Endoparasite Resistance Flashcards
Tolerance
the drug is not effective against that parasite and has not ever been.
Pyrantel is not effective treatment against whipworms. The worms are tolerant of this drug treatment
Resistance
Ability of worms in a populaiton to survive drug treatments that are generally effective against the same species and stage of infection at the same dose
Caused by changes in allele frequencies of resistance genes
Results in drug selection
Natural Susceptibility or Natural Variability
Refers to differences in response by an organism or population to a drug relative to other individuals or populations unrelated to prior exposure or pior selection
Sometimes it is difficult to differentiate true resistance form the natural range of susceptibility that exists as a bell curve in every population of pests
Susceptibily - >90%
Undetermined 80 - 90%
Resistant - <80%
Genetic mechanisms of parasiticide resistance
- Alteration of a gene
- different alleles of enzymes or receptors
- Change in gene expression
- Change in promoter or gene amplification
- Selective expression of particular isotypes
- gene deletion
Single Nucleotide polymorphisms
- A DNA sequence variation occurring when a single nucleotide in the genome differs between members of a species or paired chromosomes in an individual
- Haemonchus contortus
- B-tubulin gene
Where do resistant worms come from
- Huge genetic diversity in parasite populations
- Haemonchus contortus → 5000 eggs/female/day
- 300 female worms / animal
- 100 animals
- >1,000,000,000 eggs per week
- Resistant worms exist within populations prior to introduction of drug
- Resistance actually = change in allele frequency rather than induced appearance of new alleles
Allele Frequency and drug selection
Resistance occurs within classes
- Resistance to one drug in class = resistance to all others
- same mechanisms
- Apparent exceptions due to relative potency and are generally short-lived
- Albendazole > fenbendazole
- Oxibendazole kills fenbendazole resistance cyathostomes
- Mozidectin kills ivermectin-resistant Haemonchus
- Topical moxidectin kills other ML-resistant D. immitis
New Drug Classes are NOT the answer
- Depsipeptides
- Emodepside
- Aminoacetonitrile Derivatives
- Monepantel
- New drug calsses not “the answer” for very long unless change approach to use
- high risk of having no effective anthelmintics to use in near future
- Costs >$200M to develop new drug
When Suspect Resistance
- FEC remain high or clinical signs persist following treatment
- knowledge of prevalence of resistance in area helps
- Must also consider Treatment Failure
- inadequate dose
- Drug inactive due to storage, expiration
- Parasites not susceptible (wrong drug)
- FEC performed improperly
- timing, technique, not quantitative
Other important Considerations
- Different parasites have different innate drug sensitivity
- dose-limiting parasite
- Therapeutic dose is much greater than what is required to kill most species
- Some species more likely to develop resistance
- Fecundity / egg production
- Length of life cycle
- Life span of adult worms
- Susceptibility in different stages
Practices that may encourage resistance
- Frequent treatments
- > 3 times per year
- Selecting for multiple generations
- long-lasting treatments
- Treatments that target multiple life stages
- Treating all animals at the same time
- Treating when few larvae on pasture
- Treating and moving to clean pasture
Goals of Deworming:
Large Animals
- Maintain herd health
- can the animals handle a small number of worms?
- Reduce environmental contamination
- Treat the animals that would benefit most
- Can we identify these animals
- Preserve anthelmintic efficacy
Goals of Deworming:
Small Animal
- Keep the animal healthy
- how may heartworms can an animal tolerate?
- Protect public health
- hookworms
- Roundworms
Reduce environmental Contamination
- Selective treatment
- achieve equivalent parsite control and maintain large refugia
- 20% of animals shedding 80% of the eggs
- Quarantine new arrivals
- in some situations you should only introduce if FEC is negative
- Reduce stocking density
FAMACHA
- Reduces selection pressure on parasite population
- identify and treat only those sheep / goats that are carrying heavy burdens
- Leave others that have smaller worm burdens due to natural immunity non-treated so the “shed” low numbers of eggs
- maintaining a population of susceptible worms
- Selecting for herd immunity
- if a particular animal has to be treated multiple times (2-3), it is culled from herd, thereby eliminating poor-genetics
