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Module 18: Ruminant Production > Anthelmintic Resistance & Use > Flashcards

Anthelmintic Resistance & Use Flashcards

1
Q

what are cattle helminths

A

Ostertagia ostertagi*

Cooperia oncophora*

Dictyocaulus viviparus

Fasciola hepatica*

Calicophoron daubneyi

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2
Q

what are sheep and goat helminths

A

Haemonchus contortus*

Teladorsagia circumcincta*

Trichostrongylus spp*

Nematodirus battus*

Fasciola hepatica*

Calicophoron daubneyi

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3
Q

what are horse helminths

A

Small strongyles*

Parascaris equorum*

Strongyloides westeri

Anoplocephala spp

Oxyuris equi*

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4
Q

what is the most common cause of PGE in sheep

A

Teladorsagia circumcincta

Haemonchus contortus

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5
Q

what is the lifecycle of haemonchus contortus

A

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

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6
Q

what are the anthelmintic groups (5)

A

Benzimidazoles (1-BZ)

Levamisole (2-LV)

Macrocyclic lactones (3-ML)

Amino-acetonitrile derivatives (4-AD)

Paraherquamide derivatives (5-SI0

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7
Q

what are the mechanisms of action of benzimidazoles

A

bind to B-tubulin

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8
Q

what are the mechanisms of action of levamisole

A

nicotinic acetylcholine receptors agonists

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9
Q

what is the mechanism of action of macrocyclic lactones

A

glutamate-gated chloride channel agonists

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10
Q

what amino acetonitrile derivatives

A

deg3 acetylcholine receptor agonists

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11
Q

what is the mechanism of action of paraherquamide derivatives

A

nicotinic acetylcholine receptor antagonists

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12
Q

what is anthelmintic resistance

A

A heritable reduction in the sensitivity of a parasite population to the action of a drug

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13
Q

how does resistance arise

A

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

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14
Q

how are parasites highly adaptable

A

Parasite populations are large and genetically diverse

Mutations arise frequently and (if beneficial) spread rapidly

Haemonchus contortus very fecund!

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15
Q

how many mutations can H. contortus produce every day

A

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

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16
Q

how can you measure resistance

A
  1. fecal egg count reduction test (FECRT)
  2. lab bioassays
  3. molecular tests
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17
Q

how can fecal egg count reduction tests be used to measure resistance

A

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)

18
Q

how can lab bioassays be used to measure resistance

A

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

19
Q

why is there a need for molecular tests

A

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

20
Q

what are the molecular tests for macrocylic lactones

A

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

21
Q

what are potential mechanisms of resistance

A
  1. reduced sensitivity to drug
  2. reduced uptake
  3. removal of drug
22
Q

how can there be reduced sensitivity to a drug

A

Change in target binding site

Altered expression/composition of ion channel

23
Q

how does reduced uptake to drugs occur

A

Change in tegument/cuticle or amphid

24
Q

how does removal of a drug cause resistance

A

Increased expression of ABC transporters (P-glycoproteins)

25
Q

how do we control parasites and resistance generally

A

Ideally, aim for a reduced reliance on anthelmintics

  • Resistance
  • Residues
  • Ecotoxicity
26
Q

what are alternative methods of control of parasites

A

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)

27
Q

what are the SCOPs guidelines to reduce resistance and control parasites (8)

A
  1. work out a control strategy with your vet
  2. use effective quarantine strategy to prevent importation of resistant worms in introduced sheep or goats
  3. test for anthelmintic resistance
  4. admin anthelmintics effectively
  5. use anthelmintics only when necessary
  6. select the appropriate anthelmintic for the task
  7. adopt strategies to preserve susceptible worms on farm
  8. reduce dependence on anthelmintics
28
Q

how do you quarantine animals according to SCOPs to prevent intro of resistant worms

A

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

  1. Yard all new sheep fro 24-48 hours
  2. Treat with recommended products
  3. Isolate on contaminated pasture (has been grazed by sheep this season for 3 weeks

Also considered scab (injectable moxidectin or OP dip)

29
Q

what are common causes of anthelmintic failure (4)

A
  1. Resistance
  2. Dosing with insufficient anthelmintic
  • Underestimation of animal’s weight
  • Poorly maintained dosing equipment
  • Poor technique
  1. Failure to follow manufacturer’s instructions
  • Not storing products correctly
  • Using products past their use by date
  • Mixing anthelmintics with other products
  1. Use of the incorrect drug and/or misdiagnosis
30
Q

what are whole flock treatments

A

Common practice

Treat all animals of a certain age simultaneously

31
Q

what are targeted selective treatment (TST)

A

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

32
Q

how is performance measured to use a targeted selective treatment (TST)

A

FMACHA H. contortus only (mucous membrane colour)

BCS lumbar vertebrae AUS/NZ

Growth rate UK (automated weigh pens)

33
Q

what are the benefits of using a targeted selective treatment

A

No negative effect on pasture contamination

Reduces reliance on anthelmintics

Promotes ‘refugia’

Slows development of resistance

34
Q

what is refugia

A

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

35
Q

how can new groups of anthelmintics be used strategically

A

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)

36
Q

what is the latest advice for moxidectin (3-ML)

A

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)

37
Q

why is there major concerns for ML resistance

A

Major concerns for resistance:

Long half life = underdosing

Passing to lambs in milk = underdosing

Used for sheep soap = off target selection

38
Q

why is there ML resistance in cattle

A

Persistence

Ectoparasites: mites, lice, flies

Eprinomectin zero milk withdrawal

most commonly used

39
Q

what is the drug of choice to kill liver fluke

A

Triclabendazole (TCBZ) is drug of choice

40
Q

what stage does Triclabendazole (TCBZ) act on in liver flukes

A

active against both adults and juveniles

41
Q

what alternatives can be used to

A

closantel or nitroxynil for chronic infection with adult flukes in spring

Module 18: Ruminant Production (25 decks)

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