Anticoccidial Efficacy of a New Polyether Antibiotic, Salinomycin, in Comparison to Monensin and Lasalocid in Battery Trials1

Anticoccidial Efficacy of a New Polyether Antibiotic, Salinomycin, in Comparison to Monensin and Lasalocid in Battery Trials1

Anticoccidial Efficacy of a New Polyether Antibiotic, Salinomycin, in Comparison to Monensin and Lasalocid in Battery Trials1 THOMAS T. MIGAKI, LARRY ...

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Anticoccidial Efficacy of a New Polyether Antibiotic, Salinomycin, in Comparison to Monensin and Lasalocid in Battery Trials1 THOMAS T. MIGAKI, LARRY R. CHAPPEL 2 , and WILLIAM E. BABCOCK Animal Health Research Department, Pfizer, Inc., Terre Haute, Indiana 4 7808 (Received for publication September 16, 1978)

1979 Poultry Science 58:1192-1196 INTRODUCTION Salinomycin ( C o x i s t a c ) 3 is a m o n o c a r b o x y lic acid p o l y e t h e r antibiotic p r o d u c e d b y Streptomyces albus through f e r m e n t a t i o n (Kinashi et al, 1973). T h e chemical structure of salinomycin c o n t a i n s a u n i q u e tricyclic spiroketal ring system which distinguishes it from monensin and lasalocid (Kinashi et al, 1 9 7 3 ; a n d Mitani et al, 1975). Salinomycin complexes preferentially with t h e m o n o v a l e n t alkali metal ions Na+ and K + and mediate their t r a n s p o r t across m e m b r a n e s (Kinashi et al, 1 9 7 3 ; and Reed and Lardy, 1 9 7 2 ) . This effect m a y a c c o u n t for t h e activity of salinomycin against gram-positive bacteria, m y c o b a c t e r i a , some filimentous fungi a n d coccidia (Danforth et al, 1 9 7 0 ; and Miyazaki et al, 1 9 7 4 ) . R e c e n t studies d e m o n s t r a t e d t h a t salinomycin has a cidal effect on coccidia and acts early in t h e life cycle (Chappel, 1977). In this paper t h e efficacy of salinomycin against various species

'This study was presented at the 67th Annual Meeting of the Poultry Science Association, Inc., Clemson, SC, 1978. 2 Present address: Medical Research Laboratories, Pfizer, Inc., Groton, CT 06340. 3 Trademark of Pfizer Inc.

of avian coccidia is c o m p a r e d t o t w o o t h e r p o l y e t h e r i o n o p h o r e s , m o n e n s i n (Ruff et al, 1 9 7 6 ; and S h u m a r d and Callender, 1 9 6 7 ) and lasalocid (Mitrovic and Schildknecht, 1 9 7 4 ; a n d R e i d e i a / . , 1975).

EXPERIMENTAL PROCEDURES Male broiler chicks (Hubbards) were purchased from a commercial h a t c h e r y at a day of age and held in wire-floored b r o o d e r batteries until trial initiation. T h e birds were from 9 t o 2 4 days old w h e n t h e y were transferred to wire-floored finishing batteries, weighed, and allotted at r a n d o m i n t o t r e a t m e n t s . Salinom y c i n at levels of 3 0 and 6 0 p p m was c o m pared t o m o n e n s i n at 50 and 100 p p m in 9 trials, lasalocid at 37.5 and 75 p p m in t w o trials, and t o b o t h c o m p o u n d s at t h e levels indicated in four trials. An equal n u m b e r of infected, n o n m e d i c a t e d chicks (controls) were included in each trial. T h e r e were t h r e e pens of 10 chicks each per t r e a t m e n t in each trial. T h e t r e a t m e n t rations were given beginning one day before inoculation with different c o m b i n a t i o n s of Eimeria spp. (Table 1). T h e basal ration for three trials contained 22% protein and a p p r o x i m a t e l y 3 1 4 6 kcal of ME/kg, and t h e ration in

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ABSTRACT Broiler chicks were given salinomycin in the feed at levels of 30 and 60 ppm in battery trials to measure the efficacy against six major species of Eimeria. Comparisons to nonmedicated chicks (controls) and chicks given monensin at 50 and 100 ppm or lasalocid at 37.5 and 75 ppm were made. Factors measured were the severity of coccidia lesions, mortality, and weight gain. The efficacy of salinomycin, monensin, and lasalocid in preventing lesions differed in many respects. The lesion control of salinomycin at 60 ppm was excellent against E. acervulina, E. mivati, E. necatrix, and E. tenella, and slightly reduced against E. maxima and E. brunetti. The lesion control of monensin at 100 ppm was excellent against E. mivati and E. necatrix, and slightly reduced against E. tenella, E. acervulina, E. maxima, and E. brunetti. The lesion control of lasalocid at 75 ppm was excellent against E. brunetti, slightly reduced against E. maxima, E. necatrix, and E. tenella, and lowest against E. acervulina. Based upon all measurements, salinomycin at 60 ppm was comparable or superior to monensin at 100 ppm and lasalocid at 75 ppm. At 30 ppm, salinomycin was more effective overall than monensin at 50 ppm or lasalocid at 37.5 ppm. The relative potency of each anticoccidial agent was clearly evident in these data.

ANTICOCCIDIAL EFFICACY OF SALINOMYCIN TABLE 1. Age of chicks and Eimeria spp. used in each test

Experiment number 6-2

E. acervulina, E. maxima, E. tenella E. mivati, E. necatrix E. acervulina, E. brunetti E. acervulina, E, brunetti E. maxima, E. tenella E. necatrix, E. tenella E. acervulina, E. maxima E. brunetti, E. tenella E. maxima, E. brunetti E. brunetti, E. tenella E. mivati, E. maxima E. acervulina, E. necatrix E. acervulina, E. tenella E. mivati, E. necatrix E. brunetti, E. maxima

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Initial age of chicks (days)

10 9 10 17 16 17 14 16 15 17 15 17 24 15 17

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the remaining 12 trials contained 22.3% protein and approximately 2820 kcal of ME/kg. The appropriate drugs were added to the rations and thoroughly mixed. The coccidia cultures were recent field isolates or pure cultures. The field isolates were obtained through courtesy of Northeast Laboratories (Waterville, ME) and the pure cultures from Lilly Research Laboratories, Hess and Clark, and University of Georgia. History of prior exposure to drug(s) by these cultures is not known. The inoculum dose was predetermined by titration and given by inoculating a mixture of sporulated oocysts by crop intubation utilizing a blunted 2 ml pipette. Seven days after inoculation the surviving birds were weighed and killed for examination. Coccidiosis lesions were scored by a modification of the method by Johnson and Reid (1970). Lesions caused by E. acervulina, E. mivati, E. maxima, and E. brunetti were scored on a basis from 0 (normal) to 2 (most severe), and E. necatrix and E. tenella lesions were scored from 0 to 3. Dead birds were not given a lesion score. Records of mortality and post mortem observations were maintained.

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RESULTS

The efficacy of salinomycin, monensin, and lasalocid in preventing coccidia lesions for each species tested is shown (Table 2). These data

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6-3 6-4 6-5 6-6 6-9 6-12 6-13 6-15 7-1 7-2 7-3 7-8 7-9 7-10

Eimeria spp.

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MIGAKI ET AL.

1194

TABLE 3. Summary of coccidiosis mortality and weight gain in trials testing salinomycin, monensin, and lasalocid Weight gain a

Mortality (No.)

(%)

(g)

Index

Nonmedicated Salinomycin, 30 ppm Salinomycin, 60 ppm

15 15 15

114 5 3

25.3 1.1 .7

93.7 236.1 256.8

100.0 252.0 274.1

Nonmedicated Monensin, 50 ppm Monensin, 100 ppm

13 13 13

89 18 0

22.8 4.6 .0

94.2 205.3 243.0

100.0 217.9 258.0

Nonmedicated Lasalocid, 37.5 ppm Lasalocid, 75.0 ppm

6 6 6

61 4 0

33.9 2.2 .0

94.1 244.8 286.9

100.0 260.1 304.9

TVeight gain of surviving birds.

provide a good measurement of the strengths, weaknesses, and potency of each drug against the parasite. The efficacy of salinomycin at 60 ppm was excellent against E. acervulina (100%), E. mivati (100%), E. necatrix (100%), and E. tenella (90%), and slightly reduced against E. maxima (81%) and E. brunetti (70%). The efficacy of monensin at 100 ppm was excellent against E. mivati (98%) and E. necatrix (95%) and slightly reduced against E. tenella (87%), E, acervulina (85%), E. maxima (78%), and E. brunetti (68%). The efficacy of lasalocid at 75 ppm was excellent against E. brunetti (96%), slightly reduced against E. maxima (88%), E. necatrix (88%), and E. tenella (78%), and least effective against E. acervulina (26%). Lesions were controlled less effectively at the lower levels of drug tested. The response for salinomycin at 30 ppm was greater than for either monensin at 50 ppm or lasalocid at 37.5 ppm against E. acervulina, E. mivati, and E. necatrix, and approximately equal to monensin but superior to lasalocid in controlling lesions of E. tenella. Lasalocid at 37.5 ppm was superior, however, to monensin and salinomycin at the lower levels in controlling lesions of E. maxima and E. brunetti. A summary across trials where each drug was used showed overall that salinomycin, monensin, and lasalocid were similar with respect to mortality and weight gain (Table 3). All three anticoccidials were included at both levels in four trials (Table 4). Lesion scores were significantly (P<.05) reduced in birds given salinomycin at 30 and 60 ppm,

monensin at 100 ppm, and lasalocid at 37.5 and 75 ppm in comparison to controls. The higher level of each compound was significantly (P<.05) more efficacious in controlling lesions than the lower level. The mortality among birds given monensin at 50 ppm was greater than the mortality in the other medicated treatments in two of the four tests, but the differences overall among medicated treatments were not significant. The differences between medicated treatments and control in mortality was significant (P<.05). The average gain for chicks given monensin at 50 ppm was significantly (P<.05) lower than the other medicated treatments. The differences in weight gains among the other medicated treatments were not significant. DISCUSSION Based upon the measurements of lesion scores, coccidiosis mortality, and weight gain, salinomycin at 60 ppm was a highly efficacious broad spectrum anticoccidial agent. Salinomycin at 60 ppm was comparable or superior to monensin at 100 ppm and lasalocid at 75 ppm, and at 30 ppm salinomycin showed greater overall activity than did monensin at 50 ppm or lasalocid at 37.5 ppm. The latter data do not support the use of these levels in commercial practice, but do indicate the relative potencies of the anticoccidial agents tested. ACKNOWLEDGMENT The technical assistance of Estel Arnold, Jr. and Richard Sweet is gratefully acknowledged.

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Treatment

No. of tests

63.3 135.3 85.3 100.7 96.2 b

Weight gain (g) E. necatrix, E. tenella E. acervulina, E. maxima E. brunetti, E. tenella E. maxima, E. brunetti Average

.5*

266.7 220.3 227.7 230.3 236.2 a

0 0 2 0

1.16 1.02 1.44 1.44 1.26b

30

0 0 0 0 0*

.06 .40 .28 .46 .30 a

60

276.7 259.3 286.7 274.3 274.2 a

Salinomyci in

78.0 140.0 104.7 253.7 144. l b

7 0 9 0 4a

2.52 1.84 2.10 1.28 1.94 c

50

a,b,c, Averages within parameters with the same superscript are not significantly different at the 5% level.

17 0 11 8 9b

2.38 1.95 2.02 1.86 2.05 c

Mortality E. necatrix, E. tenella E. acervulina, E. maxima E. brunetti, E. tenella E. mdxima, E. brunetti Average

Lesion scores E. necatrix, E. tenella E. acervulina, E. maxima E. brunetti, E. tenella E. maxima, E. brunetti Average

Eimeria spp.

Infected nonmedicated Mon

TABLE 4. Efficacy of salinomycin, monensin, and lasalocid against various Eimeria

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MIGAKI ET AL.

1196 REFERENCES

Reed, P. W., and H. A. Lardy, 1972. A23187: A divalent cation ionophore. J. Biol. Chem. 247: 6970-6977. Reid, W. M., J. Johnson, and J. Dick, 1975. Anticoccidial activity of lasalocid in control of moderate and severe coccidiosis. Avian Dis. 19:12—18. Ruff, M. D., W. M. Reid, and A. P. Rahn, 1976. Efficacy of different feeding levels of monensin in the control of coccidiosis in broilers. Amer. J. Vet. Res. 37:963-967. Shumard, R. F., and M. E. Callender, 1967. Monensin, a new biologically active compound. VI. Anticoccidial activity. Antimicrob. Agents and Chemother., 369-377.

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Chappel, L. R., 1977. Unpublished data. Danforth, H. D., M. D. Ruff, W. M. Reid, and R. L. Miller, 1977. Anticoccidial activity of salinomycin in battery raised broiler chickens. Poultry Sci. 56:926-932. Johnson, J., and W. M. Reid, 1970. Anticoccidial drugs: Lesion scoring techniques in battery and floor-pen experiments with chickens. Exp. Parasitol. 2 8 : 3 0 - 3 6 . Kinashi, H., N. Otake, H. Yonehara, S. Sato, and Y. Saito, 1973. The structure of salinomycin, a new member of the polyether antibiotics. Tetrahedron Letters 49:4955-4958. Mitrovic, M., and E. G. Schildknecht, 1974. Anticoccidial activity of lasalocid (X-537A) in chicks. Poultry Sci. 53:1448-1455. Mitani, M., T. Yamanishi, and Y. Miyazaki, 1975. Salinomycin: A new monovalent cation ionophore.

Biochem. Biophysical Res. Comm. 66:1231-1236. Miyazaki, Y., M. Shibuya, H. Sugawara, O. Kawaguchi, C. Hirose, J. Nagatsu, and S. Esumi, 1974. Salinomycin, a new polyether antibiotic. J. Antibiotics 2 7 : 8 1 4 - 8 2 1 .