Competitive, uncompetitive, and mixed inhibitors of the alkaline phosphatase activity associated with the isolated brush border membrane of the tapeworm Hymenolepis diminuta

Several compounds were tested as inhibitors of the alkaline phosphatase (AlkPase) activity associated with the isolated brush border membrane of the tapeworm, Hymenolepis diminuta. Molybdate, arsenate, arsenite and beta-glycerophosphate (BGP) were competitive inhibitors of the hydrolysis of p-nitrophenyl phosphate, while levamisole and clorsulon were uncompetitive and mixed inhibitors, respectively. Molybdate was also a competitive inhibitor of the hydrolysis of BGP and 5'-adenosine monophosphate, and levamisole was an uncompetitive inhibitor of BGP hydrolysis. The apparent inhibitor constants (Ki') for molybdate and levamisole were virtually identical regardless of the substrate, and these data support the hypothesis that the AlkPase activity is represented by a single membrane-bound enzyme with low substrate specificity. Quinacrine, Hg2+, and ethylenediaminetetraacetate were also potent inhibitors of the AlkPase activity, but the mechanisms by which these latter three inhibitors function were not clear.     

The association between frequency of thiabendazole treatment and the development of resistance in field isolates of Ostertagia spp. of sheep

Martin P. J., Anderson N., Lwin T., Nelson G. and Morgan T. E. 1984. The association between frequency of thiabendazole treatment and the development of resistance in field isolates of Ostertagia spp. of sheep. International Journal for Parasitology14: 177–181. Isolates of Ostertagia spp. were obtained from grazing sheep 3,4 and 5 years after nil, planned (five per year) and regular (3-weekly) treatments with thiabendazole (TBZ). Levels of resistance to TBZ were measured by an in vitro egg hatch assay and a controlled anthelmintic efficiency assay. Isolates from planned treatment groups showed an increase in the level of resistance; the lethal concentrations of TBZ to 50% of eggs (LC₅₀s) were 3, 3 and 6 times the LC₅₀s of isolates from nil treatment groups for years 3, 4 and 5 respectively. The LC₅₀s of isolates from regular treatment groups were 14 times higher than those from nil treatment groups in each year. To assess the potential for an increase in level of resistance, additional egg assays were done 14 days after treatment with 44 mg kg^t?1 of TBZ on sheep infected with the planned group isolates for each year. This treatment raised the LC₅₀S for years 3, 4 and 5 respectively by 3, 2 and 1–5 times the LC₅₀s of the same isolates which had not been exposed to additional TBZ treatment. The controlled anthelmintic efficiency assay using 44 mg kg^t?1 of TBZ produced a significant reduction in the number of adult and immature worms from the nil isolate but failed significantly to reduce the number of worms from the planned and regular isolates. A three component analysis resolved the nonlinear trends of the log dose-probit plots in egg hatch assays for isolates from planned treatment groups into subpopulations of susceptible, hybrid and resistant individuals each with different levels of resistance. The proportions of these subpopulations changed in accordance with the level of resistance observed in each year.     

Survey of parasite control programs used in captive wild ruminants

The purpose of this study was to document, through a mailed questionnaire survey, the methods of parasite control currently used in captive wild ruminants. There was a 69% overall response to the survey. The majority of respondents indicated that they used parasite surveillance and identification techniques similar to those used for domestic ruminants. Of the four major anthelmintic drug classes, the benzimidazoles and ivermectin were used most commonly. Many of the parasite control programs had high treatment frequencies which were similar to dosing frequencies reported to result in anthelmintic resistance in domestic animals. Lack of effectiveness by benzimidazoles was perceived to be a problem by many respondents.     

Trichostrongylus colubriformis: effect of anthelmintics on ingestion and oviposition

The effects of the anthelmintics ivermectin, levaminsole, oxfendazole, piperazine citrate, pyrantel pamoate, tetramisole, and thiabendazole on ingestion and oviposition by Trichostrongylus colubriformis were determined. Six of the compounds reduced in vitro feeding at the tested doses while all drugs reduced in vivo feeding after treatment of the host. Additionally, in vitro or in vivo exposure to most anthelmintics decreased oviposition during subsequent in vitro assay. Invermectin had the most pronounced effect on in vivo and in vitro feeding and egg release. The neuromuscular activities of pharyngeal pumping and egg ejection may be suitable systems for rapid determinations of anthelmintic effects.     

Haemonchus contortus: in vitro and in vivo anthelmintic activity of aqueous and hydro-alcoholic extracts of Hedera helix

In vitro anthelmintic activity of crude extracts of the ripe fruits of Hedera helix was investigated on eggs and adult nematode parasites Haemonchus contortus. Aqueous extract of H. helix was also evaluated for in vivo anthelmintic activity at dose of 1.13 and 2.25 g/kg in sheep artificially infected with H. contortus. ED(50) for egg hatch inhibition was 0.12 and 0.17 mg/ml for aqueous and hydro-alcoholic extracts, respectively. There was no statistically significant difference in the activity of the two extract types (p>0.05). Hydro-alcoholic extract showed better in vitro activity against adult parasites compared to the aqueous extract. Significant faecal egg count reduction (FECR) was detected in groups treated with both doses of H. helix (p<0.05) on day 2 post-treatment. On day 7 post-treatment significant reduction was detected only for higher dose of H. helix (p<0.05) while on day 14 post-treatment there was no significant FECR in both groups treated with H. helix. The percentage of larvae recovered from culturing faeces obtained from groups of sheep treated with lower and higher doses of H. helix was 47.52% and 36.07%, respectively, which was significantly lower than (p<0.05) that recovered from the control group (60%). Significant (p<0.05), dose dependent total worm count reduction (WCR) was observed for groups of sheep treated with H. helix. Increasing the dose of H. helix improved the efficacy against the male than the female parasites. Treatment with both doses of H. helix helped the animals maintain their packed cell volume (PCV) unlike the untreated control group. The overall findings of the current study indicated that H. helix has a potential anthelmintic benefit and further in vitro and in vivo evaluation of the different parts and fractions is needed to make use of this plant for therapeutic purposes.     

No Evidence for Resistance to Fenbendazole in Trichostrongylus tenuis,a Nematode Parasite of the Red Grouse

ABSTRACT The parasitic nematode Trichostrongylus tenuis has a detrimental effect on red grouse (Lagopus lagopus scoticus) at the individual and population levels. Treatment using grit coated with the anthelmintic fenbendazole hydrochloride reduces parasite infection and increases grouse density. However, a frequent and low dose of anthelmintic increases selection pressure for parasite resistance, a serious practical and economic problem. We used an egg hatch assay to test resistance of T. tenuis from 12 moors in northern England, which differed in grit treatment intensity. The anthelmintic concentration that prevented 50% and 95% of T. tenuis eggs from hatching (ED₅₀ and ED₉₅, respectively) did not differ among moors and were not related to treatment. We suggest annual monitoring and responsible anthelmintic use to prevent resistance so that medicated grit continues to enhance red grouse management.     

Comparison of efficacy of moxidectin and ivermectin in the treatment of Strongyloides fulleborni infection in rhesus macaques

BACKGROUND: Strongyloides infection may result in clinical disease or confound experimental protocols that utilize non-human primates. There is presently a Strongyloides fulleborni infection rate of approximately 27% in the Tulane National Primate Research Center's breeding colonies despite the routine therapeutic and prophylactic use of ivermectin. METHODS: A study was conducted to determine if moxidectin treatment offers advantages to the intestinal parasite control program. A total of 150 rhesus macaques (Macaca mulatta) that were removed from the breeding colonies due to illness were selected for the study. The animals were randomly assigned to treatment groups with 75 receiving ivermectin and 75 receiving moxidectin. Egg counts were performed on fecal samples collected pre- and post-treatment. RESULTS: Both treatments resulted in decreases in the number of eggs/g in the post-treatment sample as compared with the pre-treatment sample; however, no significant difference was found between treatment groups. CONCLUSIONS: With the data demonstrating a similar efficacy in both ivermectin and moxidectin treated macaques, the benefit of moxidectin treatment relates to biosafety and topical application.