Anthelmintic Resistance & Use Flashcards
what are cattle helminths
Ostertagia ostertagi*
Cooperia oncophora*
Dictyocaulus viviparus
Fasciola hepatica*
Calicophoron daubneyi
what are sheep and goat helminths
Haemonchus contortus*
Teladorsagia circumcincta*
Trichostrongylus spp*
Nematodirus battus*
Fasciola hepatica*
Calicophoron daubneyi
what are horse helminths
Small strongyles*
Parascaris equorum*
Strongyloides westeri
Anoplocephala spp
Oxyuris equi*
what is the most common cause of PGE in sheep
Teladorsagia circumcincta
Haemonchus contortus
what is the lifecycle of haemonchus contortus
Adult worms in abomasum, blood feeders
Mate and produce eggs
Eggs develop to L1, L2 and L3 is infective stage and is ingested
L3 travels to abomasum where it moults to L4 which berries into mucosa and can arrest or emerge as adult worms
what are the anthelmintic groups (5)
Benzimidazoles (1-BZ)
Levamisole (2-LV)
Macrocyclic lactones (3-ML)
Amino-acetonitrile derivatives (4-AD)
Paraherquamide derivatives (5-SI0
what are the mechanisms of action of benzimidazoles
bind to B-tubulin
what are the mechanisms of action of levamisole
nicotinic acetylcholine receptors agonists
what is the mechanism of action of macrocyclic lactones
glutamate-gated chloride channel agonists
what amino acetonitrile derivatives
deg3 acetylcholine receptor agonists
what is the mechanism of action of paraherquamide derivatives
nicotinic acetylcholine receptor antagonists
what is anthelmintic resistance
A heritable reduction in the sensitivity of a parasite population to the action of a drug
how does resistance arise
Mutations conferring anthelmintic resistance are found in untreated parasite populations at a low frequency
Anthelmintic treatment exerts a strong selection pressure on the parasite population
Only resistant parasite survive to reproduce and resistance mutations are passed on to the next generation
- A direct and unavoidable consequence of using anthelmintics to control worm populations is selection for individuals that are resistant to chemicals used
Animal movement facilities spread of resistance
how are parasites highly adaptable
Parasite populations are large and genetically diverse
Mutations arise frequently and (if beneficial) spread rapidly
Haemonchus contortus very fecund!
how many mutations can H. contortus produce every day
2000 eggs per female worm per day
500 female worms per sheep
500 sheep per flock
= 500 million eggs onto pasture per day
Mutation rate of 1-2 per genome per generation
how can you measure resistance
- fecal egg count reduction test (FECRT)
- lab bioassays
- molecular tests
how can fecal egg count reduction tests be used to measure resistance
FEC before and after treatment (efficacy <95% = resistance)
Most commonly used test, simple to perform
Drug type and timing important (7 days post treatment for 2-LV, 14 days for 1-BZ and 4-AD, 14+ days for 3-ML)
how can lab bioassays be used to measure resistance
Expose parasites to different anthelmintics and measure response
Ex. larval development = assay ‘DrenchRite’ commercially available in Australia and USA
All current tests are labour intensive and insensitive
why is there a need for molecular tests
Early stage:
- Can be managed, but difficult to diagnose
Late stage:
- Easy to diagnose, but too late!
Molecular tests are needed to allow sensitive diagnosis, to monitor treatment and to plan control strategies
what are the molecular tests for macrocylic lactones
Point mutations in gene encoding B-tubulin (drug target)
Phe (TCC) to Tyr (TAC) substitution at codon 200 (F200Y) of B-tubulin isotope 1 confers resistance
F200y mutation is a reliable marker and can be detected with PCR or pyrosequencing
what are potential mechanisms of resistance
- reduced sensitivity to drug
- reduced uptake
- removal of drug
how can there be reduced sensitivity to a drug
Change in target binding site
Altered expression/composition of ion channel
how does reduced uptake to drugs occur
Change in tegument/cuticle or amphid
how does removal of a drug cause resistance
Increased expression of ABC transporters (P-glycoproteins)
how do we control parasites and resistance generally
Ideally, aim for a reduced reliance on anthelmintics
- Resistance
- Residues
- Ecotoxicity
what are alternative methods of control of parasites
Resistant or resilient sheep (genetic selection)
H. contortus killed vaccine licensed in Australia and South Africa
T. circumcincta recombinant vaccine at research stage
Grazing strategies (rotation, stocking density, mature ewes)
what are the SCOPs guidelines to reduce resistance and control parasites (8)
- work out a control strategy with your vet
- use effective quarantine strategy to prevent importation of resistant worms in introduced sheep or goats
- test for anthelmintic resistance
- admin anthelmintics effectively
- use anthelmintics only when necessary
- select the appropriate anthelmintic for the task
- adopt strategies to preserve susceptible worms on farm
- reduce dependence on anthelmintics
how do you quarantine animals according to SCOPs to prevent intro of resistant worms
Use of both new compounds (4-AD and 5-SI) recommended = SCOPs gold standard
Or one new compound plus moxidectin (3-ML) = SCOPs silver standard
- Yard all new sheep fro 24-48 hours
- Treat with recommended products
- Isolate on contaminated pasture (has been grazed by sheep this season for 3 weeks
Also considered scab (injectable moxidectin or OP dip)
what are common causes of anthelmintic failure (4)
- Resistance
- Dosing with insufficient anthelmintic
- Underestimation of animal’s weight
- Poorly maintained dosing equipment
- Poor technique
- Failure to follow manufacturer’s instructions
- Not storing products correctly
- Using products past their use by date
- Mixing anthelmintics with other products
- Use of the incorrect drug and/or misdiagnosis
what are whole flock treatments
Common practice
Treat all animals of a certain age simultaneously
what are targeted selective treatment (TST)
The preferred option
Only proportion of animals are treated (80% of worms are found in 20-30% of the hosts)
Happy factor = animals performing as expected don’t require an anthelmintic
how is performance measured to use a targeted selective treatment (TST)
FMACHA H. contortus only (mucous membrane colour)
BCS lumbar vertebrae AUS/NZ
Growth rate UK (automated weigh pens)
what are the benefits of using a targeted selective treatment
No negative effect on pasture contamination
Reduces reliance on anthelmintics
Promotes ‘refugia’
Slows development of resistance
what is refugia
Free-living stages of parasite on pasture as either eggs or larvae and parasites in untreated sheep
Not exposed to anthelmintic
Maintaining the population ‘in refugia’ offers means of maintaining genetic susceptibility
Dose and move no longer recommended
how can new groups of anthelmintics be used strategically
Amino-acetonitrile derivatives (4-AD) monepantel ‘Zolvix’ = initially effective against most worms resistant to other classes of anthelmintic but resistance emerges rapidly
Paraherquamide derivatives (5-SI) derquantel ‘startect’ = licensed in combo with Abamectin (3-ML)
what is the latest advice for moxidectin (3-ML)
Persistent action, particularly 2% injectable
Sheep scab
Often used in ewes at lambing to control ‘spring rise’
Latest advice from SCOPs is use moxidectin a maximum of once per year (if used for scab, don’t use in ewes at lambing)
why is there major concerns for ML resistance
Major concerns for resistance:
Long half life = underdosing
Passing to lambs in milk = underdosing
Used for sheep soap = off target selection
why is there ML resistance in cattle
Persistence
Ectoparasites: mites, lice, flies
Eprinomectin zero milk withdrawal
most commonly used
what is the drug of choice to kill liver fluke
Triclabendazole (TCBZ) is drug of choice
what stage does Triclabendazole (TCBZ) act on in liver flukes
active against both adults and juveniles
what alternatives can be used to
closantel or nitroxynil for chronic infection with adult flukes in spring
