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PubMed1996

Pharmacology of anthelmintic resistance.

Anthelmintic resistance has compromised the control of nematode parasites in several animal-based industries. Studies of resistance have not only improved our understanding of this phenomenon but also shed light on physiological systems of parasitic helminths. In addition, research on molecular aspects of anthelmintic resistance may provide selectable markers for use in future transfection studies with helminths. Several anthelmintics act on helminth neuromuscular systems. Drugs such as levamisole are cholinergic agonists and, based on pharmacological studies, levamisole-resistant nematodes appear to have altered acetylcholine receptors. It is likely that anticholinesterase anthelmintics share cross resistance with levamisole. Ivermectin appears to be a glutamate agonist. In vitro studies of ivermectin-resistant nematodes suggest that IVM receptors are located on pharyngeal and somatic muscle. The free-living nematode Caenorhabditis elegans may provide a model for anthelmintic resistance. It has been useful in cloning drug receptors from parasites but differences between its life history and habitat compared with parasitic nematodes may limit its usefulness for studying resistance in these parasites.

Animals↗
PubMed2006

Anthelmintic resistance in New Zealand: a perspective on recent findings and options for the future.

A recent national survey on anthelmintic resistance in cattle and sheep in New Zealand indicated that the magnitude of the problem has increased from very low levels only a few years ago to disturbingly high levels now. There is a particular problem with multiple resistance to all three action families of anthelmintic currently available in Ostertagia (= Teladorsagia) spp in sheep, and to both macrocyclic lactones (ML) and benzimidazoles in Cooperia spp in cattle. The prevalence and extent of resistance indicate that all cattle farmers and most sheep farmers should now be using a combination anthelmintic on most occasions just to achieve effective control of all parasites. Despite this, the presence of resistant parasites has generally not been appreciated by the majority of affected farmers, possibly because most have not formally tested to determine the resistance status of nematodes on their farms. Anthelmintics will remain the cornerstone of gastrointestinal nematode control in sheep and cattle for the foreseeable future but to ensure their continued effectiveness farmers need to be constantly aware of the need to maintain adequate reservoirs of unselected nematodes, i.e. worms in refugia, to minimise the expansion of the resistant population. High-risk practices in relation to selection of resistance need to be identified and avoided or at least their use limited. These include: treating adult animals where there is no identified need, moving newly treated animals onto 'clean' pasture, and failing to effectively quarantine-drench bought-in animals. None of these are new concepts but many have not been adopted or practised. In particular, sheep farmers should endeavour to avoid treating ewes pre-lambing with long-acting anthelmintics. Farmers needs to negotiate a balance between achieving good parasite control and the sustainability of their control options.

Animal Husbandry↗
PubMed1986

Multiple anthelmintic resistance in Trichostrongylus colubriformis.

Following the failure of anthelmintic treatment to control an outbreak of trichostrongylosis in sheep, multiple resistance to levamisole and oxfendazole was confirmed in field strains of Trichostrongylus colubriformis at the CSIRO Pastoral Research Laboratory, Armidale. Resistance in Trichostrongylus spp to levamisole was also confirmed on an adjoining farm. From the results of an experiment where lambs were treated at the recommended dose rate with one or both anthelmintics, it was estimated that 32% of T. colubriformis were resistant to levamisole, 19% to oxfendazole, and 12% to both drugs. Simultaneous administration of levamisole and oxfendazole resulted in an additive anthelmintic effect. Naphthalophos (36.6 to 51.2 mg/kg) was 93% efficient against the multiple resistant strain. The similar histories of anthelmintic usage at the CSIRO Pastoral Research Laboratory and on the northern tablelands of New South Wales generally, suggest that multiple anthelmintic resistance in T. colubriformis may soon emerge as a problem on the northern tablelands.

Animals↗
PubMed1989

Survey of internal parasites in Western Australian pig herds. 2. Relationship to anthelmintic usage and parasite control practices.

The housing, management and internal parasite control practices used in piggeries in Western Australia was surveyed by interviewing the owner/manager of 100 randomly selected piggeries. At the time of the interview 20 faecal samples were collected from pigs and examined for evidence of internal parasites. Most herds (80%) in which anthelmintics were used, had evidence of nematode infection. Some pig producers were using an anthelmintic that was ineffective against nematode species present while some herds had nematodes that should have been controlled by the anthelmintic being used. Prevalence of nematode infection was higher in pigs run in paddocks than in pigs housed intensively. Washing sows prior to farrowing was associated with a lower prevalence of nematode infection. The findings suggested that pig producers should ensure that the anthelmintic used is effective against the nematodes present in their pigs. It was concluded that administering anthelmintics as a single dose in the feed may not be the most effective method of deworming pigs.

Animal Husbandry↗
PubMed1989

Anthelmintic drug resistance in the UK.

The term 'anthelmintic drug resistance' describes the heritable ability of some nematode parasites to survive treatment with anthelmintic drugs at the recommended therapeutic dose levels. Genes for resistance appear to be present in many of the important pathogenic nematodes of ruminants and horses. Under intensive management systems, where heavy reliance is placed on anthelmintic drugs for worm control, the selection of resistant genotypes may result in increased reports of the drugs failing to control the nematode populations against which they are aimed. Anthelmintic resistance has been reported from many parts of the world, and in some countries multiple drug-resistant strains have emerged. In the UK, recent investigations indicate an increasing level of resistance to benzimidazoles among nematodes of sheep and horses. The incidence, diagnosis, epidemiology and implications of anthelmintic resistance are discussed.

Animals↗
PubMed1999

Anthelmintic treatment of dairy cows and its effect on milk production.

The results of more than 80 experiments on gastrointestinal parasitism and the impact of anthelmintic treatment on milk production in dairy cattle were reviewed. Abattoir surveys of culled dairy cows, faecal egg counts in milking cows, and serological tests and worm counts in cull cows in milk production studies were collated to assess the level of parasitism in dairy herds. The studies were divided into four general categories: induced infections in previously uninfected cattle; naturally infected cattle treated in mid-lactation; naturally infected cattle treated one to three times during the dry period and/or just before or just after parturition; and naturally infected cattle treated repeatedly from early lactation or given strategic treatments throughout the year. In most studies, the milk production of anthelmintic-treated cattle was compared with that of untreated controls. The anthelmintics investigated included members of the organophosphate, benzimidazole, imidazothiazole and macrocyclic lactone groups. The number of experiments in which the medicated (or uninfected) group had a higher milk yield was compared with the number of experiments in which the control (or infected) group had a higher yield. Overall, the studies demonstrated that grazing dairy cattle are likely to be infected with gastrointestinal nematode parasites, usually Ostertagia ostertagi and Cooperia species. These infections may be present as inhibited larvae, and a periparturient or spring rise is associated with their emergence. There is, at present, no reliable means of determining whether a cow or a herd may be parasitised subclinically at a level sufficient to interfere with milk production. In 70 of 87 experiments (80 per cent) there was an increase in milk production (P < 0.001) after anthelmintic treatment, with a median increase of 0.63 kg/day. In each of the four trial categories, a majority of the studies showed that anthelmintic treatment increased milk production. The yield of milk fat by the medicated cows was greater than by the controls in 26 of the 35 experiments in which that variable was studied (P < 0.01).

Animals↗
PubMed2000

Evaluation of anthelmintic activity in captive wild ruminants by fecal egg reduction tests and a larval development assay.

The effectiveness of anthelmintics was evaluated in four herds of captive ruminants, wapiti (Cervus elaphus), Armenian red sheep (Ovis orientalis), giraffe (Giraffa camelopardalis), and pronghorn (Antilocapra americana), by the use of fecal egg reduction tests (FERTs) and a commercial larval development assay (LDA) designed to evaluate susceptibility or resistance of nematodes to anthelmintics. Haemonchus sp. was the predominant nematode in the red sheep, giraffe, and pronghorn herds, whereas Ostertagia sp. and Trichostrongylus sp. were predominant in the wapiti. The LDA data indicated susceptibility by the worms to benzimidazoles except in the red sheep flock, which showed a high level of resistance. High levels of resistance to levamisole were seen in the worm populations from the wapiti and red sheep, moderate resistance in the pronghorn herd, and susceptibility in the giraffe herd. Worms were susceptible in all four herds to a combination of benzimidazole/levamisole. There was suspected avermectin resistance by Trichostrongylus sp. in the wapiti herd and by Haemonchus sp. in the giraffe. The FERTs agreed with the LDA in showing the Haemonchus in the giraffe was susceptible to fenbendazole and had suspected resistance to ivermectin, whereas Haemonchus in the red sheep and pronghorn were susceptible to ivermectin. There was correlation between the tests evaluating anthelmintics. The LDA is useful as a screening test in the selection of an anthelmintic for use in grazing ruminants, but the effectiveness of a drug in a host species may depend as much on the dose used, and the method of administration, as it does on the parasite's sensitivity to the anthelmintic.

Animals↗
PubMed2003

Evaluation of prevalence and clinical implications of anthelmintic resistance in gastrointestinal nematodes in goats.

OBJECTIVE: To determine prevalence of resistance to all anthelmintics that are commonly used to treat gastrointestinal nematodes (GINs) in goats. DESIGN: Prospective study. ANIMALS: 777 goats. PROCEDURE: On each farm, goats were assigned to 1 of 5 treatment groups: untreated controls, albendazole (20 mg/kg [9.0 mg/lb], p.o., once), ivermectin (0.4 mg/kg [0.18 mg/lb], p.o., once), levamisole (12 mg/kg [5.4 mg/lb], p.o., once), or moxidectin (0.4 mg/kg, p.o., once), except on 3 farms where albendazole was omitted. Fecal samples were collected 2 weeks after treatment for determination of fecal egg counts (FECs), and percentage reductions were calculated by comparing data from anthelmintic-treated and control groups. Nematode populations were categorized as susceptible, suspected resistant, or resistant by use of guidelines published by the World Association for the Advancement of Veterinary Parasitology. RESULTS: Resistance to albendazole was found on 14 of 15 farms, and resistance to ivermectin, levamisole, and moxidectin was found on 17, 6, and 1 of 18 farms, respectively. Suspected resistance to levamisole and moxidectin was found on 4 and 3 farms, respectively. Resistance to multiple anthelmintics (albendazole and ivermectin) was found on 14 of 15 farms and to albendazole, ivermectin, and levamisole on 5 of 15 farms. Mean overall FEC reduction percentages for albendazole, ivermectin, levamisole, and moxidectin were 67, 54, 94, and 99%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Anthelmintic resistance in GINs of goats is highly prevalent in the southern United States. The high prevalence of resistance to multiple anthelmintics emphasizes the need for reexamination of nematode control practices.

Albendazole↗
PubMed2006

Anthelmintic and nutritional effects of heather supplementation on Cashmere goats grazing perennial ryegrass-white clover pastures.

To investigate anthelmintic and nutritional effects of heather supplementation in goats grazing perennial ryegrass-white clover pastures, 40 dry Cashmere goats were randomly assigned to 4 treatments in a 2 x 2 factorial arrangement: 2 grazing management treatments (supplementation with heather vs. nonsupplementation) and 2 anthelmintic treatments (treatment vs. nontreatment). Goats grazed continuously from May to September 2004. At the end of the grazing period, the number of dead goats due to gastrointestinal parasitism was 1 in the group supplemented with heather and dosed with anthelmintic, 4 in the group that received neither supplementation nor anthelmintic, and 0 in the other 2 groups. For goats that did not receive anthelmintic treatment, the percentage of heather in the diet was negatively correlated with fecal egg count in August (r = -0.59, P < 0.05) and September (r = -0.49, P < 0.1) and positively correlated (r = 0.54, P < 0.05) with BW changes during the grazing season. Therefore, the correlation coefficient between BW change and fecal egg count was negative (r = -0.62, P < 0.05). Rumen ammonia concentrations were always lower in supplemented goats (P < 0.05). However, VFA concentrations were greater in goats consuming heather (58.9 vs. 50.9 mmol/L), which suggests that ruminal fermentation was not adversely affected by consumption of tannins. Heather availability in the vegetation might represent a valuable opportunity and sustainable method to control gastrointestinal nematode infections in a goat production system based on grazing perennial ryegrass-white clover pastures.

Ammonia↗
PubMed2001

Refugia--overlooked as perhaps the most potent factor concerning the development of anthelmintic resistance.

Anthelmintic resistance involving particularly the gastrointestinal nematodes of small ruminants is escalating globally, to the extent that in certain countries, such as South Africa, it has already reached alarming proportions, and is affecting practically all the anthelmintics. In this paper it is argued that the high levels of resistance in nematodes of veterinary importance indicate that the drugs have been used incorrectly. It is suggested that the phenomenon of refugia plays a much more important role in the selection of anthelmintic resistance than other phenomena that are more frequently investigated and recommended for counteracting it, such as reduced drenching frequency and avoiding under-dosing. While refugia is commonly mentioned in passing in most papers on anthelmintic resistance, it is, almost without exception, not incorporated in the final control/ management proposals. On the strength of the conclusions arrived at in the present paper strategies such as the drench-and-move system in which all the animals in a flock are drenched before they are moved to pastures containing few or no worms in refugia, and the system of strategic drenching on safe pastures should be condemned and never recommended. If such strategies are indeed unavoidable, the farmer should be warned that the farming system would probably not be sustainable even in the short term, in view of the generally high levels of resistance already present in most of the important sheep-producing regions. Farmers should be educated to consider refugia above all else when designing worm management programmes. Finally there seems to be too much complacency concerning the possibility that anthelmintic resistance may also escalate in cattle, eventually to reach the proportions that it has in sheep.

Animal Husbandry↗
PubMed2001

A survey on anthelmintic resistance in nematode parasites of sheep in Lusaka, Zambia.

While surveys in Southern Africa indicate anthelmintic resistance of gastrointestinal nematodes to be common in small ruminants in South Africa, Kenya and Zimbabwe there have been no reports of resistance in Zambia. The objective of this study was to determine whether anthelmintic resistance occurs in Zambia, and to obtain information on nematode control practices in the country. During the rainy season six commercial sheep farms were selected in and around Lusaka and Chisamba. Worm control practices were gauged by means of a questionnaire, and the Faecal Egg Count Reduction Test was performed for assessing anthelmintic efficacy of albendazole, levamisole and ivermectin. On all farms anthelmintic treatment was the only approach used to control nematode infections. Frequency of treatment varied from twice a year to every 6 weeks and drugs of different anthelmintic groups were alternated within the same year. There was a wide range in faecal egg counts of individual sheep before treatment, with some individual counts of up to 87000. Larval identification showed that Haemonchus was almost the only genus recovered from the faecal cultures before and after treatment. Albendazole resistance was found on five of the six farms. On each of the four farms where ivermectin gave less than 95% reduction in egg counts, there was resistance to albendazole as well. Levamisole showed an efficacy of 95% or higher on all six farms.

Albendazole↗
PubMed1991

Anthelmintic resistance in nematode parasites of sheep in Denmark with special emphasis on levamisole resistance in Ostertagia circumcincta.

This study was undertaken to elucidate the presence of anthelmintic resistance in nematode parasites of sheep in Denmark. Twenty two flocks of sheep were selected for Faecal Egg Count Reduction (FECR) tests, based on a prior history of either the same anthelmintic, or anthelmintic class having been used 3 times or more over the previous 5 years. Evidence of anthelmintic resistance was detected in 7 flocks. Two flocks showed FECR of 88% and 94% after treatment with thiabendazole, FECR of another 2 were 90% and 94% following treatment with fenbendazole. Three flocks showed FECR of 73%, 89% and 94%, respectively following the use of levamisole. Ostertagia circumcincta was isolated from 1 of the latter flocks and subjected to an in vivo controlled slaughter assay. Following treatment with levamisole at the recommended dose rate of 7.5 mg/kg, FECR was 44.5% and worm counts were reduced by 67.7%. These results were further substantiated by an in vitro egg hatch paralysis assay and by measuring pepsinogen levels in treated and non-treated lambs. This is the first instance of anthelmintic resistance in sheep nematodes in Scandinavia.

Animals↗
PubMed1991

Concurrent infections with the ruminant nematodes Haemonchus contortus and Trichostrongylus colubriformis in jirds, Meriones unguiculatus, and use of this model for anthelmintic studies.

Haemonchus contortus- and Trichostrongylus colubriformis-infected jirds (Meriones unguiculatus) are useful for anthelmintic studies. With concurrent infections of these parasites established in the jird, questions of not only anthelmintic activity, but to some extent spectrum, could be assessed in a single model system. This report outlines a model using immunosuppressed (0.02% hydrocortisone in feed) jirds concurrently infected with H. contortus and T. colubriformis. Immunosuppressed jirds were inoculated with approximately 1,000 exsheathed infective larvae of each species, treated per os on day 10 postinoculation (PI), and killed on day 13 PI. Stomachs and small intestines were removed, opened longitudinally, incubated in distilled water at 37 C for 5 hr, fixed in formaldehyde solution, and stored for subsequent examination. Contents of both organs were examined using a stereomicroscope (15-45 x). Various standard anthelmintics were evaluated in the model; modern broad-spectrum ruminant anthelmintics (benzimidazoles, febantel, ivermectin, levamisole hydrochloride, and milbemycin D) are active uniformly and in most cases at doses comparable to those required for efficacy against these parasites in ruminants. This model, using worms of 2 genera living in distinct sites, allows preliminary evaluation of anthelmintic activity and spectrum for experimental compounds in a single cost- and resource-efficient experiment.

Animals↗
PubMed1995

[Incidence of Parascaris equorum in foals and their mares after strategic use of wide-spectrum anthelmintics for several years].

In this epidemiological survey 30 foals and their mares from seven breeding farms were investigated. Six farms used wide spectrum anthelmintics strategically at least for three years, on one farm no anthelmintic prophylaxis was practiced. Excretion of P.-equorum-eggs occurred in all breeding farms and in 80% of the foals, but in only one mare. In foals infection with roundworms was detected at the earliest 85 days post partum. Before first shedding of P.-equorum-eggs wide spectrum anthelmintics had been administered to two and to one foal(s) one and two times, respectively, to four animals three times and to one foal each four, five, six and seven times. After metaphylactic use of wide spectrum anthelmintics in the control of an infection with roundworms or other helminths, eggs of P. equorum were found in one foal already 12, 17, 54, 55, 70 and 71 days after treatment with Ivomec-P each and 65 days after use of Panacur in one foal. After application of Banminth roundworm eggs were detected 12, 27, 45, 47, 49 and 62 days in one foal each and 19 and 56 days in two foals each. In eight foals each P.-equorum-eggs were noticed 72 and 196 days after anthelmintic treatment.

Animals↗
PubMed1994

Variability in susceptibility to anthelmintics of the lungworm Muellerius capillaris first-stage larvae. Relationship to dairy-goat farms and previous exposure to febantel treatment.

Seven dairy-goat farms, located in central, western France, were studied in order to assess the variability in susceptibility of the lungworm Muellerius capillaris first-stage larvae (L1) to 3 different anthelmintics in relation to farm origin, by means of motility tests. The motility tests were performed by mixing larval suspensions with pyrantel (PYR), thiabendazole (TBZ) or ivermectin (IVE) solutions (3 concentrations x 3 incubation durations). The same anthelmintic tests were repeated 7 and 21 d after febantel (probenzimidazole) treatment of the goats. Before the treatment of goats, the average ratio (x 100) of L1 motility compared with control were very different for the 3 anthelminthics: 44, 30 and 59, respectively for TBZ, PYR and IVE. The ratios of L1 motility were the same at days 7 and 21 after the treatment of goats. The susceptibility of L1 to anthelmintics varied a great deal from 1 farm to another when goats had not been previously treated, whereas L1s from the same farms were the same after treatment of goats. The occurrence of different motilities of L1 with the anthelmintic tests from 1 farm to another should be related to the existence of different populations of M capillaris. The L1 motilities were reduced after anthelmintic treatment of goats suggesting a temporary effect on populations of M capillaris females shedding L1.

Animals↗
PubMed1996

[Spectrum of species and incidence of endoparasites in foals and their mother mares from breeding farms with and without anthelmintic prophylaxis in upper Bavaria].

In this epidemiological study 37 foals and mares were included, which have been coproscopically examined in regular intervals over a period lasting up to 13 months. The animals derived from nine breeding farms. In three of these farms no anthelmintics were used before this investigation, whereas in six farms at least three years before regular prophylactic treatments with anthelmintics have been carried out. This investigation revealed no differences in the species spectrum of endoparasites as well as in the incidence of infections as regards to the breeding farms with and without anthelmintic prophylaxis, however, significant differences between foals and mares. At least nine species were established in foals, Strongyloides westeri in 54.1% of the animals, Parascaris equorum in 64.9%, small strongyles, whose third stage larvae showed either eight or 12 intestinal cells, in 83.8%, Anoplocephala perfoliata in 16.2%, Eimeria leuckarti in 64.9%, Giardia in 5.4%, Cryptosporidium parvum in 2.7% and Gasterophilus intestinalis in 21.6%. Parasitic infections with two or more species were found in 83.8% of the foals. The species spectrum of endoparasites in mares from breeding farms without anthelmintic prophylaxis consisted of at least three species of small strongyles, whose third stage larvae were characterized by eight, 12 or 16 intestinal cells. In mares from breeding farms practising regular anthelmintic prophylaxis, however, at least seven species were ascertained, the same small strongyles, P. equorum, A. perfoliata, E. leuckarti and G. intestinalis.

Aging↗
PubMed2004

TOMOCOMD-CARDD, a novel approach for computer-aided 'rational' drug design: I. Theoretical and experimental assessment of a promising method for computational screening and in silico design of new anthelmintic compounds.

In this work, the TOMOCOMD-CARDD approach has been applied to estimate the anthelmintic activity. Total and local (both atom and atom-type) quadratic indices and linear discriminant analysis were used to obtain a quantitative model that discriminates between anthelmintic and non-anthelmintic drug-like compounds. The obtained model correctly classified 90.37% of compounds in the training set. External validation processes to assess the robustness and predictive power of the obtained model were carried out. The QSAR model correctly classified 88.18% of compounds in this external prediction set. A second model was performed to outline some conclusions about the possible modes of action of anthelmintic drugs. This model permits the correct classification of 94.52% of compounds in the training set, and 80.00% of good global classification in the external prediction set. After that, the developed model was used in virtual in silico screening and several compounds from the Merck Index, Negwer's handbook and Goodman and Gilman were identified by models as anthelmintic. Finally, the experimental assay of one organic chemical (G-1) by an in vivo test coincides fairly well (100%) with model predictions. 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.

Animals↗
PubMed1990

Population dynamics of Trichostrongylus colubriformis in sheep: computer model to simulate grazing systems and the evolution of anthelmintic resistance.

A computer model was developed to simulate Trichostrongylus colubriformis populations, their level of resistance to the common anthelmintics, host mortalities and acquired immunity. Predictions were based on sheep management practices such as lambing, weaning, sheep/paddock rotation, anthelmintic treatment, the use of controlled release devices (capsules) for anthelmintic delivery and daily meteorological records to determine the development and survival of infective larvae (L3) on pasture. Evolution of drug resistance was determined by a simple genetic system which allowed for up to three genes, each with two alleles, to give a maximum of 27 genotypes associated with one drug or three genotypes for each of three drugs. The model was validated against egg counts, L3 counts on pasture and host mortalities observed in a grazing trial, however, aspects of the model such as the development of drug resistance and use of the model in a variety of climatic zones have yet to be tested against field observations. The model was used to examine the impact of grazing management and capsule use on anthelmintic resistance and sheep production over 20 years using historical weather data. Predictions indicated that grazing management can play a dominant role in parasite control and that capsule use will reduce sheep mortalities and production losses, and in some circumstances will not cause a substantial increase in anthelmintic resistance for up to 5 years.

Animals↗