Efficacy of moxidectin, nemadectin and ivermectin against an ivermectin-resistant strain of Haemonchus contortus in sheep.

The efficacies of ivermectin, nemadectin and moxidectin were evaluated when administered orally to lambs infected with either a susceptible laboratory strain of Haemonchus contortus or a strain reported to be resistant to ivermectin. Groups of 24 Dorset cross Cheviot cross Suffolk lambs were infected with either the susceptible or resistant strain of H contortus and allocated to treatment groups according to their faecal egg counts 27 days after infection. One day later the lambs were dosed orally with one of the three anthelmintics at 0.2 mg/kg bodyweight, and they were killed and surviving worms were recovered 13 or 14 days after treatment. Against the ivermectin resistant strain, ivermectin did not significantly reduce the egg count or the numbers of adult H contortus; however, both nemadectin and moxidectin reduced the nematode egg counts and the numbers of H contortus by 99 and 100 per cent, respectively. Against the susceptible strain, all the anthelmintics reduced the egg counts by 100 per cent as early as four days after treatment and reduced the numbers of susceptible H contortus by 100 per cent. No adverse reactions to any of the drugs were observed.     

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)     

Duration of the persistent activity of moxidectin against Haemonchus contortus in sheep

SUMMARY Weaned lambs were infected with Haemonchus contortus 35,28,21,14 and 7 days after treatment with moxidectin at 0.2 mg/kg and 35 and 14 days after treatment with ivermectin at the same dose rate. Worm counts 14 days after infection showed that moxidectin prevented the establishment of over 99% of infective larvae for 28 days and reduced the establishment rate at 35 days by 96%, relative to ivermectin. There was no difference in the protective efficacy of ivermectin at 14 or 35 days. The persistence of moxidectin is likely to provide advantages in nematode control, particularly when used as a strategic early summer treatment or as a pre-lambing treatment to ewes. Implications of the persistent activity of moxidectin for the development of resistance during the decay phase are discussed.     

Efficacy of abamectin against ivermectin-resistant strain of Trichostrongylus colubriformis in sheep

The efficacy of two formulations of abamectin, i.e. oral and injectable was determined against ivermectin-resistant strain of T. colubriformis in sheep. Twenty-four lambs were infected with 10,000 third stage larvae of ivermectin-resistant strain of T. colubriformis. Twenty-four days post-infection, the lambs were divided randomly into four groups of six animals each according to egg counts. The first group was left untreated and kept as a control. The second group was treated with ivermectin (oral) at 0.2mg kg(-1) body weight. The third group was treated with oral formulation of abamectin at 0.2mg kg(-1) body weight. The fourth group was treated with injectable formulation of abamectin at 0.2mg kg(-1) body weight. Fecal egg count and controlled slaughter tests were employed to determine the efficacy of abamectin (oral and injection) against ivermectin-resistant strain of T. colubriformis in sheep. Reduction in arithmetic mean fecal egg counts achieved by ivermectin (oral), abamectin (oral) and abamectin (injection) was 66, 98 and 76%, respectively 10 days after treatment. Ivermectin (oral), abamectin (oral) and abamectin (injection) reduced arithmetic mean worm burden by 63, 97 and 74%, respectively. The findings demonstrated that abamectin oral formulation was more effective than abamectin injection against ivermectin-resistant strain of T. colubriformis in sheep.     

The difference in efficacy of ivermectin oral, moxidectin oral and moxidectin injectable formulations against an ivermectin-resistant strain of Trichostrongylus colubriformis in sheep

AIM: To evaluate the efficacy of ivermectin oral, moxidectin oral and moxidectin injectable formulations against an ivermectin-resistant strain of Trichostrongylus colubriformis in sheep. METHODS: Twenty-four mixed breed lambs were infected with 15,000 infective third-stage larvae of an ivermectin-resistant strain of T. colubriformis which had originally been isolated from a goat farm in Northland in 1997. Twenty-six days post infection, the lambs were divided into 3 treatment groups and a control group (n=6 lambs/group). Treatment consisted of either ivermectin oral formulation (0.2 mg/kg), moxidectin oral formulation (0.2 mg/kg), or moxidectin injectable formulation (0.2 mg/kg). Faecal egg counts (FECs) were determined at 0, 3, 5, 7 and 10 days after treatment. All animals were necropsied 12 days after treatment and worm counts were performed. Larval development assays were conducted 24 days post infection. A further 3 lambs were infected with 15,000 infective third-stage larvae of a fully susceptible strain of T. colubriformis for comparative purposes in the larval development assay. The efficacy of the moxidectin injectable formulation was also confirmed in these 3 lambs. RESULTS: The FEC reduction test at day 10 after treatment revealed 62%, 100% and 0% reductions in arithmetic-mean FECs for ivermectin oral, moxidectin oral and moxidectin injectable groups, respectively. The ivermectin oral, moxidectin oral and moxidectin injectable formulations achieved 62%, 98% and 4% reductions in arithmetic-mean worm burdens, respectively. Larval development assays showed resistance ratios for ivermectin of 4:1, avermectin B2 of 2.7:1, ivermectin aglycone of 37:1, moxidectin of 1.4:1, thiabendazole of 14.6:1 and levamisole of 1.8:1. CONCLUSIONS: The moxidectin oral formulation provided a high degree of control against ivermectin-resistant T. colubriformis whereas the moxidectin injectable formulation had very low efficacy. Ivermectin aglycone was the analogue of choice for diagnosis of ivermectin resistance in T. colubriformis in the larval development assay.     

The effects of ivermectin and moxidectin on egg viability and larval development of ivermectin-resistant Haemonchus contortus

The in vivo effects of ivermectin and moxidectin on egg viability and larval development of ivermectin-resistant Haemonchus contortus were examined over time after anthelmintic treatment of sheep. Twenty merino sheep, (12 months old) were allocated to five treatment groups and infected with ivermectin-resistant H. contortus. Thirty one days later, the sheep were treated with intraruminal ivermectin capsules, oral ivermectin, oral moxidectin or injectable moxidectin at the manufacturer's recommended dosages, or left untreated. At various times up to 112 days after treatment, faecal egg counts (FEC) were determined and development rates of infective larvae (L3) cultured in faeces or on agar were measured. Eggs in faecal cultures from ivermectin capsule treated sheep showed reduced L3 development percentages in comparison to faecal cultures from untreated sheep. Eggs from ivermectin capsule treated sheep, isolated from faeces, and cultured on agar showed similar L3 development to eggs from control sheep. These results demonstrate an inhibitory effect of excreted ivermectin in faeces on larval development of ivermectin-resistant H. contortus. L3 development in faecal culture from animals receiving oral ivermectin were reduced for only 3 days after treatment. Faecal egg counts and development of L3 larvae in both culture systems from moxidectin treated sheep were low, due to the high efficacy of the drug. Egg counts in moxidectin treated sheep were reduced by approximately 90% 24h after treatment, before decreasing to almost 100% at 48h, suggesting that the current quarantine recommendation of holding sheep off pasture for 24h after treatment may still lead to some subsequent pasture contamination with worm eggs.     

Decreased ivermectin and moxidectin sensitivity in Haemonchus contortus selected with moxidectin over 14 generations.

Ivermectin resistance in the nematode Haemonchus contortus has been reported in many parts of the world and many ivermectin resistant isolates have been found to have reduced sensitivity to moxidectin. However, it is unclear whether parasites that are selected with moxidectin would demonstrate reduced sensitivity to ivermectin. In this study, the effects of moxidectin and ivermectin on an unselected strain and a strain of H. contortus derived from the unselected strain but selected over 14 generations with moxidectin, were compared in jirds. The recovery of adult worms and fourth stage (L4) larvae following treatment were compared between strains and anthelmintics. Moxidectin-selected H. contortus showed reduced sensitivity to ivermectin as well as to moxidectin. Doses of 0.1 mg/kg of moxidectin and 0.4 mg/kg of ivermectin were necessary to obtain an efficacy of 95% or above against the moxidectin-selected strain of H. contortus compared with 0.025 mg/kg for moxidectin and 0.1 mg/kg for ivermectin required for a similar efficacy in the unselected strain.     

Characterization of moxidectin resistant Trichostrongylus colubriformis and Haemonchus contortus

The development of moxidectin resistance (MOX-R) in sheep parasitic gastrointestinal nematodes already carrying multiple resistances to other anthelmintic groups has made control of these strains very difficult. The anthelmintic resistance patterns of MOX-R strains of Trichostrongylus colubriformis and Haemonchus contortus were characterized to provide an insight into the remaining role of anthelmintics in the control of such strains. Homozygous MOX-R individuals of both genera were unaffected by moxidectin. For MOX-R heterozygotes a dose rate of 200 microg/kg abamectin (ABA) given orally removed 25% of H. contortus while 200 microg/kg MOX given orally achieved a 72% reduction. Doubling the dose rate of ABA improved the mean efficacy to 37%. Consequently, in H. contortus, the degree of dominance differs markedly between the two anthelmintics. A dose rate of 8 mg/kg levamisole and 185 mg/kg napthalophos achieved >95% reduction in worm count of the MOX-R homozygous H. contortus but only 85 and 7%, respectively against the MOX-R homozygous T. colubriformis.     

Reduced efficacy of ivermectin, abamectin and moxidectin against field isolates of Haemonchus contortus

OBJECTIVES: To investigate the reduced efficacy of ivermectin, abamectin and moxidectin against two field isolates of Haemonchus contortus. These isolates were identified on separate properties in the New England region of New South Wales. PROCEDURE: Reduced efficacy of macrocyclic lactone anthelmintics against two field isolates of H contortus was suspected. These isolates were obtained from sheep on separate farms and pen trials were performed to investigate the efficacy of macrocyclic lactones. The percentage efficacy was calculated for moxidectin, ivermectin and closantel against the isolate from one farm (VHR23) and for moxidectin, ivermectin and abamectin against the isolate from the second (VHR29). The persistent activity of moxidectin against both isolates was investigated. RESULTS: Ivermectin and closantel were found to have efficacies below 80% against established populations of VHR23. Moxidectin was effective against an established population of VHR23 but the persistent activity was reduced to 7 days. Moxidectin was also found to be effective against established populations of VHR29, however, ivermectin and abamectin were found to have efficacies below 80%. There was no evidence of persistent activity of moxidectin against VHR29. CONCLUSION: A reduction in efficacy of abamectin and/or ivermectin against field isolates of H. contortus was identified from two farms in the New England region of New South Wales. The persistent effect of moxidectin was reduced against both isolates.     

捻转血矛线虫Hc38基因DNA疫苗对绵羊免疫保护性效果评价

为了研究基因疫苗对绵羊的免疫保护效果,本研究构建了捻转血矛线虫(H.contortus)Hc38基因DNA疫苗.将H.contortus Hc38基因保守结构域克隆到真核表达载体pcDNA3.1中,免疫鼠8d后用RT-PCR检测到该疫苗在鼠肌肉组织中进行了转录.将纯化的DNA疫苗免疫绵羊后,用western blot和ELISA方法检测疫苗在绵羊体内的翻译和诱导IgG的产生.二免后2周用10 000条H.contortus第3期幼虫攻击实验动物,检测绵羊粪便虫卵排出、成虫数量等免疫保护性指标.该H.contortus Hc38 DNA疫苗与对照组比较,免疫组绵羊排出虫卵减少66.6%、成虫减少33.1%.特别值得注意的是免疫组的静脉注射方式产生抗体最高,相应羊的虫卵数和成虫数低.本实验证明Hc38基因DNA疫苗对绵羊虫卵及成虫发育具有明显的抑制作用.     

Efficacy of anthelmintic properties of medicinal plant extracts against Haemonchus contortus

The development of anthelmintic resistance has made the search for alternatives to control gastrointestinal nematodes of small ruminants imperative. Among these alternatives are several medicinal plants traditionally used as anthelmintics. This present work evaluated the efficacy of ethyl acetate, acetone, and methanol dried leaf and seed extracts of five medicinal plants were tested in vitro ovicidal and larvicidal activities on Haemonchus contortus. The in vitro assay was based on egg hatch assay (EHA) and larval development assay (LDA), all plant extracts were evaluated at five concentrations 50, 25, 12.5, 6.25 and 3.13 mg/ml. The leaf and seed ethyl acetate, acetone and methanol of Annona squamosa, Eclipta prostrata, Solanum torvum, Terminalia chebula, and Catharanthus roseus extracts were showed complete inhibition (100%) at the maximum concentration tested (50 mg/ml). The overall findings of the present study have shown that our experimental plant extracts contain possible anthelmintic compounds.     

Efficacy of anthelmintic properties of medicinal plant extracts against Haemonchus contortus

The development of anthelmintic resistance has made the search for alternatives to control gastrointestinal nematodes of small ruminants imperative. Among these alternatives are several medicinal plants traditionally used as anthelmintics. This present work evaluated the efficacy of ethyl acetate, acetone, and methanol dried leaf and seed extracts of five medicinal plants were tested in vitro ovicidal and larvicidal activities on Haemonchus contortus. The in vitro assay was based on egg hatch assay (EHA) and larval development assay (LDA), all plant extracts were evaluated at five concentrations 50, 25, 12.5, 6.25 and 3.13 mg/ml. The leaf and seed ethyl acetate, acetone and methanol of Annona squamosa, Eclipta prostrata, Solanum torvum, Terminalia chebula, and Catharanthus roseus extracts were showed complete inhibition (100%) at the maximum concentration tested (50 mg/ml). The overall findings of the present study have shown that our experimental plant extracts contain possible anthelmintic compounds.     

Efficacy of levamisole and netobimin against Haemonchus contortus in lambs in Louisiana

Efficacy of levamisole was evaluated in a suspected levamisole-resistant population of Haemonchus contortus in the Louisiana State University sheep flock. The efficacy of netobimin also was evaluated against this population of Haemonchus. In trial 1, 5 lambs naturally infected with H contortus were given 8 mg of levamisole/kg of body weight as a drench, and 5 lambs were not treated (controls). Nematode recovery after slaughter indicated 0% efficacy against H contortus. In trial 2, 30 nematode-free lambs were each given 8,300 F1 generation infective larvae of H contortus, which were derived from parent H contortus that survived 2 levamisole treatments in lambs being maintained in a nematode-free environment. Ten lambs were treated with 8 mg of levamisole/kg as a drench, 10 were treated with 20 mg of netobimin/kg as a drench, and 10 were not treated (control). Nematode recovery after slaughter revealed 62.3% and 99.8% efficacy for levamisole and netobimin, respectively, against H contortus.     

Hypergastrinaemia of sheep infected with Haemonchus contortus

Radioimmunoassay of plasma gastrin has shown that a hypergastrinaemia occurs in yearling sheep, after infection with 10(6) infective third stage larvae of Haemonchus contortus. Plasma gastrin concentrations began to rise two to four days after infection, that is, at about the same time as, or slightly before, the abomasal pH was observed to increase.     

Amphidial structure of ivermectin-resistant and susceptible laboratory and field strains of Haemonchus contortus

The development of anthelmintic resistance by nematode parasites is a growing problem for veterinarians, pet owners, and producers. The intensive use of the macrocyclic lactones for the treatment of a variety of parasitic diseases has hastened the development of resistance to this family of parasiticides. As a result, resistance to ivermectin, moxidectin, nemadectin, and doramectin by Haemonchus contortus has been documented throughout the world.

Sensory neurons located in the cephalic end of nematodes are in close contact with the external environment. Through these neurons, important chemical and thermal cues are gathered by the parasite. Examination of serial electron micrographs of ivermectin-susceptible and ivermectin-resistant H. contortus allows for comparison of neuronal structure, arrangement of neurons within the amphidial channel, and distance of the tip of the dendritic processes to the amphidial pore. The latter of these characteristics provides a useful means by which to compare the association between the neurons and the external environment of the worm.

Comparison of parental laboratory strains of ivermectin-susceptible strains of H. contortus with related selected, ivermectin-resistant strains and with a wild-type ivermectin-susceptible field strain of H. contortus from Louisiana reveal that the ivermectin-resistant worms examined have markedly shorter sensory cilia than their ivermectin-susceptible parental counterparts. Additionally, the amphidial neurons of ivermectin-resistant worms are characterized by generalized degeneration and loss of detail, whereas other neurons outside of the channels, such as the labial and cephalic neurons, are normal in structure. These findings raise a number of questions regarding the relationship between amphidial structure and ivermectin resistance as well as the role of amphids as a means of entry for ivermectin. While shortened amphidial sensilla are associated with ivermectin resistance, it remains unclear if such a structural modification facilitates survival of nematodes exposed to macrocyclic lactones.