An eprinomectin extended-release injection formulation providing nematode control in cattle for up to 150 days.

A series of 10 dose confirmation studies was conducted to evaluate the persistent activity of an extended-release injectable (ERI) formulation of eprinomectin against single point challenge infections of gastrointestinal and pulmonary nematodes of cattle. The formulation, selected based on the optimal combination of high nematode efficacy, appropriate plasma profile, and satisfactory tissue residue levels, includes 5% poly(D,L-lactide-co-glycolic)acid (PLGA) and is designed to deliver eprinomectin at a dose of 1.0mg/kg bodyweight. Individual studies, included 16-30 cattle blocked based on pre-treatment bodyweight and randomly allocated to treatment with either ERI vehicle or saline (control), or the selected Eprinomectin ERI formulation. Treatments were administered once at a dose volume of 1 mL/50 kg bodyweight by subcutaneous injection in front of the shoulder. In each study, cattle were challenged with a combination of infective stages of gastrointestinal and/or pulmonary nematodes 100, 120 or 150 days after treatment and were processed for parasite recovery according to standard techniques 25-30 days after challenge. Based on parasite counts, Eprinomectin ERI (1mg eprinomectin/kg bodyweight) provided >90% efficacy (p<0.05) against challenge with Cooperia oncophora and Cooperia surnabada at 100 days after treatment; against challenge with Ostertagia ostertagi, Ostertagia lyrata, Ostertagia leptospicularis, Ostertagia circumcincta, Ostertagia trifurcata, Trichostrongylus axei, and Cooperia punctata at 120 days after treatment; and against challenge with Haemonchus contortus, Bunostomum phlebotomum, Oesophagostomum radiatum and Dictyocaulus viviparus at 150 days after treatment. Results of a study to evaluate eprinomectin plasma levels in cattle treated with the Eprinomectin ERI formulation reveal a characteristic second plasma concentration peak and a profile commensurate with the duration of efficacy. These results confirm that the Eprinomectin ERI formulation can provide high levels of parasite control against a range of nematodes of cattle for up to 5 months following a single treatment.

Nematode burdens of pastured cattle treated once at turnout with eprinomectin extended-release injection.

The efficacy of eprinomectin in an extended-release injection (ERI) formulation was evaluated against infections with third-stage larvae or eggs of gastrointestinal and pulmonary nematodes in cattle under 120-day natural challenge conditions in a series of five studies conducted in the USA (three studies) and in Europe (two studies). For each study, 30 nematode-free (four studies) or 30 cattle harboring naturally acquired nematode infections (one study) were included. The cattle were of various breeds or crosses, weighed 107.5-273 kg prior to treatment and aged approximately 4-11 months. For each study, animals were blocked based on pre-treatment bodyweight and then randomly allocated to treatment: ERI vehicle (control) at 1 mL/50 kg bodyweight or Eprinomectin 5% (w/v) ERI at 1 mL/50 kg bodyweight (1.0 mg eprinomectin/kg) for a total of 15 and 15 animals in each group. Treatments were administered once on Day 0 by subcutaneous injection in front of the shoulder. In each study, all animals grazed one naturally contaminated pasture for 120 days. At regular intervals during the studies, fecal samples from all cattle were examined for nematode egg and larval counts. In four studies pairs of tracer cattle were used to monitor pasture infectivity at 28-day intervals before and/or during the grazing period. All calves were weighed before turnout onto pasture and at regular intervals until housing on Day 120. For parasite recovery, all study animals were humanely euthanized 27-30 days after removal from pasture. Cattle treated with Eprinomectin ERI had significantly (p<0.05) fewer strongylid eggs (≤1 egg per gram; egg count reduction≥94%) than the control cattle and zero lungworm larvae at each post-treatment time point. At euthanasia, cattle treated with Eprinomectin ERI had significantly (p<0.05) fewer of the following nematodes than the ERI vehicle-treated (control) cattle with overall reduction of nematode counts by >92%: Dictyocaulus viviparus (adults and fourth-stage larvae (L4), Bunostomum phlebotomum, Cooperia curticei, Cooperia oncophora, Cooperia punctata, Cooperia surnabada, Cooperia spp. inhibited L4, Haemonchus contortus, Haemonchus placei, Haemonchus spp. inhibited L4, Nematodirus helvetianus, Nematodirus spp. inhibited L4, Oesophagostomum radiatum, Oesophagostomum spp. inhibited L4, Ostertagia leptospicularis, Ostertagia lyrata, Ostertagia ostertagi, Ostertagia spp. inhibited L4, Trichostrongylus axei, Trichostrongylus colubriformis, Trichostrongylus spp. inhibited L4, Trichuris discolor, and Trichuris ovis. Over the 120-day grazing period, Eprinomectin ERI-treated cattle gained between 4.8 kg and 31 kg more weight than the controls. This weight gain advantage was significant (p<0.05) in three studies. All animals accepted the treatment well. No adverse reaction to treatment was observed in any animal in any study.

Therapeutic efficacy of eprinomectin extended-release injection against induced infections of developing (fourth-stage larvae) and adult nematode parasites of cattle.

The therapeutic efficacy of eprinomectin in an extended-release injection (ERI) formulation was evaluated against induced infections of developing fourth-stage larval or adult gastrointestinal and pulmonary nematodes of cattle in a series of six studies under two identical protocols (three each for developing fourth-stage larvae or adults) conducted in the USA, Germany or the UK (two studies at each location, one per stage). Each study initially included 16 nematode-free cattle. The cattle were of various breeds or crosses, weighed 109-186.5 kg prior to treatment, and were approximately 4-7 months old. The animals were blocked based on pre-treatment bodyweight and then randomly allocated to treatment: eprinomectin ERI vehicle (control) at 1 mL/50 kg body weight or eprinomectin 5% ERI at 1 mL/50 kg bodyweight (1.0 mg eprinomectin/kg) for a total of eight and eight animals in each group. Treatments were administered once on Day 0 by subcutaneous injection in front of the shoulder. In each study, cattle were infected with a combination of infective third-stage larvae or eggs of gastrointestinal and pulmonary nematodes. Inoculation was scheduled so that the nematodes were expected to be fourth-stage larvae or adults at the time of treatment. For parasite recovery, all study animals were humanely euthanized and necropsied 14-15 (adult infections) or 21-22 days after treatment (developing fourth-stage larval infections). When compared with the vehicle-treated control counts, efficacy of eprinomectin ERI against developing fourth-stage larvae and adults was ≥98% (p<0.05) for the following nematodes: Dictyocaulus viviparus, Bunostomum phlebotomum, Cooperia curticei, C. oncophora, C. surnabada, C. punctata, Haemonchus contortus, H. placei, Nematodirus helvetianus, Oesophagostomum radiatum, Oes. venulosum, Ostertagia leptospicularis, O. ostertagi, O. circumcincta, O. pinnata, O. trifurcata (developing fourth-stage larval infections only), Strongyloides papillosus, Trichostrongylus axei, T. colubriformis, and Trichuris ovis (adult infections only). All animals accepted the treatment well. No adverse reaction to treatments was observed in any animal in any study.

Persistence of the activity of topical ivermectin against biting lice (Bovicola bovis).

To assess the persistence of the activity of topical ivermectin against a natural challenge with biting lice (Bovicola bovis), 90 mixed-breed cattle that had been treated to remove lice, were blocked by bodyweight within sex and randomly allocated to three treatments: untreated control, doramectin at 200 micrograms/kg by subcutaneous injection, and ivermectin at 500 micrograms/kg by topical application. Forty-five pens were blocked into three groups of 15, and the blocks of pens were randomly allocated to three 14-day challenge periods starting 21, 28 and 35 days after treatment. There were five pens per treatment for each challenge period, and one B bovis-infested donor calf was introduced into each pen containing two principal calves at the start of the challenge period for that block of pens. The calves were examined thoroughly for B bovis seven, 14 and 21 days after the introduction of the donors. There were no significant differences between the control and doramectin groups for the numbers of animals infested, or the geometric mean louse counts at the final examination for any of the challenge periods. At the final examination for each challenge period, the louse counts of the cattle treated with topical ivermectin were all zero, and significantly (P < 0.05) fewer cattle treated with topical ivermectin were infested than either the controls or cattle treated with doramectin.

Persistent efficacy of abamectin and doramectin against gastrointestinal nematodes of cattle.

OBJECTIVE: To assess the persistent activity of injectable formulations of abamectin and doramectin against gastrointestinal nematodes of cattle. DESIGN: Controlled slaughter study assessing residual efficacy. PROCEDURE: Nematode-free calves were treated with abamectin or doramectin (each at a dose of 200 micrograms/kg) and infections then induced with repeated doses of infective larvae of Trichostrongylus axei, Haemonchus placei, Ostertagia ostertagi and Cooperia species. The duration of challenge ranged from 14 to 28 days. The calves were slaughtered at either 38/39 or 45/46 days after the treatments and nematodes recovered from the gastro-intestinal tract. RESULTS: Significant reductions in numbers of O ostertagi occurred for both abamectin and doramectin treatments (> 93%) relative to counts in untreated calves, when challenge was administered up to 21 days after treatment. For T axei and Cooperia spp significant reductions occurred when the challenge occurred for 14 days after treatment (99%). Although differences from untreated animals were not significant, the results for H placei suggested high efficacy (> 85%) for up to 21 days for doramectin and up to 28 days for abamectin. CONCLUSIONS: There was no significant difference between abamectin and doramectin for any parasite at any challenge point, indicating that there is equivalent persistent activity of doramectin and abamectin against important gastrointestinal nematodes of cattle.

Evaluation of ivermectin and milbemycin oxime efficacy against Dirofilaria immitis infections of three and four months' duration in dogs.

OBJECTIVES: To determine the efficacy of ivermectin (IVM) and milbemycin oxime (MBO) against induced heartworm infection, where monthly treatment is started 3 or 4 months after infection, and to monitor microfilaremia and antigenemia. ANIMALS: 21 heartworm-naive Beagles. PROCEDURES: Each of 21 dogs was given 50 infective larvae of Dirofilaria immitis by SC inoculation. One group of 5 dogs served as nonmedicated controls, 2 groups of 5 dogs received IVM at 6 micrograms/kg of body weight or MBO at 500 micrograms/kg for 12 months beginning at postinfection (PI) month 4, and 2 groups of 3 dogs received IVM or MBO for 13 months beginning at PI month 3. Blood collected at intervals not > 1 month beginning at PI month 4 was examined for microfilariae and antigen. Dogs were euthanatized at PI month 16. RESULTS: Adult worm counts, relative to controls, were reduced in the 4-month treatment groups by 95.1 (P < 0.01) and 41.4% for IVM and MBO, respectively. The difference between the IVM and MBO groups was significant (P < 0.01). Live worms were found in all MBO-treated (range, 8 to 27) and control dogs (range, 12 to 39) and in 3 of 5 IVM-treated dogs (range, 2 to 4). In the 3-month treatment groups, worm counts were reduced by 97.7 (P < 0.01) and 96.8% (P < 0.01) for IVM and MBO, respectively. Microfilariae were seen in all control dogs and in only 2 of the 16 treated dogs. The antigen response of MBO-treated dogs in the 4-month treatment group was only slightly weaker than that for control dogs. In all other treated dogs, this response was delayed and weaker. CONCLUSION: Ivermectin is highly (> or = 95%) and significantly more effective than MBO against induced heart-worm infection when 1 year of monthly prophylactic dosing is started 4 months after infection. CLINICAL RELEVANCE: In some cases of owner compliance failure, monthly administration of IVM gives a high level of protection against young adult heartworms.

Efficacy of an ivermectin and pyrantel pamoate combination against adult hookworm, Ancylostoma braziliense, in dogs.

A chewable tablet incorporating ivermectin and pyrantel was tested in 12 Beagle dogs for efficacy against the adult hookworm, Ancylostoma braziliense. The dogs were administered infective larvae of A braziliense orally. Twenty-one days after infection the dogs were weighed and allocated randomly to receive either an oral treatment with ivermectin and pyrantel in a beef-based chewable tablet or no treatment. The chewable tablet was a commercially available product, which was made to deliver ivermectin at 6 micrograms/kg and pyrantel at 5.0 mg/kg to each dog. Seven days after treatment the dogs were euthanased, necropsied, and examined for adult hookworms. At necropsy, no adult A braziliense was observed in any of the 6 treated dogs and all 6 dogs that had been left untreated were infected with adult A braziliense (range, 48 to 161). It was concluded that this combination product is 100% efficacious against adult A braziliense.

Treatment and control of sheep scab (Psoroptes ovis) with ivermectin under field conditions in South Africa.

Four trials including 11,266 sheep were conducted in South Africa to evaluate the efficacy of the systemic parasiticide ivermectin against field outbreaks of sheep scab (Psoroptes ovis) when two doses of approximately 200 micrograms/kg were administered subcutaneously seven days apart (days 0 and 7). As sheep scab is a notifiable disease in South Africa, it was not possible to include an untreated control group. The prevalence of clinically affected animals in the four treated flocks varied from 0.4 per cent to 99 per cent before the two treatments. After the treatments, there were no signs of active clinical infection in any of the sheep between days 28 and 30, or at subsequent examinations. P ovis mites were recovered from scrapings from 114 of 127 indicator sheep before the treatment but no mites were recovered from them between days 28 and 30 or 42 and 58 after the treatments.

The efficacy of ivermectin against Thelazia rhodesii (Desmarest, 1828) in the eyes of cattle.

One hundred cattle with confirmed natural infections of Thelazia rhodesii were included in three studies to evaluate the efficacy of ivermectin for the treatment of eyeworm infection. Thelazia rhodesii were counted in situ in each eye of each animal on Day 0 (prior to treatment) and the cattle were paired by the number of worms, within categories of sex, age or number of infected eyes. Within each pair, one animal was randomly assigned to serve as an untreated control, while the other was treated subcutaneously with ivermectin at 200 micrograms kg-1 body weight. Eight days later, parasites were recovered from each eye separately, identified and counted. In each study, significantly (P less than 0.01) fewer T. rhodesii were collected on Day 8 from ivermectin-treated cattle than from controls. Overall, the reduction in numbers of T. rhodesii collected from treated cattle was greater than 99% (P less than 0.05) relative to controls, with reductions of 100% being recorded in two of the three studies.

Efficacy of topically applied ivermectin against sarcoptic mange (Sarcoptes scabiei var. bovis) of cattle.

A total of 12 adult cattle with sarcoptic mange were included in a study to confirm the efficacy of ivermectin applied topically at 500 micrograms/kg against Sarcoptes scabiei var. bovis. Animals were allocated by restrictive randomization according to mite counts to serve as untreated controls or were treated with a topical formulation of ivermectin applied along the backline on healthy skin. Mites were counted in epidermal scrapings made prior to treatment and at 7, 14, 21, 28, 42 and 56 days thereafter. Except for three mites recovered from one animal on day 28, no mites were found after day 14 over the remainder of the trial in scrapings from animals treated with ivermectin. Differences in the numbers of mites recovered from animals treated with ivermectin and those found on controls were significant (P less than 0.05) for counts carried out on days 14-56. Clinical signs of mange resolved following treatment, whereas the extent of lesions and severity of clinical signs increased in the control animals over the trial period.

Efficacy of ivermectin against Parafilaria bovicola and lesion resolution in cattle.

Thirty-two cattle were included in a study to confirm the efficacy of ivermectin administered at 200 micrograms kg-1 against Parafilaria bovicola and to determine the time required for resolution of the lesions caused by the parasite. Four treated and four control animals were slaughtered over 2 days starting 15, 30, 50 or 70 days after treatment. The number, distribution and surface area of carcass lesions, and the weight of tissue trimmed to render the carcasses aesthetically acceptable, were recorded and parasites were recovered from subcutaneous tissues. Significantly (P less than 0.01) fewer worms were recovered from ivermectin-treated cattle slaughtered 50 or 70 days after treatment than from controls. Reductions in the mean number and surface area of lesions, and in the weight of tissue trimmed, were statistically significant (P less than 0.05) for the ivermectin-treated group slaughtered 70 days after treatment and approached significance (P less than 0.1) for the ivermectin group slaughtered 50 days after treatment.

Evaluation of the safety of ivermectin administered in a beef-based formulation to ivermectin-sensitive Collies.

Twenty-four Collies sensitive to the toxic effects of ivermectin, when administered at high dosages, were studied to evaluate the effects of repeated monthly treatment with an ivermectin beef-based formulation at amounts up to 10 times the dosage recommended for heartworm prevention in dogs. Collies were treated 3 times at 30-day intervals at rates of 12, 36, or 60 micrograms of ivermectin/kg of body weight, or with vehicle. Complete physical and neurologic examinations were performed on all dogs prior to the first treatment and after the final treatment. Clinical observations and ivermectin reaction scores were recorded daily for each dog throughout the study. Clinical or neurologic signs characteristic of ivermectin toxicosis were not observed for any dog during the study. Single episodes of vomiting were recorded for 2 vehicle-treated dogs and 2 dogs treated with ivermectin at 12 micrograms/kg from 6 to 21 days after treatment. At the end of the study, all dogs were challenge-exposed with ivermectin at 120 micrograms/kg to reconfirm their sensitivity to this class of compounds. All dogs developed signs typical of ivermectin toxicosis during the subsequent 48- to 72-hour period. Results of this study demonstrated that ivermectin can be administered repeatedly without adverse effects at rates up to 60 micrograms/kg (10 times the recommended use level) to Collies known to be sensitive to this drug.

Efficacy of ivermectin delivered from an intraruminal sustained-release bolus against natural infestations of five African tick species on cattle.

The efficacy of ivermectin delivered by an orally administered prototype sustained-release bolus over approximately 90 days was evaluated against natural infestations of five African tick species. Twenty cattle, allocated by restricted randomization based on counts of standard Boophilus decoloratus, were allocated to two groups and were either given an ivermectin bolus or designated as non-medicated controls. All cattle grazed a single pasture of native grasses for 20-40 days before treatment and until trial termination. Starting on Days 27, 40, 68 and 82 after bolus administration, four replicates were confined to individual tick-collection stanchions for 4 to 5-day periods. Ticks recovered from these cattle were counted by species, sex, and stage and degree of repletion; engorged females were weighed and incubated to determine the number which oviposited. For the other replicates, half-body counts of adult ticks (classified by species, sex and degree of repletion by females) were made at 1- and 2-week intervals through Day 90. Among replicates confined to stanchions periodically, fewer (P less than 0.05) engorged adult female B. decoloratus, Hyalomma spp., Rhipicephalus appendiculatus and Rhipicephalus evertsi evertsi were collected from bolus-treated cattle than from controls. Numbers of engorged adult female Amblyomma hebraeum were reduced, but differences were not statistically significant (P greater than 0.10). Among cattle maintained continuously on pasture, tick numbers were reduced on the ivermectin-treated groups. A significant (P less than 0.05) treatment by linear time effect was seen for all adult ticks counted except R. appendiculatus. A significant (P less than 0.05) treatment by quadratic time effect was seen for A. hebraeum, B. decoloratus and R. evertsi evertsi, and overall treatment differences were significantly different (P less than 0.05) for these species. The differences tended to increase with time. Except for Boophilus, reductions in tick numbers on treated animals relative to controls were not readily apparent. There were no adverse reactions attributable to ivermectin treatment or the presence of the bolus. Each treated animal retained its bolus throughout the trial, based on metal detection.

Control of induced infestations of three African multihost tick species with sustained-release ivermectin.

The efficacy of ivermectin, released intraruminally from a 28-day-delivery device was evaluated in two titration studies against induced infestations of adult Rhipicephalus appendiculatus, R. evertsi and Hyalomma truncatum on cattle. Cattle were given a sufficient number of devices to release ivermectin at approximately 20, 40, 60 or 80 micrograms kg-1 day-1 at a steady-state rate 7-28 days after administration. Tick mortality was recorded, engorged female ticks were weighed and individually incubated, and reproductive data were recorded to determine a reproductive index for the species at various dose levels. Mortality of male and female ticks compared to that of controls was directly related to the daily dose of ivermectin, as was the number of ticks not engorging. Ticks fed on ivermectin-treated cattle had a smaller mass when engorged and laid smaller egg-masses, both absolutely and as a proportion of engorged mass. The index of reproduction of R. appendiculatus was reduced by more than 99.9% at 20 micrograms kg-1 day-1, and the reproductive indices of R. evertsi and H. truncatum were reduced by more than 99.9% at dose rates of 40 micrograms kg-1 day-1 and above. Practical implications of the application of sustained-release ivermectin for the control of multihost ticks and tick-borne diseases are discussed.

Prophylactic efficacy of sustained-release ivermectin against induced nematode infestations in cattle.

The efficacy of sustained-release ivermectin was evaluated against challenge infestations of gastro-intestinal nematodes in a laboratory study involving 12 treated and 12 untreated control cattle. A weighted, orally administered osmotically activated device designed to lodge in the rumeno-reticulum and to deliver ivermectin at a dosage rate of approximately 8 mg/day for a 120-day period, was administered to treated cattle. Animals were challenged with infective larvae of Bunostomum phlebotomum and Oesophagostomum radiatum approximately 4 weeks, and with Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei and Cooperia pectinata approximately 4 and 6 weeks after bolus administration. No parasites were recovered from ivermectin-treated animals, representing 100% efficacy (p less than 0.01) against challenge infestations with larvae of all of the above species. Efficacy against an incidental infestation of Trichuris spp was 92% (p less than 0.01).

Control of cattle mange in southern Africa using ivermectin.

Seven trials including 768 cattle were conducted in South Africa and Namibia to evaluate the efficacy of the systemic parasiticide ivermectin when administered subcutaneously at a dose rate of 200 micrograms/kg against sarcoptic (Sarcoptes scabiei var. bovis), chorioptic (Chorioptes bovis) and psoroptic (Psoroptes ovis var. bovis) mange mites. The efficacy of a single treatment against Psoroptes and Sarcoptes was greater than against Chorioptes. There was marked clinical cure in all treated cases with loss of crusts and hair regrowth. The number of cases of psoroptic mange in two large herds, of which 42.4% of 724 animals were clinically affected prior to mass treatment, was reduced by 99.3% following a single subcutaneous treatment with ivermectin; a single animal from which mites were recovered may not have been treated. The apparent prevalence and prospects for control and eradication of cattle mange in South Africa and Namibia are discussed.

Efficacy of ivermectin against the pig mange mite Sarcoptes scabiei var. suis.

The efficacy of a single subcutaneous dose of ivermectin at 300 micrograms/kg was evaluated against Sarcoptes scabiei in a commercial herd of 146 pigs of which more than 80% were naturally clinically affected with mange. All pigs, except 6 control animals, were treated with ivermectin on Day 0. Scrapings for mite recovery were made from 12 treated animals and 6 controls at the time of treatment and 28 and 42 days later. No mites were recovered from pigs after treatment while live mites were present in scrapings from all control animals. No treated pigs had active lesions at examination on Day 42. The results are discussed in relation to recommendations for a control program for Sarcoptes scabiei in pigs.

Control of induced infestations of adult Amblyomma hebraeum with sustained release ivermectin.

The efficacy of ivermectin, administered in a sustained release formulation by intraruminal pumps at approximate daily dose rates of 20, 40 and 60 micrograms/kg, was evaluated in 16 cattle against induced infestations of 3 strains of adult Amblyomma hebraeum. Engorged female ticks were mass-measured and incubated, and reproductive data recorded. There was an increase in mortality of male and female ticks compared to that of controls with increasing daily dose of ivermectin, and a decrease in the number of ticks engorging. Ticks fed on ivermectin-treated cattle had a smaller mass when engorged and laid smaller egg masses, both absolutely and as a proportion of engorged mass. Index of reproduction was reduced 100% at 60 micrograms/kg/day, greater than 99% at 40 micrograms/kg/day and 96% at 20 micrograms/kg/day. Differences occurred between the 3 strains of A. hebraeum used in the study, especially with regard to engorged mass and reproductive variables. Practical implications of the application of sustained release ivermectin for the control of A. hebraeum, specifically with reference to heartwater (Cowdria ruminantium), are discussed.

Efficacy of ivermectin against ectoparasites of cattle in South Africa.

The efficacy of various formulations of ivermectin administered at the recommended dose rate of 200 micrograms/kg was evaluated in cattle infested with mange mites (Sarcoptes scabiei var. bovis.), lice (Linognathus vituli and Damalinia bovis) and ticks (Boophilus decoloratus, Amblyomma hebraeum, Rhipicephalus appendiculatus and Hyalomma spp.) in 8 trials conducted in South Africa. Mange mites (S. scabiei) were eliminated from animals treated subcutaneously, resulting in marked clinical recovery. Oral administration reduced the numbers of, but did not eliminate these mites. Sucking lice (L. vituli) were eliminated from animals treated orally or subcutaneously. Numbers of biting lice (D. bovis) were reduced but not eliminated, subcutaneous injection being more effective than oral drenching. Subcutaneous injection with ivermectin every 14 d over a period of 84 d significantly reduced numbers of engorged female R. appendiculatus and A. hebraeum. Numbers of Boophilus spp. and Hyalomma spp. were also reduced. A single subcutaneous injection resulted in significantly fewer engorged female B. decoloratus on treated animals for up to 28 d after treatment. In one trial significantly fewer A. hebraeum males occurred on treated animals for up to 28 d after treatment. Too few R. evertsi were present in these trials to evaluate the effect of ivermectin against this parasite.