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.
Benzimidazole resistance in equine cyathostomins in India. Benzimidazole resistance is a major hindrance to the control of equine cyathostominosis throughout the world. There is a paucity of knowledge on the level of benzimidazole resistance in small strongyles of horses in India. In the present study, allele-specific PCR (AS-PCR) that detects F200Y mutation of the isotype 1 β-tubulin gene and faecal egg count reduction test (FECRT) were used for detecting benzimidazole resistance in equine cyathostomin populations in different agro-climatic zones of Uttar Pradesh, India. Results of the FECRT revealed prevalence of benzimidazole resistance in cyathos...
Plasma disposition, milk excretion and parasitological efficacy of mebendazole in donkeys naturally infected by Cyathostominae. Mebendazole (MBZ) has been licensed for use in horses and donkeys, however there are no data available in the literature regarding its pharmacokinetic disposition and efficacy in donkeys. This study was designed to determine the plasma disposition, milk excretion and anthelmintic efficacy of MBZ in donkeys naturally infected by Cyathostominae. The animals were allocated to three groups, each of six donkeys. One group was untreated control (C-group) and the others were treated using a paste formulation of MBZ administered per os at the manufacturer's recommended horse dosage of 10 mg/kg body we...
Comparison of the larvicidal efficacies of moxidectin or a five-day regimen of fenbendazole in horses harboring cyathostomin populations resistant to the adulticidal dosage of fenbendazole. Despite widespread acknowledgement of cyathostomin resistance to adult icidal dosages of benzimidazole (BZD) anthelmintics, many strongyle control programs continue to feature regularly scheduled larvicidal treatment with fenbendazole (FBZ). However, no studies have been conducted to evaluate the efficacy of larvicidal regimens against encysted cyathostomins in a BZD-resistant (BZD-R) population. A masked, randomized, controlled clinical study was conducted with 18 juvenile horses harboring populations of cyathostomins that were considered BZD-R on the basis of fecal egg count reduction (FECR)...
Anthelmintic resistance in equine helminth parasites – a growing issue for horse owners and veterinarians in New Zealand? There is growing concern that given the high frequency with which anthelmintics are being administered to many horses, anthelmintic resistance amongst equine helminth populations will be an increasing problem, rendering many of the currently available products unusable with little prospect of new products becoming available, at least in the near future. Worldwide, much reliance has been placed on the macrocyclic lactone (ML) group of anthelmintics, but resistance has been reported to these products as well as to the two other major anthelmintic classes used in this species, the benzimidazoles ...
Anthelmintic resistance in equine nematodes. Anthelmintics have been applied indiscriminately to control horse nematodes for over 40 years. Three broad-spectrum anthelmintic classes are currently registered for nematode control in horses: benzimidazoles (fenbendazole, oxibendazole), tetrahydropyrimidines (pyrantel) and macrocyclic lactones (ivermectin, moxidectin). Generally, control strategies have focused on nematode egg suppression regimens that involve the frequent application of anthelmintics to all horses at intervals based on strongyle egg reappearance periods after treatment. The widespread use of such programmes has substantial...
Deep amplicon sequencing of preselected isolates of Parascaris equorum in β-tubulin codons associated with benzimidazole resistance in other nematodes. The development of anthelmintic resistance (AR) to macrocyclic lactones in the equine roundworm Parascaris equorum has resulted in benzimidazoles now being the most widely used substance to control Parascaris infections. However, over-reliance on one drug class is a risk factor for the development of AR. Consequently, benzimidazole resistance is widespread in several veterinary parasites, where it is associated with single nucleotide polymorphisms (SNPs) in drug targets encoded by the β-tubulin genes. The importance of these SNPs varies between different parasitic nematodes, but it has been h...
Characterisation of the inflammatory cytokine response to anthelmintic treatment in ponies. Anthelmintic treatments have been associated with local inflammatory reactions. Since each class of anthelmintic has unique mechanisms of action affecting different subpopulations of parasites, we hypothesised that they will also induce characteristic proinflammatory responses. Objective: To determine the effect of anthelmintic class on the proinflammatory response post treatment. Methods: Ponies naturally infected with cyathostomins and other parasites after pasture grazing were left untreated or treated with representatives of 3 different classes of anthelmintics: fenbendazole (benzimidazole...
Anthelmintic resistance in important parasites of horses: does it really matter? Parascaris equorum and cyathostomins are currently considered the most important parasites of horses and have traditionally been controlled with anthelmintics belonging to three drug classes: benzimidazoles, the tetrahydropyrimidine pyrantel, and macrocyclic lactones. Unfortunately, resistance to benzimidazoles, and to a lesser extent pyrantel, is widespread in cyathostomins around the world. Furthermore, resistance to macrocyclic lactones appears to be in the early stages of development in cyathostomins in multiple locations. In contrast, P. equorum populations have remained susceptible to th...
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...