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Histomonastatic Activity of Nifursol in Turkeys
Histomonastatic Activity of Nifursol in Turkeys R. D . V A T N E , R. R. B A R O N AND N . F. M O R E H O U S E Salsbury Laboratories, Charles City, Iowa 50616 (Received for publication September 3, 1968)
A
During our investigation of nitrofuran derivatives, a new compound was discovered which affords excellent protection against blackhead disease at low feed concentrations and which has a high margin of safety in recipient turkeys. This paper reports the investigation of the antihistomonal activity of 3,5-dinitrosalicylic acid, 5-nitrofurfurylidene hydrazide (Berndt el al., 1969) which is hereafter referred to as Nifursol,* its United States Adopted N a m e . EXPERIMENTAL PROCEDURES
Laboralory Experimenls—Single Injection. Nonsexed Broad Breasted Bronze and Broad White turkeys purchased from commercial hatcheries were reared in bat* Active ingredient in the product Salfuride.
teries with wire-mesh floors. All poults received a standard ration prior to and during the experiments. At approximately six weeks of age, poults were transferred to individual cages with wire-mesh floors. At this time poults were grouped according to weights so t h a t all experimental groups were approximately equal. Poults were orally inoculated on the first day of the test with approximately 1,000 embryonated Heterakis gallinarum ova known to harbor Histomonas meleagridis. Experiments were routinely 28 days in duration although poults in some experiments were held for additional periods to ascertain the relapse incidence of histomoniasis. Poults received medicated feed for the first 21 days and nonmedicated feed during the final seven days as well as during any additional holding periods. Bird weights and feed consumption data were recorded weekly in all experiments. Droppings of individual birds were checked for abnormalities caused by histomoniasis from the ninth day postinfection to the end of each experiment. Poults which died during an experiment were examined for cecal and liver lesions of blackhead. Poults surviving at the termination of experiments were also necropsied and the presence or absence of lesions recorded. Outdoor Pen Experiments—Continuous Exposure. Three experiments, each involving 240 day-old Broad Breasted Bronze or Broad White turkeys, were conducted. In each experiment turkeys were divided into six groups of 40 per group and placed in floor pens of a brooder house for the first eight weeks. All groups received a stan-
590
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L T H O U G H activity against black- head disease (histomoniasis) in chickens and turkeys has been proved for several structurally diverse compounds during the past 20 years, this disease remains one of the most costly to turkey producers. Among the most noteworthy types of these compounds are certain arsonic acids, nitrothiazoles, quinolines, imidazoles and nitrofurans. McGregor (1953) reported t h a t furazolidone, when administered at one part in 8,000 parts of feed, had a small degree of prophylactic value. One of six other nitrofurans tested (NF-153) was of slight value when administered from two days prior to infection and continued for 29 days. Furazolidone has not been used extensively by poultrymen, however, because other compounds have provided better efficacy at less cost.
591
HlSTOMONASTATIC ACTIVITY OF NlFURSOL
Poults were rotated between lots twice weekly to help insure a uniform blackhead challenge. Bird weight and feed consumption data were recorded biweekly. Surviving poults and those which died during experiments were examined for cecal and liver lesions of blackhead. RESULTS AND DISCUSSION
Table 1 is a summary of experiments to determine the histomonastatic activity of Nifursol fed to turkeys following their infection with a single oral inoculum of H.
TABLE 1.—Chemoprophylactic efficacy of Nifursol against histomoniasis in turkeys. Poults were infected with a single oral inoculum of approximately 1,000 embryonated Heterakis gallinarum ova
% Feed cone. 0.00063 0.00125 0.0015 0.002 0.0025 0.003 0.004 0.005 0.006 0.0075 0.01 0.015 0.025 0.03 0.04 0.05 0.1 0.2 Infected Controls
No. expts.
Total No. birds
Clinical signs a n d / o r postmortem lesions
%
Blackhead mortality
%
No. birds
Efficacy
No. birds
Efficacy
0 16.7 50 63.8 77.4 86.5 87.9 94.7 100 96.8 99 100 100 100 100 100 100 100
18 10 5 18 5 1 0 0 0 0 0 0 0 0 0 0 0 0
0 44.5 75 70 96.4 98.6 100 100 100 100 100 100 100 100 100 100 100 100
—
312
—
3 3 1 6 14 7 6 29 5 23 11 3 3 3 2 4 1 1
18 18 20 58 137 74 58 283 49 185 100 17 7 18 2 12 4 4
18 15 10 21 31 10 7 15 0 5 1 0 0 0 0 0 0 0
46
312
312
gallinarum ova. Graded Nifursol concentrations ranging from 0.00063 to 0.2% were fed. Concentrations of 0.015% and above provided total blackhead protection as determined by the absence of clinical signs of the disease during experiments and by the absence of lesions on postmortem examination at the termination of experiments. No blackhead mortality occurred in poults receiving concentrations between 0.004 and 0.2%. Only 5 of 185 poults fed a concentration of 0.0075% and 15 of 283 poults fed a concentration of 0.005% demonstrated clinical signs or postmortem lesions. A gradual depletion of activity paralleled the reduction of drug concentration in the feed. The lowest concentration with definite histomonastatic activity was 0.00125% which allowed survival of 4 4 . 5 % of the poults. No activity was demonstrated by the 0.00063% concentration. Overall efficacy provided by the various concentrations is particularly significant because the blackhead challenge given to these poults was uniform and extremely severe.
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dard ration. Three groups in each experiment were fed different concentrations of Nifursol, two groups were fed different concentrations of a commercially available histomonastat, and one group received no medication. All poults were moved to outdoor pens at eight weeks of age where those of Experiment 1 were kept for 24 weeks and those of Experiments 2 and 3 for 16 weeks. T h e six pens, each approximately four by six meters, had been occupied in previous years by blackhead infected turkeys. Soil in these lots was further contaminated by suspension of Heterakis-'miected chickens in wire cages over each lot. Although earthworms were infrequently found in the lots, it is probable that consumption of them by poults provided an additional source of infection. Earthworms collected from soil approximately one foot outside the periphery of the lots were fed to poults in experiments not directly related to this study. A high percentage of the poults died of histomoniasis. These findings would substantiate those reported b y Lund (1966) t h a t earthworms are important vectors in blackhead transmission. A roof covering all lots, prevented direct sunlight from drying the soil surface and, therefore, allowed an environment which favored existence of free histomonads, H. gallinarum ova and earthworms.
592
R. D. VATNE, R. R. BARON AND N. F. MOREHOUSE TABLE 2.—Relapse incidence of histomoniasis in poults following withdrawal of Nifursol from the feed
F ™ w d o i Days held C nC Z :J°cIJ1 after No.
infection 0.003 0.004 0.005 0.005 0.006 0.0075
medication birds withdrawn 35 35 21 35 35 21
Postmortem lesions
%
Blackhead mortality
No. birds Relapse 1 0 1 0 1 0
15 16 19 16 18 15
No. % birds Relapse
6.7 0 5.3 0 5.6 0
1 0 1 0 1 0
6.7 0 5.3 0 5.6 0
TABLE 3.—Effect of Nifursol on growth and feed use of turkeys exposed to histomoniasis by a single oral inoculation of approximately 1,000 Heterakis gallinarum ova Growth % Feed cone. 0.005 Nonmed. Noninf. 0.0075 Nonmed. Noninf. 0.01 Nonmed. Noninf.
No. of groups 11 11 7 7 5 5
Total No. birds 160 160 108 107 88 90
Mean gain (gms.) 1,159 1,160 1,266 1,214 1,330 1,280
Peed
%
Response -0.1
—
4.3
—
3.9
—
Efficiency 2.13 2.07 1.98 2.02 1.91 2.01
%
Response -3.0
—
2.0
—
5.0
—
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Blackhead mortality occurred in all of the 312 infected nonmedicated controls of these experiments. The tendency for histomoniasis relapse to occur in turkeys following withdrawal of medication has been discussed by several investigators (Morehouse and McGuire, 1950; Joyner and Kendall, 1955; Horton-Smith and Long, 1956). Table 2 summarizes the relapse incidence in several experiments following withdrawal of Nifursol from the feed. This medication had been fed for 21 days. In some experiments poults were individually caged following withdrawal of medication and in other experiments they were individually caged for a period and then transferred to a floor pen. Poults demonstrating clinical signs of blackhead were never placed in a floor pen but were kept in individual cages. No relapse occurred in 15 poults held on nonmedicated feed for 35 days after having received medication at a concentration of 0.0075%. Relapse occurred in 1 of 18 poults held 35 days which had re-
ceived medication at 0.006%. One of 19 poults which had received medication at 0.005% relapsed within a 21 day period. A group of poults receiving medication at the same concentration, however, were held for 35 days without any relapse. No relapse occurred in 16 poults held for 35 days after receiving medication at 0.004%. One of 15 poults held for 35 days relapsed after receiving medication at 0.003%. All three poults which relapsed showed clinical signs of blackhead by the 14th day after receiving nonmedicated feed. Overall results indicate that poults held after receiving medication at concentrations of 0.003 and 0.004% are not markedly more susceptible to relapse than poults receiving approximately double these concentrations. Weight gains and feed efficiency data from poults receiving 0.005, 0.0075 and 0.01% feed concentrations of Nifursol are summarized in Table 3. The data of these three dosages are shown because they are the feed concentrations utilized in the outdoor pen experiments described elsewhere in this paper. The mean weight gain of 11 test groups (160 poults) receiving a 0.005% feed concentration of Nifursol was 1,159 gms. while the 11 nonmedicated noninfected groups (160 poults) gained approximately the same amount, 1,160 gms. The average number of gms. of feed utilized per gm. of live weight was 2.13 for the medicated
593
HlSTOMONASTATIC ACTIVITY OF NlFURSOL
TABLE 4.—Chemoprophylactic efficacy of Nifursol against histomoniasis in turkeys. Poults were exposed to soil continuously contaminated with droppings from chickens infected with Heterakis gallinarum Experiment 1 % Drug in feed 0.005 0.0075 0.01 Nonmed.
No. birds 38 37 35 40
Postmortem lesions No. birds 2 1 0 40
Blackhead mortality
% Without No. lesions birds 94.7 97.3 100 0
0 0 0 40
%
Survival 100 100 100 0
TABLE 5.—Chemoprophylactic efficacy of Nifursol against histomoniasis in turkeys. Poults were exposed to soil continuously contaminated with droppings from chickens infected with Heterakis gallinarum Experiment 2
% Drug in feed 0.005 0.0075 0.01 Nonmed.
No. birds 38 38 39 40
Postmortem lesions
Blackhead mortality
N o . % Without No. birds lesions birds 5 4 5 39
86.9 89.5 87.2 2.5
2 0 0 33
%
Survival 94.7 100 100 18.5
1 conducted in the outdoor sheltered pens. The three feed concentrations of Nifursol, 0.005, 0.0075, and 0.01%, afforded 100% protection to poults against blackhead mortality. Only 2 of 38 poults receiving the drug at 0.005% and 1 of 37 poults fed the drug at 0.0075% possessed mild cecal lesions at necropsy. All nonmedicated birds died of histomoniasis. Table 5 summarizes efficacy data obtained with Nifursol in Experiment 2 which was conducted in the outdoor highexposure pens. The 0.0075 and 0.01% drug concentrations in the feed provided 100% protection from blackhead mortal" ity. The 0.005% concentration permitted survival of 94.7% (36 of 38) of the poults. At necropsy, one poult receiving the 0.01% concentration had several small liver lesions and mild cecal lesions. Four others had only mild cecal lesions. Groups receiving the 0.005 and 0.0075% drug concentrations had five and four turkeys, respectively, that possessed mild cecal lesions but no liver lesions. No evidence of blackhead disease was found in the liver or ceca of the other turkeys. Thirty-three of 40 nonmedicated control poults died of blackhead during this experiment and one additional bird exhibiting advanced signs of the disease at termination of the experiment died two days later. Thirty-nine of the control group possessed cecal lesions, and of these, 37 also had developed liver lesions. Table 6 shows results of Experiment 3
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poults and 2.07 for the nonmedicated poults, a difference of 3%. Nifursol fed at a 0.0075% concentration to seven groups totaling 108 poults produced a mean weight gain of 1,266 gms. or 4.3% more than the 1,214 gm. gain of seven groups totaling 107 nonmedicated poults. The average feed efficiency for the medicated and nonmedicated noninfected poults was 1.98 and 2.02, respectively, a difference of 2%. Five groups (88 poults) receiving a 0.01% feed concentration of Nifursol had a mean gain of 1,330 gms. compared to 1,280 gms. for five groups (90 poults) which received no medication, a difference of 3.9%. Feed efficiency for the medicated and nonmedicated noninfected poults was 1.91 and 2.01, respectively, a difference of 5%. Antihistomonal efficacy of Nifursol when administered continuously from dayold to maturity at 0.005, 0.0075, and 0.01% feed concentrations was further studied in outdoor pen experiments where continuous exposure to blackhead was provided. Little, if any exposure to blackhead was available during the first eight weeks while the poults were kept in clean brooder houses but continuous exposure was provided in the outdoor pens from eight weeks of age until the experiments were terminated at 24 weeks as in Experiment 1 or at 16 weeks for Experiments 2 and 3. Table 4 shows the results of Experiment
594
R. D. VATNE, R. R. BARON AND N. F. MOREHOUSE
TABLE 6.—Chemoprophylaclic efficacy of Nifursol against hislomoniasis in turkeys. Poults were exposed to soil continuously contaminated with droppings from chickens infected with Heterakis gallinarum Experiment 3
% Drug in feed
No. birds
Postmortem ]lesions
No. birds
35 37 37 39
0.005 0.0075 0.01 Nonmed.
2 0 0 37
Blackhead mortality
% Without No. lesions birds 94.3 100 100 5.1
%
Survival
0 0 0 36
100 100 100 7.7
TABLE 7.—Effect of Nifursol on growth and feed use of turkeys raised under conditions of high exposure to hislomoniasis in outside pens Experiment 1
%
Feed cone. 0.005 8 Wks. 16 Wks. 24 Wks. 0.0075 8 Wks. 16 Wks. 24 Wks. 0.01 8 Wks. 16 Wks. 24 Wks. Nonmed. 8 Wks. 16 Wks.
Growth No. poults
Mean wt. (gms.)
%
Response
Feed Efficiency
TABLE 8.—Effect of Nifursol on growth and feed use of turkeys raised under conditions of high exposure to histomoniasis in outside \ Experiment Z
%
Response
Feed 40 39 38
2,177 5,262 8,301
1.67 2.63
5.6
39 37 37
2,132 5,534 8,573
1.70 2.57 4.01
4.0
39 36 35
2,087 5,398 8,346
1.67 2.62 4.02
40 0
2,041
—
Feed
Growth
% 0.005 8 Wks. 16 Wks. 0.0075 8 Wks. 16 Wks. 0.01 8 Wks. 16 Wks. Nonmed. 8 Wks. 16 Wks.
No. poults
Mean wt. (gms.)
%
Effi-
%
Response
ciency
Response
1.77 3.06
2.2
1.79 2.99
1.1
1.77 2.93
2.2
40 37
2,540 5,988
3.7
40 38
2,495 5,942
1.9
40 39
2,540 5,897
3.7
40 7
2,449 3,765
— — — — —
1.81 14.97
— — — — —
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conducted in the sheltered lots. Drug concentrations in the feed of 0.005, 0.0075, and 0.01% provided 100% protection from mortality. Postmortem examination of all poults which had received medication revealed that only two birds possessed blackhead lesions. One possessed only liver lesions and one possessed only cecal lesions. Both of these birds had received medication at the 0.005% concentration. As in the laboratory experiments, the Nifursol medicated feed was well tolerated and good growth was obtained for all three dosage levels used in experiments conducted in outside pens. Table 7 shows results from Experiment 1. At eight weeks of age (prior to blackhead exposure) the turkeys receiving the 0.005% feed concentration averaged 2,177 gms., which was 6.7% heavier than the nonmedicated con-
trols; at the 0.0075% concentration the average was 2,132 gms., a difference of 4.4%; and at the 0.01% concentration the average was 2,087 gms. or a difference of 2.2% over the controls. Because high mortality had occurred among the nonmedicated poults at 16 weeks and because there were no survivors of this group at 24 weeks, weight comparisons between medicated and nonmedicated groups would not be meaningful. However, it will be noted that the female Broad White turkeys receiving the 0.005, 0.0075, and 0.1% feed concentrations, at 24 weeks of age, averaged 8,301, 8,573, and 8,346 gms., respectively. In Experiment 2 (Table 8), the mean weight of turkeys receiving the 0.005, 0.0075, and 0.01% feed concentrations of Nifursol at eight weeks were 2,540, 2,495, and 2,540 gms., respectively, or 3.7, 1.9, and 3.7% more than that of the nonmedicated birds. At 16 weeks the mean weights were 5,988, 5,942, and 5,897 gms. as compared to 3,765 gms. for the seven survivors of the nonmedicated group. Feed use of the turkeys receiving Nifursol at 0.005, 0.0075, and 0.01% feed concentrations was 1.77, 1.79, and 1.77 gms. of feed per gm. of live weight, respectively, during the first eight weeks as compared to 1.81 gms. for the nonmedicated turkeys. This was a difference
H l S T O M O N A S T A T I C A C T I V I T Y OF
TABLE 9.—Effect of Nifursol on growth and feed use of turkeys raised under conditions of high exposure to histomoniasis in outside pens Experiment 3 Growth
Feed
c/
Snf
P™
lis
^v?
11
%
/ l~' •. Response 0.005 8 Wks. 16 Wks. 0.0075 8 Wks. 16 Wks. 0.01 8 Wks. 16 Wks. Nonmed. 8 Wks. 16 Wks.
39 35
1,950 5,352
39 37
3,132 5,625
39 37
2,177 5,715
39 3
1,950 5,443
Effi
"
ciency
% Response
595
medicated turkeys of this experiment but the feed use ratios were not calculated because of the high mortality from blackhead in the nonmedicated turkeys. While these experiments on Nifursol were designed only to determine its antihistomonal efficacy and relative safety to turkeys, there was a noticeable tendency toward higher weight gains and improved feed efficiency among the groups of Nifursol recipients. Additional experiments designed for statistical evaluation are required to assess the real effect of Nifursol on growth and feed use of turkeys, but it is evident that Nifursol had no adverse effect on turkeys as shown by these two criteria. SUMMARY
Histomonastatic activity of 3,5-dinitrosalicylic acid, 5-nitrofurfurylidene hydrazide (Nifursol) was determined in poults which (1) had received a single oral inoculum of Heterakis gallinarum ova or (2) were raised on soil which was contaminated continuously by droppings from Heterakis-infected chickens suspended in wire cages above the lots. Poults receiving a single infection were protected from blackhead mortality by feeding Nifursol concentrations varying from 0.004 through 0.2%. The lowest effective concentration was 0.00125% which allowed for survival of 44.5% of the poults. All nonmedicated control birds died of histomoniasis. Nifursol was administered to poults receiving a continuous exposure to blackhead in outdoor pens at feed concentrations of 0.005, 0.0075, and 0.01%. In Experiment 1, these dosages prevented all blackhead mortality whereas all nonmedicated poults died of histomoniasis. In Experiment 2, concentrations of 0.0075 and 0.01% prevented blackhead mortality and the 0.005% concentration allowed for survival of 94.7% of the poults whereas
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of 2.2, 1.1, and 2.2% between the three medicated groups and the control group. While the 16 weeks feed efficiency was recorded in Table 8 for the medicated and nonmedicated turkeys of this experiment, the feed use ratios were not calculated because the high blackhead mortality among the nonmedicated turkeys gives a spuriously high feed efficiency for the seven poults which survived in this experiment. Data on the growth and feed use of the turkeys in Experiment 3 are shown in Table 9. The mean weight of turkeys receiving the 0.005, 0.0075, and 0.01% feed concentrations of Nifursol at eight weeks of age were 1,950, 3,132, and 2,177 gms., respectively, or 0.0, 9.3, and 11.2% more than that of the nonmedicated birds. At 16 weeks the mean weights were 5,352, 5,625, and 5,715 as compared to 5,443 gms. for the three survivors of the nonmedicated control turkeys. Feed use of the turkeys receiving Nifursol at 0.005, 0.0075, and 0.01% feed concentrations was 1.75, 1.74, and 1.69 gms. of feed per gm. of live weight, respectively, during the first eight weeks as compared to 1.81 gms. for the nonmedicated turkeys. This was a difference of 3.4, 4.0, and 7.1% between the medicated groups and the control group. As in Experiment 2, the 16 week feed efficiency was recorded for the medicated and non-
NlFURSOL
596
R. D. VATNE, R. R. BARON AND N. F. MOREHOUSE
REFERENCES Berndt, E. W., H. Van Essen, B. G. Held and R. D.
Vatne. A potent new preventive of histomoniasis in turkeys. In press. Horton-Smith, C , and P. L. Long, 1956. Further observations on the chemotherapy of histomoniasis (blackhead) in turkeys. J. Comp. Path. Therapeutics 66 (4): 378-388. Joyner, L. P., and S. B. Kendall, 1955. The use of 2amino-5-nitrothiazole in control of histomoniasis. Vet. Rec. 67: 180-182. Lund, E. E., E. E. Wehr and D. J. Ellis, 1966. Earthworm transmission of Heterakis and Hislomonas to turkeys and chickens. J. Parasit. 52 (5): 899-902. McGregor, J. K., 1953. Preliminary observations on the use of certain nitrofuran compounds in the control of enterohepatitis (blackhead) in turkeys. J. Amer. Vet. Med. Assoc. 122: 312-314. Morehouse, N. F., and W. C. McGuire, 1950. Experiments in chemotherapy of blackhead in turkeys. Proc. Iowa Acad. Sci. 57: 475-482.
The Influence of Maternal Diet on Egg Size and Progeny Performance in Meat-Type Hens J. R. AITKEN, E. S. MERRITT AND R. J. CURTIS 1 Animal Research Institute, Canada Department of Agriculture, Ottawa, Ontario2 (Received for publication September 3, 1968)
H
ATCHING egg size and its relationship to parent reproductive performance and progeny growth have been the subject of a number of investigations, because of the potential importance in the production of poultry meat (Goodwin, 1961; Merritt and Gowe, 1965). The high positive relationship between the size of the egg and the size of the hatched chick has been recognized, but it has generally been regarded that the relationship is no longer of practical significance by the time the bird reaches market age. Goodwin (1961) has shown, however, that on an intra-strain basis a 1 gram increase in egg 1
Experimental Station, Canada Department of Agriculture, Fredericton, N. B. 2 Contribution No. 294, Animal Research Institute, Canada Department of Agriculture, Ottawa.
weight can result in a 5 gram increase in market body weight (9 weeks). He found even larger inter-strain relationships in the same study. It has been well established from a number of intra-strain genetic studies that egg size and body size are positively correlated genetically, so that the relationship reported by Goodwin and others could to some extent be of genetic origin. On the other hand, numerous environmental factors such as age, diet, disease and management have been demonstrated to affect egg size. Much less attention has been paid to the possible effects of environmentally induced differences in egg size on subsequent growth. The present study was undertaken to investigate this question, using diet as the means of influencing
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only 18.5% of the nonmedicated poults survived. In Experiment 3, concentrations of 0.005, 0.0075, and 0.01% prevented all blackhead mortality whereas only 7.7% of the nonmedicated poults survived. Turkeys receiving 0.005, 0.0075, and 0.01% feed concentrations of Nifursol attained good weights and feed efficiency values during their growing period. From these data, it is concluded that this compound not only provided high efficacy against heavy blackhead exposure but that it produced no adverse effects in the turkeys.
A
During our investigation of nitrofuran derivatives, a new compound was discovered which affords excellent protection against blackhead disease at low feed concentrations and which has a high margin of safety in recipient turkeys. This paper reports the investigation of the antihistomonal activity of 3,5-dinitrosalicylic acid, 5-nitrofurfurylidene hydrazide (Berndt el al., 1969) which is hereafter referred to as Nifursol,* its United States Adopted N a m e . EXPERIMENTAL PROCEDURES
Laboralory Experimenls—Single Injection. Nonsexed Broad Breasted Bronze and Broad White turkeys purchased from commercial hatcheries were reared in bat* Active ingredient in the product Salfuride.
teries with wire-mesh floors. All poults received a standard ration prior to and during the experiments. At approximately six weeks of age, poults were transferred to individual cages with wire-mesh floors. At this time poults were grouped according to weights so t h a t all experimental groups were approximately equal. Poults were orally inoculated on the first day of the test with approximately 1,000 embryonated Heterakis gallinarum ova known to harbor Histomonas meleagridis. Experiments were routinely 28 days in duration although poults in some experiments were held for additional periods to ascertain the relapse incidence of histomoniasis. Poults received medicated feed for the first 21 days and nonmedicated feed during the final seven days as well as during any additional holding periods. Bird weights and feed consumption data were recorded weekly in all experiments. Droppings of individual birds were checked for abnormalities caused by histomoniasis from the ninth day postinfection to the end of each experiment. Poults which died during an experiment were examined for cecal and liver lesions of blackhead. Poults surviving at the termination of experiments were also necropsied and the presence or absence of lesions recorded. Outdoor Pen Experiments—Continuous Exposure. Three experiments, each involving 240 day-old Broad Breasted Bronze or Broad White turkeys, were conducted. In each experiment turkeys were divided into six groups of 40 per group and placed in floor pens of a brooder house for the first eight weeks. All groups received a stan-
590
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L T H O U G H activity against black- head disease (histomoniasis) in chickens and turkeys has been proved for several structurally diverse compounds during the past 20 years, this disease remains one of the most costly to turkey producers. Among the most noteworthy types of these compounds are certain arsonic acids, nitrothiazoles, quinolines, imidazoles and nitrofurans. McGregor (1953) reported t h a t furazolidone, when administered at one part in 8,000 parts of feed, had a small degree of prophylactic value. One of six other nitrofurans tested (NF-153) was of slight value when administered from two days prior to infection and continued for 29 days. Furazolidone has not been used extensively by poultrymen, however, because other compounds have provided better efficacy at less cost.
591
HlSTOMONASTATIC ACTIVITY OF NlFURSOL
Poults were rotated between lots twice weekly to help insure a uniform blackhead challenge. Bird weight and feed consumption data were recorded biweekly. Surviving poults and those which died during experiments were examined for cecal and liver lesions of blackhead. RESULTS AND DISCUSSION
Table 1 is a summary of experiments to determine the histomonastatic activity of Nifursol fed to turkeys following their infection with a single oral inoculum of H.
TABLE 1.—Chemoprophylactic efficacy of Nifursol against histomoniasis in turkeys. Poults were infected with a single oral inoculum of approximately 1,000 embryonated Heterakis gallinarum ova
% Feed cone. 0.00063 0.00125 0.0015 0.002 0.0025 0.003 0.004 0.005 0.006 0.0075 0.01 0.015 0.025 0.03 0.04 0.05 0.1 0.2 Infected Controls
No. expts.
Total No. birds
Clinical signs a n d / o r postmortem lesions
%
Blackhead mortality
%
No. birds
Efficacy
No. birds
Efficacy
0 16.7 50 63.8 77.4 86.5 87.9 94.7 100 96.8 99 100 100 100 100 100 100 100
18 10 5 18 5 1 0 0 0 0 0 0 0 0 0 0 0 0
0 44.5 75 70 96.4 98.6 100 100 100 100 100 100 100 100 100 100 100 100
—
312
—
3 3 1 6 14 7 6 29 5 23 11 3 3 3 2 4 1 1
18 18 20 58 137 74 58 283 49 185 100 17 7 18 2 12 4 4
18 15 10 21 31 10 7 15 0 5 1 0 0 0 0 0 0 0
46
312
312
gallinarum ova. Graded Nifursol concentrations ranging from 0.00063 to 0.2% were fed. Concentrations of 0.015% and above provided total blackhead protection as determined by the absence of clinical signs of the disease during experiments and by the absence of lesions on postmortem examination at the termination of experiments. No blackhead mortality occurred in poults receiving concentrations between 0.004 and 0.2%. Only 5 of 185 poults fed a concentration of 0.0075% and 15 of 283 poults fed a concentration of 0.005% demonstrated clinical signs or postmortem lesions. A gradual depletion of activity paralleled the reduction of drug concentration in the feed. The lowest concentration with definite histomonastatic activity was 0.00125% which allowed survival of 4 4 . 5 % of the poults. No activity was demonstrated by the 0.00063% concentration. Overall efficacy provided by the various concentrations is particularly significant because the blackhead challenge given to these poults was uniform and extremely severe.
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dard ration. Three groups in each experiment were fed different concentrations of Nifursol, two groups were fed different concentrations of a commercially available histomonastat, and one group received no medication. All poults were moved to outdoor pens at eight weeks of age where those of Experiment 1 were kept for 24 weeks and those of Experiments 2 and 3 for 16 weeks. T h e six pens, each approximately four by six meters, had been occupied in previous years by blackhead infected turkeys. Soil in these lots was further contaminated by suspension of Heterakis-'miected chickens in wire cages over each lot. Although earthworms were infrequently found in the lots, it is probable that consumption of them by poults provided an additional source of infection. Earthworms collected from soil approximately one foot outside the periphery of the lots were fed to poults in experiments not directly related to this study. A high percentage of the poults died of histomoniasis. These findings would substantiate those reported b y Lund (1966) t h a t earthworms are important vectors in blackhead transmission. A roof covering all lots, prevented direct sunlight from drying the soil surface and, therefore, allowed an environment which favored existence of free histomonads, H. gallinarum ova and earthworms.
592
R. D. VATNE, R. R. BARON AND N. F. MOREHOUSE TABLE 2.—Relapse incidence of histomoniasis in poults following withdrawal of Nifursol from the feed
F ™ w d o i Days held C nC Z :J°cIJ1 after No.
infection 0.003 0.004 0.005 0.005 0.006 0.0075
medication birds withdrawn 35 35 21 35 35 21
Postmortem lesions
%
Blackhead mortality
No. birds Relapse 1 0 1 0 1 0
15 16 19 16 18 15
No. % birds Relapse
6.7 0 5.3 0 5.6 0
1 0 1 0 1 0
6.7 0 5.3 0 5.6 0
TABLE 3.—Effect of Nifursol on growth and feed use of turkeys exposed to histomoniasis by a single oral inoculation of approximately 1,000 Heterakis gallinarum ova Growth % Feed cone. 0.005 Nonmed. Noninf. 0.0075 Nonmed. Noninf. 0.01 Nonmed. Noninf.
No. of groups 11 11 7 7 5 5
Total No. birds 160 160 108 107 88 90
Mean gain (gms.) 1,159 1,160 1,266 1,214 1,330 1,280
Peed
%
Response -0.1
—
4.3
—
3.9
—
Efficiency 2.13 2.07 1.98 2.02 1.91 2.01
%
Response -3.0
—
2.0
—
5.0
—
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Blackhead mortality occurred in all of the 312 infected nonmedicated controls of these experiments. The tendency for histomoniasis relapse to occur in turkeys following withdrawal of medication has been discussed by several investigators (Morehouse and McGuire, 1950; Joyner and Kendall, 1955; Horton-Smith and Long, 1956). Table 2 summarizes the relapse incidence in several experiments following withdrawal of Nifursol from the feed. This medication had been fed for 21 days. In some experiments poults were individually caged following withdrawal of medication and in other experiments they were individually caged for a period and then transferred to a floor pen. Poults demonstrating clinical signs of blackhead were never placed in a floor pen but were kept in individual cages. No relapse occurred in 15 poults held on nonmedicated feed for 35 days after having received medication at a concentration of 0.0075%. Relapse occurred in 1 of 18 poults held 35 days which had re-
ceived medication at 0.006%. One of 19 poults which had received medication at 0.005% relapsed within a 21 day period. A group of poults receiving medication at the same concentration, however, were held for 35 days without any relapse. No relapse occurred in 16 poults held for 35 days after receiving medication at 0.004%. One of 15 poults held for 35 days relapsed after receiving medication at 0.003%. All three poults which relapsed showed clinical signs of blackhead by the 14th day after receiving nonmedicated feed. Overall results indicate that poults held after receiving medication at concentrations of 0.003 and 0.004% are not markedly more susceptible to relapse than poults receiving approximately double these concentrations. Weight gains and feed efficiency data from poults receiving 0.005, 0.0075 and 0.01% feed concentrations of Nifursol are summarized in Table 3. The data of these three dosages are shown because they are the feed concentrations utilized in the outdoor pen experiments described elsewhere in this paper. The mean weight gain of 11 test groups (160 poults) receiving a 0.005% feed concentration of Nifursol was 1,159 gms. while the 11 nonmedicated noninfected groups (160 poults) gained approximately the same amount, 1,160 gms. The average number of gms. of feed utilized per gm. of live weight was 2.13 for the medicated
593
HlSTOMONASTATIC ACTIVITY OF NlFURSOL
TABLE 4.—Chemoprophylactic efficacy of Nifursol against histomoniasis in turkeys. Poults were exposed to soil continuously contaminated with droppings from chickens infected with Heterakis gallinarum Experiment 1 % Drug in feed 0.005 0.0075 0.01 Nonmed.
No. birds 38 37 35 40
Postmortem lesions No. birds 2 1 0 40
Blackhead mortality
% Without No. lesions birds 94.7 97.3 100 0
0 0 0 40
%
Survival 100 100 100 0
TABLE 5.—Chemoprophylactic efficacy of Nifursol against histomoniasis in turkeys. Poults were exposed to soil continuously contaminated with droppings from chickens infected with Heterakis gallinarum Experiment 2
% Drug in feed 0.005 0.0075 0.01 Nonmed.
No. birds 38 38 39 40
Postmortem lesions
Blackhead mortality
N o . % Without No. birds lesions birds 5 4 5 39
86.9 89.5 87.2 2.5
2 0 0 33
%
Survival 94.7 100 100 18.5
1 conducted in the outdoor sheltered pens. The three feed concentrations of Nifursol, 0.005, 0.0075, and 0.01%, afforded 100% protection to poults against blackhead mortality. Only 2 of 38 poults receiving the drug at 0.005% and 1 of 37 poults fed the drug at 0.0075% possessed mild cecal lesions at necropsy. All nonmedicated birds died of histomoniasis. Table 5 summarizes efficacy data obtained with Nifursol in Experiment 2 which was conducted in the outdoor highexposure pens. The 0.0075 and 0.01% drug concentrations in the feed provided 100% protection from blackhead mortal" ity. The 0.005% concentration permitted survival of 94.7% (36 of 38) of the poults. At necropsy, one poult receiving the 0.01% concentration had several small liver lesions and mild cecal lesions. Four others had only mild cecal lesions. Groups receiving the 0.005 and 0.0075% drug concentrations had five and four turkeys, respectively, that possessed mild cecal lesions but no liver lesions. No evidence of blackhead disease was found in the liver or ceca of the other turkeys. Thirty-three of 40 nonmedicated control poults died of blackhead during this experiment and one additional bird exhibiting advanced signs of the disease at termination of the experiment died two days later. Thirty-nine of the control group possessed cecal lesions, and of these, 37 also had developed liver lesions. Table 6 shows results of Experiment 3
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poults and 2.07 for the nonmedicated poults, a difference of 3%. Nifursol fed at a 0.0075% concentration to seven groups totaling 108 poults produced a mean weight gain of 1,266 gms. or 4.3% more than the 1,214 gm. gain of seven groups totaling 107 nonmedicated poults. The average feed efficiency for the medicated and nonmedicated noninfected poults was 1.98 and 2.02, respectively, a difference of 2%. Five groups (88 poults) receiving a 0.01% feed concentration of Nifursol had a mean gain of 1,330 gms. compared to 1,280 gms. for five groups (90 poults) which received no medication, a difference of 3.9%. Feed efficiency for the medicated and nonmedicated noninfected poults was 1.91 and 2.01, respectively, a difference of 5%. Antihistomonal efficacy of Nifursol when administered continuously from dayold to maturity at 0.005, 0.0075, and 0.01% feed concentrations was further studied in outdoor pen experiments where continuous exposure to blackhead was provided. Little, if any exposure to blackhead was available during the first eight weeks while the poults were kept in clean brooder houses but continuous exposure was provided in the outdoor pens from eight weeks of age until the experiments were terminated at 24 weeks as in Experiment 1 or at 16 weeks for Experiments 2 and 3. Table 4 shows the results of Experiment
594
R. D. VATNE, R. R. BARON AND N. F. MOREHOUSE
TABLE 6.—Chemoprophylaclic efficacy of Nifursol against hislomoniasis in turkeys. Poults were exposed to soil continuously contaminated with droppings from chickens infected with Heterakis gallinarum Experiment 3
% Drug in feed
No. birds
Postmortem ]lesions
No. birds
35 37 37 39
0.005 0.0075 0.01 Nonmed.
2 0 0 37
Blackhead mortality
% Without No. lesions birds 94.3 100 100 5.1
%
Survival
0 0 0 36
100 100 100 7.7
TABLE 7.—Effect of Nifursol on growth and feed use of turkeys raised under conditions of high exposure to hislomoniasis in outside pens Experiment 1
%
Feed cone. 0.005 8 Wks. 16 Wks. 24 Wks. 0.0075 8 Wks. 16 Wks. 24 Wks. 0.01 8 Wks. 16 Wks. 24 Wks. Nonmed. 8 Wks. 16 Wks.
Growth No. poults
Mean wt. (gms.)
%
Response
Feed Efficiency
TABLE 8.—Effect of Nifursol on growth and feed use of turkeys raised under conditions of high exposure to histomoniasis in outside \ Experiment Z
%
Response
Feed 40 39 38
2,177 5,262 8,301
1.67 2.63
5.6
39 37 37
2,132 5,534 8,573
1.70 2.57 4.01
4.0
39 36 35
2,087 5,398 8,346
1.67 2.62 4.02
40 0
2,041
—
Feed
Growth
% 0.005 8 Wks. 16 Wks. 0.0075 8 Wks. 16 Wks. 0.01 8 Wks. 16 Wks. Nonmed. 8 Wks. 16 Wks.
No. poults
Mean wt. (gms.)
%
Effi-
%
Response
ciency
Response
1.77 3.06
2.2
1.79 2.99
1.1
1.77 2.93
2.2
40 37
2,540 5,988
3.7
40 38
2,495 5,942
1.9
40 39
2,540 5,897
3.7
40 7
2,449 3,765
— — — — —
1.81 14.97
— — — — —
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conducted in the sheltered lots. Drug concentrations in the feed of 0.005, 0.0075, and 0.01% provided 100% protection from mortality. Postmortem examination of all poults which had received medication revealed that only two birds possessed blackhead lesions. One possessed only liver lesions and one possessed only cecal lesions. Both of these birds had received medication at the 0.005% concentration. As in the laboratory experiments, the Nifursol medicated feed was well tolerated and good growth was obtained for all three dosage levels used in experiments conducted in outside pens. Table 7 shows results from Experiment 1. At eight weeks of age (prior to blackhead exposure) the turkeys receiving the 0.005% feed concentration averaged 2,177 gms., which was 6.7% heavier than the nonmedicated con-
trols; at the 0.0075% concentration the average was 2,132 gms., a difference of 4.4%; and at the 0.01% concentration the average was 2,087 gms. or a difference of 2.2% over the controls. Because high mortality had occurred among the nonmedicated poults at 16 weeks and because there were no survivors of this group at 24 weeks, weight comparisons between medicated and nonmedicated groups would not be meaningful. However, it will be noted that the female Broad White turkeys receiving the 0.005, 0.0075, and 0.1% feed concentrations, at 24 weeks of age, averaged 8,301, 8,573, and 8,346 gms., respectively. In Experiment 2 (Table 8), the mean weight of turkeys receiving the 0.005, 0.0075, and 0.01% feed concentrations of Nifursol at eight weeks were 2,540, 2,495, and 2,540 gms., respectively, or 3.7, 1.9, and 3.7% more than that of the nonmedicated birds. At 16 weeks the mean weights were 5,988, 5,942, and 5,897 gms. as compared to 3,765 gms. for the seven survivors of the nonmedicated group. Feed use of the turkeys receiving Nifursol at 0.005, 0.0075, and 0.01% feed concentrations was 1.77, 1.79, and 1.77 gms. of feed per gm. of live weight, respectively, during the first eight weeks as compared to 1.81 gms. for the nonmedicated turkeys. This was a difference
H l S T O M O N A S T A T I C A C T I V I T Y OF
TABLE 9.—Effect of Nifursol on growth and feed use of turkeys raised under conditions of high exposure to histomoniasis in outside pens Experiment 3 Growth
Feed
c/
Snf
P™
lis
^v?
11
%
/ l~' •. Response 0.005 8 Wks. 16 Wks. 0.0075 8 Wks. 16 Wks. 0.01 8 Wks. 16 Wks. Nonmed. 8 Wks. 16 Wks.
39 35
1,950 5,352
39 37
3,132 5,625
39 37
2,177 5,715
39 3
1,950 5,443
Effi
"
ciency
% Response
595
medicated turkeys of this experiment but the feed use ratios were not calculated because of the high mortality from blackhead in the nonmedicated turkeys. While these experiments on Nifursol were designed only to determine its antihistomonal efficacy and relative safety to turkeys, there was a noticeable tendency toward higher weight gains and improved feed efficiency among the groups of Nifursol recipients. Additional experiments designed for statistical evaluation are required to assess the real effect of Nifursol on growth and feed use of turkeys, but it is evident that Nifursol had no adverse effect on turkeys as shown by these two criteria. SUMMARY
Histomonastatic activity of 3,5-dinitrosalicylic acid, 5-nitrofurfurylidene hydrazide (Nifursol) was determined in poults which (1) had received a single oral inoculum of Heterakis gallinarum ova or (2) were raised on soil which was contaminated continuously by droppings from Heterakis-infected chickens suspended in wire cages above the lots. Poults receiving a single infection were protected from blackhead mortality by feeding Nifursol concentrations varying from 0.004 through 0.2%. The lowest effective concentration was 0.00125% which allowed for survival of 44.5% of the poults. All nonmedicated control birds died of histomoniasis. Nifursol was administered to poults receiving a continuous exposure to blackhead in outdoor pens at feed concentrations of 0.005, 0.0075, and 0.01%. In Experiment 1, these dosages prevented all blackhead mortality whereas all nonmedicated poults died of histomoniasis. In Experiment 2, concentrations of 0.0075 and 0.01% prevented blackhead mortality and the 0.005% concentration allowed for survival of 94.7% of the poults whereas
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of 2.2, 1.1, and 2.2% between the three medicated groups and the control group. While the 16 weeks feed efficiency was recorded in Table 8 for the medicated and nonmedicated turkeys of this experiment, the feed use ratios were not calculated because the high blackhead mortality among the nonmedicated turkeys gives a spuriously high feed efficiency for the seven poults which survived in this experiment. Data on the growth and feed use of the turkeys in Experiment 3 are shown in Table 9. The mean weight of turkeys receiving the 0.005, 0.0075, and 0.01% feed concentrations of Nifursol at eight weeks of age were 1,950, 3,132, and 2,177 gms., respectively, or 0.0, 9.3, and 11.2% more than that of the nonmedicated birds. At 16 weeks the mean weights were 5,352, 5,625, and 5,715 as compared to 5,443 gms. for the three survivors of the nonmedicated control turkeys. Feed use of the turkeys receiving Nifursol at 0.005, 0.0075, and 0.01% feed concentrations was 1.75, 1.74, and 1.69 gms. of feed per gm. of live weight, respectively, during the first eight weeks as compared to 1.81 gms. for the nonmedicated turkeys. This was a difference of 3.4, 4.0, and 7.1% between the medicated groups and the control group. As in Experiment 2, the 16 week feed efficiency was recorded for the medicated and non-
NlFURSOL
596
R. D. VATNE, R. R. BARON AND N. F. MOREHOUSE
REFERENCES Berndt, E. W., H. Van Essen, B. G. Held and R. D.
Vatne. A potent new preventive of histomoniasis in turkeys. In press. Horton-Smith, C , and P. L. Long, 1956. Further observations on the chemotherapy of histomoniasis (blackhead) in turkeys. J. Comp. Path. Therapeutics 66 (4): 378-388. Joyner, L. P., and S. B. Kendall, 1955. The use of 2amino-5-nitrothiazole in control of histomoniasis. Vet. Rec. 67: 180-182. Lund, E. E., E. E. Wehr and D. J. Ellis, 1966. Earthworm transmission of Heterakis and Hislomonas to turkeys and chickens. J. Parasit. 52 (5): 899-902. McGregor, J. K., 1953. Preliminary observations on the use of certain nitrofuran compounds in the control of enterohepatitis (blackhead) in turkeys. J. Amer. Vet. Med. Assoc. 122: 312-314. Morehouse, N. F., and W. C. McGuire, 1950. Experiments in chemotherapy of blackhead in turkeys. Proc. Iowa Acad. Sci. 57: 475-482.
The Influence of Maternal Diet on Egg Size and Progeny Performance in Meat-Type Hens J. R. AITKEN, E. S. MERRITT AND R. J. CURTIS 1 Animal Research Institute, Canada Department of Agriculture, Ottawa, Ontario2 (Received for publication September 3, 1968)
H
ATCHING egg size and its relationship to parent reproductive performance and progeny growth have been the subject of a number of investigations, because of the potential importance in the production of poultry meat (Goodwin, 1961; Merritt and Gowe, 1965). The high positive relationship between the size of the egg and the size of the hatched chick has been recognized, but it has generally been regarded that the relationship is no longer of practical significance by the time the bird reaches market age. Goodwin (1961) has shown, however, that on an intra-strain basis a 1 gram increase in egg 1
Experimental Station, Canada Department of Agriculture, Fredericton, N. B. 2 Contribution No. 294, Animal Research Institute, Canada Department of Agriculture, Ottawa.
weight can result in a 5 gram increase in market body weight (9 weeks). He found even larger inter-strain relationships in the same study. It has been well established from a number of intra-strain genetic studies that egg size and body size are positively correlated genetically, so that the relationship reported by Goodwin and others could to some extent be of genetic origin. On the other hand, numerous environmental factors such as age, diet, disease and management have been demonstrated to affect egg size. Much less attention has been paid to the possible effects of environmentally induced differences in egg size on subsequent growth. The present study was undertaken to investigate this question, using diet as the means of influencing
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only 18.5% of the nonmedicated poults survived. In Experiment 3, concentrations of 0.005, 0.0075, and 0.01% prevented all blackhead mortality whereas only 7.7% of the nonmedicated poults survived. Turkeys receiving 0.005, 0.0075, and 0.01% feed concentrations of Nifursol attained good weights and feed efficiency values during their growing period. From these data, it is concluded that this compound not only provided high efficacy against heavy blackhead exposure but that it produced no adverse effects in the turkeys.