PARASITE CONTROL: WHERE AND WE NOW AND WHERE ARE WE GOING? David Bartram Cape Wools 9th World Merino Conference, 29 April – 01 May 2014, Stellenbosch, Western Cape, South Africa. Goeie môre Ons gaan nou braai STRUCTURE • Background • Guidelines for sustainable use of anthelmintics • Summary BACKGROUND IMPORTANCE RESISTANCE DEVELOPMENT PREVALENCE TIMELINE FROM ANTHELMINTIC INTRODUCTION TO FIRST RESISTANCE Symbol Anthelmintic group Compound Launch First report of AR 1-BZ benzimidazoles thiabendazole 1961 1964 2-LV imidothiazole levamisole 1970 1979 3-ML avermectins ivermectin 1981 1988 milbemycin moxidectin 1991 1995 4-AD amino-acetonitrile derivative monepantel 2009 20131 5-SI spiroindole derquantel 2011 none 1. Scott et al 2013 Vet Parasitol. 198, 166-171; Leathwick et al 2013 Abstracts of 24th International Conference of WAAVP, p249 WHAT IS ANTHELMINTIC RESISTANCE? Resistance is the heritable ability of a parasite to tolerate a normally effective dose of anthelmintic WHY IS RESISTANCE MANAGEMENT IMPORTANT FOR THE FARMER? • Production losses occur even when the parasitism caused by anthelmintic resistance is subclinical • Growth performance is increased by the use of an anthelmintic which is fully effective • Performance benefits can greatly exceed the cost of using an effective anthelmintic Leathwick et al 2008 NZ Vet J. 56, 184-195 Macchi et al 2001 NZ Vet J. 49, 48-53 Miller et al 2012 Vet Parasitol. 186, 376-381 Sutherland et al 2010 Vet Parasitol. 171, 300-304 THE IMPORTANCE OF ANTHELMINTIC RESISTANCE • Resistance is an inevitable consequence of good worm control • Resistant worms do not cause more serious disease than susceptible worms • Once resistance has emerged in a flock/herd worms can no longer be controlled effectively using that anthelmintic class • In most flocks/herds worms can still be adequately controlled when resistance is present • Anthelmintic resistance makes it harder and more expensive to prevent production losses to worms DEVELOPMENT OF ANTHELMINTIC RESISTANCE • Anthelmintic resistance develops through the selection of ancient resistance alleles present in the parasite population • Surviving parasites pass these alleles to their offspring so the allele frequency increases during subsequent parasite generations if selection is maintained • Long-term reversion to susceptibility does not occur PREVALENCE OF ANTHELMINTIC RESISTANCE • In sheep, T. circumcincta or H. contortus resistance to BZ, LV and/or ML anthelmintics is now common in many countries worldwide Group 1 - BZ 1-BZ Benzimidazoles – β tubulin binding Group 2 - LV 2-LV Imidazothiazoles – nAChR agonist* Group 3 - ML 3-ML Macrocyclic lactones – modulate glutamate-gated chloride channels Group 4 - AD 4-AD Amino-acetonitrile derivatives – nAChR agonist* ML Group 5 - SI 5-SI Spiroindole – nAChR antagonist* * Act at different nAChR subtypes. Limited binding at heterologous receptor subtypes. Each subtype is the product of several genes. Ruiz-Lancheros et al 2011 International Journal for Parasitology 41, 455-461 AD LV SI ANTHELMINTIC CLASS LABELLING SOUTH AFRICA 1. Macrocyclic lactones 2. Benzimidazoles 3. Imidothiazoles (incl. levamisole) 4. Salicylanilides 5. Nitrophenols 6. Sulphonamides 7. Organophosphors 8. Isoquinolines 9. Miscellaneous (incl. monepantel) 10.Spiroindoles ANTHELMINTIC CLASS LABELLING UK AND IRELAND 1-BZ 2-LV 5-SI 3-ML 4-AD SUSTAINABLE ANTHELMINTIC USE GUIDELINES FOR BEST PRACTICE PLAN ANNUAL DOSING STRATEGY WITH MEDICINE PRESCRIBER • Tailor the worm control strategy to the individual farm – avoid ‘blue-prints’ INCLUDE AN EFFECTIVE MULTIPLE ACTIVE WORMER Combinations of different chemical classes with similar spectrum of action: 1. Enable the effective control of roundworms in the presence of single or multiple drug resistance 2. Delay the development of resistance to the component anthelmintic classes MULTIPLE ACTIVE FORMULATIONS SHEEP ORAL DRENCH BZ + LV albendazole + levamisole ML + LV abamectin + levamisole ML + BZ + LV abamectin + oxfendazole + levamisole ML + BZ + LV + closantel abamectin + albendazole + levamisole + closantel OP + BZ + LV naphthalophos + levamisole + fenbendazole SI + ML derquantel + abamectin QUARANTINE ANTHELMINTIC TREATMENT OF INTRODUCED SHEEP • Treat all introduced sheep with an effective anthelmintic on arrival • DQL-ABA QUARANTINE ANTHELMINTIC TREATMENT OF INTRODUCED SHEEP • Hold for 24 to 48 hours • Turn onto contaminated pasture WAS HE QUARANTINE TREATED FOR PARASITES WHEN INTRODUCED TO THE NEW FARM? • ‘Deveronvale Perfection’, a Scottish ram, sold for £ 231,000 (€ 270,000) in 2009 • New world record for the most expensive sheep ADMINISTER WORMERS EFFECTIVELY • Dose at the rate recommended for the heaviest in the group • Weigh animals – do not guess • Ensure dosing equipment is properly calibrated RR Homozygous resistant Survives full dose RS Heterozygous SS Homozygous susceptible Killed at the full therapeutic anthelmintic dose ADMINISTER WORMERS EFFECTIVELY • Ensure that the dosing technique is correct – Gently place nozzle of drench gun over back of tongue and depress the trigger – Swallowed into rumen ADMINISTER WORMERS EFFECTIVELY •Ensure products are stored correctly and are within expiry date •Do not mix wormers with any other products USE WORMERS ONLY WHEN NECESSARY USE GRAZING MANAGEMENT TO REDUCE CHALLENGE USE WORMERS ONLY WHEN NECESSARY TARGETED TREATMENT – CONSIDER FAECAL EGG COUNTS AS A GUIDE USE WORMERS ONLY WHEN NECESSARY TREATMENT OF ADULT EWES AND RAMS IN VIVO TESTS FOR ANTHELMINTIC EFFICACY • Drench test / wormer test • Faecal Egg Count Reduction Test (FECRT) • Controlled Efficacy Test TEST FOR ANTHELMINTIC RESISTANCE ON THE FARM DRENCH TEST ENSURE SOME SUSCEPTIBLE WORMS SURVIVE SOURCES OF REFUGIA • Free-living stages of nematodes in the environment at the time of treatment • Any life-cycle stage in the host which is refractory to a particular anthelmintic treatment, but not resistant, e.g. histotropic larvae • Nematodes in animals which are left untreated Fleming et al 2006 J Vet Intern Med 20, 435-444 ENSURE SOME SUSCEPTIBLE WORMS SURVIVE DO NOT MOVE IMMEDIATELY TO CLEAN PASTURE AFTER DOSING • Clean pasture • reseeded by ploughing • areas where sheep have not grazed in the last two years • Areas where sheep have not grazed since last year will be the cleanest, followed by silage aftermaths particularly after two cuts of silage • Dose, return to same pasture for a few days then move to the cleanest high quality pastures available EVIDENCE FOR GLOBAL WARMING GLOBAL WARMING HAS MULTIPLE EFFECTS ON PARASITISM ENSURE SOME SUSCEPTIBLE WORMS SURVIVE SOURCES OF REFUGIA • Temperate climates – majority of worm population is free-living on pasture – escapes anthelmintic treatment – dilutes resistant worms surviving treatment • Hot, dry summers – proportion of free-living worm stages is lower, because they rapidly desiccate and die ENSURE SOME SUSCEPTIBLE WORMS SURVIVE LEAVE SOME ANIMALS UNTREATED – TARGETED SELECTIVE TREATMENT (TST) • Decision support system which identifies individual animals that require treatment on the basis of their relative performance against the rest of the flock/herd • Treatments only given to those individuals not performing as expected; animals meeting or exceeding their expected rate of liveweight gain are left untreated • How many to leave untreated? • Depends on wormer efficacy FAMACHA TEST – HAEMONCHUS CONTORTUS ENSURE SOME SUSCEPTIBLE WORMS SURVIVE LEAVE SOME ANIMALS UNTREATED – TARGETED SELECTIVE TREATMENT (TST) The Five Point Check Bath , G.F. & van Wyk, J.A. (2009) The Five Point Check© for targeted selective treatment of internal parasites in small ruminants. Small Ruminant Research 86, 6-13 AVOID KEEPING SHEEP AND GOATS TOGETHER • Share many worm species • Differences between the PK of anthelmintic drug absorption and elimination – goats metabolise drugs more rapidly – more frequent ruminoreticulum bypass • Adult goats do not become fully immune OTHER METHODS OF WORM CONTROL POTENTIAL TO REDUCE RELIANCE ON ANTHELMINTICS • Vaccination – Haemonchus contortus • Bioactive forages – e.g. chicory • Protein nutrition • Nematophagous fungi • Selection for host resilience/ resistance Nematode Extraction System - NemESys SUMMARY DELAYING THE DEVELOPMENT OF ANTHELMINTIC RESISTANCE • Plan annual dosing strategy with the medicine prescriber • Include an effective multiple active wormer (two or more different chemical classes) • Avoid bringing resistant worms onto the farm • Administer wormers effectively • Use wormers only when necessary (targeted treatment) • Use a chemical class which is effective on the farm concerned • Test for anthelmintic resistance on the farm • Ensure some susceptible worms survive (in refugia) CLOSING THOUGHT… “ Whenever man comes up with a better mousetrap, nature immediately comes up with a better mouse. ” – James Carswell
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