, each developmental stage feeds upon same host.
    Three host species: Hyalomma, complete different larval stages on different hosts.
   Control Strategies:
    Housing of animals in tick proof buildings. Cracks and crevices are big source of ticks for this
      purpose caulking (tape) of wall and roof is done.
    Herbage and wastage of farm (dung) should be burned slowly and by the smoke produced the
      ticks are killed.
    Separate housing of cattle and buffalo. Cattle are more susceptible but if kept together, buffalo
      may also get infestation due to stress.
    Sahiwal cattle is resistant to ticks due to some factors like its skin moves, hairs are short, and
      straight and secretion from skin (sebaceous).
    Pasteur of grazing of cattle and buffalo should also be separated.
    Quarantine measures; new animal in herd should be kept separately first and observed for any
      disease.
    Manual removal of ticks but do not twist it in hand because it causes Crimean Cango
      Hemorrhagic Fever in humans. Always remove ticks with forceps in anti-clock wise direction.
    Clearance of vegetation.
    Use of Acaricides, in the form of dip, injection, pour on, ear tags etc
    For dips different preparations like Ecofleeece: 2 ml/2 litres water, Cypermethrin: 2 ml/2 litres
      water, delta 25 (deltamethrin 2.5 %): 2 ml/litre, Negovan (organophosphate),
    Ivomec: 1 ml/50 Kg or 200 µg/Kg s/c.
     Tick vaccines are available but not in Pakistan. Tick guard vaccine prepared in Australia,
         Endosymbiotic relationship can be broken down. Some fungus if grown in Pasteur then the
         larval stages of tick can be controlled. Similarly in body there are some microorganisms which
         are useful for ticks; if we control them, we can control ticks.
     Development of resistant tick breeds.
     Ethnoveterinary Practices:
Salt is applied on body of animal. Taramira oil mixed in simple oil and applied on body or 250 mg of
terpentine is soaked in water and next morning mix with ice or cold water and 100 g salt is added and
applied to animals.
osteomalacia and there is development of fracture.
Treatment:
Carbonate of iron: 120 g
Finely ground bone meal: 500 g
Common salt: 240 g
Powdered gention: 140 g
Fenugreek 140 g
Equally mix these and a full table spoon is given 3 times daily.
Vitomineral D is given.

				
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