namalika karunaratne nserc-irc agm 2016...ionophore toxicity in poultry normal cell ionic gradient...
TRANSCRIPT
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NAMALIKA KARUNARATNE
NSERC -IRC AGM 2016
Ionophore toxicity in poultry
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Outline
Anti-coccidials classification
Ionophores
Mode of action
Ionophore toxicity
Possible causes for ionophore toxicity
Clinical signs
Gross pathology and histopathology
Diagnosis and treatment
Take home message
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Anti-coccidials classification
Anti-coccidials
Ionophores Chemical drugs
Commercial name
Active ingredient
Amprol Amprolium
Nicarbaz Nicarbazin
Zoamix Zoalene
Coyden Clopidol
Robenz Robenidine
Deccox Decoquinate
Clinacox Diclazuril
Commercial name
Active ingredient
Coban Monensin
Monteban Narasin
BioCox 120G
Salinomycin Salinomycin 60
Sacox 120
Coxistac
Avatec Lasalocid
Cygro Maduramicin
Elanco poultry anticoccidial reference guide
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Ionophores
Ionophores are polyether compounds used in control of coccidiosis
Fermentation products of Streptomyces and other fungi species
They form lipid soluble complexes with cations & facilitate specific ion transport across biological membranes
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Ionophore classification
Classification – based on affinity for cations
Monovalent ionophores Tend to combine with Na+ and K+
Eg – monensin, narasin, salinomycin
Monensin – choice of product for poultry
Broad-spectrum activity against coccidia
Slow development of drug resistance
Divalent ionophores Combines with Na+, K+ as well as with Ca2+, Mg2+
Eg- lasalocid
+ & ++
+
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Mode of action
Most ionophores act against 1st & 2nd asexual cycle of coccidia
• Act on sporozoites and merozoites
Some act against sexual stages of the life cycle
Chapman, 2010
(MERCK Animal Health)
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Activity of anticoccidials in coccidial life cycle
Elanco, map
outs
ide
insid
e
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Mode of action
Ionophores form lipid soluble complexes with cations (Na+, K+, Ca2+ & Mg2+) & interfere with normal transport of cations across surface membranes of parasite / modify permeability
Alteration of normal concentration gradients of ions
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Mode of action
Increased intracellular Na+ inhibits mitochondrial functions
Excessive increase of intracellular Ca2+ exceeds the ability of mitochondria to effectively sequester Ca2+ & it causes membrane damage, cell swelling and bursting
Na+ Cl-
H2O
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Recommended dosage
Ionophore Broiler chickens dosage
(ppm) Turkey dosage (ppm)
Monensin 100 100 (up to 12 wks)
Narasin 70 Toxic
Lasalocid 105 100
(up to 14 wks female /16 wks male)
Salinomycin 60 Toxic
Maduramycin 5 5
Elanco poultry anticoccidial reference guide
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Narrow safety margin
Drug Optimal dose
(ppm) Lowest level of toxicity (ppm)
Monensin 100-125 121-150
Narasin 60-80 80-100
Lasalocid 75-125 125-150
Salinomycin 60-75 100
Dowling, 1992
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Ionophore toxicity in poultry
Normal cell ionic gradient is maintained by transport complexes – Na+K+ATPase / Ca2+Mg2+ATPase / Na+Ca2+ counter transport system
Ionophore toxicity – disrupt normal ionic gradients of cells
Excess Ca2+ overload causes mitochondrial damage, and it will leads to reduced cellular energy and muscle necrosis
Less Ca2+ for muscle contraction
Deplete intracellular ATP levels as higher expenditure of ATP to maintain normal ionic balance inside cells
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Possible causes for ionophore toxicity
Accidental overdose
Uneven distribution of drug in feed
Contamination of feed
Some dietary interactions – protein and fat source/level, minerals
Dehydration (turkeys)
Interactions with other drugs
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Compatibility with other drugs
Ionophore Virginiamycin Bacitracin
Bacitracin* (7 days)
Zn Bacitracin Flavomycin
(ppm)
Monensin
11 55 110 2
Narasin
11 55
Lasalocid 11 55
110 (5-15 d)
Salinomycin 11 55 110 2
Maduramycin 11 4.4 2
Elanco poultry anticoccidial reference guide
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Interaction with other drugs
Check the compatibility with other drugs
• Drug label
• Veterinarian
Toxicity cases have reported
• Monensin + sulphaquinoxaline/sulphamethazine/ sulphadimethoxine
• Monensin/narasin/salinomycin + erythromycin
Dowling, 1992
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Effect of fat level & source
Diet containing monensin (150 ppm) • Significantly decrease feed intake & weight gain
Fat (Soybean oil/SO) 3 vs. 6% • Increase weight gain, FI and feed efficiency
• Fat affect on drug metabolizing enzymes
• High energy in fat alleviate growth depression
Effect of fat source (SO vs. beef tallow) • Increasing SO level alleviate growth depressing effect compare to tallow
• Unsaturated fat increase the activity of drug metabolizing enzymes
Bartov, 1987
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Effect of protein source
Monensin (100 & 120 ppm) containing corn-SBM diet
• No significant depression of growth and feed utilization
Medium & high animal protein (fish meal) diet (13 & 24.5%)
• Significant reduction of performance compare to SBM
• Less potassium level in fish meal compare to SBM
Bartov & Jensen, 1980
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Effect of protein level
Monensin supplementation (140 ppm) - corn-SBM diet
• Reduced growth rate 18 & 10% in chicks fed CP 20 & 24%
• Increasing CP to 28% further alleviated the adverse effect of monensin on weight gain
Welch, 1986
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Effect of dietary potassium
Monensin (140 & 160 ppm) in diet
Fish meal or/& poultry by-product vs. SBM
• Growth depression with animal protein compare to SBM
• Addition of K (0 VS. 0.3%) into diet counteracted the growth depression effect
• K improves electrolyte balance
Hector, 1982
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Clinical signs
Incoordination
Leg weakness
Abnormal gait / toe walking
Diarrhoea
Ruffled feathers
Reduced feed intake
weight depression
Decreased egg production – broiler breeders
Paralysis and death
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Salinomycin toxicity - turkeys
Sternal recumbency with neck and limbs outstretched
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Salinomycin toxicity - turkeys
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Clinical signs
Dyspnea – difficulty in breathing
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Gross pathology
Emaciation /dehydration
Generalized congestion
Myocardial enlargement
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Gross pathology
Emaciation /dehydration
Generalized congestion
Myocardial enlargement
Hydropericardium
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Gross pathology
Emaciation /dehydration
Generalized congestion
Myocardial enlargement
Hydropericardium
Ascites
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Gross pathology
Emaciation /dehydration
Generalized congestion
Myocardial enlargement
Hydropericardium
Ascites
Egg peritonitis
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Gross pathology
Emaciation /dehydration
Generalized congestion
Myocardial enlargement
Hydropericardium
Ascites
Egg peritonitis
Spleen atrophy
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Gross pathology
Emaciation /dehydration
Generalized congestion
Myocardial enlargement
Hydropericardium
Ascites
Egg peritonitis
Spleen atrophy
Liver degeneration
Enlarged kidneys
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Salinomycin toxicosis - turkeys
C
(A) Growth retardation in 35 days old poults, (B) Pica, (C) Spleen atrophy
Koutoulis, 2013
C
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Normal histology of muscle tissue
Inflammatory & degenerative lesions of muscle tissue
The Poultry Site
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Differential diagnosis
Nutritional (focal) myopathy – vitamin E & selenium deficiency Sodium chloride (salt) toxicity Botulism Myopathic mycotoxins Newcastle disease
Marek’s disease
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Diagnosis
Recovery of remaining birds in the affected flock when removed from the feed & presence of clinical signs
Gross pathology lesions are not pathognomonic
Presence of histological myopathies
Increased concentrations of ionophores in feed
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Treatment
No known antidote or treatment for ionophore toxicity
When suspected, immediately change the feed to another ration until complete the diagnosis
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Take home message
Use the exact dose of ionophores / species relevance
Prevent contamination of feed
Check drug compatibility when using ionophores with other drugs / consult veterinarians
Immediately change the feed to another ration if ionophore toxicity is suspected in a flock
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Acknowledgements
Dr. Jenny Fricke
Dr. Hank Classen
Tennille Knezacek
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Questions ?