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Biomedical subjects

I A Sutherland

Publications and source records attributed to I A Sutherland.

At least 19 recordsLinked to original sources

Validation of candidate bovine reference genes for use with real-time PCR.

Accurate quantification with real-time PCR requires the use of stable endogenous controls. Recently, there has been much debate concerning the stability of commonly used reference or housekeeping genes. To address this concern, a number of statistical approaches have been designed to analyse data and assist in determining the most appropriate reference genes for experimental comparisons. In this study, three programs, BestKeeper, Norm Finder, and geNorm were used to assess four candidate reference genes: 18S rRNA, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), acidic ribosomal protein large (RPLP0) and beta-actin, for use in expression profiling of individuals from divergent cattle genotypes subject to parasitic challenge with the cattle tick Boophilus microplus. Results demonstrated beta-actin and GAPDH were the most suitable reference genes in blood and could be used either individually or combined as an index to normalise data. RPLP0 was identified as the least stable gene, while 18S rRNA was omitted as being too highly expressed. As the recommendations on the most suitable reference genes varied between the programs, it is recommended that more than one should be utilised, to ensure the most robust experimental tools are selected.

Actins↗

Drenching adult ewes: implications of anthelmintic treatments pre- and post-lambing on the development of anthelmintic resistance.

AIMS: To test the hypothesis that peri-parturient anthelmintic treatment of adult ewes, either pre-lambing with a controlled- release capsule (CRC) or at tail-docking with a short-acting oral formulation, would increase the rate of development of anthelmintic resistance, as compared to not drenching ewes and giving an additional drench to lambs in the autumn. Also, to evaluate the potential of routinely leaving 15% of the heaviest lambs untreated when drenching, as a means of slowing the development of anthelmintic resistance. METHODS: A replicated farmlet trial was run from 1999- 2004. Eleven farmlets, each consisting of five paddocks, were initially seeded with Ostertagia (=Teladorsagia) circumcincta and Trichostrongylus colubriformis parasites, these being a mixture of albendazole-susceptible and -resistant isolates to yield a 96% reduction in faecal nematode egg count (FEC) on drenching. Four prescriptive drenching regimes were applied; Treatments 1-3 were replicated three times and Treatment 4 twice. Treatments were as follows. Treatment 1: Ewes were given an albendazole CRC pre-lambing, and any ewes exceeding 65 kg liveweight were given two capsules simultaneously; lambs were given a five-drench preventive programme of treatments, orally, of albendazole on Days 0, 21, 42, 70 and 98 after weaning. Treatment 2: Ewes were given a single oral treatment of albendazole at docking (2-3 weeks after lambing), and lambs were given the same five-drench preventive programme as in Treatment 1. Treatment 3: Ewes remained untreated, while lambs were given a six-drench preventive programme of treatments, orally, of albendazole on Days 0, 21, 42, 70, 98 and 126 after weaning. Treatment 4: Ewes remained untreated, while lambs were given the same six-drench preventive programme as in Treatment 3, but the heaviest 15% of lambs were left untreated each time. Albendazole-resistance status was measured at least twice-yearly, using faecal egg count reduction tests (FECRTs) and larval development assays (LDA). In addition, controlled slaughter of drenched and undrenched tracer lambs was undertaken in the last 3 years. RESULTS: Resistance to albendazole increased most rapidly in Treatment 1, as measured by FECRT and LDA results, and worm burdens in tracer lambs. In Treatment 2, resistance developed slower than in Treatment 1 but faster than in Treatments 3 and 4, as measured by LDA; resistance in Treatment 2 developed more quickly than in Treatment 4, as measured by FECRTs. There was no significant difference between Treatments 3 and 4, although this approached significance in Ostertagia spp, as measured by LDA. CONCLUSIONS: Anthelmintic treatments to adult ewes around lambing time are likely to be more selective for resistance than additional treatments administered to lambs in the autumn. Farmers wishing to slow the emergence of anthelmintic resistance on their farms should look to minimise the administration of peri-parturient treatment of ewes. A trend to slower development of resistance where a proportion of lambs were left untreated at each drench suggests further work on this aspect of management of resistance is warranted.

Albendazole↗

Comparison of high-speed counter-current chromatography instruments for the separation of the extracts of the seeds of Oroxylum indicum.

Analytical Milli high-speed counter-current chromatography (HSCCC) was used for the selection and optimization of the two-phase solvent system to separate flavonoids from the extracts of the seeds of Oroxylum indicum. The optimum solvent system obtained from Milli-CCC was also the best solvent system for preparative HSCCC and led to the successful separation of two crude flavonoids from the seeds of O. indicum by Lab/Prep (laboratory preparative) HSCCC using different sized coils. Four flavonoids were isolated by preparative HSCCC: baicalein-7-O-diglucoside (25.0 mg, 92% purity), baicalein-7-o-glucoside (50.4 mg; 95% purity), baicalein (75 mg; purity 98%) and chrysin (100 mg; purity 98%).

Bignoniaceae↗

Countercurrent chromatographic separation: a hydrodynamic approach developed for extraction columns.

In countercurrent chromatography (CCC) both stationary and mobile liquids undergo intense mixing in the variable force field of a coil planet centrifuge and the separation process, like the separation in conventional solvent extraction column, is influenced by longitudinal mixing in the phases and mass transfer between them. This paper describes how the residence time distribution (or the elution profile) of a solute in CCC devices and the interpretation of experimental peaks, can be described by a recently developed cell model of longitudinal mixing. The model considers a CCC column as a cascade of perfectly mixed equal-size cells, the number of which is determined by the rates of longitudinal mixing in the stationary and mobile phases. Experiments were carried out to demonstrate the validation of the model and the possibility of predicting the partitioning behaviour of the solutes. The methods for estimating model parameters are discussed. Longitudinal mixing rates in stationary and mobile phases have been experimentally determined and experimental elution profiles are compared with simulated peaks. It is shown that using the cell model the peak shape for a solute with a given distribution constant can be predicted from experimental data on other solutes.

Countercurrent Distribution↗

Resistance to prophylactic treatment with macrocyclic lactone anthelmintics in Teladorsagia circumcincta.

Sixty-four Romney ewe lambs were allocated to 12 groups on the basis of liveweight. Four groups (n=5) were administered oral ivermectin (IVM), 4 (n=6) oral moxidectin (MOX) and the remaining 4 (n=5) controlled-release capsules containing IVM (IVM-CRCs). Nine and 10 days later, the groups within each treatment type were challenged with infective-stage larvae (L3) of 1 of 4 different isolates of Teladorsagia circumcincta (two doses each of 5000 L3). The first of these (S) was known to be anthelmintic-susceptible; the second (OR) was a multiple anthelmintic-resistant strain recovered from the field following therapeutic failure of both ivermectin and moxidectin and subsequently maintained in the laboratory without further anthelmintic selection; the third (R) was derived from OR but had been passaged for five generations indoors with each generation being screened with all three broad-spectrum anthelmintic classes; and the fourth (RxS) was an F1 cross between the R and S isolates. As anticipated, because of its limited residual activity, IVM had no significant effect on the establishment, 9 and 10 days post-treatment, of any of the parasite isolates. In contrast MOX, which has greater residual activity, was highly effective at preventing the establishment of the S isolate but showed no significant effect against the OR, R or RxS isolates. The IVM-CRC was also highly effective at preventing the establishment of the S isolate and furthermore it significantly reduced establishment of both the OR and RxS isolates, although it had no significant effect against the R isolate. The results suggest that with respect to the establishment of T. circumcincta L3s following anthelmintic treatment, macrocyclic lactone (ML) resistance is effectively a dominant trait in the presence of MOX, while it behaves as a partially dominant/recessive trait under treatment with IVM-CRCs. The potential implications of this finding in relation to selection for ML resistance in T. circumcincta are discussed.

Abomasum↗

Modeling the performance of pilot-scale countercurrent chromatography: scale-up predictions and experimental verification of erythromycin separation.

Biosynthesis of polyketide antibiotics, such as erythromycin A (EA), can result in the formation of analogues of the main compound that are chemically and structurally extremely similar. The large-scale purification of these antibiotics by conventional high-performance liquid chromatography (HPLC) can be prohibitively expensive due to the large volume of both solvent and adsorbent required. This study examines the feasibility of using a novel pilot-scale countercurrent chromatography (CCC) machine as an alternative to HPLC. CCC is a low-pressure (typically <4000 kN m(-2)) liquid-liquid chromatographic technique that allows the separation of solutes on the basis of their partitioning between two immiscible liquid phases. The effects of mobile phase flow rate, column rotational speed, and sample injection volume on the attainable yield and purity of EA were investigated. Our results show that, at a mobile phase flow rate of 40 mL min(-1), a rotational speed of 1200 rpm, and an injection volume of 100 mL (10 g total erythromycin), EA could be satisfactorily fractionated with a purity of approximately 92% (w/w) and a recovery yield of approximately 100% (w/w). The total solute throughput was estimated to be 0.41 kg day(-1). More importantly, we demonstrated simple and predictive linear scale-up of the CCC separation based on data obtained from a single laboratory-scale CCC chromatogram, and verified this experimentally. The retention time and peak width of the target compound at the pilot scale could be predicted to within 4% for operation at a range of mobile-phase flow rates and injection volumes. This predictable nature of CCC separations, unlike HPLC methods, can greatly reduce process development times and enable a complete process-scale operating scenario to be planned.

Chromatography, Liquid↗

The effect of anthelmintic capsules on the egg output and larval viability of drug-resistant parasites.

Challenge with an equal mix of drug-resistant and drug-susceptible larvae of Teladorsagia circumcincta resulted in infections in groups of lambs (n = 6) either untreated or given controlled-release capsules, containing either albendazole or ivermectin. Lambs treated with albendazole capsules contained similar numbers of adult worms at necropsy to the other groups but had no detectable faecal egg count. Animals treated with ivermectin capsules had similar worm burdens and faecal egg counts to the control group but the worms had significantly higher numbers of eggs in utero. These results provide evidence for suppression of egg production by both anthelmintic treatments. The observation that albendazole caused a significant reduction in the developmental success of parasite eggs also has implications for the use of faecal egg count as an indicator for pasture contamination with resistant parasites. In two further groups of lambs, either untreated or given albendazole capsules, treatment caused a significant reduction in egg count and adult worm burden of Trichostrongylus colubriformis. No significant effects were observed on in utero egg counts or egg viability and the apparent effect on the number of eggs produced in faeces per adult female was not significant (p = 0.077). There was, therefore, no evidence that albendazole controlled-release capsules caused suppression of egg output in this species.

Albendazole↗

Resistance to therapeutic treatment with macrocyclic lactone anthelmintics in Ostertagia circumcincta.

Eighty-eight lambs were allocated to one of four groups which were then dosed with 10,000 infective-stage larvae (L3) of one of four populations of Ostertagia circumcincta; the first (S) was an isolate known to be anthelmintic-susceptible; the second (OR) was a multiple anthelmintic-resistant isolate which had been recovered from the field following therapeutic failure of both ivermectin and moxidectin and subsequently maintained in the laboratory without further anthelmintic selection. The third (R) was derived from OR but had been passaged for five generations in the laboratory with each generation being screened with all three broad-spectrum drench families; the fourth (R x S) was an F1 cross between the S and R isolates. On patency, each of the four infection groups was sub-divided into five treatment groups, one of which received no anthelmintic while the others were administered either oral ivermectin (IVM-oral), controlled-release capsules containing ivermectin (IVM-CRCs), oral moxidectin (MOX-oral) or injectable MOX (MOX-inj). Neither formulation of IVM reduced FEC in the R, R x S and OR infected lambs compared to their untreated controls, but significant reductions were observed in all cases following MOX-oral or MOX-inj treatment. Similarly, neither IVM formulation significantly reduced the numbers of R or R x S worms compared to their untreated controls, although the numbers of OR worms were reduced in both cases (P<0.05). Direct comparisons of efficacy across the isolates, however, indicated that neither formulation was any more effective against R x S or OR worms than against the more highly selected R worms. In contrast, both MOX formulations significantly reduced worm numbers of all the resistant isolates compared to their respective untreated controls; furthermore, worm burdens of R x S were reduced significantly more than burdens of R (P<0.05). Reductions in OR burdens, which were intermediate between the two, did not differ significantly from either. The results are consistent with published work on Haemonchus contortus, which suggests that macrocyclic lactone (ML) resistance is expressed as a dominant trait under treatment with IVM. However, these data differ from the H. contortus studies in suggesting that ML resistance in O. circumcincta may effectively be rendered incompletely dominant or recessive by treatment with MOX.

Administration, Oral↗

Increased burdens of drug-resistant nematodes due to anthelmintic treatment.

Nine groups of lambs were challenged with 500 drug-resistant (R) Ostertagia circumcincta infective-stage larvae (L3) twice-weekly for 6 weeks; 3 of the groups were also given 500 susceptible (S) L3 and another 3 given 3000 L3 twice-weekly. One week prior to parasite challenge, 1 group of each dose rate was administered ivermectin-capsules (IVM-CRCs). Following challenge, a second group from each dose rate was administered oxfendazole to remove susceptible parasites. The remaining groups received no drug treatment throughout the trial. No significant difference in faecal egg count was observed between the groups. The groups left untreated did not differ significantly in resulting worm burden. However, the percentage of the total L3 challenge recovered as 4th-stage larvae or adult worms demonstrated a density-dependent relationship and declined with increasing challenge. Those groups treated with anthelmintic to remove S worms prior to necropsy also showed density dependency as worm burdens were lower at the highest dose rate. In the groups administered IVM-CRCs, no dose-dependent effect on worm burden was observed. These differences resulted in more worms being present at the highest dose rate in the IVM-CRC-treated animals than in those animals treated orally with anthelmintic. Adult female worms from the IVM-CRC high challenge group were significantly longer and contained more eggs in utero than those in the other high challenge groups. These results demonstrate that where resistance is present, IVM-CRCs can modify the density-dependent regulation of the parasite population, resulting in the acquisition of larger resistant worm burdens than might otherwise be expected. This could accelerate the build-up of resistant worm populations and decrease the time until treatment failure.

Animals↗

Production and immunological responses associated with controlled-release-capsule vs 5-drench preventive anthelmintic programmes for parasite control in lambs.

AIMS: To determine whether: a) using a controlled-release anthelmintic capsule (CRC) instead of a programme of 5 oral drenches administered at 3-4 week intervals, would delay the development of anti-parasite immunity in lambs; b) the use of ivermectin instead of albendazole, administered either as a CRC or as a programme of 5 oral drenches, would delay the development of anti-parasite immunity in lambs; c) lambs treated with CRCs would have higher liveweight gains than lambs drenched orally 5 times at 3-4 week intervals, and; d) delayed onset of anti-parasite immunity is associated with reduced liveweight gains in the period following anthelmintic treatment. METHODS: Three field trials were conducted, 1 on a research farm and 2 on commercial sheep farms, in which groups of 30 lambs were treated with either a CRC containing albendazole, a CRC containing ivermectin, 5 oral drenches with albendazole, or 5 oral drenches with ivermectin, administered at 3-4 week intervals. Liveweights and faecal nematode egg counts (FECs) were recorded in all trials. Immunoglobulin-G (IgG) antibody levels to Ostertagia circumcincta and Trichostrongylus colubriformis adult and larval antigens were measured in Trials 1 and 3, and fleece weights and resistance of animals to nematode challenge infection were measured in Trial 1. RESULTS: CRC-treated lambs had higher levels of antibodies to O. circumcincta infective-stage larvae (L3) than orally drenched lambs in Trial 3, but no other immunological differences due to mechanism of delivery were detected. Antibody levels were lower in lambs treated with ivermectin than albendazole, as a CRC or oral drench in Trial 1, but this was not associated with any measurable effects on FEC or productivity. No significant differences (p>0.05) were detected between drench types (albendazole vs ivermectin) or delivery mechanisms (CRC vs oral drenching) in any of the production parameters measured, in any of the trials. Albendazole-CRCs failed to control FECs in all 3 trials. CONCLUSIONS: Although some differences between treatments in antibody levels were detected these were not associated with measurable differences in level of parasitism or productivity of lambs. CRC use did not appear to offer substantial gains in productivity over a structured programme of 5 oral drenches administered at 3-4 week intervals.

Journal Article↗

Microvascular changes in the peripheral microcirculation of women with chronic pelvic pain due to congestion.

OBJECTIVE: Pelvic venous congestion is a common finding in women with chronic pelvic pain. While the pathophysiology of this condition is poorly understood, there are clear indications that it involves vascular dysfunction. The present studies sought abnormalities in microvascular function in these patients. DESIGN: Prospective longitudinal study. SETTING: A teaching hospital tertiary referral. POPULATION: Eighteen women with pelvic congestion and 13 normal women. METHODS: Parameters of microcirculatory function were measured in the calves of women using venous congestion plethysmography during the midfollicular and midluteal phases of the menstrual cycle. The women with pelvic congestion were studied again after treatment for the condition. MAIN OUTCOME MEASURES: Isovolumetric venous pressure, microvascular filtration capacity and limb blood flow. RESULTS: Of the measured parameters of microvascular function, only isovolumetric venous pressure (Pvi) was significantly higher in women with congestion when compared to the controls during the same phase of the cycle. There were no menstrual cycle related differences in any of the other measured parameters in either patients or controls. Following successful treatment for the condition, values of Pvi in women with pelvic congestion were significantly reduced, achieving a level similar to that observed in the controls. CONCLUSION: The observed changes in Pvi suggest that this parameter is intimately associated with the pathophysiology of pelvic congestion. The increase in Pvi, without alterations in other measured microvascular parameters, may be attributable to systemic increases in postcapillary resistance secondary to neutrophil activation. These findings support the notion of systemic microvascular dysfunction in these women.

Adult↗

Theileria annulata: attenuation of a schizont-infected cell line by prolonged in vitro culture is not caused by the preferential growth of particular host cell types.

Flow cytometry and monoclonal antibodies to bovine leucocyte surface antigens were used to identify the types of host cells that the sporozoites of Theileria annulata infect in cattle, to determine whether virulent schizont-infected cell lines (lines) differed phenotypically from avirulent lines, and to establish whether attenuation in vitro was accompanied by the preferential growth of particular host cell types. The surface antigens of four pairs of T. annulata (Ta) (Hisar) lines derived ex vivo and in vitro, including the virulent ex vivo-derived Ta Hisar S45 line, were consistent with a myeloid origin for all lines, irrespective of their derivation. The profiles of lines derived from cattle inoculated with a virulent line showed that the schizonts liberated from inoculated cells had transferred to myeloid cells. A number of other lines infected with different stocks of T. annulata expressed myeloid markers; a single line expressed CD21, a B cell marker. During prolonged in vitro culture, the parasites in the ex vivo (virulent)- and in vitro (avirulent)-derived Ta Hisar S45 myeloid lines became clonal, as defined by glucose phosphate isomerase (GPI) polymorphism, and the virulent line became attenuated. The two lines retained phenotypic profiles indicative of a myeloid origin but coexpressed some lymphoid antigens (CD2, CD4, CD8), although not CD3. Cloned schizont-infected lines, representing the three parasite GPI isotypes which constituted the virulent line, expressed similar patterns of myeloid and lymphoid markers to the virulent parent line. Some schizont-infected clones failed to establish as lines during the early weeks of culture because the cells died as the parasites differentiated into merozoites at 37 degrees C, the temperature at which schizont-infected cells normally grow exponentially. These results provided no evidence that prolonged culture induces preferential growth or loss of particular host cell types. However, a number of the alterations in host cell surface antigens induced by prolonged culture were shown to be linked to permanent changes in the parasite genome.

Animals↗

Industrial scale-up of countercurrent chromatography: predictive scale-up.

This study describes how scale-up in countercurrent chromatography (CCC) can be simply predicted on a process scale CCC device by running a preliminary analytical-sized sample and having knowledge of the stationary-phase retention at scale-up conditions. Results have shown that simple experimentation can lead within a day to a process with the capability of several kilograms per day (tons per year) compound yield, and that this is feasible with benchtop CCC units.

Journal Article↗

Relationship between retention, linear velocity and flow for counter-current chromatography.

A recent paper by Du et al. [J. Chromatogr. A, 835 (1999) 231] showed a very good correlation between the retention of stationary phase and the square root of mobile phase flow (F(1/2)) for 12 different phase systems in counter-current chromatography. This paper shows there is a relationship between the above retention and the linear velocity of the mobile phase. In this way, Du et al.'s results can be related to the kinematics of the mobile phase flow in the tubing. This will open the door for further engineering analysis of this fluid dynamic phenomenon.

Chromatography, Liquid↗

Hand performance assessment of ten people with rheumatoid arthritis when using a range of specified saucepans.

PURPOSE: The aim of the pilot study was to provide information about the design and use of saucepan handles to enable clinicians and designers to specify and provide products that are more appropriate for use by people with Rheumatoid Arthritis (RA). The objectives were: to evaluate aspects of new handle design for saucepans in terms of their ease of use for people with RA; document hand grip strength and configuration (grip patterns); record relevant anthropometric data to aid the development of new designs and perform an assessment of lifting techniques used in conjunction with perceived optimum handle configuration. METHOD/RESULTS: Observation and video footage show that subjects continued to use familiar, but damaging, ways of lifting the saucepan even after extensive joint protection training by occupational therapists. Grip strengths recorded using a sphygmomanometer were similar to those found by other studies. The anthropometric measurements taken from the sample group were found to be within available anthropometric surveys of able-bodied people. However, hand length within the sample group with RA was longer than the equivalent in surveys of able-bodied subjects. CONCLUSIONS: Subjects preferred the narrower handles with some surface texture to the larger and more rounded tapered handles. Large handled saucepans were found not to be viable due to the constraints of UK cooking hob sizes and existing British Standards relating to saucepan specification.

Anthropometry↗

Nematode parasites of sheep: a survey of epidemiological parameters and their application in a simple model.

We review the literature on parameter values relevant to the epidemiology of strongyle nematode infections of domestic sheep. Information is subdivided by parasite genus, country of origin and climate type. While field observations have been made in a large number of countries, the bulk of studies under controlled conditions have been conducted in Australia, New Zealand and the UK. For these countries, experiments and parameters are interpreted in terms of a previously published model of nematode dynamics, and are used to calculate the basic reproduction number. Average values range from less than 6 for Haemonchus contortus in New Zealand and a winter rainfall region of Australia, to more than 16 for Ostertagia circumcincta in New Zealand and the UK. Additional considerations of the effects of climate and the annual replacement of host stock show that for conditions favourable for parasite transmission this is a robust indicator of parasite epidemiology. When climate variation and annual replacement are added to the model, it is shown to reasonably describe the qualitative behaviour of an experimental data set, indicating it to be a useful tool for further investigation of some of the underlying assumptions of sheep-nematode dynamics.

Animals↗

Selection for drug-resistant nematodes during and following extended exposure to anthelmintic.

Five groups of ten 7-month-old Romney lambs were challenged twice-weekly (2 x 3,000) with either Ostertagia circumcincta (Groups 1-3) or Trichostrongylus colubrifornzis (Groups 4 and 5) infective-stage larvae (L3) following administration of controlled release capsules (CRC) containing either albendazole (ABZ-CRC) (Groups 2 and 5) or ivermectin (IVM-CRC) (Group 3). Larval challenge comprised a mixture of equal numbers of drug-susceptible and -resistant L3 (OR/TR:OS/TS) during the 14-week period of drug release. Positive faecal egg counts (FEC) were recorded in each group during this period. Eggs recovered from faeces were used in an egg hatch assay (EHA) utilizing different concentrations of ABZ. O. circumcincta eggs from Groups 2 and 3 had significantly higher LC50 values than Group 1; eggs of T. colubriformis from the ABZ-CRC treated Group 5 had a higher LC50 than control Group 4. Following the exhaustion of drug release, larval challenge was changed to consist of only susceptible parasites and EHA performed wveekly to determine whether LC50 declined, which would indicate dilution or replacement of drench survivors. In those animals challenged with O. circumcincta, LC50 values were still significantly higher in Groups 2 and 3 at week 19 than in the previously untreated Group 1. For T. colubriformis, LC50 values declined steadily following exhaustion of drug release and were not significantly different between Groups 4 and 5 by week 20. This decline in LC50, and corresponding rise in FEC, was largely the result of 3 animals which dominated with high FEC. The remaining 6 animals showed little decline in LC50 or rise in FEC. The results demonstrate the ability of persistent drugs to screen for resistant parasites and establish that the period of selective advantage for drug-resistant parasites of both species is significantly longer than the period of drug release from CRCs.

Albendazole↗

Ivermectin-resistant Ostertagia circumcincta from sheep in the lower North Island and their susceptibility to other macrocyclic lactone anthelmintics.

AIM: To confirm the ivermectin resistance status of a strain of Ostertagia circumcincta which was isolated from a sheep farm in the lower North Island of New Zealand and to assess the susceptibility of this strain to other macrocycliclactone anthelmintics. METHODS: Twenty-five lambs housed indoors were each infected with 12,000 L3 larvae of the above parasite strain. Approximately 3 weeks after infection the lambs were allocated to 1 of 4 treatment groups (3 groups of 6, and 1 group of 7 lambs), one of which remained untreated while the others were drenched orally with ivermectin, moxidectin or abamectin at 0.2 mg/kg liveweight. Faecal egg counts (FECs) before and after treatment, and post-mortem worm burdens 10 days after treatment were examined to assess efficacies of each anthelmintic. RESULTS: Treatment with ivermectin reduced the mean FEC by only 18% and the mean worm burden by only 42%, whereas moxidectin and abamectin reduced FECs by 92% and worm burdens by 95%. CONCLUSION: These results, together with a similar case described recently from the South Island , confirm the emergence of ivermectin resistance in nematode parasites of sheep in New Zealand. The superior efficacy of moxidectin and abamectin in this case indicates that, following the emergence of resistance to ivermectin, some short-term practical use may still be made of these other anthelmintics. However, their continued use will undoubtedly result in increased levels of resistance and eventual therapeutic failure of these products also.

Journal Article↗