Controlled evaluation of fenbendazole as a bovine anthelmintic.

Calves experimentally infected with Haemonchus, Ostertagia, and Cooperia, and to lesser degrees with Trichostrongylus, Oesophagostomum, Nematodirus, and Bunostomum were used in a controlled experiment to record the anthelmintic efficacy of a benzimidazole compound methyl 5-(phenylthio)-2-benzimidazolecarbamate at dosage levels of 3.5, 5, and 7.5 mg/kg bodyweight. With the 3 dosages, reductions of Haemonchus were 96.7, 99.2, and 99.8%; of Ostertagia, 97.2, 97.2, and 99.5%; and of Cooperia, 99.9, 99.9, and 99.9%. Pronounced reductions were also recorded for Trichostrongylus, Nematodirus, Oesophagostomum, Trichuris, and Capillaria, but these populations were too numerically small or too unevenly distributed within the control groups to be given much emphasis. The experimental parasitic populations which developed in the 10 control calves amounted to 91, 763 worms (total).     

Evaluation of fenbendazole as an extended anthelmintic treatment regimen for swine

Fenbendazole was given in the feed to swine at a cumulative dosage of 9 mg/kg of body weight over a period of 3, 6, and 12 days to compare efficacy. Four treatment groups of ten 2- to 3-month-old pigs each, with a mean of 15 kg of body weight per group, received 3 mg of fenbendazole/kg/day for 3 days, 1.5 mg/kg/day for 6 days, 0.75 mg/kg/day for 12 days, and no medication. Medicated feed was scheduled so that all treated pigs reached the last day of treatment on the same day, thus making the time between the last treatment and necropsy equal for all groups. Ascaris suum and Trichuris suis were the target species, their presence before treatment being determined by fecal egg counts and at necropsy by worm counts. At necropsy, 9 control pigs were infected with A suum (mean of 18.0 worms/pig), and all control pigs had T suis infection (mean of 36.5 worms/pig). All 3 treatment schedules were 100% effective in removal of A suum; and for T suis, the 3-day regimen was 100% effective, the 6-day regimen, 99.2%, and the 12-day regimen, 91.0%.     

Laboratory investigations on pigs with the new anthelmintic fenbendazole.

The efficacy of fenbendazole was investigated in piglets infected artificially with Hyostrongylus rubidus and Oesophagostomum spp. After administration of 3.5 mg/kg, five-day-old stages of H rubidus were reduced by 72.5 per cent; an effect of 78.4 per cent, 96.0 per cent and 100 per cent was achieved against five-day-old, 16-day-old and 42-day-old stages, respectively, of H rubidus using a dose of 5 mg/kg. A 55 per cent effect was obtained against five-day-old stages after the administration of 3.5 mg/kg. A dose of 5 mg/kg reduced five-day-old, 16-day-old and 42-day-old stages of Oesophagotomum spp by 72.6 per cent, 44 per cent and 100 per cent respectively.     

The anthelmintic efficacy of fenbendazole against a mixed nematode infection in sheep.

Fenbendazole (methyl-5-(phenylthio)-2-benzimidazole carbamate) at dose rates of 5 mg/kg and above was 100 per cent effective in eliminating a naturally acquired Dictyocaulus filaria infection in sheep. The drug was 100 per cent effective in eliminating concurrent infections of adult Trichostrongylus axei, Haemonchus contortus, Haemonchus placei, Ostertagia circumcincta, Ostertagia ostertagii, Cooperia oncophora, Cooperia mcmasterii, Nematodirus spathiger, Neumatodirus filcollis, Oesophagostomum venulosum and Chabertia ovina. Fenbendazole was 93 per cent and 97 per cent effective at doses of 5 and 10 mg/kg respectively in removing infection with adult T colubriformis, and post-treatment worm-egg production was completely suppressed in surviving female worms. No adverse side-effects were observed in treated sheep at either of the two dose rates used.     

Toxicity investigation of fenbendazole, an anthelmintic of swine

The toxicity of fenbendazole, an anthelmintic for use in swine, was tested by feeding 8 growing pigs 2,000 mg of fenbendazole/kg of body weight daily for 14 days. A transient leukopenia developed on day 6, but values returned to base line on day 18, 4 days after discontinuation of dosing. Sorbitol dehydrogenase values were significantly (P less than 0.05) increased from day 4 and returned to base line on day 20. Marked gross or histopathologic lesions were not found.     

Modulation of porcine biotransformation enzymes by anthelmintic therapy with fenbendazole and flubendazole

Fenbendazole (FEN) and flubendazole (FLU) are benzimidazole anthelmintics often used in pig management for the control of nematodoses. The in vivo study presented here was designed to test the influence of FLU and FEN on cytochrome P4501A and other cytochrome P450 (CYP) isoforms, UDP-glucuronosyl transferase and several carbonyl reducing enzymes. The results indicated that FEN (in a single therapeutic dose as well as in repeated therapeutic doses) caused significant induction of pig CYP1A, while FLU did not show an inductive effect towards this isoform. Some of the other hepatic and intestinal biotransformation enzymes that were assayed were moderately influenced by FEN or FLU. Strong CYP1A induction following FEN therapy in pigs may negatively affect the efficacy and pharmacokinetics of FEN itself or other simultaneously or consecutively administered drugs. From the perspective of biotransformation enzyme modulation, FLU would appear to be a more convenient anthelmintic therapy of pigs than FEN.     

Clinical and parasitological evaluations of levamisole as a treatment for bovine stephanofilariasis

Field trials were carried out with two formulations of levamisole for treatment of chronic inflammatory lesions on the muzzle and teats of cattle, caused by Stephanofilaria okinawaensis in the enzootic area of the disease, Ishigaki Island, Okinawa Prefecture, Japan.Cattle were treated orally with levamisole hydrochloride (10% powder) at a dose of 7.5 g/100 kg of body weight once (64 cattle) or twice with an interval of 3 or 4 weeks (five cattle each). Lesions on the muzzle and tests disappeared or were reduced within 4 weeks of the first medication. In some cattle a sign of recurrence was observed 8 weeks after medication.Parasitological and histological examinations were carried out 1 week carried out 1 week (10 cattle), 4 weeks (12 cattle), and 8 weeks (13 cattle) after single oral administration of levamisole hydrochloride. No Stephanofilaria worms were detected at 1 week after medication. A small number of worms were detected at 4 weeks and more were observed 8 weeks after medication.A levamisole phosphate solution (18.2%) was injected subcutaneously once into one teat of each of three cattle, or twice into the neck with a 4-week interval between treatments (five cattle). The dose was 2 ml/teat (364 mg of active ingredient) or 2 ml/45 kg of body weight for the side of the neck. There was marked improvement as with oral medication with levamisole hydrochloride powder.     

Further observations on the characteristics of a bovine parainfluenza-3 variant.

Calves were inoculated with a bovine para-influenza-3 variant to determine its pathogenicity and the stability of its cytopathic feature and its inability to agglutinate chicken erythrocytes. The inoculated calves and one contact animal developed an immune response without significant clinical illness. The clinical response in calves was similar to that induced by the parent virus strain. The variant was shown to retain its characteristic cytopathic effect for Madin Darby bovine kidney cells and its property of hemagglutination following one passage in the natural host.     

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.     

Acute toxicity of paraherquamide and its potential as an anthelmintic.

Paraherquamide, an oxindole alkaloid metabolite of Penicillium paraherquei and P charlesii, is a new anthelmintic with potential broad-spectrum use. In initial trials, it had an excellent safety profile in cattle and sheep at doses efficacious against a dozen or more helminths, but recently it produced unexpected and severe toxicosis in dogs at doses far below those that were safe in the ruminants. To provide data on which to build rational safety tests in the future, we tested the acute toxicity of paraherquamide administered PO to male CD-1 mice and compared its profile with the most potent anthelmintic known, ivermectin. The estimated doses lethal to 50% of a group of mice were 14.9 and 29.5 mg/kg of body weight for paraherquamide and ivermectin, respectively. The no-effect doses were 5.6 and 18.0 mg/kg for paraherquamide and ivermectin, respectively. Signs of intoxication in paraherquamide-treated mice, if they developed, emanated within 30 minutes of administration, irrespective of dose, and consisted of either mild depression with complete recovery or a 5- to 10-minute period of breathing difficulty followed by respiratory failure and death by 1 hour after treatment. Gross necropsy findings in paraherquamide-treated mice that died in the high-dose group were normal. Ivermectin-related toxicity was slower and more predictable, taking place over a 3-day period, with dose-dependent signs of intoxication consisting of tremors, ataxia, recumbency, coma, and death. Necropsy of ivermectin-treated mice that died in the high-dose group revealed dehydration, a condition most likely resulting from the coma-induced state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Laboratory investigations in sheep with a new anthelmintic.

The efficacy of fenbendazole against the following gastrointestinal nematodes was tested in experimentally infected lambs: O circumcincta, H contortus, T colubriformis and N filicollis. As low a dose as 0.5 mg per kg reduced the egg output of a patent infection with H contortus and T colubriformis by 85 per cent to 100 per cent. A dose of 3.5 mg per kg has a 100 per cent effect on three or 10-day-old stages of H contortus and one of more than 99 per cent or 100 per cent T colubriformis. The same dose reduces seven-day-old stages of O circumcincta and N filicollis by more than 94 per cent or 100 per cent, while 10 mg per kg produces a 100 per cent elimination of seven-day-old stages of O circumcincta. In field trials and efficacy of more than 99 per cent was determined after oral dosage with 5.0 mg per kg against Ostertagia, Haemonchus, Trichostrongylus, Cooperia, Nematodirus and Chabertia. Fenbendazole has a wide therapeutic-toxic dose ratio. Discoloration of the wool does not occur. Fenbendazole can be administered as a drench or with the feed.