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Diclazuril, a New Broad-Spectrum Anticoccidial for Chickens
Diclazuril, a New Broad-Spectrum Anticoccidial for Chickens 3. Floor-Pen Trials O. VANPARIJS, R. MARSBOOM, L. HERMANS, and L. Van der FLAES Janssen Pharmaceutica, B-2340 Beerse, Belgium (Received for publication March 8, 1989) ABSTRACT Diclazuril is a benzeneacetonitrile showing great promise as a broad-spectrum anticoccidial agent for chickens, turkeys, and rabbits. The high anticoccidial activity of diclazuril in chickens, as first reported in dose-titration studies and battery trials, was confirmed in three floor-pen trials. The efficacy was demonstrated against six major pathogenic species of Eimeria after artificial infection with one or more species. The experimental data indicated that diclazuril, at dose levels of .5, .75, 1, and 2 ppm, had a high anticoccidial activity in terms of preventing mortality, suppressing or reducing lesion scores, and allowing for normal weight gains as well as productivity. The performances obtained with diclazuril was generally comparable with that of salinomycin at 60 ppm and that of lasalocid at 90 ppm. (Key words: diclazuril, coccidiosis, poultry, floor pen, efficacy) 1990 Poultry Science 69:60-64 INTRODUCTION
Laboratory dose-titration experiments (Vanparijs et al., 1989c) and battery trials (Vanparijs et al., 1989d) have indicated that diclazuril at 1 ppm in the feed is highly effective against the six major pathogenic species of Eimeria in poultry. The broadspectrum activity of diclazuril has also been demonstrated against three pathogenic species of Eimeria in turkeys (Vanparijs et al., 1989a) and against intestinal and hepatic coccidiosis in rabbits (Vanparijs et al., 1989b). Floor-pen trials are essential for the evaluation of anticoccidials; such trials also provide additional information about general behavior, feed consumption, and feed conversion (Brewer and Kowalski, 1970). The present study evaluated the efficacy of diclazuril against six major pathogenic species of Eimeria in three floor-pen trials conducted under simulated conditions for commercial growing using chickens artificially infected with coccidia. MATERIALS AND METHODS
Animals and Housing Facilities. In each of the three trials, 2,000 Hubbard broilers of mixed sexes (1 day old) were used. They were obtained from a commercial hatchery (De Biest Hatchery, Kruishoutem, Belgium). The chickens were divided in replicate groups of 50 birds per pen of 3.40 m2. All 40 pens had
concrete floors with wooden sidewalls up to .5 m and new peat litter. Heating was supplied by thermostatically controlled electric heat bulbs and was decreased gradually from 32 C at the start of the trials to 18 C at the end of the experiments. Artificial lighting and ventilation were provided continuously. Feed and water were available on an ad libitum basis. Eimeria Isolates. The species used were E. tenella and E. acervulina, two pathogenic laboratory strains isolated from the field in Belgium and maintained without medication for many years in the laboratory, and four other pathogenic species, the Houghton (Huntingdon, Cambridgeshire, England, U.K.) strains of E. necatrix, E. brunetti, E. maxima, and E. mitis provided by H. D. Chapman. The birds were artificially infected with either one or more Eimeria species when they were 14 days of age by giving the sporulated oocysts in 1 kg of wet feed per pen, administered after a starvation period of 2 h at infective doses per bird as follows: E. acervulina, 500,000 (Trial 1); E. maxima, 50,000 (Trial 1); and E. tenella, 50,000 (Trial 1); E. brunetti, 100,000 (Trial 2); E. necatrix, 50,000 (Trial 2); and E. mitis, 500,000 (Trial 3). Medication. The feed used for this trial was a commercial broiler ration (Huybrechts, Arendonk, Belgium) without any anticoccidial and containing avoparcin (Avotan®, Cyanamid Benelux, Mont-St.-Guibert, Belgium) at 10 ppm used as a growth promoter. The medicated feed was prepared by blending diclazuril
60
61
DICLAZURIL, AN ANTICOCCIDIAL AGENT FOR CHICKENS
(Clinacox®, Janssen Pharmaceutica, Beerse, Belgium) as a .5% carrier-coated, formulated compound to obtain the desired concentration. Before administration, a sample of all mixtures was analyzed to confirm the drug concentration. In all trials, medicated feed was available from Day 1 until 6 wk of age. The medication design is shown in Table 1. In Trials 1 and 2, diclazuril was administered at .5, 1, and 2 ppm. Diclazuril was compared with salinomycin (Sacox ®, Hoechst AG, Frankfurt, FRG) at 60 ppm and with infected, unmedicated controls. In Trial 3, diclazuril was administered at .5, .75, 1, and 2 ppm. Diclazuril was compared with lasalocid (Avatec ®, Hoffmann-La Roche, Nutley, NJ) at 90 ppm and with infected, unmedicated controls. Criteria for Evaluation. Body weights were recorded at 14, 28, and 42 days of age. Five birds per pen were autopsied for lesion scores on Day 21 using the method described by Johnson and Reid (1970). Death losses and the weight of dead birds were recorded daily. Necropsy was performed to determine the cause of death. Feed consumption was recorded. Feed conversion was calculated on Day 42. The productivity index (Voeten and Brus, 1966) was calculated at the end of the experiment on Day 42 using the following formula: Productivity index = [(body weight out)2 (10,000)]/[(number of days) (number of birds) (feed consumption)]. Statistical Analysis. The data were analyzed by a one-way ANOVA using the Statistical Analysis System (SAS Institute, 1982). Duncan's multiple range test (Duncan, 1957) was used to separate means.
RESULTS
Trial 1. At .5, 1, and 2 ppm, diclazuril prevented mortality and morbidity; whereas a mortality of 11% was recorded for the infected, unmedicated controls (Table 2). On Day 42, BW was significantly higher in both the diclazuril-medicated and salinomycin-medicated groups. Lesions were not detected in the medicated groups infected with E. acervulina and E. tenella. For the birds infected with E. maxima, lesion scores were greatly reduced in the group treated with diclazuril at 1 ppm, compared with diclazuril at .5 ppm, and with salinomycin. The efficacy of the reference drug salinomycin at 60 ppm was generally comparable to diclazuril at all dose levels. Feed conversion and productivity were significantly better in all medicated groups. Trial 2. The anticoccidial efficacy of diclazuril against a mixed infection of E. brunetti and E. necatrix is summarized in Table 3. There was no coccidiosis-related mortality in the medicated groups; whereas a mortality of 2.3% was recorded for the infected, unmedicated controls. The BW for the diclazuril groups were not significantly different from those of the salinomycin group. On Day 21, the lesion scores were very high (4.33) in the infected, unmedicated controls but were much lower in all of the diclazurilmedicated groups. Although substantially lower, the lesion scores in the salinomycin group were higher than in the diclazuril-treated groups. Feed conversion for the salinomycin group was significantly better than for the groups treated with 1 and 2 ppm of diclazuril,
TABLE 1. Medication design, diclazuril and six pathogenic species o/Eimeria given to chickens in three floor-pen trials
Medication IUC1 Diclazuril Diclazuril Diclazuril Diclazuril Salinomycin Lasalocid
Concentration of drug in feed (ppm) 0 .5 .75 1 2 60 90
'IUC = Infected, unmedicated controls.
Trial 1 Trial 2 E. maxima, E. tenella 8 8 8 8 8
E. brunetti, E. necatrix replicates, SO birds per pen 8 8 8 8 8
Trial 3 E. mitts 6 7 7 7 7 6
60
.5
11 0 0 0 0
(%)
Coccidiosisrelated mortality
.37 .38 .38 .37 .37
Day 14 .89* l.Ol1* 1.03b .99° 1.09"
Day 28 1.77" 1.87" 1.91" 1.85" 1.92"
Day 42
Body weight (kg)
2.3 0 0 0 0
3.39" 2.19b 1.30"1 1.55' 1.851
.30 .31 .32 .31 .30
Day 14 ,93 b .99" .99" .97" .98a
Day 28 1.87b 1.93" 1.94" 1.93" 1.95"
Day 42
4.33" .43 c .18',cd .08 d 1.13b
E. brunetti + E
Lesion scores, D
Mean of replicate values Body weight (kg)
Valucs within a column with no common superscript are significantly different (P<.05).
.5 1 2 60
0
Coccidiosisrelated mortality
IUC = Infected, unmedicated controls.
a_d
IUC1 Diclazuril Diclazuril Diclazuril Salinomycin
Medication
Concentration of drug in feed (ppm)
3.19"
TABLE 3. Trial 2, anticoccidial activity of diclazuril, performance in chickens a with a mixture of Eimeria brunetti and Eimeria necatrix in floor-pen
'lUC = Infected, unmedicated controls.
Lesion scor E. acervulina E. maxim
Mean of replicate values
"^Values within a column with no common superscript are significantly different (P<05).
IUC1 Diclazuril Diclazuril Diclazuril Salinomycin
Medication
Concentration of drug in feed (PP"0
TABLE 2. Trial 1, anticoccidial activity of diclazuril, performances in chickens artificially of Eimena acervulioa, Eimena maxima, and Eimena tenella in floor-pen
63
DICLAZURIL, AN ANTICOCCIDIAL AGENT FOR CHICKENS
but comparable to the feed conversion of the group treated with .5 ppm of diclazuril. There were no differences between the treated groups with regard to productivity indices. Trial 3. The anticoccidial activity against E. mitis is shown in Table 4. The coccidiosisrelated mortality was very low (1.3%) in the infected, unmedicated controls and was absent in the medicated groups. The final live weight for all of the diclazuril-medicated groups was comparable to that of the lasalocid group. On Day 21, the lesion scores were very low or were absent in the medicated groups but were different from the scores for the infected, unmedicated controls. Feed conversion and productivity indices for the medicated groups were significandy better than the values for the infected, unmedicated controls. The productivity indices for the diclazuril-medicated groups exceeded the productivity of the lasalocid group.
•a.
DISCUSSION
s.
The floor-pen trials in the present study confirm the results obtained in the laboratory dose-titration studies and the battery trials. The body weights on Day 14 were comparable for all groups in the three trials, demonstrating a normal growth with or without medication. On Day 28 (seven days after infection), the weight gain for all medicated groups of Trials 1 and 2 was significandy better than that of the infected, unmedicated controls, thus proving the pathogenicity of the infection. In Trial 3 {E. mitis), the weight decrease among the infected controls on Day 28 was less pronounced than in the other trials. For broiler chickens, artificially infected with one or more of the major pathogenic Eimeria species, performance and productivity were greatly improved after medication with diclazuril at dose levels between .5 and 2 ppm. The productivity number is a complementary evaluation of growth performances by using economical parameters such as feed efficiency, average daily growth, and mortality. The productivity index is particularly useful for comparing various breeds of broiler chickens or various growth promoters and therapeutics. These results are comparable with those obtained with the reference drugs salinomycin and lasalocid at 60 and 90 ppm, respectively. The high degree of efficacy exhibited in the
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VANPARUS ET AL.
present study by both ionophore reference drugs, was closely related to the anticoccidial activity obtained by Danforth et al. (1977) using salinomycin and by Mitrovic and Schildknecht (1974) using lasalocid. The data reported here confirm the high and broadspectrum efficacy of diclazuril at 1 ppm against coccidiosis in broiler chickens. ACKNOWLEDGMENTS
The authors wish to technical assistance and Devocht for secretarial help of P. Lewi for the greatly appreciated.
thank H. Geerts for J. Frederick and Y. work. The valuable statistical analysis is
REFERENCES Brewer, R. N., and L. M. Kowalski, 1970. Coccidiosis: Evaluation of anticoccidial drugs in floor-pen trials. Exp. Parasitol. 28:64-71. Danforth, H. D., M. D. Ruff, W. M. Reid, and J. Johnson, 1977. Anticoccidial activity of salinomycin in floor pen experiments with broilers. Poultry Sci. 56: 933-938.
Duncan, D. B., 1957. t-Test and intervals for comparisons suggested by the data. Biometrics 31:339-359. 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. Mitrovic, M., and E. G. Schildknecht, 1974. Anticoccidial activity of lasalocid (x-537A) in chicks. Poultry Sci. 53:1448-1455. SAS Institute, 1982. Pages 191-193 in: SAS User's guide. SAS Inst. Inc., Cary, NC. Vanpanjs, O., L. Hermans, L. Van der Flaes, and R. Marsboom, 1989a. Efficacy of diclazuril against turkey coccidiosis in dose titration studies. Avian Dis. 33: 422-424. Vanpanjs, O., L. Hermans, L. Van der Flaes, and R. Marsboom, 1989b. Efficacy of diclazuril in the prevention and cure of intestinal and hepatic coccidiosis in rabbits. Vet. Parasitol. 32:109-117. Vanpanjs, O., R. Marsboom, and L. Desplenter, 1989c. Diclazuril, a new broad spectrum anticoccidial in chickens. 1. Dose titration studies and pilot floor-pen trials. Poultry Sci. 68:489-495. Vanparijs, O., R. Marsboom, L. Hermans, and L. Van der Flaes, 1989d. Diclazuril, a new broad spectrum anticoccidial in chickens. 2. Battery trials. Poultry Sci. 68: 496-500. Voeten, A. C , and D.H.J. Brus, 1966. The production number as a criterion for the breeding results of broiler chickens. Tijdschr. Diergeneeskd. 91:1233-1240.
Laboratory dose-titration experiments (Vanparijs et al., 1989c) and battery trials (Vanparijs et al., 1989d) have indicated that diclazuril at 1 ppm in the feed is highly effective against the six major pathogenic species of Eimeria in poultry. The broadspectrum activity of diclazuril has also been demonstrated against three pathogenic species of Eimeria in turkeys (Vanparijs et al., 1989a) and against intestinal and hepatic coccidiosis in rabbits (Vanparijs et al., 1989b). Floor-pen trials are essential for the evaluation of anticoccidials; such trials also provide additional information about general behavior, feed consumption, and feed conversion (Brewer and Kowalski, 1970). The present study evaluated the efficacy of diclazuril against six major pathogenic species of Eimeria in three floor-pen trials conducted under simulated conditions for commercial growing using chickens artificially infected with coccidia. MATERIALS AND METHODS
Animals and Housing Facilities. In each of the three trials, 2,000 Hubbard broilers of mixed sexes (1 day old) were used. They were obtained from a commercial hatchery (De Biest Hatchery, Kruishoutem, Belgium). The chickens were divided in replicate groups of 50 birds per pen of 3.40 m2. All 40 pens had
concrete floors with wooden sidewalls up to .5 m and new peat litter. Heating was supplied by thermostatically controlled electric heat bulbs and was decreased gradually from 32 C at the start of the trials to 18 C at the end of the experiments. Artificial lighting and ventilation were provided continuously. Feed and water were available on an ad libitum basis. Eimeria Isolates. The species used were E. tenella and E. acervulina, two pathogenic laboratory strains isolated from the field in Belgium and maintained without medication for many years in the laboratory, and four other pathogenic species, the Houghton (Huntingdon, Cambridgeshire, England, U.K.) strains of E. necatrix, E. brunetti, E. maxima, and E. mitis provided by H. D. Chapman. The birds were artificially infected with either one or more Eimeria species when they were 14 days of age by giving the sporulated oocysts in 1 kg of wet feed per pen, administered after a starvation period of 2 h at infective doses per bird as follows: E. acervulina, 500,000 (Trial 1); E. maxima, 50,000 (Trial 1); and E. tenella, 50,000 (Trial 1); E. brunetti, 100,000 (Trial 2); E. necatrix, 50,000 (Trial 2); and E. mitis, 500,000 (Trial 3). Medication. The feed used for this trial was a commercial broiler ration (Huybrechts, Arendonk, Belgium) without any anticoccidial and containing avoparcin (Avotan®, Cyanamid Benelux, Mont-St.-Guibert, Belgium) at 10 ppm used as a growth promoter. The medicated feed was prepared by blending diclazuril
60
61
DICLAZURIL, AN ANTICOCCIDIAL AGENT FOR CHICKENS
(Clinacox®, Janssen Pharmaceutica, Beerse, Belgium) as a .5% carrier-coated, formulated compound to obtain the desired concentration. Before administration, a sample of all mixtures was analyzed to confirm the drug concentration. In all trials, medicated feed was available from Day 1 until 6 wk of age. The medication design is shown in Table 1. In Trials 1 and 2, diclazuril was administered at .5, 1, and 2 ppm. Diclazuril was compared with salinomycin (Sacox ®, Hoechst AG, Frankfurt, FRG) at 60 ppm and with infected, unmedicated controls. In Trial 3, diclazuril was administered at .5, .75, 1, and 2 ppm. Diclazuril was compared with lasalocid (Avatec ®, Hoffmann-La Roche, Nutley, NJ) at 90 ppm and with infected, unmedicated controls. Criteria for Evaluation. Body weights were recorded at 14, 28, and 42 days of age. Five birds per pen were autopsied for lesion scores on Day 21 using the method described by Johnson and Reid (1970). Death losses and the weight of dead birds were recorded daily. Necropsy was performed to determine the cause of death. Feed consumption was recorded. Feed conversion was calculated on Day 42. The productivity index (Voeten and Brus, 1966) was calculated at the end of the experiment on Day 42 using the following formula: Productivity index = [(body weight out)2 (10,000)]/[(number of days) (number of birds) (feed consumption)]. Statistical Analysis. The data were analyzed by a one-way ANOVA using the Statistical Analysis System (SAS Institute, 1982). Duncan's multiple range test (Duncan, 1957) was used to separate means.
RESULTS
Trial 1. At .5, 1, and 2 ppm, diclazuril prevented mortality and morbidity; whereas a mortality of 11% was recorded for the infected, unmedicated controls (Table 2). On Day 42, BW was significantly higher in both the diclazuril-medicated and salinomycin-medicated groups. Lesions were not detected in the medicated groups infected with E. acervulina and E. tenella. For the birds infected with E. maxima, lesion scores were greatly reduced in the group treated with diclazuril at 1 ppm, compared with diclazuril at .5 ppm, and with salinomycin. The efficacy of the reference drug salinomycin at 60 ppm was generally comparable to diclazuril at all dose levels. Feed conversion and productivity were significantly better in all medicated groups. Trial 2. The anticoccidial efficacy of diclazuril against a mixed infection of E. brunetti and E. necatrix is summarized in Table 3. There was no coccidiosis-related mortality in the medicated groups; whereas a mortality of 2.3% was recorded for the infected, unmedicated controls. The BW for the diclazuril groups were not significantly different from those of the salinomycin group. On Day 21, the lesion scores were very high (4.33) in the infected, unmedicated controls but were much lower in all of the diclazurilmedicated groups. Although substantially lower, the lesion scores in the salinomycin group were higher than in the diclazuril-treated groups. Feed conversion for the salinomycin group was significantly better than for the groups treated with 1 and 2 ppm of diclazuril,
TABLE 1. Medication design, diclazuril and six pathogenic species o/Eimeria given to chickens in three floor-pen trials
Medication IUC1 Diclazuril Diclazuril Diclazuril Diclazuril Salinomycin Lasalocid
Concentration of drug in feed (ppm) 0 .5 .75 1 2 60 90
'IUC = Infected, unmedicated controls.
Trial 1 Trial 2 E. maxima, E. tenella 8 8 8 8 8
E. brunetti, E. necatrix replicates, SO birds per pen 8 8 8 8 8
Trial 3 E. mitts 6 7 7 7 7 6
60
.5
11 0 0 0 0
(%)
Coccidiosisrelated mortality
.37 .38 .38 .37 .37
Day 14 .89* l.Ol1* 1.03b .99° 1.09"
Day 28 1.77" 1.87" 1.91" 1.85" 1.92"
Day 42
Body weight (kg)
2.3 0 0 0 0
3.39" 2.19b 1.30"1 1.55' 1.851
.30 .31 .32 .31 .30
Day 14 ,93 b .99" .99" .97" .98a
Day 28 1.87b 1.93" 1.94" 1.93" 1.95"
Day 42
4.33" .43 c .18',cd .08 d 1.13b
E. brunetti + E
Lesion scores, D
Mean of replicate values Body weight (kg)
Valucs within a column with no common superscript are significantly different (P<.05).
.5 1 2 60
0
Coccidiosisrelated mortality
IUC = Infected, unmedicated controls.
a_d
IUC1 Diclazuril Diclazuril Diclazuril Salinomycin
Medication
Concentration of drug in feed (ppm)
3.19"
TABLE 3. Trial 2, anticoccidial activity of diclazuril, performance in chickens a with a mixture of Eimeria brunetti and Eimeria necatrix in floor-pen
'lUC = Infected, unmedicated controls.
Lesion scor E. acervulina E. maxim
Mean of replicate values
"^Values within a column with no common superscript are significantly different (P<05).
IUC1 Diclazuril Diclazuril Diclazuril Salinomycin
Medication
Concentration of drug in feed (PP"0
TABLE 2. Trial 1, anticoccidial activity of diclazuril, performances in chickens artificially of Eimena acervulioa, Eimena maxima, and Eimena tenella in floor-pen
63
DICLAZURIL, AN ANTICOCCIDIAL AGENT FOR CHICKENS
but comparable to the feed conversion of the group treated with .5 ppm of diclazuril. There were no differences between the treated groups with regard to productivity indices. Trial 3. The anticoccidial activity against E. mitis is shown in Table 4. The coccidiosisrelated mortality was very low (1.3%) in the infected, unmedicated controls and was absent in the medicated groups. The final live weight for all of the diclazuril-medicated groups was comparable to that of the lasalocid group. On Day 21, the lesion scores were very low or were absent in the medicated groups but were different from the scores for the infected, unmedicated controls. Feed conversion and productivity indices for the medicated groups were significandy better than the values for the infected, unmedicated controls. The productivity indices for the diclazuril-medicated groups exceeded the productivity of the lasalocid group.
•a.
DISCUSSION
s.
The floor-pen trials in the present study confirm the results obtained in the laboratory dose-titration studies and the battery trials. The body weights on Day 14 were comparable for all groups in the three trials, demonstrating a normal growth with or without medication. On Day 28 (seven days after infection), the weight gain for all medicated groups of Trials 1 and 2 was significandy better than that of the infected, unmedicated controls, thus proving the pathogenicity of the infection. In Trial 3 {E. mitis), the weight decrease among the infected controls on Day 28 was less pronounced than in the other trials. For broiler chickens, artificially infected with one or more of the major pathogenic Eimeria species, performance and productivity were greatly improved after medication with diclazuril at dose levels between .5 and 2 ppm. The productivity number is a complementary evaluation of growth performances by using economical parameters such as feed efficiency, average daily growth, and mortality. The productivity index is particularly useful for comparing various breeds of broiler chickens or various growth promoters and therapeutics. These results are comparable with those obtained with the reference drugs salinomycin and lasalocid at 60 and 90 ppm, respectively. The high degree of efficacy exhibited in the
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VANPARUS ET AL.
present study by both ionophore reference drugs, was closely related to the anticoccidial activity obtained by Danforth et al. (1977) using salinomycin and by Mitrovic and Schildknecht (1974) using lasalocid. The data reported here confirm the high and broadspectrum efficacy of diclazuril at 1 ppm against coccidiosis in broiler chickens. ACKNOWLEDGMENTS
The authors wish to technical assistance and Devocht for secretarial help of P. Lewi for the greatly appreciated.
thank H. Geerts for J. Frederick and Y. work. The valuable statistical analysis is
REFERENCES Brewer, R. N., and L. M. Kowalski, 1970. Coccidiosis: Evaluation of anticoccidial drugs in floor-pen trials. Exp. Parasitol. 28:64-71. Danforth, H. D., M. D. Ruff, W. M. Reid, and J. Johnson, 1977. Anticoccidial activity of salinomycin in floor pen experiments with broilers. Poultry Sci. 56: 933-938.
Duncan, D. B., 1957. t-Test and intervals for comparisons suggested by the data. Biometrics 31:339-359. 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. Mitrovic, M., and E. G. Schildknecht, 1974. Anticoccidial activity of lasalocid (x-537A) in chicks. Poultry Sci. 53:1448-1455. SAS Institute, 1982. Pages 191-193 in: SAS User's guide. SAS Inst. Inc., Cary, NC. Vanpanjs, O., L. Hermans, L. Van der Flaes, and R. Marsboom, 1989a. Efficacy of diclazuril against turkey coccidiosis in dose titration studies. Avian Dis. 33: 422-424. Vanpanjs, O., L. Hermans, L. Van der Flaes, and R. Marsboom, 1989b. Efficacy of diclazuril in the prevention and cure of intestinal and hepatic coccidiosis in rabbits. Vet. Parasitol. 32:109-117. Vanpanjs, O., R. Marsboom, and L. Desplenter, 1989c. Diclazuril, a new broad spectrum anticoccidial in chickens. 1. Dose titration studies and pilot floor-pen trials. Poultry Sci. 68:489-495. Vanparijs, O., R. Marsboom, L. Hermans, and L. Van der Flaes, 1989d. Diclazuril, a new broad spectrum anticoccidial in chickens. 2. Battery trials. Poultry Sci. 68: 496-500. Voeten, A. C , and D.H.J. Brus, 1966. The production number as a criterion for the breeding results of broiler chickens. Tijdschr. Diergeneeskd. 91:1233-1240.