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The Efficacy of Recently Developed Sulfonamides Against Fowl Typhoid*
POULTRY S C I E N C E July, 1946, Vol. XXV, No. 4
EARL N.
MOORE
University of Delaware, Newark, Delaware (Received for publication January 21, 1946)
T
HE application of sulfonamide therapy to poultry practice appears to offer a significant advancement in the control of certain poultry diseases. Most of the work with these drugs, as therapeutic agents in connection with poultry diseases have been tested on a small scale and therefore must still be considered in the experimental stages of development. However, the antibacterial action of these drugs against closely related organisms affecting other species indicates that beneficial action may be expected. Fortunately, sulfonamides differ in the " rate and amount of absorption from the intestinal tract. Thus high concentrations can be obtained in the gastro-intestinal tract as well as in the blood stream by the use of different sulfa-drugs. The phenomenal success of certain sulfa-drugs in combating systemic and enteric infections among the armed forces is common knowledge. It is not surprising that these sulfa* Published as Miscellaneous Paper No. 6 with the approval of the Director of the Delaware Agricultural Experiment Station. Contribution of the Department of Animal and Poultry Industry, January 10,1946.
drugs are also giving encouraging results against poultry diseases whether the habitat of the causative organisms are in the intestinal tract or of a septicemic nature. Fowl typhoid is a septicemic disease but the common portal of entry of the organism is thought to be through the intestinal tract. LITERATURE REVIEW An extensive literature review is thought to be unnecessary, yet it may be of interest to report some of the experiments dealing with the value of sulfonamide therapy against certain poultry diseases. Delaplane and Stuart (1941) reported on the value of sulfathiazole as a specific against fowl coryza caused by Hemophilus gallinarum. Since then it has been successfully used in the field, particularly against acute cases of the disease. In 1942 Horton-Smith and Taylor (1942) showed that 2 percent of sulphamethazine in the feed prevented symptoms of coccidiosis when administered 96 hours after birds had been infected with Eimeria tenella. In 1943 these authors concluded that a saturated solution of sulfamethazine substituted for drinking
307
Downloaded from http://ps.oxfordjournals.org/ at University of California, San Diego on June 7, 2015
T h e Efficacy of Recently Developed Sulfonamides Against Fowl Typhoid*
308
EARL N. MOORE
water, had a curative effect upon coccidiosis even after showing clinical symptoms. Swales (1944) confirmed the findings of these authors with regards to the inhibit-
coccidiosis. Most favorable results were obtained from the use of sulfaguanidine as a prophylactic. This drug is now being used extensively in the field even though
TABLE 1.—Tests comparing the ckemotherapeutic value of 5 sulfonamides against S. gallinarum infection, with the introduction of several variables Date
No. chicks
Age
Quantity inoculum
Inoculation method
Treatment
C4
5/17
6
5 wks.
2 cc.
Intraperit.
P2 C3
5/17 5/17
9 6
4 wks. 5 wks.
2 cc. 2 cc.
Intraperit. Intraperit.
PI
5/17
6
3 wks.
2 cc.
Intraperit.
P3
5/22
10
4 wks.
2 cc.
Intraperit.
P4
5/23
6
4 wks.
2cc.
Intraperit.
PS
5/23
6
4 wks.
2cc.
Intraperit.
P6 P7
5/23 5/17
7 6
5 wks. 3 wks.
2cc. 2 cc.
Rectally Intraperit.
C5
5/22
6
8 wks.
5 cc.
Rectally
C6
5/22
6
8 wks.
5 cc.
Rectally
C2
5/17
15 wks.
5 cc.
P8
5/23
6 6
3 wks.
5 cc.
f3 Rectally \3 Intraperit. Rectally
El
5/7
6
4 mos.
2 cc.
Intraperit.
E2
5/7
6
4 mos.
2 cc.
Intraperit.
E3 E4 CI CIA C7
5/7 5/7 5/17 5/17 5/22
3 3 1 1 28
4 mos. 4 mos. 15 wks. 15 wks. 1 wk.
2 cc. unexposed 5 cc. unexposed unexposed
Intraperit.
1.0 percent Sulfathalidine None 0.5 percent Sulfathalidine 1.0 percent Sulfathalidine 0.5 percent Sulfasuxidine 0.5 percent Sulfasuxidine 1.0 percent Sulfasuxidine None 1.0 percent Sulfamerazine 0.5 percent Sulfamerazine 1.0 percent Sulfamerazine 0.2 percent Sulfonamide #2 0.4 percent Sulfonamide #1 0.2 percent Sulfonamide #1 0.2 percent Sulfonamide #2 None None None None None
Intraperit.
No. deaths deaths 3
50.0
6 5
66.6 83.3
2
33.3
5
50.0
2
33.3
2
33.3
6 1
85.7 16.7
0
0.0
1
16.7
0
0.0
0
0.0
3
50.0
0
0.0
2 0 1 0 0
66.6 00 100.0 0.0 0.0
Lot numbers dated 5/17 were exposed 5 days before treatment. Lot numbers dated 5/7 and 5/22 were exposed same day as treatment. Lot numbers dated 5/23 were exposed one day after treatment.
ing effect of sulphamethazine upon E. tenella and also states that, "In addition to being of value as a prophylactic, it has a definite curative effect upon established infections even when the clinical disease has progressed to the state of intestinal hemorrhage." Levine (1941) has conducted several carefully controlled experiments on the use of different sulfa drugs against avian
it is expensive and often not available to poultrymen. Field results are often encouraging. Dr. Levine has recently expressed his opinion that it is of limited value in a coccidiosis-control program. He stresses the importance of using good sanitation and management practices along with the feeding of an adequate diet. Severens, Roberts and Card (1945) tested seven sulfonamides with respect to
Downloaded from http://ps.oxfordjournals.org/ at University of California, San Diego on June 7, 2015
Lot No.
EFFICACY OF SULFONAMIDES AGAINST FOWL TYPHOID
309
1 We are indebted to Sharp and Dohme for the supplies of sulfonamides used in connection with this work. Sulfonamide compound number 1 (SSI) and number 2 (SS2) contain a mixture of sulfamerazine, sulfathaladine and sodium carbonate.
EXPERIMENTAL RESULTS
The first difficulty encountered in conducting this study on the chemotherapeutic value of certain sulfonamides
Downloaded from http://ps.oxfordjournals.org/ at University of California, San Diego on June 7, 2015
pounds mentioned are water soluble and they are designed to release 2 sulfonamides, one of which is supposed to produce a high concentration in the blood stream and the other is sparingly absorbed from the intestinal tract. Sulfasuxidine and sulfathalidine are not readily absorbed from the intestinal tract. Welch and associates (1943) state that, "Sulfamerazine is more rapidly absorbed than sulfadiazine, produces a high concentration in the blood with a smaller dose than with sulfadiazine, and it is more slowly excreted by the kidney in a form more soluble than sulfadiazine in neutral or acid urine. Studies in chickens indicate that the drug has no greater potentiality for the production of neuropathologic changes than has sulfadiazine." The two sulfonamide compounds used are water soluble and so they were placed in the drinking water in concentrations varying from 0.2 to 0.4 percent. SulfaMATERIALS AND METHODS suxidine, sulfathalidine and sulfamerazine Chicks used in this work were reared were mixed in the. feed by a mechanical and maintained in an isolated room in mixer, designed especially to prepare battery brooders until the time of inocuexperimental diets. Concentrations of 0.5 lation. Inoculated birds were placed in and 1.0 percent of these three sulfonaexhibition coops or battery brooders in a mides were fed. separate experimental room. A 24-hour. Although birds of different ages were broth culture of Salmonella gallinarum of used, it gave us some desired information. proven pathogenicity was used for the The drugs appear to be equally successful inoculum in all cases. Due to the limited against birds of the different ages studied. facilities available it was necessary to use This is fortunate for in the Delmarva birds of different ages as recorded in the table which follows, but it did not appear peninsula the disease seems to have no reto interfere appreciably with the experi- spect for age, since it is found in young chicks as well as in laying flocks. The birds mental results. used in this study were mostly crossbred The drugs used were sulfonamide com- chicks produced at the University Poultry pound number 1, sulfonamide compound Farm and transferred as day old chicks to number 2, sulfasuxidine, sulfathalidine the isolation quarters. and sulfamerazine.1 The first two comtheir ability to reduce mortality from pullorum disease. They stated that "Sulfadiazine and sulfamerazine were found to be the most effective, judged by both mortality and rate of gain of the surviving chicks. Sulfasuxidine, phthalyl-sulfathiazole and sulfanilamide were the least effective of the drugs used, while sulfa thiazole and sulfaguanidine were intermediate in their effect. Sulfamerazine and sulfadiazine also proved effective in preventing mortality, if administered after development of visible symptoms of pullorum disease." They found that there exists a close agreement between the amount of free sulfonamide found in the blood, and the effectiveness of the drug. They also state that, "At 9 months of age, female survivors which had been treated when one day old with sulfadiazine and sulfamerazine gave negative reactions to pullorum agglutination tests.
310
EARL N. MOORE
from fowl typhoid as are the sulfonamide compounds and sulfamerazine. It should be noted before making comparisons between these various drugs that some birds were inoculated on May 17 and others on May 22 and May 23. Treatments for all groups with the exception of E.l, E.2, E.3, and E.4 were started on May 22 and continued for 13 days. Treatments for lots E.l, E.2, E.3, and E.4 were begun on the day of inoculation and continued for 28 days. Although it is impossible to make direct comparisons between the sulfathalidine and sulfasuxidine treated groups, since they were inoculated on different dates, it is apparent that neither of them are as effective in reducing mortality from this disease as the other three sulfa-drugs. Sulfathalidine was of little value in reducing losses from fowl typhoid after the birds had begun to show early symptoms. Sulfamerazine and sulfonamide compound number 2 appear to be of definite value. These findings are in. agreement with those of Severens, Roberts and Card who demonstrated that sulfamerazine (also sulfadiazine) was highly effective in reducing mortality in 3 day old chicks which had been artificially inoculated as day old chicks (with Salmonella pullorum) and were beginning to show symptoms of pullorum disease when the treatment was started. No toxic effect was noted after feeding these 5 sulfa-drugs to chickens in concentrations as high as 1.0 percent for 13 days. The two sulfonamide compounds were given for 4 weeks to the E. groups with no apparent ill effects. Specimens have been saved from the kidneys and other visceral organs for the purpose of making histopathological examination when time permits. Birds surviving this experiment have been placed in an isolated building for
Downloaded from http://ps.oxfordjournals.org/ at University of California, San Diego on June 7, 2015
against fowl typhoid was to obtain a pathogenic culture. In addition, the culture to be of value must maintain its virulency at a fairly uniform level. A total of 6 cultures were used in the preliminary studies before finding a culture of fairly high, uniform virulency. This culture was obtained from Dr. P. R. Edwards of Kentucky and was designated as Ith. 13. Later another culture designated as Mk was isolated by the author from a Delaware flock which had an acute outbreak and it too has proved satisfactory for inoculation purposes. These two cultures were combined and used as a source of inoculum on all experimental birds except for lots E.l, E.2, E.3, and E.4, where only Ith. 13 was used. In the preliminary transmission studies the S. gallinarum organisms were given orally. This mode of transmission did not give as uniform results as when the organisms were injected intra peritoneally or rectally. For this reason, all experimental cultures reported in tljis paper were administered by one or the other of these methods. Intraperitoneal inoculations are preferred to rectal injections due to the possibility of a portion of the inoculum escaping through the vent as the inoculating instrument is withdrawn or in case the bird defecates soon after inoculation. The results of this experiment are given in Table 1. I t will be noted that there are a number of variables introduced with regards to inoculation date, age of chicks, dosage of inoculum, site of injection and dosage of drugs. Due to these variables and the small number of experimental birds used, this study merely serves as a test to demonstrate the relative value of these 5 sulfonamides against fowl typhoid. It is evident that there is a significant difference in the therapeutic value of the drugs. Sulfathalidine and sulfasuxidine are not as effective in preventing losses
EFFICACY OF SULFONAMIDES AGAINST FOWL TYPHOID
311
SUMMARY
Five sulfonamides were tested to determine their value in protecting birds artificially inoculated with S. gallinarum. Sulfamerazine and two sulfonamide compounds (Sharp and Dohme) were found to be highly effective in reducing the mortality which ranged from 0.0 to 16.7 percent, except in lot number E l which received 0.2 percent of sulfonamide number 1 and showed a mortality of 50 percent. Sulfathalidine and sulfasuxidine were less effective. The mortality rate varied from 33.3 percent to 83.3 percent for the latter two sulfa-drJgs. A direct comparison can-
, 1943. Curative effect of sulfamethazine against avian coccidiosis. Vet. Record 55: 109— 110. Levine, P. P., 1941. Chemotherapy in the control of avian coccidiosis. Proc. 45th Ann. Meet. U. S. Livestock Sanitary Assoc., Chicago, 111. Dec. 3-5, 1941: 118-120. Severens, J. M., E. Roberts and L. E. Card. 1945. The effect of sulfonamides in reducing mortality from pullorum disease in the domestic fowl. Poultry Sci. 24: 155-158. Swales, W. E., 1944. On the chemotherapy of cecal coccidiosis of chickens. Canadian Jour. Res. (D) 22: 131-140. Welch, A. D., Paul A. Mattis, Albert R. Latven, Wilbur Mi Benson and Ethol H. Shiels, 1943. A comparison of sulfamerazine with sulfadiazine on the basis of absorption, excretion and toxicity. Jour, of Pharmacol, and Exp. Therapeut. 77: 357-391.
Downloaded from http://ps.oxfordjournals.org/ at University of California, San Diego on June 7, 2015
further observation. At the time they not be made between these two drugs in were moved from the experimental room this experiment since the sulfathalidine an agglutination test was made on 16 was given 5 days after exposure, while the birds. Included were the 6 birds in C2 sulfasuxidine was given at the time of inwhich received 0.2 percent sulfonamide oculation or one day before. number 2, 3 survivors in C4 receiving 1.0 Due to the variables introduced in this percent sulfathalidine, the lone survivor experiment and the small number of exof C3 which received 0.5 percent sulfa- perimental birds used, this study merely thaladine and the 6 birds in C5 which re- serves to demonstrate the relative efceived 0.5 percent sulfamerazine. All ficiency which might be expected from birds gave a complete reaction to the tube the 5 sulfa-drugs used. Further research agglutination test with the exception of will be conducted to determine the true the birds in C5 which received 0.5 percent value of the more promising drugs under sulfamerazine. They were either negative field conditions. or gave mild reactions. The birds in this REFERENCES cage were inoculated 5 days later than Delaplane, J. P., and H. O. Stuart, 1941. The chemothe other groups which probably accounts therapeutic value of sulfathiazole in preventing for this difference in reaction. The entire and treating infectious coryza (Hemophilus galgroup of survivors will be blood tested at linarum infection) in chickens. Jour. Am. Vet. intervals in the future to determine Med. Assoc. 99:41-43. whether they lose their reaction to the Horton-Smith, C , and E. L. Taylor, 1942. Chemotherapeutic value of sulfamethazine against avian agglutination test following the use of the coccidiosis. Vet. Record. 54: 516. five sulfa-drugs.
EARL N.
MOORE
University of Delaware, Newark, Delaware (Received for publication January 21, 1946)
T
HE application of sulfonamide therapy to poultry practice appears to offer a significant advancement in the control of certain poultry diseases. Most of the work with these drugs, as therapeutic agents in connection with poultry diseases have been tested on a small scale and therefore must still be considered in the experimental stages of development. However, the antibacterial action of these drugs against closely related organisms affecting other species indicates that beneficial action may be expected. Fortunately, sulfonamides differ in the " rate and amount of absorption from the intestinal tract. Thus high concentrations can be obtained in the gastro-intestinal tract as well as in the blood stream by the use of different sulfa-drugs. The phenomenal success of certain sulfa-drugs in combating systemic and enteric infections among the armed forces is common knowledge. It is not surprising that these sulfa* Published as Miscellaneous Paper No. 6 with the approval of the Director of the Delaware Agricultural Experiment Station. Contribution of the Department of Animal and Poultry Industry, January 10,1946.
drugs are also giving encouraging results against poultry diseases whether the habitat of the causative organisms are in the intestinal tract or of a septicemic nature. Fowl typhoid is a septicemic disease but the common portal of entry of the organism is thought to be through the intestinal tract. LITERATURE REVIEW An extensive literature review is thought to be unnecessary, yet it may be of interest to report some of the experiments dealing with the value of sulfonamide therapy against certain poultry diseases. Delaplane and Stuart (1941) reported on the value of sulfathiazole as a specific against fowl coryza caused by Hemophilus gallinarum. Since then it has been successfully used in the field, particularly against acute cases of the disease. In 1942 Horton-Smith and Taylor (1942) showed that 2 percent of sulphamethazine in the feed prevented symptoms of coccidiosis when administered 96 hours after birds had been infected with Eimeria tenella. In 1943 these authors concluded that a saturated solution of sulfamethazine substituted for drinking
307
Downloaded from http://ps.oxfordjournals.org/ at University of California, San Diego on June 7, 2015
T h e Efficacy of Recently Developed Sulfonamides Against Fowl Typhoid*
308
EARL N. MOORE
water, had a curative effect upon coccidiosis even after showing clinical symptoms. Swales (1944) confirmed the findings of these authors with regards to the inhibit-
coccidiosis. Most favorable results were obtained from the use of sulfaguanidine as a prophylactic. This drug is now being used extensively in the field even though
TABLE 1.—Tests comparing the ckemotherapeutic value of 5 sulfonamides against S. gallinarum infection, with the introduction of several variables Date
No. chicks
Age
Quantity inoculum
Inoculation method
Treatment
C4
5/17
6
5 wks.
2 cc.
Intraperit.
P2 C3
5/17 5/17
9 6
4 wks. 5 wks.
2 cc. 2 cc.
Intraperit. Intraperit.
PI
5/17
6
3 wks.
2 cc.
Intraperit.
P3
5/22
10
4 wks.
2 cc.
Intraperit.
P4
5/23
6
4 wks.
2cc.
Intraperit.
PS
5/23
6
4 wks.
2cc.
Intraperit.
P6 P7
5/23 5/17
7 6
5 wks. 3 wks.
2cc. 2 cc.
Rectally Intraperit.
C5
5/22
6
8 wks.
5 cc.
Rectally
C6
5/22
6
8 wks.
5 cc.
Rectally
C2
5/17
15 wks.
5 cc.
P8
5/23
6 6
3 wks.
5 cc.
f3 Rectally \3 Intraperit. Rectally
El
5/7
6
4 mos.
2 cc.
Intraperit.
E2
5/7
6
4 mos.
2 cc.
Intraperit.
E3 E4 CI CIA C7
5/7 5/7 5/17 5/17 5/22
3 3 1 1 28
4 mos. 4 mos. 15 wks. 15 wks. 1 wk.
2 cc. unexposed 5 cc. unexposed unexposed
Intraperit.
1.0 percent Sulfathalidine None 0.5 percent Sulfathalidine 1.0 percent Sulfathalidine 0.5 percent Sulfasuxidine 0.5 percent Sulfasuxidine 1.0 percent Sulfasuxidine None 1.0 percent Sulfamerazine 0.5 percent Sulfamerazine 1.0 percent Sulfamerazine 0.2 percent Sulfonamide #2 0.4 percent Sulfonamide #1 0.2 percent Sulfonamide #1 0.2 percent Sulfonamide #2 None None None None None
Intraperit.
No. deaths deaths 3
50.0
6 5
66.6 83.3
2
33.3
5
50.0
2
33.3
2
33.3
6 1
85.7 16.7
0
0.0
1
16.7
0
0.0
0
0.0
3
50.0
0
0.0
2 0 1 0 0
66.6 00 100.0 0.0 0.0
Lot numbers dated 5/17 were exposed 5 days before treatment. Lot numbers dated 5/7 and 5/22 were exposed same day as treatment. Lot numbers dated 5/23 were exposed one day after treatment.
ing effect of sulphamethazine upon E. tenella and also states that, "In addition to being of value as a prophylactic, it has a definite curative effect upon established infections even when the clinical disease has progressed to the state of intestinal hemorrhage." Levine (1941) has conducted several carefully controlled experiments on the use of different sulfa drugs against avian
it is expensive and often not available to poultrymen. Field results are often encouraging. Dr. Levine has recently expressed his opinion that it is of limited value in a coccidiosis-control program. He stresses the importance of using good sanitation and management practices along with the feeding of an adequate diet. Severens, Roberts and Card (1945) tested seven sulfonamides with respect to
Downloaded from http://ps.oxfordjournals.org/ at University of California, San Diego on June 7, 2015
Lot No.
EFFICACY OF SULFONAMIDES AGAINST FOWL TYPHOID
309
1 We are indebted to Sharp and Dohme for the supplies of sulfonamides used in connection with this work. Sulfonamide compound number 1 (SSI) and number 2 (SS2) contain a mixture of sulfamerazine, sulfathaladine and sodium carbonate.
EXPERIMENTAL RESULTS
The first difficulty encountered in conducting this study on the chemotherapeutic value of certain sulfonamides
Downloaded from http://ps.oxfordjournals.org/ at University of California, San Diego on June 7, 2015
pounds mentioned are water soluble and they are designed to release 2 sulfonamides, one of which is supposed to produce a high concentration in the blood stream and the other is sparingly absorbed from the intestinal tract. Sulfasuxidine and sulfathalidine are not readily absorbed from the intestinal tract. Welch and associates (1943) state that, "Sulfamerazine is more rapidly absorbed than sulfadiazine, produces a high concentration in the blood with a smaller dose than with sulfadiazine, and it is more slowly excreted by the kidney in a form more soluble than sulfadiazine in neutral or acid urine. Studies in chickens indicate that the drug has no greater potentiality for the production of neuropathologic changes than has sulfadiazine." The two sulfonamide compounds used are water soluble and so they were placed in the drinking water in concentrations varying from 0.2 to 0.4 percent. SulfaMATERIALS AND METHODS suxidine, sulfathalidine and sulfamerazine Chicks used in this work were reared were mixed in the. feed by a mechanical and maintained in an isolated room in mixer, designed especially to prepare battery brooders until the time of inocuexperimental diets. Concentrations of 0.5 lation. Inoculated birds were placed in and 1.0 percent of these three sulfonaexhibition coops or battery brooders in a mides were fed. separate experimental room. A 24-hour. Although birds of different ages were broth culture of Salmonella gallinarum of used, it gave us some desired information. proven pathogenicity was used for the The drugs appear to be equally successful inoculum in all cases. Due to the limited against birds of the different ages studied. facilities available it was necessary to use This is fortunate for in the Delmarva birds of different ages as recorded in the table which follows, but it did not appear peninsula the disease seems to have no reto interfere appreciably with the experi- spect for age, since it is found in young chicks as well as in laying flocks. The birds mental results. used in this study were mostly crossbred The drugs used were sulfonamide com- chicks produced at the University Poultry pound number 1, sulfonamide compound Farm and transferred as day old chicks to number 2, sulfasuxidine, sulfathalidine the isolation quarters. and sulfamerazine.1 The first two comtheir ability to reduce mortality from pullorum disease. They stated that "Sulfadiazine and sulfamerazine were found to be the most effective, judged by both mortality and rate of gain of the surviving chicks. Sulfasuxidine, phthalyl-sulfathiazole and sulfanilamide were the least effective of the drugs used, while sulfa thiazole and sulfaguanidine were intermediate in their effect. Sulfamerazine and sulfadiazine also proved effective in preventing mortality, if administered after development of visible symptoms of pullorum disease." They found that there exists a close agreement between the amount of free sulfonamide found in the blood, and the effectiveness of the drug. They also state that, "At 9 months of age, female survivors which had been treated when one day old with sulfadiazine and sulfamerazine gave negative reactions to pullorum agglutination tests.
310
EARL N. MOORE
from fowl typhoid as are the sulfonamide compounds and sulfamerazine. It should be noted before making comparisons between these various drugs that some birds were inoculated on May 17 and others on May 22 and May 23. Treatments for all groups with the exception of E.l, E.2, E.3, and E.4 were started on May 22 and continued for 13 days. Treatments for lots E.l, E.2, E.3, and E.4 were begun on the day of inoculation and continued for 28 days. Although it is impossible to make direct comparisons between the sulfathalidine and sulfasuxidine treated groups, since they were inoculated on different dates, it is apparent that neither of them are as effective in reducing mortality from this disease as the other three sulfa-drugs. Sulfathalidine was of little value in reducing losses from fowl typhoid after the birds had begun to show early symptoms. Sulfamerazine and sulfonamide compound number 2 appear to be of definite value. These findings are in. agreement with those of Severens, Roberts and Card who demonstrated that sulfamerazine (also sulfadiazine) was highly effective in reducing mortality in 3 day old chicks which had been artificially inoculated as day old chicks (with Salmonella pullorum) and were beginning to show symptoms of pullorum disease when the treatment was started. No toxic effect was noted after feeding these 5 sulfa-drugs to chickens in concentrations as high as 1.0 percent for 13 days. The two sulfonamide compounds were given for 4 weeks to the E. groups with no apparent ill effects. Specimens have been saved from the kidneys and other visceral organs for the purpose of making histopathological examination when time permits. Birds surviving this experiment have been placed in an isolated building for
Downloaded from http://ps.oxfordjournals.org/ at University of California, San Diego on June 7, 2015
against fowl typhoid was to obtain a pathogenic culture. In addition, the culture to be of value must maintain its virulency at a fairly uniform level. A total of 6 cultures were used in the preliminary studies before finding a culture of fairly high, uniform virulency. This culture was obtained from Dr. P. R. Edwards of Kentucky and was designated as Ith. 13. Later another culture designated as Mk was isolated by the author from a Delaware flock which had an acute outbreak and it too has proved satisfactory for inoculation purposes. These two cultures were combined and used as a source of inoculum on all experimental birds except for lots E.l, E.2, E.3, and E.4, where only Ith. 13 was used. In the preliminary transmission studies the S. gallinarum organisms were given orally. This mode of transmission did not give as uniform results as when the organisms were injected intra peritoneally or rectally. For this reason, all experimental cultures reported in tljis paper were administered by one or the other of these methods. Intraperitoneal inoculations are preferred to rectal injections due to the possibility of a portion of the inoculum escaping through the vent as the inoculating instrument is withdrawn or in case the bird defecates soon after inoculation. The results of this experiment are given in Table 1. I t will be noted that there are a number of variables introduced with regards to inoculation date, age of chicks, dosage of inoculum, site of injection and dosage of drugs. Due to these variables and the small number of experimental birds used, this study merely serves as a test to demonstrate the relative value of these 5 sulfonamides against fowl typhoid. It is evident that there is a significant difference in the therapeutic value of the drugs. Sulfathalidine and sulfasuxidine are not as effective in preventing losses
EFFICACY OF SULFONAMIDES AGAINST FOWL TYPHOID
311
SUMMARY
Five sulfonamides were tested to determine their value in protecting birds artificially inoculated with S. gallinarum. Sulfamerazine and two sulfonamide compounds (Sharp and Dohme) were found to be highly effective in reducing the mortality which ranged from 0.0 to 16.7 percent, except in lot number E l which received 0.2 percent of sulfonamide number 1 and showed a mortality of 50 percent. Sulfathalidine and sulfasuxidine were less effective. The mortality rate varied from 33.3 percent to 83.3 percent for the latter two sulfa-drJgs. A direct comparison can-
, 1943. Curative effect of sulfamethazine against avian coccidiosis. Vet. Record 55: 109— 110. Levine, P. P., 1941. Chemotherapy in the control of avian coccidiosis. Proc. 45th Ann. Meet. U. S. Livestock Sanitary Assoc., Chicago, 111. Dec. 3-5, 1941: 118-120. Severens, J. M., E. Roberts and L. E. Card. 1945. The effect of sulfonamides in reducing mortality from pullorum disease in the domestic fowl. Poultry Sci. 24: 155-158. Swales, W. E., 1944. On the chemotherapy of cecal coccidiosis of chickens. Canadian Jour. Res. (D) 22: 131-140. Welch, A. D., Paul A. Mattis, Albert R. Latven, Wilbur Mi Benson and Ethol H. Shiels, 1943. A comparison of sulfamerazine with sulfadiazine on the basis of absorption, excretion and toxicity. Jour, of Pharmacol, and Exp. Therapeut. 77: 357-391.
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further observation. At the time they not be made between these two drugs in were moved from the experimental room this experiment since the sulfathalidine an agglutination test was made on 16 was given 5 days after exposure, while the birds. Included were the 6 birds in C2 sulfasuxidine was given at the time of inwhich received 0.2 percent sulfonamide oculation or one day before. number 2, 3 survivors in C4 receiving 1.0 Due to the variables introduced in this percent sulfathalidine, the lone survivor experiment and the small number of exof C3 which received 0.5 percent sulfa- perimental birds used, this study merely thaladine and the 6 birds in C5 which re- serves to demonstrate the relative efceived 0.5 percent sulfamerazine. All ficiency which might be expected from birds gave a complete reaction to the tube the 5 sulfa-drugs used. Further research agglutination test with the exception of will be conducted to determine the true the birds in C5 which received 0.5 percent value of the more promising drugs under sulfamerazine. They were either negative field conditions. or gave mild reactions. The birds in this REFERENCES cage were inoculated 5 days later than Delaplane, J. P., and H. O. Stuart, 1941. The chemothe other groups which probably accounts therapeutic value of sulfathiazole in preventing for this difference in reaction. The entire and treating infectious coryza (Hemophilus galgroup of survivors will be blood tested at linarum infection) in chickens. Jour. Am. Vet. intervals in the future to determine Med. Assoc. 99:41-43. whether they lose their reaction to the Horton-Smith, C , and E. L. Taylor, 1942. Chemotherapeutic value of sulfamethazine against avian agglutination test following the use of the coccidiosis. Vet. Record. 54: 516. five sulfa-drugs.