PHARMACOLOGY - Anthelmintic Resistance Flashcards
What is anthelmintic resistance?
Anthelmintic resistance is a heritable reduction in the sensitivity of a parasite population to an anthelmintic drug
What is side resistance?
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
What is multi-drug resistance?
Multi-drug resistance is where a parasote population is resistant to multiple classes of anthelmintic drugs
(T/F) Anthemintic resistance can be reversed
FALSE. There is little to no evidence of reversal of anthelmintic resistance
How does anthelmintic resistance arise?
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
What are the potential mechanisms of anthelmintic resistance?
Reduced sensitivity to the drug
Reduced drug uptake
Increased efflux of the drug
What can caused reduced sensitivity to anthelmintic drugs?
Genetic mutations resulting in a change in the target binding site for the anthelmintic drug
What can cause increased efflux of anthelmintic drugs?
Increased expression of P-glycoproteins
Why is it so challenging to identify relevant genetic differences in helminths which contribute to anthelmintic resistance?
Helminths have very large and complex genomes which high levels of genetic variation throughout different helminth populations
Which mechanisms can be used to measure anthelmintic resistance?
Faecal egg count reduction test (FECRT)
Laboratory bioassays
Molecular tests
How do you carry out a faecal egg count reduction test (FECRT)?
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
What is the main benefit of faecal egg count reduction tests (FECRT)?
Easy test
What are the limitations of faecal egg count reduction tests (FECRT)?
- 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
- 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
- Labour intensive
- Low sensitivity test
When should you take the follow up sample for a faecal egg count reduction test (FECRT) for levamisole?
7 days post treatment
When should you take the follow up sample for a faecal egg count reduction test (FECRT) for benzimidazoles?
14 days post treatment
When should you take the follow up sample for a faecal egg count reduction test (FECRT) for amino acetonitrile derivatives?
14 days post treatment
When should you take the follow up sample for a faecal egg count reduction test (FECRT) for macrocyclic lactones?
At least 14 days post treatment
What are laboratory bioassays?
Laboratory bioassays expose parasites to different anthelmintics and measure their response to each drug
What are the limitations of laboratory bioassays?
Labour intensive
Low sensitivity test
What are the most sensitive tests for anthelmintic resistance?
Molecular tests are the most sensitive tests for anthelmintic resistance
Which class of anthelmintics has a developed molecular tests for detecting resistance?
Benzimidazoles
What is the molecular test for detecting resistance in benzimidazoles?
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
What are the guidelines to reduce anthelmintic resistance on farms?
- Determine a helminth control strategy with the vet
- Use effective quarantine strategies to prevent the introduction of resistant helminths to the farm
- Test for anthelmintic resistance
- Administer anthelmintics effectively
- Use anthelmintics only when necessary
- Select appropriate anthelmintics
- Adopt strategies to preserve anthelmintic susceptible helminths on the farm (‘in refugia’)
- Reduce dependence on anthelmintics
Which quarantine strategy should be followed to prevent introducing resistance helminths onto sheep farms?
- Yard all new sheep on arrival to the farm for 24 to 48 hours
- Treat incoming sheep with recommended anthelmintics
- Isolate the sheep on contaminated pasture for 3 weeks
Why should you yard newly introduced sheep on arrival?
Yarding new sheep on arrival minimises the number of helminth eggs already within the gastrointestinal tract of the sheep to be dropped onto pasture, and allows time for the anthelmintic treatment to work
What is the ‘gold standard’ anthelmintic treatment for quarantined sheep?
Orange (amino acetonitrile derivatives) and purple (Paraherquamide derivatives)
What is the ‘silver standard’ anthelmintic treatment for quarantined sheep?
One of the newel anthelmintic products (orange or purple) and a macrocyclic lactone
Why is it important to use more than one anthelmintic drug when treating quarantined sheep?
Using more than one anthelmintic drug reduces the chances of any resistant helminths surviving the treatment
Why is the ‘silver standard’ anthelmintics often more realistic than the ‘gold standard’?
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)
What are the common causes of failure of anthelmintic treatment?
Anthelmintic resistance
Underdosing the anthelmintic
Failure to follow the manufacturers instructions
Use of incorrect drug/misdiagnosis
What can cause underdosing of anthelmintics?
Underestimation of animal weight
Poorly maintained dosing equipment
Poor dosing technique
What is the preferred method of anthelmintic treatment?
Targeted selective treatment (TST)
What is targeted selective treatement (TST)?
Targeted selective treatment (TST) is treatment of individual animals with anthelmintics when monitoring performance indicates subclinical infection
Which methods can be used to monitor animal performance for targeted selective treatment?
Measure daily liveweight gains
FAMACHA
What are the advantages of targeted selective treatments (TST)?
Reduce anthelmintic use but maintain good performance
Promotes refugia
What is ‘refugia’?
‘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
Why are ‘dose and move’ anthelmintic protocols no longer recommended?
‘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’
Why is moxidectin so widely used on farms?
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
What are the major risk factors for resistance to moxidectin?
Using moxidectin too frequently or administering suboptimal doses can create strong selective pressure on parasite populations and drive resistance
What is the latest advice for the use of moxidectin?
The latest advice is to use moxidectin a maximum of once per year on farms
What are the alternative parasite control methods?
Grazing management
Selective breeding for resistance and resilience
Vaccinations
Which ovine nematode has a vaccine ?
Haemonchus contortus
However has to be imported with a special import lisence
SCOPS, COWS and NADIS are all useful websites for this topic!!
