moxidectin and Trichostrongyloidiasis

Resistance to levamisole and the benzimidazoles appears to be achieved by one or, at most, two mechanisms in the common trichostrongyloid parasites of sheep. For the avermectin/milbemycin anthelmintic class the picture is more complex. In-vitro assays employing the free-living stages of trichostrongyloid nematodes were used to investigate structure-activity relationships for the avermectins/milbemycins. While avermectin/milbemycin-susceptible isolates of Haemonchus contortus, Trichostrongylus colubriformis and Ostertagia circumcincta were found to differ in their intrinsic sensitivities to avermectin/milbemycin inhibition of larval development and L3 motility, structure-activity profiles against all three species were similar. In-vivo avermectin/milbemycin resistance was associated with a reduced sensitivity to avermectin/milbemycin inhibition of larval motility and/or development in some, but not all, isolates. Where a reduced sensitivity to avermectin/milbemycin inhibition of larval development was observed, different groups of resistant isolates displayed different structure-activity profiles. Many avermectin/milbemycin-resistant isolates showed an increased sensitivity to paraherquamide. These in-vitro data have allowed the classification of avermectin/milbemycin-resistant isolates into a number of distinct types. Study of the inheritance of avermectin/milbemycin resistance in two resistance types suggests that the in-vitro differences between resistant isolates reflect important differences in the mechanism of resistance present. The kinetics of expulsion of H. contortus, T. colubriformis and O. circumcincta from sheep following treatment with ivermectin indicate that, in vivo, the critical action of avermectins/milbemycin against O. circumcincta may be different to that which results in H. contortus and T. colubriformis elimination. This observation provides some explanation for the differences between resistant isolates. If, for different species, the critical event(s) leading to expulsion are different, then it follows that the mechanisms of resistance observed may also differ.

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Drug Resistance; Indolizines; Ivermectin; Larva; Macrolides; Sheep; Sheep Diseases; Spiro Compounds; Trichostrongyloidea; Trichostrongyloidiasis

The use of moxidectin (MXD) in the treatment of small lungworm infestation (Cystocaulus ocreatus, Muellerius capillaris, Neostrongylus linearis and Protostronglylus rufescens) in sheep, was evaluated. Twenty-one sheep naturally infested with small lungworms, were divided into three groups (n = 7) and treated as follows: group A with moxidectin 1% injectable solution at a dose rate of 0.2mgkg(-1) bodyweight, group B with moxidectin 0.1% oral drench at a dose rate of 0.2 mgkg(-1) bodyweight and group C being controls. Before treatment, mean faecal larval counts were 30.7, 21.1 and 26.7 lpg in group A, B and C, respectively; 14 days after treatment respective counts were 0.4, 2.3 and 63.0 lpg, (percentage reduction after moxidectin administration >96.0%); 60 days after treatment respective counts were 0.0, 0.0 and 26.4 lpg, (percentage reduction after moxidectin administration 100%). It is concluded that treatment of small lungworm infestation of sheep can be effected by using moxidectin.

Topics: Administration, Oral; Animals; Antinematodal Agents; Feces; Female; Injections, Subcutaneous; Lung; Macrolides; Parasite Egg Count; Sheep; Sheep Diseases; Statistics, Nonparametric; Trachea; Trichostrongyloidea; Trichostrongyloidiasis

A field experiment and a controlled efficacy trial were conducted to demonstrate resistance of cattle trichostrongylid nematodes to endectocidal compounds in grazing cattle on the Humid Pampa, Argentina. Male Polled Hereford calves, aged 9-11 months old, with a history of frequent treatments with compounds of the avermectin/milbemycin class, were used for the trial. The field experiment involved six groups of 10 animals each, which were subcutaneously treated with either ivermectin (IVM), long-acting ivermectin (LA-IVM), moxidectin (MXD) or doramectin (DRM) at a dosage of 0.2mg/kg BW. A fifth group was treated orally with fenbendazole at a dosage of 5mg/kg BW; the sixth group of calves served as non-treated control. Faecal samples were collected from each animal on the day of treatment and at 14 days after treatment. Nematode egg counts were performed to estimate the faecal egg count reduction test (FECRT). The FECRT showed that reductions were 65% (IVM), -20% (LA-IVM) and 85% (DRM). Egg counts from calves treated with MXD or fenbendazole were reduced by 95 and 100%, respectively. For the controlled efficacy trial, six animals with the highest egg counts from the IVM, LA-IVM and non-treated control groups, were necropsied on day 18 after treatment to determine numbers and nematode species in the abomasum and small intestine. The results indicated that efficacy against Cooperia oncophora was 62.7 and 48% for IVM and LA-IVM, respectively. Neither of the IVM formulations showed efficacy against Trichostrongylus spp. in the small intestine. However, the absence of Trichostrongylus spp. in some animals of both treated and control groups precluded a valid assessment of efficacy or resistance. It was concluded that resistance of trichostrongylid nematodes to the avermectin/milbemycin class of compounds in grazing cattle of the Humid Pampa, Argentina, may be strongly established on farms where cattle are treated at frequent intervals throughout the year.

Topics: Animal Husbandry; Animals; Anthelmintics; Anti-Bacterial Agents; Argentina; Cattle; Cattle Diseases; Drug Resistance; Feces; Female; Fenbendazole; Ivermectin; Macrolides; Male; Trichostrongyloidea; Trichostrongyloidiasis

Resistance to ivermectin and moxidectin was explored by a faecal egg count reduction test in two sheep flocks with suspected anthelmintic resistance. The FECRT confirmed one suspicion, with a mean percentage of reduction in egg excretion within the treated groups of 0% for ivermectin (CI 95%: -228 to 58) and 13% for moxidectin (CI 95%: -152 to 70). This was further explored by a controlled efficacy test. An experimental infection of 18 naïve lambs was set up using infective larvae isolated from this flock (5000 L3/lamb). Compared to the control group, abomasal worm burdens (Teladorsagia circumcincta) were reduced by 90% [CI 95%: 81.5-94.8] and 85% [CI 95%: 72.4-92.2] after ivermectin (p<0.05) and moxidectin (p<0.05) treatment respectively. Again, compared to the control group, there was a reduction for intestinal strongyles (Trichostrongylus colubriformis) of 100% and 99% [CI 95%: 97.5-99.7] for ivermectin and moxidectin respectively. No difference was found between the efficacy of moxidectin and ivermectin. Pharmacokinetic values indicated that the strongyles were submitted to anthelmintic concentrations usually lethal to them. This trial demonstrated the first multiple resistance of ovine strongyles in France.

Topics: Abomasum; Animals; Antinematodal Agents; Cecum; Drug Resistance; Feces; Female; France; Intestine, Small; Ivermectin; Macrolides; Male; Nematode Infections; Parasite Egg Count; Sheep; Sheep Diseases; Trichostrongyloidea; Trichostrongyloidiasis; Trichostrongylus

To elucidate the molecular mechanism of host resistance, we characterized the jejunal transcriptome of Angus cattle selected for parasite resistance for over 20 years in response to infection caused by the intestinal worm Cooperia oncophora. The transcript abundance of 56 genes, such as that of mucin 12 (MUC12) and intestinal alkaline phosphatase (ALPI), was significantly higher in resistant cattle. Novel splicing variants, exon skipping events, and gene fusion events, were also detected. An algorithm for the reconstruction of accurate cellular networks (ARACNE) was used to infer de novo regulatory molecular networks in the interactome between the parasite and host. Under a combined cutoff of an error tolerance (ϵ = 0.10) and a stringent P-value threshold of mutual information (1.0 × 10(-5)), a total of 229,100 direct interactions controlled by 20,288 hub genes were identified. Among these hub genes, 7651 genes had ≥ 100 direct neighbors while the top 9778 hub genes controlled more than 50% of total direct interactions. Three lysozyme genes (LYZ1, LYZ2, and LYZ3), which are co-located in bovine chromosome 5 in tandem and are strongly upregulated in resistant cattle, shared a common regulatory network of 55 genes. These ancient antimicrobials were likely involved in regulating host-parasite interactions by affecting host gut microbiome. Notably, ALPI, known as a gut mucosal defense factor, controlled a molecular network consisting 410 genes, including 14 transcription factors (TF) and 10 genes that were significantly regulated in resistant cattle. Several large regulatory networks were controlled by TF, such as STAT6, SREBF1, and ELF4. Gene ontology (GO) processes significantly enriched in the regulatory network controlled by STAT6 included lipid metabolism. Our findings provide insights into the immune regulation of host-parasite interactions and the molecular mechanisms of host resistance in cattle.

Topics: Animals; Antinematodal Agents; Cattle; Cattle Diseases; Feces; Female; Fenbendazole; Gene Expression Profiling; Gene Regulatory Networks; Genetic Predisposition to Disease; Intestinal Diseases, Parasitic; Intestine, Small; Macrolides; Male; Parasite Egg Count; Protein Isoforms; RNA, Messenger; Trichostrongyloidea; Trichostrongyloidiasis

Administration of long-acting anthelmintics to pregnant ewes prior to lambing is a common practice in New Zealand. Today, most of these products contain macrocyclic lactone (ML) actives, which because of their lipophilic nature, are detectable in the milk of treated animals and in the plasma of their suckling offspring. This study was conducted to confirm the transfer of ML actives to lambs in the ewe's milk, and to assess whether this could result in selection for ML resistant nematodes in the lamb. Ninety, twin bearing Romney ewes were treated before lambing with a long-acting injectable formulation of moxidectin, a 100-day controlled release capsule (CRC) containing abamectin and albendazole, or remained untreated. After lambing, seven ewes from each treatment group were selected for uniformity of lambing date and, along with their twin lambs, relocated indoors. At intervals, all ewes and lambs were bled, and samples of ewe's milk were collected, for determination of drug concentrations. Commencing 4 weeks after birth all lambs were dosed weekly with 250 infective larvae (L3) of either an ML-susceptible or -resistant isolate of Teladorsagia circumcinta. At 12 weeks of age all lambs were slaughtered and their abomasa recovered for worm counts. Moxidectin was detected in the plasma of moxidectin-treated ewes until about 50 days after treatment and in their lambs until about day 60. Abamectin was detected in the plasma of CRC-treated ewes until the last sample on day 80 and in the plasma of their lambs until about day 60. Both actives were detectable in milk of treated ewes until day 80 after treatment. Establishment of resistant L3 was not different between the treatment groups but treatment of ewes with moxidectin reduced establishment of susceptible L3 by 70%, confirming the potential of drug transfer in milk to screen for ML-resistance in the suckling lamb.

Topics: Animals; Animals, Suckling; Anthelmintics; Drug Resistance; Female; Lactation; Macrolides; Milk; Nematode Infections; Sheep; Sheep Diseases; Trichostrongyloidea; Trichostrongyloidiasis

The prevalence of anthelmintic resistance in Northern Ireland sheep flocks was evaluated between July and October 2011. Sampling kits were sent to 172 flock owners and returns were received from 91. Within this survey population, 27 flock owners used benzimidazole products, 10 used levamisole products, 15 used avermectin products, 26 used milbemycin products and 4 flock owners used the amino acetonitrile derivative, Monepantel. The remaining 9 flock owners used combination drenches (broad spectrum wormer plus fasciolicide). However, 15 sets of samples were ineligible for faecal egg count reduction testing due to either too low an egg count or insufficient faecal volume. Treatment efficacy below 95%, indicating significant resistance, was detected in 81% (n=24) of flocks tested for benzimidazole resistance; in 14% (n=1) of flocks tested for levamisole resistance; and in 50% (n=7) and 62% (n=13) of flocks tested for avermectin and milbemycin resistance, respectively. Monepantel resistance was absent in all (n=3) flocks tested. Combination products (broad spectrum nematocide plus flukicide) containing levamisole were entirely effective, while treatment efficacy below 95% was detected in 60% (n=3) of flocks where the nematocide in the combination product was a benzimidazole. Where parasite identification based on coproculture was completed, Trichostrongylus was the dominant genus detected in all cases post-treatment, indicating the occurrence of anthelmintic-resistant Trichostrongylus spp. populations. Benzimidazole efficacy was highest in treating Trichostrongylus spp. (51%) and lowest when treating Teladorsagia spp. Levamisole was 100% effective in treating Cooperia, but ineffective (0%) in treating Trichostrongylus spp. Avermectin efficacy was highest when treating Haemonchus contortus (100%) and Teladorsagia spp. (73%), with a marginally lower efficacy against Trichostrongylus spp. (71%). Moxidectin efficacy was 33% against Trichostrongylus spp., 68% against Teladorsagia spp., 97% against Cooperia spp. and 100% against Haemonchus contortus infections.

Topics: Aminoacetonitrile; Animals; Anthelmintics; Antinematodal Agents; Benzimidazoles; Drug Resistance; Feces; Gastrointestinal Diseases; Ivermectin; Levamisole; Macrolides; Northern Ireland; Parasite Egg Count; Prevalence; Sheep; Sheep Diseases; Sheep, Domestic; Treatment Outcome; Trichostrongyloidea; Trichostrongyloidiasis

The anthelmintic sensitivity of two field-derived isolates (designated FI001 and FI004) of cattle nematodes from beef farms in Scotland were investigated in a controlled efficacy test (CET). Efficacies of ivermectin pour-on (IVM-PO), IVM injectable (IVM-INJ) and moxidectin pour-on (MOX-PO) formulations were assessed. In each group, five helminth-naïve calves were infected experimentally with 50,000 third stage larvae from either isolate and administered with anthelmintic at the manufacturers' recommended dose rate 28 days later. For each isolate, nematode burdens were compared between treatment and control groups to determine efficacy. Nematode species composition, based on data derived from the untreated control groups' burden estimations, were 39 and 14% Cooperia oncophora and 61 and 86% Ostertagia ostertagi for isolates FI001 and FI004, respectively. Macrocyclic lactone resistance in C. oncophora was confirmed for both FI001 and FI004 isolates. Efficacies (as determined by nematode burden analysis) of 4, 21 and 31% for FI001, and 10, 1 and 74% for FI004, were obtained for IVM-INJ, IVM-PO and MOX-PO, respectively. Efficacy based on faecal egg count reduction at seven days post anthelmintic administration were 8, 99 and 100% for FI001, and 37, 20 and 100% for FI004 for IVM-INJ, IVM-PO and MOX-PO, respectively. In summary, this study details two macrocyclic lactone resistant isolates of C. oncophora obtained from cattle from two distinct geographical locales in the UK.

Topics: Animals; Anthelmintics; Cattle; Cattle Diseases; Drug Resistance; Female; Ivermectin; Lactams, Macrocyclic; Macrolides; Male; Parasite Egg Count; Trichostrongyloidea; Trichostrongyloidiasis; United Kingdom

Selection for milbemycin resistance in a population of Teladorsagia circumcincta was examined in a sheep flock in which a lack of persistence of an oral dose of 0.2 mg/kg moxidectin against T circumcincta had previously been identified. A faecal egg count reduction test also showed resistance to benzimidazole, levamisole and avermectin anthelmintic groups. Bioassays were used to compare the moxidectin-resistant T circumcincta with another previously characterised benzimidazole-, levamisole- and ivermectin-resistant (MTci5) strain that had been isolated from a sheep flock in the same region in south-east Scotland and with an anthelmintic-susceptible (MTci3) strain of T circumcincta. The mean ED(50) value (the concentration of drug required to prevent 50 per cent of eggs from hatching) obtained for thiabendazole in egg hatch assays was higher in the moxidectin-resistant T circumcincta than in the ivermectin-resistant MTci5 strain. The inclusion of the cytochrome p450 inhibitor piperonyl butoxide in larval feeding inhibition assays increased the level of ivermectin resistance in vitro in the ivermectin- and moxidectin-resistant populations, but not in the ivermectin-susceptible MTci3 strain of T circumcincta.

Topics: Animals; Anthelmintics; Benzimidazoles; Drug Resistance, Multiple; Feces; Ivermectin; Macrolides; Parasite Egg Count; Sheep; Sheep Diseases; Thiadiazoles; Trichostrongyloidea; Trichostrongyloidiasis

To compare the effectiveness of a single long-acting injection of moxidectin, given in either summer or winter, with a two-summer ('standard') treatment strategy for controlling gastrointestinal nematodes in spring-lambing Merino ewes.. A replicated study over 2 years in the high winter rainfall environment of western Victoria.. Measures of worm infection were worm egg counts of ewes and total worm counts of tracer lambs. Measures of production were body weight, proportion of pregnant ewes and number of weaned lambs.. The egg counts of ewes given the standard strategy followed a characteristic pattern, rising to 300 to 600 eggs per gram before the second summer treatment in February. During this time, ewes given long-acting moxidectin in December had zero or negligible counts. There were no consistent differences between tracer worm counts or production measures for the two groups treated in summer, but when data from both years were pooled, the total egg output from December to May was significantly lower for ewes treated with long-acting moxidectin in December. Ewes not treated during summer had lower body weights, and higher worm egg counts and tracer worm counts, showing that this was not a suitable strategy at that time of the year. However, following treatment with long-acting moxidectin in winter, ewes had rapid compensatory weight gain and lower egg output than ewes treated in summer.. A single injection of long-acting moxidectin in December is an effective treatment strategy for Merino ewes lambing in spring.

Topics: Analysis of Variance; Animals; Antinematodal Agents; Body Weight; Feces; Female; Larva; Macrolides; Parasite Egg Count; Pregnancy; Pregnancy Complications, Parasitic; Seasons; Sheep; Sheep Diseases; Trichostrongyloidea; Trichostrongyloidiasis; Victoria

Topics: Animals; Anthelmintics; Drug Resistance; Feces; Macrolides; Sheep; Sheep Diseases; Trichostrongyloidea; Trichostrongyloidiasis

A computer model that simulates the population dynamics and epidemiology of three major species of parasitic nematodes of sheep found in the UK (Telodorsagia [Ostertagia] spp., Haemonchus spp. and Trichostrongylus spp.) is described. The model has been developed as a tool for veterinarians and advisors to aid in the implementation of integrated parasite control strategies designed to optimise anthelmintic usage and delay the development of resistance on UK farms. The model represents the parasite life cycle, flock dynamics and the response of individuals with different susceptible and resistant genotypes to the major broad-spectrum classes of anthelmintic available in the UK. Where possible, UK data have been used for the model parameters. The model allows worm control simulations on individual UK farms. Inputs include environmental and farm management variables which impact on the epidemiology of the disease, e.g. regional weather data; flock stocking rates; initial pasture larval contamination levels and species proportions; lambing dates; timing of flock movements to clean pastures; and removal of lambs during the year. Farm management data, as well as nematode egg outputs and grass larval counts, were collected from eight UK farms over a 1-year period for initial validation of the model outputs. The management data for each farm were used as inputs for each model run and model outputs for nematode egg counts from ewes and lambs were compared to the observed data for each farm. Statistical analysis of results shows a positive correlation for observed and simulated counts and regression analysis suggests an acceptable fit between the data. Comparison of observed and simulated outputs for resistance were possible for only one farm due to low numbers of worms developing in the laboratory tests. Additional studies will be necessary before resistance data can be reliably compared. Further validation studies are proposed to ensure that the model is robust and applicable across a diverse range of farm types. The model will be used to demonstrate the advantage, in terms of delaying resistance development, of current guidelines for anthelmintic use and management practices for worm control in sheep.

Topics: Animals; Anthelmintics; Computer Simulation; Decision Support Techniques; Feces; Female; Gastroenteritis; Ivermectin; Larva; Macrolides; Models, Biological; Parasite Egg Count; Sheep; Sheep Diseases; Trichostrongyloidea; Trichostrongyloidiasis; United Kingdom

Control of a benzimidazole-, levamisole- and ivermectin-resistant population of Teladorsagia circumcincta was attempted using moxidectin administered orally at the manufacturer's recommended dose rate of 200 microg/kg bodyweight. Ewes were dosed after lambing with the aim of controlling their periparturient rise in faecal egg output and lambs were dosed at six-week intervals throughout the summer. This regimen failed to suppress the establishment of significant numbers of infective helminth larvae on the pasture, resulting in unsatisfactory lamb production. Oral dosing with moxidectin was effective in removing adult female burdens of ivermectin-resistant T. circumcincta, but the effect of the drug did not persist against the resistant helminth population.

Topics: Administration, Oral; Animals; Animals, Newborn; Anthelmintics; Benzimidazoles; Feces; Female; Gastrointestinal Diseases; Ivermectin; Levamisole; Macrolides; Parasite Egg Count; Sheep; Sheep Diseases; Trichostrongyloidea; Trichostrongyloidiasis

Anthelmintic efficacies against juvenile developing populations of Teladorsagia species that were known to be resistant to anthelmintics from all three broad spectrum families were examined using a controlled efficacy test. Fenbendazole (FBZ), levamisole (LEV), ivermectin (IVM), combinations of these anthelmintics and moxidectin (MOX) were assessed in parasite naïve lambs artificially infected with 8,000 third stage larvae (Tci5) and treated orally 8-day post-infection with the compounds at the manufacturers recommended dose rates, FBZ, 5 mg/kg body weight (BW); LEV, 7.5 mg/kg BW; IVM, 0.2 mg/kg BW; MOX (0.2 mg/kg BW). The lambs were slaughtered 14-day post-treatment. The arithmetic mean worm burden reductions resulting from oral treatments with FBZ; IVM; LEV; FBZ+IVM; FBZ+LEV; FBZ, LEV+IVM or MOX were 36%, 82%, 38%, 86%, 60%, 88% and 97%, respectively. The results illustrate that combination treatments showed improved efficacies against the juvenile population compared to individually administered treatments but that these improvements were not wholly effective. Moxidectin was the only treatment that was over 95% effective, though caution should be noted when advising the use of MOX prophylactically since 3% of the infection still survived this treatment. Treatments directed at juvenile stages of Tci5 were less effective, with the exception of IVM, compared to a similar trial using Tci5 where the same treatments were directed against a predominantly adult population. No interaction was detected comparing the timings of treatments and its effectiveness with the exception of IVM (two-way ANOVA, p < 0.05). These findings suggest that, on the whole, the selection processes for anthelmintic resistance (AR) may occur at an early stage of development within the parasites, having severe implications for the early detection of AR.

Topics: Abomasum; Animals; Antinematodal Agents; Drug Resistance; Drug Therapy, Combination; Fenbendazole; Gastrointestinal Diseases; Ivermectin; Levamisole; Macrolides; Sheep Diseases; Trichostrongyloidea; Trichostrongyloidiasis

The anthelmintic resistance status of two field isolates derived from farms (farm A and B) located near Edinburgh were examined using both controlled efficacy tests (CET) and faecal egg count reduction tests (FECRT). Efficacies against fenbendazole (FBZ), levamisole (LEV) and ivermectin (IVM) and, for one isolate, against combinations of these anthelmintics and moxidectin were determined in naïve lambs, artificially infected with the isolates and treated with the compounds at the manufacturers recommended dose rates. (FBZ, 5mg/kg bodyweight (BW); LEV, 7.5mg/kg BW; IVM, 0.2mg/kg BW; Moxidectin (MOX) 0.2mg/kg BW). In both field isolates, the predominant species found pre-treatment and the only species found post-treatment was Teladorsagia circumcincta. Resistance to FBZ, LEV and IVM was confirmed in CET and FECRT on farm A and to the latter two compounds on farm B, which had a history of benzimidazole resistance and where TBZ resistance was also demonstrated using an egg hatch assay (EHA). For the farm A isolate CET efficacies against FBZ; IVM; LEV; FBZ + IVM; FBZ + LEV; FBZ, LEV + IVM and MOX were 59, 60, 88, 94,93, 92 and 98%, respectively. The CET efficacies for the farm B isolate were 51% and 72% for LEV and IVM, respectively.

Topics: Abomasum; Animals; Antinematodal Agents; Drug Resistance; Drug Therapy, Combination; Feces; Fenbendazole; Gastrointestinal Diseases; Ivermectin; Levamisole; Macrolides; Parasite Egg Count; Scotland; Sheep; Sheep Diseases; Trichostrongyloidea; Trichostrongyloidiasis

The effect of 1% moxidectin/cydectin at 0.2 mg/kg live weight on gastrointestinal nematodes and on the growth of calves, weaners and cows was investigated in five communal areas on the highveld of Zimbabwe. Three field experiments were carried out between March 1996 and June 1997. In experiment 1, treatment was administered in all five areas at the end of the rainy season in March 1996, followed by a further treatment at the beginning of the dry season in May/June 1996. In experiment 2, the treatment was administered in three areas at the end of the rainy season in March 1997. In experiment 3, treatment was administcred in one area at the beginning of the dry season in April 1997. Large numbers of eggs were present in the faeces of calves and weaners at the start of experiments 1 and 2. Epg values were lower in cows and in all age categories in experiment 3. There was a statistically significant reduction in epg values in calves, weaners and cows following treatment with a reduction of 90-99% in all cases except in cows in experiment 3, where no meaningful assessment was possible owing to the low egg counts in both the treated and control cows. The dominating larval types in faecal cultures were Cooperia and Haemonchus. Trichostrongylus, Oesophagostomum and Bunostomum were also found. Following treatment, Haemonchus was suppressed far more than Cooperia. This may be related to a longer residual effect against abomasal parasites like Haemonchus in comparison to small intestinal worms like Cooperia. Anthelmintic treatment conferred significant weight gain advantages (p < 0.05) on treated calves. weaners and cows. The weight gains are discussed in relation to disease and nutrition.

Topics: Animal Husbandry; Animals; Anthelmintics; Anti-Bacterial Agents; Cattle; Cattle Diseases; Climate; Feces; Female; Gastroenteritis; Injections; Intestine, Large; Macrolides; Male; Parasite Egg Count; Random Allocation; Seasons; Trichostrongyloidea; Trichostrongyloidiasis; Zimbabwe

Thirty-five castrate or intact Holstein male calves, ranging in weight from 122 to 210kg, were used in the study. On study Days -15 and -14, all study calves were treated with fenbendazole 10% paste at 10mg/kg to remove existing nematode infections. All cattle had zero egg counts on Day -1. Experimental infections of a mixed species inoculum were administered to all calves on Day 0. The inoculum consisted of Cooperia spp. (primarily C. punctata, but also C. pectinata, C. spatulata, C. oncophora and C. surnabada-total 40,961); Ostertagia ostertagi-1550; Trichostrongylus colubriformis-4996; and Oesophagostomum radiatum-38. Necropsy results from two of three monitor calves slaughtered on Day 6 after infection indicated that Day 6 was an appropriate time to evaluate efficacy of moxidectin against fourth larval stages (L(4)). The remaining 32 calves were randomly allotted to four groups of eight based on body weights. Eight calves (Group 1) were treated with moxidectin 0.5% pour-on at 0.5mg/kg on Day 6 to evaluate efficacy against nematode larval stages; eight control calves (Group 2) were matched with these principals. Eight calves (Group 3) were also treated with moxidectin pour-on at the same dosage on Day 23 in order to determine efficacy against adult nematodes; eight control calves (Group 4) were matched with these principals. In both cases, principals and controls of the Days 6 and 23 treatments were necropsied at 14-15 days after treatment. C. punctata was the only species found in a sufficient number of controls to evaluate moxidectin efficacy against the L(4). Moxidectin pour-on was not effective (P<0.05) against C. punctata L(4) by arithmetic means, but was highly effective based on geometric means. Regardless of whether arithmetic or geometric means were used for percent efficacy calculations, moxidectin pour-on was demonstrated to be highly effective (>99%) against the adult stages of C. oncophora, C. punctata, C. spatulata, C. surnabada, Cooperia spp. adult females and T. colubriformis adults.

Topics: Administration, Topical; Animals; Anti-Bacterial Agents; Antinematodal Agents; Cattle; Cattle Diseases; Dose-Response Relationship, Drug; Larva; Macrolides; Male; Random Allocation; Trichostrongyloidea; Trichostrongyloidiasis; Trichostrongylus

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Drug Resistance; Feces; Goat Diseases; Goats; Ivermectin; Macrolides; Parasitic Sensitivity Tests; Trichostrongyloidea; Trichostrongyloidiasis; Victoria

Duplicate studies in France and Northern Ireland were carried out to determine the persistent efficacy of topical moxidectin and doramectin against natural infections of Cooperia oncophora. In each study, groups of 15 nematode-naïve calves were treated either with topical doramectin or moxidectin, and put out to graze on pasture contaminated with C. oncophora infective larvae. The persistent efficacy for preventing establishment of infection was assessed by the time to faecal egg excretion of C. oncophora eggs. It was found that the moxidectin treatment prevented infection for less than 10 days and the effect of doramectin lasted for 24 days.

Topics: Administration, Topical; Animals; Anthelmintics; Anti-Bacterial Agents; Cattle; Cattle Diseases; Feces; France; Ivermectin; Macrolides; Male; Northern Ireland; Parasite Egg Count; Random Allocation; Trichostrongyloidea; Trichostrongyloidiasis

The observation that the total abundance of adult nematodes in the abomasum of Svalbard reindeer increases between October and April suggests adaptation to cope with the Arctic winter. Here we investigate the extent to which selection has led to similar life-history strategies in the 3 most numerous trichostrongyle species. The life-histories are found to differ markedly. We use flexible statistical models for the abundance and dispersion of parasites in the host population. One of the taxa, Marshallagia marshalli, was most abundant and had its highest egg output in the winter. In contrast, the abundance of the most common taxa, Ostertagia gruehneri, m. gruehneri was stable or declined from autumn to late winter, and the closely related taxa, O. gruehneri, m. arcticus, showed a similar over winter drop. The faecal egg output of these 2 taxa was highest in summer, as found in temperate trichostrongyle species. Despite the apparent contamination of summer pastures with O. gruehneri, calves showed negligible burdens until their second summer and the abundance of infection reached an asymptote within their third year. In contrast, the abundance of M. marshalli in calves showed a rapid increase over the first summer and by late winter was similar to peak levels found in adults (8000 worms). This increase could not be accounted for by the developing abomasum larvae population and is therefore evidence for transmission over the winter for this taxa. While M. marshalli showed little between-year variation, O. gruehneri showed 2-fold fluctuation in the abundance of infection. O. gruehneri may therefore play a role in the fluctuating population dynamics of the host. Since there was no apparent decline in abundance with host age in any of the 3 taxa there was no evidence of reindeer mounting an immune response.

Topics: Abomasum; Age Factors; Animals; Anthelmintics; Anti-Bacterial Agents; Arctic Regions; Binomial Distribution; Feces; Female; Macrolides; Male; Models, Biological; Norway; Ostertagia; Ostertagiasis; Parasite Egg Count; Population Dynamics; Prevalence; Random Allocation; Reindeer; Seasons; Trichostrongyloidea; Trichostrongyloidiasis

The nematocidal effectiveness of moxidectin, administered topically at the rate of 500 mcg/kg BW, was determined for lactating dairy cows. Naturally infected animals were given either topical vehicle or moxidectin (Cydectin Pour-On Fort Dodge Animal Health) at the rate of 1 ml/10 kg BW (10 animals per treatment group), and sacrificed 14-18 days post-treatment for nematode enumeration. 100% efficacies were recorded for Ostertagia lyrata males, Cooperia punctata males and Oesophagostomum radiatum L4, with treatment group differences in geometric means significant (P < 0.05) for all. Populations of Trichostrongylus L4 and adult O. radiatum were also reduced by 100%, but low prevalence rates in the control animals precluded meaningful statistical inference. Nematode populations for which efficacies ranged from 96.7 to 99.6% (based on geometric means) and for which treatment group differences were significant (P < 0.05) included Ostertagia spp. adult females, inhibited L4 and developing L4, O. ostertagi adult males, Trichostrongylus axei adults and Cooperia spp. adult females. For all nematodes combined, moxidectin was 98.9% efficacious. In addition to exhibiting excellent nematocidal effectiveness, topical moxidectin was demonstrated to be safe, with animal health and milk production unaffected during the study.

Topics: Abomasum; Administration, Topical; Animals; Anthelmintics; Anti-Bacterial Agents; Cattle; Cattle Diseases; Female; Intestine, Large; Intestine, Small; Lactation; Macrolides; Male; Nematode Infections; Oesophagostomiasis; Oesophagostomum; Ostertagia; Ostertagiasis; Parasite Egg Count; Prevalence; Random Allocation; Trichostrongyloidea; Trichostrongyloidiasis

The efficacy of orally administered moxidectin was determined against four benzimidazole-resistant nematode isolates. At the start of the trial, 30 lambs were each infected experimentally with 20,000 third stage larvae (5000 Haemonchus contortus, 7000 Teladorsagia circumcincta, 3000 Trichostrongylus colubriformis and 5000 Cooperia curticei); 28 days later they were allocated randomly to three groups of 10: one untreated group, one group treated orally with fenbendazole (5 mg/kg bodyweight) and one group treated orally with moxidectin (0.2 mg/kg). Samples of faeces were taken five and 10 days after treatment and the lambs were killed 10 days after treatment. Fenbendazole reduced the average number of nematode eggs in faeces by 95 per cent and the average number of worms by 25 to 45 per cent according to the species. The efficacy of moxidectin against these benzimidazole-resistant isolates was 100 per cent. No adverse reactions to either of the drugs were observed.

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Benzimidazoles; Drug Resistance; Feces; Haemonchiasis; Intestinal Diseases, Parasitic; Macrolides; Male; Nematode Infections; Parasite Egg Count; Sheep; Sheep Diseases; Trichostrongyloidiasis; Trichostrongylosis

The concentration of moxidectin, a macrocyclic lactone endectocide, in the blood serum of cattle resulting from single and daily subcutaneous injections and oral dosing was determined as a function of time. When given as a single subcutaneous (SC) injection, the drug peaked between 4 and 6 h post-treatment. As a single oral dose, the peak serum level occurred at 1 day post-treatment. Daily SC injections and oral doses resulted in a gradual increase in blood serum level over the 21 days of treatment but did not reach a plateau during this time. Horn flies, Haematobia irritans (Linnaeus), feeding on the blood of treated cattle drawn on Day 21 of daily treatment showed a decline in survival and egg production, but a negligible effect on egg hatching. Dose-mortality data on adult horn flies showed an LC-50 and LC-90 value of 10 ppb and 19 ppb in the blood, respectively. Moxidectin was also found to have larvicidal activity against the immature stages of the horn fly in the manure of treated cattle. Moxidectin administered at 100, 50 and 25 micrograms kg-1 as a daily oral medication was 100% effective in eliminating trichostrongyle egg counts by Day 3 of the treatment. Counts remained negative to the end of the trial.

Topics: Administration, Oral; Animals; Anthelmintics; Anti-Bacterial Agents; Cattle; Cattle Diseases; Feces; Female; Injections, Subcutaneous; Insecticides; Macrolides; Male; Manure; Muscidae; Oviposition; Parasite Egg Count; Trichostrongyloidea; Trichostrongyloidiasis

Macrocyclic lactone endectocides include two chemically distinct compounds moxidectin, a milbemycin, and ivermectin, an avermectin. The significance of the chemical differences between these compounds in relation to nematode resistance remains to be established. Reported studies indicate that moxidectin at the recommended dose rate of 0.2 mg/kg controls identified strains of nematodes, isolated from sheep and goats, with demonstrated resistance to ivermectin. This reflects the significantly greater potency of moxidectin against the 3 genera of nematodes most commonly involved in anthelmintic resistance, Haemonchus, Ostertagia and Trichostrongylus. Moxidectin, in recommended strategic treatment programmes, should reduce the risk of further development of resistance to the macrocylic lactone endectocides.

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Drug Resistance; Goat Diseases; Goats; Ivermectin; Macrolides; Sheep; Sheep Diseases; Trichostrongyloidiasis

Topics: Administration, Topical; Animals; Anthelmintics; Anti-Bacterial Agents; Cattle; Cattle Diseases; Feces; Female; Injections, Subcutaneous; Macrolides; Ostertagia; Ostertagiasis; Parasite Egg Count; Trichostrongyloidea; Trichostrongyloidiasis

Three groups of 11 naturally infected crossbred beef calves were injected subcutaneously with moxidectin 1 per cent injectable at 0.2 or 0.3 mg moxidectin/kg bodyweight or with the unmedicated vehicle. Nematode infections had been acquired during grazing from December to April. Based on the faecal egg counts and total worm counts of the control calves at necropsy (11 to 13 days after treatment) most of the calves had heavy parasitic burdens. Ostertagia ostertagi was predominant and the mean numbers of adults, developing fourth stage larvae (L4) and inhibited early L4 were 45,906, 10,061 and 68,918, respectively. Haemonchus placei and Trichostrongylus axei were also present in the abomasa. Three species of Cooperia, Oesophagostomum radiatum L4 and T colubriformis adults were found in the intestinal tract. Both dosages of moxidectin were equally effective (P < 0.05) against all the abomasal nematodes (99.9 to 100 per cent) and the intestinal tract nematodes (99.4 to 100 per cent). No adverse reactions to the moxidectin treatment were observed. Abomasal pathology characteristic of heavy O ostertagi infection was observed in the control calves, but not in the treated calves.

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Cattle; Cattle Diseases; Feces; Female; Haemonchiasis; Intestinal Diseases, Parasitic; Macrolides; Nematode Infections; Oesophagostomiasis; Ostertagiasis; Parasite Egg Count; Trichostrongyloidiasis; Trichostrongylosis

Moxidectin, a systemic insecticide, was evaluated for its efficacy against the migrating first instars of the common cattle grub, Hypoderma lineatum, and against nematode egg production in beef cattle. It was observed that all three levels (0.1, 0.2 and 0.4 mg moxidectin kg-1) were 100% effective against cattle grubs when administered as a s.c. injection. The same levels of treatment were very effective (90-100%) in reducing trichostrongyle nematode egg production. However, there was a slight indication that at least one species, Cooperia oncophora, was not completely eliminated, as it was observed that small numbers of eggs began to appear after 2 weeks post-treatment when there had been no opportunity for reinfection.

Topics: Animals; Anti-Bacterial Agents; Antinematodal Agents; Cattle; Cattle Diseases; Feces; Female; Hypodermyiasis; Injections, Subcutaneous; Insecticides; Macrolides; Male; Oviposition; Parasite Egg Count; Random Allocation; Trichostrongyloidea; Trichostrongyloidiasis

Haemonchus contortus- and Trichostrongylus colubriformis-infected jirds (Meriones unguiculatus) are useful for anthelmintic studies. With concurrent infections of these parasites established in the jird, questions of not only anthelmintic activity, but to some extent spectrum, could be assessed in a single model system. This report outlines a model using immunosuppressed (0.02% hydrocortisone in feed) jirds concurrently infected with H. contortus and T. colubriformis. Immunosuppressed jirds were inoculated with approximately 1,000 exsheathed infective larvae of each species, treated per os on day 10 postinoculation (PI), and killed on day 13 PI. Stomachs and small intestines were removed, opened longitudinally, incubated in distilled water at 37 C for 5 hr, fixed in formaldehyde solution, and stored for subsequent examination. Contents of both organs were examined using a stereomicroscope (15-45 x). Various standard anthelmintics were evaluated in the model; modern broad-spectrum ruminant anthelmintics (benzimidazoles, febantel, ivermectin, levamisole hydrochloride, and milbemycin D) are active uniformly and in most cases at doses comparable to those required for efficacy against these parasites in ruminants. This model, using worms of 2 genera living in distinct sites, allows preliminary evaluation of anthelmintic activity and spectrum for experimental compounds in a single cost- and resource-efficient experiment.

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Benzimidazoles; Bithionol; Diethylcarbamazine; Gerbillinae; Guanidines; Haemonchiasis; Macrolides; Piperazine; Piperazines; Pyrantel Tartrate; Rodent Diseases; Trichostrongyloidiasis