Anthelmintics

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