Internship

These Contents are not included in these Notes,

Please study from some other source.

 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 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 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 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 4-5 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.