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PubMedDate not supplied

Multispecies and multiple anthelmintic resistance on cattle nematodes in a farm in Argentina: the beginning of high resistance?

There are very few resistance records on cattle nematodes. South American successive records have been increasing rapidly since the year 2000. In Argentina, increasing dissatisfaction based on the exclusive use of macrocyclic lactones has prompted the use of benzimidazoles in the Pampean region. The studied farm is located in the Argentina humid Pampas and had apparently poor results after anthelmintic treatments. Evaluation of resistance was firstly based on faecal egg reduction after treatment in November 2001 and June 2002 and was complemented with worm counts obtained by necropsy in June 2002. The study reports that the reduction of faecal egg excretion after benzimidazole (reduction 31-79%) or ivermectin treatments (76-97%) in November 2001 was insufficient and these poor results were confirmed in June 2002 (benzimidazoles (65-89%) and ivermectin (47-77%)). Several methods for evaluating faecal egg count reduction were performed and yielded different results. A new method based on the estimated faecal egg counts (corrected from the initial faecal egg counts and animal type using a general linear model) was used and gave higher flexibility in the interpretation of putative resistance to anthelmintics. From necropsy results, it could be concluded that Cooperia oncophora was resistant to avermectins and benzimidazoles and that Cooperia punctata, Ostertagia ostertagi and Haemonchus placei were resistant to benzimidazoles. This case of multispecies and multidrug resistance is probably not unique and could reflect the emergence of resistances in Argentina. This emergence is probably due to the intensive use of anthelmintics, the absence of refugia, and the frequent circulation of infected cattle.

Albendazole↗
PubMed2005

Gastrointestinal nematode infection in sheep--a review of the alternatives to anthelmintics in parasite control.

Efforts to curb production losses caused by nematode parasitism in sheep have led to the development of a number of control methods to complement or replace anthelmintics. The need for alternative control measures stems from the emergence of anthelmintic-resistant parasitic nematodes with reports of multi-class resistance to these drugs now emerging. A number of these control methods such as predacious microfungi, protein supplementation, plant extracts in feed and vaccines have demonstrated potential to control infection but require development and examination under natural conditions. Breeding for natural resistance to nematode infection has already shown success in controlling the disease under natural conditions. Selection for resistance is currently based on fecal egg count measurements but identification of genetic indicators of resistance will provide a more efficient method of selection. Current quantitative trait loci for nematode resistance include the MHC genes, interferon gamma gene, IgE gene and microsatellites on chromosome 1, 5 and 6. This paper reviews the current alternatives to anthelmintics to control infection, with an emphasis on breeding for host resistance and identification of genetic indicators of resistance.

Animals↗
PubMed2006

Resistance to a triple combination of broad-spectrum anthelmintics in naturally-acquired Ostertagia circumcincta infections in sheep.

AIM: To measure the efficacy of two macrocyclic lactone-levamisole-benzimidazole combination drenches against naturally-acquired abomasal nematode infections on a sheep farm in the North Island, New Zealand. METHODS: Eighteen lambs carrying naturally-acquired worm burdens were removed from pasture and randomly allocated to one of three equal-sized groups, consisting of an untreated control group and two treatment groups. One treatment group was given a single oral dose of a triple-combination anthelmintic administered at the manufacturer's recommended dose rate of 0.2 mg/kg ivermectin, 7.5 mg/kg levamisole and 5.0 mg/kg albendazole. The other treatment group received a similar dose of another triple-combination drench consisting of 0.2 mg/kg abamectin, 8.0 mg/kg levamisole and 4.5 mg/kg oxfendazole. Worm counts were carried out post mortem on the abomasa of all animals in all groups, 10 days after treatment. RESULTS: While the abamectin-levamisole-oxfendazole combination was highly effective against all three abomasal nematode species present, the ivermectin-levamisole-albendazole combination was not. In the latter instance, a reduction of only 78% was achieved against infections of Ostertagia (=Teladorsagia) circumcincta. CONCLUSIONS: These results provide evidence of resistance to an ivermectin-levamisole-albendazole combination drench by O. circumcincta. CLINICAL RELEVANCE: Besides representing the first confirmed report of resistance to a combination drench consisting of three broad-spectrum anthelmintics, the present results provide further evidence of the continuing escalation of multiple anthelmintic resistance in sheep nematodes in New Zealand.

Albendazole↗
PubMed2006

Field studies investigating anthelmintic resistance in young cattle on five farms in New Zealand.

AIM: To investigate the efficacy of pour-on anthelmintics against field strains of parasitic nematodes in young cattle on five farms in New Zealand. METHODS: Faecal nematode egg count (FEC) reduction (FECR) tests were carried out on five calf-rearing farms using pour-on formulations of levamisole, ivermectin, eprinomectin, and the simultaneous administration of levamisole and ivermectin. Faecal samples were collected per rectum before treatment and about 7, 14, 21 and 28 days after treatment, for FEC and faecal nematode larval culture. RESULTS: Resistance (i.e. <95% reduction in FEC) of Cooperia oncophora to ivermectin and eprinomectin was identified on all five farms. There was limited evidence of possible emerging resistance in Ostertagia spp to ivermectin but not eprinomectin, in short-tailed larvae of Cooperia spp to ivermectin and eprinomectin, and in Trichostrongylus spp to ivermectin, eprinomectin and levamisole used separately. Levamisole was effective against C. oncophora, but had variable efficacy against Ostertagia spp in the calves in this study. Simultaneous treatment with levamisole and ivermectin pour-on formulations were effective against all genera on all farms. CONCLUSIONS: To effectively manage roundworm parasites in their calves farmers need to be aware of the resistance status of the parasites on their farms. Levamisole is likely to be an effective anthelmintic on most farms at times of the year when the impact of Ostertagia spp is not high. Simultaneous administration of levamisole and ivermectin pour-on anthelmintics to cattle is likely to control both ML-resistant C. oncophora and stages of Ostertagia spp that are not controlled by levamisole alone.

Animals↗
PubMed1990

Efficacy of some commercial formulations of anthelmintics on Haemonchus contortus and Trichostrongylus columbianum.

The anthelmintic action of five commercially formulated anthelmintics: Assiazine, Banminth, Nemafax, piperazine and levamisole has been evaluated by observing the effect on egg hatch, motility and mortality of the larvae of Trichostrongylus columbianum and Haemonchus contortus. Assiazine and levamisole inhibited egg-hatch of the helminth ova dose-dependently. Nemafax, Banminth, and piperazine did not inhibit egg hatch. Levamisole and Banminth affected the motility of the helminth larvae with subsequent death after 24h. The other anthelmintics used did not adversely affect the helminth larvae as compared with the untreated control group.

Animals↗
PubMed2003

Modulation of the multidrug resistance (MDR) system in the nematode Haemonchus contortus by changing cholesterol content: effects on resistance to anthelmintics.

OBJECTIVES: The efficiency of the anthelmintics used to treat small domestic ruminants infected with nematodes is compromised by the emergence of resistant parasites. Both specific and non-specific mechanisms of resistance exist. The non-specific mechanisms involve multiple resistance phenomena and are dependent on the multidrug resistance (MDR) system, which is also responsible for the development of chemotherapy-resistant tumour cells. We showed previously that the system also exists in nematodes. Membrane 'pumps', known as P-glycoproteins (Pgp), are activated in the MDR system. The nature of the membrane, in particular the lipids, appears to condition the activity of the pumps. Thus, we studied the effects of cholesterol on drug transport activity in the nematode Haemonchus contortus. MATERIALS AND METHODS: We used methyl-beta-cyclodextrin to carry out cholesterol depletion and cholesterol loading experiments. The resulting changes in resistance were estimated by measuring changes in drug transport (a) by means of in vitro egg hatch assays in the presence of a benzimidazole anthelmintic, thiabendazole and (b) by measuring the transport of rhodamine 123 (R123), a specific substrate of Pgp. We used biochemical assays to estimate the cholesterol concentration in the parasites. RESULTS: Changes in the cholesterol content induced changes in anthelmintic resistance; cholesterol depletion gave increased resistance and cholesterol loading gave decreased resistance. These changes also altered the transport of R123. CONCLUSION: Cholesterol depletion or cholesterol loading allow modulation of xenobiotic resistance in nematode eggs as they do in tumour cells. The effect appears to be correlated with changes in the function of membrane P-glycoproteins. The lipid environment thus influences the nematode Pgp activity.

Animals↗
PubMed1992

Antibody responses to natural Dictyocaulus viviparus exposure in first year grazing cattle using vaccination or different kinds of anthelmintic treatment.

In two field trials vaccination or different anthelmintic treatments against Dictyocaulus viviparus infections were used in 6 groups of first year grazing cattle. The antibody response to lungworm infections was determined using an ELISA. Cattle treated once or repeatedly at long intervals with levamisole developed clinical signs of dictyocaulosis. The detection of anti-D. viviparus antibodies at the end of the grazing season confirmed that these anthelmintic treatments were not able to prevent lungworm infections. Cattle that received strategically administered treatments with ivermectin remained clinically healthy. These cattle were seronegative until the end of the trial which proved the efficacy of the strategic control. Cattle that received an intraruminal slow release bolus did not develop clinical disease. However one animal shed lungworm larvae and the herd became seropositive at the end of the grazing season indicating a history of infection. The serological examination of a cattle herd at the end of the grazing season is able to demonstrate a history of lungworm infections and to determine the efficacy of anthelmintic control measures.

Animals↗
PubMed2000

A study on the time of ovicidal effect of some anthelmintics in Djallonke sheep and its implication for the control of parasitic helminth infections.

The time lag between the administration of five different anthelmintics and the exertion of their ovicidal effect on worm eggs was monitored in five groups of Djallonke sheep. In this experiment, all the animals in all treated groups and an untreated control group were grazed together. Worm egg output and the number of infective strongylate nematode larvae (L3s) recovered from fecal cultures from each group were observed every four hours for 72 h. The earliest time observed for the occurrence of ovicidal effect resulting in the absence of L3s in fecal cultures was 8 h after the administration of the anthelmintics. However, this time was not the same for all the anthelmintics. The implication of the results are discussed in relation to its application for worm control.

Albendazole↗
PubMed1981

The isolation of a field strain of Haemonchus contortus in Queensland showing multiple anthelmintic resistance.

Following the apparent failure of levamisole to control infections of Haemonchus contortus in sheep at Lawes in south eastern Queensland, a strain of this parasite was isolated at the Animal Research Institute, Yeerongpilly. This strain was used to infect sheep at Yeerongpilly and the Merrindale Research Station, Victoria where four experiments to classify the resistance pattern of the parasite were carried out. Resistance to thiabendazole was first suspected in 1969, and these experiments confirmed that resistance to this drug was still present. They also showed that a strong degree of resistance had been developed to both levamisole and morantel tartrate. Other benzimidazole anthelmintics and also the organophosphorus compound naphthalophos were only moderately effective against the original isolate but rafoxanide, nitroxynil and phenothiazine were almost 100% effective. Other highly effective chemicals were disophenol and closantel. After passaging the strain for four generations with both levamisole and albendazole, resistance to both naphthalophos and the newer benzimidazole anthelmintics increased dramatically. This is the first report of a field strain of H. contortus exhibiting resistance to benzimidazole, non-benzimidazole and organophosphorus anthelmintics.

Albendazole↗
PubMed1985

Resistance to benzimidazole anthelmintics in field strains of Ostertagia and Nematodirus in sheep.

Resistance to a range of benzimidazole anthelmintics was investigated in 2 strains of Ostertagia spp. One strain (SR80) had been exposed to fenbendazole, oxfendazole and thiabendazole, the other strain (KR79) only to thiabendazole. Both strains showed a high degree of resistance to albendazole, fenbendazole, oxfendazole and thiabendazole, which had efficiencies of 11-38% and 0-60% against all developmental stages of SR80 and KR79, respectively. There was no significant reduction in the KR79 worm count by thiabendazole at 132 mg kg-1 given either as a single dose or divided into 12 equal portions, one administered every 6h. Nematodirus spp were also found to be resistant to all benzimidazoles tested. Levamisole at 7 mg kg-1 and naphthalophos at 30 mg kg-1 had efficiences of 89 and 66%, respectively, against SR80 Ostertagia and 99 and 19% against Nematodirus, all but the last of these being significant reductions in worm burdens. The resistant SR80 Ostertagia occurred on a research station, but possibly originated from a property which 3 years earlier had supplied ewes to the station. The use of benzimidazole anthelmintics and subsequent grazing on worm-free pasture may have enhanced the level of resistance. A relationship was established between egg counts and adult worm counts 10 days post-treatment, which suggested that for Ostertagia the worm count could be predicted from the geometric mean egg count from about 10 animals. Thus, where an Ostertagia population is suspected of being resistant, an anthelmintic efficiency assay using pre- and post-treatment faecal egg counts should provide a satisfactory diagnostic procedure.

Animals↗
PubMed1998

Survey of anthelmintic resistance on Danish horse farms, using 5 different methods of calculating faecal egg count reduction.

This study reports on the prevalence of anthelmintic resistance in strongyles of horses in Denmark. Of 5 methods used for the calculation of faecal egg count reduction (FECR) the method recommended by the World Association for the Advancement of Veterinary Parasitology, for the detection of resistance in sheep was the most sensitive procedure for detecting resistance. Using this method benzimidazole resistance was detected on 33 of 42 farms (79%) examined. Pyrantel was tested on 15 farms and FECR tests indicate resistance on 3 (30%) farms. On 2 farms on which resistance to pyrantel was detected resistance to benzimidazoles was also detected. On one of 16 farms examined ivermectin resistance was indicated at Day 14 but not at Day 19. On the 15 remaining farms ivermectin was effective. Due to the high prevalence of anthelmintic resistance in Danish horse herds it is recommended that tests of anthelmintic efficacy be conducted routinely to monitor the effectiveness of the strongyle control programmes.

Animals↗
PubMed1977

Field trials in sheep with the anthelmintic thiophanate.

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

Administration, Oral↗
PubMed1981

Use of anthelmintics for cattle in England and Wales during 1978.

A study of anthelmintic treatments received by 40,000 cattle during 1978 on a random sample of 240 farms in England and Wales showed that most were given against gastrointestinal nematodes for purposes of prophylaxis. Analysis of the data indicates that of an estimated pounds 15m spent on anthelmintics and their administration, most was far less effectively employed than it might have been. Errors of three kinds were common, some classes of cattle being dosed unnecessarily, animals being dosed at an unfavourable occasion or time of year, and anthelmintics being directed at parasites against which they had no action. Existing knowledge on the control of helminths is not effectively used; most dosing was done without advice from an identifiable source.

Animals↗
PubMed1994

Recommendations for the control of anthelmintic resistant nematodes of farm animals in the EU.

As a result of a recent European Union meeting on anthelmintic resistant nematodes of farm animals, a list was made of nine proposals for research and five to control anthelmintic resistance. The most important were the need to have standardised and new tests to monitor the development and spread of resistant nematodes in sheep, goats, horses, cattle and pigs, and for education of veterinary surgeons and farmers in the optimal control strategies to be used to delay the development of anthelmintic resistance in nematodes.

Animals↗
PubMed1995

Slowing the spread of anthelmintic resistant nematodes of horses in the United Kingdom.

The growing importance of anthelmintic resistance in cyathostomes (small strongyles) of horses poses a threat to the health and welfare of all types of horses. On the basis of published information on cyathostomes of horses, six recommendations are made for reducing the development and spread of anthelmintic resistant nematodes. The need for restraint in the use of anthelmintics, the application of epidemiological principles of worm control and a greater emphasis on pasture management are the principal recommendations.

Animals↗
PubMed1999

Nematode control practices and anthelmintic resistance in dairy calves in the south west of England.

A postal survey of worming practices on West Country dairy farms was undertaken and farmers were requested to send faecal samples for nematode egg counts. The majority of the farmers who responded had a nematode control policy which was based on a mixture of anthelmintics and pasture rotation. Sixty-five per cent turned out calves on to the same paddock each year and 57 per cent treated their stock with anthelmintics during the second year. Ninety farms submitted samples for analysis but only 16 samples contained sufficient eggs to justify repeat egg counts and only eight of these produced enough eggs for in vitro tests. The small number of positive samples, even into the latter part of the year suggests a heavy use of anthelmintics with relatively clean pasture. One Somerset farm had larvae which developed in high concentrations of ivermectin, and eggs were still being passed after two treatments with ivermectin at the manufacturer's recommended dose seven days apart. Of 100 male nematodes isolated from two of the calves, 88 were Cooperia species and 12 were Nematodirus species. A controlled trial with this isolate in eight Friesian male calves showed a 44 per cent reduction in egg counts at day 7 but no significant reduction in worm burden postmortem. This is the first reported case of ivermectin-resistant Cooperia species in cattle in the United Kingdom.

Animals↗
PubMed2004

Prevalence of anthelmintic resistant cyathostomes on horse farms.

OBJECTIVE: To determine prevalence of anthelmintic resistance in cyathostome nematodes of horses in the southern United States. DESIGN: Cross-sectional study. ANIMALS: 786 horses on 44 farms and stables in Georgia, South Carolina, Florida, Kentucky, and Louisiana. PROCEDURE: Fecal egg count (FEC) reduction tests were performed on 44 large farms and stables. Horses on each farm were treated with an oral paste formulation of fenbendazole, oxibendazole, pyrantel pamoate, or ivermectin at recommended label dosages. A mixed linear model was fitted to the percentage reduction in FEC, accounting for differences among farms, states, ages, treatments, and treatment by state interactions. RESULTS: By use of a conservative measure of resistance (< 80% reduction), the percentage of farms with anthelmintic-resistant cyathostomes was 97.7%, 0%, 53.5%, and 40.5% for fenbendazole, ivermectin, oxibendazole, and pyrantel pamoate, respectively. Mean percentage reductions in FEC for all farms were 24.8%, 99.9%, 73.8%, and 78.6% for fenbendazole, ivermectin, oxibendazole, and pyrantel pamoate, respectively. Pairwise contrasts between states for each treatment revealed that in almost all instances, there were no significant differences in results between states. CONCLUSIONS AND CLINICAL RELEVANCE: The prevalence of resistance found in this study was higher than that reported previously, suggesting that anthelmintic resistance in equine cyathostomes is becoming a major problem. Furthermore, data from these 5 southern states, which are geographically and physiographically distinct, were remarkably similar. This suggests that drug resistance in cyathostomes is highly prevalent throughout the entire southern United States and probably nationwide.

Animals↗
PubMed2005

Changes to oxfendazole chiral kinetics and anthelmintic efficacy induced by piperonyl butoxide in horses.

REASONS FOR PERFORMING THE STUDY: The study of novel pharmacological strategies to control parasitism in horses is required since many parasite species have developed resistance to anthelmintic drugs. OBJECTIVES: To evaluate the effects of piperonyl butoxide (PB) (a metabolic inhibitor) on the plasma availability and enantiomeric behaviour of oxfendazole (OFZ) given orally to horses, and to compare the clinical efficacy of OFZ given either alone or co-administered with PB in naturally parasitised horses. METHODS: Fifteen naturally parasitised crossbred male ponies were allocated into 3 groups (n = 5) and treated orally as follows: Group I (control) received distilled water as placebo; Group II was dosed with OFZ (10 mg/kg bwt); and Group III was treated with OFZ (10 mg/kg bwt) co-administered with PB (63 mg/kg bwt). Jugular blood samples were obtained over 120 h post treatment. Three weeks after treatments, all experimental horses were subjected to euthanasia. RESULTS: The observed maximum plasma concentration (Cmax) and area under the concentration vs. time curve (AUC) values for OFZ increased 3- and 5-fold, respectively, in the presence of PB. The plasma concentration profiles of fenbendazole (FBZ), a metabolite generated from OFZ, were significantly lower after the treatment with OFZ alone (AUC = 0.8 microg x h/ml) compared to those obtained after the OFZ + PB treatment (AUC = 2.7 microg x h/ml). The enhanced pharmacokinetic profiles correlated with increased anthelmintic efficacy. The combination OFZ + PB showed 100% efficacy against mature nematode parasites. The efficacy against cyathostome L3 larvae increased from 94% (Group II) to 98.7% (Group III). Consistently, the number of L4 larvae recovered from OFZ + PB treated horses (Group III) (n = 146) was significantly lower (P<0.05) than that recovered from Group II (n = 1397). CONCLUSIONS: The use of PB as a metabolic inhibitor may be useful to enhance OFZ activity against mature and migrating larvae of different parasite species in horses. POTENTIAL RELEVANCE: Metabolic inhibitors may be used to enhance the activity of benzimidazole anthelmintics and extend the effective lifespan of benzimidazole drugs in the face of increasing resistance.

Administration, Oral↗