Topic:Benzimidazoles
Benzimidazoles are a class of anthelmintic compounds used to control parasitic infections in horses. These compounds are effective against a range of gastrointestinal nematodes by interfering with the parasites' energy metabolism. Common benzimidazoles used in equine medicine include fenbendazole, mebendazole, and oxibendazole. The efficacy of benzimidazoles can be influenced by factors such as dosage, administration frequency, and the presence of resistant parasite strains. Resistance to benzimidazoles is a growing concern in equine parasitology, necessitating ongoing research into resistance mechanisms and alternative control strategies. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacodynamics, resistance patterns, and clinical applications of benzimidazoles in horse health management.
Sub-optimal efficacy of ivermectin against Parascaris equorum in foals on three Thoroughbred stud farms in the Manawatu region of New Zealand. To ascertain whether resistance was present in Parascaris equorum to the macrocyclic lactone anthelmintic ivermectin, using faecal egg count reduction tests. Methods: Thirty-nine foals aged between 11 and 28 weeks on three Thoroughbred stud farms (Farms A; n=20, B; n=5 and C; n=14) were treated with ivermectin (Day 0) and faecal egg counts (FEC) were monitored before and for 21 (Farms A and B) or 14 (Farm C) days after treatment. On Farms A and B, the foals were treated with a macrocyclic lactone/benzimidazole/praziquantel combination on Day 21 and FEC assessed on Day 35. The three farms were ...
An investigation of anthelmintic efficacy against strongyles on equine yards in Scotland. Cyathostomins comprise 50 helminth species, considered the most problematic equine endoparasites. Three classes of anthelmintic are currently licensed for their control, namely the benzimidazoles (fenbendazole), tetrahydropyrimidines (pyrantel) and macrocyclic lactones (ivermectin and moxidectin). Anthelmintic resistance in cyathostomins is common. With no new classes expected in the near future, it is essential to determine the efficacy of the available anthelmintics to inform future control programmes. Objective: To determine the efficacy of all 3 anthelmintic classes against strongyles in e...
Anthelmintic resistance in equine parasites – detection, potential clinical relevance and implications for control. During the past two decades anthelmintic resistance in equine parasites has been found in the group of small strongyle species (cyathostomins) and in the ascarid species Parascaris equorum. The ubiquitous nature and possible severe consequences of disease with these nematodes make them the prime targets of current worm control programmes. Traditional control strategies mainly rely on the strategic application of anthelmintics, currently represented by three major drug classes: benzimidazoles (BZ), the tetrahydropyrimidine pyrantel (PYR) and macrocyclic lactones (ML). Following decades of routi...
β-Tubulin genotypes in six species of cyathostomins from anthelmintic-naive Przewalski and benzimidazole-resistant brood horses in Ukraine. Resistance to benzimidazoles (BZ) in the gastrointestinal nematodes of livestock is characterised by the presence of specific polymorphisms in the β-tubulin isotype 1 protein, a component of microtubules. The most prevalent polymorphism associated with resistance in nematodes infecting cattle, sheep, and goats is found at codon 200, with minor occurrences of polymorphisms at codons 167 and 198. In the cyathostomins that infect horses, however, a polymorphism at codon 167 appears to be more common than the codon 200 polymorphism. In the present study, a focussed analysis of PCR-amplified β-tu...
Determination of genomic DNA sequences for beta-tubulin isotype 1 from multiple species of cyathostomin and detection of resistance alleles in third-stage larvae from horses with naturally acquired infections. Genetic resistance against benzimidazole (BZ) anthelmintics is widespread in cyathostomins, the commonest group of intestinal parasitic nematodes of horses. Studies of BZ-resistant nematodes of sheep, particularly Haemonchus contortus, have indicated that an anthelmintic resistance-conferring T/A polymorphism, encoding an F (phenylalanine) to Y (tyrosine) substitution, in beta-tubulin isotype 1 is present at two loci, codons 167 and 200 (F167Y, F200Y). Recent studies using complementary (c) DNA derived from BZ-susceptible and -resistant cyathostomins identified statistical differences in the f...
The little-known scenario of anthelmintic resistance in equine cyathostomes in Italy. Cyathostomes (Nematoda, Cyathostominae) cause colic, decreased performance and growth, peripheral edema, and dysorexia in equids. Also, the synchronous emergence of cyathostome larvae encysted in the colon and cecal wall causes larval cyathostominosis, which is characterized by protein-depriving enteropathy, chronic diarrhea, edema, weight loss, colitis, and may be fatal. In the past few decades, drug resistance in cyathostomes has become widespread, especially for benzimidazoles. Resistance to tetrahydropyrimidines is still confined to a few areas, and the recent reports of reduced efficacy i...
Application of a Reverse Line Blot hybridisation assay for the species-specific identification of cyathostomins (Nematoda, Strongylida) from benzimidazole-treated horses in the Slovak Republic. Five horse farms located in eastern Slovakia were investigated for the presence of benzimidazole-resistant strongyles by faecal egg count reduction test and egg hatch assay. Coprocultures were prepared for each farm from faecal samples taken pre- and post-treatment and harvested larvae were molecularly examined with a Reverse Line Blot assay. Faecal egg count reduction values ranged from 0 to 52.5% and all farms were positive for benzimidazole-resistant cyathostomins. Seven benzimidazole-resistant cyathostomin species were molecularly identified on farms before and also after treatment. These ...
Species-specific identification of equine cyathostomes resistant to fenbendazole and susceptible to oxibendazole and moxidectin by macroarray probing. Cyathostome populations in horses on two farms located in central Italy with a history of fenbendazole (FBZ) resistance were investigated with the Faecal Egg Count Reduction Test to evaluate the susceptibility to oxibendazole and moxidectin. Faecal eggs were collected pre- and post-treatment on each farm and molecularly examined with a Reverse Line Blot (RLB) assay able to unequivocally detect and identify 13 cyathostome species. Resistance to FBZ was confirmed on both farms, while oxibendazole and moxidectin demonstrated 97% and 100% efficacy, respectively. Overall eight species of cyathostom...
Anthelmintic resistance in cyathostomins of brood horses in Ukraine and influence of anthelmintic treatments on strongylid community structure. In 2004-2006, 322 brood horses from 11 horse farms were examined using the faecal egg count reduction test (FECRT) to determine the presence and distribution of anthelmintic resistance in strongylids in Ukraine. The anthelmintic drugs "Albendazole-7.5" (7.5mg of albenazole, Ukraine) at a dose of 5mg per kg body weight and "Univerm" (0.2% aversectin C, Russia) at a dose of 0.5mg per kg body weight were used. Seventy-one horses from six farms were examined in vivo to investigate the influence of anthelmintic treatment on the gastrointestinal strongylid community structure. Horses were treated wi...
The persistence of benzimidazole-resistant cyathostomes on horse farms in Ontario over 10 years and the effectiveness of ivermectin and moxidectin against these resistant strains. Three clinical trials with fecal egg count reduction tests and coproculture were conducted on 2 standardbred farms in Ontario. On Farm A, the treatment groups were mebendazole and ivermectin in trial 1, and fenbendazole and moxidectin in another. On Farm B, treatment groups were mebendazole and ivermectin. All horses treated with mebendazole or fenbendazole were subsequently treated with ivermectin or moxidectin. Strongyle eggs/g feces were estimated pre- and post-treatment using the Cornell-McMaster dilution and Cornell-Wisconsin centrifugal flotation techniques. After treatment, there was no...
Study (1991 to 2001) of drug-resistant Population B small strongyles in critical tests in horses in Kentucky at the termination of a 40-year investigation. Population B, drug-resistant small strongyles have been studied in naturally infected horses in Kentucky for more than 40 years. These parasites first were found to be resistant to phenothiazine (PTZ) and thiabendazole (TBZ), later to other parasiticides. Studies have been on evaluation of antiparasitic efficacy of several compounds, especially the benzimidazoles, against Population B small strongyles in clinical (field) tests (1959-1983) on the commercial farm of origin and in clinical and critical tests (1966-2001) at the University of Kentucky (UK) research farm. Research on these nematodes...
Plasma disposition and faecal excretion of oxfendazole, fenbendazole and albendazole following oral administration to donkeys. Fenbendazole (FBZ), oxfendazole (fenbendazole sulphoxide, FBZSO), and albendazole (ABZ) were administered orally to donkeys at 10mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment. The plasma and faecal samples were analysed by high performance liquid chromatography (HPLC). The parent molecule and its sulphoxide and sulphone (FBZSO(2)) metabolites did not reach detectable concentrations in any plasma samples following FBZ administration. ABZ was also not detected in any plasma samples, but its sulphoxide and sulphone metabolites were detected, demonstratin...
The detection of anthelmintic resistance in nematodes of veterinary importance. Before revised World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines on the detection of anthelmintic resistance can be produced, validation of modified and new methods is required in laboratories in different parts of the world. There is a great need for improved methods of detection of anthelmintic resistance particularly for the detection of macrocyclic lactone resistance and for the detection of resistant nematodes in cattle. Therefore, revised and new methods are provided here for the detection of anthelmintic resistance in nematodes of ruminants, horses and ...
Molecular diagnosis of anthelmintic resistance. Conventional and real time polymerase chain reaction-based tests have been developed for the diagnosis of anthelmintic resistance (AR) in populations of several small and large ruminant as well as horse gastro-intestinal nematode species. To date, molecular markers that correlate well with AR are available only for the detection of benzimidazole resistance. Recently, however, a single nucleotide polymorphism was found in vitro to be of functional relevance for reduced drug efficacy to macrocylic lactones. The focus of the present review, therefore, is the molecular mechanism of action of these...
Poor efficacy of the most commonly used anthelmintics in sport horse nematodes in Morocco in relation to resistance. Sport and leisure horses in Morocco are treated with several anthelmintics, organophosphates (dichlorvos), benzimidazoles (mostly thiabendazole) or tetrahydropyrimidines (mostly pyrantel pamoate) against nematodes. We studied three horse stables in Rabat, one in Meknes and one in Bouznika. Two of the Rabat and Bouznika stables had introduced a large number of horses from countries (Argentina or Europe) where resistance to benzimidazoles is frequent, whereas the Meknes stud farm remained without foreign introduction. The number of treatments was not very frequent (twice a year in adult horses) ...
[Equine strongyles. I. Development of anthelmintic resistance]. Small strongyles (cyathostomes) that are resistant against anthelmintics have become a major problem in equine medicine in the recent years. In many European countries benzimidazole-resistant cyathostomes are widespread and are now present in well over 50% of equine populations investigated. In contrast, resistance against ivermectin has not been reported despite its widespread use in the recent years. Optimising the frequency of treatments based on quantitative faecal monitoring is of great importance to preserve remaining anthelmintic efficacy.
[Equine strongyles II. Occurrence of anthelmintic resistance in Switzerland]. The occurrence of anthelmintic resistance in strongyles was investigated in 440 horses on 90 farms in Switzerland. The egg hatch assay suggested that benzimidazole (BZ)-resistance was present in 40 of 82 farms (49%). Faecal egg count reduction after pyrantel-treatment was above 96% in 14 of 15 farms. In the remaining farm the efficacy was only 80%. Ivermectin efficacy was investigated on 5 farms and the efficacy was recorded at 98-100%. Faecal cultures undertaken after treatment revealed almost exclusively larvae of the family Cyathostominae. Data about management practices, pasture hygiene an...
Changes to oxfendazole chiral kinetics and anthelmintic efficacy induced by piperonyl butoxide in horses. The study of novel pharmacological strategies to control parasitism in horses is required since many parasite species have developed resistance to anthelmintic drugs. Objective: 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 follo...
Identification of strongyle eggs from anthelmintic-treated horses using a PCR-ELISA based on intergenic DNA sequences. The efficacy of five daily fenbendazole (FBZ) treatments was tested against benzimidazole-resistant cyathostomins in naturally infected horses (n=13). Horses were treated with pyrantel embonate (PYR) to remove adult strongyles followed, 7 days later, by a 5-day course of FBZ. The PYR treatment produced an average faecal egg count reduction of 98%. All samples were negative by faecal egg count 7 days after the start of the FBZ treatment. Positive egg counts were observed from 28 days after the start of FBZ treatment and all horses displayed positive faecal egg counts by 77 days after treatment....
Beta-tubulin complementary DNA sequence variations observed between cyathostomins from benzimidazole-susceptible and -resistant populations. The molecular mechanism of benzimidazole (BZ) resistance in cyathostomins of horses is still unclear. Previous studies revealed that the TTC or TAC polymorphism in codon 200 of the beta-tubulin isotype 1 gene is not as strictly correlated with BZ resistance as in trichostrongyles in sheep. To identify further sites of polymorphism within the beta-tubulin gene related to BZ resistance, complete complementary DNAs (cDNAs) encoding beta-tubulin of adult worms of Cylicocyclus nassatus, Cyathostomum pateratum, Cyathostomum coronatum, Cyathostomum catinatum, Cylicostephanus longibursatus, and Cylico...
Effect of repeated benzimidazole treatments with increasing dosages on the phenotype of resistance and the beta-tubulin codon 200 genotype distribution in a benzimidazole-resistant cyathostomin population. This study was designed to investigate the effect of repeated treatments with increasingly high fenbendazole (FBZ) dosages on the phenotype and genotype of a benzimidazole (BZ)-resistant cyathostomin population. An experimentally infected horse was treated repeatedly with FBZ dose rates between 7.5 and 30.0 mg/kg body weight (bw) over approximately 2 years. Faecal egg counts (FECs) and larval cultures were performed weekly. A total of 45 faecal egg count reduction tests (FECRTs) were analysed, revealing a high variability during the course of experiment with a mean value in faecal egg count re...
Benzimidazole resistance in cyathostomin populations on horse farms in western Anatolia, Turkey. A cross-sectional survey was performed on ten stud farms in western Anatolia, Turkey, in order to provide the first information on the problem of anthelmintic resistance in equine strongyles in this country. Benzimidazole (BZ) resistant cyathostomin populations were detected on seven farms if pre- and post-treatment egg counts are compared in treated animals and the resistance is defined as a mean faecal egg count reduction (FECR) of <95% with a lower 95% confidence limit of <90%. Egg hatch tests using an ED(50) of 0.1 microg/ml thiabendazole as the cut-off value confirmed BZ resistance on fou...
Evaluation of a larval development assay (DrenchRite) for the detection of anthelmintic resistance in cyathostomin nematodes of horses. A larval development assay (LDA, DrenchRite) was evaluated to determine the effectiveness of this method in detecting anthelmintic resistance in cyathostomin nematodes of horses. A total of 15 horse farms from Georgia and South Carolina (USA) and Population S ponies from the University of Kentucky (USA) were included in this study. Nematode eggs were extracted from pooled fecal samples and placed into the wells of a DrenchRite plate for testing against thiabendazole (TBZ), levamisole (LEV) and 2 ivermectin (IVM) analogs (IVM-1, IVM-2). After a 7-day incubation larvae in each well were counted ...
Prevalence of benzimidazole resistance on horse farms in Germany. Faecal egg counts (FECs) were made on samples from 1383 horses on 64 farms in northern Germany between August 2000 and November 2001. There were significant differences between the mean FECs in the two years; in 2000, 59.6 per cent of 369 samples were positive and in 2001, 32.6 per cent of 1014 samples were positive for strongyle eggs. The results of a FEC reduction test indicated that resistance to fenbendazole was present on all 10 farms where it had been used, including in 33 of 60 horses tested. In contrast, treatment with ivermectin resulted in the complete elimination of nematode eggs in...
Treatment and prevention of intestinal parasite-associated disease. Since 1917, only 11 new endoparasiticides have been developed for the horse, of which five chemical classes are in common use. The selection pressure of frequent administration of deworming doses for parasite control programs has been associated with the development of resistance of small strongyle parasites to the effects of benzimidazoles and pyrantel salts. Against the background of the inevitability of the occurrence of ivermectin/moxidectin resistance, responsible use of equine anthelmintics based on the clinical pharmacology of the compounds and the biology/epidemiology of intestinal par...
Analysis of the beta-tubulin codon 200 genotype distribution in a benzimidazole-susceptible and -resistant cyathostome population. To study the prevalence of the polymorphism in position 200 of the beta-tubulin gene in the mechanism of benzimidazole (BZ) resistance in cyathostomes of horses, an allele-specific PCR was used to detect the genotype of individuals of BZ-susceptible and BZ-resistant populations. The molecular analysis of 100 adults recovered from an anthelmintic-naïve horse revealed 80% homozygous TTC/TTC individuals, 17% heterozygous TTC/TAC and 3% homozygous TAC/TAC. A naturally infected horse was treated with increasing fenbendazole (FBZ) dosages to select a BZ-resistant population of cyathostomes. The PCR...
Comparison of in vitro methods and faecal egg count reduction test for the detection of benzimidazole resistance in small strongyles of horses. The objective of the study was to compare the in vitro egg hatch test (EHT), larval development test (LDT) and in vivo faecal egg count reduction test (FECR test) for the detection of benzimidazole resistance in equine strongyles. The presence of resistant or susceptible strongyle populations was determined in 25 stud farms using the in vivo FECR test and in vitro EHT. On the basis of the FECR values, resistance to fenbendazole was detected on 15 of the 25 farms (60%). The ED50 value (anthelmintic concentration producing 50% inhibition of hatching) for suspected resistant populations varied fr...
Anthelmintic resistance in nematodes of horses. Suppressive anthelmintic treatment strategies originally designed to control Strongylus vulgaris in horses were extremely successful in reducing morbidity and mortality from parasitic disease. Unfortunately, this strategy has inadvertently resulted in the selection of drug-resistant cyathostomes (Cyathostominea), which are now considered the principal parasitic pathogens of horses. Resistance in the cyathostomes to benzimidazole drugs is highly prevalent throughout the world, and resistance to pyrantel appears to be increasingly common. However, there are still no reports of ivermectin resista...
Fenbendazole pharmacokinetics, metabolism, and potentiation in horses. The present study was designed to describe the pharmacokinetics and fecal excretion of fenbendazole (FBZ) and fenbendazole sulphoxide (FBZSO) and their metabolites in horses, to investigate the effects which concurrent feeding has on the absorption and pharmacokinetics of FBZ, and to determine the effect of coadministration of the metabolic inhibitor piperonyl-butoxide on the in vivo pharmacokinetics and in vitro liver microsomal metabolism of sulfide and sulfoxide benzimidazoles. The effect of piperonyl-butoxide on the enantiomeric genesis of the sulfoxide moiety was also investigated. Follow...
Comparative use of faecal egg count reduction test, egg hatch assay and beta-tubulin codon 200 genotyping in small strongyles (cyathostominae) before and after benzimidazole treatment. A survey on benzimidazole (BZ) resistance in small strongyles was performed on three farms in the tenth region in Chile. Samples from a total of 100 horses were tested using the faecal egg count reduction test (FECRT), the egg hatch assay (EHA) and an allele-specific PCR for the detection of beta-tubulin isotype 1 genes coding for phenylalanine (phe) or tyrosine (tyr) at codon 200. In the past, BZ-type drugs have been used within anthelmintic campaigns on all the three farms. This has predictably led to a high degree of BZ resistance at the Valdivia and Riñihue farms and to a lesser degree at...