Prevention Of Coccidia in Poultry - Solveda · 2019-11-03 · Nicarbazine enters coccidia cells and...

Prevention Of Coccidia in Poultry

› Coccidia life cycle

› Anticoccidials and prophylactic use

› Anticoccidial drugs

› Classification of anticoccidial drugs

› Anticoccidials and resistance

› Overcoming resistance

› Coccidia life cycle

› Anticoccidials and prophylactic use

› Anticoccidial drugs

› Classification of anticoccidial drugs

› Anticoccidials and resistance

› Overcoming resistance

Coccidia Life Cycle

› Life cycle of avian coccidian consists of 2 asexual cycles, whichcollectively require one or more days, and one sexual cycle.

› The life cycle consist of various stages which involve oocyst-sporozites-trophozoites-schizonts

1. Completion of 1st asexual cycle:

– Merozoites-trophozoites-schizonts

2. Completion of 2nd asexual cycle:

– Merozoites-formation of male and female gametes

3. Sexual cycle:

– Sporulating oocyst (outside the host).

Cont. …

› Whole life cycle requires 7 days for completion.

› The short life cycle and large number of sporulating oocyst ofparasites helps in increasing the chance of contamination to alarge population.

› Coccidia life cycle

› Anticoccidials and prophylactic use

› Anticoccidial drugs

› Classification of anticoccidial drugs

› Anticoccidials and resistance

› Overcoming resistance

Anticoccidials … Prophylactic Use

› Anticoccidials are given in the feed to:

1. Prevent disease

2. Minimize the economic loss often associated with sub acuteinfection.

› Prophylactic use is preferred, over treatment, because;

1. Most of the damage occurs before clinical signs becomeapparent.

2. Drugs can’t completely stop an outbreak.

Cont. …

› Most of the anticoccidials show their greatest efficacy against the1st and 2nd asexual cycle.

› Some anticoccidials show strong activity during the sexual cycle i.eday 5 and 6.

› During these days signs of anorexia and hemorrhage appear, so initiatinganticoccidials treatments during these days will provide more benefit.

› Few anticoccidials disturb the chemical metabolic pathway bywhich the drug block the specific stage of the parasite.

Cont. …

› Anticoccidials are used usually in starterrations for meat type birds raised underfloor-pen management.

Anticoccidials and Immunity

› Birds develop natural immunity against coccidia upon exposure.

› The natural development of immunity against coccidiosis mayproceed during the use of anticoccidials in the feed.

Cont. …

› In broiler, due to their short grow-outperiod, development of immunity may beof little consequence.

Cont. …

In replacement layer pullets,

› Natural immunity is important because they arelikely to be exposed to coccidial infections forextended periods after termination ofanticoccidial drugs.

Cont. …

› Anticoccidial programs for layer and breeder flocks are intended toallow immunizing infection while guarding against acute outbreaks.

› Coccidia life cycle

› Anticoccidials and prophylactic use

› Anticoccidial drugs

› Classification of anticoccidial drugs

› Anticoccidials and resistance

› Overcoming resistance

Anticoccidial drugs

› Anticoccidial drugs may be;

1. Coccidiostatic, in which growth of intracellular coccidia isarrested but development may continue after drug withdrawal.

2. Coccidiocidal, in which coccidia are killed during theirdevelopment.

Cont. …

› Some anticoccidial drugs may be coccidiostatic when given shortterm, but coccidiocidal when given long term.

› Most anticoccidials currently used in poultry production arecoccidiocidal.

Selecting Anti-coccidial

Selection of an anticoccidial is based on;

1. The ability of the drug to:– Improve weight.

– Improve feed conversion.

– Suppress the development of lesions.

2. Presence of drug residues in eggs and milk.

3. The emergence of drug resistant strains of coccidia.

› Coccidia life cycle

› Anticoccidials and prophylactic use

› Anticoccidial drugs

› Classification of anticoccidial drugs

› Anticoccidials and resistance

› Overcoming resistance

Classification Of Anticoccidials

Anticoccidials are classified as;

1. Ionophores

› They are the fermentation products of Streptomyces and otherfungi species.

2. Chemicals

› They are synthetic.

Ionophores

› Monovalent:1. Salinomycin (Salinomax®/Bio-Cox®, Sacox®, Kokcisan®)

2. Monensin (Elancoban®, Coxidin®)

3. Narasin (Monteban®)

› Monovalent glycoside:1. Maduramicin (Cygro®)

2. Semduramicin (Aviax®)

› Divalent:1. Lasalocid (Avatec®)

Chemicals

1. Robenidine (Robenz/Cycostat®)

2. Diclazuril (Clinacox®)

3. Nicarbazin + Narasin (Maxiban®)

4. Decoquinate (Deccox®)

5. Nicarbazin

Ionophores

The ionophores

They are:1. Monensin

2. Salinomycin

3. Lasalocid

4. Narasin

5. Maduramicin

6. Semduramicin

Ionophores Therapeutic Conc.

Drug Use Level (% in feed)Withdrawal

Time (days)

Monensin 0.01–0.0121 0

Narasin 0.006–0.008 0

Narasin + Nicarbazin 0.003–0.005 (of the combination) 5

Salinomycin 0.0044–0.0066 0

Semduramicin 0.0025 0

Lasalocid 0.0075–0.0125 3

Maduramicin 0.0005–0.0006 5

Cont. …

› They are extensively used as anticoccidials.

› Monensin, Lasalocid and Salinomycin are the Ionophores which areused commercially

› Monensin is choice of product for broiler chickens mainly becauseof its broad spectrum activity against majority of pathogenicspecies of coccidian and lack of development of drug resistance.

Mechanism of Action

1. Ionophores facilitate transport of Na+ ion into cells and elevatesthe intracellular concentration of Na+ ion.

2. This increased concentration of Na+ ion:

a) Inhibits certain mitochondrial functions such as substrate oxidationand ATP hydrolysis.

b) Creates osmotic difference and attract water to enter the cell.

3. Intracellular Na+ ion exchanges for extracellular Ca++

› Increases intracellular concentration of calcium ions lead tocytotoxicity.

Cont. …

› In addition some drugs directly facilitates Ca++ transport in cellsand increased intracellular concentration of Ca ++ in cardiac andskeletal muscle cells are responsible for its toxic effects in cells.

Cont. ...

Na+ - K+ - pump

Na+

Na+ - K+ - pump

K+

Osmotic Pressure

Ionophore

Na+, K+

H2O Osmosis

Destruction by

Bursting

Normal

situation

Ionophore

Na+, K+

Na+, K+

Na+, K+ Na+, K+

Na+, K+Na+, K+

Spectrum

› The ionophores affect both extra- and intracellular stages of theparasite, especially during the early asexual stages of parasitedevelopment.

Drug Tolerance

› Drug tolerance was slow to emerge in chicken coccidia, probablybecause of the biochemically nonspecific way these fermentationproducts act on the parasite.

› Recent surveys suggest that drug tolerance is now widespread, butthese products remain the most important class of anticoccidials.

Hazard effect

› Some ionophores may depress feed consumption when the dosageis above recommended levels.

Monensin

Origin

› It is a fermentation product of Streptomyces cinnamonensis and the1st antibiotic used as an anticoccidials due to its broad spectrumactivity.

Cont. …

Activity

› It acts on trophozoites and 1st generation schizonts.

› Its activity is generally within the first 2 days of life cycle ofcoccidian.

› This drug has ability to form complexes with sodium andpotassium ions in the host and the developing parasite.

› This monensin-cation complex renders membrane permeability tosodium and potassium ions.

Cont. …

Inclusion rate

› It gives protection against all species at 0.01 - 0.121% concentration in the feed.

Other actions

› It increases the weight gain and feed conversion and in some cases causessuppression of necrotic enteritis.

› It is superior over amprolium, clopidol and zoalene in control of coccidiosis.

Lasalocid

Origin

› It is another fermentation product and has a high degree ofanticoccidials activity.

Inclusion rate

› It is effective at 0.005-0.0075% concentration.

Cont. …

Other actions

› It increases weight gain, feed conversion and reduces the lesion insevere coccidiosis

› It has different ionic affinities and accepts divalent cations as wellas monovalent ions.

Salinomycin

Origin

› It was isolated from a culture of Streptomyces albus.

› It is more closely related to monensin than lasalocid. The ionic affinity is similarto that of monensin i.e. sodium and potassium ions.

Inclusion rate

› It has anticoccidials activity at 0.01 % in the feed and it was as effective as0.0121% monensin in controlling coccidiosis

Maduramicin

Origin

› It is most potent among the polyether Ionophores.

Inclusion rate

› It is given at 5-6 ppm in feed and activity is similar to that of other Ionophores

› Problem of these Ionophores is that they may cause severecardiovascular defects in animals.

Chemicals

Chemicals for Prevention of Coccidiosis in Chicken

Drug Use Level (% in feed) Withdrawal Time (days)

Amprolium 0.0125–0.025 0

Amprolium + ethopabate 0.0125–0.025 + 0.0004–0.004 0

Clopidol or meticlorpindol 0.0125–0.025 0

Decoquinate 0.003 0

Diclazuril 0.0001 0

Dinitolmide (zoalene) 0.004–0.0125 0

Halofuginone hydrobromide 0.0003 4–7

Robenidine hydrochloride 0.0033 5

Sulfadimethoxine + ormetoprim 0.0125 + 0.0075 5

Nicarbazine

› Nicarbazin was the first product to have truly broad-spectrumactivity and has been in common use since 1955.

› It is used principally as a prophylactic

› Nicarbazine has a broad spectrum activity against all Eimeria spp.

› Therapeutic dose lies near the toxic dose.

Cont. …

Mode Of Action

1. Nicarbazine enters coccidia cells and paralyze the intracellularenergy-supplying ATP.

2. Leads to the interruption of cellular energy supply and the ceaseof function of sodium-potassium ion pump.

3. Results in the abundant influx of sodium ions and with them theinflux of abundant water which causes the intracellular imbalanceof ions in the coccidia cells or the rupture of the cells and thedeath of coccidia occurs.

Cont. …

› Nicarbazine has coccidiocidal activity, mainly against the schizontswhich appear after the 1st generation.

› Marked inhibitory effect on the second generation schizonts andmoderate action on the sexual stages have been reported byMcLoughlin and Wehr.

Cont. …

Therapeutic concentration

› It is incorporated into feed to bring a final concentration of 0.0125%.

Resistance

› Some strains of coccidia which have become resistant to otherdrugs remain sensitive to nicarbazin.

Cont. …

Broilers

› The drug is suitable for administration to broiler flocks.

› 4 day withdrawal of nicarbazin is required before marketing.

› Losses from heat stress may occur in broilers if they aremedicated with nicarbazin.

Cont. …

Layers

› It reduces both egg production.

› Reduce hatchability.

› Causes depigmentation of eggs.

› Cause mottled egg yolk.

› It should not be used for laying hens.

Robenidine

Mode of action

› It allows initial intracellular development of coccidia but preventsformation of mature schizonts.

› It is coccidiostatic when given short term and coccidiocidal longterm.

› Drug resistance may develop during use.

› A 5-day withdrawal period is needed to eliminate untoward flavorcaused by residues in poultry meat.

Diclazuril and Toltrazuril

› Diclazuril and toltrazuril are highly effective against a broadspectrum of coccidia.

› Diclazuril is used mostly for prevention at 1 ppm in the feed,whereas toltrazuril is used primarily for treatment in the water.

› Coccidia life cycle

› Anticoccidials and prophylactic use

› Anticoccidial drugs

› Classification of anticoccidial drugs

› Anticoccidials and resistance

› Overcoming resistance

Anticoccidials and Resistance

› Continuous use of anticoccidial drugs promotes the emergence ofdrug-resistant strains of coccidia.

› While there is little cross-resistance to anticoccidials with differentmodes of action, there is widespread resistance to most drugs.

› Coccidia can be tested in the laboratory to determine whichproducts are most effective.

Cont. …

Reduced sensitivity/resistance

› After some time of use the efficacy of anticoccidials decreases.

Parasite

population

Anticoccidial X

No

anticoccidial

(Mathis et al., 1984; Chapman, 2007)Level of sensitivity

High Low

Timing of Resistance Development (theoretic timeline)

0

20

40

60

80

100

120

Time

Efficacy

Chemical

Ionophore

Reduced Sensitivity/Resistance

› After some time of use, the efficacy of anticoccidial decreases.

Cross-resistance

› If resistance to one product arises, other similar products will alsowork less efficient.

Cross Resistance?

Chemicals:› All have very different targets to kill parasite.

› No occurrence of cross-resistance.

Ionophores:› Have a common mode of action.

› Cross-resistance can be a problem.

› However, big differences between ionophores of different classes →

implications for cross-resistance !!!

› Coccidia life cycle

› Anticoccidials and prophylactic use

› Anticoccidial drugs

› Classification of anticoccidial drugs

› Anticoccidials and resistance

› Overcoming resistance

Overcoming Resistance

› Resistance presents a major problem.

› Various programs are used in attempts to slow or stop selectionof resistance.

Cont. …

For instance, producers may either use:

1. Rotation program

› They use one anticoccidial continuously through succeeding flocks, changeto alternative anticoccidials every 4–6 months

2. Suttle program

› Change anticoccidials during a single grow-out

Shuttle Programs

› In this program, one group of chickens is treated sequentially withdifferent drugs (usually a change between the starter and growerrations)

› Shuttle programs are common practice and offer some benefit inslowing the emergence of resistance.

Cont. …

› Many therapeutic regimens are to maximize the efficiency oftreatment and to minimize the possibility of resistance e.g.anticoccidial drugs given in sub therapeutic doses to encouragethe development of immunity and the use of compoundanticoccidial preparations are common.

Cont. …

Parasite population

Anticoccidial X

No anticoccidial

(Mathis et al., 1984; Chapman, 2007)Level of sensitivity

High Low

Rotation Program

› Changing the anticoccidial drug to one of another class after a fewcycles (can be in shuttle or full program)

› Rotation = Resting

› Helps anticoccidials to recover efficacy

(Chapman and McFarland, 2003)

Cont. ...

96

97

98

99

100

0 6 12 18 24

% W

EIG

HT

GA

IN

MONTHS

divalent ionophore monovalent ionophore

Rotation Basics

› Ionophore: up to 6 months

› Chemical full: 3 months (1 cycle)

› Chemical in shuttle: 4.5 months (2 cycles)

Cont. …

After using an ionophore– Do not use it again for at least 6 months (or other ionophore from same class)

After using a chemical– Limit use of particular chemical to once a year, if used 3 months in full, give 9

months rest.

– You can use other chemicals.

Monovalente Ionophores

Divalent Ionophore

Monovalent Glycoside

Ionophores

Monensin

Narasin

LasalocidMaduramicin

Semduramicin

Don’t forget cross-resistance

Correct Rotation

Salinomycin

0

20

40

60

80

100

120

1 2 3 4 5 6 7 8 9 10 11 12

Efficacy

Chemical

Ionophore

Rotation Reduces The Risk For Developing Resistance !!!

Anticoccidial Programs: 4 Golden Rules

1. Do not to use same anticoccidial for too long.

2. Give product a sufficiently long rest period after each period ofuse.

3. Rotate between products of different classes.

4. Use a chemical clean up once a year, it gives a very goodreduction infection pressure.

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