Anticoccidial Efficacy of Halofuginone in Turkeys Reared to Market Weight LARRY R. McDOUGALD Department of Poultry Science, University of Georgia, Athens, Georgia 30602 GREG F. MATHIS Georgia Poultry Research Inc., P.O. Box 5822, Athens, Georgia 30604 JOHN SCHWARTZ and CAREY L. QUARLES Colorado Quality Research, Inc., Fort Collins, Colorado 80526
AEF Research, Inc., Waunakee, Wisconsin 53597 ROBERT J. GRANT Animal Health Research and Development, Hoechst-Roussel Agri Vet Company Somerville, New Jersey 08876 (Received for publication December 2, 1985) ABSTRACT Floor-pen studies were conducted in three geographic locations to study the efficacy of halofuginone (3.0 ppm in feed) against important species of coccidia in turkeys. Severe coccidiosis exposure was obtained in studies in Georgia and Colorado and mild coccidiosis in Wisconsin. Coccidiosis caused by contamination of the feed with oocysts of Eimeria adenoeides, E. meleagrimitis, and E. gallopavonis was almost completely controlled by halofuginone at 3 ppm, even though intestinal lesion scores and weight loss were high in two studies. Halofuginone was also highly effective in preventing buildup of infection in pens contaminated by indirect means (movement by caretakers through the pens, etc.). Weight gains and feed conversion were best in poults receiving halofuginone, whether directly or indirectly exposed. There was no evidence that halofuginone caused any untoward reactions in the poults, even though the drug was fed until turkeys reached market weight. (Key words: halofuginone, turkeys, Meleagris gallopavo, coccidiosis, Eimeria, chemotherapy) 1986 Poultry Science 65:1664-1670
INTRODUCTION Coccidiosis in t u r k e y s is a widespread problem in t h e United States (Edgar, 1983). Because of age resistance, only t u r k e y s appear t o b e at risk, and medication p r o b l e m s are aimed at protecting t h e birds from infection until t h e y are 10 weeks old (McDougald and McQuistion, 1978). Halofuginone, used widely against coccidiosis in chickens, was d e m o n s t r a t e d effective against i m p o r t a n t species of coccidia in y o u n g t u r k e y s at 3 p p m (Edgar and Flanagan, 1 9 7 9 ; Ross, 1 9 7 4 ; Naciri et al, 1 9 8 1 ) . At 1.5 t o 1.6 p p m , halofuginone was highly effective in preventing damage from r e c e n t field isolates of Eimeria meleagrimitis, E. adenoeides, and E. gallopavonis (McDougald, 1985).
T h e p u r p o s e of this s t u d y was t o confirm t h e efficacy of halofuginone at 3 p p m u n d e r simulated field conditions, against light and heavy infections of recent field isolates of coccidia, and t o s t u d y t h e effect of halofugin o n e on growth of t u r k e y s u p to m a r k e t weight. Test facilities in Georgia, Colorado, a n d Wisconsin were selected t o represent a variety of growing conditions. MATERIALS AND METHODS Facilities. Floor-pen houses located in Color a d o , Georgia, and Wisconsin were organized with equal-sized pens on either side of a central aisle. Pens had a u t o m a t i c waterers, infra-red heat b u l b s for brooding, a d e q u a t e feeder space,
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TOM KENNEDY
EFFICACY OF HALOFUGINONE
of the mixed cultures were poured onto the feed and litter when poults were 14 days old. The "indirectly exposed" pens became exposed only by the movement of personnel from pen to pen, carrying oocysts on the feet, and by other incidental means. The initial direct exposure was given when the birds were 14 days old. Experimental Design. Each of the four experimental treatments was replicated in four pens of 25 to 30 male poults and four pens of female poults. The treatments were: 1) unmedicated, direct exposure; 2) unmedicated, indirect exposure; 3) halofuginone, 3 ppm, direct expos u r e ^ ) halofuginone, 3 ppm, indirect exposure. The pens were randomly assigned to treatments within blocks for each sex. Medicated or unmedicated rations were fed continuously to female turkeys through 15 to 17 weeks and male turkeys through 18 to 21 weeks. Data Collection. 1) When birds were 21 or 28 days old, five preselected birds were removed from each pen, and the intestinal lesion scores were recorded on a scale of 0 (no lesions) to 4 (maximum lesions), for the upper, lower, and cecal parts of the intestine (McDougald, 1976). Preselection was done randomly by wing-band numbers to avoid bias; 2) Live weights and bird per pen were recorded on Day 28 and at termination of the experiment; 3) Feed was issued, with weighback on Day 28 and at termination; 4) Mortality from all causes, and autopsy to determine the cause of death, where possible.
RESULTS
Coccidiosis Infections. The severity of infections at the three locations varied, because different isolates were used that had apparent
TABLE 1. Facilities used in coccidiosis efficacy studies
Facility
Pen size
Birds started per pen
Colorado Georgia Wisconsin
55 sq ft 50 sq ft 72 sq ft
25 30 30 6 or 29 9
Length of study
Replicates Male
Female
Male
4 4 4
4 4 4
18 21 19
Female (wk) 15 17 16
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and clean pine shavings for litter. Replications of each treatment were randomly assigned to pens within blocks of males or female birds. The size of pen replications, and stocking density are noted in Table 1. Experimental Animals, Male and female turkey poults (Nicholas, large white) were purchased as day-old from local commercial hatcheries and were taken immediately to the floor-pen house and distributed into pens. Extra poults of each sex were maintained separately to replace poults that died during the first week. Feed and water were given ad libitum throughout. Feeds and Medicaments. A commercial type of turkey starter or grower ration was used unmedicated or was mixed with Stenorol premix to produce 3 ppm of halofuginone. Samples of each feed mix were sent to American Hoechst Co. Assay results confirmed that the feeds contained the intended concentration of halofuginone. Exposure to Coccidia. Batches of coccidia were propagated from field isolates from commercial turkey flocks, supplied by S. A. Edgar, Auburn, AL. Isolates were selected that were predominantly Eimeria adenoeides, E, meleagrimitis, and E. gallopavonis. Different isolates of coccidia were used in each of the three experiments. The viability and pathogenicity of oocysts of each species was confirmed on the basis of previous infections in susceptible poults of the same age as the floor-pen birds. In each trial, sufficient oocysts were mixed into the feed to provide an average/bird of 25,000 E. adenoeides, 75,000 E. meleagrimitis, and 25,000 E. gallopavonis. The results of infection varied from trial to trial because of the difference in pathogenicity of the isolates used. In the "direct exposure" pens, measured amounts
1665
.733 .686
M F
M F
Unmedicated Indirect infection
3 ppm halofuginone Direct infection
3 ppm halofuginone Indirect infection
3
2.21 2.17
2.04 2.34 4.21 3.56
3.87 3.32
3.71 3.80
3.85 3.78
Final
.8 1.2
.4 1.0
.9 1.1
1.2 2.5
Up
0 0
0 0
0 0
0 0
Mid
0 .4 .1
.1
.2 .2
.9 1.0
Low
Day 21
0
0
0
.5
.2
.4
.2 1.5
Ceca
1 9 weeks for males, 16 weeks for females.
1.2 1.8
.4 1.3
1.1 1.7
2.3 5.0
Tot
0 0
0 0
0 0
0 .4
Up
2
0
0 0 .1
.2 .4
.5 .8
Mid
Avg intestinal lesion sscores
Average of five birds/pen, mean of eight replicates/treatment; Up = upper, Mid = middle, Low = lower, Tot = total.
30 female or 29 male poults/pen started, less 10 birds for lesion score.
11.71 7.07
11.83 7.15
2.25 2.59
2.35 2.56
Day 28
Feed conversion
against turkey coccidiosis; mild exposure (Wisconsin study)
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2
1
.625 .646
M F
Unmedicated Direct infection
.703 .683
11.38 6.95
(Kg; .610 .571
M F
11.56 6.86
Final 3
Day 28
Sex
Avg live wt 1
TABLE 2. Efficacy ofhalofuginone
0
.2
.4 .2
.5 1.0
1.1 2.1
Low
Day 28
0 0
0 0
0 0
0 0
Ceca
0
.3
.4 .2
.7 .5
1.6 3.3
Tot
S
a
D O C ALD ET AL.
M F
3 ppm halofuginone Indirect infection
3
2
1
.914 .797
M F
3 ppm halofuginone Direct infection
1.64 1.65 1.59 1.63
11.852 6.831
1.63 1.67
1.84 1.89
Day 28
0 0
0
.8 .3
.1
3.9 3.7
Up
0 0
.2 .1
.2 .1
3.2 2.6
Mid
21 weeks for males, 17 weeks for females.
Average of five birds/pen, mean of eight replicates/treatment; Up = upper, Mid = middle, Lov
2.69 2.67
2.84 2.68
2.98 2.72
2.97 2.74
Final
Feed conversion
11.747 6.640
10.679 6.240
30 birds/pen started, less 10 birds for lesion score.
.943 .823
.886 .794
M F
Unmedicated Indirect infection
10.422 6.066
M F
Unmedicated Direct infection
skg) .724 .640
Sex
Treatment
Final
3
Day 28
Avg live wt 1
.1
0 0
.5 .5
.3 .4
2.4 2.5
Ceca
0
.1
.1 .2
.1 0
.4 .2
.2 .2 1.8 1.0
1.1 1.1
Mid
1.1 1.7
1.3 1.4
Up
2
.9 1.8
.6 .8
11.7 10.6
Tot
•• lower, Tot = total.
0
.3 .2
.2 .3
2.3 1.8
Low
Day 21
Avg intestinal lesion scores
TABLE 3. Efficacy of balofuginone against moderately severe coccidiosis exposure (Georgia study)
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0 0
.2 .1
.3 .1
Low
Day 28
.3 .3
.5 .2
1.7 1.7
1.3 1.2
Ceca
.4 .5
1.1 .6
3.8 5.2
3.9 3.7
Tot
Os
2 z z
r O G
o >1
o •<
n >
m
1.036 .920
M F
M F
3 p p m halofuginone Direct infection
3 p p m halofuginone Indirect infection
3
2
1
1.027 .917
M F
Unmedicated Indirect infection
1.72 1.72
1.78 1.81
1.75 1.76
1.86 1.87
Day 28
.1
2.62 2.58 2.54 2.42
.2 .1
2.81 2.59
0 0
0
2.3 1.8
Up
2.96 2.55
Final
Feed conversion
0
0 0 .1
.2 .1
1.5 1.0
Mid
0 0
0 0
0 0
.6 .2
Low
Day 21
0 .1
.2 .3
.1 .1
2.4 1.8
Ceca
15 to 16 weeks for females, 21 to 22 weeks for males.
.1 .1
.2 .4
.4 .5
6.7 4.7
Tot
0
.1
.3 .1
1.8 1.6
.6 .9
Up
0 .1
.1 .1
1.1 1.2
.2 .1
Mid
Avg intestinal lesion scores 2
Average of five birds/pen, mean of eight replicates/treatment; Up = upper, Mid = middle, Low = lower, Tot = total.
25 birds/pen started, less 10 birds for lesion score.
11.807 7.878
11.202 7,858
11.270 7.791
10.929 7.769
(Kg) .922 .871
M F
Unmedicated Direct infection
1.130 .911
Final
Sex
Treatment
3
Day 28
Avg live w t 1
TABLE 4. Efficacy of halofuginone against turkey coccidiosis; severe exposure (Colorado study)
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0
.1 .1
.3
.2 .1
Low
Day 2 8
0
.1
.2 .3
1.2 1.3
1.1 .3
Ceca
.8 .4
.5 .4
4.3 4.1
2.0 1.3
Tot
> r o w > r
s D O C
EFFICACY OF HALOFUGINONE
low; weight gain and feed conversion were excellent; and there was no mortality from coccidiosis. The beneficial effects of coccidiosis prevention by halofuginone on performance was still apparent in the final weights and feed conversions. The indirectly exposed, unmedicated controls continued to develop coccidiosis after the 28-day weigh period and had poorer weights and feed conversion at the end. DISCUSSION Even though coccidiosis in turkeys is widespread and important in the United States (Edgar, 1983), the development of new anticoccidial drugs has not been pursued to the same extent as in other poultry. The Feed Additives Compendium (1985, Miller Publishing Co., Minneapolis) lists six drugs for prevention of coccidiosis in turkeys: amprolium, butynorate, nitrofurazone, sulfadimethoxine with ormetoprim, sulfaquinoxaline, and zoalene. Some of these drugs were approved for use more than 20 years ago, and there is no recently published evidence of their effectiveness. Because of the opportunity for resistance development in coccidia where drugs are used continuously (Jeffers and Bentley, 1980a,b; Joyner and Norton, 1970), the probability is high that there is widespread resistance to some of these drugs. Most of these drugs have a limited spectrum of activity and would not control certain species of coccidia (McDougald and McQuistion, 1978). Thus, there is a need for new products for turkeys. The anticoccidial efficacy of halofuginone against coccidia in the turkey is well established from laboratory studies (Edgar and Flanagan, 1979; Naciri et al, 1981; Ross, 1974; McDougald, 1985). The present studies confirmed that halofuginone has excellent broad-spectrum efficacy against turkey coccidia, even in the face of severe exposure. Because of the well known phenomenon of age resistance to coccidiosis in turkeys, the common practice is to feed anticoccidial drugs only to 8 to 12 weeks of age (McDougald and McQuistion, 1978). In these studies, halofuginone was fed to market weight, with no untoward effects. There was no evidence in any of the studies that halofuginone caused any undesirable side effects. REFERENCES Edgar, S. A., 1983. Distribution and importance of turkey coccidia. Poultry Sci. 62:1415. (Abstr.) Edgar, S. A., and C. Flanagan, 1979. Efficacy of
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differences, in pathogenicity, possibly caused by contaminants of less pathogenic species. Moderate to severe infections were produced in Georgia and Colorado, and mild infections in Wisconsin. Wisconsin Study. Coccidiosis was mild to moderate, with low lesion scores, no mortality from coccidiosis, and only a moderate adverse effect on weight gain and feed conversion in unmedicated controls (Table 2). The effects on gain and performance were only apparent at 28 days, immediately after the infection period. At market weight, the turkeys in infected control groups had recovered sufficiently so that there was no difference between treated and controls. Turkeys given halofuginone were completely protected against the weight-depressing and feed-wasting effects of coccidiosis at 28 days. By the end of the study, there were no differences between medicated and unmedicated treatments. Lesion scores were significantly lower in medicated groups, as compared to the unmedicated, directly infected group. Georgia Study. Severe coccidiosis was produced in unmedicated controls, as shown by the high lesion scores and depressed weight at 28 days of age (Table 3). The infection spread from directly infected pens to indirectly infected pens, producing moderate lesion scores when examined 14 days postexposure. The turkeys medicated with halofuginone were almost completely protected against infection, as shown by very low lesion scores at 7 or 14 days postexposure and significantly higher weight gains at 28 days of age. The improved gain and good feed conversion were maintained throughout the study, and were still apparent at completion. The effect was similar in male and female turkeys. There was no mortality from coccidiosis, probably, because E. adenoeides was not as prominent as some of the other species in the isolates selected for use in this study. Colorado Study. Severe coccidiosis was produced, as shown by the high lesion scores, and so were depressed weights and poor feed conversions on Day 28 in unmedicated controls (Table 4). Mortality from coccidiosis averaged 7 to 10% in unmedicated pens. The infection spread from the directly infected pens, so that lesion scores and mortality were high 14 days postexposure in the indirectly infected pens. Medication with halofuginone gave almost complete protection against infections, even in the directly infected pens. Lesion scores were very
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Stenorol (halofuginone). III. For the control of coccidiosis in turkeys. Poultry Sci. 58:1483— 1489. Jeffers, T. K., and E. J. Bentley, 1980a. Monensin sensitivity of recent field isolates of turkey coccidia. Poultry Sci. 59:1722-1730. Jeffers, T. K., and E. J. Bentley, 1980b. Experimental development of monensin resistance in Eimeria meleagrimitis. Poultry Sci. 59:1731—1735. Joyner, L. P., and C. C. Norton, 1970. The response of recently isolated strains of Eimeria meleagrimitis to chemotherapy. Res. Vet. Sci. 11:349— 353. McDougald, L. R., 1976. Anticoccidial action of monensin in turkey poults. Poultry Sci. 55:
2442-2447. McDougald, L. R., 1976. Halofuginone: laboratory titration of anticoccidial activity in young turkeys. Poultry Sci. 6 5 : 2 8 0 - 2 8 3 . McDougald, L. R., andT. E. McQuistion, 1978. Innate and acquired immunity vs. anticoccidial medication in managing coccidiosis in turkeys. Avian Dis. 22:765-770. Naciri, M., L. Conan, and P. Yvore, 1981. Efficacite comparee du monensin et de l'halofuginone dans la prevention de la coccidiose du dindon. Rec. Med. Vet. 157:287-290. Ross, B., 1974. The effect of halofuginone (Stenorol) on experimental coccidiosis infection in turkey poults. Page 24 in Proc. XV World's Poult. Congr. Downloaded from http://ps.oxfordjournals.org/ at Michigan State University on April 9, 2015