Activity of Levamisole, Pyrantel Tartrate, and Rafoxanide Against

OF WASHINGTON, VOLUME 38, NUMBER 2, JULY 1971 203

Activity of Levamisole, Pyrantel Tartrate, and Rafoxanide Against Two Thiabendazole-tolerant Isolates of Haemonchus contortus, and Two Species of Trichostrongylus, in Sheep

M. L. COLGLAZIER, K. C. KATES, AND F. D. ENZIE National Animal Parasite Laboratory, Veterinary Sciences Research Division, ARS, USDA, Beltsville, Maryland 20705

ABSTRACT: The activity of 3 of the newer anthelmintics against two local thiabendazole-tolerant isolates of Haemonchus contortus (BPL-2 and AH-2), as well as against Trichostrongylus axei and T. colubriformis, was compared in experimentally infected lambs, using the method of the controlled anthelmintic test. Twenty of the 40 lambs on test were each given per os 5,000 infective larvae of the BPL-2 isolate of H. contortus, and the other 20 were given 5,000 infective larvae of the AH-2 isolate. Also, each lamb was given 18,000 T. axei and 18,000 T. colubriformis infective larvae. Single doses of the test drugs were given to the appropriate groups of lambs 21 clays postinfection, and all lambs were killed for worm counts 6 to 7 days later. Levamisole was given at 8ing/kg of body weight, pyrantel tartrate at 25 mg/kg, and rafoxanide at 5 mg/kg. All 3 anthelmintics were markedly effective (99-100%) against the 2 isolates of H. contortus. Levamisole was very effective also (95-99%) against the 2 species of Trichostrongylus. Pyrantel tartrate was highly effective against T. axei (99%), but substantially less effective (67%) against T. colubriformis. Rafoxanide showed no activity against Trichostrongylus spp.

Previously, we reported (Colglazier, Kates, nematodes of sheep by Cornwell and Jones and Enzie, 1970) that 2 isolates of H. contortus (1969). There is only one report on the ac- from sheep showed tolerance to the standard tivity of rafoxanide against H. contortus (Eger- therapeutic dose of thiabendazole, and that 1 ton, Yakstis, and Campbell, 1970). This drug isolate (AH-2) was more tolerant than the is also active as a fasciolicide (Campbell, other (BPL-2). The literature on thiabendazole- Ostlincl, and Yakstis, 1970). resistant strains of H. contortus has been summarized (Smeal et al, 1968; Theodorides, Scott, Materials and Methods and Laderman, 1970; Colglazier et al., 1970). In related observations, Kates et al. (1971) Protocol of the controlled and Theodorides et al. (1970) found that anthelmintic test thiabendazole-tolerant strains of PI. contortus The 40 Polled Dorset lambs were raised were also resistant to parbendazole, another parasite-free except for insignificant infections benzimidazole compound. of Strongyloides papillosus and coccidia. At Because of the apparent widespread occur- the start of the experiment the lambs had a rence of thiabendazole- and parbenclazole-tol- mean age of about 8 months and a mean erant strains of H. contortus, it seemed desir- weight of about 40 kg. An equal number of able to determine the efficacy of some of the wether and female lambs were used, and the newer anthelmintics against 2 local thiabenda- two sexes were divided as equally as possible zole-tolerant isolates. It seemed appropriate among the experimental groups. Lambs were also to determine concurrently the action of also allocated to the experimental groups so these compounds against 2 common pathogenic- that the group mean weights were approxi- species of Trichostrongylus. mately the same. The test drugs were levamisole, pyrantel Each of 20 lambs (divided into 4 equal tartrate, and rafoxanide. All have shown sig- groups) was given by mouth 5,000 infective nificant activity against H. contortus, but none larvae of the BPL-2 isolate of H. contortus and has been tested extensively against thiabenda- 18,000 T. axei and 18,000 T. colubriformis in- zole-tolerant strains of the parasite. The sig- fective larvae, a total of 41,000 larvae per nificant literature on levamisole was recently lamb. The other 20 lambs were grouped and summarized by Kates et al. (1971), and that infected similarly with the AH-2 isolate of H. on pyrantel tartrate against gastrointestinal contortus and the 2 species of Trichostrongylus.

The origin of the two isolates of H. contortm was previously given by Colglazier et al. (1970). The larvae of Trichostrongylus spp. were of bovine origin. One group of 5 lambs for each isolate of H. contortiis served as un- medicated controls, and each of the other 3 groups was dosed with 1 of the 3 test drugs. Because all lambs were given equivalent infections of the two species of Trichostrongylus, the control and medicated groups for these species contained 10 lambs (Table 1). Before infecting the lambs, the freshly har- vested larvae were quantitated by making 10 representative counts of each larval suspension. From these counts the standard errors and 95% confidence intervals were calculated (Table 1). Appropriate quantities of the larval suspensions for each of the 3 nematode species were com- bined and given as a single dose to each lamb. During the course of this trial, the several groups of lambs were maintained in separate isolation pens and fed a standard maintenance ration. Single therapeutic doses of the appropriate anthelmintics were given to the test lambs 21 days postinfection as indicated below and in Table 1. All lambs were killed for worm counts 6 to 7 days later, using standard techniques as described by Colglazier et al. ? t£ (1970) and Kates et al. (1971). ss Anthelmintics used1 Levamisole, l-2,3,5,6-tetrahydro-6-phenylim- idazo (2,1-fr) thiazole hydrochloride: pure chemical for experimental use; American Cyan- amid Co., Princeton, New Jersey: 8 mg/kg of body weight. Pyrantel tartrate, trans-l-methyl-l,4,5,6-tetrahydro - 2 - [ (2-thienyl-vinyl) ] - pyrimidine tartrate: pure chemical for experimental use; Chas. Pfizer & Co., Terre Haute, Indiana: 25 mg/kg of body weight. Rafoxanide [3,5-diiodo-3/-chloro-4'-(p-chlorophenoxy)-salicylanilide]: 3.035% aqueous sus- +1 -fl pension for experimental use; Marck & Co., Rahway, New Jersey: 5 mg/kg of body weight. Results and Discussion The data (Table 1) show that all 3 anthelmintics under test were highly effective (99- 100%) against both thiabendazole-tolerant iso-

1 Mention of products used in this study does not con- stitute endorsement by the USDA.

Copyright © 2011, The Helminthological Society of Washington OF WASHINGTON, VOLUME 38, NUMBER 2, JULY 1971 205 lates of PI. contortus. This finding contrasts Literature Cited markedly with the results obtained against these Campbell, W. C., D. A. Ostlind, and J. J. Yak- isolates with thiabendazole (Colglazier et al., stis. 1970. The efficacy of 3,5-diiodo-3'-chloro- 1970). In. the latter report, aggregate data 4'-(?>clilorophenoxy)-salicylani]ide against im- from 3 trials showed that at the standard dose mature Fasciola hepatica in sheep. Res. Vet. rate of 50 mg/kg of body weight, thiabendazole Sci. 11: 99-100. removed only 67% of the BPL-2 isolate of H. Colglazier, M. L., K. C. Kates, and F. D. Enzie. contortus and only 39% of the AH-2 isolate 1970. Comparative response of two ovine iso- from experimentally infected lambs. It is ap- lates of Haemonchus contortus to thia- parent, therefore, that the 3 newer drugs used bendazole. J. Parasit. 56: 768-772. in the present trial should prove useful in treat- Cornwell, R. L. 1966. Controlled laboratory trials in sheep with the anthelmintic pyrantel ing sheep infected with these, and perhaps tartrate. Vet. Rec. 79: 590-594. other, thiabendazole-resistant strains of liae- -, and R. M. Jones. 1969. Continuous low monchus. level feed administration of pyrantel tartrate Rafoxanide is primarily a fasciolicide (Camp- in lambs. I. Prophylaxis of experimental T. bell et al., 1970), although it has activity also colubriformis infections. Brit. Vet. J. 125: against H. contortus (Egerton et al., 1970). 235-238, Our data show that this compound was inef- Egerton, J. R., J. J. Yakstis, and W. C. Campbell. fective against T. axei and T. colubriformis (0 1970. The efficacy of rafoxanide [3,5-diiodo- 3'-chloro-4'- (p-chlorophenoxy) salicylanilide] and 13%, respectively); thus, it has only against Haemonchus contortus in sheep. Res. limited usefulness against gastrointestinal Vet. Sci. 2: 382-384. nematodes of sheep. Levamisole showed excel- Gibson, T. E., and J. W. Parfitt. 1968. An lent activity against both species of Tricho- evaluation of the anthelmintic pyrantel tar- strongijlus in this trial (95 and 99%), which trate using the improved controlled test. Brit. confirms numerous reports in the literature. Vet. J. 124: 69-71. Pyrantel tartrate was highly active (99%) Kates, K. C., M. L. Colglazier, F. D. Enzie, I. L. against T. axei, but it was much less effective Lindahl, and G. Samuelson. 1971. Com- parative activity of thiabendazole, levamisole, (67%) against the intestinal species, T. colubri- and parbendazole against natural infections formis. Our results with pyrantel tartrate of helminths in sheep. J. Parasit. 57: 356-362. against T. colubriformis did not compare favor- Smeal, M. G., P. A. Gough, A. R. Jackson, and ably with those reported by other investigators. I. K. Hotson. 1968. The occurrence of Corn well (1966), using dosages of 25 and 45 strains of Haemonchus contortus resistant to mg/kg, obtained more than 90% removal of thiabendazole. Austral. Vet. J. 44: 108-109. Theodorides, V. J., G. C. Scott, and J. Lader- adult worms; and at the 25-mg dose level, man. 1970. Strains of Haemonchus con- Gibson and Parfitt (1968) reported 80% re- tortus resistant against benzimidazole anthel- moval of 28-day-old infections of this species. mintics. Am. J. Vet. Res. 31: 859-863.