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Antiprotozoal drugs Coccidia

Sporozoa (Apicomplexa) • Mostly enteric disease caused by the genera Eimeria and
Isospora
– Major economic disease of poultry
• Resistance
• Rotation and shuttle programs – changing the mode of action within a
batch of broilers
– Rapid lifecycle, massive environmental contamination
– Any young animal
– Act on extracellular stages, intracellular stages or sporulation

Ionophores
• Transport cations across membranes
– Cause osmoregulatory difficulties
– Extracellular merozoites, sporozoites
– Fermentation products
• 5 classes of drug
– Resistance to a drug in one class will confer
resistance within that class but not to the 4 others
– Toxic to horses and turkeys
– Generally in feed medications

Calnek et al. (1991) Diseases of Poultry, 9th Ed

• Divalent polyether
– Lasolocid (Bovatec)
• Monovalent polyethers
– May not be co-administered with some antibiotics - • Monovalent monoglycoside polyether
Tiamulin – Semiduramicin (Aviax)
– Maduramycin (Cygro)
• Monensin (Rumensin, Coban) • 5 day withdrawal period
– Cattle, broilers, goats
– Also a growth promoter in ruminants • Toltrazuril (Baycox)
• Alters microbial fauna in rumen →↓ VFA loss – Triazine
– No withdrawal pre-slaughter – Poultry and mammals
• Salinomycin – Water administration
– Poultry only – Broad spectrum anticoccidial and antiprotozoal
– Active v sexual and asexual stages
– Sporozoites, and intracellular asexual stages – T1/2 of 51 hours in piglets
• Narasin (Monteban) – 14 day WHP, not in layers
– Broilers only – Also active v Hepatozoon canis and possibly Neospora caninum

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• Amprolium • Clopidol (Lerbek)
– Thiamine analogue – Pyridinol
– First generation schizont – Sporozoite
– E tenella principally
• Robenidine (Cycostat)
– Guanidine derivative
• Sulphonamides – 1st generation schizonts
– First effective anticoccidials used – WHP of 5 days
– Active v asexual stages - schizonts • Nicarbazin (Carbigran)
– Not used in poultry anymore – 2nd generation trophozoites
– Prevention not treatment
– Ruminants, dogs, cats
– 4 day WHP
– Often used in combination with dihydrofolate – Not for layers
reductase/thymidylate synthase inhibitors eg – In combination with narasin = Maxiban
trimethoprim

Other sporozoa Amoebae flagellates


• Cryptosporidia,
– Nothing registered or effective off label so far
• Toxoplasma, Neospora, sarcocysts • Giardia and trichomonas in Australia
– Nothing registered • Nitroimidazoles
– Clindamycin effective v toxo, neospora? – Metronidazole (Flagyl)
– Sulphonamide/Trimethoprim (or pyrimethamine?) some activity • Effective against Giardia, Histomonas, Entamoeba
– Trimethoprim alone Trichomonas
• Horses, dogs, cats, humans – not food producing animals!!
• Babesia No MRL established
– Imidocard (Imizol) • Oral administration, well absorbed, t1/2 4-5 hours in dogs
– s.c. injection • Dosage above 100 mg/kg → adverse effects
– T1/2 3.5 hours, 28 days WHP in cattle – Dimetridazole (Emtryl)
– Not for dairy • Birds only
– Adverse effects – parasympathetic stimulation • Blackhead, canker
• Not for use in food producing birds – genotoxic

• BZs
– High doses given at 12 or 24 hour intervals for 2 or 3 days Resistance
– Fenbendazole
• FBZ 50 mg/k daily for 3 days in dogs • What is Resistance?
• FBZ 5-20 mg/kg daily for 3 days in calves The ability of a pest to
– Febantel be able to withstand
• 27-35 mg/kg/day for 3 days in dogs
the effect of a
– Albendazole
• 25 mg/kg b.i.d. for 2 days
chemical
• Trimethoprim • What causes
– Acanthamoeba
Resistance?
• Doxycycline Common factors are:
– Entamoeba, Balantidium, Toxoplasma
• Human antiprotozoal drugs have been used with some – Under-dosing
successes in dogs. Some are registered for animal use OS – Increased frequency
– Primaquine, quinacrine, atovaquone, decoquinate, furazolidine,
meglumine antimonate, paramomycin, enrofloxacin, azithromycin – Improper coverage
• See small animal pharmacology, Maddison, Page, Church, 2nd edition 2008,
Saunders/Elsevier, Philadelphia USA. – Poor application
– Poor mixing

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Resistance to parasiticides
• SPs - resistance in buffalo flies, ticks, flies, fleas,
lice.
• OP/carbamate - resistance is increasing and
widespread in places - flies, ticks, fleas
• Amitraz - widespread resistance in ticks
• BZs
• Levamisole/pyrantel
• Salicylanilides
• MLs
• Multi-resistant strains occur – ticks, fleas, worms,
flies
• Sheep blowflies are still susceptible to cyromazine

Resistance to chemicals
• 2 general mechanisms
– major single gene mutation, dominant, rare
event 1 in 106-8 individuals - eg dieldrin and OP
resistance in flies.
– genetic shift in many relevant genes - eg
anthelmintic resistance
• Selection pressure
– select only resistant individuals (square decay
curve).
– slow decline in residues may select for many
genes that contribute to resistance (residue tail)
– Cost of resistance - R is less fit eg cyromazine

Development of Resistance

A small percentage Survivors mate


genetically resistant and offspring
to a given dose of inherits
insecticide resistant traits

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Development of Resistance Development of Resistance

Pesticide treatments Resistant pests Continued Resistant pest


continues to kill face less treatment with the continues to grow
susceptible pests competition for same class of and the population
food and begin to pesticide eliminates becomes
thrive susceptible pests predominantly
resistant and leads
to pesticide failure

Integrated pest management IPM tactics


• Concept introduced by entomologists in
• Increase host resistance
the 1960s
• Utilise natural enemies, biological
• Driven by concerns about resistance to control
pesticides and pollution • Modify management practices
• IPM Strategies • Judicious use of pesticides
– Prevention or avoidance of pests – Resistance management
– Decrease of pest populations, eradication
– Decrease in crop or animal susceptibility
• Need reliable identification, diagnosis
and monitoring of pest populations
– Combination of strategies
– No action • For animals – Management practices,
– Economic threshold biological control, monitoring,
pesticides.

Strategies to control parasite Strategies to control parasite


resistance resistance
• Don’t introduce animals infected/infested with
• Decrease pesticide resistance selection pressure
resistant parasites onto your premises -
– Rotating the class of antiparasiticide used
– Use non-persistent chemicals quarantine paddock
– Using the minimum number of treatments necessary • Rely on non-chemical control
• Treat at economic threshold
– The use of combination products – cleaning up decaying organic matter and faeces
– Conserve susceptible genes around dairies to reduce Stomoxys breeding sites
• Immigration – Paddock rotation, fires natural predators
• Use of ‘refugia’ untreated and thus unselected populations of
parasites – Biological control - dung beetles
– Free living stage
– Untreated groups of animals
• Rely on breed resistance, acquired immunity.
• Increase dose to kill resistant heterozygotes or – Eg innate tick resistance in Zubu breeds
homozygotes – Mature and dry animals are much less susceptible to
• Reduce dose so some homozygous susceptible worms than weaners
survive
• Testing regularly for resistance