This is the 4th webinar in a series of webinars on worms in sheep and goats. This presentation focuses on anthelmintics and other treatment options. The presentation was prepared by Susan Schoenian, University of Maryland Extension Sheep & Goat Specialist.

1. IV. Using anthelmintics effectively Products, usage, resistance, refugia, alternatives, future

2. What is an anthelmintic? An agent that kills or causes the expulsion of parasitic worms. Also called dewormer, wormer, drench, or parasiticide.

3. There are three anthelmintic classes.Based on similar chemistries, modes of action, and cross-resistance. Benzimidazoles (BZ) Macrocylic lactones (ML) Avermectins Milbemycins Nicotinic antagonists Imidazothiazoles (IMID) Tetrahydropyrimidines (TETR)

4. 1 - Benzimidazoles (BZ) First class of modern anthelmintics (1961) FenbendazoleSafe-guard®Panacur® AlbendazoleValbazen® OxfendazoleSynanthic® ThiabendazoleTBZ Benzimidazoles kill worms by interfering with energy metabolism on a cellular level by binding to beta tubulin.

5. 1 - Benzimidazoles (white drenches) Broad spectrum Adult and 4th stage larvae of roundworms Adult liver flukes (Valbazen® only) Heads and segments of tapeworms (Valbazen® or 2x labeled dose of Safe-Guard®) Effective against hypobiotic larvae One of the drugs of choice for meningeal worm (Safe-Guard®) Wide margin of safety Do not use Valbazen® during first 30 days of pregnancy or removal of ram(s). Widespread resistance reported.

6. 2- Macrocylic lactones (ML) Newest family of anthelmintics - circa 1980’s Avermectins Ivermectin Ivomec®Primectin® EprinomectrinEprinex® DoramectinDectomax® Milbemycins Moxidectin Cydectin®Quest® Macrocylic lactones interfere with GABA-mediated neurotransmission, causing paralysis and death of the parasite.

7. 2 - Macrocylic lactones (ML) Potent Persistent activity (+/-) Broad spectrum Adult and 4th stage larvae of roundworms Some external parasites (Ivermectin: larval stages of nasal bots) Effective against hypobiotic larvae One of the drugs of choice for meningeal worm (ivermectin). Potential negative effect on dung insects. Widespread resistance reported, especially avermectins.

8. 3- Nicotinic agonists Imidazothiazoles (IMID) LevamisoleProhibit®Tramisol®Levasol® Tetrahydropyrimidines (TETR) MorantelRumatel® PyrantelStrongid® Act as agonists at nicotinic acetylcholine receptors of nematodes, causing paralysis of the worms.

9. 3 - Nicotinic agonists Levamisole Clear (yellow) dewormer Broad spectrum Adult and 4th stage roundworm larvae Hypobiotic larvae (?) Narrower margin of safety (esp. injectable) Resistance varies from high to low. Resistance is sex-linked. Rumatel Oral feed additive Effective against adult worms only Not much is known about resistance levels.

10. FDA-approved anthelmintics SHEEP GOATS Ivomec® sheep drenchIvermectin Cydectin® sheep drenchMoxidectin Prohibit® drenchLevamisole Valbazen® liquidAlbendazole Safe-Guard® suspensionFenbendazole Valbazen® liquidAlbendazole[liver flukes only] Rumatel® premixMorantel Different anthelmintics may be approved and available in different countries.

11. Withdrawal periods for FDA-approved anthelmintics Source: Animal Drugs @ FDA and product labels

12. Withdrawal periods for extra-label anthelmintics in goats Source: Food Animal Residue Avoidance Database (FARAD) and/or http://www.luresext.edu/goats/training/GoatDewormerChart.pdf

13. Anthelmintic resistanceAbility of the worms to survive anthelmintic treatment Official definition: 95% or less reduction in fecal egg count (FECRT). Widespread in parasites of sheep, goats, and horses. Has been reported in all anthelmintics. Developing in cattle parasites. Has been detected in pig parasites. Is likely (inevitable) to develop wherever anthelmintics are frequently used. There will always be some worms that survive an anthelmintic treatment. Tx

14. Anthelmintic resistanceResearch conducted by Delaware State University (2009) Varies by geographic region and individual farm. A result of past anthelmintic use. Anthelmintic resistance is PERMANENT.

17. Refugia (Worms in “refuge”) Worms that have not been exposed to anthelmintic treatment. Worms that are still susceptible to anthelmintic treatment. There will always be some worms that are resistant to a particular anthelmintic. Image source: Meat & Wool New Zealand

18. How to increase refugiaand slow (delay) anthelmintic resistance Selective deworming Do not treat everyone every time. Leave some animals untreated. Pasture management Do not put treated animals onto a clean pasture. Put untreated animals onto pasture previously grazed by treated animals.

19. Anthelmintic combinations Combining anthelmintics from two (or more) different broad spectrum groups Synergistic effect Broaden spectrum of activity Delay development of resistant worms + + Temporary “fix”

20. Preliminary dataEfficacy of anthelmintic combinations in goats 4 animals/Tx Research conducted at Langston University (OK) Initial FECs ranged from 250 to 13,500 and averaged 2,550 epg. 8.6 animals/Tx

21. Proper anthelmintic use Give proper dose based on accurate weight. Goats require higher doses of anthelmintics, usually 1.5 to 2x the sheep or cattle dose. Administer all anthelmintics orally to sheep and goats. Use drench (liquid) formulations of anthelmintics. Fasting may improve efficacy of some anthelmintic treatments.

22. Proper oral drenching technique Use proper equipment Smaller nozzle for lambs and kids Maintain equipment properly Calibrate equipment for proper dosage Hold head horizontal for drenching Insert nozzle in side of mouth Put nozzle over back of tongue Don’t rush Ensure swallowing before release. Be gentle. Avoid injury Putting the drench in the mouth will activate the esophageal groove and cause the drench to by-pass the rumen into the lower gut . . . and not work!

23. Coccidiostats A chemical agent added to animal feed that serves to retard the life cycle or reduce the population of pathogenic coccidia to the point that disease is minimized and the host develops immunity .

24. Coccidiostats Ionophores LasalocidBovatec® Rumensin®Monensin Quinolone DecoquinateDeccox® Amprolium (Rx)Corid® Affect mitochondrial function

25. Coccidiostats Do not kill coccidia. Slow down shedding of coccidia into the environment. Need to be fed ahead of risk period, at least 21 days before. Adequate consumption is a limitation to their effectiveness. Should not feed year-round risk of resistance developing Permissible under USDA natural standards (if declared).

26. Coccidiostats FDA-approved for use in sheep and goats Source: Animal Drugs @ FDA Rumensin® can be toxic to equines and dogs. There is no withdrawal period for slaughter.

27. Treating coccidiosis (Tx) Coccidiostats will not treat coccidiosis. Treatment needs to be administered to individual animals. None of the drugs that are used to treat coccidiosis are FDA-approved for sheep and/or goats. Use must meet requirements for extra label drug use. Two treatment choices Amprolium (Corid®) Sulfa drugs http://old.cvm.msu.edu/extension/Rook/ROOKpdf/coccidia.PDF

29. 5 day treatmentMimics thiamine (vitamin B1), causing a thiamine deficiency in coccidia -> starvation from malnutrition. Polioencephalomalacia (polio) is a possible side effect of treatment. http://old.cvm.msu.edu/extension/Rook/ROOKpdf/coccidia.PDF

30. 2 - SulfonamidesSsulfadimethoxine (Di-methox®, Albon®), Sulfamethazine (Sulmet®) Used to treat many infections. Common treatment for coccidiosis. Cause folic acid deficiency More effective than Corid® (?) http://old.cvm.msu.edu/extension/Rook/ROOKpdf/coccidia.PDF

31. What’s “new” in parasite control?

32. New anthelmintics STARTECT® Derquantel + abamectin New class of anthelmintic: Spiroindole (SI) Acts as a channel blocker to cause flaccid paralysis in worms. Acts on different binding sites than other anthelmintic classes. Only available in New Zealand ZOLVIX® Monepantel New class of anthelmintic: amino-Acetonitrilederivatives (ADDs) Paralyzes worms by attacking a previously undiscovered receptor (Hco-MPTL-1) only present in nematodes Available in New Zealand, Australia, Europe, UK, and South America.

34. Feed supplementDrenchCopper sulfate BolusCopper oxide wire particles (COWP) CuSO4

35. Copper oxide wire particles (COWP) http://www.attra.org/attra-pub/PDF/copper_wire.pdf Copper boluses are available for use for copper deficiency in cattle. Boluses can be repackaged into doses suitable for lambs and kids. Minimum dose is 0.5 g; as much as 2-4 g may be necessary. Effective against barber pole worm only. Mechanism of action is not known. Form of copper is poorly absorbed. http://www.attra.org/attra-pub/PDF/copper_wire.pdf

36. Natural “anthelmintics”Significant research effort underway Garlic juice Pumpkin seed Mustard seed Oregano oil Papaya Diatomaceous earth (DE) Bioactive plants (herbal) Artemisia spp. Sericealespedeza Birdsfoot trefoil Chicory Pine bark Sesquiterpene lactones Condensed tannins

38. Natural “anthelmintics” Natural “anthelmintics” are not likely to replace the therapeutic use of anthelmintics. However, they may reduce the need for anthelmintic treatments disrupting the parasite’s life cycle. They may become an important aspect of holistic or integrated parasite management systems.

39. What about a vaccine? So far, limited success in developing vaccines for internal parasites. Paravac Consortium received record €9 million EU grant to fund development of vaccines against parasitic worms. Promising vaccine for Haemonchus developed by Moredun Institute (Scotland) and currently being tested in Australia. Would the vaccine be available to U.S. producers?

40. Small Ruminant Program Thank you for your attention. Any questions? SUSAN SCHOENIANsschoen@umd.eduwww.sheepandgoat.com

41. Recordings of the 2011 Worm Webinar series are available at http://www.sheepandgoat.com/ recordings.html. PowerPoint presentations from the 2011 Worm webinar series may be viewed or downloaded from http://www.slideshare.net/schoenian. Additional questions may be sent to Susan @ sschoen@umd.edu. Small Ruminant Program