Veterinary Parasitology, 34 (1990) 289-294 289 Elsevier Science Publ ishers B.V., Amsterdam - - Pr in ted in The Netherlands

Prel iminary Trials Using a Macrocyclic Lactone Against Psoroptic Scabies of Cattle

FRED C. W R I G H T

U.S. Department of Agriculture, Agricultural Research Service, Knipling-Bushland U.S. Livestock Insects Research Laboratory, P.O. Box 232, KerrviUe, TX 78029-0232 (U.S.A.)

(Accepted for publication 2 March 1989)

A B S T R A C T

Wright, F.C., 1990. Pre l iminary trials using a macrocyclic lactone against psoroptic scabies of cattle. Vet. Parasitol., 34: 289-294.

A macrocyclic lactone, LL-F28249o~, C36H520s, was evaluated as a one- or two-injection treat- ment in different formulations and concentrations against cattle infested with Psoroptes ovis (Hering) . One inject ion of 2 mg kg - 1 or two injections of 1 mg kg - 1 of 3 % active material in either an aqueous or oil formulation failed to el iminate all of the mites. A single injection of 3 mg kg- as a 5% aqueous formulation el iminated all mites for 35 days post-injection. At lower dosages of the aqueous formulat ion (3%), the male mites appeared to be less susceptible to the acaricide t han ei ther the female or immature mites.

I N T R O D U C T I O N

Psoroptic scabies of cattle is caused by the astigmatoid mite Psoroptes ovis (Hering). The emphasis placed on the control of these mites has been reduced, but these mites continue to have the potential to create severe problems in the cattle industry (Tobin, 1962; Clymer, 1978; Fisher and Wright, 1981; Cole et al., 1984). At present, three acaricidal dips and one injectable compound are approved for use against psoroptic scabies of cattle and sheep in the U.S.A. by the Animal Plant Health Inspection Service, U.S. Department of Agriculture. The approved dips are coumaphos at 0.28-0.32%, phosmet at 0.15-0.25% and hot lime-sulfur at 2.0%. The injectable material, ivermectin, is approved for use at 200/tg kg-1 of body weight. Ivermectin is a broad-spectrum parasiticide that controls internal as well as external parasites of livestock (Egerton et al., 1980; Chabala et al., 1980; Meleney et al., 1982; Drummond, 1985 ). Ivermectin is one of the avermectins and is known more precisely as 22,23-dihydroaver- mectin B1.

Recently, another series of compounds, which are related to the avermectins

290 F.C. WRIGHT

(Burg et al., 1979) and milbemycins (Yamamoto et al., 1981), have shown potential as acaricides (Carter et al., 1987; Wood et al., 1987a). These com- pounds, which are macrocyclic lactones and designated LL-F28249, are fer- mentat ion products of the act inomycete Streptomyces cyaneogriseus sp. non- cyanogenus and were isolated from a soil sample from southern Australia (Greenstein et al., 1987). The avermectins are produced by Streptomyces avermitilis (Burg et al., 1979) and the milbemycins by Streptomyces hygros- copicus sp. aureolacrimosus (Yamamoto et al., 1981). One of the more prom- ising of these new compounds has been designated LL-F28249c~ and has the chemical formula C3GH~2Os (Pankavich et al., 1987; Wood et al., 1987b ). Since there is a continuing threat of psoroptic scabies outbreaks in the U.S.A. and elsewhere, it is important that additional acaricides be available should they be needed in the fight against this destructive disease. Therefore, the objective of this study was to test the efficacy of LL-F28249c~ against psoroptic scabies of cattle.

MATERIALS AND METHODS

Sixteen heifers, 6-8 months old and of similar weight, were purchased at a local auction. Upon arrival at the laboratory, all were dipped in 0.3% couma- phos to relieve any ectoparasitic burdens such as ticks, lice and chorioptic mites. Ten days later, the cattle were placed in anti-grooming stanchions in a research barn and were manually infested with ~ 500 P. ovis collected from a donor an- imal (Riner and Wright, 1981 ). The infestations developed slowly on a few of the animals, so some were infested more than once. The infestations were al- lowed to develop undisturbed for 7 weeks. The area involved with lesions was determined by outlining the infested region on a map of the animal divided into grids (Guillot, 1981). Two pre- t rea tment skin scrapings for mites were taken (6.45 cm 2 from each side of the animal in the lesion area) and the num- bers of eggs, adult males, females and immatures found upon microscopic ex- aminat ion of these scrapings were recorded (Guillot and Meleney, 1982 ). Ac- tual numbers of mites and eggs were counted in each skin scraping or until the number of total mites reached 500.

The animals were randomly assigned to six groups of two animals each and one group of four animals (control). The cattle in Groups 1-6 were inoculated subcutaneously (SC) behind the right shoulder with a formulation of LL- F28249a supplied by American Cyanamid (Princeton, NJ) . Three formula- tions of the material were t e s t e d - an aqueous (glycerol) formulation, an oil formulation and a glycerol formal-propylene glycol formulation similar to that of ivermectin. Group 1 cattle were given one inoculation of 2 mg k g - ' using the 3% aqueous formulation. Group 2 cattle were given two inoculations of 1 mg kg- 1, 9 days apart, using the 3% aqueous formulation. Group 3 cattle were given one inoculation of 3 mg kg-1 using the 5% aqueous formulation. Group

MACROCYCLIC LACTONE AGAINST BOVINE PSOROPTIC SCABIES 291

4 cattle were given one inoculation of 2 mg kg-1 using the 3% oil formulation. Group 5 cattle were given two inoculations of 1 mg kg -1, 9 days apart, using the 3% oil formulation. Group 6 cattle were given one inoculation of 2 mg kg-1 using the 5% glycerol formal-propylene glycol formulation. Group 7 cattle served as untreated controls.

Two skin scrapings (one from each side of the animal) were taken from each animal 3, 7, 10, 14 and 21 days after the initial injection. Group 3 animals were also sampled 28, 35 and 42 days post-injection (p.i.). Two of the Group 7 ani- mals were also sampled 28 days p.i. Counts of mites and eggs were made and the percent mortality of the males, females and immatures, and number of eggs in the samples, were determined and compared among treatment groups.

R E S U L T S

The average pre-treatment weight of the heifers was 172.9 kg and lesions covered ~ 43.4% of their bodies. Table 1 shows the effect of the various treat- ments on egg production and mortality of mites throughout the study.

T A B L E 1

Percent mortality and egg counts ofPsoroptes ovis on cattle in various groups treated with a macrocyclic lactone (LL-F28249o~)

Days Treatment group post-treated

1 a 2 b 3 c 4 d 5 e 6 f 7 g

Percent mortality 0 1.8 5.1 1.3 1.3 1.8 1.4 1.9

3 68.2 59.2 73.3 32.6 19.5 66.2 4.4

7 97.5 74.8 98.4 60.5 21.3 17.4 3.8

10 98.6 50.1 100.0 55.6 31.1 21.5 6.8

14 68.8 54.5 100.0 34.2 48.7 34.1 7.2

21 73.3 54.4 100.0 20.8 58.3 11.7 10.2

28 - - 100.0 - 4.2

35 - 100.0 -

42 - 99.8 -

Ave rage egg counts per animal 0 388 357 760 930 512 573 427

3 47 24 34 42 244 92 653

7 15 1 4 4 15 195 262

10 6 1 8 2 17 123 186

14 2 1 1 0 1 144 440

21 2 47 1 46 3 216 313

28 - - 0 - - 445 35 - - 1 -

42 - - 0 -

nOne inoculation of 2 mg kg -1 3% aqueous SC; btwo inoculations of 1 mg kg -1 3% aqueous SC; Cone inoculation of 3 mg k g - 15 % aqueous SC; done inoculation of 2 mg k g - ~ 3 % oil SC; etwo inoculations of 1 m g k g - 1 3% oil SC; fone inoculation of 2 mg k g - ~ 5 % glycerol formal-propylene glycol SC; guntreated control.

292 F.C. WRIGHT

TABLE 2

Average live and dead male, female and immature mites on Group 1 animals after exposure to one injection of 2 mg kg -1 LL-F28249ol as 3% aqueous formulation

Days Males Females Immatures post - t rea tment

Live Dead Live Dead Live Dead

0 107 8 153 6 722 9 3 56 76 74 97 200 532 7 4 67 6 210 12 445

10 6 49 2 299 4 491 14 76 19 0 98 1 53 21 25 3 3 63 3 19

Of the three groups (1, 2 and 3 ) treated with the aqueous formulation, only the animals in Group 3 (3 mg kg -1 in a 5% formulation) were found to be free of mites. However, one live male mite was found 42 days p.i. and two eggs were found in the 35-day sample. The eggs from the 35-day sample were incubated, but failed to hatch. The population of live mites on Group 1 animals (2 mg kg-1 in a 3% formulation) was reduced greatly by 10 days p.i., but the popu- lation then increased. Egg counts were reduced, but not eliminated. The mor- tality of the different life stages was essentially the same at 7 days p.i. ( ~ 95% ). However, the mortality of male mites fell to 20% by 14 days p.i., but both females and immatures had high mortality until the 21-day p.i. samples (Table 2). One injection of 1 mg kg -1 of the 3% formulation (Group 2) pro- duced~ 75% mortality by 7 days p.i., but the second injection at 9 days p.i. did not further reduce the population. By 21 days p.i., egg counts were also begin- ning to increase.

Neither of the groups (4 and 5 ) receiving the 3% oil-based formulation were free of mites during the study. Egg counts were reduced initially, but were increasing at the end of the sampling period.

The mite population on the animals treated with the 5% ivermectin-type formulation (Group 6 ) was reduced initially, but recovered rapidly. Egg counts remained relatively high throughout the study.

DISCUSSION

Since cattle and sheep with psoroptic scabies are quarantined in the U.S.A., the only acaricides approved for use are those which kill all of the mites on the animals with either one or two treatments, generally 10 days apart. Therefore, complete elimination of all mites and eggs by candidate acaricides must be accomplished before those compounds can be considered.

Of the formulations and concentrations of LL-F28249c~ tested, one injection

MACROCYCLIC LACTONE AGAINST BOVINE PSOROPTIC SCABIES 293

at 3 mg kg -1 of the 5% aqueous formulation gave the best results (Group 3), achieving a complete kill of the mites. The one live mite discovered on the last sampling day could have come from possible contamination. Additional sam- ples scraped from the most productive site, as determined by visual examina- tion on each side of this animal, failed to produce further live mites. No eggs were found on the last sampling day and those found on Day 35 p.i. did not hatch. Thus, the effect of this compound on the production of eggs appeared to be similar to that seen when cattle infested with these mites were treated with ivermectin (Guillot and Wright, 1984; Wright and Guillot, 1984). In the previous studies, ivermectin produced a 96% decline in the number of eggs 3 days p.i. The present study showed a 95% decline in eggs 3 days after injection (Table 1 ).

The aqueous formulation produced higher kills of mites at similar dosages than did the oil or ivermectin-type formulations. Mite mortality with the oil formulation increased more slowly and never achieved the control given by the aqueous formulation. Results with the ivermectin-type formulation were sim- ilar to those with the oil formulation. Since formulations of acaricides are so critical to absorption and effectiveness, this is an area where additional re- search is needed. Ivermectin, when administered as an injection against pso- roptic scabies of cattle, is approved at a dosage of 200/~g kg -1. This is 15-fold less than the concentration required in our study, but with an appropriate formulation this gap may be reduced. At a dosage of 3 mg kg -1, LL-F28249a would have to be formulated at a much higher concentration than 5%, so that the volume required to treat a grown animal ( ~ 400 kg) would be less than the bulky 24 ml now required.

A possible sex difference in the susceptibility of the mites to one injection of 2 mg kg -1 of the 3% aqueous formulation was detected (Group 1). After an initial peak in percent kills for all life stages, the mortality of the male mites was reduced rapidly and they were killed less rapidly than the females and immatures. This was not observed using the same formulation with two injec- tions of I mg kg- 1 of the 3% material or with one injection of 3 mg kg- ~ of the 5 % material. No sex differences in relation to susceptibility were detected with the other formulations. However, the overall percent mortality of all life stages of mites with other treatments was also much less.

Even though LL-F28249a required a high dose level (in relation to ivermec- tin) to be fully effective against psoroptic scabies of cattle, it does exhibit po- tential as a possible acaricide for the control of P. ovis. Additional research should be carried out to test the effectiveness of this material in other formu- lations against scabies mites and other ectoparasites.

ACKNOWLEDGMENTS

The technical assistance of Jayme C. Riner is gratefully acknowledged. I also thank Dr. Irwin B. Wood, American Cyanamid Company, Princeton, NJ, for supplying the acaricide used in the study and for preparing the injections.

294 F.C. WRIGHT

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