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Control of cyathostome infections in mares treated at parturition with ivermectin.

Six mares were treated on the day of parturition with an intramuscular injection of 0.2 mg kg-1 ivermectin and placed in a pasture free of equine parasites as soon as possible after foaling. The mares and their foals were compared with a similar group of untreated mares and foals on an adjoining pasture. The experimental data was derived from mare and foal fecal egg counts, foal necropsies and pasture larval counts. Ivermectin administered to mares on the day of parturition, when combined with movement to parasite-free pastures, significantly lowered the cyathostome (small strongyle) egg production for 4 months. This reduced cyathostome exposure was reflected in lower worm-burdens in their foals for 5 months. The results indicate that ivermectin will effectively control equine strongyles when mares and their foals are moved to parasite-free pastures.

Animals↗

The prophylactic effect of ivermectin treatment of calves, three weeks after turnout, on gastro-intestinal helminthiasis.

In two grazing experiments carried out in 1982 and 1983 the prophylactic effect on gastro-intestinal helminthiasis of a single ivermectin treatment of calves 3 weeks after turnout was studied in animals which were turned out early on contaminated pasture and in calves which were turned out late on mown pasture. A single ivermectin treatment 3 weeks after early turnout did not prevent heavy helminth infections. However, such single treatment of calves 3 weeks after a late turnout on mown pasture appears to be a promising way of preventing heavy infections. Late turnout on mown pasture without anthelmintic treatment was not enough to prevent heavy infections. Ivermectin treatment was more effective against Ostertagia spp. than against Cooperia spp. There was no effect on the faecal egg output of Nematodirus helvetianus. Predominantly due to the dry summer, infections were lighter in 1983 than in 1982. These lower infections, and possibly also a delay in the onset of inhibition and differences in helminth strains, may explain the lower proportion of inhibited development in Ostertagia spp. in 1983 than in the comparable groups in 1982.

Animals↗

Evaluation of the parasitological and production responses of a cow/calf operation to an anthelmintic program with ivermectin.

The efficacy of a treatment schedule using ivermectin, given subcutaneously at the rate of 200 micrograms kg-1, to control gastrointestinal parasitism and its effect on liveweight gains was assessed. Two herds with a total of 466 Hereford X Brangus cow/calf pairs were used. Each herd was on six pasture plots of comparable size, stocking rate, and quality and quantity of forage. Pasture groups were paired across the two herds. Pasture groups from one herd were randomly assigned to nonmedicated control and the other three to ivermectin treatment. Treatment assignments per pasture group were reversed in the other herd. The control group contained 118 cows and 112 calves and the medicated group 121 cows and 115 calves. Cows were treated in early July and the calves in late July or early August. Cattle from one herd were weighed on Days -28, 0 (day of cow treatment), 30 (day of calf treatment), 58, and 86, while the other herd was weighed on Days -29, 0 (day of cow treatment), 27 (day of calf treatment), 61, and 89. Day 0 was not the same calendar day for the two herds. Fecal samples for parasite egg counts were obtained from the rectum on weight days from five cows and six calves from each pasture; in most cases the same cattle were sampled each time. Calves treated with ivermectin gained (P less than 0.05) more weight than control calves between day of treatment for cows and the end of the trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Systemic efficacy of ivermectin against Dermanyssus gallinae (De Geer, 1778) in fowls.

The efficacy of ivermectin on females of a laboratory strain of Dermanyssus gallinae was tested. Ivermectin produced a noticeable systemic effect on the mites when inoculated intra-abdominally into infested chickens at rates greater than 0.6 mg kg-1. The concentrations efficacious against D. gallinae (1.8-5.4 mg kg-1) were unfavourably close to those causing toxicity in experimental birds (greater than or equal to 5.4 mg kg-1). Ivermectin administered at 5.4 mg kg-1 was active for 70 h post inoculation.

Animals↗

Selection of ivermectin-resistant Trichostrongylus colubriformis in lambs.

A mixed population of Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus colubriformis was passed for four generations through lambs. In successive passages and on Day 6 (D6), lambs were dosed subcutaneously with ivermectin at 100, 200, 250 and 225 micrograms kg-1 body weight, respectively. No larvae of H. contortus were recovered after the first passage and following the third drug exposure only T. colubriformis was present. Larvae of the selected strain of T. colubriformis developed to third stage, sheathed larvae in vitro in concentrations of ivermectin that inhibited development of larvae from the original strain of T. colubriformis. A definitive control test was then run with 45 lambs, to compare this selected strain to the original strain. The treatments were 150 micrograms kg-1 subcutaneous (SC) D6, 200 micrograms kg-1 SC D6, 200 micrograms kg-1 intraruminal (IR) D6 and 200 micrograms kg-1 SC D21; all treatments were compared to non-treated controls, selected or original strain as applicable. The D6 IR and D6 SC 150 micrograms kg-1 treatments were greater than 99% effective in both strains, although the D6 SC 200 micrograms kg-1 treatment was 85 and 48% effective in the original and selected strain, respectively. The D21 200 micrograms kg-1 was only 58% effective against the selected strain. There was significant (P less than 0.001) differences between the original and selected strains of T. colubriformis for both fecal egg output and worm counts. The exposure of four generations of immature T. colubriformis to ivermectin selected for partial resistance.

Animals↗

The effect of ivermectin treatment against inhibited early third stage, late third stage and fourth stage larvae and adult stages of the cyathostomes in Shetland ponies and spontaneous expulsion of these helminths.

A controlled and critical test on the efficacy of ivermectin against larval and adult stages of the cyathostomes was carried out in six yearling castrated male Shetland ponies. The ponies grazed together as one group from 3 May to 4 October 1990, after which they were housed. Three ponies were treated with ivermectin on 29 October while the others served as controls. The shedding of helminths in the faeces was followed in all ponies until necropsy on 14 November. Comparison of worm counts of both groups before and after necropsy showed no evidence for an effect of ivermectin against inhibited early third stage larvae (EL3) and mucosal late third stage (LL3) and fourth stage larvae (L4). However, a high, but not 100%, efficacy was observed against adults and lumenal L4. A remarkable observation was the high incidence of spontaneous expulsion of L4 and adult populations of some species in two of the untreated ponies.

Animals↗

Oral and parenteral administration of ivermectin to reindeer.

The anti-parasitic effect of the orally administered paste formulation of ivermectin (Ivomec) in reindeer was evaluated by means of a trial designed to compare the efficacies of orally and s.c. administered ivermectin at the same dosage (0.2 mg kg-1 body weight) in naturally infected adult reindeer (n = 92). Both formulations were 100% effective against larvae of the warble fly, Oedemagena tarandi, while oral treatment was less efficacious than s.c. injection against parasitic nematodes. Both formulations, but particularly the injectable ivermectin treatment, increased the weight gain of pregnant females compared to that of those not treated.

Administration, Oral↗

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.

Animals↗

Immune responses of pony foals during repeated infections of Strongylus vulgaris and regular ivermectin treatments.

Ten helminth-free pony foals divided into three groups were used in this study. Eight foals were each experimentally infected per os with 50 Strongylus vulgaris infective larvae weekly for 4 weeks, at which time one foal died of acute verminous arteritis. The remaining seven foals subsequently received 50 S. vulgaris infective larvae every 2 weeks for an additional 20 weeks. Four of the infected foals remained untreated (Group 1) and three of the infected foals were given ivermectin at 8, 16 and 24 weeks post initial infection (Group 2). Two foals served as controls (Group 3). Foals in Group 1 developed eosinophilia, which was sustained throughout the course of infection. A mild eosinophilia also developed in Group 2 foals; however, the eosinophil numbers were markedly reduced for 3 weeks after each ivermectin treatment. Only foals in Group 1 developed significant (P less than 0.05) hyperproteinemia, hyperbetaglobulinemia and a reversal of the albumin/globulin (A/G) ratio 4 weeks after initial infection. Significant (P less than 0.05) IgG anti-S. vulgaris ELISA titers developed in foals in Groups 1 and 2 3 weeks after infection and were sustained for the duration of the experiment. Western blot analysis of soluble somatic antigens of S. vulgaris adult female and male worms probed with sera from foals in Groups 1 and 2 revealed only subtle differences between these animals. The blastogenic reactivity of peripheral blood mononuclear cells (PBMC) to phytohemagglutinin and concanavalin A was not significantly different between groups. Peripheral blood mononuclear cells from foals in Groups 1 and 2 developed significant (P less than 0.05) blastogenic reactivity to S. vulgaris soluble adult somatic antigen when examined at 25 weeks after infection. Mesenteric lymph node cells from foals in Group 2, although not statistically significant, were more reactive to antigen than were the mesenteric lymph node cells from foals in Group 1 when examined at 27 weeks after infection. These results suggest that significant alterations in the immune response of ponies to S. vulgaris does not occur after intravascular killing of larvae by ivermectin treatments.

Animals↗

Effects of ivermectin on two afrotropical dung beetles, Onthophagus gazella and Diastellopalpus quinquedens (Coleoptera: Scarabaeidae).

Subcutaneous injection of 0.2 mg kg-1 ivermectin to heifers negatively affected larvae of the afrotropical dung beetles, Diastellopalpus quinquedens and Onthophagus gazella, developing in the dung. Although closely related, the two species seem to differ in susceptibility; 28% of brood masses made of dung voided 2 days after treatment contained third instar D. quinquedens, whereas O. gazella died as first instars in dung voided up to 8 days after treatment. Folding of the head capsules and lack of mandibular wear in the dead O. gazella larvae suggest that ivermectin could be absorbed through the integument and prevent normal feeding and distension of the head capsule. In addition, the surviving third instar O. gazella in dung voided 16 days after treatment had significantly reduced clypeal and mandibular widths. The dung burial activity, mainly by D. quinquedens, estimated in a field experiment was not affected by ivermectin residues in the dung.

Animals↗

The degradation of dung produced by cattle treated with an ivermectin slow-release bolus.

Eight female calves of the Deutsches Fleckvieh breed, weighing 161-207 kg, were each treated at turnout on 16 May 1989 with one ivermectin sustained-release intraruminal bolus designed to release ivermectin at 12 mg day-1 for approximately 120 days. Eight animals remained as untreated controls. A third group of eight unmedicated tracer calves was not considered as part of this evaluation. All 24 animals grazed together on a single pasture throughout the study. On Days 21/22, 70 and 119, 15 faecal pats were selected from each treatment group and ranked according to surface area; within each group of three consecutively ranked pairs of pats, two pairs were randomly allocated as observation pats and the third as a sampling pat. The surface area of observation pats was measured, photographs taken, and dry matter, crude ash and organic matter determined at various intervals following deposition. A 1/4 sample collected from sampling pats 3, 7, 14 and 28 days after deposition was weighed and examined for Coleoptera (adults and larvae), Diptera larvae and nematodes. No differences between groups were seen in respect of organic matter content, numbers or frequency of adult Coleoptera species and soil nematodes. A decrease in numbers of Coleoptera larvae, Diptera larvae and dung-specific nematodes was observed in pats from ivermectin-treated cattle. Based on the evaluation of the surface area, a delay in the degradation rate of pats from treated compared with those from untreated animals was seen; however, the difference was statistically not significant (P > 0.05).

Animals↗

Field trials to confirm the efficacy of ivermectin jetting fluid for control of blow fly strike in sheep.

Fifty-two field trials, involving 14,296 sheep, were conducted to confirm the efficacy and safety of ivermectin jetting fluid against blow fly strike in sheep in Australia. A total of 7143 sheep were treated by hand-jetting with a 0.03 mg ml-1 solution of ivermectin, while 7153 sheep were untreated controls. The percent reduction in the cumulative incidence of strikes within the treatment area for ivermectin-treated sheep in comparison with untreated controls, was 96.5%, 95.8% and 93.5% at 10, 12 and 13/14 weeks after treatment, respectively. There were no adverse reactions to treatment.

Administration, Topical↗

Ivermectin resistant Haemonchus contortus in Louisiana lambs.

Fifteen weaned crossbred (Suffolk x Louisiana Native) lambs were treated with albendazole (10 mg kg-1) to remove existing nematode infections. They were inoculated with Haemonchus contortus infective larvae from a residual population surviving treatment with the oral formulation of ivermectin (0.2 mg kg-1). One group of five lambs remained untreated, another group of five was treated with the injectable formulation of ivermectin (0.2 mg kg-1), and a third group of five was treated with the oral formulation of ivermectin (0.2 mg kg-1). Subsequent to the treatments, there was essentially no difference in mean fecal egg count or mean number of H. contortus recovered at necropsy between the three groups.

Albendazole↗

Thin-layer chromatographic detection of ivermectin in cattle serum.

A study was conducted on the detection of ivermectin (22,23-dihydroavermectin B1) in cattle serum by thin-layer chromatography (TLC) after derivatization of this parasiticide by the known reaction with trifluoroacetic anhydride-1-methylimidazole and visual examination of the chromatograms under long-wavelength ultraviolet light. By derivatization of reference samples of ivermectin in acetonitrile, approximately 0.1 ng of a highly fluorescent material, tentatively identified as 2,5,6-tetradehydro-5,7-dideoxy-22,23-dihydroavermectin B1, could be detected on silica-gel thin layer plates. Extraction of fortified serum samples with methyl tert.-butyl ether followed by derivatization, hydrolysis, partitioning between water-hexane and TLC gave a limit of detection of 1-2 ng/ml. With these simple techniques ivermectin could be detected in cattle serum for 3-4 weeks after subcutaneous treatment of Hereford heifers.

Animals↗

Determination of acidic pharmaceuticals, antibiotics and ivermectin in river sediment using liquid chromatography-tandem mass spectrometry.

Analytical methods have been developed for the determination of eight acidic pharmaceuticals and two metabolites, seven antibiotics and the parasiticide ivermectin in a selected river sediment. The sediments were solvent extracted with ultrasonic assistance. A solid phase extraction (SPE) clean-up step was performed thereafter. The acidic compounds clofibric acid, diclofenac, fenoprofen, gemfibrozil, ibuprofen, 2-hydroxy-ibuprofen, indomethacin, ketoprofen, naproxen and the parasiticide ivermectin were measured in the negative mode by LC-APCI-tandem MS, whereas the antibiotics clarithromycin, erythromycin, roxithromycin, sulfadiazine, sulfamethazine, sulfamethoxazole and trimethoprim were detected in the positive mode by LC-ESI-tandem MS. Bezafibrate could not be determined in the sediment using the method developed. The limit of quantification (LOQ) ranged from 0.4 to 8 ng g(-1) for the acidic pharmaceuticals, sulfadiazine and ivermectin and was 20 ng g(-1) for the other antibiotics.

Acids↗

Caenorhabditis elegans ivermectin receptors regulate locomotor behaviour and are functional orthologues of Haemonchus contortus receptors.

The target site for the anthelmintic action of ivermectin is a family of nematode glutamate-gated chloride channel alpha subunits (GluClalpha) that bind the drug with high affinity and mediate its potent paralytic action. Whilst the action of ivermectin on the pharyngeal muscle of nematodes is relatively well understood, its effect on locomotor activity is less clear. Here we use RNAi and gene knockouts to show that four GluClalpha subunits are involved in regulating the pattern of locomotor activity in Caenorhabditis elegans. A Haemonchus contortus orthologue of these subunits, HcGluClalpha3, has been shown to be expressed in the motor nervous system and here we have shown that it is a functional, as well as a structural, orthologue by virtue of the observation that it can restore normal motor movement in the C. elegans GluClalpha mutant, avr-14(ad1032), when expressed under the control of the avr-14 promoter. This supports the contention that ivermectin exerts its paralytic action on parasitic nematodes through activation of GluCl channels in the motor nervous system. Furthermore, functional complementation in C. elegans provides a method to further the understanding of this important class of anthelmintic targets.

Animals↗

A randomized, double-blind, controlled trial of the effects of ivermectin at normal and high doses, given annually or three-monthly, against Onchocerca volvulus: ophthalmological results.

A three-year randomized, controlled, double-blind trial was conducted in Cameroon to determine whether ivermectin, given at three-monthly intervals and/or at high doses (800 microg/kg), had a greater effect on adult Onchocerca volvulus than standard doses (150 microg/kg annually). As several patients complained of transitory subjective visual problems after treatment, some of them being of an unexpected type, we organized two series of detailed ophthalmological examinations to evaluate whether they were associated with ocular lesions. Analysis showed that these complaints were significantly more frequent in the two groups treated with high doses of ivermectin than in the reference group. In the ophthalmological examinations, the only differences recorded between the groups were a lower prevalence and mean number of microfilariae in the anterior chamber in the groups treated three-monthly, and, at the first examination round, a higher prevalence of early lesions of the iris in the group treated at high doses annually. These findings do not allow us to explain the cause of the transitory ocular complaints, nor why they were more frequent in the groups treated at high doses. However, one may conclude that using doses of ivermectin higher than the standard one should be considered with caution.

Adolescent↗

First case of ivermectin-induced severe hepatitis.

Loiasis, caused by the filarial parasite Loa loa, is endemic in West and Central Africa. Ivermectin has been shown to be an effective treatment of loiasis. We report the case of a 20-year-old woman originally from Cameroon who was infected by the L. loa parasite and developed severe hepatitis, identified 1 month after a single dose of ivermectin. Liver biopsy showed intralobular inflammatory infiltrates, confluent necrosis and apoptosis, compatible with drug-induced liver disease. To our knowledge, this is the first case of ivermectin-induced severe liver disease published in the literature.

Adult↗