Comparison of the anthelmintic efficacy of oxfendazole or ivermectin administered orally and ivermectin administered subcutaneously to sheep during the periparturient period

The suppression of nematode egg output in faeces was measured in ewes treated just before lambing with either oxfendazole or ivermectin by oral drench or with ivermectin by subcutaneous injection. Ivermectin and oxfendazole given orally were similarly effective, whereas ivermectin given by subcutaneous injection extended the period of suppressed egg output by about one week. The more persistent anthelmintic effect of ivermectin given subcutaneously was probably due to its extended half-life in the plasma of treated sheep. Plasma pepsinogen activity was less in the sheep given anthelmintic than in the untreated controls. Ivermectin caused a significantly greater reduction in pepsinogen activity than oxfendazole and was more effective when given subcutaneously than when given orally.     

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.     

Efficacy of ivermectin against gastrointestinal nematodes in dromedary camels

The anthelmintic activity of ivermectin when administered orally and subcutaneously at a dosage of 0.2 mg/kg of body weight was evaluated in 4 trials involving 20 dromedary camels (Camelus dromedarius). Fecal egg counts were made on the day of treatment and at 2, 4, and 10 weeks after treatment. Trichostrongylid egg counts were reduced by a maximum of 100% when ivermectin was administered orally and by greater than 88% when given subcutaneously. Egg counts of Trichuris spp were reduced by greater than 85% with oral administration, but increased following subcutaneous treatment. No adverse local or systemic reactions were observed following treatment with ivermectin by either route.     

Prophylaxis of nematode infections in cattle with an indwelling rumino-reticular ivermectin sustained release bolus

Ivermectin delivered continuously from a rumino-reticular sustained release device was prophylactically effective in preventing establishment of nine nematode parasite species in multiply-exposed cattle. Ivermectin dosages which permitted less than or equal to 1% of infected control calf worm populations to establish ranged from less than 2.5 micrograms kg-1 day-1, which totally prevented infection with Dictyocaulus viviparus and Oesophagostomum radiatum, to approximately equal to 30 micrograms kg-1 day-1 required to suppress Nematodirus helvetianus to the same extent. Between these extremes, in decreasing order of sensitivity to enterical sustained release ivermectin, were Ostertagia ostertagi, Trichostrongylus axei, Haemonchus placei, Cooperia punctata, C. oncophora and T. colubriformis which were maximally affected at less than or equal to 10 micrograms kg-1 day-1 of ivermectin.     

Efficacy of ivermectin against benzimidazole-resistant nematodes of sheep

Two trials involving a total of 36 Dorset horn lambs were conducted to assess the anthelmintic efficacy of ivermectin against experimental infections of benzimidazole-resistant strains of Haemonchus contortus and Ostertagia circumcincta. Two resistant strains of each of the two species were used and in each trial the lambs were allocated to three groups. One group was given 200 micrograms ivermectin/kg bodyweight orally, the second group was given 5 mg oxfendazole/kg bodyweight orally and the third group remained untreated as controls. Fourteen days after treatment the lambs were necropsied. Ivermectin was found to be more than 99 per cent to 100 per cent effective against all four benzimidazole-resistant strains, whereas oxfendazole was 78.6 per cent and 83.8 per cent effective against the H contortus strains, and 25.6 per cent and 39.8 per cent effective against the O circumcincta strains.     

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.     

Dose-titration studies of ivermectin against experimental Ancylostoma caninum and Uncinaria stenocephala infections

Dose-titration trials of ivermectin were conducted on pups with dual experimental infections of 4th-stage larvae or adult Ancylostoma caninum and Uncinaria stenocephala. Ivermectin was administered orally or subcutaneously at dosages of 0.006, 0.012, or 0.024 mg/kg of body weight. Maximal or near maximal (greater than or equal to 96% to 100%) anthelmintic effect was observed for both stages of development for each hookworm species by either route of administration at a dosage of 0.024 mg/kg. Responses for all of the aforementioned categories were linearly related to increasing log dosage of ivermectin, with common slopes (regression coefficients). Regression analysis also provided estimates of the minimal dosages required to produce maximal reduction in worm burden for each stage, species, and route of administration. The estimated ivermectin dosages for maximal efficacy ranged from a low of 0.014 mg/kg for adult A caninum by oral treatment to 0.044 mg/kg for 4th-stage larvae of U stenocephala by oral treatment.     

Influence of ivermectin and clorsulon treatment on productivity of a cow-calf herd on the southern Oregon coast.

The reproductive performance of beef cows and the weight gain of their calves was evaluated after oral administration of clorsulon or clorsulon in combination with the subcutaneous administration of ivermectin. One hundred and fifty pregnant cows harboring infections of Fasciola hepatica were assigned to one of three treatment groups: Group 1 comprising 50 unmedicated controls; Group 2, 50 cows treated with clorsulon orally at 7 mg kg-1; Group 3, 50 cows treated with clorsulon orally at 7 mg kg-1 and ivermectin subcutaneously at 200 micrograms kg-1. Weights and body condition scores of the cows were measured and fecal and blood samples were taken at trial initiation and days 158 and 270. Pregnancy status was also determined at day 270. Weights and body condition scores were measured for the calves at days 158 and 270. Adjusted 205 day weaning weight of the calves was calculated and analyzed for differences between treatment groups. Four sets of tracer calves were used periodically throughout the trial to monitor the helminth challenge to the herd. Both gastro-intestinal nematodes and liver flukes were transmitted to the tracer calves during the entire trial. Even in the face of continual helminth challenge, beef cows treated with combined clorsulon/ivermectin conceived approximately 2 weeks earlier than their untreated counterparts and their calves had better body condition scores and weights than untreated calves.     

Prophylactic efficacy of an ivermectin sustained-release bolus against challenge exposure with gastrointestinal and pulmonary nematode infective larvae in calves

Twelve Holstein calves were used to determine the prophylactic efficacy of ivermectin against challenge exposure with gastrointestinal and pulmonary nematodes. Two groups of 6 calves (mean body weight, 205 kg) each were formed by restricted randomization according to body weight. Group-1 calves served as nonmedicated controls. Each calf of group 2 was orally given one prototype sustained-release bolus designed to deliver ivermectin at a continuous daily dose of 8 mg. Third-stage nematode infective larvae were given to the calves on posttreatment days 28 and 42. The calves were euthanatized 77 or 78 days after treatment. Ivermectin was 100% effective (P less than 0.05) in preventing the establishment of infection by Haemonchus placei, Ostertagia ostertagi, Cooperia spp (C punctata, C oncophora, C surnabada), Nematodirus helvetianus, Oesophagostomum radiatum, and Dictyocaulus viviparus and was greater than 99% effective against Trichostrongylus axei. Incidental infection by Trichuris spp was reduced by 94% (P = 0.08).     

Influence of the route of administration on efficacy and tissue distribution of ivermectin in goat

The tissue concentration and efficacy of ivermectin after per os and subcutaneous administration were compared in goats experimentally infected with Trichostrongylus colubriformis (ivermectin-susceptible strain, INRA). Infected goats (n = 24) were treated per os (n = 9) or subcutaneously (n = 9) with ivermectin, 0.2 mg/kg, or kept as not treated controls. The faecal egg counts and small intestine worm counts were determined. Ivermectin concentration was measured in the plasma, gastrointestinal tract, lung, skin or hair, liver and adipose tissues at 0, 2, 7 and 17 days post-treatment. The efficacy of ivermectin against T. colubriformis infection in goat was 98.7 and 99.9% for subcutaneous and oral administration, respectively. Ivermectin concentration declined with time and only residual concentration was measured at 17 days post-treatment in plasma and gastrointestinal tract. Ivermectin concentration was higher after subcutaneous compared to per os injection in most of the tissue examined. In skin, hair and subcutaneous adipose tissue ivermectin persisted at significant concentrations 17 days post-treatment for both routes of administration. In our experimental conditions, ivermectin provides similar efficacy against T. colubriformis after subcutaneous or per os administration in goat. However, the lower ivermectin levels in tissues after per os administration suggest that the lasting of efficacy may be shortened after per os compared to subcutaneous administration especially in animals with poor body condition in pasture where re-infection occurs quickly after anthelmintic treatment.     

Resistance of Teladorsagia circumcincta in goats to ivermectin in the Netherlands

Resistance of Teladorsagia circumcincta in goats to ivermectin In 2005, suspected ivermectin resistance of gastrointestinal nematodes was investigated in 17 goats on a farm in the Netherlands, using a faecal egg count reduction test combined with faecal larval cultures. Eight goats were treated orally with 0.2 mg/ kg ivermectin on 1 August 2005 and the other nine goats served as untreated controls. Faeces were collected from all goats on 1 August and on 12 August. Faecal egg counts were reduced by 80.6% in goats receiving ivermectin. On the basis of faecal larval cultures and the egg counts, ivermectin was found to be 100% effective against Haemonchus contortus, 15.0% effective against Teladorsagia circumcincta, and 93.3% effective against Trichostrongylus spp. The effect of levamisole and oxfendazole on gastrointestinal nematodes was also evaluated. Nine goats were treated subcutaneously with 5 mg/kg levamisole and seven goats orally with 4.5 mg/kg oxfendazole on 12 September On the basis of faecal egg counts performed on 12 and 22 September, levamisole reduced the total egg count by 95.4% and oxfendazole reduced the egg count by 85.8%. Differentiation of pooled faecal larval cultures revealed that levamisole was 99.9% effective against H. contortus, 81.9% effective against T. circumcincta, and 99.5% against Trichostrongylus spp. Oxfendazole was 75.5% effective against H. contortus, 33.2% effective against T. circumcincta, and 100% effective against Trichostrongylus spp. On 28 October the nine goats that were still present on the farm were orally treated with 0.4 mg/kg ivermectin. Faecal egg counts and differentiation of pooled larval cultures of faecal samples collected on 28 October and 9 November, respectively, revealed that total egg counts were reduced by 93.1%. Ivermectin was 49.1% effective against T. circumcincta but 100% effective against H. contortus and Trichostrongylus spp. Thus H. contortus appears to be resistant to oxfendazole and T. circumcinta appears to be resistant to oxfendazole and ivermectin. This is the first documented case of ivermectin resistance of a gastrointestinal nematode of small ruminants in the Netherlands.     

Evaluation of anthelmintic properties of extracts from some plants used as livestock dewormers by pastoralist and smallholder farmers in Kenya against Heligmosomoides polygyrus infections in mice

Parasitic nematodes are among the most common and economically important infectious diseases of grazing livestock, especially in small ruminants in the tropics and subtropics in Kenya the control of gastrointestinal nematode infections in sheep and goats is usually made with synthetic anthelmintics but substantial levels of anthelmintic resistance have been recorded. A number of medicinal plants, that may provide possible alternatives, and are used by pastoralists and smallholder farmers in Kenya as deworming agents for their livestock and equines, namely Aframomum sanguineum, Dodonea angustifolia, Hildebrandtia sepalosa, Myrsine africana, Rapanea melanophloeos from Kenya, and Azadirachta indica from Kenya and Malaysia, together with the chemicals embelin and santonin that occur in some of these plants, were evaluated against Heligmosomoides polygyrus in mice. Commercial anthelmintics, namely ivermectin, pyrantel and piperazine, were also investigated, both to validate the mouse model system and to assess efficacy of these drugs against H. polygyrus. Pyrantel and ivermectin were highly effective in reducing the numbers of H. polygyrus worms as well as eggs in faeces of the mice, but piperazine had a lower activity. Application of santonin and M. africana significantly reduced the number of total worm counts (TWC) but not faecal egg counts (FEC). The use of embelin, R. melanophloeos and A. indica reduced FEC but not TWC. In all cases, however, reductions were well below the a priori level of 70% required for biological significance. A. sanguineum, D. angustifolia and H. sepalosa had no effect on either TWC or FEC. In conclusion, none of the plant preparations had any biologically significant anthelmintic effect in this monogastric host-parasite model system.     

Effect of ivermectin in heifers on mortality and egg production of Psoroptes ovis

Ten stanchioned heifers, heavily infested with Psoroptes ovis (Hering), were each given a single subcutaneous injection of 200 micrograms of ivermectin/kg. Another 10 heavily infested heifers (stanchioned) were injected subcutaneously with the solvent system (vehicle) used to formulate the ivermectin. Treatment with the vehicle did not reduce mite populations or total egg counts. The 10 heifers treated with ivermectin had an immediate reduction in live mite and egg counts (an increase in the percentage of mortality of mites) and were completely free of psoroptic mites by 20 days after treatment. Ivermectin was equally effective against adult and immature psoroptic mites.     

Treatment with ivermectin of sarcoptic mange in pigs

Ivermectin injectable solution (1% w/v) was highly effective against Sarcoptes scabiei var suis when administered subcutaneously once to swine at 300 mcg/kg body weight. There were significantly (P < 0.05) fewer Sarcoptes mange mites counted on pigs treated with ivermectin than on untreated pigs at each count up to day 56 after treatment. The results indicate ivermectin should provide an efficient, practical means of control of sarcoptic mange in intensive piggeries.     

Anthelmintic efficacy of ivermectin in naturally parasitized cats

Ivermectin was administered per os [( PO]; n = 15) or subcutaneously [( SC]; n = 3) to naturally parasitized cats at 10 (n = 6), 100 (n = 6), or 300 (n = 6) micrograms/kg of body weight. Nontreated control cats were given sterile isotonic saline solution PO (n = 5) or SC (n = 1). Qualitative fecal examinations were performed on each cat 1 day before treatment and 14 days after treatment. Cats were euthanatized 14 days after treatment, at which time parasites from the gastrointestinal tracts were recovered, identified, and enumerated. Lungs and urinary bladders were examined histologically or by digestion (lungs only) for Capillaria spp and/or Aelurostrongylus abstrusus. Ivermectin was effective in removing Ancylostoma spp at all doses, but removal of Toxocara cati required 300 micrograms of ivermectin/kg. Efficacies against A abstrusus, Capillaria spp, and Physaloptera spp could not be determined definitively. Ivermectin had no effect on Dipylidium caninum, Hydatigera taeniaeformis, Spirometra mansonoides, or Isospora spp. Adverse reactions were not observed in cats given ivermectin PO; however, 3 cats given ivermectin SC reacted as though they experienced pain at the injection site.     

Cetirizine in horses: pharmacokinetics and effect of ivermectin pretreatment

The pharmacokinetics of the histamine H(1)-antagonist cetirizine and the effects of pretreatment with the antiparasitic macrocyclic lactone ivermectin on the pharmacokinetics of cetirizine were studied in horses. After oral administration of cetirizine at 0.2 mg/kg bw, the mean terminal half-life was 3.4 h (range 2.9-3.7 h) and the maximal plasma concentration 132 ng/mL (101-196 ng/mL). The time to reach maximal plasma concentration was 0.7 h (0.5-0.8 h). Ivermectin (0.2 mg/kg bw) given orally 1.5 h before cetirizine did not affect its pharmacokinetics. However, ivermectin pretreatment 12 h before cetirizine increased the area under the plasma concentration-time curve by 60%. The maximal plasma concentration, terminal half-life and mean residence time also increased significantly following the 12 h pretreatment. Ivermectin is an inhibitor of P-glycoprotein, which is a major drug efflux transporter in cellular membranes at various sites. The elevated plasma levels of cetirizine following the pretreatment with ivermectin may mainly be due to decreased renal secretion, related to inhibition of the P-glycoprotein in the proximal tubular cells of the kidney. The pharmacokinetic properties of cetirizine have characteristics which are suitable for an antihistamine, and this substance may be a useful drug in horses.     

The distribution and some pharmacokinetic parameters of ivermectin in pigs

Ivermectin was injected subcutaneously into five pigs at the usual dose rate of 300 µg/kg and found to distribute well to all tissues and body fluids which were sampled 24 h post-injection. Ivermectin was detected in the contents and mucus at all levels of the gastrointestinal tract. The drug was excreted in bile, with high concentrations of the drug in the intestines and faeces. High concentrations of ivermectin were measured in skin, ears and ear wax, suggesting that the drug should be effective in the treatment of ectoparasitic infestations, particularly ear mites. The high lipid solubility of the drug may explain the high concentrations found in ear wax and skin. Ivermectin was also detected in the body fluids and tissues of an untreated pig penned with the treated animals. Direct contact appeared to be necessary for transfer of ivermectin from the treated to the untreated pig but coprophagia or urine drinking is a possible explanation.The pharmacokinetics of ivermectin administered subcutaneously at a dose rate of 300 µg/kg to six pigs were studied. There was marked individual variation in the pharmacokinetics of ivermectin. In one pig the area under the plasma concentration-time curve was particularly high. This may reflect individual variation in uptake and excretion of the drug. The mean elimination half-life of the drug was 35.2 h, suggesting that the drug is cleared slowly from pigs with drug detectable in plasma for 6–10 days. This persistence should allow a short period of protection before re-infection with parasites.     

Efficacy of ivermectin as an anthelmintic in leopard frogs.

Ivermectin administered cutaneously at dosages of 2 mg/kg of body weight eliminated nematode infections in leopard frogs. Three clinical trials were conducted. In the first trial, 5 groups of 11 frogs were given ivermectin IM at dosages of 0, 0.2, 0.4, 2, or 20 mg/kg. All frogs given ivermectin IM at dosages of 2.0 mg/kg or greater died. In trial 2, 44 frogs, allotted to 5 groups, were given ivermectin cutaneously at 0, 0.2, 2, or 20 mg/kg. Cutaneously administered ivermectin was not toxic at dosages up to 20 mg/kg. In trial 3, nematode infections were eliminated in all 10 frogs treated cutaneously with ivermectin at 2.0 mg/kg.     

Comparison of ivermectin, oxfendazole and levamisole for use as anthelmintics during the periparturient period in sheep

Ewes synchronised with progestin impregnated sponges to reduce the spread of lambing were treated during the periparturient period with anthelmintic. The suppression of nematode egg output in faeces was measured in ewes given ivermectin either by subcutaneous injection or orally, or oxfendazole or levamisole orally. Ivermectin and oxfendazole reduced the output of eggs in the faeces of the ewes significantly (P less than 0.05) and the period of suppressed egg output was extended when ivermectin was given by subcutaneous injection. Plasma pepsinogen activity was estimated as a measure of abomasal damage. Pepsinogen values were significantly (P less than 0.001) lower in those animals treated with ivermectin by subcutaneous injection than in control animals. Levamisole showed a poorer response in terms of the output of eggs in faeces than either ivermectin or oxfendazole.     

Ivermectin effects on motor coordination and contractions of isolated rat diaphragm

Ivermectin, the antiparasitic drug from the macrocyclic lactones class raises attention due to its high efficiency against nematodes and arthropods and very specific toxic and side effects that it may produce in host. Dominant clinical symptoms of adverse effects and toxicity of ivermectin in animals are tremor, ataxia, CNS depression and coma which often results in mortality. In our study increasing intravenous doses of ivermectin, (6 or more times higher than therapeutic dose: 1.25, 2.5, 3.75, 5.0, 6.25 and 7.5 mg/kg), caused dose-dependent disturbance of motor coordination in treated rats. The median effective dose (ED50) that was able to impair the rota-rod performance in rats treated 3 min before testing was 2.52 mg/kg. This effect weakens over time, while in the rats treated 60 min before the rota-rod test, ED50 of ivermectin was 4.21 mg/kg. Whereas, all tested doses of ivermectin did not cause any other clinical symptoms of toxicity. Ivermectin has no effect on the contractions of isolated diaphragm caused by the EFS, which effectively blocked mecamylamine (100 μM) and pancuronium (1 and 2 μM). Effect on motor coordination is the first detectable clinical symptom of ivermectin toxicity and apparently is a result of its central effects.