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Introduction Bill Burdett, D.V.M., Intervet Inc. Bovine Nematode Resistance An Overview.

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Presentation on theme: "Introduction Bill Burdett, D.V.M., Intervet Inc. Bovine Nematode Resistance An Overview."— Presentation transcript:

1 Introduction Bill Burdett, D.V.M., Intervet Inc. Bovine Nematode Resistance An Overview

2 Introduction Todays Discussion Resistance (R) – what is it? Major nematodes of cattle Classes of dewormers Methods of R detection Characteristics of nematode infection Fecal sampling Case histories of R Using combinations of dewormers

3 Introduction Defining Resistance What R is not: It is not the development of superworms. (Anthelmintic Resistance Roundtable, 2005) Some disagreement as to whether or not it is truly mutation per se How does it occur? We are simply creating an environment where that particular genetic makeup survives. (Dr. Cliff Monahan, OhSU, Anthelmintic Resistance Roundtable, 2005)

4 Introduction Defining Resistance You are not changing something in the worm. By giving dewormers, we are not inducing resistance – we are simply providing an environment for the resistant parasites to flourish and multiply. (Dr. Dwight Bowman, Cornell U., Anthelmintic Resistance Roundtable, 2005) <90% worm egg reduction following use of a specific dewormer = resistance

5 Introduction Scope of the Problem Huge in sheep and goats Becoming a major issue in cattle, particularly to the endectocides (macrocyclic lactones - avermectins and milbemycins – ivermectin, doramectin, eprinomectin, and moxidectin)

6 Introduction Risk Factors for Resistance Frequent use of same drug class Subtherapeutic drug levels from under dosing and/or persistance in the environment at low levels

7 Introduction Drug Level Time 70 – 80 days Lethal Dose EndectocidesFenbendazole 24 hours Parasite Resistance CONCEPT ILLUSTRATION

8 Introduction Major Cattle Nematodes Predominant genera = Ostertagia and Cooperia Less predominant genera = Haemonchus, Trichostrongylus, Oesophagostomum, Strongyloides, Trichuris, Nematodirus, and Monezia

9 Introduction Broad Spectrum Nematode Dewormers Group 1 = benzimadazoles (BZ) (attack parasites metabolic system) Group 2 = imidazoles (levamisole, LEV) and hydropyrimidines (pyrantel/morantel) Group 3 = macrocyclic lactones (avermectins and milbemycins, ML) (attack parasites nervous system)

10 Introduction Methods of Resistance (R) Detection Fecal Egg Reduction Count Test (FERCT) for R to any dewormer (only test available for macrocyclic lactones) Egg hatch test for BZ R Microagar larval development test for BZ and LEV R

11 Introduction Methods of Resistance (R) Detection PCR based test for BZ R in strongyles of sheep and goats, cattle, and horses Real time PCR for quantitative determination of gene frequency Controlled efficacy test – gold standard

12 Introduction FERCT Nematode eggs counted on initial fecal exam Eggs counted again at defined times following treatment, e.g. 14 days % reduction determined Only reliable if > 25% of worms resistant

13 Introduction FERCT Original product pour on? Confirmation of R using an injectable or oral to eliminate possible problems with malabsorption Cattle Ideal to use animals with minimum count of 100 epg (higher in sheep) 17, e.g. 20 cattle per each anthelmintic tested MLs persistant activity (label) second sample at X days post-treatment depending on species recommended combined with larval cultures (for appropriate species)

14 Introduction Egg Hatch Test for BZ Discriminating doses of Thiabendazole (TBZ) (relatively high solubility in water) used to determine % of hatch Discriminating dose (DD) = dose that prevents hatching of 99% of susceptible eggs DD for H. contortus, T. circumcincta, and T. colubriformis have been established for sheep

15 Introduction Egg Hatch Test for BZ % of eggs hatching = % of BZ R Will probably not indicate eggs that are heterozygous for R unless genes for R are dominant Discriminating dose not established for cattle

16 Introduction Microagar Larval Development Test Age of eggs not important as long as not starting to hatch Relies on development of eggs to L3 larvae Speciated at the end of the test Only reliable for BZ and LEV Has not been adequately evaluated, e.g. discriminating doses, for bovine, to assure its efficacy

17 Introduction Molecular (PCR) Based Tests BZ only Only when diagnosis can be obtained from pooled larval DNA samples will routine testing take place Testing of single stages too expensive

18 Introduction Pertinent Things to Remember And Some Examples of Combination Use and Resistance

19 Introduction Facts Calves 3-4 months of age and grazing for at least 2 weeks most susceptible and likely to have most eggs Moisture and warm temperatures (>40°F) Nematodirus – few eggs but very detrimental to calves

20 Introduction Facts Small number of animals typically shed most of the eggs, e.g. the 80/20 rule, particularly as animals age Recommended minimum number of samples = 20 Sampling too few animals in a group will likely under represent the small percentage of high egg shedding animals Standard deviation exceeds the mean

21 Introduction Facts Heritability of egg shedding = Nematodes drive a Th2 immune response which tends to counter a Th 1 response Th1 response necessary for good immunity to intracellular pathogens such as viruses Single most significant factor of economic loss from internal parasite infection = appetite suppression

22 Introduction Facts Physiological responses to GI nematodes Anorexia Increased flow rate of feedstuffs through gut Increases muscle mass in intestinal tract Decreased fluid absorption

23 Introduction Combining FBZ and Avermectin First feedyard trial (moderate egg counts,e.g. in the 30s per gram) demonstrated extra 18 lbs. gain for FBZ + Ivomec pour on versus Ivomec pour on alone (+$20.08) Second feedyard trial (low egg counts, 7-9 per gram) showed extra 20 lbs. FBZ + Ivomec pour on versus Dectomax injectable alone ($9.31)

24 Introduction Combining FBZ and Avermectin Third feedyard trial (moderate egg counts, 150s per 3 grams) demonstrated reduced egg counts favoring FBZ or FBZ + Ivermectin injectable versus Ivermectin injectable but no difference in economic return Dr. Tom Elam economic evaluation of the three trials showed an advantage of using both FBZ and an avermectin of $22.19, $9.01, and $4.20, respectively

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