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D M Leathwick

Publications and source records attributed to D M Leathwick.

At least 37 records · Page 2Linked to original sources

The epidemiology of nematode infections of sheep.

Nematode parasites have been a major factor limiting sheep production in New Zealand for more than 100 years. Twenty-nine species of nematodes were unintentionally introduced with sheep into New Zealand, but it is principally species of Haemonchus, Ostertagia, Trichostrongylus, Nematodirus and Cooperia that are associated with production losses and clinical disease. The seasonal dynamics of nematode infection are the consequence of complex inter-relationships between the sheep, their husbandry and the prevailing climate. The patterns of pasture contamination by nematode eggs and then larvae and the subsequent levels of infection in ewes and lambs are broadly similar throughout New Zealand. Numbers of infective larvae on pasture build up over summer to a peak in autumn/early winter with, in some years, a spring peak derived from the parturient rise in faecal nematode egg counts (FEC), expressed in eggs per gram of faeces (epg), in lactating ewes. The immune capability of lambs is initially low but increases with the magnitude and duration of exposure to infection. Once significant immunity has developed (usually by 10-12 months of age), sheep are capable of markedly restricting parasite infection, except during times of disease, malnutrition or stress. For the effective control of nematode parasites, farmers have come to rely almost exclusively on broad-spectrum anthelmintics. However, issues relating to resistance, residues and eco-toxicity increasingly threaten the sustainability of chemotherapy. In order to maintain present levels of parasite control and productivity in the long term, farmers need to integrate management practices aimed at minimising animal exposure to parasites with reduced reliance on anthelmintics.

Journal Article↗

Anthelmintic resistance in New Zealand.

Anthelmintic resistance was first confirmed in New Zealand in 1979 and since then has become common-place; more than 50% of sheep farms now have detectable levels of resistance to one or more chemical classes of anthelmintic. Farmer drenching practices have changed little over the last 15-20 years and are clearly exerting a significant level of selection for resistance. In the absence of new chemical classes of anthelmintics, current parasite control practices will be unsustainable in the long-term. Once substantial resistance has developed, significant reversion to susceptibility is unlikely and re-introduction of failed drugs is likely to result in the re-emergence of control problems. The number of anthelmintic treatments applied is not necessarily a reliable indicator of selection pressure and should not be the only factor considered in strategies for minimising the development of resistance. The relative potential of the different anthelmintics now available, particularly the long-acting products, to select for resistance varies with the way they are used and with other epidemiological and management factors; generalisations about their respective roles in the development of resistance are often unreliable. In many cases, literal extrapolation of recommendations for the management of resistance from Australia to New Zealand is unsupportable, given the differences in climate, parasite ecology and farming practices between the 2 countries. In the absence of a refuge for susceptible genotypes, as occurs when anthelmintic treatments are used as a means of generating low-contamination 'safe' pasture for young stock, the rapid development of resistance is likely. Anthelmintic treatments applied to animals with a high level of immunity, or which become immune while the anthelmintic is active, are likely to select for resistance faster than treatments applied to non-immune stock.

Journal Article↗

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↗

The effect of continuous drug exposure on the immune response to Trichostrongylus colubriformis in sheep.

The effect of albendazole (ABZ)-capsule (CRC) administration on parasite establishment and immunity to ABZ-resistant (RES) and -susceptible (SUS) T. colubriformis was measured in Romney lambs. During 12 weeks of twice-weekly dosing with 3000 parasite larvae (L3), eggs were observed in faeces from CRC-treated and untreated lambs given RES L3, but not CRC-treated lambs given SUS L3. Following the period of trickle challenge all lambs were drenched and, 1 week later, dosed with 20000 SUS L3. Resulting worm burdens were higher in control lambs than in those previously treated with CRCs and challenged with SUS, which in turn were higher than those in the CRC-treated or -untreated lambs previously challenged with RES L3. During the period of trickle challenge, the number of peripheral eosinophils and titres of anti-L3 and anti-adult antibody were raised only in those groups given RES L3. There was no effect of CRC administration. Following drench and challenge, antibody titres and eosinophil numbers increased in the control animals but not in those groups which had received previous trickle infection. The results demonstrate that the larval challenge alone resulted in incomplete though substantial protection against subsequent parasite challenge. The use of CRCs may potentially impact on subsequent animal performance and selection for anthelmintic resistance through a reduced level of immunity.

Albendazole↗

The establishment rate of Ostertagia circumcincta and Trichostrongylus colubriformis in lactating Romney ewes.

The ability of lactating Romney ewes to resist establishment of ingested infective-stage larvae (L3) of Ostertagia circumcincta and Trichostrongylus colubriformis was measured in the field. Three groups of seven single-lamb-bearing ewes were selected on the basis of uniformity of lambing date from a large flock held on pasture. Either 2, 4 or 6 weeks after parturition, groups of ewes were dosed with 24000 L3 of known oxfendazole-resistant parasite strains; 12000 of each species. Ten to 14 days later the ewes, along with their lambs, were transferred from the field to indoor pens. Twenty-five days after the challenge dose the ewes were drenched with oxfendazole to remove any field-derived infection and 3 days later slaughtered for worm counts. Mean establishment of the resistant parasites was low at all times, with the highest rate recorded being 6.1% for O. circumcincta 2 weeks after parturition. Establishment of O. circumcincta 4 and 6 weeks after parturition, and of T. colubriformis at all times, never exceeded 2%. By comparison, mean establishment in lambs held indoors and parasite free for 13 weeks prior to infection, was 24.9% and 47.1% for O. circumcincta and T. colubriformis, respectively. These results indicate that the lactating ewes were exhibiting a substantial ability to prevent establishment of ingested larvae. The results of this and other similar studies suggest that the dynamics of parasitism in lactating Coopworth and Romney ewes in New Zealand is substantially different to that in Merino ewes in Australia, and that these differences influence optimal strategies for the management of anthelmintic resistance in the two countries.

Animals↗

The immune response of sheep to larval challenge with Ostertagia circumcincta and O. ostertagi.

One of three groups of sheep was challenged twice-weekly with infective-stage larvae (L3) of the sheep parasite O. circumcincta, another with the cattle parasite O. ostertagi while the third received no larval challenge. Positive faecal egg counts (FEC) and a rise in plasma pepsinogen levels were observed only in those animals given O. circumcincta. Anti-O. circumcincta L3 IgG titres were rapidly elevated during parasite challenge with either O. circumcincta or O. ostertagi. Throughout the experiment, no rise in anti-adult IgG titres or eosinophil numbers was observed in peripheral blood in any group. On evidence of self-cure of the trickle-infection, determined by a reduction in FEC, all groups were drenched and challenged with 15,000 O. circumcincta L3. No effect of previous challenge on parasite establishment or FEC was observed, although egg viability was significantly reduced in both groups given prior challenge. Significant differences in adult female worm length were observed between groups. Those recovered from animals previously challenged with O. circumcincta were shorter than from those given O. ostertagi which were in turn shorter than those from previously unchallenged animals. In utero egg counts were significantly lower in worms from animals previously challenged with O. circumcincta than in those from unchallenged control animals. The results indicate that a level of immunity to O. circumcincta can be conferred by exposure to O. ostertagi.

Abomasum↗

Moxidectin: persistence and efficacy against drug-resistant Ostertagia circumcincta.

In order to determine whether the efficacy of moxidectin against Ostertagia circumcincta is enhanced by its persistency, therapeutic efficacy was compared at intervals after treatment and with that of ivermectin, a closely related but more transient endectocide. Groups of 7-month-old New Zealand Romney lambs were infected with a strain of O. circumcincta known to be resistant to moxidectin. At patency of the infections, groups of lambs were treated with either moxidectin or ivermectin at the manufacturer's recommended dosages, or left untreated. At 3, 6 and 10 days post-treatment, faecal egg count was measured and groups of lambs were slaughtered for estimation of adult worm burden. Drug-resistant worm burdens were significantly reduced in those animals treated with moxidectin but not in those treated with ivermectin. No effect of time of slaughter on worm burden was observed with either drug, demonstrating that the higher therapeutic efficacy of moxidectin against this parasite was not due to an increased period of drug exposure. Faecal egg counts in the moxidectin treated animals increased with time after treatment indicating a temporary suppression of egg output by surviving worms. The implications of these findings on selection for anthelmintic resistance are discussed.

Animals↗

Variation between hosts in the developmental success of the free-living stages of trichostrongyle infections of sheep.

Variation between hosts of different ages and genotypes in the developmental success of trichostrongylid parasite eggs from sheep was investigated in two trials. The percentage development to infective third-stage larvae of eggs collected from lambs and adult ewes infected with Ostertagia circumcincta was compared in an indoor trial. In addition, sheep previously bred for either high or low faecal egg count and grazed outdoors on parasite contaminated pasture were sampled; egg development, faecal egg count, generic profile and faecal dry matter were measured. In both trials, development to L3 was significantly lower in eggs derived from adult ewes than from lambs and, in the field trial, from animals selected for low faecal egg count. The observed differences could not be accounted for by variations in faecal egg count, faecal dry matter content nor by differences in the generic composition of worm egg output. Although not shown conclusively, the results are consistent with an immune mechanism influencing the development of free-living stages of gastrointestinal nematodes outside the host. These results have significant implications for our understanding of parasite epidemiology, particularly as it relates to sources of pasture contamination.

Age Factors↗

The effect of continuous drug exposure on the immune response of lambs challenged with drug-susceptible or drug-resistant nematode larvae.

Groups of lambs either with or without controlled-release albendazole (ABZ) capsules (CRCs) were challenged twice weekly for 6 weeks with either drug-susceptible or drug-resistant Ostertagia circumcincta and Trichostrongylus colubriformis. Groups with and without CRCs remained unchallenged as controls. There was minimal establishment of drug-susceptible parasites of either species in those lambs with CRCs. However, drug-resistant parasites of both species established adult worm burdens in the presence of the capsules. The humoral immune response, as measured by the serum antilarval (L3) antibody (Ab) titre, was pooled for weeks 4-6 and compared for each group. With the exception of anti-T. colubriformis Ab in group 2, anti-L3 Ab titres were significantly higher in all the parasite-challenged groups as compared to the control animals. Also, with the exception of anti-resistant O. circumcincta Ab levels in the CRC-treated animals (group 5), no significant difference was observed in Ab titres between the four groups challenged with either resistant or susceptible larvae. The results demonstrate the inability of CRCs to prevent establishment of drug-resistant parasites and that immune stimulation is not inhibited by the capsules.

Albendazole↗

Prophylactic efficacy of persistent anthelmintics against challenge with drug-resistant and susceptible Ostertagia circumcincta.

Three groups of newly-weaned Romney lambs were given either a standard oral dose of albendazole, a controlled-release capsule containing albendazole, or a standard oral dose of moxidectin. At 10, 20, 30 and 40 days after treatment, sub-groups of lambs were given 10,000 infective-stage larvae of either a drug-resistant or a drug-susceptible strain of Ostertagia circumcincta. The recommended oral dose of albendazole removed 32 per cent of the resistant strain and over 99.9 per cent of the susceptible O. circumcincta. The recommended oral dose of moxidectin removed 91 per cent of the resistant strain and over 99.9 per cent of the susceptible parasites. None of the lambs treated with controlled-release capsules was challenged at 20 or 30 days after treatment. Twenty-one days after challenge, samples of faeces were taken to determine the presence of nematode eggs and cultured to establish the proportion of eggs developing to infective-stage larvae (L3). Abomasa were recovered after slaughter and worm burdens determined. In the lambs given controlled-release capsules only the resistant parasites were able to establish, and there were significantly fewer than in the lambs treated orally with albendazole. The proportion of the eggs from resistant parasites which developed to L3 was not reduced by the presence of the capsules. Oral moxidectin provided no protection against the establishment of the resistant strain and viable L3 were recovered after challenge with resistant parasites 10 days after treatment; however, the establishment of susceptible O. circumcincta was reduced by more than 99 per cent. The establishment of the susceptible parasites in the lambs treated with moxidectin increased with time and was not significantly lower than in the other groups by 30 days after treatment.

Administration, Oral↗

Evaluation of a larval development assay for the detection of anthelmintic resistance in Ostertagia circumcincta.

Two experiments were carried out to evaluate a larval development assay for the detection of anthelmintic resistance in O. circumcincta. In Experiment I, the dose responses to levamisole (LEV), thiabendazole (TBZ) and ivermectin (IVM) of 8 isolates of O. circumcincta were measured 34 days after infection (DAI). Four of these isolates were shown to be resistant to 1 or more anthelmintics. With 2 exceptions, all isolates considered to be resistant had higher LD50 values than the susceptible isolates for that anthelmintic. One exception was isolate RM8, which was considered to be resistant to all 3 anthelmintics based on faecal egg count reduction tests in goats, but the LD50 value for LEV did not differ from that for the susceptible isolates. The other exception was an isolate considered to be susceptible to TBZ which had a relatively high LD50 value. In an unrelated trial that was prompted by this finding, this isolate was confirmed to be benzimidazole-resistant. Isolate RM8 and an isolate susceptible to all 3 anthelmintics (SK2) were used in the second experiment, which was conducted to monitor changes in the LD50 values of LEV, TBZ and IVM over time following a single infection of 35,000 infective larvae in young sheep. Faecal samples were collected weekly from 24 to 115 DAI. With all 3 anthelmintics, the LD50 values increased with time to a peak around 50-60 DAI, and then declined to levels similar to those observed soon after patency. This trend was consistent for both isolates. The highest mean LD50 values for isolates SK2 for IVM and TBZ and RM8 for IVM and RM8, respectively, were 1.7 and 1.8 times, and 2.2 and 2.9 times higher than the initial mean LD50 values. There was a clear distinction in LD50 values between isolates at each sampling day for both IVM and TBZ. However, as a consequence of the changes in LD50 values with time, the peak LD50 values of IVM for isolate SK2 were higher than the minimum LD50 values of isolate RM8. As there was no apparent difference in LEV efficacy between these 2 isolates, the data were pooled. The highest mean LD50 value was 2.3 times higher than the initial LD50 value.

Animals↗

The death rate of Ostertagia circumcincta and Trichostrongylus colubriformis in lactating ewes: implications for anthelmintic resistance.

Lactating adult Romney ewes were infected, 4 weeks post-lambing, with benzimidazole (bz) resistant strains of Ostertagia circumcincta and Trichostrongylus colubriformis. Commencing 4 weeks after the initial infection the ewes were subjected to challenge 3 times weekly with 5000 L3 of bz-susceptible strains of both parasite species. At weekly intervals over the following 6 weeks, groups of ewes were drenched with a bz anthelmintic (oxfendazole) to remove bz-susceptible parasites and slaughtered to determine adult worm burdens of the bz-resistant parasites. The O. circumcincta infection declined exponentially with a mean daily death rate of 10.6% day-1 and no worms were recovered after 4 weeks or more of challenge. The T. colubriformis infection did not decline significantly over the 6 weeks of continuous challenge, indicating that the death rate could not be distinguished from zero. The upper 95% confidence limit for the death rate of T. colubriformis was 4.9%. The implications of these death rates on selection for drug resistance following ewe drenching during the post-partum period are discussed with selection pressure likely to be greater for T. colubriformis than for O. circumcincta.

Animals↗