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Parasite resistance in us cattle

Parasite Resistance in US Cattle
Donald H. Bliss1, PhD; Robert D. Moore2, MS; William G. Kvasnicka3, DVM
1Veterinary Parasitologist, MidAmerica Ag Research, 3705 Sequoia Trail, Verona, WI 53593
2College of Agriculture, Biotechnology & Natural Resources, University of Nevada, Reno, NV 89557
37131 Meadow View, Shawnee, KS 66227

Abstract
s’ensuivre à l’insu des producteurs sauf si ces derni-ers ont un moyen simple de déterminer l’efficacité du Parasite resistance to the macrocyclic lactones produit. Le test de la réduction du nombre d’œufs fécaux (ivermectin, doramectin, eprinomectin, and moxidec- est un simple test recommandé par l’American Associa- tin) is receiving considerable attention in the US cattle tion of Veterinary Parasitologists (AAVP) qui permet aux industry at a time when the economics of parasitism praticiens d’aider les producteurs à déterminer le plus constitute one of the most important factors involved facilement si les vermicides qu’ils utilisent sont encore in beef production. Knowing whether a dewormer is effectifs. Ce test fécal implique une vérification fécale au effective is extremely important to an operation. If para- moment du traitement et ensuite 14 jours après traite- sites become resistant to a particular product or product ment. Entre l’automne 2007 et l’été 2008, l’accès gratuit formulation, a serious problem can develop unknowingly au laboratoire a été offert aux praticiens bovins à la unless producers have an easy way to determine product grandeur des États-Unis afin de leur permettre de faire efficacy. The fecal egg count reduction test (FECRT) is a le test fécal pour leurs clients. Un protocole standardisé simple test recommended by the American Association a été adopté impliquant un minimum de 20 échantil- of Veterinary Parasitologists (AAVP) as the best way lons par groupe de traitement aux deux moments for the practitioner to help producers verify that the d’échantillonnage. Les résultats sont consignés dans une dewormer(s) they are using is effective. The FECRT in- banque de données nationale sous la tutelle d’Intervet/ volves conducting a fecal check at the time of treatment Schering-Plough Animal Health et de l’université de and again 14 days following treatment. In the fall of 2007 Nevada-Reno. Plus de 58 cliniques vétérinaires dans 19 continuing through the summer of 2008, free lab support états participent déjà au programme. Il y a plus de 119 was offered to bovine practitioners throughout the US tests distincts impliquant 4765 échantillons avec une to conduct FECRTs with their clients. This was done panoplie de produits et de formulations. Ces données according to a standard protocol involving a minimum confirment que la résistance aux lactones macrocycliques of 20 samples per treatment group at each collection est étendue et il faut donc une vigilance soutenue de la time. The results are being recorded in a national data part du corps professionnel vétérinaire car le problème base supported by Intervet/Schering-Plough Animal semble maintenant au point critique et il y a des pertes Health and the University of Nevada-Reno. Over 58 de millions de dollars de production en jeu. veterinary clinics in 19 states have already participated in this program, with over 119 separate tests involving Introduction
4,765 samples using a wide range of products and for-mulations. These data confirm that macrocyclic lactone Deworming beef and dairy cattle in the US has resistance is widespread and that continued vigilance is evolved over the past 25 years to become a standard required by the veterinary profession, since the problem recommended practice on many progressive operations, now appears to be at a critical stage with millions of with emphasis on the economic benefits of deworming. dollars in production losses at stake.
Each year, more producers are preventively deworm-ing their cattle at strategic times of the year to prevent Résumé
economic losses caused by parasitism, rather than waiting to deworm cattle until after these animals are La résistance des parasites aux lactones macro- harboring heavy burdens and significant damage to the cycliques (ivermectine, doramectine, éprinomectine et animals has already occurred. Most producers are con- moxidectine) attire beaucoup l’attention de l’industrie cerned about deworming at the optimal time to achieve du bétail aux États-Unis à un moment où les retom- maximum benefit. These producers appreciate having bées économiques des parasites constituent l’un des highly efficacious formulations that are safe and easy principaux facteurs touchant la production bovine. Il to apply, and trust that the efficacy claim approved for est extrêmement important qu’une opération connaisse l’efficacité des vermicides. Si les parasites développent The economic importance of parasitism is chang- une résistance à un produit particulier ou à une formula- ing as animal production becomes more efficient due to tion particulière du produit, un sérieux problème peut continued improvements in genetic, nutrition, implant technologies, and disease control measures. A recent ing programs practiced and the overall management study from Iowa State University identified parasite goals of the operation. The success or failure of these control as the single most important economic factor in strategically timed programs depend upon a number of producing beef efficiently. This study identified parasites factors, one of the most important being the ability of as a major detriment to efficient production and that the anthelmintic to stop parasite eggs being shed back parasites are responsible for adding as much as $190 per on the pastures, especially during the early part of the animal to the cost of raising beef cattle.25 The economics grazing season. If the anthelmintic fails to stop worm- of parasitism calculated for this analysis came from the egg shedding and cattle continue to shed worm eggs effects of parasitism upon reproductive efficiency, rate back on the pasture following treatment, the potential of gain, feed efficiency, carcass quality, milk production for pasture cleanup is greatly reduced or, in many cases, and the immune system through reduced mortality and The failure of the endectocide pour-ons to elimi- It is apparent that as animals become more ef- nate worm egg shedding was identified soon after the ficient, it takes fewer parasites to cause economic loss endectocide pour-ons were first introduced on the U.S. than in less efficient animals. Studies at the University market.8,16,23,34 This continual shedding predisposed the of Wisconsin demonstrated that cows in early lactation surviving parasites and their progeny to develop resis- had greater production loss due to parasite exposure tance to the macrocyclic lactone (ML) compounds used than cows exposed to parasites later in lactation when in the pour-on formulations. Since parasite survival production stresses were much less.5 A second study at and continual egg shedding is occurring while these the University of Wisconsin showed that improvement chemical compounds are still active in the animals and in milk production due to deworming was greatest in the their feces, both the worms themselves and the eggs best managed herds.4 It takes fewer parasites, therefore, being shed on the pasture are exposed to the chemical to cause economic loss in a dairy cow milking 30,000 residue of the compounds in the feces. This reduced ef- lb (13,636 kg) of milk per lactation than one milking ficacy and continual product exposure by the parasites 15,000 lb (6,818 kg) per lactation or in a feedlot animal over time creates the potential for parasite resistance gaining 4.4 lb (2 kg) per day versus an animal gaining to develop to these compounds.13,14,27 This problem is 2.2 lb (1 kg) per day. The more efficient an animal is, the compounded by the “persistent efficacy” feature by these greater impact parasites can have on maintaining this pour-on products. Based on FDA approvals, these prod- efficiency. When parasites are missed by an inefficient ucts exhibit persistent residues in the animals ranging dewormer or because of anthelmintic resistance, unless from 14 to 42 days following treatment depending upon detected quickly, these parasites can be very damaging the product involved. The persistent residues indicate to an operation not only through production losses, but prolonged exposure of the surviving parasites in the also by the continued contamination of the animal’s gastrointestinal tract and parasite offspring (larvae) environment ensuring future infections.
surviving in the manure to the ML compounds, thereby Based on research conducted on the benefits of greatly increasing the chance for development of para- strategically timed deworming, considerable efforts site resistance to these compounds.2 Recent data, in fact, have been made to teach veterinarians, nutritionists, indicate that parasite resistance is now a real threat pharmaceutical representatives, feed company repre- in operations where ML pour-ons have been used for sentatives and producers about these benefits.6,8,11,22,31,32,33 A number of companies have created FDA approved The reason for the reduced efficacy with ML pour- formulations that facilitate the ease of deworming for ons has been identified as the lack of consistent and the producer. These formulations include many non- adequate level of absorption by the endectocide pour- handling forms such as medicated blocks, medicated ons into the bloodstream, when compared to injectable free-choice minerals, medicated range cube or cake formulations of the same products.15 Blood level de- supplements, medicated complete feeds and top-dressed terminations following treatment with doramectin in feed formulations, liquid supplements as well as topi- an injectable formulation demonstrated 90% absorbed while the pour-on formulation was only 15% absorbed. The goal of strategically timed anthelmintic appli- Absorption data is given as follows: 200 mg/kg inject- cation is to prevent economic loss and reduce environ- able ML will deliver a maximum plasma concentration mental parasite contamination by eliminating worm-egg with a mean of 32ng/ml, while a 500 mg/kg pour-on ML shedding for a period of time at least equal to the life will deliver a maximum plasma concentration with a cycle of the parasites removed.1,6,20 This strategy entails mean of 12ng/ml. This reduced blood level (12ng/ml more than simply applying a dewormer. The timing versus 32ng/ml) indicates that many animals may not of the deworming is very important, and things to be be receiving a therapeutic dose following treatment considered include the season of the year, type of graz- with the ML pour-on formulations and the parasites and their offspring are predisposed to possible parasite efficacy value of 74.7% was achieved for moxidectin in resistance. Also, the adult parasites and newly develop- Phase 1 of the second trial and an efficacy value of 0% ing adults that survive pour-on treatment continue to in the second phase of the second trial. Fenbendazole produce eggs that are shed back into the environment maintained an efficacy value of greater than 95% in both of the animals, making these ML pour-ons unsuitable trials. The fecal worm-egg count results from this study for use in a strategic deworming program. revealed that the parasites which survived the first ML The history of the detection of anthelmintic resis- treatment were refractory to a second ML treatment, tance in cattle began as early as 1997 when a FECRT indicating that the ML pour-ons selected for resistant conducted in New Zealand showed that the ML pour-ons parasites during the first exposure were then resistant (moxidectin and ivermectin) failed to control parasites to further treatment by any ML compound. as well as an ML injectable formulation (doramectin).17 Then in 1999, a FECRT conducted in Louisiana showed Materials and Methods
weekly samples taken for eight weeks following treat-ment with ivermectin pour-on and doramectin pour-on The fecal worm egg reduction test (FECRT) is ranged from 50 to 79% efficacy for doramectin and 43% now recommended as a field test to determine whether to 85% for ivermectin.37 This study demonstrated that treatment is successful and that a FECRT with efficacy parasite resistance was already present in Louisiana. less than 90% indicates that anthelmintic resistance is The first field study where parasite resistance was con- present.13,35,37 In the fall of 2007 and continuing through firmed with worm counts at necropsy in a critical efficacy the end of the summer of 2008, a nationwide survey was study was conducted in Wisconsin.16,32 In this study, the set-up to determine the scope and scale of ML resistance. efficacy of doramectin, moxidectin, eprinomectin and FECRTs were offered free to veterinary clinics all across Ivomec® Plus (Merial) was tested. Comparing worm the US by Intervet/Schering-Plough Animal Health as counts to non-medicated control cattle, the efficacy of a valuable tool for practitioners to test whether a par- moxidectin was 88.0%, doramectin was 64.1%, eprino- ticular product of choice was working for their clients. mectin was 73.1% and Ivomec® Plus was 0%. All four A standard protocol was provided for each participating compounds were identified as resistant, with efficacies far below the desired efficacy of 90% or greater.32 Each participating clinic would identify a cooperat- Eprinomectin and moxidectin were further inves- ing producer with a minimum of 20 parasitized animals tigated using the FECRT protocol in two separate com- between six months and two year olds to conduct each mercial beef herds owned by the University of Illinois test. All sampling was done under the supervision of the at the Dixon Spring Agricultural Station in Simpson, participating clinic. Each participating veterinary clinic Illinois to investigate whether the repeated use of eprino- was offered two trials per clinic conducted free, plus each mectin or moxidectin would lead to parasite resistance.16 clinic received additional compensation for their time In the first phase of the first trial, 30 animals in each involved in setting up and conducting the tests. Samples herd received eprinomectin pour-on according to label were collected at the time of treatment and again 14- directions (0.5mg/kg BW). In the second phase, treated days later. These samples were kept cool and sent with animals from the first trials were ranked based on post- ice packs to one of three separate parasitology labs for treatment worm egg counts, blocked and randomly as- analysis using the Modified Wisconsin Sugar Flotation signed to one to two treatment groups. Fifteen animals Method.11 All samples were blinded to treatment, and from each herd received eprinomectin pour-on (0.5mg/kg pre-treatment and post-treatment samples from the BW), while the remaining 15 animals from each herd same location were sent to the same lab. received fenbendazole oral paste (5mg/kg BW). In the first phase of the second trial, 30 animals in each herd received moxidectin pour-on according to label directions (0.5mg/kg BW). In the second phase, treated animals Fifty-eight veterinary clinics located in 19 states from the first trials were ranked based on post-treat- have participated in the survey on parasite resistance, ment worm-egg counts, blocked and randomly assigned conducting 119 FECRTs involving 4,765 samples. The ef- to one to two treatment groups. Fifteen animals from ficacy of the injectable ML formulations was tested in 26 each herd received moxidectin pour-on (0.5mg/kg BW), tests showing the efficacy of Ivomec® (Merial) at 76.2%, while the remaining 15 animals from each herd received Ivomec® Plus (Merial) at 42.6%, Dectomax® (Pfizer, Inc.) at 89.9%, Cydectin® (Ft Dodge Animal Health) at Results demonstrated that an efficacy value of 98.1% and ivermectin (generic) at 50.0%. The overall 84.8% was achieved for eprinomectin in Phase 1 of the efficacy of the ML injectable formulations was 72.5% first trial and an efficacy value of 5.5% in the second (Table 1). The efficacy of the ML pour-on formulations phase of the first trial. Results demonstrated that an was tested in 60 tests showing the efficacy of Ivomec® Table 1. Efficacy of macrocyclic lactone injectable formulations from FECRTs* conducted by veterinary practitioners
and submitted to Intervet’s national database.
Injections:
** All samples taken at treatment and again two weeks post-treatment.
Table 2. Efficacy of macrocyclic lactone pour-ons from FECRTs* conducted by veterinary practitioners and submit-
ted to Intervet’s national database.
Pour-ons:
* Fecal egg count reduction tests. **All samples taken at treatment and again two weeks post-treatment. at 72.3%, ivermectin (generic) at 59.7%, Dectomax® mintic resistance to any product as efficacy values of at 78.9% and Cydectin® at 67.2%. The overall efficacy below 90%.15,38 Positive worm-egg counts two weeks fol- of the ML pour-ons was 66.1% (Table 2). The efficacy lowing treatment indicate incomplete kill, however, egg of Safe-Guard®/Panacur® was tested in 24 tests with counts don’t identify the size of the residue population 1,016 samples with a mean pre-treatment egg count of parasites which remain in an animal after treatment. of 67eggs/3gm and a mean post-treatment egg count An extensive feedlot production study involving over of 0.4 egg/3gm for an overall efficacy of 99.4% (Table 700 yearling cattle showed that a mean fecal worm-egg 3). In nine trials, a combination treatment was given, count of 9.0 epg decreased gain by 4.2%, while a high with either Safe-Guard® or Panacur® given at the same worm burden with a mean fecal worm egg count of 47.0 time as a ML injectable or ML pour-on formulation with epg decreased gain by 13.3%.33 The overall summary either Ivomec®, Dectomax®, or Cydectin®. These tests of all ML injectable formulations in 26 tests involving involved 261 samples, with a mean pre-treatment count 884 cattle was a mean egg count of 21.8 eggs/3gm and of 152.1 eggs/3gm and a mean post-treatment count 19.0 eggs/3gm for the ML pour-ons in 60 tests conducted of 0.1 egg/3gm for an overall efficacy of 99.9% mean with 2,486 cattle. Since these tests were conducted across 19 states, it is evident that ML resistance is now widespread and the cost of ML resistance to US cattle Discussion
producers may be in the millions of dollars. The dilemma which occurs for the US cattle pro- The World Association for the Advancement of ducer is that for many, ML formulations are an impor- Veterinary Parasitology (WAAVP) has defined anthel- tant part of their arsenal of products used to control Table 3. Efficacy of various Safe-Guard®/Panacur® formulations from FECRTs* conducted by veterinary practi-
tioners and submitted to Intervet’s national database.
Safe-Guard®/Panacur® Overall summary** * Fecal egg count reduction tests. **All samples taken at treatment and again two weeks post-treatment. Table 4. Efficacy of Safe-Guard®/Panacur® in combination with various macrocyclic lactone formulations from
FECRTs* conducted by veterinary practitioners and submitted to Intervet’s national database.
Safe-Guard/Panacur Drench plus:Ivomec® Inj. * Fecal egg count reduction tests. **All samples taken at time of treatment and again two weeks post-treatment. external parasite (lice, mites, grubs and flies). In nine 3. Bisset SA: Efficacy of a topical formulation of ivermectin against tests in 261 cattle, where fenbendazole was given at the naturally acquired gastro-intestinal nematodes in weaner cattle. New same time as a ML injectable or ML pour-on formulation, 4. Blackburn BL, Hanrahan LA, Hendrix CM, Lindsay DS: Evaluation the FECRT indicated a mean efficacy of 99.9% across all of three formulations of fenbendazole (10% suspension, 0.5% pellets nine tests (Table 4). From these tests, it appears that and 20% premix) against nematode infections in cattle. Am J Vet Res whenever a ML formulation is used for external parasite control, it should be used simultaneously with a non-ML 5. Bliss DH, Todd AC: Milk production by Wisconsin dairy cattle after deworming with Baymix®. Veterinary Medicine/Small Animal Clini- internal parasiticide to prevent losses due to internal cian (September) 1034-1038, 1973.
parasitisms and to prevent the further transfer of ML 6. Bliss DH, Todd AC: Milk losses in dairy cows after exposure to infective trichostrongylid larvae: Veterinary Medicine/ Small Animal Clinician, 1612-1617 (October) 1977.
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Technologies in Modern Beef Production. Ames, Iowa State University, 12. Bliss DH, KvasnickaWG: Failure of avermectins to control an outbreak of parasitic gastro-enteritis in a cow/calf herd. In: Proc 49th 28. Majia MF, Fernandez Igartua BM, Schmidt EE, Cabaret J: Mul- Am Assoc Vet Parasitol. Philadelphia, PA, July 24-28 (Abstract 42), tispecies and multiple anthelmintic resistance on cattle nematodes in a farm in Argentina: the beginning of high resistance? Vet Res 13. Bumgarner SC, Brauer MA, Corwin RM, Thomas EA, Myers GH, Strategic deworming for spring-calving beef cow/calf herds. Am J Vet 29. Prichard RK, Hall CA, Kelly JD, Martin ICA, Donald AD: The problem of anthelmintic resistance in nematodes. Aus Vet J 56:239- 14. Campbell WC, Benz GW: Ivermectin: a review of efficacy and safety. J Vet Pharmacol Therap 7:1-16, 1984.
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naturally acquired nematode infection of beef calves. Vet Parasitol 24. Kvasnicka WG, Krysl LJ, Torell RC, Bliss DH: Cow/calf herd investigation: fenbendazole in a strategic deworming program. The 38. Woods IB, Amaral NK, Bairden K, Duncan JK, Kassai T, Malone Compendium, Food Animal Parasitology, April, 18:113-177, 1996.
JB, Pankavich JA, Reinecke RK, Slocombe O, Taylor SM, Vercruysse 25. Kvasnicka WG, Bliss DH, Torrel RC: Evaluation of anthelmintic J: World Association for the Advancement of Veterinary Parasitology treatments in cattle grazing Great Basin rangeland in Nevada and (W.A.A.V.P.) second edition of guidelines for evaluation the efficacy of California. In: Proc 42nd Am Assoc Vet Parasitol. Reno, NV, July 12-22 anthelmintics in ruminants (bovine, ovine, caprine). Vet Parasistol 26. Kvasnicka WG, Bliss DH: Field efficacy of endectocide pour-on formulations against gastrointestinal nematodes. In: Proceedings of the 47th Am Assoc Vet Parasitol. Nashville, TN, July 13-16, 2002.

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