IV. Using anthelmintics effectively Products, usage, resistance, refugia, alternatives, future
May 11, 2015
IV. Using anthelmintics effectivelyProducts, usage, resistance, refugia, alternatives, future
What is an anthelmintic?An agent that kills or causes the expulsion of parasitic worms.Also called dewormer, wormer, drench, or parasiticide.
There are three anthelmintic classes.Based on similar chemistries, modes of action, and cross-resistance.
1. Benzimidazoles (BZ)
2. Macrocylic lactones (ML)1) Avermectins2) Milbemycins
3. Nicotinic antagonists1) Imidazothiazoles (IMID)2) Tetrahydropyrimidines (TETR)
1 - Benzimidazoles (BZ) First class of modern anthelmintics (1961)
1. FenbendazoleSafe-guard®Panacur®
2. AlbendazoleValbazen®
3. OxfendazoleSynanthic®
4. Thiabendazole TBZ
Benzimidazoles kill worms by interfering with energy metabolism on a cellular level by binding to beta tubulin.
1 - Benzimidazoles (white drenches)
• Broad spectrum1. Adult and 4th stage larvae of roundworms2. Adult liver flukes
(Valbazen® only)3. Heads and segments of tapeworms
(Valbazen® or 2x labeled dose of Safe-Guard®)
4. Effective against hypobiotic larvae5. 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.
2- Macrocylic lactones (ML) Newest family of anthelmintics - circa 1980’s
1) Avermectinsa) Ivermectin
Ivomec®Primectin®
b) EprinomectrinEprinex®
c) DoramectinDectomax®
2) Milbemycinsa) Moxidectin
Cydectin®Quest® Macrocylic lactones interfere with GABA-mediated
neurotransmission, causing paralysis and death of the parasite.
2 - Macrocylic lactones (ML)• Potent
• Persistent activity (+/-)
• Broad spectrum1. Adult and 4th stage larvae of
roundworms2. Some external parasites
(Ivermectin: larval stages of nasal bots)
3. Effective against hypobiotic larvae4. One of the drugs of choice for
meningeal worm (ivermectin).
• Potential negative effect on dung insects.
• Widespread resistance reported, especially avermectins.
3- Nicotinic agonists
1) Imidazothiazoles (IMID)a) Levamisole
Prohibit®Tramisol®Levasol®
2) Tetrahydropyrimidines (TETR)a) Morantel
Rumatel®b) Pyrantel
Strongid®
Act as agonists at nicotinic acetylcholine
receptors of nematodes, causing
paralysis of the worms.
3 - Nicotinic agonists
1. 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.
2. Rumatel– Oral feed additive– Effective against adult worms only– Not much is known about resistance levels.
FDA-approved anthelmintics
SHEEP1. Ivomec® sheep drench
Ivermectin2. Cydectin® sheep drench
Moxidectin3. Prohibit® drench
Levamisole4. Valbazen® liquid
Albendazole
GOATS1. Safe-Guard® suspension
Fenbendazole2. Valbazen® liquid
Albendazole[liver flukes only]
3. Rumatel® premixMorantel
Different anthelmintics may be approved and available in different countries.
Withdrawal periods for FDA-approved anthelmintics
AnthelminticSheep Goats
Meat Milk Meat Milk
Valbazen® suspension 7 days Not est. 7 days Not est.
Prohibit® drench 3 days Not est. NA NA
Cydectin® drench 7 days Not est. NA NA
Ivomec® drench 11 days Not est. NA NA
Rumatel® premix NA NA 30 days Not est.
Safe-Guard® suspension NA NA 6 days Not est.
Source: Animal Drugs @ FDA and product labels
Withdrawal periods for extra-label anthelmintics in goats
Anthelmintic Meat Milk
Valbazen® suspension 9 days 7 days
Safe-Guard® @ 2x label dose 16 days 4 days
Ivomec® sheep drench 14 days NA
Prohibit® drench(1 packet/262 ml water) 4 days NA
Cydectin® pour-on (orally) 23 days NA
Cydectin® sheep drench 14 days NA
Cydectin® injectable 120 days NA
Source: Food Animal Residue Avoidance Database (FARAD) and/or http://www.luresext.edu/goats/training/GoatDewormerChart.pdf
Anthelmintic resistanceAbility of the worms to survive anthelmintic treatment
• Official definition: 95% or less reduction in fecal egg count (FECRT).
a) Widespread in parasites of sheep, goats, and horses. Has been reported in all anthelmintics.
b) Developing in cattle parasites.
c) 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
Anthelmintic resistanceResearch conducted by Delaware State University (2009)
Anthelmintic % farms
Fenbendazole 97
Ivermectin 56
Moxidectin 50
Levamisole 2819 goat and 13 sheep farms in MD, DE, PA, VA, and WV were tested for anthelmintic resistance using the larval development assay at the University of Georgia.
• Varies by geographic region and individual farm.• A result of past anthelmintic use.• Anthelmintic resistance is PERMANENT.
Anthelmintic Sheep Goat
Fenbendazole 5/5 5/5
Ivermectin 3/4 5/5
Moxidectin 2/4 1/5
Levamisole 1/4 0/54 sheep and 5 goat farms in the Mid-Atlantic region were tested for anthelmintic resistance using the FECRT and larval development assay.
Causes of anthelmintic resistance
❶ Frequent deworming
• Treating all animals at the same time.
• Putting treated animals onto a clean pasture.
Causes of anthelmintic resistance❷ Under-dosing
– Not weighing animals– Inability to accurately
estimate weights– Not calibrating equipment for
heaviest animals in group.
• Using anthelmintics with residual activity– Persistent-activity anthelmintics– Injectables– Pour-ons
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
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.
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”
Preliminary dataEfficacy of anthelmintic combinations in goats
Treatment FECR %Albendazole 76Levamisole 39
Moxidectin 74
Albandazole + levamisole 85
Albendazole + moxidectin 98
Levamsiole + moxidectin 98Albendazole + levamisole + moxidectin 99
Copper oxide wire particles (2 g) 28
Control 14
Initial FECs ranged from 250 to 13,500 and averaged 2,550 epg. 8.6 animals/Tx
Treatment FECR %
Moxidectin 100
Levamisole 14
Albendazole 21
Levamisole + albendazole 94
Levamisole + albendazole + moxidectin 100
4 animals/Tx
Research conducted at Langston University (OK)
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.
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!
CoccidiostatsA 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 .
Coccidiostats
1. Ionophoresa) Lasalocid
Bovatec®
b) Rumensin®Monensin
2. Quinolonea) Decoquinate
Deccox®
3. Amprolium (Rx)Corid®
Affect mitochondrial function
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).
Coccidiostats FDA-approved for use in sheep and goats
Trade name Ingredient Dosage Approved species and class
Bovatec® Lasalocid 15-70 mg/d20-30 g/ton of feed Sheep in confinement
Deccox® Decoquinate 22.7 mg/100 lbs. BW13.6 g/ ton of feed
Young, non-lactating sheep and goats
Rumensin® Monensin 20 g/ton of feed Goats in confinement
Corid® Amprolium Consult with veterinarian Extra-label
Source: Animal Drugs @ FDA
Rumensin® can be toxic to equines and dogs.
There is no withdrawal period for slaughter.
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 choices1. Amprolium (Corid®)2. Sulfa drugs
http://old.cvm.msu.edu/extension/Rook/ROOKpdf/coccidia.PDF
1 - Corid® (amprolium)
• Labeled as an aid in the prevention and treatment of coccidiosis in beef and dairy cattle.
21 day prevention 5 day treatment
• Mimics 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
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
What’s “new” in parasite control?
New anthelmintics
ZOLVIX® • Monepantel• New class of anthelmintic: amino-
Acetonitrile derivatives (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.
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
Copper for internal parasite controlRisk: copper toxicity in sheep
1. Dietary Mineral mix Feed supplement
2. DrenchCopper sulfate
3. BolusCopper oxide wire particles (COWP) CuSO4
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
Natural “anthelmintics”Significant research effort underway
• Garlic juice• Pumpkin seed• Mustard seed• Oregano oil• Papaya • Diatomaceous earth (DE)• Bioactive plants (herbal)
– Artemisia spp. – Sericea lespedeza– Birdsfoot trefoil– Chicory– Pine bark
Sesquiterpene lactonesCondensed tannins
Nematode-trapping fungusDuddingtonia flagrans
• Spores are fed to livestock as part of their diet.
• Spores pass through digestive tract of livestock and are deposited in the feces.
• Spores germinate alongside worm eggs.
• Spores trap and feed on newly emerging larvae.
No commercial product (yet)Image source: Louisiana State University
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.
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?
Thank you for your attention.
Any questions?
SUSAN [email protected]
www.sheepandgoat.com
SMALL RUMINANT PROGRAM
• 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 @ [email protected].
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