Anthelmintic Resistance

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Anthelmintic Resistance

To understand for which drugs and for which parasites anthelmintic resistance has been reported in the UK

5 classes

BZS

LEV

ML

AD

SI

Others

Praziquantel

Horses

Anti-tapeworm

Depsipeptide + Emodepside

Profender

Cat nematodes

Flukicides

Work against liver fluke

Triclabendazole

Albendazoles

Closantel

Oxyclozanide

Nitroxynil

Spectrum of activity

Some target immature parasites

Some only adults

Species of parasites

Efficacy diff in sheep + cattle

Cant transfer treatment

Resistance in cattle + sheep

Combination drugs

2 drugs

Diff classes

Diff spectrum of activity

Enhance treatment

Legislation ??

Strategies for control

Prophylaxis = prevent high levels of parasite infection by reducing transmission , thus reducing incidence of disease/ production losses

Interval dosing = treat at regular intervals based on egg reappearance period (ERP)

Strategic dosing = treat when parasite number highest to disrupt seasonal cycle of transmission

Targeted dosing = treat on basis of diagnostic indicators

Resistance = when parasites usually killed by a specific drug at a specific dose are no longer killed by it

Heritable

BZs = extensive resistance

LEV = resistance evident

MLs = resistance emerging

Resistant parasites

Sheep + goats

Nematodes

Haemonchus contortus

Teladorsagia circumcinta

Nematodirus battus

Trichostrongylus spp

Trematodes

Fasciola hepatica

Cow

Nematodes

Cooperia oncophora

Ostertagia ostertagi

Trematodes

Fasciola hepatica

Horse

Nematodes

Cyathostomin spp

Parascaris equorum

Resistance inevitable

Natural consequence of drug treatment

Rate of selection from resistance can be greatly reduced to preserve drug efficacy for as long as possible

Refugia

Proportion of population not selected by drug treatment

In refuge

Pool of sensitive genes

Dilute resistant genes

Best for nematodes

What level? When ? Which host? How many hosts?

Nematode populations v large + genetically diverse

Resistant parasites v small part of population

Role of random mutation

Selection enriches for resistant parasites until they dominate

How nematodes become resistant

Variation

Let of mutations

Random during treatment

Change at target site

Altered metabolism of drug - can't reach target site

Inc efflux of drug of drug - can't reach target site

Suspect resistance

FEC remains high

Clinical signs persist after Tx

Diagnosis

FECRT - faecal egg count reduction tests

FEC 10-14 d after Tx

Compare post TX mean of control group to means of drug treated groups

Analysis

Effective >95% reduction

Equicocal 90-95%

Check again

Resistance <90%

Why else do drugs fail ?

Inadequate dose

Activity reduced

Parasite species/stage present weren't susceptible

Errors in methods

Control

Selective Tx

Refugia

Other methods of control where possible

SCOPS

COWS

TST

Grazing management

Host genetic resistance