Anthelmintics

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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.

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Anthelmintics

  1. 1. IV. Using anthelmintics effectively<br />Products, usage, resistance, refugia, alternatives, future <br />
  2. 2. What is an anthelmintic?<br />An agent that kills or causes the expulsion of parasitic worms.<br />Also called dewormer, wormer, drench, or parasiticide.<br />
  3. 3. There are three anthelmintic classes.Based on similar chemistries, modes of action, and cross-resistance.<br />Benzimidazoles (BZ)<br />Macrocylic lactones (ML)<br />Avermectins<br />Milbemycins<br />Nicotinic antagonists<br />Imidazothiazoles (IMID)<br />Tetrahydropyrimidines (TETR)<br />
  4. 4. 1 - Benzimidazoles (BZ) First class of modern anthelmintics (1961)<br />FenbendazoleSafe-guard®Panacur®<br />AlbendazoleValbazen®<br />OxfendazoleSynanthic®<br />ThiabendazoleTBZ<br />Benzimidazoles kill worms by interfering with energy metabolism on a cellular level by binding to beta tubulin.<br />
  5. 5. 1 - Benzimidazoles (white drenches)<br />Broad spectrum<br />Adult and 4th stage larvae of roundworms<br />Adult liver flukes (Valbazen® only)<br />Heads and segments of tapeworms (Valbazen® or 2x labeled dose of Safe-Guard®)<br />Effective against hypobiotic larvae<br />One of the drugs of choice for meningeal worm (Safe-Guard®)<br />Wide margin of safety<br />Do not use Valbazen® during first 30 days of pregnancy or removal of ram(s).<br />Widespread resistance reported.<br />
  6. 6. 2- Macrocylic lactones (ML) Newest family of anthelmintics - circa 1980’s<br />Avermectins<br />Ivermectin Ivomec®Primectin®<br />EprinomectrinEprinex®<br />DoramectinDectomax®<br />Milbemycins<br />Moxidectin Cydectin®Quest®<br />Macrocylic lactones interfere with GABA-mediated neurotransmission, causing paralysis and death of the parasite.<br />
  7. 7. 2 - Macrocylic lactones (ML)<br />Potent<br />Persistent activity (+/-)<br />Broad spectrum<br />Adult and 4th stage larvae of roundworms<br />Some external parasites<br />(Ivermectin: larval stages of nasal bots)<br />Effective against hypobiotic larvae<br />One of the drugs of choice for meningeal worm (ivermectin).<br />Potential negative effect on dung insects.<br />Widespread resistance reported, especially avermectins. <br />
  8. 8. 3- Nicotinic agonists<br />Imidazothiazoles (IMID)<br />LevamisoleProhibit®Tramisol®Levasol®<br />Tetrahydropyrimidines (TETR)<br />MorantelRumatel®<br />PyrantelStrongid® <br />Act as agonists at nicotinic acetylcholine receptors of nematodes, causing paralysis of the worms.<br />
  9. 9. 3 - Nicotinic agonists<br />Levamisole<br />Clear (yellow) dewormer<br />Broad spectrum<br />Adult and 4th stage roundworm larvae<br />Hypobiotic larvae (?)<br />Narrower margin of safety (esp. injectable)<br />Resistance varies from high to low.<br />Resistance is sex-linked.<br />Rumatel<br />Oral feed additive<br />Effective against adult worms only<br />Not much is known about resistance levels.<br />
  10. 10. FDA-approved anthelmintics<br />SHEEP<br />GOATS<br />Ivomec® sheep drenchIvermectin<br />Cydectin® sheep drenchMoxidectin<br />Prohibit® drenchLevamisole<br />Valbazen® liquidAlbendazole<br />Safe-Guard® suspensionFenbendazole<br />Valbazen® liquidAlbendazole[liver flukes only]<br />Rumatel® premixMorantel<br />Different anthelmintics may be approved and available in different countries.<br />
  11. 11. Withdrawal periods for FDA-approved anthelmintics<br />Source: Animal Drugs @ FDA and product labels<br />
  12. 12. Withdrawal periods for extra-label anthelmintics in goats<br />Source: Food Animal Residue Avoidance Database (FARAD) and/or http://www.luresext.edu/goats/training/GoatDewormerChart.pdf<br />
  13. 13. Anthelmintic resistanceAbility of the worms to survive anthelmintic treatment<br />Official definition: 95% or less reduction in fecal egg count (FECRT).<br />Widespread in parasites of sheep, goats, and horses. Has been reported in all anthelmintics.<br />Developing in cattle parasites.<br />Has been detected in pig parasites.<br />Is likely (inevitable) to develop wherever anthelmintics are frequently used.<br />There will always be some worms that survive an anthelmintic treatment.<br />Tx<br />
  14. 14. Anthelmintic resistanceResearch conducted by Delaware State University (2009)<br />Varies by geographic region and individual farm.<br />A result of past anthelmintic use.<br />Anthelmintic resistance is PERMANENT.<br />
  15. 15. Causes of anthelmintic resistance<br /><ul><li> Frequent deworming</li></ul>Treating all animals at the same time.<br />Putting treated animals onto a clean pasture.<br />
  16. 16. Causes of anthelmintic resistance<br /><ul><li> Under-dosing</li></ul>Not weighing animals<br />Inability to accurately estimate weights<br />Not calibrating equipment for heaviest animals in group.<br />Using anthelmintics with residual activity<br />Persistent-activity anthelmintics<br />Injectables<br />Pour-ons<br />
  17. 17. Refugia (Worms in “refuge”)<br />Worms that have not been exposed to anthelmintic treatment.<br />Worms that are still susceptible to anthelmintic treatment.<br />There will always be some worms that are resistant to a particular anthelmintic.<br />Image source: Meat & Wool New Zealand<br />
  18. 18. How to increase refugiaand slow (delay) anthelmintic resistance<br />Selective deworming<br />Do not treat everyone every time.<br />Leave some animals untreated.<br />Pasture management<br />Do not put treated animals onto a clean pasture.<br />Put untreated animals onto pasture previously grazed by treated animals.<br />
  19. 19. Anthelmintic combinations<br />Combining anthelmintics from two (or more) different broad spectrum groups<br />Synergistic effect<br />Broaden spectrum of activity<br />Delay development of resistant worms<br />+<br />+<br />Temporary “fix”<br />
  20. 20. Preliminary dataEfficacy of anthelmintic combinations in goats<br />4 animals/Tx<br />Research conducted at Langston University (OK)<br />Initial FECs ranged from 250 to 13,500 and averaged 2,550 epg. 8.6 animals/Tx<br />
  21. 21. Proper anthelmintic use<br />Give proper dose based on accurate weight.<br />Goats require higher doses of anthelmintics, usually 1.5 to 2x the sheep or cattle dose.<br />Administer all anthelmintics orally to sheep and goats.<br />Use drench (liquid) formulations of anthelmintics.<br />Fasting may improve efficacy of some anthelmintic treatments.<br />
  22. 22. Proper oral drenching technique<br />Use proper equipment<br />Smaller nozzle for lambs and kids<br />Maintain equipment properly<br />Calibrate equipment for proper dosage<br />Hold head horizontal for drenching<br />Insert nozzle in side of mouth<br />Put nozzle over back of tongue<br />Don’t rush<br />Ensure swallowing before release.<br />Be gentle.<br />Avoid injury<br />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!<br />
  23. 23. Coccidiostats<br />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 .<br />
  24. 24. Coccidiostats<br />Ionophores<br />LasalocidBovatec®<br />Rumensin®Monensin<br />Quinolone<br />DecoquinateDeccox®<br />Amprolium (Rx)Corid®<br />Affect mitochondrial function<br />
  25. 25. Coccidiostats<br />Do not kill coccidia.<br />Slow down shedding of coccidia into the environment.<br />Need to be fed ahead of risk period, at least 21 days before.<br />Adequate consumption is a limitation to their effectiveness.<br />Should not feed year-round <br />risk of resistance developing<br />Permissible under USDA natural standards (if declared).<br />
  26. 26. Coccidiostats FDA-approved for use in sheep and goats<br />Source: Animal Drugs @ FDA<br />Rumensin® can be toxic to equines and dogs.<br />There is no withdrawal period for slaughter.<br />
  27. 27. Treating coccidiosis (Tx)<br />Coccidiostats will not treat coccidiosis.<br />Treatment needs to be administered to individual animals.<br />None of the drugs that are used to treat coccidiosis are FDA-approved for sheep and/or goats.<br />Use must meet requirements for extra label drug use.<br />Two treatment choices<br />Amprolium (Corid®)<br />Sulfa drugs<br />http://old.cvm.msu.edu/extension/Rook/ROOKpdf/coccidia.PDF<br />
  28. 28. 1 - Corid® (amprolium)<br />Labeled as an aid in the prevention and treatment of coccidiosis in beef and dairy cattle.<br /><ul><li>21 day prevention
  29. 29. 5 day treatment</li></ul>Mimics thiamine (vitamin B1), causing a thiamine deficiency in coccidia -> starvation from malnutrition.<br />Polioencephalomalacia (polio) is a possible side effect of treatment.<br />http://old.cvm.msu.edu/extension/Rook/ROOKpdf/coccidia.PDF<br />
  30. 30. 2 - SulfonamidesSsulfadimethoxine (Di-methox®, Albon®), Sulfamethazine (Sulmet®)<br />Used to treat many infections.<br />Common treatment for coccidiosis.<br />Cause folic acid deficiency <br />More effective than Corid® (?)<br />http://old.cvm.msu.edu/extension/Rook/ROOKpdf/coccidia.PDF<br />
  31. 31. What’s “new” in parasite control?<br />
  32. 32. New anthelmintics<br />STARTECT®<br />Derquantel + abamectin<br />New class of anthelmintic: Spiroindole (SI)<br />Acts as a channel blocker to cause flaccid paralysis in worms.<br />Acts on different binding sites than other anthelmintic classes.<br />Only available in New Zealand<br />ZOLVIX® <br />Monepantel<br />New class of anthelmintic: amino-Acetonitrilederivatives (ADDs)<br />Paralyzes worms by attacking a previously undiscovered receptor (Hco-MPTL-1) only present in nematodes<br />Available in New Zealand, Australia, Europe, UK, and South America.<br />
  33. 33. Copper for internal parasite controlRisk: copper toxicity in sheep<br />Dietary<br /><ul><li>Mineral mix
  34. 34. Feed supplement</li></ul>DrenchCopper sulfate<br />BolusCopper oxide wire particles (COWP) <br />CuSO4<br />
  35. 35. Copper oxide wire particles (COWP) http://www.attra.org/attra-pub/PDF/copper_wire.pdf<br />Copper boluses are available for use for copper deficiency in cattle.<br />Boluses can be repackaged into doses suitable for lambs and kids.<br />Minimum dose is 0.5 g; as much as 2-4 g may be necessary.<br />Effective against barber pole worm only.<br />Mechanism of action is not known.<br />Form of copper is poorly absorbed.<br />http://www.attra.org/attra-pub/PDF/copper_wire.pdf<br />
  36. 36. Natural “anthelmintics”Significant research effort underway<br />Garlic juice<br />Pumpkin seed<br />Mustard seed<br />Oregano oil<br />Papaya <br />Diatomaceous earth (DE)<br />Bioactive plants (herbal)<br />Artemisia spp. <br />Sericealespedeza<br />Birdsfoot trefoil<br />Chicory<br />Pine bark<br />Sesquiterpene lactones<br />Condensed tannins<br />
  37. 37. Nematode-trapping fungusDuddingtoniaflagrans<br />Spores are fed to livestock as part of their diet.<br />Spores pass through digestive tract of livestock and are deposited in the feces.<br />Spores germinate alongside worm eggs.<br />Spores trap and feed on newly emerging larvae.<br /><ul><li>No commercial product (yet)</li></ul>Image source: Louisiana State University<br />
  38. 38. Natural “anthelmintics”<br />Natural “anthelmintics” are not likely to replace the therapeutic use of anthelmintics.<br />However, they may reduce the need for anthelmintic treatments disrupting the parasite’s life cycle.<br />They may become an important aspect of holistic or integrated parasite management systems.<br />
  39. 39. What about a vaccine?<br />So far, limited success in developing vaccines for internal parasites.<br />Paravac Consortium received record €9 million EU grant to fund development of vaccines against parasitic worms.<br />Promising vaccine for Haemonchus developed by Moredun Institute (Scotland) and currently being tested in Australia.<br />Would the vaccine be available to U.S. producers? <br />
  40. 40. Small Ruminant Program<br />Thank you for your attention.<br />Any questions?<br />SUSAN SCHOENIANsschoen@umd.eduwww.sheepandgoat.com<br />
  41. 41. Recordings of the 2011 Worm Webinar series are available at http://www.sheepandgoat.com/ recordings.html.<br />PowerPoint presentations from the 2011 Worm webinar series may be viewed or downloaded from http://www.slideshare.net/schoenian.<br />Additional questions may be sent to Susan @ sschoen@umd.edu.<br />Small Ruminant Program<br />
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