PHARMACOLOGY - Anthelmintic Resistance

Question 1

What is anthelmintic resistance?

Answer 1

Anthelmintic resistance is a heritable reduction in the sensitivity of a parasite population to an anthelmintic drug

Question 2

What is side resistance?

Answer 2

Side resistance describes how when a parasite population develops resistance to one product within a class of anthelmintic drugs, all of the other products within that class will be affected as they share the same mechanism of action

Question 3

What is multi-drug resistance?

Answer 3

Multi-drug resistance is where a parasite population is resistant to multiple classes of anthelmintic drugs

Question 4

(T/F) Anthemintic resistance can be reversed

Answer 4

FALSE. There is little to no evidence of reversal of anthelmintic resistance

Question 5

How does anthelmintic resistance arise?

Answer 5

Anthelmintic resistance arises as anthelmintic treatment exerts a strong selection pressure on the parasite population and thus only the individuals with mutations conferring anthelmintic resistance will survive to reproduce and resistant mutations will be passed onto the next generation. And thus, resistance is an inevitable consequence of anthelmintic treatment

Question 6

What are the potential mechanisms of anthelmintic resistance?

Answer 6

Reduced sensitivity to the drug
Reduced drug uptake
Increased efflux of the drug

Question 7

What can cause reduced sensitivity to anthelmintic drugs?

Answer 7

Genetic mutations resulting in a change in the target binding site for the anthelmintic drug

Question 8

What can cause increased efflux of anthelmintic drugs?

Answer 8

Increased expression of P-glycoproteins

Question 9

Why is it so challenging to identify relevant genetic differences in helminths which contribute to anthelmintic resistance?

Answer 9

Helminths have very large and complex genomes with high levels of genetic variation throughout different helminth populations

Question 10

Which mechanisms can be used to measure anthelmintic resistance?

Answer 10

Faecal egg count reduction test (FECRT)
Laboratory bioassays
Molecular tests

Question 11

How do you carry out a faecal egg count reduction test (FECRT)?

Answer 11

To carry out a faceal egg count reduction test (FECRT), you do a faecal egg count before and after anthelmintic treatment and if the efficacy of the treatment is less than 95%, the parasite population is resistant

Question 12

What is the main benefit of faecal egg count reduction tests (FECRT)?

Answer 12

Easy test

Question 13

What are the limitations of faecal egg count reduction tests (FECRT)?

Answer 13

1. Some anthelmintic drugs will temporarily cease the production of eggs and thus you can have resistant helminths that have survived the treatment but their egg production has been temporarily ceased. So, if you follow up the faecal egg count too soon after treatment, the egg count could still be ceased however the resistant helminths are still alive so the faecal egg count may not accurately reflect the drug efficacy
2. Faecal egg count reduction tests (FECRT) do not identify the species of helminths within the sample, and thus while the FECRT may refect adequate drug efficacy, the remaining eggs could be from a pure population of resistant species
3. Labour intensive
4. Low sensitivity test

Question 14

When should you take the follow up sample for a faecal egg count reduction test (FECRT) for levamisole?

Answer 14

7 days post treatment

Question 15

When should you take the follow up sample for a faecal egg count reduction test (FECRT) for benzimidazoles?

Answer 15

14 days post treatment

Question 16

When should you take the follow up sample for a faecal egg count reduction test (FECRT) for monepantel?

Answer 16

14 days post treatment

Question 17

When should you take the follow up sample for a faecal egg count reduction test (FECRT) for macrocyclic lactones?

Answer 17

At least 14 days post treatment

Question 18

What are laboratory bioassays?

Answer 18

Laboratory bioassays expose parasites to different anthelmintics and measure their response to each drug

Question 19

What are the limitations of laboratory bioassays?

Answer 19

Labour intensive
Low sensitivity test

Question 20

What are the most sensitive tests for anthelmintic resistance?

Answer 20

Molecular tests are the most sensitive tests for anthelmintic resistance

Question 21

Which class of anthelmintics has a developed molecular test for detecting resistance?

Answer 21

Benzimidazoles

Question 22

What is the molecular test for detecting resistance in benzimidazoles?

Answer 22

There is a molecular test developed to detect resistance in the benzimidazoles as we know the mechanisms of resistance to this class of anthelmintics is a point mutation in the gene encoding for B-tubulin, which is the target site for the mechanism of action of the benzimidazoles. This mutation can be detected using PCR or pyrosequencing

Question 23

What are the guidelines to reduce anthelmintic resistance on farms?

Answer 23

1. Determine a helminth control strategy with the vet
2. Use effective quarantine strategies to prevent the introduction of resistant helminths to the farm
3. Test for anthelmintic resistance
4. Administer anthelmintics effectively
5. Use anthelmintics only when necessary
6. Select appropriate anthelmintics
7. Adopt strategies to preserve anthelmintic susceptible helminths on the farm (‘in refugia’)
8. Reduce dependence on anthelmintics

Question 24

Which quarantine strategy should be followed to prevent introducing resistant helminths onto sheep farms?

Answer 24

Treat incoming sheep with recommended anthelmintics, and yard all of these new sheep on arrival to the farm for 24 to 48 hours. Isolate the sheep on contaminated pasture (has been grazed by sheep this season) for 3 weeks to promote refugia

Question 25

Why should you yard newly introduced sheep on arrival?

Answer 25

Yarding new sheep on arrival minimises the number of helminth eggs (which may be from resistant parasites) already within the gastrointestinal tract of the sheep to be dropped onto pasture, and allows time for the anthelmintic treatment to work

Question 26

Why is it important to isolate quarantined sheep on contaminated pasture for 3 weeks?

Answer 26

Turning the quarantined sheep out onto contaminated pasture ensures that any surviving resistant helminths mix with susceptible worms to dilute the resistant genes

Question 27

What is the 'gold standard' anthelmintic treatment for quarantined sheep?

Answer 27

Orange (monepantel) and purple (derquantel and abamectin)

Question 28

What is the 'silver standard' anthelmintic treatment for quarantined sheep?

Answer 28

One of the newer anthelmintic products (orange or purple) and a macrocyclic lactone

Question 29

Why is it important to use more than one anthelmintic drug when treating quarantined sheep?

Answer 29

Using more than one anthelmintic drug reduces the chances of any resistant helminths surviving the treatment

Question 30

Why is the 'silver standard' anthelmintics often more realistic than the 'gold standard'?

Answer 30

The 'silver standard' anthelmintic protocol is less expensive than the 'gold standard', and if you use an injectable macrocyclic lactone this will also cover sheep scab (psoroptes ovis)

Question 31

What are the common causes of failure of anthelmintic treatment?

Answer 31

Anthelmintic resistance Underdosing the anthelmintic Failure to follow the manufacturers instructions Use of incorrect drug/misdiagnosis

Question 32

What can cause underdosing of anthelmintics?

Answer 32

Underestimation of animal weight Poorly maintained dosing equipment Poor dosing technique

Question 33

What is the preferred method of anthelmintic treatment?

Answer 33

Targeted selective treatment (TST)

Question 34

What is targeted selective treatement (TST)?

Answer 34

Targeted selective treatment (TST) is treatment of individual animals with anthelmintics when monitoring performance indicates subclinical infection

Question 35

Which methods can be used to monitor animal performance for targeted selective treatment?

Answer 35

Measure daily liveweight gains FAMACHA

Question 36

What are the advantages of targeted selective treatments (TST)?

Answer 36

Reduce anthelmintic use but maintain good performance Promotes refugia

Question 37

What is 'refugia'?

Answer 37

'Refugia' is the concept of leaving some parasites unexposed to anthelmintics, thereby reducing the selection pressure which drives anthelmintic resistance, by maintaining genetic susceptibility to anthelmintics. *(This can be through not treating adult animals which have immunity to worms and thus won't be experiencing clinical or subclinical disease, however still shed eggs)*. ## Footnote https://www.youtube.com/watch?v=Ly8jwhLF9yU&t=266s

Question 38

Why are 'dose and move' anthelmintic protocols no longer recommended?

Answer 38

'Dose and move' protocols involve giving a dose of anthelmintic drugs to animals, then moving them to clean pasture. However, this is no longer recommended as only the resistant helminths will survive and contaminate the clean pasture with purely resistant parasites, contributing to anthelmintic resistance. It is important to avoid this and to keep parasite populations 'in refugia'

Question 39

Why is moxidectin so widely used on farms?

Answer 39

Moxidectin is well liked by farmers as it has a persistant action and can be used for both nematode and sheep scab treatment and control

Question 40

What are the major risk factors for resistance to moxidectin?

Answer 40

Using moxidectin too frequently or administering suboptimal doses can create strong selective pressure on parasite populations and drive resistance

Question 41

What is the latest advice for the use of moxidectin?

Answer 41

The latest advice is to use moxidectin a maximum of once per year on farms

Question 42

What are the alternative parasite control methods?

Answer 42

Grazing management Selective breeding for resistance and resilience Vaccinations

Question 43

Which ovine nematode has a vaccine ?

Answer 43

Haemonchus contortus | However has to be imported with a special import lisence

Question 44

SCOPS, COWS and NADIS are all useful websites for this topic!!