Moxidectin: systemic activity against common cattle grubs (Hypoderma lineatum) (Diptera: Oestridae) and trichostrongyle nematodes in cattle

Veterinary Parasitology, 41 (1992) 203-209 Elsevier Science Publishers B.V., Amsterdam

203

Moxidectin: systemic activity against common cattle grubs (Hypoderma lineatum) (Diptera: Oestridae) and trichostrongyle nematodes in cattle* ** P.J. Scholl, F.S. Guillot 1 and G.T. Wang 2 US Department of Agriculture, Agricultural Research Service, Knipling-Bushland US Livestock Insects Research Laboratory, P.O. Box 232, Kerrville, TX 78029, USA (Accepted 18 September 1991 )

ABSTRACT Scholl, P.J., Guillot, F.S. and Wang, G.T., 1992. Moxidectin: systemic activity against common cattle grubs (Hypoderma lineatum) (Diptera: Oestridae) and trichostrongyle nematodes in cattle. Vet. Parasitol., 41: 203-209. Moxidectin, a systemic insecticide, was evaluated for its efficacy against the migrating first instars of the common cattle grub, Hypoderma lineatum, and against nematode egg production in beef cattle. It was observed that all three levels (0.1,0.2 and 0.4 mg moxidectin kg- ~) were 100% effective against cattle grubs when administered as a s.c. injection. The same levels of treatment were very effective (90-100%) in reducing trichostrongyle nematode egg production. However, there was a slight indication that at least one species, Cooperia oncophora, was not completely eliminated, as it was observed that small numbers of eggs began to appear after 2 weeks post-treatment when there had been no opportunity for reinfection.

INTRODUCTION

Moxidectin is a macrocyclic lactone endectocide which is derived from the actinomycete Streptomyces cyaneogriseus noncyanogenus. A 1% cattle injectable formulation of this c o m p o u n d is under development by American Cyanamid Company for the control of both internal and external parasites of *This paper reports the results of research only. Mention of a pesticide or a proprietary product does not constitute a recommendation for use by the USDA, nor does it imply registration under the Federal Insecticide, Fungicide and Rodenticide Act as amended. **In cooperation with American Cyanamid Co., Princeton, N J, Agreement No. 58-7mnl-8-106. Ipresent address: Department of Entomology, Louisiana State University, Baton Rouge, LA 70803, USA. 2Present address: Agricultural Research Division, American Cyanamid Co., Princeton, NJ 08540, USA.

© 1992 Elsevier Science Publishers B.V. All rights reserved 0304-4017/92/$05.00

204

P.J. SCHOLLE3"AL.

beef cattle. This research was part of a series of experiments designed to determine the optimal dose of moxidectin for the control of external parasites of beef cattle. Since the experimental animals also harbored a natural infection of gastrointestinal parasites, egg counts in fecal samples were also included to monitor the efficacy of moxidectin against nematode egg production. MATERIALS A N D M E T H O D S

Twenty-eight Hereford heifer calves were purchased from a single source near Stonewall, Texas. Weights averaged 177 kg, with a range of 131-227 kg. Endoparasites were acquired through natural infections. Based on fecal egg counts, the calves were infected with trichostrongyles, Nematodirus spp., whipworms ( Trichuris spp. ) and tapeworms (Moniezia spp. ). Calves were infested with common cattle grubs, Hypoderma lineatum (Villers), from 6 to 21 January 1988, using a controlled, natural infestation technique modified from Weintraub ( 1961 ). Female warble flies were tethered and mated to beheaded males, and allowed to oviposit on the hairs along the backline of stanchioned animals. Spermathecae of mated flies were removed to check for fertilization following oviposition. After 5 days in a controlled-temperature environment (about 30°C), the hair with the attached eggs was clipped from the animal to determine the status of egg hatching. All hatched larvae were assumed to have entered the animal. Animals were ranked from heaviest to lightest infestations of H. lineatum and blocked by this criterion into groups of four animals. Each member of a ranked block of four animals was randomly assigned to one of four treatment groups of seven animals each to insure a balanced grub infestation challenge among the treatments (Table 1). On 7 June 1988, the seven animals in each of Groups 1, 2 and 3 were s.c. injected in the neck, anterior to the left shoulder blade, with moxidectin 1% TABLE 1 Summary of animal weights, dose volumes, grub larvae infestations and trichostrongyle egg counts on Day 0 Group Moxidectin (mg kg ~body weight)

Mean Moxidectin Grub Trichostrongyle egg weight (kg) 1% injectable larvae count per 3 g (ml per animal) per animal Range Mean _+SE

1 2 3 4

166.3 175.3 181.6 177.2

0.4 0.2 0.1 0

SE, standard error.

6.65 3.51 1.82 3.62

68-182 90-191 53-178 70-186

28- 664 17- 810 153- 628 24-1180

318__ + 81.8 498__ + 87.5 466_+ 73.1 406+136.6

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EFFICACY OF MOXIDECTIN AGAINST CATTLE GRUBS

injectable at 0.4, 0.2 or 0.1 mg moxidectin kg-1 body weight, respectively. Group 4 animals were injected with a blank carrier at a dose volume of 1 ml per 50 kg body weight. Recording of warbles appearing on the back of animals began on 18 August 1988, based on a calculated average of 237 days post-infestation to the date of first grub cut. Grub counts continued every 2 weeks until 9 January 1989. The peak warble count, which represented the total number of grubs coming to the back of each animal, was recorded. Fecal samples were taken from the rectum to ensure freshness and to avoid possible contamination from other animals. Nematode egg production was measured at 20 and 7 days before treatment, and at 0, 3, 7, 14, 87 and 148 days post-treatment. Animals remained in stanchions for 14 days post-treatment to prevent reinfection and were then returned to pasture. Three gram fecal samples were analyzed using the Wisconsin sugar double-flotation technique (Cox and Todd, 1962 ). Parasite eggs were differentiated into trichostrongyle group, Nematodirus spp., Trichuris spp. and Moniezia spp. (Soulsby, 1982). Geometric mean peak grub counts and geometric mean egg counts were used to calculate percent efficacy as follows Percent efficacy -

(control-treated) control

× 100

Animal grub counts and trichostrongyle egg production values were logarithmically transformed (log 10 ( x + 1 )) and data analyzed by a one-way analysis of variance (ANOVA). Means were compared by the least significant difference (LSD). Percent effectiveness was calculated by averaging the logarithmically transformed data and then back-transforming to obtain a treatment estimate. For the trichostrongyle egg counts, an 'optimal' dose of moxidectin was calculated by fitting a linear plateau model (Anderson and Nelson, 1984) to the data. TABLE 2 Titration of moxidectin 1o~/0injectable against H. lineatum Group

Moxidectin (mg kg- 1 body weight)

Mean larval infestation

1

0.4 0.2 0.1 0

113 134 111 118

2 3 4

*P
Geometric mean peak grub counts per animal (18 Sep. 1988-9 Jan. 1989)

Percent efficiency

0

100"

0 0 40.3

100" 100" -

Day - 7 31 May

211.6 (10-860) _+ 101.4

~Treatment is 7 June 1988. 2Animals placed on pasture. 3n=6.

Mean 3 Range SE

Group 4: Controls (n = 7)

272.3 (57-648) +70.6

Day 01 7 June

338.1 (31-1466) _+ 176.6

406.7 (24-1180) _+ 136.6

345.6 318.1 (53-1126) (28-664) +- 129.9 +_81.8 Group 2:0.2 m g kg-~ moxidectin 1% s.c. ( n = 7) Mean 3 335.9 433.3 498.3 Range (119-566) (129-714) (17-810) SE +-55.5 +-78.0 +_87.5 Group 3." 0.1 m g kg - ~ moxidectin l % s.c. ( n = 7) Mean 3 263.6 427.1 466.3 Range (77-512) (40-1069) (153-698) SE _+50.1 _+ 122.9 + 73.1

Mean 3 Range SE

Group 1:0.4 m g kg -1 moxidectin l% s.c. ( n = 7)

Day - 2 0 18 May

Summary of trichostrongyle egg count per 3 g sample

TABLE 3

22.9 (0-60) _+9.2

35.6 (3-116) _+ 14.5 342.3 (27-806) _+87.9

0.0 (0-0) _+0

0.0 (0-0) +_0

374.3 (24-1196) _+ 138.6

0.0 (0-0) +_0

Day + 7 14 June

0.0 (0-0) +_0

Day + 3 10 June

584.7 (22-1161) + 125.4

81.3 (0-188) _+23.9

13.7 (0-48) +_7.3

0.0 (0-0) _+0

Day + 142 21 June

231.4 (83-565) _+74.9

101.0 (0-260) +- 29.7

86.4 (32-167) _+ 19.6

129.3 (0-657) +82.1

Day + 8 7 2 September

563.1 (55-1110) + 140.6

172.0 (2-405) +- 65.7

145.0 (4-464) +_54.7

113.9 (0-427) _+59.9

Day + 148 28 October

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EFFICACY OF MOXIDECTIN AGAINST CATTLE GRUBS

207

RESULTS AND DISCUSSION

Moxidectin given at 0.1, 0.2 or 0.4 mg kg -1 body weight provided 100% efficacy against the c o m m o n cattle grub (Table 2 ). No warbles were observed arriving to the back of any treated calves during the observation period from mid-September to early January. However, every control animal had grub infestations during this same period with an average of 40.3 grub warbles per animal. Therefore, the m i n i m u m effective dose of moxidectin against H. lineatum is below 0.1 mg kg-~ and the c o m m o n cattle grub is not a limiting species for establishing the recommended dosage of moxidectin. Based on pre-treatment trichostrongyle egg counts, the nematode infections were considered to be moderate (Table 1 ). The degrees of Nematodirus spp. and Trichuris spp. infections were too low to allow the assessment of anthelmentic efficacy. Moxidectin at all doses tested was ineffective against tapeworms (Moniezia spp. ) and coccidia (Eimeria spp. ). There were no statistically significant pre-treatment differences in Day 0 egg counts ( P > 0.25 ). Moxidectin at 0.4 mg kg- 1 completely eliminated eggs from fecal samples for at least 2 weeks (Table 3 ). Eggs were not detectable in the 0.2 mg kg- 1 fecal samples for the first week post-treatment, but began to TABLE 4 Efficacy of moxidectin against trichostrongyle egg production Group

Geometric mean trichostrongyle egg counts ~

Moxidectin ( m g kg -1 body weight)

0 1 2 3 4

0.4 0.2 0.1 0

205 a 344 a 412 a 243 a

+3

+7

+14

+87

+148

36 a 72 a 49 a 159 a

25 b

0c 0c

0c 0c

0c 4c

20 b

12 b

41 b

220 a

237 a

392 a

72 ab 55 ab 393 a

~Trichostrongyle egg counts per 3 g fecal sample using the Wisconsin sugar double-flotation technique. On each day, m e a n s with the same superscript are not significantly different ( P > 0.05 ). TABLE 5 Percent efficacy o f moxidectin c o m p a r e d with control trichostrongyle egg counts Group

1 2 3 4

Moxidectin

0.4 0.2 0.1 0

Percent efficacy at days post-treatment 3

7

14

87

148

100 100 91 0

100 100 95 0

100 99 90 0

77 55 69 0

94 82 86 0

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P.J. SCHOLL ET AL.

appear in samples at low levels 14 days after treatment. Moxidectin at 0.1 mg kg- 1drastically reduced (Table 4 ) mean trichostrongyle eggs in fecal samples to below 20 the first week post-treatment and maintained very low egg counts throughout the 2 week study period. The non-treated controls maintained a relatively constant parasite burden, as indicated by a geometric mean of 159393 eggs per 3 g sample. When compared with the control egg counts (Table 5), moxidectin at 0.2 and 0.4 mg kg -1 achieved 99-100% efficacy against trichostrongyle nematodes for 2 weeks. Although the 0.1 mg kg-l group allowed a small amount of nematode egg production in the animals, the percent efficacy was still above 90% during the 2 week post-treatment period. Trichostrongyle egg counts increased slightly in all groups at 87 and 148 days post-treatment as reinfection occurred. Fecal samples were taken from the four animals (nos. 993, 51, 12 and 9) in the 0.2 mg kg-1 group producing low numbers of eggs on Day 14 (Table 3) and were sent to American Cyanamid in New Jersey for identification. The infective larvae from these samples were identified as Cooperia oncophora. CONCLUSION Moxidectin at 0.1,0.2 and 0.4 mg kg- 1was highly effective (100%) against

H. lineatum, the tzommon cattle grub, and trichostrongyle nematode egg production (90-100%); however, it was ineffective against tapeworms (Moniezia spp. ) and coccidia (Eimeria spp. ). Additionally, the finding of a low number of C. oncophora eggs in four animals in Group 2 on Day 14 post-treatment may indicate that, at least for this species, the effect of the drug on the nematodes may not cause 100% elimination. Since the animals were stanchioned during this period, there was not opportunity for reinfection during the first 14 days. Therefore, at least for Cooperia spp., the higher dose may be required in order to achieve 100% efficacy against all trichostrongyle species. ACKNOWLEDGEMENTS We thank C.C. Barrett, D. Ingenhuett, J.J. Matter and B.K. Shelley of this laboratory for technical support during the course of this study; also A.R. Silverberg, Information Services, and H. Berg, Clinical Laboratory, American Cyanamid Company, Princeton, New Jersey, for statistical analysis and nematode identification services, respectively. REFERENCES Anderson,R.L. and Nelson, L.A., 1984. Recentdevelopmentsin the use of linear-plateaumodels to estimateresponserelationships. In: H.A. David and H.T. David (Editors), Statistics: An

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Appraisal. Proceedings of the 50th Annual Conference of the Iowa State Statistical Laboratory. Iowa State University Press, Ames, IA, pp. 371-392. Cox, D.D. and Todd, A.C., 1962. Survey of gastrointestinal parasitism in Wisconsin dairy cattle. J. Am. Vet. Med. Assoc., 141: 706-709. Soulsby, E.J.L., 1982. Helminths, Arthropods and Protozoa of Domesticated Animals. 7th Edn. Lea and Febiger, Philadelphia, and Ballibre Tindall, London, 809 pp. Weintraub, J., 1961. Inducing mating and oviposition of the warble flies Hypoderma bovis (L). and H. lineatum (De Viii. ) (Diptera: Oestridae) in captivity. Can. Entomol., 93:149-156.