Resistance to benzimidazole anthelmintics by trichostrongyles in sheep and goats in north-west Cameroon.

Following the routine use of tiabendazole at monthly intervals for several years, the trichostrongyle parasites of sheep and goats on a government research station in North-West Cameroon had become resistant to benzimidazole anthelmintics.     

Multigeneric resistance to benzimidazole anthelmintics in sheep

Benzimidazole resistance involving several gastrointestinal nematode genera on a single sheep farm in New Zealand is reported for the first time. A controlled slaughter trial showed that at the recommended dose rate of 12.5 mg/kg, mebendazole had efficacies of 0, 60, 66, 90, 54 and 38% against Haemonchus contortus, Ostertagia spp., Nematodirus spp., intestinal Trichostrongylus spp., Strongyloides spp. and Oesophagostomum venulosum, respectively. The relevance of such multigeneric resistance to possible future options for controlling anthelmintic resistant sheep trichostrongylids is briefly discussed.     

Multigeneric resistance to benzimidazole anthelmintics in four sheep flocks

Clinical parasitism associated with multigeneric resistance to benzimidazole anthelmintics was investigated in four sheep flocks during February and March 1989. The genera considered resistant were Haemonchus and Nematodirus spp. on all four farms and Trichostrongylus and Ostertagia spp. on three of the four farms. It is suggested that when investigating cases of suspected drench resistance, postdrenching worm counts are useful to help identify the resistant worm species present.     

Multigeneric resistance to benzimidazole anthelmintics in four sheep flocks

Clinical parasitism associated with multigeneric resistance to benzimidazole anthelmintics was investigated in four sheep flocks during February and March 1989. The genera considered resistant were Haemonchus and Nematodirus spp. on all four farms and Trichostrongylus and Ostertagia spp. on three of the four farms. It is suggested that when investigating cases of suspected drench resistance, post-drenching worm counts are useful to help identify the resistant worm species present.     

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

SUMMARY: Resistance to a range of benzimidazole anthelmintics was investigated in 2 strains of Ostertagia spp. One strain (SRBO) 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.     

Pharmacokinetic comparison of six anthelmintics in sheep,goats, and cattle

This study was initiated to determine whether a comparative pharmacokinetic (PK) approach could be used to expand the pool of approved anthelmintics for minor ruminant species. Accordingly, the PK profiles of six anthelmintics (levamisole, albendazole, fenbendazole, moxidectin, doramectin, and ivermectin) in sheep, goats, and cattle were determined. The PK values determined for each anthelmintic included T_max, T_last, C_max, AUC, AUC/dose, and C_max/dose. The results of this study demonstrate that a comparative PK approach does not show commonality in the way these six anthelmintics are individually processed by these three ruminants. While some drugs demonstrated identical PK profiles between sheep and goats, none of these drugs demonstrated PK profiles in sheep and goats comparable to the PK profiles found in cattle. The results from this study suggest drug approval across these three ruminants is not a viable concept. However, the resulting PK profiles for each combination of drug and ruminant species represents a new dataset that can be used to support the US FDA Center for Veterinary Medicine's Minor Use/Minor Species indexing process for drug approvals in minor species such as sheep and goats.     

In vitro ruminal biotransformation of benzimidazole sulphoxide anthelmintics: enantioselective sulphoreduction in sheep and cattle

The comparative in vitro sulphoreduction of the (+) and (-) enantiomers of albendazole sulphoxide (ABZSO) and oxfendazole (OFZ) by ruminal fluid obtained from sheep and cattle, was investigated, under anaerobic conditions, in this study. Ruminal fluid samples were obtained from Holstein steers fitted with a permanent rumen fistula and from Corriedale lambs via an oesophageal tube. Albendazole sulphoxide, incubated as either the racemic (rac) mixture or as each individual enantiomeric form, was extensively sulphoreduced to form albendazole (ABZ) by ruminal fluid from both species. The concentrations of ABZ formed at different incubation times were between 55 and 158% greater after the incubation of cattle ruminal fluid with (+) ABZSO, compared with that produced when (-) ABZSO was the incubated substrate. Similarly, the concentrations of ABZ were 1.3--3.0-fold higher when (+) ABZSO was incubated with sheep ruminal fluid. Significantly higher rates of depletion were observed for the (+) enantiomeric form when ABZSO was incubated with ruminal fluid from both species. The rates of ABZ formation from both ABZSO enantiomeric forms were significantly higher in sheep compared with cattle ruminal fluid. Fenbendazole (FBZ) was the metabolite formed after the incubation of the racemic form of OFZ with ruminal fluid obtained from both species. The metabolic profile of both OFZ enantiomers followed a similar pattern to that observed for ABZSO enantiomers. A bi-directional chiral inversion of one enantiomer into its antipode was observed. The (+) enantiomer appeared in the incubation medium when (-) ABZSO was the incubated substrate, and also the (-) antipode was detected after (+) ABZSO incubation with ruminal fluid obtained from both species. The results reported here demonstrate an enantioselective ruminal sulphoreduction of ABZSO and OFZ (substrate enantioselectivity). These findings contribute to interpret the chiral behaviour of benzimidazole-sulphoxide anthelmintics.     

Efficacy of three broad-spectrum anthelmintics against gastrointestinal nematode infections of goats

Groups of 10 goats, harbouring both naturally acquired and experimental infections of gastrointestinal nematodes, were drenched with either levamisole (5 mg kg-1), albendazole (3.8 mg kg-1) or parbendazole (15 mg kg-1), or remained untreated. Haemonchus contortus was the numerically dominant infection, with Strongyloides papillosus, Trichostrongylus colubriformis and Oesophagostomum columbianum also present. At 5-6 days post-treatment, goats were killed and necropsied. Post-mortem worm counts showed that the reduction in mean total worm burdens was 57.4% in levamisole-treated animals, 71.1% in the albendazole group and 85.1% in the parbendazole group. Reductions for H. contortus were 80.2, 87.9 and 83.9% in the levamisole-, albendazole- and parbendazole-treated groups, respectively. These data indicate that the anthelmintics in question are not being applied at an adequate dose rate for goats, and/or resistance to anthelmintics is occurring in the field in Pernambuco State, northeast Brazil.     

宁夏羊胃肠道线虫对现行驱虫药的抗药性调查

采用粪便虫卵减少试验对宁夏地区所属灵武、贺兰、盐池、吴忠、中宁、中卫、永宁和银川市郊8个县（市）的12个绵羊场、6个山羊场进行了丙硫苯咪唑和阿维菌素抗药性的随机调查。结果表明：在用丙硫苯咪唑调查的10个绵羊场和6个山羊场中，虫卵减少率在95％以下和95％的置信域下限在90％以下的有山羊场2个、绵羊场2个，证明对丙硫苯咪唑有抗药性；1个绵羊场和1个山羊场的虫卵减少率是96．3％、95．9％，但95％置信域的下限在90％以下，具有抗药性可疑；山羊群中丙硫苯咪唑的抗药性为33．3％，绵羊群为20．0％。用同样的方法调查了1个山羊场和5个绵羊场（其中有4个羊场曾执行了丙硫苯咪唑的试验），查出1个山羊场和1个绵羊场对阿维菌素具有抗药性可疑，其虫卵减少率分别为97．3％和95．5％，置信域下限在90％以下。揭示了宁夏地区羊消化道线虫对现行驱虫药的抗药状态，为今后防治提供了依据。     

用丙硫苯咪唑检测羊线虫抗药性的体外虫卵孵化试验

为探讨用丙硫苯咪唑进行体外虫卵孵化试验检测羊线虫对苯并咪唑类药物的抗药性,对23个羊场的25份田间样品用丙硫苯咪唑和噻苯咪唑进行了虫卵孵化试验并与先前减卵试验（faecal egg count re-duction test,FECRT）的结果比较。结果表明,25份样品中,丙硫苯咪唑和噻苯咪唑对受检虫卵的半数致死量（LD50）均值分别为0.050 1和0.054 0μg/mL,差异不显著。FECRT检测有抗药性的4个羊场,75%的样品对丙硫苯咪唑和噻苯咪唑的LD50均值均在0.1μg/mL以上,只有1个羊场的的LD50值分别为0.068 9μg/mL（丙硫苯咪唑）和0.071 2μg/mL（噻苯咪唑）。检测为可疑的2个羊场,其样品的LD50值为0.04～0.07μg/mL;FECRT检测敏感的蠕虫群体的LD50均在0.04μg/mL以下。此外,丙硫苯咪唑用纯的二甲基亚砜溶解和稀释后于4℃保存7 d,LD50值变化不大,提示药效无明显下降,而保存14 d后药效有下降趋势。     

Efficacy of some anthelmintics on an ivermectin-resistant strain of Haemonchus contortus in sheep

Following evidence of reduced efficacy of ivermectin in a field population of Haemonchus contortus in Brazil, this strain of the parasite was submitted to a controlled anthelmintic test. Eighty worm-free lambs were randomly split into two groups of 40. Each lamb in the first group was infected with 5000 third stage larvae (L3) of the ivermectin-resistant strain; the remaining 40 lambs were each infected with 5000 L3 of a H. contortus strain of known susceptibility to the major groups of anthelmintic compounds used in sheep. On Day 28 post-infection, each group was subdivided according to egg counts and at random into four sub-groups of ten lambs, each of which was treated with albendazole (ABZ) at 3.8 mg kg-1, levamisole (LEV) at 7.5 mg kg-1 or ivermectin (IVM) at 0.2 mg kg-1, or was left as untreated control. At slaughter, 7 days later, all the anthelmintics reduced worm burdens in animals infected with the susceptible strain (ABZ 98.9%, LEV and IVM 100%). By contrast, in the lambs infected with the ivermectin-resistant strain, LEV was 99.8% effective, but ABZ reduced worm counts by only 14.7% and IVM by only 10.4%. Interestingly at necropsy on Day 7 post-treatment, the egg counts in the resistant strain treated with ABZ had been reduced by 92.5%, although worm counts were reduced by only 14.7%.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effectiveness of benzimidazole-levamisole combination drenches in the presence of resistance to both benzimidazole and levamisole anthelmintics in New Zealand sheep

Examination of 25 cases of multiple benzimidazole and levamisole resistance, identified in sheep by faecal egg count reduction testing at the Batchelar, Lincoln and Invermay Animal Health Laboratories, showed that benzimidazole-levamisole combinations provided effective control in eight (47%) of 17 cases in which they were tested. Overall, the use of combination drenches resulted in average improvements in faecal egg count reductions of 25.6% (p<0.01) and 23.2% (p<0.05), respectively, over those achieved by the use of benzimidazole or levamisole drenches alone. The results suggest that instances of multiple resistance in which combination drenches might be effective are unlikely to be predictable either by identification of the parasites involved, or from the levels of benzimidazole or levamisole resistance present.     

Simultaneous resistance to two or more broad-spectrum anthelmintics by gastrointestinal nematode parasites of sheep and goats

The detection, by means of faecal egg count reduction tests and larval cultures, of two cases of multiple anthelmintic resistance in goats and two in sheep, is reported. The former cases appeared to involve resistance to all three broad-spectrum drench groups (benzimidazole, levamisole, ivermectin) by mainly Ostertugia spp., the latter resistance to two of them (benzimidazole, levamisole) bv Trichostrondus spp. (New Zealand Veterinary Journal 38, 114–117, 1990)     

Simultaneous resistance to two or more broad-spectrum anthelmintics by gastrointestinal nematode parasites of sheep and goats

The detection, by means of faecal egg count reduction tests and larval cultures, of two cases of multiple anthelmintic resistance in goats and two in sheep, is reported. The former cases appeared to involve resistance to all three broad-spectrum drench groups (benzimidazole, levamisole, ivermectin) by mainly Ostertagia spp., the latter resistance to two of them (benzimidazole, levamisole) by Trichostrongylus spp.     

The comparative efficacy of four broad spectrum anthelmintics against some experimentally induced trichostrongylid infections in sheep and goats

A controlled slaughter trial was undertaken to compare the efficacies of oxfendazole (5 mg/kg), morantel citrate (10 mg/kg), levamisole (8 mg/kg) and ivermectin (0.2 mg/kg) against experimentally induced infections of adult Haemonchus contortus, Ostertagia spp., Trichostrongylus colubriformis and Cooperiacurticei in sheep and goats. Ivermectin and oxfendazole achieved similar levels of efficacy in both hosts against all four worm genera as did levamisole and mortantel against H. contortus and C. curticei. Against Ostertagia spp. and T. colubriformis, however, the latter two drugs were less effective in goats than sheep. Neither the numbers of Ostertagia spp. removed from goats by levamisole (81% reduction) nor the numbers of T. colubriformis removed from goats by morantel (56% reduction) were statistically significant (P>0.05).     

A routine diagnostic assay for the detection of benzimidazole resistance in parasitic nematodes using tritiated benzimidazole carbamates

Resistance to benzimidazoles (BZs) in parasitic nematodes has recently been shown to be due to a reduction in the ability of BZs to bind the structural protein, tubulin, in resistant isolates. Based on these observations the development and standardisation of a routine diagnostic assay has been undertaken by measuring the binding of tritiated mebendazole to crude supernatants of L3 larvae. The assay is rapid, requiring less than 2 h, and is robust, highly reproducible and sensitive to minor changes in the resistance status of parasite populations. Investigation of the routine application and validity of this assay has been documented using 24 isolates of known resistance status from the species Haemonchus contortus, Trichostrongylus colubriformis and Ostertagia circumcincta: In all cases the observed binding and calculated susceptibility factors were in accordance with their respective resistance status.