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PubMed2001

Anthelmintic resistance on goat farms in Georgia: efficacy of anthelmintics against gastrointestinal nematodes in two selected goat herds.

Gastrointestinal nematode (GIN) parasitism is a major constraint to production of goats in the southeastern United States. The conventional method of control used by producers in this region is frequent use of anthelmintics during the warm season. Overuse of anthelmintics has led to an increase in the incidence of anthelmintic resistance in many parts of the world, but data on prevalence of anthelmintic resistance in GIN of goats in the southeastern United States are very limited. To address this issue, anthelmintic efficacy was determined in goat herds at the Fort Valley State University, Agricultural Research Station (FVSU-ARS) and the University of Georgia, College of Veterinary Medicine (UGA-CVM) using fecal egg count reduction (FECR) tests and DrenchRite((R)) larval development assays (LDA). At FVSU-ARS, 2-year-old Spanish goat does were randomly allocated to one of nine different treatment groups (n = 10): albendazole (ABZ; 20mg/kg body weight (BW)), fenbendazole (FBZ; 20mg/kg BW), ivermectin (IVM; 0.4 mg/kg BW), doramectin (DRM; 0.4 mg/kg BW), moxidectin (MOX; 0.4 mg/kg BW), levamisole (LEV; 12 mg/kg BW), morantel tartrate (MOR; 10mg/kg BW), a combination of IVM (0.4 mg/kg BW) and ABZ (20 mg/kg BW), and untreated controls. At UGA-CVM, goats were randomly allocated to one of five different treatment groups (n = 8): ABZ (20 mg/kg BW), IVM (0.4 mg/kg BW), MOX (0.4 mg/kg BW), LEV (12 mg/kg BW), and untreated controls. All drugs in both experiments were administered orally. Anthelmintic efficacy was calculated by comparing 14-day post-treatment FEC of treated and control animals, and percent reductions were interpreted using the World Association for the Advancement of Veterinary Parasitology guidelines for resistance. For the LDA, nematode eggs were isolated from pooled fecal samples of untreated control goats in each herd and used to perform DrenchRite((R)) assays. In the FVSU-ARS herd, MOX, LEV, the combination of IVM and ABZ, IVM, DRM, ABZ, MOR, and FBZ reduced FEC by 100, 91, 88, 78, 76, 62, 48, and 10%, respectively. In the UGA-CVM herd, MOX, LEV, ABZ and IVM, reduced FEC by 100, 94, 87, and 0%, respectively. In both herds moxidectin was the only drug tested that was fully effective. Results of the LDA were in agreement with results of the FECR tests for both herds. These data demonstrate the presence of GINs resistant to all three major anthelmintic classes in both goat herds.

Animals↗
PubMed1981

Resistance to benzimidazole anthelmintics in equine strongyles. 1. Frequency, geographical distribution and relationship between occurrence, animal husbandry procedures and anthelmintic usage.

A survey was conducted to determine whether benzimidazole resistant populations of equine strongyles are present in New South Wales and north central Victoria; what is their frequency and geographical distribution; which species are involved; and whether different methods of parasite control could be related to the occurrence and frequency of anthelmintic resistant populations. Resistant populations of strongyles were found over wide areas of New South Wales and in north central Victoria. There was no relationship between geographical location and the occurrence of benzimidazole resistance. The species involved were small strongyles of the sub-family Cyathostominae. There was a direct correlation between the occurrence of resistance (including the level at which it is present) and the frequency of use of benzimidazole anthelmintics. Examination of management practices showed that resistance is not an important problem on farms where different chemical classes of anthelmintics were used in a slow rotation programme; combination anthelmintic therapy (for example, benzimidazole/piperazine/organophosphates) was used and anthelmintic treatment was given at intervals of not less than 16 weeks. Tentative suggestions are made for the control of small strongyles in the light of an emerging resistance problem.

Animal Husbandry↗
PubMed1988

Anthelmintic resistance in the field: changes in resistance status of parasitic populations in response to anthelmintic treatment.

Changes in anthelmintic resistance in nematode parasites were monitored in sheep grazing on 2 separate farms, but with the same anthelmintic treatment program, over 16 years. High levels of benzimidazole resistance emerged in Ostertagia and Trichostrongylus spp populations on both farms following 9 years of continuous use of this class of drug. Subsequently, variations in the levels of resistance occurred for the same species between farms and between species on the same farm. A change to levamisole for 2 years resulted in a significant reversion towards benzimidazole susceptibility, but a concomitant rise in levamisole resistance, in Ostertagia on one farm. However, benzimidazole resistance increased rapidly following the re-introduction of oxfendazole into the anthelmintic treatment program. Results from both farms illustrate the pitfalls of using one anthelmintic class for an extended period and provide indirect support for the alternation of anthelmintic classes at approximately yearly intervals.

Animals↗
PubMed1989

Changes in anthelmintic resistance status of Haemonchus contortus and Trichostrongylus colubriformis exposed to different anthelmintic selection pressures in grazing sheep.

This experiment was designed to study, over a 5-year-period, the effect of different frequencies of treatment with three different anthelmintic groups, namely, benzimidazoles, levamisole and ivermectin, and different frequencies of alternation between them, on existing levels of anthelmintic resistance in the nematode parasites Haemonchus contortus and Trichostrongylus colubriformis of grazing sheep. No evidence of ivermectin resistance emerged, even in suppressively treated groups. Likewise, H. contortus failed to develop resistance to levamisole under a similar selection regimen. Thiabendazole was shown to select positively against levamisole resistance in T. colubriformis resulting in significantly greater susceptibility to this drug than for the natural reversion which occurred in the untreated control. There was no evidence that an anthelmintic treatment combined with a movement of sheep to pastures of low infectivity selected more rapidly for resistance than where the same number of treatments were given to set-stocked sheep. Rotation between anthelmintic groups at yearly intervals appeared to be more beneficial in delaying resistance than rotation of drugs with each treatment.

Animals↗
PubMed1978

The anthelmintic efficacy of non-benzimidazole anthelmintics against benzimidazole resistant strains of Haemonchus contortus and Trichostrongylus colubriformis in sheep.

The anthelmintic efficacy of 6 non-benzimidazole compounds and thiabendazole against standardised, benzimidazole resistant strains of H. contortus and T. colubriformis in sheep was determined using a controlled test. All compounds were administered intraruminally at their recommended therapeutic dose rates and 4 of the compounds were also assessed at half their recommended therapeutic dose rates. Levimisole at a dose of 6.4 mg/kg body weight, morantel at 4.4 mg/kg and 8.8 mg/kg, naphthalophos at 6.25 mg/kg and 12.5 mg/kg, rafoxanide at 7.5 mg/kg and phenothiazine at 530 mg/kg were 98% or more effective in removing adult infections of benzimidazole resistant H. contortus. Rafoxanide at 3.75 mg/kg, phenothiazine at 265 mg/kg and carbon tetrachloride at 0.05ml/kg were less effective, removing 80%, 73% and 72% respectively of the benzimidazole resistant H. contortus worm burdens. Against the benzimidazole resistant T. colubriformis levamisole at 6.4 mg/kg, and morantel at 4.4 mg/kg and 8.8 mg/kg removed 99%, 68% and 86% respectively of the adult infections. All other anthelmintics had little or no efficacy at the dose rates tested. Thiabendazole at 44 mg/kg had no significant effect against these strains of H. contortus and T. colubriformis. Several non-benzimidazole anthelmintics have shown high efficacy in this experiment and should be suitable for treating infections with benzimidazole resistant H. contortus. Of the anthelmintics tested, only levamisole and morantel show high efficacy against benzimidazole resistant T. colubriformis.

Animals↗
PubMed1994

Theoretical perspectives on anthelmintic drug discovery: interplay of transport kinetics, physicochemical properties, and in vitro activity of anthelmintic drugs.

This multidisciplinary study demonstrates the utility of the biophysical model approach to assess biological activity of anthelmintics in light of drug-delivery principles. The relationships between drug absorption and efficacy for a set of structurally disparate anthelmintics were determined in cultures of Haemonchus contortus, a nematode that parasitizes the ruminant gastrointestinal tract. Uptake, parameterized by the permeability coefficient, Pe, was shown to occur by absorption across the cuticle. Rates of drug appearance in nematode carcasses paralleled rates of drug disappearance from the medium, and absorption reached an apparent equilibrium within a few hours. The parasite/medium partition coefficient, K, was derived from the ratio of drug concentration in the parasite vs the medium at equilibrium. Pe and K values for each anthelmintic were correlated with lipophilicity (as measured by the partition coefficient (PC) in n-octanol/water) and both parameters plateaued at log PC approximately 2.5, with maximum Pe approximately 8 x 10(-4) cm/min and log K < or = 2.0. Absorption kinetics were related to in vitro potency by monitoring motility of H. contortus. The time required to reduce motility by 50% (t* 50) and Pe were used to calculate Cn*, the drug concentration in the parasite at t* 50, as an indicator of intrinsic potency. The quantitative interplay of apparent biological activity expressed as t* 50, dose, and intrinsic potency highlights the important contribution of drug-uptake kinetics.

Absorption↗
PubMed1981

Anthelmintic treatment of equids: capabilities and limitations. Critical tests of nine anthelmintic agents on ponies.

A number of good anthelmintic drugs are currently available which eliminate gastrointestinal nematodes of equids with over 90% success. This is shown by comparing results of critical tests conducted with 9 anthelmintic agents on ponies using the following dosages: 19 mg/kg for Pyrantel embonate, 10 mg/kg for Oxfendazole, 10 mg/kg for Mebendazole, 5 mg/kg for Albendazole, 40 mg/kg for Dichlorvos, 44 mg/kg for Thiabendazole, 7.5 mg/kg, for Fenbendazole, 20 mg/kg for Cambendazole and 7 mg/kg for Parbendazole. From 6 to 9 ponies were treated with each of these anthelmintic agents. Based on total activity of various parasites involved, there was no significant difference in activity of any of the nine agents. With respect to Trichonema spp., or small strongyles, which are most numerous and most common in equids, statistical analysis enabled all nine products to be classified into three groups as follows: group 1, with the most active being Oxfendazole and Pyrantel embonate; group 2; including Thiabendazole, Mebendazole, Albendazole and Cambendazole; group 3, with Parbendazole, Fenbendazole et Dichlorvos. Results with large strongyles sometimes vary quite significantly. Dichlorvos and Pyrantel embonate should be recommended against Strongylus spp.; Mebendazole and dichlorvos against pinworms; Cambendazole against Strongyloïdes westeri; Pyrantel embonate, Cambendazole and Dichlorvos against Parascaris equorum; and Dichlorvos, Mebendazole with Trichlorfon and Pyrantel embonate with Trichlorfon against bots. No activity against Trichostrongylus axei, Anoplocephala spp. was noted with any of the nine agents tested.

Animals↗
PubMed1991

Interaction of benzimidazole anthelmintics with Haemonchus contortus tubulin: binding affinity and anthelmintic efficacy.

The ability of various benzimidazoles (BZs) to bind tubulin under different conditions was assessed by determining their IC50 values (the concentration of unlabeled drug required to inhibit 50% of the labeled drug binding), Ka (the apparent equilibrium association constant) and Bmax (the maximum binding at infinite [BZ] = [drug-receptor]). The ability of unlabeled benzimidazoles--fenbendazole, mebendazole (MBZ), oxibendazole (OBZ), albendazole (ABZ), rycobendazole (albendazole sulfoxide, ABZSO), albendazole sulfone, oxfendazole (OFZ), and thiabendazole--to bind tubulin was determined from their ability to inhibit the binding of [3H]MBZ or [3H]OBZ to tubulin in supernatants derived from unembryonated eggs or adult worms of Haemonchus contortus. The binding constants (IC50, Ka, and Bmax) correlated with the known anthelmintic potency (recommended therapeutic doses) of the BZ compounds except for OFZ and ABZSO whose Ka values were lower than could be expected from anthelmintic potency. The binding of [3H]ABZ or [3H]OFZ to tubulin in supernatants derived from BZ-susceptible and BZ-resistant H. contortus was compared. [3H]ABZ demonstrated saturable high-affinity binding but [3H]OFZ bound with low affinity. The high-affinity binding of [3H]ABZ was reduced for the R strain. Tubulin bound BZ drugs at 4 degrees C with lower apparent Ka than at 37 degrees C.

Albendazole↗
PubMed2000

[Anthelmintic resistance in gastrointestinal Strongylidae in sheep and goats: new data on prevalence, epidemiology, preventive measures and alternatives to anthelmintic drugs].

Anthelmintic-resistant gastrointestinal nematodes represent the major problem in controlling of parasites of small ruminants in central Europe. This article gives a brief update on the prevalence of resistant populations in sheep and goat farms in Europe. New data on the selection and spread of anthelmintic resistance are reported and recommendations are given for minimising further increases in the incidence of resistant populations. New strategies which may play a role in integrated control programs in the future, e.g. vaccination and the development of nematode-resistant breeds of animals or of nematophagous fungi are briefly discussed.

Animals↗
PubMed1977

The effect of route of administration on the anthelmintic efficacy of benzimidazole anthelmintics in sheep infected with strains of Haemonchus contortus and Trichostrongylus colubriformis resistant or susceptible to thiabendazole.

Observations of erratic anthelmintic activity of fenbendazole against known standardised thiabendazole-resistant strains of Haemonchus contortus and Trichostrongylus colubriformis in sheep were investigated. Fenbendazole at a dose rate of 10 mg/kg body weight was administered by oral, intra-ruminal or intra-abomasal routes, and was most effective against both resistant strains following intra-ruminal administration. In addition thiabendazole, oxibendazole, fenbendazole, parbendazole and mebendazole plus two unrelated compounds, levamisole and morantel tartrate, were used at one and a half times their suggested or recommended therapeutic dose rate against thiabendazole-resistant strains of H contortus and T colubriformis in sheep; each drug being administered by the intra-ruminal or intra-abomasal routes. Fenbendazole was more effective against both strains following intra-ruminal administration. Parbendazole was more effective against the resistant strain of T colubriformis following intra-ruminal administration. At the dose rate chosen for the other benzimidazoles used against these resistant strains, there was no difference in anthelmintic efficacy due to route of administration. Levamisole was highly effective against both resistant strains, irrespective of the route of administration. In the groups treated with morantel tartrate, the results obtained were difficult to interpret due to mortalities and a highly variable response in the surviving sheep. Fenbendazole, thiabendazole and mebendazole when used at their suggested or recommended therapeutic dose rate in sheep, were highly effective against known thiabendazole-susceptible strains of H contortus and T colubriformis following both intra-ruminal or intra-abomasal administration.

Abomasum↗
PubMed1984

[2-(Guanidino)-anilides and related compounds. Synthesis and anthelmintic effect. 3. Anthelmintics].

Anilides bearing a guanidino, thioallophanato, isothioallophanato or amidino group in the ortho position were synthesised (6) for investigations of their anthelmintic effects, and tested against sheep trichostrongylides. The most active anilides are those containing a 5-alkylthio, 5-alkylsulphinyl (alkyl = C3H7, C4H9), 5-phenylthio, 5-phenylsulphinyl or 4-phenylsulphonyloxy group, and a guanidino group substituted at both nitrogen atoms by a methoxycarbonyl group. The most active anthelmintic anilides are the form-, propion-, butyr- and methoxy-acetanilides (e.g. 60, 61, 66, 95, 100, 110). Of the guanidines unsubstituted at N' and N", the 2-guanidino-5-phenylthio-2-methoxyacetanilide (123) and the 2-guanidino-5-phenylsulphinyl-2-methoxyacetanilide (152) were more active than parbendazole. From the class of bismethoxycarbonylguanidines (6 alpha), which are also the most interesting products in terms of stability, febantel (110, Rintal) has been introduced into veterinary practice for the treatment of nematode infections in horses, cattle, sheep and swine.

Aniline Compounds↗
PubMed1981

A residual anthelmintic 2,6-diiodo-4-nitrophenol (Disophenol). Methods of testing its anthelmintic efficacy.

A subcutaneous injection of 2,6-diiodo-4-nitrophenol (Disophenol) at 10 mg/kg sheep leaves a residue bound to serum albumin which is lethal to Haemonchus contortus for 3 months after treatment. In the larval anthelmintic test, susceptible worm free sheep are dosed so that either third stage larvae (L3), or fourth stage larvae (L4) or 5th and adult stages are present on the day of treatment but slaughter is delayed to allow these larval stages to develop to adults because the larger worms are more easily seen, identified and counted. The larval anthelmintic test in sheep had to be altered and sheep killed within a few days of treatment, because the residues may be more effective against subsequent stages of development. Disophenol was greater than 60% effective against L3 of Oesophagostomum columbianum and L4 of H. contortus in greater than 60% of sheep (Class B). It rose to greater than 80% effective against adult H. contortus in greater than 80% of sheep (Class A). Against H. contortus it maintained Class A for 32 days, fell to Class B from 45--76 days and Class C (greater than 50% effective in greater than 50% of sheep) at 91 days after treatment respectively. In the RSA a treatment in December followed by another in March would protect sheep adequately against H. contortus for the entire season.

Animals↗
PubMed1994

Overberg research projects. XVI. First-stage larval reduction test versus the controlled anthelmintic test to assess the efficacy of anthelmintics against nematode parasites of sheep.

Results of a first-stage larval reduction test (L1RT) were compared with those of a controlled anthelmintic test (CAT) done on naturally infected sheep which grazed on spray-irrigated grass/legume pastures at Tygerhoek Experimental Farm near Riviersonderend in the southern Cape Province. The 3 anthelmintics used were morantel, ivermectin and levamisole. According to the L1RT, treatments reduced the geometric means of Strongyloides by 74.2 to 95.2% and those of the adults of all the other genera (Haemonchus, Nematodirus, Oesophagostomum, Teladorsagia, Trichostrongylus and Trichuris) by 99.4 to 99.75%. By contrast the results of the CAT were more variable, placing the reliability of the L1RT in doubt. In addition, the CAT could also evaluate the effect against fourth larval stage Teladorsagia.

Animals↗
PubMed1996

In vitro characterization of anthelmintic susceptibility of field isolates of the pig nodular worm Oesophagostomum spp., susceptible or resistant to various anthelmintics.

A larval development assay (LDA) and an egg hatch paralysis assay (EHPA) were used to measure the sensitivity to anthelmintics of eggs and larvae of nodular worms (Oesophagostomum spp.) in pigs. The tests were carried out using in vivo defined resistant and susceptible isolates of Oesophagostomum dentatum, O. quadrispinulatum and Oesophagostomum spp. For measurement of pyrantel/morantel and levamisole sensitivity the LDA was found able to distinguish between susceptible or resistant isolates of Oesophagostomum. The EHPA was able to detect levamisole resistance, but the test failed to show differences in response to pyrantel between pyrantel susceptible and resistant lines. The possible routine application of LDA and EHPA in the diagnosis of anthelmintic resistance in Oesophagostomum spp. is discussed.

Animals↗