The Activity of Glycarbylamide, Trithiadol, and Nicarbazin Against Eimeria tenella in Chickens D. K. MCLOUGHLIN, J. L. GARDINER AND D. K. CHESTER
Animal Disease and Parasite Research Division, Agricultural Research Service, U. S. Department of Agriculture, Beltsville, Maryland (Received for publication January 11, 1960)
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MATERIALS AND METHODS
A total of 1,592 one-week-old, coccidiafree chicks were used in these experiments. Except where otherwise stated, these were straight run, mixed breed chicks. In all instances the birds were grouped by weight, according to the method suggested by Gardiner and Wehr (1950). Each group, comprised of 16 to 20 chicks, was housed in a small, unheated, wire-floored, metal brooder. The groups which received coccidiostats were started on the appropriate medicated mash (0.003 percent glycarbylamide, 0.06 percent Trithiadol,* or 0.0125 percent nicarbazin) 24 hours prior to inoculation, and medicated continuously for the 14-day postinoculation experimental *0.05 percent bithionol +0.01 percent methiotriazamine in finished formulation made up from proprietary premix.
period. Inoculations of sporulated Eimeria tenella oocysts, suspended in 0.5 ml. of water, were made directly into the crop with the aid of a 5-ml. pipette. In the comparative efficacy studies, an uninoculated, medicated control group (UMC) was used for each drug, in addition to an uninoculated, unmedicated control group (UUC), and an inoculated, unmedicated control group (IUC) for each of the four experiments in the series. During the course of the experiments, observations were made on the various groups for coccidial-induced morbidity and mortality. At the end of this period all surviving birds were weighed, necropsied, and the cecal lesions evaluated in the usual manner (cf. Gardiner et al., 1952). In addition, feed consumption records were kept for each group. RESULTS
A. Comparative efficacy oj glycarbylamide, Trithiadol, and nicarbazin. A total of 631 straight run chicks were used in the four experiments of this series. In one experiment, the inoculum was 100,000 E. tenella oocysts per bird, and in the others it was 200,000 oocysts. The salient data from these four experiments have been combined and are presented in Table 1. Furthermore, the growth data obtained for each of the eight groups, as well as for the four feeding regimens, have been compared by the use of Duncan's multiple range test (1955). The resultant rankings of the principal and control groups are presented in Tables 2 and 3. All three drugs afforded some protection
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LYCARBYLAMIDE, Trithiadol, and nicarbazin are relatively new coccidiostats, which are currently widely used. Nicarbazin has been the subject of considerable experimentation, but there is little in the literature regarding the other drugs. The results of a preliminary study of the comparative efficacy of these compounds and others were reported by McLoughlin and Chester (1959). This preliminary study suggested further investigation of the ability of glycarbylamide, nicarbazin, and Trithiadol to reduce mortality and morbidity caused by cecal coccidiosis in chickens. The results of this study are presented herein.
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ACTIVITY OF COCCIDIOSTATS TABLE 1.—Response of chicks exposed and unexposed to Eimeria tenella in the presence of various anticoccidials as compared with their unmedicated controls Weight per surviving bird Birds
Mean* PercentFeed age conver- cecal lesion Start End Gain UUC** sion value (gms.) (gms.) (gms.) gain per factor surviving bird
No. deaths
0.003% glycarbylamide, inoculated 0.003% glycarbylamide, uninoculated
80
1
1.3
89
262
173
117
2.50
0.10
79
0
0.0
89
247
158
107
2.61
0.00
0.06% Trithiadol, inoculated 0.06% Trithiadol, uninoculated
80
15
18.8
90
242
152
103
3.65
1.33
79
0
0.0
89
245
156
105
2.69
0.00
0.0125% nicarbazin, inoculated 0.0125% nicarbazin, uninoculated
80
0
0.0
89
250
161
109
2.74
0.00
79
0
0.0
89
223
134
90
3.79
0.00
Inoculated-unmedicated control Uninoculated-unmedicated control
77
25
32.5
89
209
120
81
6.60
1.97
77
0
0.0
89
237
148
100
2.87
0.00
* Value of lesions: 0 = n o lesions; 1 = barely recognizable lesions; 2 = cecal walls thickened, small to medium cores; 3 = cecal walls thick, large cores or much blood; 4=bird died of coccidiosis. ** UUC=uninoculated, unmedicated controls.
from mortality due to experimental coccidiosis. No deaths occurred among the nicarbazin-protected birds. The mortality was slightly more than 1 percent in the glycarbylamide-medicated groups and approxiTABLE 2.-—Rank of rate of growth of the surviving chicks in the eight groups Regimen 0.003% glycarbylamide 0.0125% nicarbazin 0.003% glycarbylamide 0.06% Trithiadol 0.06% Trithiadol Unmedicated 0.0125% nicarbazin Unmedicated (A) (B, C , D , E )
Experimental condition
Rank
inoculated inoculated uninoculated inoculated uninoculated uninoculated uninoculated inoculated ( E , F ) (G,H)*
A B C D E F G H
* The results of the tests of significance are presented so that any two groups (designated by the letters A, B, C, etc.) appearing in the same parentheses do not differ significantly from one another. Any two different groups not appearing in the same parentheses do differ significantly.
mately 19 percent in the Trithiadol-treated groups. This compared with more than 32 percent mortality in the inoculated, unmedicated controls. The inoculated, glycarbylamide-medicated groups made significantly better weight gains than did the other seven groups. Moreover, when the data for both inoculated and uninoculated groups on each TABLE 3.—Rank of rale of growth exhibited by the surviving inoculated, and the uninoculated chicks on the various feeding regimens Rank
Regimen 0.003% glycarbylamide 0.06% Trithiadol 0.0125% nicarbazin Unmedicated (A) (B) (C)
A B C D (D)*
* The results of the tests of significance are presented so that any two groups (designated by the letters A, B, etc.) not appearing in the same parentheses differ significantly.
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No. started
Mortality (percent)
Regimen
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D. K. MCLOUGHLIN, J. L. GARDINER AND D. K.
Each experiment in this series consisted of 10 groups with 16 to 20 birds per group. The 8 glycarbylamide- or nicarbazin-medicated groups were given 0, 1,000, 5,000, 25,000, 50,000, 100,000, 200,000, or 40,000 sporulated E. tenella oocysts, and the IUC groups were given 200,000 oocysts per bird. In addition, there was also an UUC group for each experiment in the series. A total of 775 birds were used in the four tests with glycarbylamide. The birds in two of these experiments were straight run, mixed breed, and in the others were leghorn-type cockerels. One hundred and eighty-six of the latter type were used in the single experiment involving nicarbazin. Mortality ranged from 0 to 30 percent in the IUC groups of the glycarbylamide series and was 25 percent for this group in the nicarbazin experiment. In neither case did a predictable pattern of weight gain emerge. With both drugs, certain of the groups which received the weaker inocula outgained both the UUC and the UMC, as well as the groups that received the greater numbers of oocysts. In the glycarbylamide series, susceptibility of the chickens to the infection—as indicated by morbidity and mortality in the inoculated, unmedicated controls—had no perceivable effect upon the rate of weight gain exhibited by the various principal groups. This was true regardless of the strength of the inoculum. DISCUSSION Glycarbylamide, Trithiadol, and nicarbazin all afforded protection against the effects of cecal coccidiosis in one-week-old chicks. This agrees with the preliminary findings of McLoughlin and Chester (1959) on the efficacy of these drugs against E. tenella in somewhat older birds. In the present study, only nicarbazin gave complete protection against mortality and morbidity. The death rate from cecal coccidi-
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feeding regimen are considered simultaneously, it can be seen from Table 3 that the groups receiving glycarbylamide had significantly better weight gains, followed by Trithiadol-medicated,nicarbazin-medicated, and unmedicated control groups, in that order. Feed conversion data obtained from such short term experiments, with the additional stress factors of the experimental conditions, are of little significance. However, it is interesting to note that the glycarbylamide-medicated groups had the most efficient feed conversion among the inoculated, medicated groups, as well as for the uninoculated, medicated groups. In 3 of 4 replicates in which glycarbylamide was used and in 2 of 4 in which nicarbazin was employed, the inoculated, medicated groups made better weight gains than did the UUC groups. Furthermore, in 3 of 4 replicates involving glycarbylamide and in all 4 in which nicarbazin was used, the inoculated, medicated groups exhibited better weight gains than did their respective UMC groups. The ratio of the weight gain of the inoculated, medicated group to that of its UMC was greatest when the degree of infection was greatest and least when the infection was lease severe. The severity of the infection in any replicate was judged by the morbidity and mortality exhibited by the IUC for that particular replicate. Although this finding was not substantiated in the other replicates that had intermediate degrees of infection, the results suggested that with respect to nicarbazinand glycarbylamide-medicated birds, the intensity of the infection might influence weight gains in the direction opposite from that expected. For this reason the following experiments, using graded dosages of oocysts, were conducted. B. The effects of graded doses of E. tenella oocysts on chicks fed mash medicated with glycarbylamide or nicarbazin.
CHESTER
ACTIVITY OF COCCIDIOSTATS
In some instances the interesting phenomenon of inoculated, medicated birds showing better weight gains than uninoculated, medicated birds has been observed occasionally in several experiments conducted in this laboratory since the ones herein reported. Edgar (1958), working with birds from 3 days to 16 or more weeks of age, and with a number of coccidiostats
and several species of coccidia, reported that: "In general, particularly when it was demonstrated that coccidiosis had been present between the 4th and 8th week, regardless of coccidiostatic drug, coccidiainoculated pens made slightly higher gains with slightly lower feed conversions than respective non-inoculated pens." Neither Edgar's observations nor those reported here offer any explanation for this phenomenon. From the data in the present report it is apparent that, under the experimental conditions involved, neither the size of the inoculation nor the degree of the resultant infection play a significant role in influencing the rate of gain of birds exposed to E. tenella in the presence of an effective coccidiostat. SUMMARY AND CONCLUSIONS 1. The data presented indicate that glycarbylamide, Trithiadol, and nicarbazin are all effective as prophylactics for cecal coccidiosis of chickens. 2. Under the experimental conditions of this study, nicarbazin was the most efficacious in controlling morbidity and mortality associated with coccidiosis caused by Eimeria tenella. 3. Birds fed glycarbylamide made better weight gains and had more efficient feed conversion than did respective groups fed either of the other medicants. 4. In some instances, it was observed that infected, medicated birds made better weight gains than did their respective uninfected, medicated controls. Attempts to demonstrate that this was associated with the severity of the infection were unsuccessful. ACKNOWLEDGMENT The authors are indebted to Dr. R. A. Damon of the Livestock Research Staff, Biometrical Service, Agricultural Research Service, USDA, for the statistical analysis of the data presented.
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osis was less than 2 percent among those birds protected by glycarbylamide, as compared with 19 percent mortality in groups of similar birds fed Trithiadol. Some blood was seen occasionally in the droppings of the inoculated, nicarbazinmedicated groups as well as in those of similar groups medicated with the other drugs. There was no evidence, however, of pathological changes in the ceca of the nicarbazin-medicated groups at necropsy, which indicated a rapid recovery from any infection that might have been present. Only 2 of the 79 glycarbylamide-medicated birds which survived the infection showed any pathological changes in the ceca on postmortem examination. This number compared with 26 of the surviving 65 Trithiadol-medicated chicks and with 29 of the 52 surviving inoculated, unmedicated controls. These findings suggest that, under the conditions of these experiments, nicarbazin and glycarbylamide almost completely prevent cecal pathology caused by E. tenella. It has been reported by Edgar (1958), and others, that the occasional failure of nicarbazin-medicated birds raised under field conditions to develop immunity to E. tenella is due to the nearly complete suppression of development of the coccidian in the presence of this drug. However, McLoughlin et al. (1957, 1958) have shown that under laboratory conditions, if the initial inoculation is severe enough to induce the development of resistance in unmedicated birds, a comparable degree of resistance also develops in chickens fed nicarbazin.
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D. K. MCLOUGHLIN, J. L. GARDINER AND D. K. CHESTER Helm. Soc. Washington, 17: 25-26. McLoughlin, D. K., and D. K. Chester, 1959. The comparative efficacy of six anticoccidial compounds. Poultry Sci. 38: 353-355. McLoughlin, D. K., R. Rubin and D. R. Cordray, 1957. The development of immunity to cecal coccidiosis in the presence of nicarbazin: Preliminary report. Poultry Sci. 36: 1003-1005. McLoughlin, D. K., R. Rubin and D. R. Cordray, 1958. Further studies on the development of immunity to cecal coccidiosis in the presence of nicarbazin. Poultry Sci. 37: 813-816.
The Effect of Elevated Ambient Temperatures on the Thyroxine Secretion Rate of Chickens 1 R. W. HENINGER, W. S. NEWCOMER AND ROLLIN H. THAYER Departments of Physiology and Pharmacology and Poultry Science, Oklahoma State University, Stillwater (Received for publication January 11, 1960)
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XPERIMENTAL data indicate that the thyroids of both birds (Hoffman and Shaffner, 1950) and mammals (Dempsey and Astwood, 1943) respond to a cold environment with an increase in the rate at which thyroxine is secreted. Ample evidence is also available on the effect of high ambient temperatures on thyroxine secretion rate in mammals (Pipes and Turner, 1946), however comparable data on birds are not available. Since the normal body temperature of birds is higher (7-9°F. for the chicken) than that of mammals, and since birds have no sweat glands to aid in heat dissipation, it is of interest to estimate thyroxine secretion rate as an indication of thyroid function of birds under "high" environmental temperatures. Basic information of this nature is important as a foundation for an attempt to regulate the 1
Published with the approval of the Director of the Oklahoma Agricultural Experiment Station. Portion of a thesis presented by the senior author in partial fulfillment of the requirements for the Master's degree.
adverse effects of high ambient temperatures during the summer months in southern parts of the country. MATERIALS AND METHODS Two-day old White Rock cockerels were grown for three weeks at environmental temperatures of 75, 95 and 105°F. Immediately following this growth period, the cockerels were subjected to a 10-day assay period in which the thyroid secretion rate was determined under the same environmental conditions as for the growth period. On arrival in the laboratory, each chick was weighed, banded and placed at random into one of four lots. There were between 25 and 28 chicks in each of the four lots. The chicks were housed in conventional batteries during the entire growing period. A forced-draft incubator with a floor space of 270 square feet and a volume of 1,770 cubic feet was used as an animal chamber to maintain the temperature and relative humidity at constant levels. Arrangement of the batteries within the incubator was such that all lots received approximately
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REFERENCES Duncan, D. B., 1955. Multiple range and multiple F tests. Biometrics, 11: 1-42. Edgar, S. A., 1958. Control of coccidiosis in chickens and turkeys by immunization. Proc. Assoc. Southern Agric. Workers, 55th Ann. Convention: 203-204. Gardiner, J. L., M. M. Farr and E. E. Wehr, 1952. The coccidiostatic action of nitrophenide on Eitneria tenella. J. Parasit. 38: 517-524. Gardiner, J. L., and E. E. Wehr, 1950. Selecting experimental groups of chicks by weight. Proc.