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.     

Efficacy of topically applied ivermectin against Boophilus microplus (Canestrini, 1887) in cattle

Systemic efficacy of ivermectin applied topically was evaluated against the cattle tick, Boophilus microplus. Twenty cattle with induced infestations were randomly allocated to five groups of equal size based on the numbers of engorged female ticks which fell through the slatted floor of individual pens during the 3 days prior to treatments. Control cattle were non-medicated. Cattle in three groups were given ivermectin at 200, 500 or 1000 mcg kg-1 in a topical formulation applied along the backline from the withers to the rump; cattle in the fifth group were given ivermectin in an injectable formulation subcutaneously at 200 mcg kg-1. Individual 24-h tick collections were made three times weekly for 5 weeks after treatment. Engorged female B. microplus were incubated to determine effects on reproduction. Based on the numbers of engorged female B. microplus collected following treatments, overall efficacy of ivermectin applied topically at 200, 500 and 1000 mcg kg-1 was 50, 85 and 91%, respectively, whereas ivermectin given at 200 mcg kg-1 subcutaneously was 80% effective. The index of reproduction for ivermectin given topically was reduced by 84, 94 and 95%, respectively, and that for ivermectin subcutaneously was 94%. No significant differences (P greater than 0.05) were found for these variables between ivermectin given topically at 500 or 1000 mcg kg-1 versus 200 mcg kg-1 given subcutaneously.     

EVALUATION OF THE POTENTIAL OF SYSTEMIC SLOW RELEASE CHEMICAL TREATMENTS FOR CONTROL OF THE CATTLE TICK (BOOPHILUS MICROPLUS) USING IVERMECTIN

SUMMARY Stall and field trials with cattle infested with various acaricide-resistant strains of cattle tick, have demonstrated the potential of ivermectin as a systemic tickicide. A dosage of 200 μg/kg, administered subcutaneously to animals naturally infested in the field, gave satisfactory tick control for 21 days, after an initial lag period of 2 days immediately following treatment, during which significant numbers of ticks survived. Daily subcutaneous treatments, administered so as to simulate slow release, indicated that a dosage of 15 μg/skg/day should give complete tick control if the chemical could be released continuously from a subcutaneous implant. The potency of ivermectin, assessed by in vitro tests against engorged adults, suggests that the tickicidal activity could be associated with the parent compound per se rather than a metabolite.     

Ability of adults of Amblyomma hebraeum (Acarina: Ixodidae) to feed repeatedly on sheep and cattle

Adult Amblyomma hebraeum ticks were exposed at 14-day intervals on five sheep on 46 occasions and on three cattle on 15 occasions to determine the effects of repeated feeding. The engorged weight and percentage of ticks which fed successfully on sheep declined significantly at first but subsequently they increased. On cattle there was no progressive decline in engorged weight, although the percentage which fed successfully declined significantly and was lower than that for sheep. This decline was attributed to increased grooming by cattle and was the only apparent mechanism by which resistance was expressed.     

The efficacy of ivermectin against larvae of the screw-worm fly (Chrysomya bezziana)

An in vitro technique for screening systemic insecticides against larvae of the screw-worm fly, Chrysomya bezziana is described. Susceptibilities of screw-worm larvae of different ages to ivermectin (MK-933) were determined. Based on 24 h larval mortality, the LD50 of 1-,2-,3-,4- and 5-day larvae was 0.01, 0.02, 0.03, 0.2 and 0.4 ppm of ivermectin. LD50 based on adult emergence following treatment of 4- and 5-day larvae was 0.02 and 0.05 ppm. The LD99.9 for 4-day larvae based on 24 h larval mortality and adult emergence was 11.0 and 0.15 ppm respectively and for 5-day larvae, was 44.3 and 0.4 ppm respectively. Pen and field trials with cattle infested with screw-worm fly demonstrated the potential of ivermectin as a systemic insecticide. Dosages of 50, 100 and 200 micrograms/kg, of ivermectin administered subcutaneously to experimentally infested cattle gave complete control for 6, 12 and 14 days respectively. Ivermectin at 200 micrograms/kg caused 100% mortality of screw-worm larvae up to 2 days old at the time of treatment with 70, 64 and 21% mortality of 3-, 4- and 5-day old larvae at the time of treatment. The residual protection from a single dose of 200 micrograms/kg was 16 to 20 days. When bull calves were treated with ivermectin at a dose of 200 micrograms/kg at the time of castration and branding, none of the 77 treated animals sustained a screw-worm strike in the scrotal area compared with 47 strikes (44%) in the 106 control cattle.     

Failure of ivermectin and eprinomectin to control Amblyomma parvum in goats: characterization of acaricidal activity and drug pharmacokinetic disposition

The therapeutic efficacies of ivermectin (subcutaneous injection) and eprinomectin (topical treatment) given at two different dosage levels to goats naturally infested with Amblyomma parvum were assessed. Treatments included subcutaneous injection of ivermectin at 0.2 and 0.4mg/kg and extra-label pour-on administration of eprinomectin at 0.5 and 1mg/kgb.w. Ivermectin and eprinomectin failed to control Amblyomma parvum on goats. Treatment with ivermectin resulted in a low number of engorged female ticks in relation to untreated control goats and, at the highest dose rate (0.4mg/kg), the female engorgement weights were significantly lower and the pre-oviposition period significantly longer than those observed in ticks recovered from untreated control goats. The tick efficacy assessment was complemented in a separate group of tick-free goats with a pharmacokinetic characterization of eprinomectin (topically administered at 0.5, 1.0 and 1.5mg/kg) and ivermectin (subcutaneous treatment given at (0.2 and 0.4mg/kg) in goats. Heparinized blood samples were taken between 0 and 21 days post-treatment. Higher and more persistent drug plasma concentrations were recovered after the subcutaneous treatment with ivermectin compared to those obtained for eprinomectin topically administered. The understanding of the relationship among the pattern of drug absorption, the kinetic disposition and the resultant clinical efficacy is relevant to improve the poor performance observed for ivermectin and eprinomectin against A. parvum on goats.     

Effect of ivermectin on the control of ear mites (Psoroptes cuniculi) in naturally infested rabbits.

We examined the efficacy of ivermectin in the control of ear mites (Psoroptes cuniculi) in rabbits. The study involved 40 female and 35 male rabbits that were known to be naturally infested with ear mites. After a period of acclimation to the animal care facilities, the rabbits were ranked on the visual appearance of any ear lesion and the number of mites on glycerin-dipped ear swabs. The rabbits were then randomly assigned to 1 of 4 treatment groups; vehicle only (group 1), 50 micrograms of ivermectin/kg of body weight (group 2), 100 micrograms of ivermectin/kg (group 3) and 200 micrograms of ivermectin/kg (group 4). The rabbits were treated by SC injections on day 0 and day 14 of the trial; thus, the total dose of ivermectin given to groups 1 through 4, was 0, 100, 200, or 400 micrograms/kg, respectively. The study ended 2 weeks after the last treatment. Ear lesions of the treated rabbits improved significantly (P less than 0.001). By 28 days after the first treatment, the mean number of mites on the ear swabs (both ears) was 57.5 for untreated rabbits and 9.1, 0.5, and 2.5, respectively, for rabbits in groups 2, 3, and 4. The mean number of mites recovered from the ears of the untreated rabbits at necropsy was 24,297. For groups 2, 3, and 4, the mean number of mites recovered from the ears was 5,352, 96, and 96, respectively. The efficacy of treatment with a total dose of 100 micrograms/kg was 77.96%, with 200 micrograms/kg was 99.61%, and for 400 micrograms/kg was 99.61%.     

Resistance of restrained Bos taurus dairy bull calves to the bont tick Amblyomma hebraeum (Acarina: Ixodidae)

Three infestations of restrained Jersey and Friesland bull calves with adult Amblyomma hebraeum did not affect the rate of engorgement of female ticks and resulted in an insignificant decline in the mean engorgement weight of female ticks recovered from the Friesland group. Repeated infestations significantly affected the egg-laying capacity of engorged female ticks recovered from both groups of hosts. The Friesland calves manifested an enhanced resistance to the larvae and nymphs of Amblyomma hebraeum resulting in prolonged attachment, and a significant decline in engorgement rate of these instars compared with the Jersey group. Skin reaction tests using crude tick extracts yielded antigen-specific hypersensitivity reactions which were not related to resistance to A. hebraeum. Histological changes at the attachment site associated with tick rejection are discussed in relation to host resistance mechanisms.     

Chemical control of Haematobia irritans with 0.5% topical ivermectin solution in cattle.

A field trial was conducted to evaluate the efficacy of a topical formulation of ivermectin administered at the dose of 500 micrograms/kg against horn flies (Haematobia irritans) in cattle. Eighty-eight cattle in four herds naturally exposed to horn flies were used in the trial. Replicates were formed of two herds. Within replicates, one herd was randomly allocated to the untreated control and the other to the ivermectin treatment group. Horn fly counts were taken on the treatment day (Day 0) and on Days 7, 14, 21, 28, and 35 post-treatment. There were no horn flies on any cattle in the treatment group, whereas all the control cattle were continuously infested by horn flies on each examination day.     

The pharmacodynamics of ivermectin in sheep and cattle

The concentrations of ivermectin in the gastrointestinal tract of sheep and cattle were determined after subcutaneous administration of ivermectin. Ivermectin was not detected (limit of detection 1 ng/ml) in abomasal and ruminal fluids either after a normal therapeutic dose of 200 micrograms/kg or even at an increased dose of 2000 micrograms/kg. It was also not detected in abomasal and ruminal fluids of a sheep infected with the abomasal parasite Ostertagia circumcincta. However, ivermectin was detectable at similar concentrations in abomasal mucus and in small intestinal mucus. Excretion of ivermectin was high in bile but the concentrations in small intestinal mucus, distal and proximal to the bile duct opening, were similar. It is hypothesized that the low efficacy of ivermectin against small intestinal nematodes compared with abomasal nematodes is not due to differences in ivermectin concentrations in the predilection sites but is probably due to tachyphylaxis in the nematodes allowing the small intestinal nematodes to re-establish before they have left their predilection site. Ivermectin was excreted in the milk of ewes at concentrations similar to those in plasma. Lambs suckling ivermectin-treated ewes received about 4% of a normal therapeutic dose (200 micrograms/kg) via the milk.     

Efficacy of orally administered powdered aloe juice (Aloe ferox) against ticks on cattle and ticks and fleas on dogs

The efficacy of orally administered powdered aloe juice (Aloe ferox) was evaluated against ticks on cattle and against ticks and fleas on dogs. Twelve calves were each infested over a 25-day period with approximately 4000 larvae of Rhipicephalus (Boophilus) decoloratus and allocated to 3 groups of 4 calves each. Three days after the last larval infestation and daily for 22 days thereafter, the calves in 1 group were fed 5 mg/kg body weight and those in another 25 mg/kg body weight of powdered aloe juice incorporated in game maintenance pellets, while the animals in the 3rd group received only pellets. Detached female ticks were collected daily and counted and the weights and the fertility of groups of 50 engorged female ticks collected from the animals were ascertained. The powdered aloe juice in the game maintenance pellets had no effect on the tick burdens of the calves or on the fertility of the ticks. Six dogs, in each of 2 groups, were treated daily for 15 consecutive days, commencing on Day -5 before the 1st tick infestation, with either 0.39 g or 0.74 g of powdered aloe juice, administered orally in gelatin capsules, while a 3rd group of 6 dogs served as untreated controls. All the dogs were challenged with Haemaphysalis leachi on Days 0 and + 7, and with Ctenocephalides felis on Days + 1 and + 8, and efficacy assessments were made 1 day after flea and 2 days after tick challenge, respectively. Treatment was not effective against ticks or fleas on the dogs.     

Pen studies on the control of cattle tick (Rhipicephalus (Boophilus) microplus) with Metarhizium anisopliae (Sorokin)

Three field trials were conducted over 12 months to assess the pathogenicity of Metarhizium anisopliae to parasitic stages of Rhipicephalus (Boophilus) microplus on dairy heifers under different environmental conditions. Two isolates were selected based on their high optimal growth temperature (30 degrees C), good spore production characteristics and ability to quickly kill adult engorged ticks in the laboratory. Spores were formulated in an oil emulsion and applied using a motor driven spray unit. Surface temperatures of selected animals were monitored, as were the ambient temperature and relative humidity. Unengorged ticks sampled from each animal immediately after treatment were incubated in the laboratory to assess the efficacy of the formulation and application. Egg production by engorged ticks collected in the first 3 days after treatment was monitored. Side counts of standard adult female ticks were conducted daily, before and after treatment to assess the performance of the fungus against all tick stages on the animals. In each trial the formulation rapidly caused 100% mortality in unengorged ticks that were removed from cattle and cultured in the laboratory. A significant reduction in egg production was recorded for engorged ticks collected in the 3 days post-treatment. However, there was little effect of the formulation on the survival of ticks on cattle, indicating that there is an interaction between the environment of the ticks on the cattle and the biopesticide, which reduces its efficacy against ticks.     

Detection of Babesia bigemina in cattle of different genetic groups and in Rhipicephalus (Boophilus) microplus tick

Babesia bigemina infections were investigated in four genetic groups of beef cattle and in Rhipicephalus (Boophilus) microplus engorged female ticks. Blood samples and engorged female ticks were collected from 15 cows and 15 calves from each of the following genetic groups: Nelore, Angus x Nelore, Canchim x Nelore, and Simmental x Nelore. Microscopic examination of blood smears and tick hemolymph revealed that merozoites of B. bigemina (6/60) as well as kinetes of Babesia spp. (9/549) were only detected in samples (blood and ticks, respectively) originated from calves. PCR-based methods using primers for specific detection of B. bigemina revealed 100% infection in both calves and cows, regardless the genetic group. Tick infection was detected by nested-PCR amplifications showing that the frequency of B. bigemina was higher (P<0.01) in female ticks collected from calves (134/549) than in those collected from cows (52/553). The frequency of B. bigemina was similar in ticks collected from animals, either cows or calves, of the four genetic groups (P>0.05).     

Efficacy of topically administered ivermectin against chorioptic and sarcoptic mange of cattle

The efficacy of topically administered ivermectin against Chorioptes bovis and Sarcoptes scabiei var bovis on cattle was evaluated in five studies involving a total of 68 cattle. Treatment with ivermectin solution at a dose rate of 500 micrograms/kg bodyweight topically once was fully effective against C bovis and S scabiei when applied to healthy skin. Efficacy against S scabiei was impaired when the formulation was applied over areas of severe lesions caused by this parasite, presumably due to reduced absorption of ivermectin.     

Comparison of the efficacy of dermal formulations of ivermectin and levamisole for the treatment and prevention of Dictyocaulus viviparus infection in cattle

Four groups of six parasite-naive calves were infected at seven day intervals with three doses of infective larvae of Dictyocaulus viviparus. Twenty-one days after the first dose three of the groups were treated either with an injectable formulation of ivermectin at a dose rate of 200 micrograms/kg bodyweight, or with pour-on preparations of levamisole at 10 mg/kg or ivermectin at 500 micrograms/kg. On day 28 two calves from each group were slaughtered and their burdens of lungworms counted. On day 35 the remaining calves were reinfected with D viviparus infective larvae at a rate of 80 L3/kg. The levamisole preparation was 94.6 per cent effective and both ivermectin preparations were 100 per cent effective against the initial infections. The ivermectin-treated calves were protected from the reinfection which subsequently became patent in the levamisole-treated and control calves.     

Chemical control of the heartwater vectors

This paper reviews available literature on the efficacy of acaricides against Amblyomma hebraeum and other tick species, and presents information on tests done with registered chemicals in the laboratory. Little published information is available on the efficacy of chemicals specifically against A. hebraeum. A host of formulations are registered for use as acaricides on cattle, sheep, and goats in South Africa and thus, by implication, against this species. Resistance has only been described to arsenic and toxaphene in Southern Africa; the other registered products are generally considered to be effective. In contrast, many efficacy tests of various chemicals in different formulations against other Amblyomma spp. have been described. These publications have mainly emanated from the USA, where bite-wounds of these ticks serve as oviposition sites for screwworm flies. In this paper, Amblyomma maculatum and Amblyomma variegatum are included as potential heartwater vectors. The acaricidal efficacy of a number of compounds, representative of different chemical classes, was tested in South Africa against an arsenic and organochlorine resistant strain of A. hebraeum. The engorged adult female immersion method was used. A disconcerting discovery was that several of these registered products failed to control this tick when used at their recommended concentrations. It is concluded that many chemicals which fail against A. hebraeum on cattle do so because of insufficient persistence. Exposure of this tick to lower levels of existing chemicals, but for longer periods, ought to provide satisfactory control for many years.     

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.     

The effect of the bont tick (Amblyomma hebraeum) on the weight gain of Africander steers

The effects of the bont tick Amblyomma hebraeum on the productivity of cattle need to be quantified in order to design economically optimal control programs. Liveweight gains (LWGs) of three groups of Africander steers, maintained in the same pasture and exposed to zero, medium or high numbers of larvae, nymphs and adults of the tick, were measured. Larvae and nymphs had no significant effect on LWG but adults had a large, statistically significant effect (P less than 0.05). The tick-free group had an average LWG of 20 kg more than the heavily infested group after 3.5 months. No mortality was recorded from ticks or tick-borne diseases during the experiment. There was no relationship between the number of engorging adult female ticks counted and loss of LWG of individual animals. The latter suggests that exposure to ticks as well as engorgement by female ticks causes losses. The loss per adult female that completed engorgement was estimated, by relating the LWGs of individual animals to their tick infestations, to be 4 +/- 2 g per adult female tick. An alternative estimate, made by comparing the average LWG and tick infestations of each treatment group, was equal to 10 +/- 4 g. This latter estimate includes the effect of challenge (and rejection) as well as tick feeding and so was accepted as giving the best estimate. Screw-worm fly (Chrysomya bezziana) struck an average of 7.5% of the cattle infested with ticks in any week but the effects on the productivity of the cattle were minimized by immediate treatment. There was a significant, positive correlation between the incidence of screw-worm fly strike and the numbers of adult ticks counted on the experimental animals. The results provide data for calculating losses caused by A. hebraeum in different parts of its geographical range.     

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.     

Evaluation of Metarhizium anisopliae (Hyphomycetes) for the control of Boophilus microplus (Acari: Ixodidae) on naturally infested cattle in the Mexican tropics

The efficacy of Metarhizium anisopliae on the control of Boophilus microplus in cattle infested naturally in the Mexican tropics was evaluated. The study was carried out on a ranch in Veracruz, Mexico. Twenty steers were randomly allocated into two groups of 10 cattle. Animals were naturally infested with B. microplus. Animals in the treated group were sprayed with M. anisopliae (strain Ma34) at a concentration of 1x10(8)conidia/ml every 15 days (four treatments). The other group remained as untreated control. Standard engorged female ticks were recorded on days 0, 1, 3, 5, 7 and 14 post-treatment. From the second application treatment (day 7) to the end of the experiment, animals in the treated group had lower tick infestation (P<0.05) with an efficacy of 40.0-91.2%. The results demonstrate the efficacy of repeated treatment with M. anisopiae (Ma34 strain) to control natural infestation of engorged female B. microplus on cattle in the Mexican tropics.