Prevention Of Coccidia In Poultry

Prevention Of Coccidia in Poultry

Plan of Talk

Coccidia life cycle Anticoccidials and prophylactic use Anticoccidial drugs Classification of anticoccidial drugs Anticoccidials and resistance Overcoming resistance

Plan of Talk

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, which collectively 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. Short life cycle and large number of sporulating oocyst of

parasites helps in increasing the chance of contamination to a large population.

Plan of Talk

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 prevent disease and to minimize the economic loss often associated with subacute infection.

Prophylactic use is preferred, over treatment, because 1. Most of the damage occurs before clinical signs become

apparent. 2. Drugs cannot completely stop an outbreak.

Cont. …

Most of the anticoccidials show their greatest efficacy against the 1st and 2nd asexual cycle.

Some anticoccidials show strong activity during the sexual cycle i.e ., day 5 and 6.– During these days signs of anorexia and hemorrhage

appear, so initiating anticoccidials treatments during these days will provide more benefit.

Few anticoccidials disturb the chemical metabolic pathway by which the drug block the specific stage of the parasite.

Cont. …

Anticoccidials are used usually in starter rations for meat type birds raised under floor-pen management.

Anticoccidials and Immunity

Birds develop natural immunity against coccidia upon exposure.– The natural development of immunity against coccidiosis

may proceed during the use of anticoccidials in the feed.

Cont. …

In broiler, due to their short grow-out period, development of immunity may be of little consequence.

Cont. …

In replacement layer pullets, natural immunity is important because they are likely to be exposed to coccidial infections for extended periods after termination of anticoccidial drugs.

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

Plan of Talk

Coccidia life cycle Anticoccidials and prophylactic use Anticoccidial drugs Classification of anticoccidial drugs Anticoccidials and resistance Overcoming resistance

Anticoccidial drugs

The agents used for the prevention and control of coccidia infections are termed as anticoccidial drugs. They may be;

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

2. Coccidiocidal, in which coccidia are killed during their development.

Cont. …

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

Most anticoccidials currently used in poultry production are coccidiocidal.

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.

Plan of Talk

Coccidia life cycle Anticoccidials and prophylactic use Anticoccidial drugs Classification of anticoccidial drugs Anticoccidials and resistance Overcoming resistance

Classification Of Anticoccidials

Anticoccidials may be;1. Polyether ionophore anticoccidials = ‘Ionophores’ 2. Synthetic anticoccidials = ‘Chemicals’

Polyether ionophore anticoccidials = ‘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®)

Synthetic anticoccidials = ‘Chemicals’

1. Robenidine (Robenz/Cycostat®)2. Diclazuril (Clinacox®)3. Nicarbazin + Narasin (Maxiban®)4. Decoquinate (Deccox®) 5. Nicarbazin

The ionophores

The ionophores

They are: 1. Monensin2. Salinomycin3. Lasalocid4. Narasin5. Maduramicin6. Semduramicin

Ionophores Therapeutic Conc.

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

Monensin 0.01–0.0121 0Narasin 0.006–0.008 0Narasin + Nicarbazin 0.003–0.005 (of the combination) 5Salinomycin 0.0044–0.0066 0Semduramicin 0.0025 0Lasalocid 0.0075–0.0125 3Maduramicin 0.0005–0.0006 5

Cont. …

Ionophores are the fermentation products of Streptomyces and other fungi species.

They are extensively used as anticoccidials. Monensin, Lasalocid and Salinomycin are the Ionophores

which are used commercially Monensin is choice of product for broiler chickens mainly

because of its broad spectrum activity against majority of pathogenic species of coccidian and lack of development of drug resistance.

Mechanism of Action

Ionophores facilitate transport of Na+ ion into cells and elevates the intracellular concentration of Na+ ion.

This increased concentration of Na+ ion:1. Inhibits certain mitochondrial functions such as substrate oxidation

and ATP hydrolysis.2. Creates osmotic difference and attract water to enter the cell.

Intracellular Na+ ion exchanges for extracellular Ca++– Increases intracellular concentration of calcium ions lead to

cytotoxicity.

Cont. …

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

Cont. ... Ionophore

Na+ - K+ - pump

Na+

Na+ - K+ - pump

K+

Osmotic Pressure

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 the parasite, especially during the early asexual stages of parasite development.

Drug Tolerance

Drug tolerance was slow to emerge in chicken coccidia, probably because of the biochemically nonspecific way these fermentation products act on the parasite.

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

Hazard effect

Some ionophores may depress feed consumption when the dosage is above recommended levels.

Monensin

Origin It is a fermentation product of Streptomyces cinnamonensis and

the 1st antibiotic used as an anticoccidials due to its broad spectrum activity.

Activity It acts on trophozoites and 1st generation schizonts. Its activity is generally within the first 2 days of life cycle of

coccidian. This drug has ability to form complexes with sodium and

potassium ions in the host and the developing parasite. This monensin-cation complex renders membrane permeability to

sodium 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 causes suppression 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 of

anticoccidials activity. Inclusion rate It is effective at 0.005-0.0075% concentration. Other actions It increases weight gain, feed conversion and reduces the

lesion in severe coccidiosis It has different ionic affinities and accepts divalent cations as

well as 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 similar to 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 as 0.0121% 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 severe cardiovascular 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-spectrum activity 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 Action1. Nicarbazine enters coccidia cells and paralyze the

intracellular energy-supplying ATP. 2. Leads to the interruption of cellular energy supply and the

cease of function of sodium-potassium ion pump. 3. Results in the abundant influx of sodium ions and with them

the influx of abundant water which causes the intracellular imbalance of ions in the coccidia cells or the rupture of the cells and the death of coccidia occurs.

Cont. …

Nicarbazine has coccidiocidal activity, mainly against the schizonts which appear after the 1st generation.

Marked inhibitory effect on the second generation schizonts and moderate action on the sexual stages have been reported by McLoughlin and Wehr.

Cont. …

Therapeutic concentrationIt is incorporated into feed to bring a final concentration of 0.0125%.

ResistanceSome strains of coccidia which have become resistant to other drugs 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 are

medicated with nicarbazin.

Layers It reduces both egg production and the proportion of fertile

eggs that hatch. It also causes depigmentation of eggs, mottled egg yolk and

poor hatchability, so it should not be used for laying hens.

Robenidine

Mode of action It allows initial intracellular development of coccidia but

prevents formation of mature schizonts. It is coccidiostatic when given short term and coccidiocidal

long term. Drug resistance may develop during use. A 5-day withdrawal period is needed to eliminate untoward

flavor caused by residues in poultry meat.

Diclazuril and Toltrazuril

Diclazuril and toltrazuril are highly effective against a broad spectrum of coccidia.

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

Plan of Talk

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 of drug-resistant strains of coccidia.

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

Coccidia can be tested in the laboratory to determine which products are most effective.

Cont. …

Reduced sensitivity/resistanceAfter some time of use the efficacy of anticoccidials decreases.

Parasite population

Anticoccidial X

No anticoccidial

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

Timing of Resistance Development (theoretic timeline)

0

20

40

60

80

100

120

Efficacy

Chemical

Ionophore

Time

Resistance and Cross Resistance

Reduced sensitivity/resistance

After some time of use

The efficacy of anticoccidials decreases

Cross-resistance

If resistance to one product arises

Other similar products will also work

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 !!!

Plan of Talk

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

selection of resistance.

Cont. …

For instance, producers may either:1. Use one anticoccidial continuously through succeeding

flocks, change to alternative anticoccidials every 4–6 months (rotation program)

2. Change anticoccidials during a single grow-out (shuttle program)

Shuttle Programs

In which one group of chickens is treated sequentially with different drugs (usually a change between the starter and grower rations), are common practice and offer some benefit in slowing the emergence of resistance.

Cont. …

Many therapeutic regimens are to maximize the efficiency of treatment and to minimize the possibility of resistance e.g. anticoccidial drugs given in sub therapeutic doses to encourage the development of immunity and the use of compound anticoccidial preparations are common.

Cont. …

Parasite population

Anticoccidial X

No anticoccidial

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

Rotation Program

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

(Chapman and McFarland, 2003)

Rotation = RestingHelps Anticoccidials To Recover Efficacy

0 6 12 18 2496

97

98

99

100

divalent ionophore monovalent ionophore

Months

% w

eigh

t gai

n

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.

Monensin

Narasin

LasalocidMaduramicin

Semduramicin

Don’t forget cross-resistance

Correct Rotation

Monovalente Ionophores

Divalent Ionophore

Monovalent Glycoside

Ionophores

Salinomycin

1 2 3 4 5 6 7 8 9 10 11 120

20

40

60

80

100

120

Efficacy

ChemicalIonophore

Rotation Reduces The Risk For Developing Resistance !!!

Anticoccidial Programs: Four Golden Rules

1. Do not to use same anticoccidial for too long.2. Give product a sufficiently long rest period after each period

of use.3. Rotate between products of different classes.4. Use a chemical clean up once a year, it gives a very good

reduction infection pressure.