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At least 19 recordsLinked to original sources
PubMed1978

The anthelmintic efficacy of non-benzimidazole anthelmintics against benzimidazole resistant strains of Haemonchus contortus and Trichostrongylus colubriformis in sheep.

The anthelmintic efficacy of 6 non-benzimidazole compounds and thiabendazole against standardised, benzimidazole resistant strains of H. contortus and T. colubriformis in sheep was determined using a controlled test. All compounds were administered intraruminally at their recommended therapeutic dose rates and 4 of the compounds were also assessed at half their recommended therapeutic dose rates. Levimisole at a dose of 6.4 mg/kg body weight, morantel at 4.4 mg/kg and 8.8 mg/kg, naphthalophos at 6.25 mg/kg and 12.5 mg/kg, rafoxanide at 7.5 mg/kg and phenothiazine at 530 mg/kg were 98% or more effective in removing adult infections of benzimidazole resistant H. contortus. Rafoxanide at 3.75 mg/kg, phenothiazine at 265 mg/kg and carbon tetrachloride at 0.05ml/kg were less effective, removing 80%, 73% and 72% respectively of the benzimidazole resistant H. contortus worm burdens. Against the benzimidazole resistant T. colubriformis levamisole at 6.4 mg/kg, and morantel at 4.4 mg/kg and 8.8 mg/kg removed 99%, 68% and 86% respectively of the adult infections. All other anthelmintics had little or no efficacy at the dose rates tested. Thiabendazole at 44 mg/kg had no significant effect against these strains of H. contortus and T. colubriformis. Several non-benzimidazole anthelmintics have shown high efficacy in this experiment and should be suitable for treating infections with benzimidazole resistant H. contortus. Of the anthelmintics tested, only levamisole and morantel show high efficacy against benzimidazole resistant T. colubriformis.

Animals↗
PubMed1977

The effect of route of administration on the anthelmintic efficacy of benzimidazole anthelmintics in sheep infected with strains of Haemonchus contortus and Trichostrongylus colubriformis resistant or susceptible to thiabendazole.

Observations of erratic anthelmintic activity of fenbendazole against known standardised thiabendazole-resistant strains of Haemonchus contortus and Trichostrongylus colubriformis in sheep were investigated. Fenbendazole at a dose rate of 10 mg/kg body weight was administered by oral, intra-ruminal or intra-abomasal routes, and was most effective against both resistant strains following intra-ruminal administration. In addition thiabendazole, oxibendazole, fenbendazole, parbendazole and mebendazole plus two unrelated compounds, levamisole and morantel tartrate, were used at one and a half times their suggested or recommended therapeutic dose rate against thiabendazole-resistant strains of H contortus and T colubriformis in sheep; each drug being administered by the intra-ruminal or intra-abomasal routes. Fenbendazole was more effective against both strains following intra-ruminal administration. Parbendazole was more effective against the resistant strain of T colubriformis following intra-ruminal administration. At the dose rate chosen for the other benzimidazoles used against these resistant strains, there was no difference in anthelmintic efficacy due to route of administration. Levamisole was highly effective against both resistant strains, irrespective of the route of administration. In the groups treated with morantel tartrate, the results obtained were difficult to interpret due to mortalities and a highly variable response in the surviving sheep. Fenbendazole, thiabendazole and mebendazole when used at their suggested or recommended therapeutic dose rate in sheep, were highly effective against known thiabendazole-susceptible strains of H contortus and T colubriformis following both intra-ruminal or intra-abomasal administration.

Abomasum↗
PubMed1977

Nippostronglylus brasiliensis infection in the rat: effect of iron and protein deficiency and dexamethasone on the efficacy of benzimidazole anthelmintics.

Malnutrition, anaemia, and gut parasites are commonly interrelated. Using the Nippostrongylus brasiliensis-rat model, the effect of iron and protein deficiency on the efficacy of benzimidazole anthelmintics was studied. It was demonstrated that the anthelmintics mebendazole and fenbendazole were significantly less effective in eradicating parasites when animals were deficient in iron and protein. This decreased efficacy of anthelmintics in iron and protein deficiency could not be overcome by intraperitoneal administration of the drug. Since nutritional deficiencies may act via impairment of the immune response, anthelmintic efficacy was determined in adequately nourished rats treated with the immunosuppressive drug dexamethasone. A similar decrease in efficacy of mebendazole was shown when these animals were treated with dexamethasone. Thus it is possible that lowered anthelmintic efficacy in iron and protein deficient animals is mediated by immune deficiency. These findings may be relevant to anthelmintic programmes in malnourished communities.

Animals↗
PubMed1979

Nippostrongylus brasiliensis infection in the rat: effect of iron and protein deficiency on the anthelmintic efficacy of mebendazole, pyrantel, piperazine, and levamisole.

The benzimidazole anthelmintics mebendazole and fenbendazole have been shown to be much less effective against Nippostrongylus brasiliensis infections in the rat on a combined iron and protein deficient diet. In the present experiments it was shown that the anthelmintic efficacy of mebendazole was significantly impaired in the rat on either an iron deficient or a protein deficient diet. Furthermore, iron and protein deficiency reduced the efficacy of the anthelmintics pyrantel and piperazine but not levamisole. The finding that nutritional deficiencies reduce anthelmintic efficacy may well be relevant to worm eradication programmes in iron deficient and protein calorie malnourished populations.

Anemia, Hypochromic↗
PubMed1978

Anthelmintic efficacy of oxfendazole in calves.

Oxfendazole, methyl [5-(Phenylsulfinyl)-1H-benzimidazol-2-yl]carbamate given to calves at dose level of 2.5 mg/kg as a paste, as a bolus, or as a drench resulted in excellent (97 to 100%) anthelmintic efficacy against mature Ostertagia ostertagi, Trichostrongylus axei, Cooperia oncophora, C mcmasteri, C pectinata, C punctata, Nematodirus helvetianus, Trichostrongylus longispicularis, Chabertia ovina, and Oesophagostomum radiatum. Against the early 4th stage larvage of O ostertagia and N helvetianus, these formulations had anthelmintic efficacies of 71% to 87% and 21% to 65%, respectively. As the result of differences in drug intake by individual calves, a pelleted feed additive given as top dress on chopped alfalfa hay gave an unsatisfactory mean anthelmintic response. Anthelmintic action in individual calves ranged from none to 98--100%.

Administration, Oral↗
PubMed1978

The efficacy of anthelmintics against third stage larvae of Ancylostoma caninum in Mastomys natalensis.

Investigations have been carried out on the multimammate rat (Mastomys natalensis), orally infected with 1000 third stage larvae of Ancylostoma caninum per animal, to evaluate the larvicidal efficacy of anthelmintics in this paratenic host. The oral or subcutaneous administration of 19 anthelmintics and filaricides revealed good activity for levamisole, cambendazole, and mebendazole against 15-day-old Ancylostoma larvae which were located in the muscular tissue. Similarly, good results were obtained with levamisole and cambendazole against the migrating third stage larvae, by treatment two to six days after infection. The benzimidazole derivatives, thiabendazole, oxibendazole, parbendazole, and fenbendazole showed marked activity only at high dosage rates. The anthelmintics methyridine, amoscanate, pyrantel tartrate, morantel tartrate; the microfilaricidal organophosphates dichlorvos, fenthion, and haloxon; as well as the micro- or macrofilaricidal drugs diethylcarbamazine, nitrofurantoin, nifurtimox, suramin sodium, and thiacetarsamide sodium failed to show larvicidal activity even in high dosages. The average larval recovery rate after oral infection with 1000 third stage larvae, in untreated control animals, was 14.85%.

Ancylostoma↗
PubMed1977

Field trials in sheep with the anthelmintic thiophanate.

Productivity and tolerance trials were conducted with the anthelmintic thiophanate (Nemafax; May & Baker) in sheep in the United Kingdom. Tolerance studies, conducted in sheep of various types under several management systems, in which thiophanate was given orally at recommended dosage (50 to 100 mg/kg), or multiples thereof, in single or repeated doses showed that treatment was in all cases well tolerated. Thiophanate administered at 75 mg per kg or 250 mg per kg to groups of growing lambs with low faecal egg counts produced no post treatment depression of weight gain. When breeding ewes were treated with thiophanate at 150 mg per kg on days 14, 21 and 28 after introduction of rams to the flock, the anthelmintic produced no adverse effect on lambing performance. Trials to assess the beneficial effects of treatment were conducted in weaned lambs naturally infected with gastrointestinal nematodes. Groups of lambs were treated monthly with either thiophanate or tetramisole at recommended dosages. The two anthelmintics produced similar weight gains in the lambs and these were significantly better than those of untreated controls. In untreated controls faecal egg counts increased markedly and the clinical condition of these animals deteriorated.

Administration, Oral↗
PubMed1976

An economic analysis of two schemes for the anthelmintic control of helminthiasis in weaned lambs.

The economic benefit obtained from 2 schemes for the strategic control of helminthiasis in weaned lambs has been assessed in the Western District of Victoria. The results were compared with those from sheep in control groups which were given a single anthelmintic treatment during an outbreak of helminthosis. Mortality in sheep receiving the critical treatment scheme of 2 appropriately timed anthelmintic treatments was 12%, compared with 22% in the group receiving the traditional series of summer and autumn treatments, and 26% in the control group. As a result of this difference in mortality rate, the critical treatment scheme was the most profitable control strategy at 1970-71 prices, yielding a net benefit of $70 per 100 sheep in comparison with the control group which received no strategic treatment. This is 538% return on funds invested in anthelmintic treatment. The benefit from this scheme was not unduly affected by variation in wool or sheep prices, nor to possible differences in mortality rate within the expected range. The traditional treatment scheme also yielded positive net returns, but the results were adversely affected by a small change in mortality rate and therefore could not be recommended for routine use on commerical farms.

Animals↗
PubMed1977

Levamisole: anthelmintic activity in calves following dermal application.

A series of seven experiments designed to evaluate the anthelmintic efficacy of levamisole (1-tetramisole) by dermal application is described. This work involved use of 181 artificially infested calves. The drug was formulated at a concentration of 10% m/v levamisole base in a solvent system promoting dermal absorption and was applied to both sides of the spine in the lumber region at a dose rate of 10 mg levamisole base per kg livemass. A consistent performance was achieved in these investigations, the results from all of which were based upon necropsy findings. Efficacy of treatment was assessed against the third and fourth larval stages and fifth stage larvae/adult worms of six nematode species; the respective efficacies obtained were Haemonchus placei 72,0%; 99,3%; and 100%: Ostertagia ostertagi 85,5%; 38,1% and 74,5%: Cooperia spp. 98,9%; 99,9% and 100%: Bunostomum phlebotomum 83,0%; 100% and 98,5%: Oesophagostomum radiatum 47,4%; 94,9% and 99,6% and Dictyocaulus viviparus 79,5%; 94,1%; 90.9% (fifth stage larvae) and 93,8% (adult worms). The anthelmintic efficacy of levamisole in these experiments is of the same order as that achieved by orthodox methods of administration at dose rates between 7,5 and 10,0 mg levamisole HC1 per kg livemass. These findings add a new dimension to the use of levamisole and to anthelmintic therapy in general.

Administration, Topical↗
PubMed2022

Genomic landscape of drug response reveals mediators of anthelmintic resistance.

Like other pathogens, parasitic helminths can rapidly evolve resistance to drug treatment. Understanding the genetic basis of anthelmintic drug resistance in parasitic nematodes is key to tracking its spread and improving the efficacy and sustainability of parasite control. Here, we use an in vivo genetic cross between drug-susceptible and multi-drug-resistant strains of Haemonchus contortus in a natural host-parasite system to simultaneously map resistance loci for the three major classes of anthelmintics. This approach identifies new alleles for resistance to benzimidazoles and levamisole and implicates the transcription factor cky-1 in ivermectin resistance. This gene is within a locus under selection in ivermectin-resistant populations worldwide; expression analyses and functional validation using knockdown experiments support that cky-1 is associated with ivermectin survival. Our work demonstrates the feasibility of high-resolution forward genetics in a parasitic nematode and identifies variants for the development of molecular diagnostics to combat drug resistance in the field.

Ivermectin↗
PubMed2025

Discovery of Human PIM Kinase Inhibitors as a Class of Anthelmintic Drugs to Treat Intestinal Nematode Infections.

Soil-transmitted helminth (STH) infections affect one-fourth of the global population and pose a significant threat to human and animal health, with limited treatment options and emerging drug resistance. Trichuris trichiura (whipworm) stands out as a neglected disease, necessitating new drugs to address this unmet medical need. We discovered that several different chemical series of related human Provirus Integration sites for Moloney murine leukemia virus (PIM) family kinase inhibitors possess potent anthelmintic activity by using whole-worm motility assays. Systematic structure-activity relationship (SAR) studies based on the pan-PIM kinase inhibitor CX-6258 were conducted to identify compounds displaying improved in vitro motility inhibition of both adult hookworm (Ancylostoma ceylanicum) and adult whipworm (Trichuris muris) nematodes. A broad kinase selectivity screen of >450 human kinases confirms PIM1 kinase and others as potential targets for CX-6258 and analogues thereof. In addition, we demonstrated that CX-6258 significantly reduced worm burden and egg counts in the T. muris infection model of mice, establishing it as a new oral small molecule anthelmintic therapeutic.

Animals↗
PubMed1975

Disruption of spermatogenesis in Fasciola hepatica by some anthelmintics.

Eight-weeks old F. hepatica were recovered from rabbits and rats that had been treated with known fasciolicides and anthelmintics between 4 and 40 h previously. Examination of the surviving flukes showed that spermatogenesis was significantly disrupted by most of the fasciolicides but by none of the other anthelmintics. It is suggested that disruption of spermatogenesis is particularly associated with compounds showing activity against mature F. hepatica.

Animals↗
PubMed1977

The response of nematodes in vivo and in vitro to some anthelmintics.

Dietary feeding of drugs for 5 days to mice infected with Nematospiroides dubius and Hymenolepis nana detected all modern anthelmintics examined except stilbazium. A simple test using eggs of Nematodirus spathiger and adult Nippostrongylus brasillensis to detect anthelmintics in vitro is reported.

Animals↗
PubMed1978

Methyl 6-(phenylsulfinyl)imidazo[1,2-a]pyridine-2-carbamate, a potent, new anthelmintic.

A series of methyl imidazo-[11,2-a]pyridine-2-carbamates was synthesized for anthelmintic testing. The preparation of this class of compounds was simplified by utilization of a novel one-step condensation of the appropriately substituted 2-aminopyridine and methyl chloroacetylcarbamate. The most potent compound, methyl 6-(phenylsulfinyl)-imidazo[1,2-a]pyridine-2-carbamate, was orally effective against a broad range of helminths in sheep and cattle, at a dosage of 2.5 mg/kg. Limited trials in swine and dogs demonstrated anthelmintic activity at higher dosages. Limited observations in sheep and cattle indicated that, in both species, a single oral dose of 200 mg/kg was well tolerated.

Animals↗
PubMed1976

Synthesis of 1- and 2-substituted indazoles as anthelmintic agents.

Selective synthesis of 1- and 2-acyl-, alkoxycarbonyl-, and carbamoylindazoles are described. Spectroscopic data which were the basis for structural assignments are presented. These compounds, particularly methyl 2H-indazole-2-carboxylate and N-heptyl-N-methyl-2H-indazole-2-carboxamide, lack the spectrum of anthelmintic activity of the benzimidazole and benzotriazole anthelmintics to which they are structurally related.

Animals↗
PubMed1975

Novel phosphate anthelmintics. 3. Alkyl and aryl 1-methyleneallyl phosphates, phosphonates, and phosphinates.

A series of new highly chlorinated 1-methyleneallyl ("butadienyl") dialkyl phosphates and related phosphonates and phosphinates has been synthesized and assessed for anthelmintic activity in mice against the tapeworm Hymenolepis nana and the pinworm Syphacia obvelata. Highest activity was observed with diethyl 2,3,3-trichloro-1-dichloromethyleneallyl ("perchlorobutadienyl") phosphate (14), while replacement of both ethoxy groups by methoxy and larger alkoxy or phenyl groups gave less efficacious compounds. In general, chlorine depletion of the 1,3-butadien-2-yl moiety or saturation of one double bond reduced anthelmintic responses.

Animals↗
PubMed1979

Anthelmintic efficiency of oxfendazole, fenbendazole and levamisole against naturally acquired infections of Ostertagia ostertagi and Trichostrongylus axei in cattle.

The anthelmintic efficiencies of oxfendazole, fenbendazole and levamisole, each at 4 dose rates spanning the manufacturers' recommended dosages were compared in beef cattle with naturally acquired infections of Ostertagia ostertagi and Trichostrongylus axei. In 8 of the 9 cases tested there was no significant increase in anthelmintic efficiency due to increased dose rates of any of the drugs. Percentage efficiencies and their standard errors, calculated from mean worm counts of pooled data for adult worms, developing 4th stage and early 4th stage larvae of O. ostertagi, were respectively, 86.9+/-4.2, 77.4+/-6.1, 74.5+/-7.3 for oxfendazole, 93.7+/-2.0. 80.7+/-6.8, 59.6+/-13.9 for fenbendazole and 69.7+/-6.9, 39.4+/-14.8, 31.2+/-22.6 for levamisole. Counts of O. ostertagi from cattle treated with oxfendazole and fenbendazole were not significantly different, but both were significantly lower than those from cattle given levamisole. Efficiency against T. axei exceeded 99% for all drugs. Practical implications for therapy and preventative control of ostertagiasis are discussed.

Animals↗