Animal grazing selectivity and plant chemistry issues impact on the potential of Rhagodia preissii as an anthelmintic shrub

Rhagodia preissii had shown significant in vitro anthelmintic activity in a previous study, we examined the effect of including this shrub in the diet of sheep infected with Trichostrongylus colubriformis. Worm-infected merino wethers were grazed for 7 weeks on either R. preissii or annual pasture, and faecal egg counts (FECs) were conducted weekly. Plant material was collected weekly from eaten and uneaten plants, and analysed for levels of plant secondary metabolites (tannins, oxalates, saponins) and in vitro anthelmintic activity. While mean FECs were consistently lower in sheep grazing R. preissii compared to pasture (reductions of 20-74%), the differences were not significant. There was no relationship between grazing preference (eaten or uneaten) and in vitro anthelmintic activity of plant extracts. The levels of saponins and oxalates did not correlate with grazing preference or in vitro anthelmintic activity, while tannins were not responsible for the anthelmintic activity. While the identity of the grazing deterrent and in vitro anthelmintic compounds remain unknown, the presence of plants which were both highly preferred by the sheep and showed in vitro anthelmintic activity indicates a potential to develop the species as an anthelmintic shrub through selection of shrub populations dominated by such plants.     

A model for nematodiasis in New Zealand lambs: The effect of drenching regime and grazing management on the development of anthelmintic resistance

A model for nematodiasis in lambs was expanded to incorporate both the contribution of ewes to nematode epidemiology and the genetic parameters required to simulate the development of anthelmintic resistance in the nematode population. The expanded model was used to assess the impact of various drench and grazing management strategies for ewes and lambs on the rate of development of anthelmintic resistance. Three grazing management options, under a range of drenching schedules, were compared: one in which lambs and ewes were rotationally grazed as separate flocks over the same area after weaning (common grazing); a second in which lambs were grazed, after weaning, on areas from which ewes were excluded (separate grazing); and a third in which lambs were moved to “safe” pasture at weaning and again in early autumn (integrated control). Drenching strategies examined under the first 2 grazing options included a 5 lamb-drench “preventive” programme with 0, 1, 2, 3 or 4 additional lamb drenches, and 0 or 1 ewe drench treatment at either tail-docking or mating. Under the third grazing option, lambs were given either 1 or 2 drench treatments at or following each move to safe pasture and ewes 0 or 1 drench treatment at either tail-docking (i.e., 3–4 weeks after lambing) or mating. Model output suggests that drenching ewes prior to any lamb drenching programme is likely to significantly increase selection for drench resistance by pre-selecting the larval challenge to the lambs and, under some grazing systems, by reducing the diluting effect of eggs of susceptible genotypes passed by undrenched ewes. The results highlight the potential importance of undrenched ewes as a refuge for susceptible worm genotypes and indicate that on its own, drenching frequency is likely to be a poor indicator of selection pressure for resistance and thus of limited value in selecting strategies for the management of anthelmintic resistance.     

Changes in anthelmintic resistance status of Haemonchus contortus and Trichostrongylus colubriformis exposed to different anthelmintic selection pressures in grazing sheep

This experiment was designed to study, over a 5-year-period, the effect of different frequencies of treatment with three different anthelmintic groups, namely, benzimidazoles, levamisole and ivermectin, and different frequencies of alternation between them, on existing levels of anthelmintic resistance in the nematode parasites Haemonchus contortus and Trichostrongylus colubriformis of grazing sheep. No evidence of ivermectin resistance emerged, even in suppressively treated groups. Likewise, H. contortus failed to develop resistance to levamisole under a similar selection regimen. Thiabendazole was shown to select positively against levamisole resistance in T. colubriformis resulting in significantly greater susceptibility to this drug than for the natural reversion which occurred in the untreated control. There was no evidence that an anthelmintic treatment combined with a movement of sheep to pastures of low infectivity selected more rapidly for resistance than where the same number of treatments were given to set-stocked sheep. Rotation between anthelmintic groups at yearly intervals appeared to be more beneficial in delaying resistance than rotation of drugs with each treatment.     

Worm control and anthelmintic resistance: adventures with a model

There are three common questions asked of parasitologists about anthelmintic resistance. Does it matter? How do you prevent it? Can you help me (it's here!)? In short, the respective answers are yes, read on the read on. Elizabeth Barnes, Robert Dobson and Ian Barger examine these issues in the context of nematode parasite control in grazing sheep. With the aid of a model, they examine some important factors that influence drug resistance and how farm management decisions and worm genetics modify these factors. They also explore the likely impact of new technologies on drug resistance and how efficient they need to be to sustain good worm control.     

Long-term effects of short-term provision of protein-enriched diets on resistance to nematode infection, and live-weight gain and wool growth in sheep.

Weaner sheep that had been hand-fed on diets containing increasing concentrations of protein for a 9-week period (when uninfected, or infected with Haemonchus contortus) were studied during the next 69 weeks when put on to pasture as a single, unsupplemented flock. During the 9-week period, groups of 12 sheep (six infected, six uninfected) were offered one of five iso-energetic (9.0 MJ kg(-1)) diets containing 10, 13, 16, 19 or 22% crude protein. All sheep were treated with anthelmintic at the end of the 9 weeks and then put out to pasture for 69 weeks, where they were all subject to the same environmental variables including nematode larval challenge. During the grazing period, animals that had previously received the higher protein diets consistently had higher live-weight gain and wool production, higher antibody responses to both H. contortus and Trichostrongylus colubriformis antigenic challenge in vitro, and lower faecal nematode egg counts than did the lambs previously offered the lower protein diets. Faecal egg counts of the grazing sheep that had been artificially infected with H. contortus while being hand-fed were similar to those of the uninfected sheep and there was no interaction between previous infection and dietary protein concentration. We conclude that short periods of enhanced post-weaning nutrition can have long-term and perhaps life-long effects on production.     

Characterization of immune responses against gastrointestinal nematodes in weaned lambs grazing willow fodder blocks

A 131-day rotational grazing experiment was conducted in the summer autumn of 2007/2008 to compare effects of feeding condensed tannin (CT)-containing willow (Salix spp.) fodder blocks (i.e., silvopastoral system) or perennial ryegrass (Lolium perenne)/white clover (Trifolium repens) control pasture upon the immune response to gastrointestinal nematode parasite infection in Romney weaned lambs. Groups of lambs (n = 40) were allocated to either willow fodder blocks or control pasture; half of each group (n = 20) were regularly-drenched with anthelmintic at approximately 21 day intervals, whilst the remaining 20 weaned lambs were not drenched unless pre-determined faecal nematode egg counts (FEC) were reached, when all weaned lambs in that group were drenched with anthelmintic (i.e., trigger-drenching). Metabolizable energy and CT concentrations were higher in willow fodder versus pasture herbages. Weaned lambs grazing willow fodder blocks had lower live weight gain (92 g/day) and carcass weight (14.4 kg) than those grazing control pasture (134 g; 15.3 kg), with no effect of anthelmintic drenching. Regular anthelmintic treatment maintained similar and low FEC up to day 82, which then increased, whilst trigger-drenched lambs grazing willow fodder blocks had higher FEC than lambs grazing control pasture on three out of eight occasions. As judged by faecal larval cultures, grazing willow fodder blocks reduced the relative proportions of abomasal-dwelling parasites (Haemonchus contortus and Teladorsagia spp.). Trigger-drenched willow fodder block-fed sheep had higher platelet, eosinophil, total white blood cell and lymphocyte counts, greater CD21⁺ and greater γδ (Gamma Delta) TCR⁺ (T cell receptor) lymphocyte subsets than control pasture-fed sheep, and higher plasma levels of Immunoglobulin A (IgA) specific for carbohydrate larval antigen (CarLa) on day 105 (P<0.001). None of these parameters were affected by grazing treatment in regularly-drenched lambs. Higher immunological measurements in trigger-drenched lambs grazing willow fodder blocks could be due to higher larval intake and/or to the effects of secondary compounds in willow fodder blocks priming the immune system. Further research is required to separate these effects.     

Tracking gastrointestinal nematode risk on cattle farms through pasture contamination mapping

Gastrointestinal nematode (GIN) parasites in grazing cattle are a major cause of production loss and their control is increasingly difficult due to anthelmintic resistance and climate change. Rotational grazing can support control and decrease reliance on chemical intervention, but is often complex due to the need to track grazing periods and infection levels, and the effect of weather on larval availability. In this paper, a simulation model was developed to predict the availability of infective larvae of the bovine GIN, Ostertagia ostertagi, at the level of individual pastures. The model was applied within a complex rotational grazing system and successfully reproduced observed variation in larval density between fields and over time. Four groups of cattle in their second grazing season (n = 44) were followed throughout the temperate grazing season with regular assessment of GIN faecal egg counts, which were dominated by O. ostertagi, animal weight and recording of field rotations. Each group of cattle was rotationally grazed on six group-specific fields throughout the 2019 grazing season. Maps and calendars were produced to illustrate the change in pasture infectivity (density of L3 on herbage) across the 24 separate grazing fields. Simulations predicted differences in pasture contamination levels in relation to the timing of grazing and the return period. A proportion of L3 was predicted to persist on herbage over winter, declining to similar intensities across fields before the start of the following grazing season, irrespective of contamination levels in the previous year. Model predictions showed good agreement with pasture larval counts. The model also simulated differences in seasonal pasture infectivity under rotational grazing in systems that differed in temperature and rainfall profiles. Further application could support individual farm decisions on evasive grazing and refugia management, and improved regional evaluation of optimal grazing strategies for parasite control. The integration of weather and livestock movement is inherent to the model, and facilitates consideration of climate change adaptation through improved disease control.     

Selection of different genotype larvae and adult worms for anthelmintic resistance by persistent and short-acting avermectin/milbemycins

To understand the factors that influence selection for anthelmintic resistance, it is necessary to examine the impact of drug treatment, particularly persistent drugs, on all phases of the worm life cycle. The efficacy of various avermectin/milbemycin anthelmintics was determined against resident worms, incoming larvae (L3) and development of eggs in faecal culture. Homozygote-resistant and maternal and paternal F1-heterozygote genotypes of Haemonchus contortus were used to infect sheep before or after treatment with ivermectin (IVM) oral, IVM capsule, moxidectin (MOX) oral or MOX injectable. Total worm count and quantitative larval culture were used to determine efficacy against parasitic and free-living stages, respectively. Selection for resistance by IVM capsules occurred at the adult and L3 stages because of poor efficacy against these stages for all resistant genotypes. However, the selective advantage of these surviving worms was reduced due to the low development of their eggs to L3 in faecal culture. For MOX, selection for resistance predominantly occurred after treatment because of high efficacy against resident adult worms of all resistant genotypes but poor efficacy against resistant L3 ingested after drug administration. The results indicated no evidence of sex-linked inheritance for IVM resistance. Mean IVM efficacies against homozygous and heterozygous resistant adult worms were not different, and IVM capsule efficacy against incoming L3 was approximately 70% for all resistant genotypes, consistent with a dominant trait. MOX was highly effective against adults of all resistant genotypes and approximately 76% effective against incoming L3 regardless of resistance genotype, also consistent with a dominant trait. These results will enable the impact of persistent drugs on worm control and anthelmintic resistance to be estimated. The results indicate that IVM capsules should not be used in populations where avermectin/milbemycin resistance is present.     

The effect of selection with levamisole on benzimidazole resistance in Ostertagia spp. of sheep

A field population of Ostertagia spp. (predominantly O. circumcincta) in sheep, found to be resistant to oxfendazole, was exposed to selection with1 levamisole in the laboratory and the field. Progeny of the survivors of a single dose of levamisole in penned sheep showed a significantly lower level of resistance to oxfendazole in an anthelmintic assay, and a similarly lower level of resistance to the ovicidal activity of thiabendazole in vitro compared with the progeny of the survivors of a single dose of oxfendazole, although they remained more resistant than a known susceptible strain of 0. circumcincta. The progeny of worms present in grazing sheep after three doses of levamisole at 4-weekly intervals, and subjected to the same tests, behaved in a similar fashion. They also showed a substantial fall in benzimidazole resistance compared with the progeny of worms not exposed to any anthelmintic for 6 months. The results suggested that levamisole selected positively against benzimidazole resistance. In these circumstances some form of alternation in the use of different anthelmintics could delay the development of a high level of resistance and maintain the practical usefulness of existing anthelmintics.     

The Dynamics, Prevalence and Impact of Nematode Infections in Organically Raised Sheep in Sweden

A three-year survey (1997–99) was carried out on organically reared sheep flocks throughout Sweden. The aim was to determine the prevalence and intensity of nematode infections and to establish relationships between sheep management practices and parasite infections. Faecal samples from ewes and lambs were collected from 152 organic flocks around lambing-time and during the grazing-period for analysis. Results were compared with the different management practices that farmers use to prevent parasitism in their flocks. A high proportion of the flocks was infected with nematodes. The most prevalent species were Haemonchus contortus, Teladorsagia circumeincta, Trichostrongylus axei, T. colubriformis and Chabertia ovina and infections progressively increased during summer in lambs grazing on permanent pastures. Severity of parasitic infection in lambs was highly dependent on egg output from the ewes. H. contortus was found in 37% of the flocks, even at latitudes approximating the Polar Circle. Nematodirus battus was recorded for the first time in Sweden during the course of this study. Lambs turned out onto permanent pasture showed higher nematode faecal egg counts (epg) than lambs that had grazed on pastures, which had not carried sheep the previous year. This beneficial effect of lambs grazing non-infected pastures persisted if the ewes were treated with an anthelmintic before turn-out and if the lambs were kept on pastures of low infectivity after weaning. In lambs, the prevalence and the magnitude of their egg counts were higher during autumn in flocks where lambs were slaughtered after 8 months of age, compared with flocks where all lambs were slaughtered before this age. These results will be used in providing advice to farmers of ways to modify their flock management in order to minimise the use of anthelmintics, but at the same time efficiently produce prime lambs.     

The role of parasite epidemiology in the management of grazing cattle

Epidemiology of ruminant helminths is the foundation on which strategic parasite control programmes are designed. Without this information one is not able to use anthelmintics to provide the optimal benefits for controlling both the adult worm and the pasture larval populations. The absence of strategic programmes generally results in using anthelmintics at the convenience of the producer, which may have little if any impact on parasite populations. The design of a strategic parasite control programme requires a knowledge of the dynamics of egg shedding from the host and the resulting pasture larval populations. It is important to know if larvae are available when animals are turned out onto pasture, when larval populations reach their maximal numbers and when they are induced to become hypobiotic. The goal is to keep pasture larval populations as low as possible. The use of pasture rotation adds another dimension to control programmes. The longer a pasture is allowed to remain fallow, the lower the pasture larval burden will be when it is grazed next. However, when we use intensive rotational grazing, animals may return to the pasture about 28 days later, when the larvae resulting from the eggs shed in the previous grazing are infective. This practice forces cattle to eat all of the forage available, including the grass closest to the faecal pat, where most of the infective larvae are available. If we treated cattle before turning them onto a clean rotationally grazed pasture, we should be able to control parasitism. Using a long-acting anthelmintic should enhance helminth control in rotationally grazed pastures and actually help to clean the pastures. Another grazing management practice is to alternately graze different species. This programme with the strategic use of anthelmintics should reduce parasitism in both host species.     

A suitable model for the utilization of Duddingtonia flagrans fungus in small-flock-size sheep farms

Effective alternatives to anthelmintic treatment of nematode parasite infections of sheep are required because of the high prevalence of drug resistance. Within this context, the nematode-trapping fungus Duddingtonia flagrans has become a valuable component of various integrated control strategies. Toward this objective, a small quantity of lyophilized D. flagrans chlamydospores (10⁶ spores per animal) was administered to sheep in a one-year plot study. Animals grazing on native pasture were divided into two homogeneous groups and were kept in 1-ha paddocks in the southern region of Brazil. The oral administration of chlamydospores led to a significant reduction (p < 0.05) in the number of nematode eggs per gram of feces and in the larval availability on herbage (difference of 37.6%) in comparison to the control group. Control animals needed to be dewormed three times during the experiment, whereas the fungus-treated animals maintained a low parasite load, independent of seasonal variation. Although D. flagrans cannot serve as a panacea for nematode parasite control of livestock, it represents a significant advance toward rationalizing the use of endoparasitic drugs in small animals.     

Control of nematode parasites by grazing management—II. Decontamination of sheep and cattle pastures by varying periods of grazing with the alternate host

Commencing in December 1970, paddocks of a uniform series of sheep pastures were grazed for 6, 12 or 24 weeks by either yearling steers is or yearling ewes. Cattle pastures were treated similarly. All ewes and steers were pre-dosed with anthelmintic.At the conclusion of alternate grazing the effectiveness of the grazing treatments was evaluated by grazing each paddock for 1 month with either ten worm-free lambs (sheep pastures) or three wormfree calves (cattle pastures). The test animals were then slaughtered for total worm counts. The grazing of sheep pastures with cattle for 6, 12 or 24 weeks from December onwards resulted in reductions in numbers of Haemonchus contortus and Trichostrongylus colubriformis in test lambs. In comparison with continuous grazing by sheep, Nematodirus spp was only reduced after 24 weeks grazing by cattle. Cattle pastures grazed by sheep for 6 weeks showed no reduction in numbers of Ostertagia ostertagi or Cooperia oncophora in test calves. However after 12 weeks with sheep, numbers of O. ostertagi though not C. oncophora were reduced and after 24 weeks of alternate grazing both these species were reduced.Calves following the 6 week sheep treatments acquired both Haemonchus contortus and Trichostrongylus colubriformis and the calves from the 12 week sheep treatment paddock also carried H. contortus. For sheep the only evidence of cross-transmission was the occurrence of small numbers of Cooperia oncophora in test lambs from the 24 week cattle grazing treatment.The results provide evidence that sequential stocking with cattle and sheep in conjunction with anthelmintic treatment is an effective management strategy for preparing parasitologically safer pastures, but further information is required to determine the optimum timing of sequential stocking in farming situations.     

Trends and challenges in the effective and sustainable control of Haemonchus contortus infection in sheep. Review

Haemonchosis, with its very wide distribution, has become a very important production constraint in sheep farms in tropical, subtropical and temperate regions worldwide. Various intrinsic and extrinsic factors determine the survival of Haemonchus contortus and hence the development of the disease in the animal. In general, control of gastrointestinal nematode infestation in sheep relies heavily on anthelmintic treatments. However, the indiscriminate use of these drugs has led to the widespread emergence of drug resistant strains of parasites, that has necessitated the development and use of various parasite control methods such as grazing management, biological agents and vaccines and the selection of resistant breeds of animals, with or without moderate use of anthelmintics. The ultimate goal of such control programs is to enhance productivity, while minimising risks regarding drug resistance and consumer and environmental concerns. This review attempts to highlight the different methods employed in the control of haemonchosis in sheep and the practical limitations associated with both control programs and the internal and external factors associated with the parasite and its microenvironment.     

Anthelmintic resistance and the control of ovine ostertagiasis: a drug action model for genetic selection

A site-specific genetic prediction model is presented, which examines the influences of different anthelmintic treatment regimens on selecting for drug resistance within a sheep management system. The model exploits the power of modern microcomputers to integrate factors such as parasite strain, geographic location, management practice and genetic fitness to identify effective control regimens which do not lead to resistant Ostertagia circumcincta strains over a 30-year horizon. The potential use of the model as a farm level management-support tool is discussed.     

Possibilities to breed for resistance to nematode parasite infections in small ruminants in tropical production systems

Gastrointestinal nematode parasitism is the most important disease affecting livestock production systems in developing countries, particularly small ruminant production systems. Of particular importance are infections with the strongyle Haemonchus contortus. Integrated disease control strategies are required, including improved management, nutrition and wise use of anthelmintic chemicals. Increasingly, selection of sheep or goats for improved nematode resistance is viewed as a valuable option to complement other control measures. Breeding for resistance is possible because of the existence of extensive genetic variation in resistance, both within and between breeds of sheep and goats. Such breeding schemes are most likely to be based on choice of appropriate breeds adapted to the local environmental conditions, followed by phenotypic selection for resistance. Goal and selection objective traits are likely to include performance (e.g. growth rate) under conditions of parasite challenge, faecal egg count (FEC) and measures of anaemia. With current technologies, genetic markers are likely to be too expensive and logistically difficult to incorporate into breeding schemes in tropical or developing countries. Genotype by environment interactions may be expected, particularly when comparing animals in environments that differ in the extent of parasite challenge or differ in the quality of available nutrition. However, there is no reason to expect antagonistic genetic relationships between performance and resistance, and selection indices should be readily constructed that improve both performance and resistance. If FEC is decreased, then pasture contamination should also decrease, leading to additional benefits for all sheep grazing the same pasture. Finally, breeding for nematode resistance should lead to lasting and sustained improvements in resistance or tolerance. There is no empirical evidence to suggest that nematodes will evolve rapidly in response to resistant hosts, and mathematical models based on genetic and biological principles also suggest that resistance should be sustainable.     

Development and application of a delayed-release anthelmintic intra-ruminal bolus system for experimental manipulation of nematode worm burdens

In order to quantify the impact of parasites on host population dynamics, experimental manipulations that perturb the parasite-host relationship are needed but, logistically, this is difficult for wild hosts. Here, we describe the use of a delayed-release anthelmintic delivery system that can be administered when the hosts can be captured and its activity delayed until a more appropriate period in the host-parasite cycle. Our model system is Svalbard reindeer infected with a nematode parasite, Marshallagia marshalli, which appears to accumulate during the Arctic winter. To determine the extent to which this occurs and the effect on host fitness, reindeer need to be treated with anthelmintics in late autumn but they can only be caught and handled in April. To solve this problem, we devised an intra-ruminal capsule that releases the anthelmintic from up to 6 months after being administered. The capsule was trialed in cannulated sheep and red deer to determine optimum capsule orifice size and release rates. Capsules were estimated to release placebo for 100-153 days followed by abamectin for 22-34 days. To test the efficacy of treatment in reindeer, capsules were administered in April and retrieved in October. All capsules had fully released the anthelmintic and treated reindeer had significantly lower worm burdens than controls. Thus, success of this system allows repeated treatment over several years to test the effect of winter parasitism on host fitness.     

The role of epidemiological knowledge and grazing management for helminth control in small ruminants

There is no single requirement more crucial to the rational and sustainable control of helminth parasites in grazing animals than a comprehensive knowledge of the epidemiology of the parasite as it interacts with the host in a specific climatic, management and production environment. In its absence, anthelmintic treatment is either given suppressively, which provokes resistance, or therapeutically, which risks clinical disease and production losses. Sustainable parasite-control programmes require knowledge of seasonal larval availability, origin of larvae contributing to any peaks and climatic requirements for worm egg hatching, larval development and survival. Control measures based on this knowledge include strategic anthelmintic treatments and various forms of grazing management. While these measures can reduce the frequency of anthelmintic treatment required, their effect on selection for drench resistance is more problematical, unless they can be combined with other forms of control to reduce our current dependence on anthelmintics.     

Deep amplicon sequencing as a powerful new tool to screen for sequence polymorphisms associated with anthelmintic resistance in parasitic nematode populations

Parasitic gastrointestinal nematodes contribute to significant human morbidity and cause billions of dollars per year in lost agricultural production. Control is dependent on the use of anthelmintic drugs which, in the case of livestock parasites, is severely compromised by the widespread development of drug resistance. There are now concerns regarding the emergence of anthelmintic resistance in parasitic nematodes of humans in response to the selection pressure resulting from mass drug administration programs. Consequently, there is an urgent need for sensitive, scalable and accurate diagnostic tools to detect the emergence of anthelmintic resistance. Detecting and measuring the frequency of resistance-associated mutations in parasite populations has the potential to provide sensitive and quantitative assessment of resistance emergence from an early stage. Here, we describe the development and validation of deep amplicon sequencing as a powerful new approach to detect and quantify the frequency of single nucleotide polymorphisms associated with benzimidazole resistance. We have used parasite communities in sheep to undertake a proof-of-concept study of this approach. Sheep provide an excellent host system, as there are multiple co-infecting trichostrongylid nematode species, each likely with a varying prevalence of benzimidazole resistance. We demonstrate that the approach provides an accurate measure of resistance allele frequencies, and can reliably detect resistance alleles down to a frequency of 0.1%, making it particularly valuable for screening mutations in the early stages of resistance. We illustrate the power of the technique by screening UK sheep flocks for benzimidazole resistance-associated single nucleotide polymorphisms at three different codons of the β-tubulin gene in seven different parasite species from 164 populations (95 from ewes and 69 from lambs) in a single MiSeq sequencing run. This approach provides a powerful new tool to screen for the emergence of anthelmintic resistance mutations in parasitic nematode populations of both animals and humans.     

Selection for anthelmintic resistance by macrocyclic lactones in Haemonchus contortus.

Two morphologically marked strains of Haemonchus contortus, CAVRS (smooth-macrocyclic lactone resistant) and McMaster (linguiform-macrocyclic lactone susceptible), were used to investigate the selection for anthelmintic resistance following exposure to ivermectin (IVM), a non-persistent anthelmintic. and a more persistent anthelmintic, oral moxidectin (MOX). Three types of selection were investigated: (1) selection of resident worms at the time of treatment (Head selection); (2) selection of incoming-larvae post-treatment (Tail selection); and (3) selection of both resident population and incoming larvae (Head + Tail selection). The experimental animals were adult sheep and lambs. In the controls where there was no anthelmintic selection, the proportion of CAVRS in the adult worm population was the same as the proportion in larvae given to both adults and lambs indicating that CAVRS and McMaster H. contortus were equally infective. There was a significant effect of anthelmintic on total worm numbers in adult sheep with MOX treated adults having less worms, but selection type was non-significant. Anthelmintic type had a significant effect on numbers of resistant worms in adult sheep with less resistant worms in the MOX treated groups, but selection type had no effect. Analysis of variance of arcsine-transformed proportions of resistant worms found that the type of anthelmintic had a highly significant effect, with MOX treated adults having a higher proportion of resistant worms, while type of selection was not significant. In the lambs, nil treated controls and IVM Head + Tail and Tail selected groups had similar geometric mean total worm burdens while Head selected had less total worms. In the MOX treated lamb groups the worm burdens were similar within selection type but less than the IVM treated groups. In the lambs, the types of selection that resulted in more resistant worms were IVM Tail, MOX Head + Tail and MOX Tail. Resistant worm numbers were similar in both adult and lamb groups with Head selection by either MOX or IVM. Moxidectin selected out higher proportions of resistant worms than did IVM in the lambs, with Tail and Head + Tail being stronger selectors than Head. Computer simulations were used to estimate the rate at which resistance developed in the field using the information generated in the present study. The anthelmintic treatments used in the simulation followed a strategic parasite control program for H. contortus in which all sheep receive three Closantel (CLS) treatments in summer. all sheep receive a broad-spectrum (BS) drench or capsule at weaning and lambs receive an additional two BS drenches insummer or no further treatment in the case of the capsule. Moxidectin, IVM-capsule and IVM were the broad spectrum anthelmintics simulated. All simulations were run four times assuming high or low efficacy against resident resistant worms and in the presence or absence of CLS resistance. The simulations indicated that the presence of CLS resistance hastened selection for macrocyclic lactone (ML) resistance. While the IVM-capsule will select most rapidly for ML resistance, IVM oral is expected to be least selective. Moxidectin treatment is intermediate, except in simulations with no CLS resistance and when MOX is assumed to be highly effective against resident ML-resistant worms, in which case MOX can be expected to select more slowly than IVM oral treatments.