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PubMed2001

Anthelmintics for the control of nematode infections in the brushtail possum (Trichosurus vulpecula).

AIMS: To determine the efficacy of eprinomectin, doramectin and a combination of albendazole and levamisole in suppressing or eliminating nematode infections or faecal egg counts (FEC) in possums naturally or experimentally infected with Parastrongyloides trichosuri, Paraustrostrongylus trichosuri and Trichostrongylus colubriformis. METHODS: To establish an effective dose of eprinomectin, groups of naturally infected possums were treated with 0, 0.5, 2.5, 5.0 or 7.5 mg/kg liveweight (LW) eprinomectin pour-on (n=6 possums/group) and changes in FEC and nematode worm counts at necropsy determined, 18 days later. Efficacy of the 7.5 mg/kg dose was re-examined in a second group of naturally infected possums (n=12) by monitoring FEC weekly for 28 days post-treatment. Persistence of the anthelmintic effect of doramectin injection was tested using nematode-free possums treated with 0, 0.2, 0.4, 0.6 or 0.8 mg/kg LW (n=3 possums/ group), which were experimentally infected 14 days later with T. colubriformis, Paraustrostrongylus trichosuri and Parastrongyloides trichosuri infective larvae. Response to treatment was assessed by FEC and nematode worm counts at necropsy, 42 days posttreatment. Efficacy of a 1.0 mg/kg dose of doramectin was subsequently examined using naturally infected possums (n=11) by monitoring FEC weekly for 28 days post-treatment. To determine the efficacy of a levamisole-albendazole combination drench, possums with naturally acquired nematode infections (n=6) were treated orally with 37.5 mg/kg LW levamisole plus 23.75 mg/kg LW albendazole on 2 occasions, 7 days apart, and response to treatment was assessed by monitoring FEC for 57 days. RESULTS: Eprinomectin 7.5 mg/kg LW reduced Paraustrostrongylus trichosuri worm counts by 98 % (p<0.05). Doramectin 0.6 mg/kg LW reduced Parastrongyloides trichosuri and Trichostrongylus spp worm counts by 99% (p<0.05) and 0.8 mg/kg LW reduced Paraustrostrongylus trichosuri by 100% (p<0.05), in possums challenged with larvae 14 days after treatment. Treating possums with a levamisole-albendazole combination orally, twice, 7-days apart, reduced FEC by 99%. CONCLUSIONS: The doses of anthelmintics required to effectively control nematodes in possums were higher than those recommended for animals for which they are currently registered. Possums tolerate the high dose rates of anthelmintics used in this study without apparent adverse effects.

Journal Article↗
PubMed2001

Breeding sheep in New Zealand that are less reliant on anthelmintics to maintain health and productivity.

Breeding sheep that are less reliant on the use of anthelmintics to maintain acceptable health and productivity is one of several options that may assist farmers to manage the growing anthelmintic-resistance problem in New Zealand and meet consumer demands to minimise drug usage in livestock. Although it has been known for many years that genetic factors contribute to the ability of sheep to cope with roundworm challenge, attempts to selectively breed for such factors have occurred only recently. Two host traits, 'resistance' and 'resilience', are thought to be involved in limiting the deleterious effects of roundworms on the health and productivity of sheep, and the associated need for treatment with anthelmintics. Over the last decade, considerable advances have been made in our understanding of the feasibility and implications of breeding for these traits under practical conditions. The experimental breeding lines developed as part of this research are now proving to be a valuable resource for further work directed at identifying genes and/or genetic markers associated with host resistance and understanding the mechanisms of host immunity to nematode parasites in ruminants. This review provides an up-to-date summary of the results of research in this field, with particular reference to dual-purpose sheep in New Zealand, and describes how this information is being applied in practical breeding programmes.

Journal Article↗
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↗
PubMed1985

Anthelmintic resistance in nematode parasites of goats.

Cases of anthelmintic resistance on 3 goat farms in Gippsland were investigated. On the first farm Haemonchus contortus, Trichostrongylus colubriformis and Ostertagia (Teladorsagia) circumcincta were found to be resistant to fenbendazole, but the first 2 species were fully susceptible to levamisole. On the second farm a population of T. colubriformis, resistant to concurrent full doses of levamisole and a benzimidazole, was found to retain this resistance when transferred to sheep. On the third farm, heavy mortality due to Ostertagia and Trichostrongylus spp burdens was arrested only by the use of concurrent full doses of levamisole and oxfendazole; no single anthelmintic was found to be effective. A disturbing rise in the incidence of clinical helminthiosis, often accompanied by anthelmintic resistance, occurred on goat farms in Gippsland early in 1984.

Animals↗
PubMed1986

Survey of anthelmintic resistance in Western Australian sheep flocks. 1. Prevalence.

Between July 1981 and December 1983, 116 randomly selected sheep farms in the south west of Western Australian were surveyed for resistance to anthelmintics. A faecal worm egg count reduction test was carried out on each farm. Anthelmintics tested were thiabendazole (44 mg/kg) and levamisole (7.5 mg/kg) given by intra-ruminal injection and comparisons were made with an untreated group on each farm. Successful tests were carried out on 84 farms and 68% of these had resistant worms present. The prevalence of thiabendazole resistant populations was for H. contortus 18%; Teladorsagia, 41% and Trichostrongylus, 48% and for levamisole resistant populations H. contortus, 10%; Teladorsagia, 41%; Trichostrongylus, 24%, and Nematodirus, 10%. Multiple resistant populations were found on 17% of farms. Although the distribution of nematode genera varied between the 400 to 750 mm and the greater than 750 mm rainfall zones there was no significant difference in the prevalence of resistance between zones. About one third of resistant populations were severely resistant (less than 60% reduction). It is likely that resistant worms were present on many farms without causing clinical disease and continued anthelmintic selection pressure will result in further development of resistance.

Animals↗
PubMed1981

Morphological Observation Of Enterobius Vermicularis Expelled By Various Anthelmintics.

When enterobiasis cases were treated with anthelmintics only for one time, the interval to recurrence was variable by different drugs used. And this phenomenon is supposedly connected with biological or developmental cycle of the worm and the consequent efficacy of the different anthelmintics. This study was undertaken to confirm this fact by studying the expelled worms morphologically to correlate the anthelmintics efficacy and stage of worm development in Enterobius vermicularis. A total of 131 children in 3 orphanages was examined by 4 anal swabs (mean positive rate, 80%). They were randomized into 5 experimental groups. Each group was treated with placebo, mebendazole, pyrantel, pyrvinium, and piperazine (70 mg/kg, single dose) respectively. After treatment, all stool were collected for 3 days to get the expelled Enterobius. A total of 6,165 pinworms was studied under the microscope. The sex was discriminated and the length was individually measured. A number of male pinworms was collected in all groups. Females of 2~11 mm in length were also collected in 5 groups. However, significantly larger number of short females was observed in mebendazole group compared with other groups. Twenty-one days after the first treatment, all children were again treated with mebendazole. Once more stool were examined. A total of 1,853 worms was collected. In mebendazole group, there were no females longer than 8.74 mm in the second treatment. In pyrvinium group, 8.31mm in lenght was the longest for female. However in control, pyrantel and piperazine groups, females of 2~11 mm in length were collected. From above results, one could conclude that the removing ability of mebendazole and pyrvinium was satisfactory for the worms in the early stage of development in Enterobius. Pyrantel and single dose of piperazine showed less effective in worm reduction ability especially on those at the early stages.

Journal Article↗
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↗
PubMed1991

Anthelmintic-induced destrobilation and its influence on calculated drug efficacy in Hymenolepis diminuta infections in rats.

Anthelmintic efficacy studies typically involve direct counts of worms remaining in the host shortly after drug treatment. Few such studies, however, have considered the phenomenon of tapeworm destrobilation when determining effective dosages. The present study reports on the frequency of drug-induced destrobilation and the subsequent regeneration of Hymenolepis diminuta in rats following treatment with niclosamide or praziquantel and its implications with respect to the apparent efficacy of these anthelmintics. Drug efficacies very similar to those reported in the literature were determined upon examination of infected animals 24 hr posttreatment. Small regenerating worms were, however, observed in the small intestine of rats 8 days after treatment, indicating that destrobilated worms were present, but overlooked, during the initial examination. Within several days posttreatment, destrobilated worms can regenerate to a size that is readily apparent in the gut contents, allowing the effective dosage to be determined with much greater confidence. Due to the demonstrated ability of these destrobilated worms to regenerate to the gravid state, it is imperative that a fully effective anthelmintic dosage be determined and administered.

Animals↗
PubMed1990

A larval development test for the detection of anthelmintic resistance in nematodes of sheep.

First stage larvae of a number of species of parasitic nematodes of sheep have been shown to develop to third stage larvae in the presence of a defined medium consisting of Earle's balanced salt solution and yeast extract. A larval development test, based on this culture technique, was used as a screen for detecting the presence of anthelmintic resistance in nematodes of sheep. It was found to be sensitive and simple to use and also appeared capable of detecting resistance to any of the main anthelmintic groups. Available anthelmintic sensitive and resistant strains of Haemonchus contortus and Ostertagia circumcincta showed differences in development when incubated in the presence of either thiabendazole, levamisole and ivermectin. These differences were expressed as the minimum inhibitory concentration required to prevent larval development over the incubation period.

Animals↗
PubMed1984

Controlled and clinical evaluations of the anthelmintic activity of a levamisole pour-on formulation against gastrointestinal nematodes in cattle.

Beef-type calves (n = 107) with naturally occurring helminth infections were used in a series of 3 controlled experiments to study the anthelmintic activity of a new pour-on formulation of levamisole. In the 1st experiment, the efficacy of a single treatment of levamisole pour-on at a rate of 10 mg/kg of body weight was determined, using a placebo pour-on in a similar volume as a control. In the 2nd experiment, calves were treated with levamisole pour-on at doses 0 (nontreated control), 7.5, 10, or 12.5 mg/kg of body weight. In the 3rd experiment, the anthelmintic efficacy of the optimal dose of levamisole pour-on (10 mg/kg of body weight) was compared with that of injectable levamisole at the recommended rate (6 mg/kg of body weight). In all 3 studies, levamisole pour-on, at a dosage of 10 mg/kg of body weight, was efficacious (90% to 100%) against the adult forms of Trichostrongylus axei, Haemonchus placei, Ostertagia ostertagi, Cooperia spp, Oesophagostomum radiatum, Nematodirus spp, and Bunostomum phlebotomum. Efficacy was moderate to good against Capillaria bovis, and poor or inconsistent against Strongyloides papillosus and Trichuris ovis. Clinical tests of anthelmintic efficacy and local tolerance of levamisole pour-on were conducted in 371 beef and dairy cattle in Mexico. Fecal egg counts were consistently reduced 2 weeks after a single application of levamisole pour-on at a dosage of 10 mg/kg of body weight. Local reactions were limited to various degrees of dry hair coat for up to 2 weeks at the application site. Hair loss or skin abnormalities were not observed in any of the treated cattle.

Animals↗
PubMed1984

Controlled field trial on the anthelmintic effectiveness of the morantel sustained-release bolus in grazing calves.

The direct and indirect anthelmintic efficacies of the morantel sustained-release bolus given to calves were assessed in a 154-day controlled field trial. A permanent calf pasture (divided into 2 lots) and naturally parasitized calves were used. The medicated calves were given the bolus at the time they were placed on the pastures. Control calves did not receive anthelmintic therapy. The effectiveness of the bolus to control parasitic gastroenteritis was determined by monitoring various parasitologic determinants. The treated calves had significantly (P less than 0.01) reduced numbers of fecal nematode eggs for every posttreatment sampling period when compared with the control calves. Tracer calves, used periodically during the study to indicate pasture larval infectivities, had equivalent worm burdens at the beginning of the trial (treated vs control pasture). Tracer calves, added later in the study to the lot with treated calves, harbored 83% to 94% fewer nematodes than did their counterparts in the lot with the controls. Plasma pepsinogen concentrations, reflective of abomasal worm burden size and/or activity, were significantly higher (P less than 0.01) in the control than in the treated calves from day 54 until trial termination. At trial termination, the treated calves weighed an average of 27.8 kg more and harbored 80.9% fewer nematodes than the control calves. The morantel sustained-release bolus is an anthelmintic delivery device that has therapeutic and prophylactic antinematode activities. To achieve its optimum performance, the bolus must be used so that the epizootiologic patterns of the predominate parasitic nematodes are effectively disrupted. Generally, internal nematode parasitisms in the calf flourish during the animal's first springtime grazing period.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1984

Effect of whole herd anthelmintic treatment on milk production of dairy cows.

Fifteen of 29 commercial dairy herds were given a series of anthelmintic treatments. The remaining herds were untreated to provide a measure of seasonal variation. In the treated herds all milking cows were treated once in the summer and the autumn and three times at monthly intervals in late winter and early spring. Any other animals grazing the same area were similarly treated. No herds had been treated with anthelmintics in the preceding year and mean herd lactations for that year were used as covariate corrections. This experimental design had the potential to detect differences in production of the order of 5 X 7 per cent (P = 0.05). Although levels of subclinical parasitism were low, anthelmintic treatment increased milk fat production by 10.8 kg (8.3 per cent) in heifers. Average response in mature cows was much smaller (3.1 per cent) and not significant. Apparent milk fat responses in individual herds were variable with no relationship to level of production in the previous year.

Abomasum↗
PubMed1980

Studies on the effect of treatment with anthelmintics on weight gain in calves, naturally infected with gastrointestinal nematodes.

To avoid disease outbreaks caused by gastro-intestinal nematodes different prophylactic measures are recommended. In this connection pasture hygienic achievements and anthelmintics are used. In practice it is often difficult to realize pasture hygienic steps as move the animals to parasite free areas and to avoid that they come back to the infected. In many cases the parasite control is limited to routine deworming. Our intention was to study if anthelmintic treatment without other measures had any effect on weight gain and number of eggs in faeces in calves naturally infected with Ostertagia ostertagi. The studies were done during two stable seasons 1975/76 and 1976/77 when the calves were treated two weeks after stabling, and during two grazing seasons 1976 and 1977 when the calves were treated 20 days or 15 and 20 days after turning out. In none of the trials any obvious influence on the weight gain and number of eggs was observed. The failing effect during the stable season might depend on the fact that the parasites to more than 90% were in inhibited L4-stage, and the failing effect during grazing, is surely an effect of reinfection when the calves remain on the infected pastures. As prophylactic measure anthelmintic treatment is of very little value if not the calves at the same time are protected against reinfection by moving to clean pastures.

Animals↗
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&#xa0;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↗
PubMed1989

An evaluation of techniques used for the detection of anthelmintic resistance in nematode parasites of domestic livestock.

In vitro and in vivo techniques used for the detection of anthelmintic resistance are reviewed in terms of their versatility, reliability, accuracy, cost and simplicity. The faecal egg count reduction test is considered the most suitable for field screening of resistance but the larval development assay is likely to prove a valuable adjunct in such investigations. Other in vitro techniques, such as egg hatch tests, larval motility and tubulin binding assays are recommended as suitable only for research investigations. Similarly, in vivo procedures such as the critical and controlled anthelmintic efficacy tests are considered to be appropriate only for specific research purposes because of the costs involved in such studies.

Animals↗
PubMed1984

Nematospiroides dubius: response of the late fourth-stage larva to anthelmintics in vitro.

Approximately 60% of fourth-stage larvae of Nematospiroides dubius recovered from mice 6 days after infection, developed to the young adult stage when cultured over a 7-day period in a complex medium in vitro. Larvae at the late fourth stage of development were found to be highly susceptible to most broad spectrum anthelmintics under in vitro conditions, the benzimidazole, imidazothiazole, pyrimidine, isothiocyanate and macrocyclic lactone compounds all being active at very low concentrations. Narrow spectrum anthelmintics active only against ascarids, pinworms, filariae, cestodes or trematodes had little or no effect on these larvae. Ineffective also were those chlorinated hydrocarbon, substituted phenol and salicylanilide compounds known to affect Haemonchus but not trichostrongylid worms in general. It is concluded that in vitro assays employing larvae of N. dubius are useful for the stringent screening of compounds for broad spectrum antitrichostrongyle activity. Used in conjunction with in vivo screens employing N. dubius in mice, they also afford means for detecting intrinsic activity against the parasite in a system free from any complicating host pharmacokinetics.

Animals↗