PaBi (13): Veterinary helminths

Question 1

Give an example of a helminth that infects sheep.

Answer 1

Haemonchus contortus

Question 2

What are the benefits of controlling veterinary parasites?

Answer 2

Improved health and welfare of the animal, reduces losses for food and economy, ensures high food quality

Question 3

What are the signs of a helminth infection in sheep?

Answer 3

Weight loss, severe abdominal pain, diarrhoea, anaemia, bottle jaw

Question 4

What is the pathogenesis of intestinal nematodes?

Answer 4

Tissue damage, impaired uptake of nutrients, loss of gut integrity

Question 5

What are the pros and cons of anthelmintics?

Answer 5

pros: cheap, safe, there’s a broad spectrum of drugs, have immediate action. cons: residues can be left in meat and milk, resistance

Question 6

What is the mode of action of benzimidazoles?

Answer 6

Binds to tubulin to prevent microtubules forming. This leads to less transport of vesicles so reduced glucose uptake and starvation of the parasite.

Question 7

What is the mode of action of the class of drugs imidazothiazoles?

Answer 7

It mimics acetyl choline and is a nicotinic receptor agonist so results in spastic paralysis of the parasite

Question 8

What is the mode of action of the ML drugs?

Answer 8

Binds to GABA receptors to stimulate permanent opening of the nerve channel and flaccid paralysis

Question 9

What is the mode of action of the AAD class of drugs?

Answer 9

Is an agonist of an AchR only found in nematodes which cause muscle contraction and interferes with mobility and growth.

Question 10

What is the function of spiroindoles?

Answer 10

Nicotinic agonists which interfere with the attachment of ACh and interferes with nerve-muscle communication causing paralysis

Question 11

What is the definition of resistance?

Answer 11

A hereditary decrease in the sensitivity of a parasite population to the action of a drug

Question 12

How widespread is resistance to anthelmintics?

Answer 12

Resistance has been reported in all the classes in between ~25-45 countries. Less resistance to AAD (only 4 countries reported resistance)

Question 13

What is prevalence?

Answer 13

How widespread something is- how many individuals are affected at one time

Question 14

What is the prevalence of resistance in the UK?

Answer 14

About 80% of farms have reported BZ resistance, 30-50% resistance to LEV and IVM, 40% of Welsh farms have multiple class resistance, no resistance to AD or SI yet

Question 15

What are some mechanisms of resistance?

Answer 15

Changes in the drug target, amplification of target genes to overcome drug action, changes in metabolism to inactivate drug, changes in distribution of the drug within the organism so it can’t reach it’s target site

Question 16

Give some examples of changes in the target site which have allowed resistance.

Answer 16

Mutation in beta tubulin gene confers resistance to BZ. Decreased affinity for LEV at the nicotinic Ach receptors. SNP mutationon GluCl subunits for ML resistance

Question 17

What metabolic changes in the parasite have allowed drug resistance?

Answer 17

Enzymatic mechanisms for handling xenobiotics, cytochrome oxidase pathway is important in Fasciola hepatica

Question 18

What is the function of P-glycoprotein homologues in parasites?

Answer 18

Over-expression allows efflux of drug and it has been involved in resistance to multiple classes of drug

Question 19

What are three tests that can be used to test for anthelmintic resistance?

Answer 19

Controlled efficacy test- animals are infected treated then killed and their gastrointestinal tract is removed an worm burden analysed. Post drench efficacy test- number of eggs counted after treatment, if there is eggs it is considered ineffective. Faecal egg count reduction test- eggs counted in faeces before and after treatment

Question 20

What genetic changes in the parasite could we look for to diagnose resistance?

Answer 20

Mutations in drug target genes, changes in gene expression of drug handling system.

Question 21

How do we manage resistance?

Answer 21

avoid under-dosing, have quarantine measures for imported stock, check annually for resistance, target treatments effectively