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PubMed1986

A survey in Louisiana of intestinal helminths of ponies with little exposure to anthelmintics.

Ponies reared with minimal or no exposure to anthelmintics were surveyed for intestinal helminths in order to estimate prevalence and intensity of parasite populations unaltered by frequent exposure to anthelmintics. Thirty-seven mixed breed ponies of varying ages were examined. Thirty-four species of nematodes and 2 species of cestodes were found. Twenty-four of the nematode species (including 1 new species) were in the subfamily Cyathostominae (small strongyles). Eighty-seven percent of the total burden of adult small strongyles in the large intestine was composed of 10 species. By comparing the results of the present survey with those of recent surveys of horses from herds which had been subjected to treatments with anthelmintics, the effect of prolonged usage of anthelmintic treatment on the prevalence of individual species possibly can be estimated. The general ranking of the 10 most common cyathostome species was similar to those described in recent surveys of horses, suggesting that anthelmintic pressure does not affect the prevalence of most cyathostome species. The lack of anthelmintic treatment appeared not to affect prevalence rates for Anoplocephala perfoliata and Anoplocephala magna when compared to other studies. Conversely, prevalence rates for Strongylus spp., Triodontophorus spp., Craterostomum acuticaudatum, Oxyuris equi, and Parascaris equorum were higher than those reported for these species in recent studies of horses.

Animals↗
PubMed1983

An economic and efficacy comparison between morantel (when administered from an intraruminal bolus) and conventional anthelmintic treatment in grazing cattle.

A economic and efficacy comparison in the control of parasitism in grazing cattle was conducted between conventional anthelmintic treatment applied according to various recommended regimes and an anthelmintic treatment delivered intraruminally at a sustained level from a specially designed bolus. The bolus used was the morantel sustained release bolus which has been designed to prevent the establishment of parasite infections so that, when administered at turnout to all cattle intended to graze the same pasture, parasitologically "safe" pastures could be produced and maintained for an entire grazing season. The various conventional anthelmintic treatment regimes used for the study were selected from the most commonly recommended and used systems of treatment found in commercial use throughout Europe. A total of 471 first-season grazing calves received the morantel sustained release bolus at spring turnout in 38 field trials conducted in Austria, Belgium, Denmark, France, West Germany, Ireland, the Netherlands, Norway, Sweden and the United Kingdom. In each trial, equal numbers of control and bolus-treated animals were maintained on separate halves of a divided pasture. In 25 of the 38 field trials, the control animals received tactical therapy with conventional anthelmintic only when exhibiting signs of parasitic gastroenteritis, while in the remaining 13 trials all animals in each control group received strategic anthelmintic treatment at specified intervals during the grazing season. Compared with control animals, significant reductions in faecal worm egg output of bolus-treated animals was recorded. Subsequent reductions in herbage larval contamination developed on pastures grazed by bolus-treated animals compared with control pastures so that, overall, the bolus-treated animals out-performed the control animals in all 38 trials by a mean of 16.3 kg (P less than 0.05). Labour and management costs (for animal treatment and handling) were substantially reduced in bolus-treated animals compared with animals receiving either tactical or strategic anthelmintic treatment.

Animals↗
PubMed1988

Anthelmintics and control.

Anthelmintic control of Ostertagia ostertagi in cattle presents some special problems because the arrested larval stage (hypobiotic EL4) tolerates all of the older anthelmintics. The only anthelmintics on the North American market that are effective against this stage as well as the adult and developing stages are ivermectin and fenbendazole. In addition to these, the newer broad-spectrum benzimidazoles and probenzimidazoles, albendazole, febantel, netobimin and oxfendazole, are effective and available in other countries. These anthelmintics can be used for prophylaxis of Type II ostertagiasis. The older anthelmintics, levamisole, morantel tartrate, thiabendazole, coumaphos, haloxon and phenothiazine, are effective against the adults and to some extent the developing stages of O. ostertagi so that they can be used to treat Type I ostertagiasis. They can also be used to prevent incoming larvae from establishing if they are administered continuously over a long period of time. This is possible with long term in-feed administration or by the use of the morantel slow release bolus. In cooler temperature regions, where cattle are housed over the winter, this bolus is given at turnout to remove any parasites in the animals and to kill incoming larvae for 60-90 days. This can prevent the build up of significant infective larvae on pasture so that very few arrested L4 larvae accumulate in the summer/autumn, effectively preventing Type II ostertagiasis from occurring later. The use of ivermectin and the newer benzimidazoles in intermittent or slow release devices should prove highly effective in the control of Type I and II ostertagiasis, as well as of subclinical ostertagiasis. To achieve maximum economic benefit, the use of anthelmintics should be based on sound epidemiological considerations, so that stock are not rapidly reinfected after treatment.

Animals↗
PubMed1984

Anthelmintic resistance and sheep management practices in south western Victoria.

Twenty-eight farms in 7 shires in south western Victoria were selected and tested for presence of benzimidazole-resistant nematodes between November 1979 and June 1981. Mean faecal egg counts of sheep were less than 100 strongyloid eggs/g on 11 farms. Faecal egg count reduction tests were conducted on the remaining 17 farms and thiabendazole was less than 90% efficient in reducing egg counts in sheep from 5 (29%) of these farms. Thiabendazole-resistant Teladorsagia circumcincta were identified at necropsy of experimentally infected treated sheep. In further studies a survey of 104 farms was conducted in the Mount Rouse and Dundas shires of western Victoria in 1981 and 1982 respectively to determine the prevalence of anthelmintic resistance in these shires. Mean faecal egg counts among weaner sheep in the winter-spring of both years were less than 100 eggs/g which indicated low levels of parasitic nematode populations. A faecal egg count reduction test was conducted on 10 farms and thiabendazole was less than 90% efficient on 3; levamisole was greater than 90% efficient in all 10 tests. Most of the surveyed farms carried Merino or Merino crossbred sheep at 10 to 15 dry sheep equivalents per ha and weaners were treated with anthelmintics 3 to 6 times per year. Management procedures based mainly on anthelmintic therapy were effective in controlling nematode populations in weaner sheep, although many producers alternated between different groups of anthelmintics within the same year contrary to current recommendations for long-term preservation of anthelmintic efficacy. It was concluded that anthelmintic resistance was not of practical importance to the majority of sheep producers in the region.

Animal Husbandry↗
PubMed1986

Control of helminthosis in lambs by strategic treatment with closantel and broad-spectrum anthelmintics.

Treatment of ewes with broad-spectrum anthelmintic in August (pre-lambing) and early November, and of lambs in early November and early February, was effective in controlling infections with Trichostrongylus spp in lambs reared on contaminated pastures under set-stocked conditions. It was ineffective in controlling infections with Haemonchus contortus; 82% of lambs had to be withdrawn from the experiment because of severe haemonchosis. Treatment with closantel (7.5 mg/kg) at the same times was very effective against H. contortus but ineffective against Trichostrongylus spp; 25% of lambs had to be withdrawn because of severe trichostrongylosis. The same schedule using broad spectrum anthelmintic and closantel administered concurrently was effective against both parasites; no lambs had to be withdrawn and the bodyweight gain of lambs was higher than in lambs treated with broad-spectrum anthelmintic or closantel alone. The results provide a basis on which to develop a preventive anthelmintic treatment program to control haemonchosis and trichostrongylosis in sheep which will allow the current high frequency of treatment with broad-spectrum anthelmintics to be reduced. Such a program may retard selection for anthelmintic resistance in Trichostrongylus spp.

Animals↗
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↗
PubMed2006

Assessment of anthelmintic resistance in nematode parasites of sheep and goats owned by smallholder farmers in eastern Ethiopia.

The anthelmintic resistance status was investigated of nematode parasites of sheep and goats owned by smallholder farmers in communities that received breeding stock from a source where a high level of anthelmintic resistance has been reported. The investigation used the faecal egg count reduction technique, whereby suitable animals within each of eight separate communities were pooled to achieve the numbers required to conduct separate tests for both sheep and goats. Anthelmintics tested were albendazole (ABZ), tetramisole (TET), a combination (ABZ + TET) and ivermectin (IVM), at the manufacturers' recommended dose rates. Results showed that there was no evidence of anthelmintic resistance in nematode parasites of either sheep an goats in any community. This indicates that dilution of resistant parasites imported with introduced breeding stock, and the low selection pressure imposed by the smallholder farmers themselves, has prevented anthelmintic resistance from emerging in nematode parasites of small ruminants in these communities.

Animals↗
PubMed1991

A possible biochemical mode of action for benzimidazole anthelmintics.

Albendazole (ABZ), cambendazole (CBZ), oxibendazole (OBZ), and thiabendazole (TBZ) are potent, orally active, broad spectrum anthelmintics widely used in human and veterinary medicine. As members of the benzimidazole series, they are closely related chemically, and it is likely that they exert their anthelmintic effects in an identical fashion. We have examined the effects of these anthelmintics on the electrical resistance of planar bimolecular lipid membranes and compared the results with those obtained with a known uncoupler, 2,4-dinitrophenol (2,4-DNP). All drugs tested markedly reduced membrane resistance at concentrations lower than 0.1 microM and were better proton conductors than 2,4-DNP by at least an order of magnitude. The sequence of proton conducting efficiency was ABZ greater than OBZ greater than TBZ greater than CBZ greater than 2,4-DNP. From 1 to 40 microM, ABZ and CBZ substantially decreased P/O (phosphorous/oxygen) ratios in coupled rat liver mitochondria in a concentration-dependent fashion using beta-hydroxybutyrate as the substrate. 2,4-DNP was also shown to decrease P/O ratios, but less effectively than the benzimidazole anthelmintics. These experiments indicate that the benzimidazole anthelmintics are lipid-soluble proton conductors that are effective in artificial (phospholipid bilayer) and natural (rat liver mitochondria) membrane systems. Dissipation of the transmembrane proton gradient should result in diminished levels of cellular ATP. In vivo treatment with a therapeutically effective dose of ABZ caused a severe disturbance in the energy balance of Hymenolepis diminuta; this was evident from a distinct drop in ATP levels, and from a decline in the ATP/ADP ratios, adenylate energy charge (AEC) and available adenylate energy (AAE) values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Potential problems associated with the controlled release of anthelmintics in grazing animals.

A high, constant and sustained release of drug appears to be a major requirement to avoid a late season rise in pasture infectivity that may result in production losses in calves in autumn or Type II osteragiasis in the following spring. The timing of administration is of crucial importance and will vary in regions of different epidemiology, such as between northern and southern United States. Lack of a standard and reliable technique for pasture larval counts has resulted in some negative or erratic results which are open to question. Although controlled release anthelmintics offer advantages of convenience, a comparison of the economic benefits at present favours prophylactic treatment of dairy heifers with conventional anthelmintics 3 and 6 weeks after spring turnout in northern regions of the Northern Hemisphere. There is a serious risk that boluses based on controlled release by diffusion will behave like slow decaying insecticides and select strongly for drug resistance, especially if farmers administer them in succession throughout the grazing season. There are, however, 2 features in the design of a controlled release device that in theory may minimize the risk of rapid selection for resistance: a high and constant release of anthelmintic followed by a rapid decline to zero as the device becomes exhausted. Under these conditions, the device may even prolong the useful life of an anthelmintic to which resistance has already developed. This paper was presented at Pfizer Symposium on The Application of Sustained Release Anthelmintic Dosage Forms in the Control of Parasites in Grazing Animals at the World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) 10th International Conference, 18-20 August 1983, Perth, W.A., Australia.

Animals↗
PubMed1993

Anthelmintics.

Anthelmintics remain the principal means for the prevention and control of subclinical and clinical ostertagiasis. The selection of an appropriate anthelmintic depends on whether one is controlling or preventing Type I ostertagiasis (caused by the establishment of adult worms derived from recently acquired infective larvae), preventing Type II (treating pre-Type II or inhibited larvae) or controlling Type II ostertagiasis (caused by the development of inhibited larvae to adults), or using the anthelmintic as part of an epidemiologically based plan to reduce pasture contamination with infective Ostertagia ostertagi larvae. In the latter case, the choice of an anthelmintic may depend on whether the targets for treatment are only adult worms and developing larvae or whether the targets include hypobiotic larvae. Thus for Ostertagia control, anthelmintics must be divided into those that normally control all stages, such as the avermectin group (ivermectin, abamectin and moxidectin) and some of the benzimidazoles (albendazole, oxfendazole and fenbendazole at appropriate dose rates), and those that only control adult worms and developing larvae (levamisole, morantel, coumaphos, phenothiazine and thiabendazole).

Animals↗
PubMed1993

Relationship between pharmacological properties and clinical efficacy of ruminant anthelmintics.

The purpose of this review article is to establish a relationship between pharmacological properties and clinical efficacy of the most widely used broad-spectrum veterinary anthelmintics. The impact of drug pharmacokinetics/pharmacodynamics on anthelmintic efficacy and resistance is discussed. We review the clinical pharmacokinetics of the currently available anthelmintics used in livestock-imidazothiazoles, tetrahydropyrimidines, benzimidazoles/pro-benzimidazoles, salicylanilides (closantel) and avermectin-type compounds. Understanding the pharmacokinetic and metabolic behaviour of broad-spectrum anthelmintics in the host, and factors modulating that behaviour, is highly important for maximizing anthelmintic utility and efficacy.

Animals↗
PubMed2005

Atom, atom-type and total molecular linear indices as a promising approach for bioorganic and medicinal chemistry: theoretical and experimental assessment of a novel method for virtual screening and rational design of new lead anthelmintic.

Helminth infections are a medical problem in the world nowadays. In this paper a novel atom-level chemical descriptor has been applied to estimate the anthelmintic activity. Total and local linear indices and linear discriminant analysis were used to obtain a quantitative model that discriminates between anthelmintic and non-anthelmintic drug-like compounds. The discriminant model has an accuracy of 90.11% in the training set, with a high Matthews' correlation coefficient (MCC=0.80). To assess the robustness and predictive power of the obtained model, internal (leave-n-out) and external validation process was performed. The QSAR model correctly classified 88.55% of compounds in this external prediction set, yielding a MCC of 0.77. Another LDA model was carried out to outline some conclusions about the possible modes of action of anthelmintic drugs. It has an accuracy of 93.50% in the training set, and 80.00% in the external prediction set. After that, the developed model was used in the virtual--in silico--screening and several compounds from the Merck Index, Negwer's Handbook and Goodman and Gilman were identified by the model as anthelmintic. Finally, the experimental assay of an organic chemical (a furylethylene derivative) by an in vivo test permits us to carry out an assessment of the model. An accuracy of 100% with the theoretical predictions was observed. These results suggest that the proposed method will be a good tool for studying the biological properties of drug candidates during the early state of the drug-development process.

Anthelmintics↗
PubMed2006

In vitro screening of six anthelmintic plant products against larval Haemonchus contortus with a modified methyl-thiazolyl-tetrazolium reduction assay.

Because of the increasing anthelmintic resistance and the impact of conventional anthelmintics on the environment, it is important to look for alternative strategies against gastrointestinal nematodes. Phytotherapy could be one of the major options to control these pathologies. Extracts or ingredients of six different plant species were tested against exsheathed infective larvae of Haemonchus contortus using a modified methyl-thiazolyl-tetrazolium (MTT) reduction assay. Pyrantel tartrate was used as reference anthelmintic. Bromelain, the enzyme complex of the stem of Ananas comosus (Bromeliaceae), the ethanolic extracts of seeds of Azadirachta indica (Meliaceae), Caesalpinia crista (Caesalpiniaceae) and Vernonia anthelmintica (Asteraceae), and the ethanolic extracts of the whole plant of Fumaria parviflora (Papaveraceae) and of the fruit of Embelia ribes (Myrsinaceae) showed an anthelmintic efficacy of up to 93%, relative to pyrantel tartrate. Based on these results obtained with larval Haemonchus contortus, the modified MTT reduction assay could be a possible method for testing plant products with anthelmintic properties.

Animals↗
PubMed1998

Anthelmintics and ion-channels: after a puncture, use a patch.

Two of three major types of anthelminitic, the avermectins and the nicotinic agonists, exert their therapeutic effect by an action on ligand-gated membrane ion-channels of nematodes. The avermectins, such as ivermectin, open glutamategated chloride channels which have so far been found only in invertebrate preparations; nicotinic anthelmintics, like levamisole, selectively gate nematode nicotinic acetylcholine receptors. We describe recent advances in the knowledge of the molecular structure of these ion-channel receptors in nematodes. Because opening of the ion-channels by these two groups of anthelmintic generates currents across cell membranes of nematodes, we can use electrophysiological methods to examine properties of the channels, the mode of action of the anthelmintics, and changes in the receptors associated with anthelmintic resistance. We illustrate some of our observations on these receptors using a two micro-electrode current-clamp technique to monitor membrane resistance (the puncture); and then some observations using The patch-clamp technique to monitor currents through individual ion-channels (the patch). The receptors for the two major groups of anthelmintics may not be homogeneous. Even in a single membrane patch from one muscle cell, nematode nicotinic acetylcholine receptors show evidence of heterogeneity and the avermectins may have multiple sites-of-action. If separate independent recessive genes are involved in production of different receptor subtypes, and if each subtype has to change to allow the development of resistance by the whole nematode, then the probability of resistance developing would be smaller than for anthelminitics with a single site-of-action. The MISER (multiple independent sites-of-action evading resistance) concept favours the development and use of anthelminitics with more than one site-of-action.

Animals↗
PubMed2000

Cross-sectional serological survey on gastrointestinal and lung nematode infections in first and second-year replacement stock in the netherlands: relation with management practices and use of anthelmintics.

A cross-sectional survey was carried out on 86 farms randomly distributed in The Netherlands. After housing following the first and the second grazing season (FGS and SGS) serum samples were collected to determine IgG levels against Cooperia oncophora and Dictyocaulus viviparus, and the pepsinogen content. A questionnaire was used to inquire on grazing management practices and the use of anthelmintic drugs. On 80.7 and 60.2% of the farms FGS and SGS animals, respectively, were treated at least once with an anthelmintic drug. The percentage for the SGS animals indicates that the use of anthelmintic drugs in those animals has increased enormously over the last 10-15 years. Generally, parasitic nematode control in the FGS is good on most farms, but it can be characterised as being overprotective. There is a tendency that if anthelmintic drugs are used in the FGS they also are used more often in the SGS. On 12 farms (14%), no anthelmintic drugs were given in the FGS and the SGS. These farms did not differ from the others with respect to management practices in any obvious way. The serological results were in general very low, indicating low levels of exposure to gastrointestinal nematode infection in both FGS and SGS animals. This was not surprising in view of the good to high level of nematode control practices reported by the farmers. Although not statistically significant, a consistent result was that serological results for the SGS animals were more often positive or on average higher on those farms where FGS parasite control tended to be excessive. For D. viviparus, a prevalence rate of 41% positive farms was found. Following comparison with previous data, it is speculated that lungworm (sero-)prevalence in replacement stock may be declining as a result of continuing high levels of parasite control in replacement stock. It is concluded that the results confirm previous surveys, lending support to the conclusion that parasitic nematode control on Dutch dairy farms, certainly in FGS calves, is good but tends to be overprotective.

Animal Husbandry↗
PubMed2003

Resistance to prophylactic treatment with macrocyclic lactone anthelmintics in Teladorsagia circumcincta.

Sixty-four Romney ewe lambs were allocated to 12 groups on the basis of liveweight. Four groups (n=5) were administered oral ivermectin (IVM), 4 (n=6) oral moxidectin (MOX) and the remaining 4 (n=5) controlled-release capsules containing IVM (IVM-CRCs). Nine and 10 days later, the groups within each treatment type were challenged with infective-stage larvae (L3) of 1 of 4 different isolates of Teladorsagia circumcincta (two doses each of 5000 L3). The first of these (S) was known to be anthelmintic-susceptible; the second (OR) was a multiple anthelmintic-resistant strain recovered from the field following therapeutic failure of both ivermectin and moxidectin and subsequently maintained in the laboratory without further anthelmintic selection; the third (R) was derived from OR but had been passaged for five generations indoors with each generation being screened with all three broad-spectrum anthelmintic classes; and the fourth (RxS) was an F1 cross between the R and S isolates. As anticipated, because of its limited residual activity, IVM had no significant effect on the establishment, 9 and 10 days post-treatment, of any of the parasite isolates. In contrast MOX, which has greater residual activity, was highly effective at preventing the establishment of the S isolate but showed no significant effect against the OR, R or RxS isolates. The IVM-CRC was also highly effective at preventing the establishment of the S isolate and furthermore it significantly reduced establishment of both the OR and RxS isolates, although it had no significant effect against the R isolate. The results suggest that with respect to the establishment of T. circumcincta L3s following anthelmintic treatment, macrocyclic lactone (ML) resistance is effectively a dominant trait in the presence of MOX, while it behaves as a partially dominant/recessive trait under treatment with IVM-CRCs. The potential implications of this finding in relation to selection for ML resistance in T. circumcincta are discussed.

Abomasum↗
PubMed2006

The effect of an indirect anthelmintic treatment on parasites and breeding success of free-living pheasants Phasianus colchicus.

In Great Britain free-living common pheasants Phasianus colchicus are often managed at high densities owing to their popularity as a quarry species. They are prone to infection by a range of parasite species including Heterakis gallinarum, Capillaria spp. and Syngamus trachea. In 1995 the efficacy of an indirect anthelmintic technique for controlling parasitic worm burdens of pheasants was determined in a pilot study on a shooting estate in the south of England. Between 2000 and 2003 a large-scale field experiment was conducted on nine estates in eastern England to determine the effect of the technique on parasite burden and pheasant breeding success. In the absence of anthelmintic treatment worm burdens increased rapidly through March and April, whereas birds given anthelmintic-treated grain had lower worm burdens during the same period. The breeding success of pheasants was significantly higher on plots provided with anthelmintic treatment, although no long-term increases in population densities were observed. The burdens of the most common parasite H. gallinarum were significantly lower in pheasants from treatment plots six weeks after the anthelmintic treatment had ceased, but spring treatment did not influence parasite burden in the following winter.

Animal Feed↗
PubMed1990

Avermectin and avermectin derivatives are antagonists at the 4-aminobutyric acid (GABA) receptor on the somatic muscle cells of Ascaris; is this the site of anthelmintic action?

The mechanism underlying the ability of the anthelmintic avermectin to paralyse the nematode Ascaris is not yet fully understood. Using conventional two-electrode electrophysiological recording techniques we have demonstrated that micromolar concentrations of ivermectin block the inhibitory GABA response on the muscle cells of the parasitic nematode Ascaris. The ability of a number of avermectin derivatives to act as receptor antagonists for the Ascaris muscle GABA receptor has been determined. This provides useful information to compare with the in vivo anthelmintic potency of these compounds. Abamectin, the most potent anthelmintic, was the most potent compound at inhibiting the GABA response whilst octahydroavermectin, a compound which lacks anthelmintic activity, did not block the GABA receptor. This is consistent with the notion that the GABA receptor antagonist properties of the avermectins could contribute to their anthelmintic action.

Animals↗