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CL 259,971: A Potent New Polyether Anticoccidial
CL 259,971: A Potent New Polyether Anticoccidial. 2. Floor-Pen Trials. S. KANTOR, R. H. SCHENKEL, and R. L. KENNETT, JR. American Cyanamid Company, Agricultural Research Division, P.O. Box 400, Princeton, New Jersey 08540 (Received for publication December 5, 1983) ABSTRACT Three floor-pen trials have confirmed the high anticoccidial activity of CL 259,971 as first reported in batteries. The optimal dosage level was shown to be 5 ppm in the diet. At this level, excellent anticoccidial activity was observed with no adverse effect on weight or performance. The results indicated that 5 ppm of CL 259,971 provided efficacy and performance comparable to arprinocid or monensin, which were used for comparison in these trials. (Key words: CL 259,971, anticoccidial, coccidiosis, broiler performance) 1984 Poultry Science 63:1506-1511 INTRODUCTION
Polyether ionophore antibiotics are the most widely used drugs to combat poultry coccidiosis throughout the major poultry raising areas of the world. CL 259,971 is a novel, very potent, polyether ionophore anticoccidial. Battery studies (Kantor and Schenkel, 1983) have indicated that the drug is optimally effective at 5 ppm against the six commercially important species of Eimeria and has an adequate margin of safety in chickens. The optimal level of 5 ppm in the diet makes CL 259,971 the most active polyether reported. Although battery studies are predictive of potential anticoccidial utility, trials with the drug under simulated commercial growing conditions are essential for a more complete evaluation. For this reason, three floor-pen studies were performed by us and are here reported. Other such studies have been performed by independent investigators and will be reported elsewhere.
MATERIALS AND METHODS
The trials were run in a poultry house containing 32 pens, each approximately 2 X 3.4 m (6.5 X 12 ft), providing a floor area of approximately 6.8 m 2 (78 ft 2 ). All of the pens had concrete floors and wood sidewalls. Each pen was individually heated with a standard 4-ft diameter brooder, fed with propane gas, and temperatures were adjusted individually to conform with standard practice as the birds aged. Each pen had one automatic dome-type waterer. During the first 2 weeks, one hanging
cylindrical feeder was used in each pen, after which a second feeder was added. All chicks were started on paper covering the litter for 1 or 2 weeks to prevent accidental coccidial infection before intentional exposure to oocysts. The birds were standard Hubbard X Hubbard cockerels and pullets received from Kerr Hatcheries, Frenchtown, NJ. Medicated feed was provided to the birds ad libitum from the day of hatch. A starter diet was used for the first 4 weeks and a finisher diet was used for the remainder of the trial (Cyanamid Diets #625 and #626, respectively, Table 1). All medication was incorporated into either of these diets. The birds received mash feed in the first two trials and crumbled, pelletted feed in the third trial. All medication was withdrawn after 42 days, 5 days before termination of the experiment. Birds were withdrawn periodically and were retained in poultry crates over paper for approximately 2 days for the collection of feces for coccidiosis monitoring. These birds were then sacrificed for lesion scoring using a modified Johnson and Reid (1970) system. Litter was also observed for oocyst contamination. Weights and feed utilization were measured periodically (Tables 2 and 3), and weight gains and feed efficiencies were calculated. Performance evaluation was based on mortality, weights, weight gain, feed efficiency (feed/gain), lesion scores, and oocyst production. Trial 1. Birds were sexed, separated, and divided into 100 birds per pen with two male and two female replicate pens per treatment. Treatments consisted of no medication; CL
1506
CL 259,971: POLYETHER ANTICOCCIDIAL
1507
TABLE 1. Cyanamid broiler starter and finisher diets Ingredients
Starter Diet #625
Finisher Diet #626 •(kg)-
Ground yellow corn Corn gluten meal, 60% Soybean meal, 49% Menhaden fish meal, 60% Meat and bone meal, 50% Poultry by-product meal, 58% Animal and vegetable fat Dicalcium phosphate Limestone Salt, iodized Vitamin mix (Roche) Mineral mix (Seaboard) L-Lysine-98
636.5 42.5 197.5 30.0
571.0 32.5 275.0 30.0 30.0
30.0 35.6
35.0 11.0
12.1 8.8 3.5 2.5 .5 .5
9.0
3.5 2.5 .5 1000.0
1000.0
3131 23.8 1.25
3234 21.3 1.08
.48 .84
.47 .76
6.17
6.81
2.7
2.6 .84 .71 .50
Calculated analysis Metabolizable energy, kcal/kg Protein, % Lysine, % Methionine, % Methionine and cystine, % Fat, % Fiber, % Calcium, % Phosphorus, total, % Phosphorus, available, %
Vitamin supplement (Roche), 2.5 kg/1000 kg feed Vitamin A, IU Vitamin D, IU Vitamin E, IU Vitamin B 1 2 , mg Riboflavin, mg Niacin, mg Pantothenic acid, mg Choline chloride, mg Menadione sodium bisulfite complex, mg Folic acid, mg Pyridoxine, mg Thiamine, mg
1.00 .79 .56
(kg supplement) 3,300,000 1,100,000 3,520 3.52 2,000 17,600 5,280 228,096 880 440 724 403
Mineral supplement (Seaboard), 1.1 kg/1000 kg feed Copper Iron Iodine Manganese Zinc Calcium
1.0% 5.0% .25% 15.0% 10.0% 12.0%
1508
KANTOR ET AL. TABLE 2. Mortality and performance after 14 days of exposure (PE) to oocysts No. birds
Treatment Trial
Medication
No. exposed
% Dead
(ppm) 1
2
3
Perform ance 14 days PE
Mean weight at exposure 1
Weight gain
Feed/gain 2
{i,\
\g)
2.5 5 7.5 10 100 120 60
374 376 376 378 377 378 375 379
1.3 .8 .5 .3 1.1 .5 0 .5
277 270 a 270 a 269 a 259 a 276 a 264 a 264 a
545 c 596ab 594ab 580abc 562bc 5 7Qabc 554 c 601a
1.80b 1.58a 1.56a 1.66 ab 1.56a 1.56a 1.60a 1.54a
Nonmedicated CL 259,971 CL 259,971 CL 259,971 Monensin
4 5 6 120
562 558 563 557 564
.4 .7 .7 .5 .4
309 a 308 a 307 a 310 a 293 b
541 a 564 a 568 a 561 a 522°
1.89b 1.77a 1.77a 1.79a 1.80a
Nonmedicated CL 259,971 CL 259,971 CL 259,971 Monensin
4 5 6 120
547 545 549 548 548
4.6 1.1* .5* 2.4* .5*
141 a 137 a 141 a 136 a 141 a
397 c 422° 489 a 476 a 475a
1.71 c 1.56 ab 1.53 a 1.51 a 1.62b
Nonmedicated CL 259,971 CL 259,971 CL 259,971 CL 259,971 Monensin Monensin Arprinocid
a
a,b,c Values within columns within trials with the same superscript letters are not significantly different (P : .05). 1 Exposure to oocysts: Trial 1 and 2 at 14 days of age; Trial 3 at 7 days of age. 2 Feed/gain = feed consumed/live weight gained. * Significantly different from nonmedicated control (P<.05).
259,971 at 2.5, 5, 7.5, or 10 ppm; COBAN®1 monensin at 100 or 120 ppm; or ARPOCOX® 2 arprinocid at 60 ppm. The principal birds were exposed to litter previously contaminated by 10 seeder birds per pen, each of which had received 10 times the recommended immunizing dose of COCCIVAC® , type D live vaccine. The seeder birds were infected 5 days prior to being placed on the litter and were left in the pens for 2 weeks prior to replacement by the principal chicks. Litter paper was removed when the principal birds were 2 weeks of age. Five birds were withdrawn for coccidiosis monitoring on days 14, 28, 42, and at the termination of the trial at 49 days.
1 COBAN,i® , registered trademark of Elanco Products Co., Indianapolis, IN. 2 ARPOCOX®, registered trademark of Merck, Sharp and Dohme, Rahway, NJ. 3 COCCIVAC®, registered trademark of Sterwin Laboratories, Inc., Opelika, AL.
Trial 2. Fifty male and 50 female chicks were included in each pen and there were six replicate pens per treatment. Treatments consisted of no medication; CL 259,971 at 4, 5, or 6 ppm; or monensin at 120 ppm. Twenty seeder birds were placed in each pen for 2 weeks before the principal birds were placed in the pens. The seeder birds had received quantities of two recent collections of oocysts obtained from litter in commercial broiler raising houses from Georgia. The combination of materials provided oocysts from E. acervulina and/or E. mivati, E. brunetti, E. maxima, E. necatrix, and E. tenella. In addition to contaminated litter, similar sporulated oocysts were also added to the drinking water of the birds at 14 days of age when the paper was removed from the litter and the birds exposed. Five birds were withdrawn for coccidiosis monitoring on days 14, 21, 28, 44 and at the termination of the trial at 49 days. Trial 3. The design of the trial was similar to Trial 2 with the exception that the birds were exposed to litter which had been contaminated by sprinkling known quantities of oocysts
CL 259,971: POLYETHER ANTICOCCIDIAL
1509
around waterers and feeders. In addition, known quantities of oocysts were added to the drinking water. The infectious material was the same as was used in Trial 2. No seeder birds were used. The birds were exposed to the contaminated litter when they were 7 days of age. Four birds were withdrawn for coccidiosis monitoring on days 7, 14, 21, 44, and at the termination of the test at 49 days. Experimental data were analyzed by analysis of variance and means were compared using the multiple range test of Duncan (1955). Mortalities were compared using exact probability (Mainland et al, 1956). RESULTS AND DISCUSSION ts
S 1 S
•
•
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•
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.
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Trial 1. Two weeks after exposure to infected litter, only the birds that received 2.5 or 5 ppm of CL 259,971 or arprinocid maintained weight gains significantly superior to the nonmedicated controls or birds receiving 120 ppm of monensin (Table 2). Although the remaining medicated treatment groups exhibited nominally superior weight gains, these were not significantly different from the nonmedicated controls. Feed efficiencies (feed/ gain) of the treated groups were superior to that of the nonmedicated controls, and only 7.5 ppm of CL 259,971 did not provide a significant improvement. This anomaly cannot be explained because the 10 ppm level provided significant improvement. Mortality in all the groups was low with no significant differences. No lesions were observed in any of the birds sacrificed 14 days after exposure, although low numbers of oocysts were found in droppings from the sacrificed birds. At the termination of the trial after 49 days and 5 days after the termination of medication, only birds receiving 2.5 or 5 ppm of CL 259,971 or 60 ppm or arprinocid weighed significantly more than the nonmedicated control birds. Birds that had received 10 ppm of CL 259,971 were significantly depressed compared to the other birds (Table 3). Improved feed efficiencies (feed/gain) were observed in the groups of birds that had received 100 ppm of monensin or 60 ppm of arprinocid. Trial 2. Although the exposure to oocysts was not sufficiently severe to provide a significant depression in the gains of the nonmedicated birds compared with the birds receiving CL 259,971, the weights of the nonmedicated birds were numerically inferior after 2 weeks of
1510
KANTOR ET AL.
TABLE 4. Average lesion scores' for species of Eimeria observed in birds sacrificed 7 days after exposure to oocysts Species Trial
Medication
2
Nonmedicated CL 259,971 CL 259,971 CL 259,971 Monensin
E. acervulina/ E. mivati
E. brunetti
E. maxima
1.67
1.12
1.67
0 0
0
E. necatrix
E. tenella
All
1.25
1.30
(ppm)
Nonmedicated CL 259,971 CL 259,971 CL 259,971 Monensin
3
4
5 6
0 Not done
120
.12
.04
4 5 6 120
2.25 c .60ab .79 b .42 a .40 a
2.08 c .17* .17 a .42ab .62 b
.79
0
0 0
0
0
2.96 c 1.08a 1.42 ab 1.38a 2.04b
1.62 b
.29
.04 0
0a 0a 0a
.40 a
.07 0
.12
.10
2.54 c 1.46b .42 a .58 a 1.33 b
2.29 b .66 a .56 a .56 a .89 a
a,b,c Scores within columns within trials with the same superscript letters are not significantly different (P = .05). 1
Maximum possible lesion score is 3.00.
exposure (Table 2). The feed efficiency of the nonmedicated birds, however, was significantly elevated. Birds receiving monensin at 120 ppm had significant weight gain depressions at this time, but because the weights of the birds at the beginning of exposure were reduced, probably because of toxicity, the difference cannot be attributed to lack of efficacy. As judged by lesions, the infection was light, but lesions from each of the five to six species were observed in the nonmedicated controls 7 days after exposure. Very few lesions from E. acervulina/mivati and E. tenella were noted in the birds receiving 4 ppm of CL 259,971, but no lesions from any of the species of Eimeria were found in the birds that received 5 ppm of CL 259,971, and, consequently, the birds receiving 6 ppm of CL 259,971 were not examined. Small numbers of lesions were observed in birds receiving 120 ppm of monensin from E. acervulina/mivati, E. brunetti, E. maxima, and E. tenella. Mortality in all groups was very light (Table 2). At 49 days, at the end of the trial, terminal weights of the birds were not different (Table 3). All the treated groups except those receiving 4 ppm of CL 259,971 had feed efficiencies significantly superior to those of the nonmedicated controls. Trial 3. The coccidial challenge to the birds was more severe in this trial than in the previ-
ous trials. Mortality was 4.6% in the nonmedicated controls (Table 2) and moderate to severe lesions from all the species of Eimeria were observed (Table 4). Medication significantly improved survival and the lesion scores of all the birds. Weight gains were significantly depressed in the nonmedicated birds when compared to the medicated birds (Table 2). Similarly, the feed efficiency of the nonmedicated birds was significantly depressed compared to the medicated groups. Birds receiving 5 or 6 ppm of CL 259,971 exhibited the best performance. Birds receiving 4 ppm of CL 259,971, although superior to those of the nonmedicated controls, were significantly inferior to the remaining treated groups. Feed efficiencies of birds receiving 120 ppm of monensin were significantly inferior. At termination at 49 days, all the medicated groups except birds receiving 4 ppm of CL 259,971 exhibited superior weights compared to the nonmedicated controls (Table 3), although all the treatment groups had similar feed efficiencies. General observations made during the three trials revealed no unusual conditions. Throughout, all the birds appeared in good condition and well colored, although in the third trial, some of the untreated birds appeared listless and with ruffled feathers for a week or two
CL 259,971: POLYETHER ANTICOCCIDIAL after exposure to oocysts. Also in the third trial, but not in the others, bloody and abnormal droppings were noted on the litter of all the treatment groups during the first 2 weeks of the infection but not thereafter. No sick birds were noted after the third week. Feathering was normal, no "bare-backs" were noted, and the numbers of feathers on the litter appeared uniform, indicating no abnormal feather eating in any of the pens. No excessive moisture was noted in the litter. Overall, it can be concluded thatCL 259,971 was an effective anticoccidial in these trials. At the potentially recommended use level of 5 ppm, CL 259,971 had no adverse effect on weight gain or performance.
1511
ACKNOWLEDGMENTS We wish to thank Cynthia R. Caterson, Angelo Gallo, Helen C. Miller, and the late Dominic Fortini for their invaluable technical assistance.
REFERENCES Duncan, D. B., 1955. Multiple range and multiple F tests. Biometries 11:1—42. Johnson, J., and W. M. Reid, 1970. Anticoccidial drugs: Lesion scoring techniques in battery and floor-pen experiments with chickens. Exp. Parasitol. 28:30-36. Mainland, D., L. Herrera, and M. I. Sutcliffe, 1956. Statistical Tables for Use with Binomial Samples. New York Univ., Coll. Med.
Polyether ionophore antibiotics are the most widely used drugs to combat poultry coccidiosis throughout the major poultry raising areas of the world. CL 259,971 is a novel, very potent, polyether ionophore anticoccidial. Battery studies (Kantor and Schenkel, 1983) have indicated that the drug is optimally effective at 5 ppm against the six commercially important species of Eimeria and has an adequate margin of safety in chickens. The optimal level of 5 ppm in the diet makes CL 259,971 the most active polyether reported. Although battery studies are predictive of potential anticoccidial utility, trials with the drug under simulated commercial growing conditions are essential for a more complete evaluation. For this reason, three floor-pen studies were performed by us and are here reported. Other such studies have been performed by independent investigators and will be reported elsewhere.
MATERIALS AND METHODS
The trials were run in a poultry house containing 32 pens, each approximately 2 X 3.4 m (6.5 X 12 ft), providing a floor area of approximately 6.8 m 2 (78 ft 2 ). All of the pens had concrete floors and wood sidewalls. Each pen was individually heated with a standard 4-ft diameter brooder, fed with propane gas, and temperatures were adjusted individually to conform with standard practice as the birds aged. Each pen had one automatic dome-type waterer. During the first 2 weeks, one hanging
cylindrical feeder was used in each pen, after which a second feeder was added. All chicks were started on paper covering the litter for 1 or 2 weeks to prevent accidental coccidial infection before intentional exposure to oocysts. The birds were standard Hubbard X Hubbard cockerels and pullets received from Kerr Hatcheries, Frenchtown, NJ. Medicated feed was provided to the birds ad libitum from the day of hatch. A starter diet was used for the first 4 weeks and a finisher diet was used for the remainder of the trial (Cyanamid Diets #625 and #626, respectively, Table 1). All medication was incorporated into either of these diets. The birds received mash feed in the first two trials and crumbled, pelletted feed in the third trial. All medication was withdrawn after 42 days, 5 days before termination of the experiment. Birds were withdrawn periodically and were retained in poultry crates over paper for approximately 2 days for the collection of feces for coccidiosis monitoring. These birds were then sacrificed for lesion scoring using a modified Johnson and Reid (1970) system. Litter was also observed for oocyst contamination. Weights and feed utilization were measured periodically (Tables 2 and 3), and weight gains and feed efficiencies were calculated. Performance evaluation was based on mortality, weights, weight gain, feed efficiency (feed/gain), lesion scores, and oocyst production. Trial 1. Birds were sexed, separated, and divided into 100 birds per pen with two male and two female replicate pens per treatment. Treatments consisted of no medication; CL
1506
CL 259,971: POLYETHER ANTICOCCIDIAL
1507
TABLE 1. Cyanamid broiler starter and finisher diets Ingredients
Starter Diet #625
Finisher Diet #626 •(kg)-
Ground yellow corn Corn gluten meal, 60% Soybean meal, 49% Menhaden fish meal, 60% Meat and bone meal, 50% Poultry by-product meal, 58% Animal and vegetable fat Dicalcium phosphate Limestone Salt, iodized Vitamin mix (Roche) Mineral mix (Seaboard) L-Lysine-98
636.5 42.5 197.5 30.0
571.0 32.5 275.0 30.0 30.0
30.0 35.6
35.0 11.0
12.1 8.8 3.5 2.5 .5 .5
9.0
3.5 2.5 .5 1000.0
1000.0
3131 23.8 1.25
3234 21.3 1.08
.48 .84
.47 .76
6.17
6.81
2.7
2.6 .84 .71 .50
Calculated analysis Metabolizable energy, kcal/kg Protein, % Lysine, % Methionine, % Methionine and cystine, % Fat, % Fiber, % Calcium, % Phosphorus, total, % Phosphorus, available, %
Vitamin supplement (Roche), 2.5 kg/1000 kg feed Vitamin A, IU Vitamin D, IU Vitamin E, IU Vitamin B 1 2 , mg Riboflavin, mg Niacin, mg Pantothenic acid, mg Choline chloride, mg Menadione sodium bisulfite complex, mg Folic acid, mg Pyridoxine, mg Thiamine, mg
1.00 .79 .56
(kg supplement) 3,300,000 1,100,000 3,520 3.52 2,000 17,600 5,280 228,096 880 440 724 403
Mineral supplement (Seaboard), 1.1 kg/1000 kg feed Copper Iron Iodine Manganese Zinc Calcium
1.0% 5.0% .25% 15.0% 10.0% 12.0%
1508
KANTOR ET AL. TABLE 2. Mortality and performance after 14 days of exposure (PE) to oocysts No. birds
Treatment Trial
Medication
No. exposed
% Dead
(ppm) 1
2
3
Perform ance 14 days PE
Mean weight at exposure 1
Weight gain
Feed/gain 2
{i,\
\g)
2.5 5 7.5 10 100 120 60
374 376 376 378 377 378 375 379
1.3 .8 .5 .3 1.1 .5 0 .5
277 270 a 270 a 269 a 259 a 276 a 264 a 264 a
545 c 596ab 594ab 580abc 562bc 5 7Qabc 554 c 601a
1.80b 1.58a 1.56a 1.66 ab 1.56a 1.56a 1.60a 1.54a
Nonmedicated CL 259,971 CL 259,971 CL 259,971 Monensin
4 5 6 120
562 558 563 557 564
.4 .7 .7 .5 .4
309 a 308 a 307 a 310 a 293 b
541 a 564 a 568 a 561 a 522°
1.89b 1.77a 1.77a 1.79a 1.80a
Nonmedicated CL 259,971 CL 259,971 CL 259,971 Monensin
4 5 6 120
547 545 549 548 548
4.6 1.1* .5* 2.4* .5*
141 a 137 a 141 a 136 a 141 a
397 c 422° 489 a 476 a 475a
1.71 c 1.56 ab 1.53 a 1.51 a 1.62b
Nonmedicated CL 259,971 CL 259,971 CL 259,971 CL 259,971 Monensin Monensin Arprinocid
a
a,b,c Values within columns within trials with the same superscript letters are not significantly different (P : .05). 1 Exposure to oocysts: Trial 1 and 2 at 14 days of age; Trial 3 at 7 days of age. 2 Feed/gain = feed consumed/live weight gained. * Significantly different from nonmedicated control (P<.05).
259,971 at 2.5, 5, 7.5, or 10 ppm; COBAN®1 monensin at 100 or 120 ppm; or ARPOCOX® 2 arprinocid at 60 ppm. The principal birds were exposed to litter previously contaminated by 10 seeder birds per pen, each of which had received 10 times the recommended immunizing dose of COCCIVAC® , type D live vaccine. The seeder birds were infected 5 days prior to being placed on the litter and were left in the pens for 2 weeks prior to replacement by the principal chicks. Litter paper was removed when the principal birds were 2 weeks of age. Five birds were withdrawn for coccidiosis monitoring on days 14, 28, 42, and at the termination of the trial at 49 days.
1 COBAN,i® , registered trademark of Elanco Products Co., Indianapolis, IN. 2 ARPOCOX®, registered trademark of Merck, Sharp and Dohme, Rahway, NJ. 3 COCCIVAC®, registered trademark of Sterwin Laboratories, Inc., Opelika, AL.
Trial 2. Fifty male and 50 female chicks were included in each pen and there were six replicate pens per treatment. Treatments consisted of no medication; CL 259,971 at 4, 5, or 6 ppm; or monensin at 120 ppm. Twenty seeder birds were placed in each pen for 2 weeks before the principal birds were placed in the pens. The seeder birds had received quantities of two recent collections of oocysts obtained from litter in commercial broiler raising houses from Georgia. The combination of materials provided oocysts from E. acervulina and/or E. mivati, E. brunetti, E. maxima, E. necatrix, and E. tenella. In addition to contaminated litter, similar sporulated oocysts were also added to the drinking water of the birds at 14 days of age when the paper was removed from the litter and the birds exposed. Five birds were withdrawn for coccidiosis monitoring on days 14, 21, 28, 44 and at the termination of the trial at 49 days. Trial 3. The design of the trial was similar to Trial 2 with the exception that the birds were exposed to litter which had been contaminated by sprinkling known quantities of oocysts
CL 259,971: POLYETHER ANTICOCCIDIAL
1509
around waterers and feeders. In addition, known quantities of oocysts were added to the drinking water. The infectious material was the same as was used in Trial 2. No seeder birds were used. The birds were exposed to the contaminated litter when they were 7 days of age. Four birds were withdrawn for coccidiosis monitoring on days 7, 14, 21, 44, and at the termination of the test at 49 days. Experimental data were analyzed by analysis of variance and means were compared using the multiple range test of Duncan (1955). Mortalities were compared using exact probability (Mainland et al, 1956). RESULTS AND DISCUSSION ts
S 1 S
•
•
• o\
•
(N
. Cst (S
.
.
. (S
.
(M ' 00
(J rt rq f Os 0 \
• o\
CN)
.a
rt •o
^
a)
rt
aj XI
«
0\ i - N r j » • t-> r^ so oo so
° — -^ -°
J3 "O tf rt rt m M r t \ 0 CO ' 0 \ 00 Q\ C\ Q\
i n so l>
; t^ r^ t^ t^ t^ r^ [ ON ON ON Ov Os 0\ » Os Os ON ON Os Os
! in m m in in in ; (N cs> csi cs! rj csi >J J J J J J,
ZuuuuuoSS<
t letters are not signifi
O 00 ON
in
Trial 1. Two weeks after exposure to infected litter, only the birds that received 2.5 or 5 ppm of CL 259,971 or arprinocid maintained weight gains significantly superior to the nonmedicated controls or birds receiving 120 ppm of monensin (Table 2). Although the remaining medicated treatment groups exhibited nominally superior weight gains, these were not significantly different from the nonmedicated controls. Feed efficiencies (feed/ gain) of the treated groups were superior to that of the nonmedicated controls, and only 7.5 ppm of CL 259,971 did not provide a significant improvement. This anomaly cannot be explained because the 10 ppm level provided significant improvement. Mortality in all the groups was low with no significant differences. No lesions were observed in any of the birds sacrificed 14 days after exposure, although low numbers of oocysts were found in droppings from the sacrificed birds. At the termination of the trial after 49 days and 5 days after the termination of medication, only birds receiving 2.5 or 5 ppm of CL 259,971 or 60 ppm or arprinocid weighed significantly more than the nonmedicated control birds. Birds that had received 10 ppm of CL 259,971 were significantly depressed compared to the other birds (Table 3). Improved feed efficiencies (feed/gain) were observed in the groups of birds that had received 100 ppm of monensin or 60 ppm of arprinocid. Trial 2. Although the exposure to oocysts was not sufficiently severe to provide a significant depression in the gains of the nonmedicated birds compared with the birds receiving CL 259,971, the weights of the nonmedicated birds were numerically inferior after 2 weeks of
1510
KANTOR ET AL.
TABLE 4. Average lesion scores' for species of Eimeria observed in birds sacrificed 7 days after exposure to oocysts Species Trial
Medication
2
Nonmedicated CL 259,971 CL 259,971 CL 259,971 Monensin
E. acervulina/ E. mivati
E. brunetti
E. maxima
1.67
1.12
1.67
0 0
0
E. necatrix
E. tenella
All
1.25
1.30
(ppm)
Nonmedicated CL 259,971 CL 259,971 CL 259,971 Monensin
3
4
5 6
0 Not done
120
.12
.04
4 5 6 120
2.25 c .60ab .79 b .42 a .40 a
2.08 c .17* .17 a .42ab .62 b
.79
0
0 0
0
0
2.96 c 1.08a 1.42 ab 1.38a 2.04b
1.62 b
.29
.04 0
0a 0a 0a
.40 a
.07 0
.12
.10
2.54 c 1.46b .42 a .58 a 1.33 b
2.29 b .66 a .56 a .56 a .89 a
a,b,c Scores within columns within trials with the same superscript letters are not significantly different (P = .05). 1
Maximum possible lesion score is 3.00.
exposure (Table 2). The feed efficiency of the nonmedicated birds, however, was significantly elevated. Birds receiving monensin at 120 ppm had significant weight gain depressions at this time, but because the weights of the birds at the beginning of exposure were reduced, probably because of toxicity, the difference cannot be attributed to lack of efficacy. As judged by lesions, the infection was light, but lesions from each of the five to six species were observed in the nonmedicated controls 7 days after exposure. Very few lesions from E. acervulina/mivati and E. tenella were noted in the birds receiving 4 ppm of CL 259,971, but no lesions from any of the species of Eimeria were found in the birds that received 5 ppm of CL 259,971, and, consequently, the birds receiving 6 ppm of CL 259,971 were not examined. Small numbers of lesions were observed in birds receiving 120 ppm of monensin from E. acervulina/mivati, E. brunetti, E. maxima, and E. tenella. Mortality in all groups was very light (Table 2). At 49 days, at the end of the trial, terminal weights of the birds were not different (Table 3). All the treated groups except those receiving 4 ppm of CL 259,971 had feed efficiencies significantly superior to those of the nonmedicated controls. Trial 3. The coccidial challenge to the birds was more severe in this trial than in the previ-
ous trials. Mortality was 4.6% in the nonmedicated controls (Table 2) and moderate to severe lesions from all the species of Eimeria were observed (Table 4). Medication significantly improved survival and the lesion scores of all the birds. Weight gains were significantly depressed in the nonmedicated birds when compared to the medicated birds (Table 2). Similarly, the feed efficiency of the nonmedicated birds was significantly depressed compared to the medicated groups. Birds receiving 5 or 6 ppm of CL 259,971 exhibited the best performance. Birds receiving 4 ppm of CL 259,971, although superior to those of the nonmedicated controls, were significantly inferior to the remaining treated groups. Feed efficiencies of birds receiving 120 ppm of monensin were significantly inferior. At termination at 49 days, all the medicated groups except birds receiving 4 ppm of CL 259,971 exhibited superior weights compared to the nonmedicated controls (Table 3), although all the treatment groups had similar feed efficiencies. General observations made during the three trials revealed no unusual conditions. Throughout, all the birds appeared in good condition and well colored, although in the third trial, some of the untreated birds appeared listless and with ruffled feathers for a week or two
CL 259,971: POLYETHER ANTICOCCIDIAL after exposure to oocysts. Also in the third trial, but not in the others, bloody and abnormal droppings were noted on the litter of all the treatment groups during the first 2 weeks of the infection but not thereafter. No sick birds were noted after the third week. Feathering was normal, no "bare-backs" were noted, and the numbers of feathers on the litter appeared uniform, indicating no abnormal feather eating in any of the pens. No excessive moisture was noted in the litter. Overall, it can be concluded thatCL 259,971 was an effective anticoccidial in these trials. At the potentially recommended use level of 5 ppm, CL 259,971 had no adverse effect on weight gain or performance.
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ACKNOWLEDGMENTS We wish to thank Cynthia R. Caterson, Angelo Gallo, Helen C. Miller, and the late Dominic Fortini for their invaluable technical assistance.
REFERENCES Duncan, D. B., 1955. Multiple range and multiple F tests. Biometries 11:1—42. Johnson, J., and W. M. Reid, 1970. Anticoccidial drugs: Lesion scoring techniques in battery and floor-pen experiments with chickens. Exp. Parasitol. 28:30-36. Mainland, D., L. Herrera, and M. I. Sutcliffe, 1956. Statistical Tables for Use with Binomial Samples. New York Univ., Coll. Med.