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PubMed1988

Development of a novel in vitro equine anthelmintic assay.

An in vitro assay involving the use of a horse strongyle (Strongylus edentatus) and the micromotility meter has been developed to test for equine anthelmintic activity. Three commercially available equine anthelmintics (dichlorvos, ivermectin, and pyrantel pamoate) and an investigational drug (p-toluoyl chloride phenylhydrazone) were evaluated in this assay at four concentrations. After a 24-h incubation, greater than or equal to 10 micrograms/ml of all four drug treatments significantly (P less than or equal to 0.05) reduced the motility of ensheathed L-3 S. edentatus larvae, thereby indicating anthelmintic activity. Pyrantel pamoate also reduced motility at 1 microgram/ml, while the hydrazone significantly increased movement at this level. At 0.1 microgram/ml, none of the treatments significantly reduced motility; one treatment (dichlorvos) significantly increased larval motility. Incubation for 48 h resulted in significant activity (reduction in motility) at greater than or equal to 1 microgram/ml with two drugs (ivermectin, pyrantel pamoate); dichlorvos and the hydrazone reduced motility at greater than or equal to 10 micrograms/ml. None of the treatments significantly reduced motility at the lowest concentration (0.1 microgram/ml); however, at 48 h, two treatments (dichlorvos, hydrazone) significantly increased motility at the lowest concentration (0.1 microgram/ml). The in vitro S. edentatus motility assay proved to be sensitive, accurate and rapid. This assay system should be a valuable addition to tests used to identify potential equine anthelmintics, monitor helminth resistance to drugs, and perhaps define the kinetics and mode of action for drugs.

Animals↗
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↗
PubMed1982

[Biological assay of anthelmintic drugs. Determination of DE 50].

Experiments on ivermectine, thiabendazole and levamisole were performed by using the Nippostrongylus brasiliensis rat model. The aim of the experiments was to study the 50% as well as 99.5% doses of the above anthelmintics. Besides this a relative evaluation of drugs was also carried out and different dose efficiencies were compared by keeping one anthelmintic as a standard. The results were obtained on the following experimental conditions: homogeneity of the group of rats (age, weight and sex), uniform infestation in all the animals (3000 larvae at day zero), administration of anthelmintics was done on day 6 and autopsy was performed on the 9th day of infection. The effectivity of anthelmintic is essentially based on the mortality of the adult worms. The mathematical expression is obtained on the basis of logarithmic values of the doses and probit percentage analysis. The graph obtained between dose vs efficiency is a straight line, so the value of DE 50 can be calculated using this straight line. The normal distribution of worms exposed to a dose was verified which justifies the statistical interpretation.

Animals↗
PubMed1981

Use of guniea pigs to assay anthelmintic resistance in ovine isolates of Trichostrongylus colubriformis.

Guinea pigs infected with Trichostrongylus colubriformis were used to develop an assay for anthelmintic resistance by determination of worm burdens following treatment with test anthelmintics. To achieve comparable efficacy with the recommended dose of thiabendazole and levamisole in sheep, dose rates in guinea pigs had to be increased two to four fold. For example, thiabendazole at 100 mg/kg in guinea pigs was 96.6 per cent effective against a thiabendazole susceptible (GS) strain of T colubriformis, but had no effect against a thiabendazole-resistant (VRSG) strain. In sheep 50 mg/kg of thiabendazole would have a similar efficacy against each strain respectively. Morantel tartrate at 10 mg/kg in guinea pigs was 99 to 100 per cent effective against the GS strain but only 54 per cent effective against a morantel resistant (PF4) strain. A slope ratio assay was used to calculate the relative potency of anthelmintics by comparing efficacies against resistant strains with efficacy against the GS strain. Resistance of the VRSG strain to thiabendazole was confirmed with a relative potency for this drug of 0.047 in guinea pigs. The PF4 strain was resistant to both thiabendazole and levamisole which had relative potencies of 0.168 and 0.255 respectively. The advantages of this statistical treatment together with the cost and time savings of the guinea pig model over a conventional critical anthelmintic assay in sheep are discussed.

Animals↗
PubMed1981

Prolonged anthelmintic effect of closantel and disophenol against a thiabendazole selected resistant strain of Haemonchus contortus in sheep.

Two long-acting anthelmintics, closantel and disophenol, were tested by treatment 90, 60 and 30 days before challenge with a thiabendazole selected laboratory strain of Haemonchus contortus. The sheep were slaughtered 28 days after infection for total worm counts. A significant reduction in the number of adults remaining at autopsy was recorded after treatment with both anthelmintics 30 and 60 days before challenge but there was zero efficacy when the animals were treated 90 days before challenge. No significant difference was exhibited between the two compounds. Variability in response was recorded between animals on the 60 day period of treatment, which for disophenol may be dose related because animals receiving the lower volumes showed higher worm counts. For both anthelmintics a variability in the rate of metabolism may be responsible. The possibility offered by both anthelmintics for treating benzimidazole resistant strains of H contortus is discussed.

Animals↗
PubMed1992

Effects of an anthelmintic treatment programme on sheep productivity in the Middle Atlas, Morocco.

This study evaluated the production advantages of the strategic anthelmintic treatment of both lambs and ewes in an area endemic for gastro-intestinal nematodes, lungworms and liver flukes. The liver fluke infections were generally chronic. The lambs were treated with albendazole (SmithKline Beecham), fenbendazole (Hoechst Roussel) or a vitamin supplement and their weight gains were followed over the next 7 months. The control group, which received a vitamin supplement only, gained 6.67 kg from July to January. The group that received fenbendazole, an anthelmintic with no activity against liver flukes, gained 10.42 kg over the study period. The third group which received albendazole, an anthelmintic with efficacy against liver flukes, gained 13.07 kg over the same period. Lamb deaths apparently due to liver flukes were 12, 4, and zero for the control, fenbendazole and albendazole groups, respectively. Similar advantages were observed in the ewes. Deaths were 16, 8, and zero in the control, fenbendazole and albendazole groups, respectively. The lambing rate in the control group was significantly lower than that in either of the 2 treated groups. The number of services per conception was significantly lower in the albendazole treated group than that in either of the other groups. These studies demonstrated the advantages of anthelmintic treatment in sheep in a helminth endemic area. While removing gastro-intestinal nematodes and lungworms improved production, the additional removal of liver flukes enhanced production gains as well as reducing deaths.

Albendazole↗
PubMed2005

Increased resistance to anthelmintics of Haemonchus contortus eggs associated with changes in membrane fluidity of eggshells during embryonation.

The embryonation of nematode eggs has been shown to increase their resistance to anthelmintics when parasites are submitted to egg hatch assays. Nevertheless, no mechanism has been suggested to explain this phenomenon. Earlier observations by other authors showed that the biochemical composition of eggshells is altered during the embryonation of eggs. The functional consequences of these changes have not been identified. We studied the changes in membrane environment (eggshells) of Haemonchus contortus eggs during the embryonation by fluidity measurements and their effects on nonspecific mechanisms of resistance to anthelmintics. We previously demonstrated that these mechanisms imply P-glycoproteins (Pgp) belonging to the multi-drug resistance (MDR) system and that the Pgp activity is very susceptible to their lipidic environment. The results obtained here show that the embryonation induced a significant and gradual increase in eggshell fluidity which was associated with an increased resistance to anthelmintics. Differences were observed between H. contortus isolates with various levels of resistance which might result from their specific biology and/or membrane composition. The membrane environment changes could act both on the solubilization of anthelmintics into the eggs and on the efflux of these lipophilic molecules by Pgp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Fecundity of anthelmintic resistant adult Haemonchus contortus after exposure to ivermectin or benzimidazoles in vivo.

A strain of Haemonchus contortus resistant to the benzimidazoles, ivermectin and salicylanilides was used to study the effect of exposure to ivermectin or oxfendazole on the number of eggs produced by adult female parasites. After anthelmintic administration there was a reduction in the faecal egg count of the infected lambs. Ivermectin caused a reduction in the number of eggs within adult parasites for up to 72 hours but this returned to higher than pre-treatment levels at 168 hours after treatment. After oxfendazole treatment there was an increase in the number of eggs stored in the adult parasites at 24 hours and then a significant reduction in the number of eggs for over 168 hours. This suggested that both ivermectin and oxfendazole have a deleterious effect on the reproductive potential of female H contortus although the parasites are resistant to these drugs. These results confirm the importance of allowing up to 10 days to elapse between the time of administration of an anthelmintic and the collecting of faecal samples when using the faecal egg count reduction test to identify anthelmintic resistance, especially when using benzimidazoles. The more prolonged effect on fecundity produced by oxfendazole may reflect the antimitotic action of the benzimidazole anthelmintics.

Animals↗
PubMed2006

In vivo anthelmintic activity of ginger against gastrointestinal nematodes of sheep.

This paper describes the anthelmintic activity of Zingiber officinale Roscoe (family Zingiberaceae) rhizome, commonly known as ginger, to justify its traditional use in veterinary medicine. Crude powder (CP) and crude aqueous extract (CAE) of dried ginger (1-3 g/kg) were administered to sheep naturally infected with mixed species of gastrointestinal nematodes. Both CP and CAE exhibited a dose- and a time-dependent anthelmintic effect with respective maximum reduction of 25.6% and 66.6% in eggs per gram (EPG) of faeces on day 10 of post-treatment. Levamisole (7.5 mg/kg), a standard anthelmintic agent, exhibited 99.2% reduction in EPG. This study shows that ginger possesses in vivo anthelmintic activity in sheep thus justifying the age-old traditional use of this plant in helminth infestation.

Animals↗
PubMed2004

Testing for direct anthelmintic effects of bioactive forages against Trichostrongylus colubriformis in grazing sheep.

The aim of the present study was to investigate potential direct anthelmintic effects of forages that contain plant secondary metabolites (PSM) towards the intestinal nematode Trichostrongylus colubriformis. For this purpose, we introduced an experimental design, which enabled us to investigate the direct anthelmintic effects of PSM-rich forages, without significant interference of possible indirect immunological effects of PSM. Sixty parasite naive sheep were infected with 8000 T. colubriformis L(3) on day 1 of the experiment. On day 28, sheep entered one of the experimental plots, which consisted of four PSM-rich forages and one control: Lotus pedunculatus (lotus), Hedysarium coronarium (sulla), Onobrychis viciifolia (sainfoin), Cichorium intybus (chicory) and Lolium perenne/Trifolium repens (grass/clover). On day 35 of the experiment, all sheep were re-infected with 8000 T. colubriformis L(3) and were killed on day 42. By day 42, all parasites of the primary infection would have been recovered as adults, whereas those of the secondary challenge would have only developed to the fourth stage larvae within a week (i.e. days 35-42). The first batch of larvae would enable us to investigate possible direct anthelmintic effects of PSM-rich forages against adult T. colubriformis, whereas the second one whether grazing on the PSM-rich forages could affect the establishment of the incoming infective larvae. Sheep grazing on lotus tended to have a lower FEC compared to sheep grazing on grass/clover (P = 0.06), whereas daily faecal output was higher in sheep grazing lotus compared to those grazing on the other forages (P < 0.05). As a consequence, daily egg output was similar in all sheep. Grazing on the PSM-rich forages for a period of 2 weeks did not affect the immature and adult parasite populations. Although the present experimental design enabled us to test the experimental hypothesis, the lack of evidence on a direct anthelmintic effect of PSM-rich forages can not be considered conclusive, as the composition of PSM-rich forages is variable within and across grazing seasons.

Animal Feed↗
PubMed1997

Anthelmintic resistance in human helminths: Learning from the problems with worm control in livestock.

During the past decade, the prevalence of anthelmintic resistance in some economically important helminths of sheep, goats and horses has increased dramatically. In some regions of Australia, South America and South Africa, anthelmintic resistance has become a serious threat to the survival of the sheep industry. Mass treatment programmes and exclusive reliance on anthelmintics for worm control in livestock are amongst the most important reasons for the development of anthelmintic resistance. In this article, Stanny Geerts, Gerald Coles and Bruno Gryseels draw the attention to a number of errors that have occurred in the control of helminths in livestock and that should be avoided in the control of worms in humans.

Journal Article↗
PubMed1998

Methimazole-mediated enhancement of albendazole oral bioavailability and anthelmintic effects against parenteral stages of Trichinella spiralis in mice: the influence of the dose-regime.

The influence of methimazole (MTZ) inhibitor of the microsomal oxidases on the systemic availability of the albendazole sulpho-metabolites (ABZS-MT) albendazole-sulphoxide (ABZSO) and albendazole-sulphone (ABZSO2) and on its anthelmintic effects was investigated in a mouse model for helminthic infections. Plasma concentrations of the ABZS-MT were measured by high performance liquid chromatography (HPLC) following treatment of Swiss CD-1 mice with albendazole (ABZ) alone or ABZ plus MTZ, at both single and repeated doses. The anthelmintic effects were assessed in age-matched mice similarly treated following infection with Trichinella spiralis. MTZ significantly (p < 0.01) increased the ABZS-MT plasma concentrations although the pharmacokinetic profile varied greatly according to the dose of ABZ administered. When ABZ was given at a single dose of 50 mg/kg followed by MTZ at 3 mg/kg, a cumulative effect was observed in the ABZS-MT plasma levels with pharmacokinetic parameters (Tmax = 24 h, Cmax= 30.88 microg/ml and AUC = 1120.80 microg h/ml) significantly ( p < 0.01) higher than those following administration of ABZ alone (Tmax = 3 h, Cmax = 11.00 microg/ml and AUC = 268.03 microg h/ml). This cumulative effect was absent following administration of ABZ at 100 mg/kg where, after reaching a maximum (Cmax = 27.23 microg/ml) at 3 h post-administration (Tmax), the ABZS-MTplasma levels felt down quickly to values under those obtained after administration of ABZ at the same dose, but alone (AUC = 362.15 microg h/ml vs. 340.15 microg h/ml, respectively). When ABZ was given at 50 mg/kg together with MTZ three times every 24 h, a rapid decrease was observed in the ABZS-MT plasma levels following administration of both the second and third doses, respectively. The pharmacokinetic profile of ABZS-MT following administration of each of the three doses of ABZ at 100 mg/kg plus MTZ was the same as that obtained after the single treatment. The rapid decrease of the ABZS-MT plasma levels observed after the sustained treatment or after the single treatment at 100 mg/kg could be due to a microsomal oxidase inductive effect (probably the cytochrome P-450) caused by ABZSO. The co-administration of MTZ significantly (p < 0.01) increased the anthelmintic effects of ABZ against both migrating and encysted larvae of T. spiralis. Repeated treatment did not improve the anthelmintic effects of the single treatment as the efficacies against both stages of the parasite were always lower or identical to those of the single treatment at the corresponding doses.

Administration, Oral↗
PubMed2004

Molecular basis of the differential sensitivity of nematode and mammalian muscle to the anthelmintic agent levamisole.

Levamisole is an anthelmintic agent that exerts its therapeutic effect by acting as a full agonist of the nicotinic receptor (AChR) of nematode muscle. Its action at the mammalian muscle AChR has not been elucidated to date despite its wide use as an anthelmintic in humans and cattle. By single channel and macroscopic current recordings, we investigated the interaction of levamisole with the mammalian muscle AChR. Levamisole activates mammalian AChRs. However, single channel openings are briefer than those activated by acetylcholine (ACh) and do not appear in clusters at high concentrations. The peak current induced by levamisole is about 3% that activated by ACh. Thus, the anthelmintic acts as a weak agonist of the mammalian AChR. Levamisole also produces open channel blockade of the AChR. The apparent affinity for block (190 microm at -70 mV) is similar to that of the nematode AChR, suggesting that differences in channel activation kinetics govern the different sensitivity of nematode and mammalian muscle to anthelmintics. To identify the structural basis of this different sensitivity, we performed mutagenesis targeting residues in the alpha subunit that differ between vertebrates and nematodes. The replacement of the conserved alphaGly-153 with the homologous glutamic acid of nematode AChR significantly increases the efficacy of levamisole to activate channels. Channel activity takes place in clusters having two different kinetic modes. The kinetics of the high open probability mode are almost identical when the agonist is ACh or levamisole. It is concluded that alphaGly-153 is involved in the low efficacy of levamisole to activate mammalian muscle AChRs.

Amino Acid Sequence↗
PubMed1995

The prevalence of anthelmintic resistance in ovine case submissions to animal health laboratories in New Zealand in 1993.

An analysis was undertaken of 177 veterinary diagnostic case submissions to two North Island and two South Island animal health laboratories for faecal egg count reduction testing in sheep during 1993 to provide some comparative data on the frequency of occurrence of anthelmintic resistance. The results suggest that resistance to anthelmintics in sheep nematodes may be more common in the South Island than the North. In both instances this mainly involved resistance to a single drench type, the benzimidazoles. The data indicated a frequency of occurrence of resistance to benzimidazole anthelmintics of 61 and 72%, to levamisole-type anthelmintics of 29 and 29% and to benzimidazole-levamisole combinations of 11 and 22% for submissions to North and South Island laboratories, respectively. In submissions from the South Island, resistance to benzimidazoles involved infections of Nematodirus spp. alone much more frequently than those from the North.

Journal Article↗
PubMed1983

Seasonal variation in anthelmintic response by cattle to dermally applied levamisole.

Four experiments in 1978-79, and 2 in 1982 designed to define the optimum dose rate of dermally applied formulations of levamisole are described. These experiments showed that the absorption of levamisole with resultant blood levels and anthelmintic activity is strongly influenced by temperature. In warm to hot conditions percutaneous absorption is rapid and high blood levels with high anthelmintic activity against Haemonchus placei, Ostertagi sp, Trichostrongylus sp, Cooperia sp, Oesophagostomum radiatum, O. venulosum and Dictyocaulus viviparus result from dose rates of 10 mg/kg or more. In cold weather the high efficacy against H. placei, Cooperia sp, and Oesophagostomum sp is unchanged, but efficacy against Ostertagia sp, T. axei and D. viviparus decreases to the extent that a mean dose rate of 20 mg/kg (range 15 to 25 mg/kg) is necessary if the anthelmintic activity of dermally applied levamisole is to match that of either parenterally or orally administered material. These anthelmintic data are supported by the levamisole blood profile which in winter months, peaks at a figure of one quarter or less of that obtained from a similar dose rate in warm conditions. The implications of this variability in action are discussed.

Animals↗
PubMed1986

The prevalence of anthelmintic resistance in sheep nematodes on the central tablelands of New South Wales.

A survey was undertaken to assess the prevalence of anthelmintic resistance in sheep nematode populations on 40 commercial farms distributed throughout the central tablelands of New South Wales. Representatives of the 2 major groups of broad spectrum anthelmintics with different modes of action (thiabendazole and levamisole) were used at the manufacturer's recommended dose rates. Efficacy was assessed on the basis of the reduction in faecal strongyle egg counts 7 days after treatment. An efficacy of less than 90% using both anthelmintics was obtained on 4 farms. Thiabendazole had an efficacy of less than 90% on a further 21 farms and levamisole had an efficacy of less than 90% on an additional 4 farms. There was no evidence of anthelmintic resistance on 8 farms, while the remaining 3 had insignificant parasite burdens. Based on larval cultures from faeces, Ostertagia and Trichostrongylus were the most significant species in resistant populations. Haemonchus burdens were sporadic and levels of resistance relatively low. Nematodirus burdens were widespread but no evidence of resistance was detected.

Animals↗
PubMed1997

Nematode control practices and anthelmintic resistance on British sheep farms.

Nearly 23 per cent of 3000 randomly selected sheep farmers returned questionnaires on strategies to control the development of anthelmintic resistance. Twenty-five per cent stated that they regularly checked the accuracy of their drenching gun, and 52 per cent stated that they weighed a few animals and treated the whole flock like the heaviest. The mean annual frequency of dosing lambs was 4.39 compared with 2.43 for ewes. Forty-eight per cent stated that they changed the anthelmintic group annually. Seventeen per cent always treated sheep brought on to their farm with ivermectin. However, only 7 per cent had had their flocks tested for anthelmintic-resistant nematodes. The responses suggest that most sheep farmers are not actively seeking to prevent the development and spread of anthelmintic-resistant nematodes.

Animal Husbandry↗
PubMed1989

Influence of helminth parasite exposure and strategic application of anthelmintics on the development of immunity and growth of swine.

Infection of pigs with the intestinal roundworm parasite Ascaris suum and strategic application of anthelmintic drugs during the growing phase of development were observed for specific effects on 1) development of immunity in feeder pigs and 2) growth rate during the finishing phase. Management treatments included maintenance in a parasite-free concrete environment, maintenance in a concrete environment and inoculation with 1,000 infective A. suum eggs every other day over a 52-d period, and maintenance on a dirtlot contaminated with A. suum and Trichuris suis eggs. Within each management environment, pigs were either untreated, treated with ivermectin or treated with fenbenzadole at strategic times during parasite exposure. Protective immunity, assessed by a challenge inoculation with A. suum eggs following management treatments, was not affected by ivermectin or fenbenzadole treatment during exposure, but adult worm burdens were reduced and the pattern of A. suum larval antigen serum antibody responses were different from those in control pigs not treated with drugs. Exposure to A. suum and treatment with anthelmintics during the growing phase reduced adult worm burdens following the finishing phase of growth. Rate, but not efficiency, of gain was significantly improved by anthelmintic treatment following natural exposure to parasites. Strategic treatment of pigs with anthelmintics following inoculation with A. suum eggs in a concrete management environment had no effect on rate of gain. Results suggest that natural exposure to parasites during the growing phase without therapeutic treatment causes permanent damage to growth potential.

Animals↗