Control of Infectious Synovitis 4. ANTIBIOTICS AND NITROFURANS 1 D. C. SHELTON, N. O. OLSON AND C. E. WEAKLEY, JR. Departments of Agricultural Biochemisty and Nutriton and Animal Husbandry, West Virginia Agricultural Experiment Station, Morgantown (Received for publication October 24, 1957)
I
EXPERIMENTAL
four grams of procaine penicillin and 90 grams of arsanilic acid per ton was added the crystalline forms of chlortetracycline hydrochloride, oxytetracycline hydrochloride, tetracycline hydrochloride, chloramphenicol, furazolidone (nf-180), furadantin (nf-153) or magnamycin. Except for magnamycin which was given at only 200 grams per ton, all other drugs were fed at 100, 200 or 300 grams per ton and started when the chicks were day old. Three control treatments were maintained as follows: (1) non-infected, (2) non-infected but injected with 0.25 ml. of yolk material taken from normal nine-day old embryos and diluted 50 percent with nutrient broth and (3) infected. The chicks were experimentally infected via the foot pad when 17 days old by injecting 0.25 ml. of a virulent chicken embryo grown culture of infectious synoTABLE 1.—A description and numerical classification of the characteristic swellings resulting from injection of the infectious synovitis agent into the foot pad of chicks
Twelve unsexed New Hampshire chicks were randomly selected, wingbanded and placed on each treatment. The basal ration was the ANRC standard chick and broiler diet suggested by Briggs et al. (1954). To this ration which contained 1
Published with the approval of the Director of the West Virginia Agricultural Experiment Station as Scientific Paper No. 562. Support provided in part by funds allocated to regional project NE-5 and by funds provided by Farm and Home Division, American Cyanamid Company, Pearl River, New York, and Chas. Pfizer and Co., Inc., Terre Haute, Indiana.
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Description of inoculated leg 0 1 2 3 4 5 6 7 8 9
Normal (no swellings) Slight swelling in the foot pad Slight swelling in the foot pad and shank Slight swelling in the foot pad, shank and hock Swelling in the foot pad Swelling in the foot pad and shank Swelling in the foot pad, shank and hock Marked swelling in the foot pad Marked swelling in the foot pad and shank Marked swelling in the foot pad, shank and hock
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N THE reports of Olson et al. (1957a) and Shelton et al. (1957) on the control of infectious synovitis, chlortetracycline and oxytetracycline were effective but erythromycin, penicillin and strepomycin were ineffective when fed continuously. These studies further indicated that a higher concentration of oxytetracycline than chlortetracycline was necessary in the feed for equivalent control. In the in ova studies conducted by Cover et al. (1956) using agents causing infectious synovitis, a difference in efficacy of these antibiotics was not reported. Studies by Peterson et al. (1955-56) gave no indication of a difference in efficacy of these antibiotics under their conditions. In view of these inconsistent reports, additional studies were conducte'd to critically evaluate the tetracycline antibiotics and other antibacterial drugs as to their efficacy in controlling infectious synovitis in laboratory birds.
611
CONTROL OF INFECTIOUS SYNOVITIS
mitted comparisons among treatments and thus was valuable in assessing the severity of the disease according to treatment. RESULTS AND DISCUSSION
Summarized results are presented in Table 2 and Figure 1. The number of infected birds, degree of swelling, number of birds in which the infection spread to joints other than those in the inoculated leg, mortality, weight gain and feed conversion ratio are given for the control and medicated chicks. Results in Figure 1
TABLE 2.—The effect of different levels of antibiotics and nitrofurans on the degree of infection, weight gain and feed conversion in birds experimentally infected with infectious synovitis Infection2 Treatment 1 Controls Non-infected Control yolk 3 Infected Chlortetracycline 100 200 300 Oxytetracycline 100 200 300 Tetracycline 100 200 300 Furazolidone (nf-180) 100 200 300 Furadantin (nf-153) 100 200 300 Chloramphenicol 100 200 300 Mdgftdtuyctn
200 1
Number"
Degree
b
Weight Extension
0
Deaths (gm)
Feed conversion
0 0 12
0 0 11
617 546 -17
2.11 2.22
0 0 0
0 0 0
0 0 0
598 557 568
2.20 2.21 2.32
12 11 4
8.75 4.67 2.17
6 0 0
0 0 0
396 523 552
2.60 2.38 2.35
12 11 12
8.75 7.50 7.83
10 3 1
4 0 0
184 460 494
3.97 2.57 2.52
12 11 4
8.16 6.83 2.64
5 3 2
2 2 1
259 408 481
3.21 2.66 2.37
12 12 12
8.67 8.75 8.92
10 12 10
10 7 6
67 25 141
8.19 16.93 4.26
12 12 12
8.83 8.83 9.00
8 10 12
7 7 10
141 97 30
4.12 5.58 12.58
12
9.00
6
5
224
3.51
0 0 12 0 0 0
0 0 9.00
•—
Level of treatment expressed as grams per ton feed. Twelve chicks per treatment. Severity of infection shown by the following: (a) Number of birds developing disease. (b) Degree—based on a scoring system of 0 to 9 and applies only to leg of inoculation. (c) Extension—number of birds where infection has extended to joints other than those in the inoculated leg. 3 Yolk material taken from nine-day old normal embryos.
2
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vitis agent 29M (Olson el al, 1956). All birds were individually examined and weighed twice weekly during the experimental period which extended for 28 days after inoculation. All birds were necopsied. In studies conducted previously the development of swellings in foot pad inoculated birds occurred in a definite pattern. Therefore, numerical values were assigned to the swellings of the inoculated leg according to the description of the swelling as listed in Table 1. Evaluation of the swellings in this manner per-
612
D. C. SHELTON, N. 0. OLSON AND C. E. WEAKLEY, J R .
INFECTED
NON-INFECTED CONTROLS 4
MORTALITY- 0
0 0
I
,
7 10 .
12
1 2 .
.
•
12
12
12
I2\
6
9
9
II
•
4 7 9 II 14 18 21 24 28 DAYS AFTER INOCULATION FIG. 1. The progressive stages of infectious synovitis in infected, non-medicated birds as shown by the degree of swelling, extension to other joints and mortality.
show the progressive stages of the infection as it developed in the infected control birds. By the ninth day the degree of swelling averaged 8.8 and an extended infection was apparent in seven of the 12 birds. By the 14th day extended infections were observed in each of the 12 birds and two birds had died. Mortality continued at a high rate for the remainder of the experimental period during which 11 of the 12 birds died. Tetracycline antibiotics. The chemical structure and the antibacterial spectrum of the tetracycline antibiotics are considered to be very similar. However, in this experiment and against the infectious synovitis agent, oral administration of chlortetracychne had greater therapeutic value than oxytetracycline. Tetracycline had the least therapeutic value of these three antibiotics (Table 2). Examination of all inoculated chicks showed typical but slight swellings present in the foot pads by the fourth day after inoculation. By the ninth day no
At each concentration (100, 200 or 300 grams per ton) of tetracycline in the feed, the infection developed and spread to a greater extent than with chlortetracychne or oxytetracycline. All birds which received the 100 gram level developed the infection and had an average degree of swelling of 8.75. Extended infections occurred in 10 of the 12 birds and four died. The weight gain (184 grams) was substantially lower than the 617, 598 or 396 grams made by the non-infected controls, 100 gram-level of chlortetracychne or the 100 gram-level of oxytetracycline, respectively. Nearly twice as much feed was required to produce a gram of gain as for the non-infected controls. As the concentration of tetracycline increased less spread and no mortality occurred. Weight
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EXTENSION- 0
swellings could be detected in any group of chicks receiving chlortetracychne irrespective of whether the concentration was 100 grams per ton or higher. Weight gains and feed conversions were essentially that of the non-infected controls. With oxytetracycline, concentrations higher than for chlortetracychne were necessary for equivalent efficacy against the synovitis agent. At 100 grams per ton all 12 birds continued to develop the infection and by the end of the experiment the average degree of swelling was 8.75 and in six birds the infection spread to to other joints. Weight gain was retarded and the feed conversion ratio was increased. As the concentration of oxytetracycline increased from 100 to 200 and to 300 grams per ton, the number of birds which developed the infection and the degree of swelling decreased. At the two higher levels the infection was localized in the inoculated leg. No mortality occurred. Weight gains and feed conversions improved as the oxytetracycline concentrations increased.
CONTROL OF INFECTIOUS SYNOVITIS
Furadantin (nf-153), chloramphenical and magnamycin in the feed had essentially no therapeutic value against infectious synovitis (Table 2). These results support previous observations that oral administration of chlortetracycline is more effective than oxytetracycline against infectious synovitis (Olson et al, 1957a; and Shelton et al., 1957). These results suggest that levels lower than 100 grams per ton of chlortetracycline given continuously may prove to give satisfactory protection against infectious synovitis. The results with nf-180 were not in agreement with those of Cosgrove (1957) who reported that 100 grams per ton of nf-180 afforded complete protection and 50 grams gave 80 percent protection in experimentally inoculated birds in which medication was begun seven days prior to the inoculation. The congruity of experimental data reported by Munro et al. (1956), Olson et al. (1957b). Olson and Shelton (1957)
and Thayer et al. (1957) have substantiated the results of this paper relative to nf-180. SUMMARY
Against the infectious synovitis agent, chlortetracycline had greater therapeutic value than oxytetracycline and tetracycline had the least therapeutic value of these three antibiotics when given orally. Furazolidone was less effective than oxytetracycline. Furadantin, chloramphenicol and magnamycin had essentially no therapeutic value. A description and a numerical classification of the characteristic swellings in the inoculated leg resulting from injection of the infectious synovitis agent into the foot pad of chicks are given. ACKNOWLED GMENT
The authors are indebted to the following companies for material gratuitously supplied during the course of this investition: Abbott Laboratories, North Chicago, Illinois for arsanilic acid; Gorton-Pew Fisheries Company, Gloucester, Massachusetts for condensed fish solubles; Harper Feed Mills, Inc., Washington Pennsylvania for dried whey products; Hess and Clark, Inc., Ashland, Ohio for nf-180 and nf-153; Farm and Home Division, American Cyanamid Comapny, Pearl River, New York for chlortetracycline hydrochloride and tetracycline hydrochloride; Limestone Corporation of America, Newton, New Jersey for Delamix, a source of trace minerals; Merck and Co., Inc., Rahway, New Jersey for B-complex vitamins, menadione, and procaine penicillin; Nopco Chemical Company, Harrison, New Jersey for vitamin A (Nopco 10) and vitamin D s (Super Nopdex 15); Parke Davis and Company, Detroit, Michigan for Chloromycetin;
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gains and feed conversions improved, but never attained those made by the noninfected controls or by the birds given comparable levels of chlortetracycline or oxytetracycline. Other antibacterial drugs. The therapeutic value of furazolidone (nf-180) against the infectious synovitis agent was much less than chlortetracycline and slightly less than oxytetracycline. Furazolidone delayed the development and spread of the disease to a limited extent. As the concentration was increased less birds became infected and the development of the infection was reduced. However, once the infection was established, the nf-180 did not appear to be very efficacious. On the other hand, chlortetracycline and oxytetracycline suppressed the development and spread to a greater extent in established cases.
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D. C. SHELTON, N. 0. OLSON AND C. E. WEAKLEY, JR.
Chas. Pfizer & Co., Inc., Terre Haute, Indiana for oxytetracycline hydrochloride and magnamycin; Shea Chemical Corporation, Baltimore, Maryland for dicalcium phosphate. REFERENCES
Studies on Energy Levels in Poultry Rations 3.
EFFECT OF CALORIE-PROTEIN RATIO OF THE RATION ON GROWTH, NUTRIENT UTILIZATION AND BODY COMPOSITION OF POULTS 1 W. E. DONALDSON,2 G. F. COMBS AND G. L. ROMOSER3 Department of Poultry Husbandry, University of Maryland, College Park (Received for publication October 24, 1957)
INTRODUCTION
G
ROWTH rate, feed consumption, body composition and feathering of broiler chickens have been shown to be influenced by the ratio of energy to protein 1 Scientific Article No. A653. Contribution No. 2843 of the Maryland Agricultural Experiment Station (Department of Poultry Husbandry). 2 Present address: Department of Poultry Husbandry, University of Rhode Island, Kingston, Rhode Island. 3 Present address: Monsanto Chemical Company, St. Louis, Missouri.
content of the ration (Baldini and Rosenberg, 1955; Combs and Romoser, 1955; Combs et al., 1955a, b; Donaldson et al., 1955, 1956; Leong et al., 1955; Matterson et al., 1955; Scott et al., 1955; and Sunde, 1956). More recently, similar observations have been made in studies with turkey rations. Lockhart and Thayer (1955) reported that poults grew best when fed a starting ration having a Calorie-protein ratio 4 of 29:1. Ferguson et al. (1956a) in4 Calories of productive energy per pound for each 1% (4.537 gms.) crude protein.
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Briggs, G. M., G. F. Combs, L. Friedman, J. C. Fritz, R. J. Lillie, F. W. Quackenbush and H. W. Titus, 1954. Standard chick and broiler diet. Animal Nutrition Research Council News Letter, Vol. 1: No. 2. Cosgrove, A. S., 1957. Laboratory and field studies with furazolidone in the prevention and treatment of avian infectious synovitis. J. Am. Vet. Med. Assoc. 130: 286-289. Cover, M. S., J. N. Galeta and E. F. Waller, 1956. The etiology of an arthritic disease of chickens. Am. J. Vet. Res. 17: 12-15. Munro, D. A., N. O. Olson and D. C. Shelton, 1956. Synovitis control. 5. Intramuscular streptomycin and a comparison of continuous and intermittent feeding of Aureomycin and furazolidone (nf-180). Poultry Sci. 35: 1161. Olson, N. O., D. C. Shelton, J. K. Bletner, D. A. Munro and G. C. Anderson, 1956. Studies of
infectious synovitis in chickens. Am. J. Vet. Res. 17: 747-754. Olson, N. 0., and D. C. Shelton, 1957. Infectious synovitis control. 8. Degree of infection and medication. Poultry Sci. 36: 1146. Olson, N. O., D. C. Shelton, J. K. Bletner and C. E. Weakley, Jr., 1957a. Infectious synovitis control. 2. A comparison of levels of antibiotics. Am. J. Vet. Res. 18: 200-203. Olson, N. O., D. C. Shelton and D. A. Munro, 1957b. Infectious synovitis control by medication. Effect of strain differences and pleuropneumonialike organisms. Am. J. Vet. Res. 18: 735-739. Peterson, E. H., R. Chalquest and H. G. Luther, 1955-56. Oxytetracycline in the prophylaxis of synovitis in experimentally infected chicks. Antibiotics Annual, 1955-56: 313-318. Medical Encyclopedia, Inc., New York, N. Y. Shelton, D. C , J. K. Bletner, N. O. Olson, G. C. Anderson and C. E. Weakley, Jr., 1957. Control of infectious synovitis. 1. Continuous feeding of antibiotics and the influence of diethylstilbestrol and coccidiostats. Poultry Sci. 36: 113— 121. Thayer, S. C , R. G. Stout and W. R. Dunlop, 1957. Observation of infectious synovitis. Poultry Sci. 36: 1163.