MidAmerica Ag Research Donald H. Bliss, Ph.D. Veterinary Parasitologist Verona, WI www.midamericaagresearch.net Iowa State Review of 170 Publications Economic Analysis of Pharmaceutical Technologies in Modern Beef Production By John D. Lawrence and Maro A. Ibarburu Authors Reviewed Five Technologies 1). Parasite Control 2). Growth Promotant 3). Sub therapeutic Antibiotics 4). Ionophores 5). Beta Agonist Value Created by Strategic Deworming Lifetime Return = $190.00 All Five Technologies = $360.00 Authors estimated value of each parameter with cow/calf, stockers and feedlot cattle. 1
Parasite Control is the first step to improving animal health. Parasite Control is Necessary for Efficient Animal Production! Parasites are a major underling cause of many problems in cattle. One of the most important problems is the parasite s effect on the immune system. A seasonal deworming program is needed to prevent production losses on most operations. Parasites are a major underling cause of many problems in cattle including slow growth, poor feed conversion and reduced reproduction performance. One of the most important problems is the parasite s effect on the immune system. Using Science to Monitor Your Deworming Programs! All grazing cattle need annual dewormings, in most cases, at least two strategic treatments are required. Not all dewormers work due to parasite resistance. Fecal worm exams are the only way to determine if deworming is successful. 2
Nutrient Use by Beef Cattle Of all the nutrients an animal consumes, parasites get their share right off the top! Nutrients left over after the parasites get their share will be used by maintenance and then on down the list Hierarchy of Nutrient Use #1 Parasites #2 Condition #3 Breeding #4 Milk Production #5 Growth #6 Fetus development #7 Maintenance 3
PREVENTION IS THE BEST STRATEGY The Economics of Deworming Cattle is Changing! Where Are The Parasites? Economic costs of parasitism is changing. It takes fewer parasites to cause economic loss in highly efficient animals. Widespread efficacy problems with pourons and injectable endecticides are leaving parasite problems undetected. Only 1% are in the cattle While 99% are on the pasture 4
Worms eggs are like weed seeds contaminating the pastures. Larvae follow moisture trails & move away from mature pats 5
Infective stage L 3 larvae are mobile and move away from pat onto the herbage to be consumed. 6
Infective L3 Larva are protected with covering sheath. 7
Gastro-Intestinal Parasites 1). EGGS AND L3 LARVAE CAN SURVIVE ON PASTURES FOR ONE YEAR. 2). THEY SURVIVE PROTECTED IN THE SOIL, IN MANURE PATS OR UNDER A GRASS MAT. 3). THEY CAN SURVIVE SEVERE WINTER CONDITIONS ESPECIALLY WITH SNOW COVER. The Life Cycle Females produce eggs which pass in manure. Hatch in 7-10 days > 50 F Below 40 F development stops. Hatch into L 1, to L 2 and then L 3. Eggs & L 3 larvae over winter DIRECT EFFECTS : Anorexia Interference with digestion Increased gut motility Disruption of fluid and mineral homeostasis Effects of Parasites Parasites Derail Growth Suppress Appetite Dewormed Cattle Parasite-Infected Cattle 8
Parasites Interfere with Production! Effects of Parasites on the Immune System Parasites Suppress the Immune System! The level of immunosuppression is directly related to the parasite burden. Fast-acting dewormer is important in heavily infected animals if dewormed at vaccination time. 9
Results of Pathogen-Immune System Interaction Changes in Mass of Draining Lymph Nodes after Infection with Ostertagia Suppression of Specific Immune Responses - TH1 (intercellular response) vs. TH2 (extracellular response). Worm Burdens Promote TH2 Production which suppress TH1 Production. Example: Seldom observe coccidiosis in worm-free cattle. Mesenteric Lymph Nodes Cooperia infection Feedlot Health Data Pasture Control FBZ Feedlot Control FBZ Control FBZ No. dead 4 0 1 0 No treated 22 13 6 4 Percent of total 4% 29% 13% 9% Normal 35 days post-infection No treatments 34 13 6 4 Percent of total 60% 23% 10% 7% Oklahoma/Colorado Strategic Deworming Trial 10
Combined Grazing-Finishing Gain (239 Days) Pasture Control FBZ Feedlot Control FBZ Control FBZ No. pens 20 20 20 20 No steers 155 160 159 160 Total gain 584 652 663 686 Daily gain 3.63 4.15 3.86 4.03 Advantage -- 68 lbs 78 lbs 103 lbs Oklahoma/Colorado Strategic Deworming Trial Parasite Resistance in Cattle Macrocyclic Lactone Resistance Resistance to Macrocyclic lactone (ivermectin type products) is true resistance -passed from one generation to the next. New problem with serious economic consequences affects many species of parasites. Growing in magnitude - now worldwide problem!! Resistance will not get better only worse! Permanent Passed from one parasite generation to another. Once ML Resistance occurs further ML treatment will no longer provide acceptable efficacy. Increased product (i.e 2X) does not work. Cross resistance between all MLs. 11
Endecticides/Macrocyclic Lactones Avermectins Ivomec Ivomec Eprinex Dectomax Generic Ivermectins Moxidectins Cydectin Endectocide pour-ons: poor efficacy promotes resistance. Continued egg-shedding on pastures following treatment causes continued contamination. Parasites and their offspring that survive treatment by pour-ons are resistance to macrocyclic lactones. Producers are unknowingly experiencing production losses due to failure of pour-ons. Injectable Endecticide vs. Pour-On Anthelmintic Comparison Fenbendazole vs. Endectocides Doramectin Injectable Dose 200 mcg/kg Plasma concentration Max=32 ng/ml plasma Doramectin Pour-On Dose 500 mcg/kg Plasma concentration Max=12 ng/ml plasma > Injectable formulation delivered 3X the amount of active ingredient to the blood. > Standard deviation for the Pour-On was extremely large at +/- 6ng/ml. Drug Level >> Treatment Fenbendazole Endectocides (Concept Illustration) Lethal Dose Selection Pressure for Resistant Parasites 72 hours Day 3 Day 4 Day 5 Day 40 Day 80 Dectomax Pour-On Formulation Product Monograph produced by Pfizer, Inc, 1998 12
Egg Counts 200 175 150 125 100 75 Mean Fecal Worm Egg Counts From Endecticide Pour- On Treated Cattle In Lousiana Rx Persistence Patency Control Doramectin Ivermectin Ivermectin Resistance Case Report 50 25 0 0 7 14 21 28 35 42 49 56 70 85 98 112 Post Treatment Days March, 2003 March-December, 2003 1,200 Cow/calf Operation in Southeastern USA Experiencing Parasite Problems. Animals in poor condition, some cow show extreme emaciation, soon cows began to die. 45 cows died altogether. Two cows were necropsied following treatment with Ivomec Pour-on and parasitism was diagnosed as cause of death. Dewormed in March (Ivomec PO), April (Ivomec PO,) May (Ivomec Injection), July (Eprinex), November (Dectomax) and December (Ivomec Plus). Animals remained in poor condition, some cow show extreme emaciation. 13
December, 2003 January-March, 2004 Merial sends Consultant (Dr. Ed Riche) to the ranch. Fecal samples taken 10-days post -treatment with Ivomec Plus shows high egg counts. Larval cultures indicate 65% Ostertagia, 26% Cooperia and 15% Trichostrongylus. All Cattle received Safe-Guard Medicated Cubes in early January and again in March. Parasite Resistant Problem Solved! 14
Intact Fecal Pats Pastures observed to have high numbers of intact fecal pats. Dung beetle activity possibly low due to extensive use of Ivomec Pour-on. Research shows that dung beetles help destroy parasitic larvae in fecal pat. High numbers of intact fecal pats indicate high larval challenge on pasture which led to the death of adult cows since ivermectin was no longer working. 15
Dung beetles are an important part of the pasture ecosystem. 1. Increased pasture yields by incorporation of organic matter into the soil. 2. Reduction of insect pest populations. 3. Prevention of pasture surface pollution. 4. Reduction of animal diseases by removing contaminated feces. 5. Return nutrients to the soil that would otherwise be tied up in fecal deposits. 6. Increased effective grazing areas of pastures covered by feces. 7. Reduced nitrogen loss in livestock feces. Deworming History of 5,500 Stockers in Wisconsin Intensive grazing system - 18+ yrs. all animal strategically timed deworming Dewormers used: Fenbendazole given free-choice in salt mineral. Veterinarian changed program to 0-6 week using Ivomec Plus? Pasture Treatment Following Spring Ivomec Plus Treatment Parasitic gastroenteritis developed in fall producer lost thousands in gain. EPG on Oct. 31 2002 = average 104 USDA Investigation on Parasite Resistance. Highest egg count animals chosen for slaughter Animals killed 14 days after drug treatment Pour-on Animals segregated 16
Worms Recovered - Critical Efficacy Study 2004 Treatment Mean ABO Mean SI (Cooperia) Mean Percent Total Reduction None 1,575 8,563 10,138 -------------- Cydectin 448 763 1,211 88.0% Panacur (FBZ) 333 17 350 96.5% Dectomax 909 2,725 3,634 64.1% Eprinex 1,733 988 2,721 73.1% FECRT (Fecal Egg Count Reduction Test) Best way to check for resistance as endorsed by USDA North American Animal Health Monitoring System (NAAHMS). Take 20 samples at the time of treatment. Take 20 samples 14-days later to check efficacy. Ivomec Plus 993 14,792 15,785 0% FECRT Results Table 1: Efficacy Summary of ML Pour-ons using the Fecal Worm Egg Count Reduction Test. 250+ Participating Veterinary Clinics. 23 States Represented. 418 Trials Completed. 17,638 Samples Analyzed. 8,839 Pre-treatment Samples. 8,799 Post-treatment Samples. No. of No. of Egg Counts/3g* Percent Products Trials Samples Pre-Rx Post-Rx Efficacy Ivomec PO 15 598 67.1 31.3 54.8% Ivermectin PO 77 3,207 64.2 30.8 52.0% Dectomax PO 22 898 65.6 23.1 64.9% Cydectin PO 21 878 55.7 14.5 70.0% Eprinex PO 3 124 15.2 3.4 77.6% --------------------------------------------------------------------------------- PO Summary 138 5,706 62.7 26.1 58.4% *All samples taken at Rx and again 14-dasys post-rx. **Updated Jan. 6, 2012 17
Table 2: Efficacy Summary for FECRT (Fecal Egg Count Reduction Test) Conducted with Injectable ML Endecticides. No. of No. of Egg Counts/3g* Percent Products Trials Samples Pre-Rx Post-Rx Efficacy Injections: Ivomec Inj. 19 869 76.5 38.0 50.3% Ivomec Plus 13 547 104.6 59.8 42.9% Dectomax Inj. 31 1,278 62.4 13.5 78.3% Cydectin Inj. 9 394 32.1 5.2 83.1% Ivermectin Inj. 13 824 90.0 46.6 48.3% Generic Ivo. Plus 5 194 97.5 45.6 50.1% ---------------------------------------------------------------------------------------- Inj. Summary: 90 4,106 74.3 30.6 58.8% *All samples taken at Rx and again 14-days post-rx. **Updated Jan. 6, 2012 Table 3: Efficacy Summary for FECRT (Fecal Egg Count Reduction Test) Conducted with Various Safe- Guard /Panacur Formulations. Number of Number of Egg Counts/3g* Percent Products Trials Samples Pre-Rx Post-Rx Efficacy(%) Panacur Drench 32 1,296 59.3 0.7 98.8% SG Drench/Paste 62 2,527 69.2 0.6 99.1% Summary Drench 94 2,901 64.4 0.8 99.8% ---------------------------------------------------------------------------------------- SG Feed 22 1,172 47.4 0.1 99.7% SG Mineral 7 265 36.4 1.4 98.9% SG 1.96% 3 116 39.5 0.2 97.3% Liquid Feed 10 388 42.3 1.4 96.6% Cubes/blocks 8 366 36.6 2.1 94.3% ----------------------------------------------------------------------------------------- Overall Summary** 144 6,130 56.7 0.8 98.5% *All samples taken at Rx and again 2 weeks post-rx. **Updated Jan. 6, 2012. Table 4: Efficacy Summary for FECRT (Fecal Egg Count Reduction Test) Conducted with Safe-Guard /Panacur in Combination with Various Endecticide. Table 5: Efficacy Summary for FECRT (Fecal Egg Count Reduction Test) Conducted for all Products Combination No. of No. of Egg Counts/3g Percent Product Trials Samples Pre-Rx Post-Rx Efficacy --------------------------------------------------------------------------------------------------------------- Safe-Guard or Panacur plus: Ivomec PO 8 272 76.4 0.3 99.6% Ivomec Inj./Plus 9 213 82.2 0.1 99.9% Ivermectin Inj./PO 24 909 60.1 0.3 99.5% Dectomax Inj./PO 5 181 97.9 0.1 99.9% Cydectin PO 1 41 134.2 0.1 99.9% ------------------------------------------------------------------------------ Combination 47 1,696 75.4 0.2 99.6% Summary *Updated Jan. 6, 2012. No. of No. of Egg Counts/3g** Percent Products Trials Samples Pre-Rx Post-Rx Efficacy Endecticide Injectable: 84 3,676 72.8 30.5 58.1% Pour-On: 131 5,110 63.9 26.6 58.3% Safe-Guard /Panacur 144 6,130 56.7 0.8 98.5% Combination Treatment*** 47 1,696 75.4 0.2 99.7% *Updated Jan. 6, 2012, **All samples taken at Rx and again 14-days post-rx. *** Safe-Guard plus an Endecticide 18
Table 6: Comparison of FECRT Efficacy for ML Pour-Ons 2008 (AABP) vs. 2011 (Dec.1) Products No. of Trials Percent No. of Trials Percent Efficacy 2008 Efficacy 2011 Efficacy Change ---------------------------------------------------------------------------------------------------------------- Ivomec 8 72.3% 14 54.4% - 17.9% Ivermectin 35 59.7% 75 52.9% - 6.8% Dectomax 8 78.9% 20 66.0% - 12.9% Cydectin 9 67.2% 19 76.0% + 8.8% ------------------------------------------------------------------------------------- Summary 60 66.1% 128 58.3% - 7.8% Table 7: Comparison of FECRT Efficacy ML Injectables: 2008 (AABP) vs. 2011 (Jan. 12) Products No. of Trials Percent No. of Trials Percent Efficacy 2008 Efficacy 2011 Efficacy Change --------------------------------------------------------------------------------------------------- Ivomec 6 76.2% 19 50.3% - 25.9% Ivomec Plus 6 42.6% 13 42.9% + 0.3% Ivermectin or Ivermectin plus 1 50.0% 13 48.3% + 1.7% Dectomax 11 90.5% 30 77.9% - 12.6% Cydectin 2 98.1% 9 83.8% - 14.3% ---------------------------------------------------------------------------------- Summary 26 72.5% 84 62.3% -10.2% Table 8: Comparison Summary of FECRT Efficacy (%) of ML (Pour-ons & Injectables) by year. Ivomec Ivo-Plus Ivermectin Decto Cydectin ----------------------------------------------------------------------- 2007 49.6 43.5 62.7 82.6 72.5 2008 64.7 ----- 58.3 50.1 95.5 2009 55.0 49.4 44.7 65.2 72.1 2010 44.5 0.0 37.6 75.9 78.3 2011 49.6 44.9 47.1 72.4 76.0 --------------------------------------------------------------------- Conclusions 1. Parasite resistance was demonstrated for all Macrocyclic Lactones by FECRT database except Cydectin and Dectomax Injectable Products. 2. Resistance appeared to be widespread from data collected throughout 23 states. 3. FECRT data indicated resistance can be overcome with chemistry change or combination use (ML plus FBZ). 4. Overall, resistance to ML Pour-on and Injectable products appears to be getting worse. 19
Summary Summary (cont.) The widespread development of parasite resistance is a very serious problem for cattle producers. To solve this problem producers need to know whether or not dewormers are working. Resistance will not improve but rather only get worse! Combination of a macrocyclic lactone plus Safe-Guard at key times will prevent parasite resistance. Key times are at arrival in feedlots, at weaning, incoming stockers and for late fall strategic treatment. Use Safe-Guard only for spring-time strategic dewormings. Combination Advantages Ability to rapidly remove parasites with Safe-Guard. Synergistic effect on different species of parasites Safe-Guard better on Intestinal parasites such as Cooperia, Trichostrongylus, & Nematodirus Avermectin s good for Inhibited Ostertagia, Lice, & Grubs Four Large Scale Feedlot Combination Trials 10,381 total cattle Evaluate the effect of Safe-Guard with Ivomec Pour On or Ivomec Injectable vs Ivomec PO Dectomax Injectable Ivomec Injectable Cydectin Injectable 20
Combination Trials: Economic Summary Trial #1 Trial #2 Trial #3 Trial #4 $22.19/hd $9.01/hd $4.20/hd $17.82/hd The Best Dewormer in the World Used at the Wrong Time Is a waste of time and money! Average: $13.31/head PREVENTION IS THE BEST STRATEGY 21
Strategic Deworming A management tool Treats both cattle & pastures Creates parasite-safe grazing season Cost effective results Improves health & production Increases profitability Larvae follow moisture trails & move away from mature pats Epidemiological Patterns of Worm Egg Counts and Pasture Larval Counts in Cattle. 12 1200 10 Pasture Larvae Fecal Eggs 10 1000 Larva/Kg DM x 103 8 6 4 2 0 8.2 8 800 6 600 5.4 4.2 4 4 400 299 3 2.9 275 2 211 221 223 199 200 121 100 98 101 0.8 0 0 0 0 0 0 0 0 1-Apr 15-Apr 1-May 15-May 1-Jun 15-Jun 1-Jul 15-Jul 1-Aug 15-Aug 1-Sep 15-Sep 1-Oct 15-Oct 1-Nov Eggs/gram feces 22
How Does Strategic Parasite Control Work? GOAL is to prevent pasture contamination during the first 60-90 days of the grazing season. Timing is Everything! Strategic deworming is key to parasite control on pasture. Mid-Spring dewormings break the cycle on pasture. Yearling cattle need more aggressive deworming schedule than brood cows. Final treatment in late fall or early winter. 23
First make sure cattle are parasite-free at the beginning of the season. How? Deworm in late fall or early winter with a combination of Safe-Guard and a pour-on (for lice control) or Safe-Guard at turnout. Second: Treat cattle strategically with Safe-Guard in Spring after grazing but before new worms begin shedding. How? Use Safe-Guard in a formulation that works for your operation, i.e., in the feed, blocks, cubes, mineral or drench. Don t use an ivermectin type product (macrocylic lactone) in the spring (after the first of March) because of the dung beetle! Rx cows if no fall treatment Grazing begins Pasture Contamination Beef Cows 6 wks From previous year Rx cows 6 wks Rx cows in south Deworm (Rx) Cows SPRING SUMMER FALL WINTER 24
Economic Benefit From Strategic Deworming in Cow/Calf Operations Location Weaning Wt Adv Improved Breeding Florida +17 lbs 10% Florida +43 lbs 10% Georgia +16 lbs 22% Hawaii +46 lbs NM Minnesota (2) +33 lbs 12% Missouri (2) +37 lbs NM Montana (2) +20 lbs NM North Dakota +30 lbs NM Oklahoma +37 lbs NM Texas (4) +32 lbs NM Summary +31 lbs 11% Pasture Contamination Stockers & Replacement heifers Purchased Rx at turnout 4 wks Rx From previous year 4 wks From previous year Rx (>90 days grazing) Deworm (Rx) retained cattle SPRING SUMMER FALL WINTER Economic Benefit From Strategic Deworming in Stocker Cattle Location Length Of Trial Improved Gain California 109 days 24 lbs Louisiana 155 days 67 lbs Missouri 132 days 67 lbs Texas 158 days 30 lbs Virginia 100 days 64 lbs Virginia 111 days 64 lbs Virginia 120 days 20 lbs Virginia 138 days 90 lbs Wyoming 112 days 14 lbs Summary 126 days 49 lbs 25
Advantages of Fenbendazole Non-Handling Formulations Cumulative dose properties. Flexible feeding period. Dose can be spread over 3-6 days. Mix in free-choice mineral. Mix in feed or top-dress. Palatability (no taste/smell). Safe in varied consumption situations. Drench or labor-free administration. Highly effective against major cattle worms. 26
Designing a Program in a Give Dairy Operation First determine the approximate level of parasitic contamination 1. High Parasite Contamination Level Cows grazing pasture during lactation When rotational grazing is practiced 2. Moderate Parasite Contamination Level 4. Extremely Low Parasite Contamination Level Cows grazing pasture only during dry period Cows with access to an exercise lot (with some grass) Cows in total confinement. Cows on a concrete dry lot. 27
Research Links Parasitism to Decreased Milk Production! Comparison of Milk Production After Parasite Exposure Relative to Stage of Lactation Group # of Cows Base Period Ave lb/day Exposure Period Ave lb/day Change Ave lb/day Production from Cows <90 days Non- Infected 10 49.96 55.15 +5.19 Infected 12 51.19 49.91-1.28 Production from Cows >90 days Non- Infected 14 45.65 44.05-1.60 Infected 12 45.73 43.75-1.98 Result of Exposure Ave lb/day -6.47 +0.38 First Step is to Profile Herd; Second Step is to Take Fecals. Visually determine chance of parasite exposure based on management conditions. Cattle need exposure to bedding, dirt pens or pasture for parasite exposure. Confirm observation with fecal worm egg counts to determine where infections are present in an operation. 28
Combination Deworming Program Deworm all animals in late fall. Beginning in the spring, deworm cows in transition or at freshening. Deworm heifers twice in the spring four weeks apart after turnout. MidAmerica Ag Research Donald H. Bliss, Ph.D. Veterinary Parasitologist Verona, WI www.midamericaagresearch.net 29
30
Merck Animal Health - Warrantee on fenbendazole for cattle. - Take samples at treatment and two weeks later. - Post treatment samples 90% clean or re-deworm for free. Merck Animal Health Provides free lab service for all fecal checks on PEC day. Warrantee on fenbendazole for cattle Post treatment samples 90% clean or re-deworm for free. Mail in to: Mid America Ag research 3705 Sequoia Trail Verona, WI 53593. Contact: www.midamericaagresearch.net Egg counts Great Basin equine parasite study 300 Strategic 6X/yr None Infrequent 250 200 150 100 50 0 4 5 5 4 6 8 3 8 36 22 14 15 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec 31
Great Basin equine parasite study Egg counts 120 100 80 Strategic YEAR TWO 6X/yr Strategic Internal Parasite Control Program for Horses Cold dry No egg shedding PASTURE Rx Rx Rx Rx Rx Rx Hot dry No egg shedding Bot Cold dry 60 40 MAR 1 APR 1 MAY 1 SEP 1 OCT 1 NOV 1 20 CORRAL - STABLE - PADDOCK 0 Sep-92 Oct-92 Nov-92 Dec-92 Jan-93 Feb-93 Mar-93 Apr-93 May-93 Jun-93 Jul-93 Aug-93 Sep-93 JAN-MAR APR-JUN JUL-SEPT OCT-DEC Rx = Treatment of all horses with a Class II dewormer Foals: Ivermectin at 30 days, monthly with Class II, then strategic Veterinarian should help make deworming decision Using the fecal exam to determine which animals need deworming. Choosing the type dewormer based on parasites found. Choosing the type dewormer based on category of animals needing deworming. Determine whether external parasites are a problem as well. 32
Fenbendazole FBZ remains a very important product to producers. Only deworming product in cattle that has maintained a high level of efficacy. Safe-Guard has maintained a 98% efficacy against all nematode parasites. Special efficacy against Monezia and Taenia tapeworms, whipworms, Nematodirus and protozoan Giardia 33