"عسى أن تكون علما ينتفع به" Prophylactic medication against coccidia in poultry

1. Prevention Of
Coccidia in Poultry

2. Plan of Talk
 Coccidia life cycle
 Anticoccidials and prophylactic use
 Anticoccidial drugs
 Classification of anticoccidial drugs
 Anticoccidials and resistance
 Overcoming resistance

3. Plan of Talk
 Coccidia life cycle
 Anticoccidials and prophylactic use
 Anticoccidial drugs
 Classification of anticoccidial drugs
 Anticoccidials and resistance
 Overcoming resistance

4. 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).

5. 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.

6. Plan of Talk
 Coccidia life cycle
 Anticoccidials and prophylactic use
 Anticoccidial drugs
 Classification of anticoccidial drugs
 Anticoccidials and resistance
 Overcoming resistance

7. 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.

8. 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.

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

10. 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.

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

12. 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.

13. Plan of Talk
 Coccidia life cycle
 Anticoccidials and prophylactic use
 Anticoccidial drugs
 Classification of anticoccidial drugs
 Anticoccidials and resistance
 Overcoming resistance

14. 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.

15. 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.

16. 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.

17. Plan of Talk
 Coccidia life cycle
 Anticoccidials and prophylactic use
 Anticoccidial drugs
 Classification of anticoccidial drugs
 Anticoccidials and resistance
 Overcoming resistance

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

19. 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®)

20. Synthetic anticoccidials = ‘Chemicals’
1. Robenidine (Robenz/Cycostat®)
2. Diclazuril (Clinacox®)
3. Nicarbazin + Narasin (Maxiban®)
4. Decoquinate (Deccox®)
5. Nicarbazin

21. The ionophores

22. The ionophores
They are:
1. Monensin
2. Salinomycin
3. Lasalocid
4. Narasin
5. Maduramicin
6. Semduramicin

23. 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

24. 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.

25. 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.

26. 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.

27. 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+

28. Spectrum
 The ionophores affect both extra- and intracellular stages of
the parasite, especially during the early asexual stages of
parasite development.

29. 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.

30. Hazard effect
 Some ionophores may depress feed consumption when the
dosage is above recommended levels.

31. 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.

32. 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.

33. 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.

34. 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

35. 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.

36. Chemicals

37. 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

38. 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.

39. Cont. …
Mode Of Action
1. 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.

40. 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.

41. 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 other
drugs remain sensitive to nicarbazin.

42. 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.

43. 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.

44. 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.

45. Plan of Talk
 Coccidia life cycle
 Anticoccidials and prophylactic use
 Anticoccidial drugs
 Classification of anticoccidial drugs
 Anticoccidials and resistance
 Overcoming resistance

46. 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.

47. 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

48. Timing of Resistance Development
(theoretic timeline)
0
20
40
60
80
100
120
Time
Efficacy
Chemical
Ionophore

49. 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

50. 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 !!!

51. Plan of Talk
 Coccidia life cycle
 Anticoccidials and prophylactic use
 Anticoccidial drugs
 Classification of anticoccidial drugs
 Anticoccidials and resistance
 Overcoming resistance

52. Overcoming Resistance
 Resistance presents a major problem.
 Various programs are used in attempts to slow or stop
selection of resistance.

53. 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)

54. 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.

55. 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.

56. Cont. …
Parasite population
Anticoccidial X
No anticoccidial
(Mathis et al., 1984; Chapman, 2007)
Level of sensitivity
High Low

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

58. (Chapman and McFarland, 2003)
Rotation = Resting
Helps Anticoccidials To Recover Efficacy
96
97
98
99
100
0 6 12 18 24
%weightgain
Months
divalent ionophore monovalent ionophore

59. Rotation Basics
 Ionophore: up to 6 months
 Chemical full: 3 months (1 cycle)
 Chemical in shuttle: 4.5 months (2 cycles)

60. 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.

61. Monensin
Narasin
Lasalocid
Maduramicin
Semduramicin
Don’t forget cross-resistance
Correct Rotation
Monovalente
Ionophores
Divalent
Ionophore
Monovalent
Glycoside
Ionophores
Salinomycin

62. 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 !!!

63. 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.