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Clinacox Efficacy profile

Clinacox Efficacy profile. Ing. Leo Suls International Marketing Manager Janssen Animal Health. Battery trials Clinacox. A.C.I. - Battery trials. PPM*. Eimeria 0 0.1 0.5 1 5 10 tenella 106 199 199 200 198 201 acervulina 134 157 190 200 201 199

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Clinacox Efficacy profile

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  1. ClinacoxEfficacy profile Ing. Leo SulsInternational Marketing Manager Janssen Animal Health

  2. Battery trials Clinacox

  3. A.C.I. - Battery trials PPM* Eimeria 0 0.1 0.5 1 5 10 tenella 106 199 199 200 198 201 acervulina 134 157 190 200 201 199 necatrix 90 186 196 197 197 198 brunetti 114 170 193 193 196 197 maxima 129 177 184 193 194 196 mitis 124 159 174 180 196 195 * CLINACOX 0.5 % PREMIX(2-5 replicates x 8 birds)

  4. Effect of 1 ppm diclazuril on lesion scores and oocyst excretion(OPG) of birds infected with a single Eimeria species(6 days p.i.) (Vanparijs, 1989) average lesion scores OPG (X 1000) IUC diclazuril IUC diclazuril E. tenella 3.5 0 469 0 E. acervulina 2.2 0 407 0 E. necatrix 3.4 0.4 74 0 E. brunetti 2.9 0.2 143 0 E. maxima 2.4 1.3 27 0 E. mitis 2.2 0.4 248 17

  5. Species Developmental stage susceptible to diclazuril E. tenella E. necatrix E. acervulina E. brunetti E. maxima trophozoites schizonts gametocytes zygote stage of action lesion inducing stages Stage of action - results

  6. When can lesions occur? • COCCIDIOCIDAL EFFECT ONLY AGAINST LATE STAGES: (E.maxima; E.brunetti) • HIGH INFECTION PRESSURE ! • MAXIMA • BRUNETTI & NECATRIX • CLEAN-UP TAKES TIME UNDERSTANDING STAGE OF ACTION IS CRUCIAL

  7. Stage of action - strain differences JAPANESE NAÏVE STRAINS: • NO OOCYST EXCRETION • CLINICAL SIGNS • ACERVULINA LESIONS (SLIGHT)

  8. Clinacox and E. maxima Example : The US label claim : “ For the prevention of coccidiosis caused by E. tenella, E. necatrix, E. brunetti, E. acervulina, E. mitis and E. maxima. Because diclazuril is effective against E. maxima later in its lifecycle, subclinical intestinal lesions may be present for a short time after infection. Diclazuril was shows in studies to reduce lesion scores and improve performance and health of birds challenged with E.maxima”

  9. Floorpen trials Clinacox

  10. Clinacox : 17 pooled floor pen trials Mean total lesion scores (MTLS), average live weight(ALW) and feed conversion (FCR) of broilers artificially infected with Eimeria species (17 pooled floorpen trials). day 28day 42 MTLS ALW FCR ALW FCR d21 d28 IUC 877b 1.836a 1.710b 2.028a 4.17a 1.89a diclazuril 1 ppm 995a 1.638c 1.827a 1.913b 0.39c 0.01b ref. products 970a 1.751b 1.779a 1.987a1.06b 0.39b

  11. Floor pen trials with shuttle programsUSA, McDougald-1991 - duration 45 days - shuttle on day 21 - treatment and infection: * diclazuril in starter and challenge on day 15 * diclazuril in grower and challenge on day 21 - lesion scores: 7 days post infection - litter oocyst counts - average liveweight, feed conversion and mortality

  12. Anticoccidial efficacy of shuttle programs with diclazurilin the starter phase. Mc Dougald - 1991 starter grower Nr of Average Feed MTLS treatment treatment repl. pens FBW (g) conversion DICLAZURIL lasalocid 18 2024 1.895 2.29 DICLAZURIL salinomycin 18 2016 1.895 1.86 DICLAZURIL narasin 18 2016 1.896 1.78 DICLAZURIL monensin 18 2003 1.899 1.77 nicarbasin salinomycin 18 1993 1.905 2.10 maduramycin salinomycin 18 1974 1.935 4.06 halofuginone salinomycin 18 1967 1.940 5.17 IUC IUC 18 1900 2.027 6.86 Challenge with mixed inoculum on day 15

  13. Anticoccidial efficacy of shuttle programs with diclazurilin the grower phase. Mc.Dougald - 1991 starter grower Nr of Average Feed MTLS treatment treatment repl. pens FBW conversion salinomycin DICLAZURIL 18 1946 1.901 1.81 Maxiban DICLAZURIL 18 1935 1.904 1.76 monensin DICLAZURIL 18 1917 1.911 1.54 nicarbazin DICLAZURIL 18 1912 1.919 1.78 salinomycin lasalocid 18 1911 1.920 4.29 Maxiban narasin 18 1877 1.930 6.18 nicarbazin salinomycin 18 1877 1.933 4.68 IUC IUC 18 1828 2.053 8.39 Challenge with mixed inoculum on day 21

  14. Anticoccidial efficacy of shuttle programs with diclazurilin the starter phase. Conway, 2001 - published starter grower Nr of Average Feed MTLS treatment treatment repl. pens FBW (g) conversion DICLAZURIL salinomycin 10 2.250a 1.847d 1.63c nicarbasin salinomycin 10 2.201b 1.876cd 1.90c Maxiban salinomycin 10 2.175b 1.903bc 3.53b zoalene salinomycin 10 2.113c 1.921b 6.50a IUC IUC 10 2.035d 2.017a 6.40a Challenge with mixed inoculum on day 15

  15. Anticoccidial efficacy of shuttle programs with diclazurilin the grower phase. Conway et al. 2001 ; published starter grower Nr of Average Feed MTLS treatment treatment repl. pens FBW conversion salinomycin DICLAZURIL 10 2.156c 1.856c 2.90c salinomycin salinomycin 10 2.023a 1.913b 9.50a salinomycin monensin 10 2.012b 1.914b 9.90a salinomycin lasalocid 10 2.037b 1.936b 8.46b IUC IUC 10 1.921b 1.994a 10.05a Challenge with mixed inoculum on day 22

  16. The field situation :

  17. Clinacox field trial results • The Netherlands • United Kingdom • France • Germany • Belgium 225 broiler flocks4.7 million broilers

  18. Clinacox field trial results • Direct house to house comparisons • Coccidiosis control : • Lesion scores • OPG counts • Broiler performance • ADG • FCR • EBI

  19. Clinacox field trial results • Netherl.: nicarb/salinomycin <=> nicarb/CLINACOX • France: nicarb/salinomycin <=> ionoph/CLINACOX ionophore full <=> ionoph/CLINACOX • U.K. Maxiban/ionoph. <=> CLINACOX/ionoph. • Belgium nicarb/monensin <=> CLINACOX full • Germany nicarb/monensin <=> CLINACOX full salinomycin full <=> CLINACOX full

  20. Broiler performance The Netherlands The Netherlands: nicarbazin / Clinacox nicarbazin / salinomycin FBW (g) ADG Adj FCR EBI Clinacox Clinacox Clinacox Clinacox 1839 45.1 1.654 243 1815 44.4 1.683 236 Reference

  21. Broiler performance Belgium Belgium: Clinacox full nicarbazin / monensin FBW (g) ADG Adj FCR EBI Clinacox Clinacox Clinacox Clinacox 1771 43.3 1.720 234 1717 41.6 1.770 219 Reference

  22. Broiler performance U.K. U.K.: Clinacox / ionophore maxiban / ionophore FBW (g) ADG Adj FCR EBI Clinacox Clinacox Clinacox Clinacox 2237 49.9 1.666 241 2147 47.9 1.767 223 Reference

  23. Broiler performance France France: ionophore (d26) / Clinacox nicarbazin / salinomycin or ionophores full FBW (g) ADG Adj FCR EBI Clinacox Clinacox Clinacox Clinacox 1676 41.5 1.821 208.4 1666 41.6 1.841 205.9 Reference

  24. Broiler performance Germany Germany: Clinacox full salinomycin full FBW (g) ADG Adj FCR EBI Clinacox Clinacox Clinacox Clinacox 1454 40.0 1.852 205.5 1441 38.7 1.906 194.8 Reference

  25. FBW (g) ADG Adj FCR EBI + 38 g + 1.2 g - 0.050 + 10.6 Broiler performance Total pool Total trial pool: 4.7 million broilers 225 crops Clinacox Clinacox Clinacox Clinacox 1795 44.0 1.743 226.3 1757 42.8 1793 215.7 Reference

  26. Conclusion • Clinacox advantageous in each type of programme • Optimal results when Clinacox in full programme or in 2nd phase of the shuttle • Improved coccidiosis control = better performance • Average improvement was 10.6 points EBI

  27. The field situation Sensitivity test UK • Anticoccidial drug sensitivity test UK , 1996 • 9 top broiler integrations UK • 5 farms per integration • 5 houses per farm • 10 mixed feaces samples per house • Evaluation : • Lesion scores • Oocyst counts • Weight gains

  28. Sensitivity test UK , 1996 • Sensitive = > 50 % reduction vs IUC • Reduced sensitivity = 30% < RS < 50 % reduction vs IUC • Resistance = < 30% reduction vs IUC

  29. Evaluation of 9 sensitivity tests in the UK Average lesion score in small intestine and reduction vs IUC Anticoccidial drug sensitivity survey UK 1996 ionophores synthetical % reduction vs IUC 50 39 37 39 42 31 46 39 79 37 50 50 50 50

  30. Evaluation of 9 sensitivity tests in the UK Sensitivity profile for intestinal coccidiosis 9 8 7 6 5 4 3 2 1 1

  31. Evaluation of 9 sensitivity tests in the UK Average lesion score in the caecum and reduction vs IUC ionophores synthetical % reduction vs IUC 37 21 25 17 25 25 59 67 67 71 80 75 46 71

  32. Evaluation of 9 sensitivity tests in the UK Sensitivity profile for caecal coccidiosis

  33. Evaluation of 9 sensitivity tests in the UK Oocyst per gram (x1000) on d 6 and d 7 and reduction vs IUC ionophores synthetical % reduction vs IUC 16 10 10 16 30 9 35 52 65 38 52 32 35 62

  34. Evaluation of 9 sensitivity tests in the UK Weight gain days -2 to +7 as % of UUC ionophores synthetical % of UUC 64 55 57 58 54 52 67 64 81 58 67 65 71 74

  35. Sensitivity test UK , 1996 • Conclusions : • = 4 years after launch !! • very good efficacy against E. Tenella • moderate activity against E.acervulina • Efficacy profile varies per integration/farm

  36. Clinacox in turkeys Battery trials : • Broad spectrum: E.Adenoides E.Gallopavonis E.Melegrimitis E.Dispersa • Potent activity : No lesions No oocyst excretion • 1 ppm is sufficient

  37. 2,500 2,000 1,500 UUC IUC average live weight (g) Clinacox 1 ppm 1,000 monensin 100 ppm 500 0 ALW at day 35 ALW at day 35 ALW at day 49 ALW at day 49 Floorpen trials - BELGIUM Average live weight on day +35 and +49

  38. 10,000 9,000 8,000 7,000 6,000 average live weight (g) 5,000 IUC 4,000 Clinacox 1 ppm 3,000 2,000 monensin 90 ppm 1,000 0 day 35 day 56 day 91 day 112 Floorpen trials - ITALY - Average Live Weights (*Means of males and females)

  39. 3,500 3,000 2,500 IUC 2,000 Clinacox 1 ppm average live weight (g) 1,500 monensin 100 ppm amprolium 125 ppm 1,000 500 0 ALW at day 28 ALW at day 28 ALW at day 35 ALW at day 35 ALW at day 56 ALW at day 56 Floorpen trials - SPAIN - Average live weight

  40. 16,506 16,238 18,000 16,000 14,000 9,616 12,000 9,269 10,000 6,797 IUC 6,492 8,000 Clinacox 1 ppm average live weight (g) 6,000 1,251 4,000 1,396 475 501 2,000 0 day 21 day 21 day 35 day 35 day 84 day 84 day 112 day 112 day 147* day 147* Floorpen trials - GERMANY - Average live weights

  41. 8,626 8,565 8,700 8,600 8,500 8,251 8,400 average live weights (g) 8,300 8,200 8,100 8,000 IUC IUC Clinacox monensin monensin 1 ppm 100 ppm 100 ppm Floorpen trials - UNITED KINGDOM - Average live weights in grams (*) at the end of the trial (day +98)

  42. Country Age at lasalocid Clinacox slaughter FBW* FBW days Austria 84-154 9.25 9.71 Germany 111-154 13.19 13.26 Poland 84 3.224 3.310 U.K. 80-83** 5.98 5.90 Italy nd 12.72 13.05 *: averages of males and females ** : Lasalocid groups slaughtered at 83 days, the Clinacox groups at 80 days Field trial results : Summary

  43. Clinacox in turkeys Conclusions • Excellent coccidiosis control • Performance of Clinacox groups superior,even at end of the grow-out • Safe, no side effects • No incompatibilities

  44. Efficacy of Clinacox in other animal spp. • Pheasant and partridges(V7179; V7913; V7972; V8223; V8316; V8318; V8772; 8372) • diclazuril effective against all tested E.spp • 1 ppm not sufficient • 2 to 4 ppm required for full efficacy • Ducks (V8077) • 1 ppm effective agains most common. E.spp • Guinea fowl (V8341) • 1 ppm effective agains most common. E.spp

  45. Clinacox in rabbits • 1 ppm dose effective to prevent • intestinal coccidiosis • liver coccidiosis

  46. Influence of diclazuril on oocyst sporulation(Löwenstein et al., 1989) preparation age of infected maduramycin diclazuril cultures cultures on control 5 ppm 1 ppm days p.i. counts (hrs) 5 144 75.7 (100) 85.4 (112.8) - - 6 120 70.4 (100) 65.8 (93.5) 45.2 (64.2) 7 96 68.0 (100) 60.8 (89.4) 30.8 (45.3) 8 96 65.7 (100) 76.4 (116.3) 20.8 (31.7) 9 96 62.9 (100) 59.8 (95.1) 38.2 (60.7) 10 96 63.1 (100) 45.9 (72.7) 21.0 (33.3) 11 72 61.2 (100) 55.1 (90.0) - - 12 168 80.3 (100) 57.4 (71.5) - - (-): no oocysts shed.

  47. Clinacox residual activity(L. Mc Dougald, USA ; Published Vet. Parasitology; V 7672)

  48. Effect on natural immunity development :Laboratory trial conducted by Dr. Louis Maes at janssen Pharmaceutica, 1994

  49. Ccoccidiosis immunisation trial Daily tricle infectionswith low doses of coccidia High challenge dose 3 weeks of age 14 days 5 weeks of age

  50. Coccidiosis immunisation trial 3 groups : • group 1 : Not immunized with trickle infection • Group 2 : Immunized with trickle infection • Group 3 : Immunized and treated with Clinacox

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