The effect of single and divided dose administration on the efficacy of fenbendazole against adult stages of benzimidazole resistant sheep trichostrongylids.

Sheep infected with benzimidazole resistant strains of Haemonchus contortus and Trichostrongylus colubriformis were used to compare the anthelmintic efficacy of fenbendazole given as a single dose or administered in a divided dose regime over five days. Statistical analysis showed no significant difference between the two methods of administration for H contortus. On the other hand, divided dose fenbendazole was significantly less effective than single doses against adult T colubriformis at dose rates of 5 and 7.5 mg/kg. In the case of H contortus a highly significant correlation coefficient between post treatment egg counts and worm counts (r = 0.789) was obtained. This suggests that reduction in faecal egg output following drug treatment would provide a useful field indication of anthelmintic performance of fenbendazole (and possibly related compounds) against benzimidazole resistant strains of this parasite.     

The efficacy of fenbendazole and albendazole against the lungworm Muellerius capillaris in goats

In five trials it was found that the daily administration of fenbendazole in the food for 1 or 2 weeks at dosages of 1.25, 2.5 or 5 mg kg-1 live weight was highly effective against Muellerius capillaris infection in goats. Treated animals had significantly lower numbers of larvae in the faeces for up to 223 days after treatment. There was no obvious difference between the different dose levels. Daily treatment for 2 weeks seemed to be slightly more effective than treatment for 1 week. Treatment for 1 week twice with an intervening period of 1 week seemed to be more effective than treatment for 2 weeks continuously. Goats given a single treatment with fenbendazole at 25 mg kg-1 had a significantly lower number of M. capillaris larvae in their faeces on Days 34 and 69 after treatment than the controls, but on Days 126 and 156 after treatment there was no significant difference between these two groups. Albendazole given daily for 2 weeks at a dose of 1.0 mg kg-1 showed a significant effect for up to 153 days after treatment, which was similar to the result of daily treatment with 1.25 mg kg-1 fenbendazole. Goats treated with albendazole twice at 10 mg kg-1 with a 1 week interval showed a significant reduction in the number of Muellerius larvae in the faeces on Day 41 after treatment, but not on Days 97 and 153 after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative plasma disposition kinetics of albendazole, fenbendazole, oxfendazole and their metabolites in adult sheep

The comparative plasma disposition kinetics of albendazole (ABZ), fenbendazole (FBZ) and oxfendazole (OFZ) following their oral administration (5 mg/kg) to adult sheep was characterized. Jugular blood samples were taken serially over a 144 h period and plasma was analysed by high performance liquid chromatography (HPLC) for ABZ, ABZ sulphoxide (ABZSO) and ABZ sulphone (ABZSO₂) (ABZ treatment), and for FBZ, OFZ and FBZ sulphone (FBZSO₂) (FBZ and OFZ treatments). While the ABZ parent drug was not detected at any time post-treatment, ABZSO and ABZSO₂ were the analytes recovered in plasma, after oral administration of ABZ to sheep. The active ABZSO metabolite was the main analyte recovered in plasma (between 0.25 and 60h post-treatment), accounting for 71 % of the total AUC. FBZ, OFZ and FBZSO₂ were the analytes detected in plasma following the oral administration of both FBZ and OFZ to sheep. Low concentrations of FBZ were found in plasma between 4 (FBZ treatment) or 8 h (OFZ treatment) and 72 h post-treatment. The plasma profile of each analyte followed a similar pattern after both treatments; OFZ being the main component detected in plasma. The plasma disposition of ABZ metabolites was markedly different to that of FBZ derivatives. ABZSO exhibited faster absorption and a higher C_max than OFZ (both treatments). Furthermore, while ABZSO declined relatively rapidly in plasma reaching non-detectable concentrations at 60 h post-ABZ administration, OFZ was found in plasma for up to 120 (FBZ treatment) and 144 h (OFZ treatment). The extended detection of OFZ in plasma in both treatments correlated with the prolonged t_1/2β (18 h) and mean residence time (MRT) (30–33 h) obtained for this metabolite compared to those of ABZSO (t_1/2β= (7.0 h); MRT= 12.5 h). These differences between the disposition of ABZ and FBZ metabolites may account for differences in their patterns of efficacy and tissue residues.     

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.     

Chirality of the sulphoxide metabolites of fenbendazole and albendazole in sheep

Two prochiral sulphide drugs, fenbendazole (FBZ) and albendazole (ABZ) were administered orally to sheep. Blood samples were analysed for parent drug and S-oxidation metabolites and the chirality of the sulphoxide metabolites was determined. The plasma concentrations of the enantiomers of the sulphoxides were never a racemate. On the contrary, the ratios were greater than 1 as soon as the sulphoxide compounds could be detected in plasma. They subsequently increased linearly throughout the time course of the kinetics, reaching the level 86:14 after FBZ and 95:5 after ABZ treatment. The major enantiomer represented 74% and 86% of the total AUC of SO.FBZ and SO.ABZ, respectively.     

Comparative efficacy of pyrethrum marc with albendazole against sheep gastrointestinal nematodes

The efficacies of pyrethrum marc and of albendazole against experimental sheep gastrointestinal nematode infection were compared. Sheep were infected orally with 10000 larvae (Haemonchus spp. (60.1%), Oesophagostomum spp. (13.9%), Trichostrongylus spp. (13.2%), Cooperia spp. (8.3%), Nematodirus spp. (3.5%), Strongyloides spp. (0.8%) and Ostertagia spp. (0.2%)). Faecal egg count reduction in albendazole-treated sheep was 100% by day 4 following treatment, compared to 37.03%, 31.3%, 38.9% and 51.8% on days 4, 6, 8 and 10 in pyrethrum marc-treated sheep. These reductions were statistically significant on days 8 and 10 post-treatment (p<0.05). The potential for using pyrethrins for helminth treatment is discussed.     

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.     

The efficacy of levamisole, and a mixture of oxfendazole and levamisole, against the arrested stages of benzimidazole-resistant Haemonchus contortus and Ostertagia circumcincta in sheep

Sheep were allowed to graze pasture that had been seeded with benzimidazole-resistant Haemonchus contortus and Ostertagia circumcincta in order to acquire a burden of arrested larvae. Following housing, sheep were dosed orally with either oxfendazole at a dose rate of 4.7 mg/kg (to confirm the benzimidazole-resistant status of the species of nematode), levamisole at a dose rate of 7.5 mg/kg, or an oxfendazole/levamisole mixture at a dose rate of 4.6 mg/kg oxfendazole and 8.1 mg/kg levamisole. The efficacies of the treatments were assessed by estimation of the arrested larval burden in the abomasum of each sheep, either at 10 or 11 days (oxfendazole and oxfendazole/levamisole mixture), or 12 or 13 days (levamisole), after treatment. Compared to the untreated controls, the protection afforded by a single dose of either levamisole or the oxfendazole/levamisole mixture was >99% against the arrested stages of both Haemonchus contortus and Ostertagia circumcincta. Treatment with oxfendazole confirmed the benzimidazole-resistance status of the two species.     

The activity of triclabendazole against immature and adult Fasciola hepatica infections in sheep

SUMMARY The efficiency of a new benzimidazole anthelmintic, triclabendazole, was tested against cumulative infections with Fasciola hepatica aged 1 to 12 weeks in sheep and compared with that of rafoxanide. At 10 mg/kg, triclabendazole was 99% effective in eliminating both immature and adult flukes. At a lower dose rate of 5 mg/kg, triclabendazole was highly effective against adults and significantly reduced the number of early immature flukes with an 87% overall reduction of fluke burden. Rafoxanide at 7.5 mg/kg showed high efficiency against adult fluke, but its effect on immatures was not significant, and overall efficiency was 64%.     

Efficacy of ivermectin against benzimidazole-resistant Nematodirus spathiger in sheep

Eighteen helminth-free lambs were randomly allocated to six groups of three. Each lamb was dosed with 3300 infective larvae pooled from two isolates of Nematodirus spathiger known to be benzimidazole resistant. One lamb from each group was treated with oral ivermectin, one with oral oxfendazole and one left untreated 21 days after infection. All lambs were humanely killed 14 days later and small intestine worm counts performed. No Nematodirus were found in the ivermectin-treated lambs. Nematodirus numbers were reduced by 13% in oxfendazole-treated lambs relative to the control lambs.     

The efficacy of mixtures of albendazole sulphoxide and levamisole against sheep nematodes resistant to benzimidazole and levamisole

Faecal egg count reduction tests and an anthelmintic efficiency assay were used to assess the efficacy of combinations of albendazole sulphoxide and levamisole against populations of Ostertagia and Trichostrongylus sp. which contained different proportions of worms resistant to both benzimidazole and levamisole anthelmintics. Compared to the effects of either drug alone, significantly greater efficacy was obtained using combinations which included dose rates similar to those recommended for the separate components. At these dose rates, the mixtures reduced mean faecal egg counts by 95% or more, and caused a reduction of 68% in adult Ostertagia sp. and more than 95% for 4th stage Ostertagia and T colubriformis. The increased efficacy of the mixtures could be accounted for by actions of the drugs acting independently.     

The efficacy of fenbendazole in the control of immature strongyle infections in ponies

The efficacy of fenbendazole against immature stages of Trichonema spp., Strongylus vulgaris and Strongylus edentatus was evaluated. Naturally infected 6 to 12 month old ponies were given single, oral doses of 0, 15, 30 and 60 mg/kg of body weight. A dose response relationship was noted between increasing dose levels and efficiency against larval trichonemes and migrating stages of S. vulgaris and S. edentatus. Dose levels of 30 mg/kg and higher removed 93 per cent of mucosal stages of Trichonema spp., while doses of 60 mg/kg removed 83 per cent and 89 per cent of the migrating larvae of S. vulgaris and S. edentatus respectively.     

Anthelmintic efficacy of albendazole against adult Dictyocaulus viviparus in experimentally infected calves.

Anthelmintic activity of albendazole against adult Dictyocaulus viviparus was evaluated in a controlled experiment. Calves were raised nematode-free to approximately 8 weeks of age and were each given 4,000 infective 3rd-stage larvae. Twenty calves with patent parasitisms were allotted to 2 groups of 10 calves each. Calves in group 1 were used as nonmedicated controls, and calves in group 2 were given albendazole in paste formulation at the dosage concentration of 7.5 mg/kg of body weight on the 30th day after administration of infective larvae. At necropsy, nonmedicated control calves had a total of 308 adult D viviparus, whereas the albendazole-treated calves had 11, for an average efficacy of 96.4%. These reductions were statistically highly significant (P less than 0.01). At necropsy, none of the treated calves was passing 1st-stage C viviparus larvae in their feces, whereas control calves were passing an average of 46 larvae/10 g of feces.