Managing anthelmintic resistance in small ruminant livestock of resource-poor farmers in South Africa

Gastrointestinal parasitism is one of the most important disease complexes of sheep and goats impacting on the resource-poor livestock farmer. Of the responsible nematodes, Haemonchus contortus, a blood-sucking worm of the abomasum, poses possibly the greatest threat. Over the past several decades, the worm has been controlled through the use of anthelmintics, but the emergence of anthelmintic resistance has threatened this chemotherapeutic approach. In Africa, the overall prevalence of anthelmintic resistance has not been extensively investigated, particularly within the resource-poor farming sector, but resistance has been reported from at least 14 countries with most of the reports emanating from Kenya and South Africa and the majority concerning H. contortus. While levels of resistance under commercial sheep farming systems in South Africa is considered to be amongst the worst in the world, resistance has also been reported from the resource-poor farming sector. Increases in productivity and reproduction of livestock and the development of markets for sale of animals are seen by international funding bodies as a way out of poverty for communities that keep livestock. This must lead to the greater need for parasite control. At such times, the risk of levels of anthelmintic resistance escalating is much greater and there is therefore a need to look at alternatives to their use. Proposed strategies include the appropriate, but judicious use of anthelmintics by application of the FAMACHA system and the use of alternatives to anthelmintics such as strategic nutrient supplementation. It is also very clear that there is a strong demand for knowledge about animal diseases, including helminthosis, and their effective management in the resource-poor livestock farming communities. This is an important challenge to meet.     

牛羊线虫抗药性及其PC检测技术研究进展

牛羊线虫病是严重影响牛羊生产性能和经济效益的主要寄生虫病，化学药物是目前防治本病的主要手段，近年来线虫抗药性。已经成为世界各地牛羊线虫控制中的首要问题。建立线虫抗药早期检测技术可以时了解抗药性及其产生的条件等，便于采取有效对策，本文简要阐述牛羊线虫抗药性的分布与检测，现有抗药性检测方法的缺点以及PCR检测技术的最新进展。     

An update on cyathostomins: Anthelmintic resistance and worm control

Intestinal nematodes are an important cause of equine disease. Of these parasites, the Cyathostominae are the most important group, both in terms of their prevalence and their pathogenicity. Cyathostomin infections are complex and control is further complicated by ever‐increasing levels of resistance to some of the commonly used anthelmintics. There are no new equine anthelmintics under development, so it is imperative that the efficacy of any currently‐effective drug classes be maintained for as long as possible. It is believed that the proportion of refugia (i.e. the percentage of parasites not exposed to a drug at each treatment) is one of the most crucial factors in determining the rate at which anthelmintic resistance develops. It is important, therefore, that levels of refugia be taken into account when designing nematode control programmes for horses. This can be assisted by knowledge of the local epidemiology of the infection, supplemented by faecal egg count analysis to identify those animals that are making the major contribution to pasture contamination. This type of rational nematode control requires equine veterinary surgeons to get involved in designing and implementing deworming programmes. The advice given must be based on a combination of knowledge of cyathostomin biology and epidemiology as well as an awareness of the parasite population's current drug sensitivity and a sound history of husbandry at the establishment. As anthelmintic resistance will be the major constraint on the future control of cyathostomins, researchers are now actively investigating this area. Studies are underway to develop tests that will enable earlier detection of anthelmintic resistance and an assay that will help identify those horses that require anthelmintic treatments targeted at intestinal wall larvae.     

Evaluation of efficacy expectations for novel and non-chemical helminth control strategies in ruminants

The interest in novel methods of controlling helminth infections in ruminants is driven primarily by the development of parasite resistance to currently available anthelmintics. While the purpose of anthelmintics is to achieve high efficacy, i.e. >90% reduction of adult and/or larval parasites in the target host animal, the purpose of novel parasite control methods is rather to assist in maintaining parasite infections below the economic threshold. The ability to maintain parasite levels below the economic threshold is related not only to the efficacy of the control method, but also to the epidemiology of the parasites, climatic conditions, the livestock management program, and integration in a sustainable parasite control program. Because of this fundamental difference, novel parasite control methods need to be evaluated using efficacy criteria different from that adopted for anthelmintics. Although the efficacy of novel parasite control methods may be demonstrated in classic dose-confirmation studies, the impact on livestock production parameters can only be evaluated when tested on-farm. In this paper, the rationale for evaluating novel methods differently from anthelmintics is reviewed, potential performance expectations are presented, and four novel parasite control methods (vaccines, nematophagous fungi, condensed tannins, and immunonutrition) are assessed based on the potential performance criteria.     

Control of helminthosis in lambs by strategic treatment with closantel and broad-spectrum anthelmintics

Treatment of ewes with broad-spectrum anthelmintic in August (pre-lambing) and early November, and of lambs in early November and early February, was effective in controlling infections with Trichostrongylus spp in lambs reared on contaminated pastures under set-stocked conditions. It was ineffective in controlling infections with Haemonchus contortus; 82% of lambs had to be withdrawn from the experiment because of severe haemonchosis. Treatment with closantel (7.5 mg/kg) at the same times was very effective against H. contortus but ineffective against Trichostrongylus spp; 25% of lambs had to be withdrawn because of severe trichostrongylosis. The same schedule using broad spectrum anthelmintic and closantel administered concurrently was effective against both parasites; no lambs had to be withdrawn and the bodyweight gain of lambs was higher than in lambs treated with broad-spectrum anthelmintic or closantel alone. The results provide a basis on which to develop a preventive anthelmintic treatment program to control haemonchosis and trichostrongylosis in sheep which will allow the current high frequency of treatment with broad-spectrum anthelmintics to be reduced. Such a program may retard selection for anthelmintic resistance in Trichostrongylus spp.     

The role of combination anthelmintic formulations in the sustainable control of sheep nematodes

Combinations of anthelmintics with a similar spectrum of activity and different mechanisms of action and resistance are widely available in several regions of the world for the control of sheep nematodes. There are two main justifications for the use of such combinations: (1) to enable the effective control of nematodes in the presence of single or multiple drug resistance, and (2) to slow the development of resistance to the component anthelmintic classes. Computer model simulations of sheep nematode populations indicate that the ability of combinations to slow the development of resistance is maximised if certain prerequisite criteria are met, the most important of which appear to concern the opportunity for survival of susceptible nematodes in refugia and the pre-existing levels of resistance to each of the anthelmintics in the combination. Combinations slow the development of a resistant parasite population by reducing the number of resistant genotypes which survive treatment, because multiple alleles conferring resistance to all the component anthelmintic classes must be present in the same parasite for survival. Individuals carrying multiple resistance alleles are rarer than those carrying single resistance alleles. This enhanced efficacy leads to greater dilution of resistant genotypes by the unselected parasites in refugia, thus reducing the proportion of resistant parasites available to reproduce with other resistant adults that have survived treatment. Concerns over the use of anthelmintic combinations include the potential to select for resistance to multiple anthelmintic classes concurrently if there are insufficient parasites in refugia; the potential for shared mechanisms of resistance between chemical classes; and the pre-existing frequency of resistance alleles may be too high on some farms to warrant the introduction of certain combinations. In conclusion, anthelmintic combinations can play an important role in resistance management. However, they are not a panacea and should always be used in accordance with contemporary principles for sustainable anthelmintic use.     

Gastrointestinal nematode control practices on lowland sheep farms in Ireland with reference to selection for anthelmintic resistance

Gastrointestinal parasitism is a widely recognised problem in sheep production, particularly for lambs. While anthelmintics have a pivotal role in controlling the effects of parasites, there is a paucity of data on how farmers use anthelmintics. A representative sample of Irish lowland farmers were surveyed regarding their parasite control practices and risk factors that may contribute to the development of anthelmintic resistance. Questionnaires were distributed to 166 lowland Irish sheep producers. The vast majority of respondents treated their sheep with anthelmintics. Lambs were the cohort treated most frequently, the majority of farmers followed a set programme as opposed to treating at sign of disease. A substantial proportion (61%) administered four or more treatments to lambs in a 'normal' year. Departures from best practice in anthelmintic administration that would encourage the development of anthelmintic resistance were observed. In conclusion, in the light of anthelmintic resistance, there is a need for a greater awareness of the principles that underpin the sustainable use of anthelmintics and practices that preserve anthelmintic efficacy should be given a very high priority in the design of helminth control programmes on each farm. To this end, given that veterinary practitioners and agricultural advisors were considered to be the farmer's most popular information resource, the capacity of these professions to communicate information relating to best practice in parasite control should be targeted.     

Resistance to benzimidazole anthelmintics in small strongyles (Cyathostominae) of horses in Denmark.

This study was undertaken to establish whether anthelmintic resistance was present in nematode parasites of horses in Denmark. Sixteen horse farms were selected for faecal egg count reduction (FECR) tests to measure the efficacy of the anthelmintic used. Resistance to benzimidazole anthelmintics was found on 13 of the 16 farms, with FECR values ranging from 80.0% to -101.3%. On the remaining 3 farms FECR was 100.0%, 99.3% and 97.2%. Results of a questionnaire study on anthelmintic usage, parasite control measures and management practices showed that horses in this study were treated on average 7.1 times/year. Horse owners changed between preparations of drugs but almost only within the same class of anthelmintics. Nine owners gave an anthelmintic treatment to purchased horses before they were introduced on the farm. On 14 farms, the same paddock was grazed every year and the average stocking rate was estimated to be 2.4 horses/ha. Strategies to avoid development of anthelmintic resistance are discussed and recommendations of parasite control on horse farms are presented.     

Anthelmintic resistance in equine parasites - detection, potential clinical relevance and implications for control

During the past two decades anthelmintic resistance in equine parasites has been found in the group of small strongyle species (cyathostomins) and in the ascarid species Parascaris equorum. The ubiquitous nature and possible severe consequences of disease with these nematodes make them the prime targets of current worm control programmes. Traditional control strategies mainly rely on the strategic application of anthelmintics, currently represented by three major drug classes: benzimidazoles (BZ), the tetrahydropyrimidine pyrantel (PYR) and macrocyclic lactones (ML). Following decades of routine and frequent anthelmintic applications, many cyathostomin populations on horse farms in industrialised countries must be considered as resistant to BZ anthelmintics. However, to date no published cases of cyathostomin disease specifically associated with anthelmintic resistance were reported. Possibly this is due to the generally subclinical and unspecific symptoms associated with cyathostomin infections. Nevertheless, exclusive reliance on the ML drug class may increase the threat of clinical disease due to drug-resistant cyathostomins. More recently, P. equorum has been reported as having developed resistance against ivermectin and moxidectin, two representatives of the ML-class. These anthelmintics are currently the most frequently used drug class in horses. This nematode species is mainly found in foals and in younger horses due to the development of immunity following exposure to infection. Infection with P. equorum can result in clinically drastic consequences such as obstruction and/or penetration of the small intestine, the latter usually leading to death. In conclusion, on horse farms the efficacy of anthelmintic treatments should be examined routinely for each drug class. Several factors can influence the rate at which anthelmintic resistance develops; high frequency of treatment being one of the most important. Modern control strategies should therefore attempt to significantly reduce anthelmintic treatments. Several pasture and farm management practices found to be negatively associated with nematode and anthelmintic resistance prevalence will be discussed in the review presented here.     

Facing the threat of equine parasitic disease

Horses worldwide are exposed to a complex mixture of intestinal parasitic helminths. When burdens are high, these parasites can seriously compromise health and welfare. Some helminth species have an extremely high prevalence and are difficult to control, not least because there is a limited understanding of their most basic biology. Furthermore, levels of resistance to some of the commonly used anthelmintics are widespread and increasing. The cyathostomins are the most common nematode species affecting equids worldwide. Within this group of parasites are more than 50 different species. Until recent research activities, little was known about the contribution that individual species make to clinical disease, parasite epidemiology and anthelmintic resistance. This review describes some of the recent research advances in the understanding of cyathostomins in these areas. As part of the research effort, molecular tools were developed to facilitate identification of the non-parasitic stages of cyathostomins. These tools have proved invaluable in the investigation of the relative contributions that individual species make to the pathology and epidemiology of mixed infections. At the more applied level, research has also progressed in the development of a diagnostic test that will allow numbers of cyathostomin encysted larvae to be estimated. This test utilises cyathostomin-specific serum antibody responses as markers of infection. As anthelmintic resistance will be the major constraint on parasite control in future, researchers are actively investigating mechanisms of drug resistance and how to improve the detection of resistance in the field. Recent developments in these areas are also outlined.     

Anthelmintic resistance in South Africa: surveys indicate an extremely serious situation in sheep and goat farming

Surveys to determine the prevalence and degree of resistance of Haemonchus spp. of sheep and goats to the available anthelmintics in South Africa indicate that small ruminant production is entering a crisis situation. Three surveys employing the faecal egg count reduction (FECR) test to determine resistance were conducted in some of the main sheep-producing areas in the summer rainfall region of South Africa, where H. contortus is the principal worm species in sheep. After analyzing the data recorded in the surveys by six different methods, including the RESO test at two different levels of confidence, the results obtained in the least stringent one (geometric mean reduction of the worm egg counts of drenched, vs untreated group of sheep) are reported in this paper, so that if any bias was obtained it would be in the favour of the anthelmintic. In Mpumalanga and KwaZulu-Natal there was anthelmintic resistance in Haemonchus spp. on all the 52 farms surveyed. Sixteen percent of the strains of H. contortus were < 60% susceptible to three of the four anthelmintics tested, and 8% of the strains were < 40% susceptible to all four of the anthelmintics. FECR tests of sheep in six localities in the Lebowa district of Northern Province indicated that even in previously disadvantaged communities where anthelmintic treatment is less intensive, anthelmintic resistance is developing, and is possibly at the level at which the situation on commercial sheep and goat farms in South Africa was 25 years ago. From the data it appears that the level of anthelmintic resistance of H. contortus in South Africa is possibly the highest that has so far been recorded in the world and that strains of it are emerging that may soon not be controllable by treatment with any of the existing anthelmintics. Farmers in the summer rainfall region, if not the whole country, must be alerted to the immediate need for testing the parasite burdens of their sheep for susceptibility to preparations in all four groups of anthelmintic compounds currently available. Alternative methods of integrated worm control, including biological, must be sought and implemented with urgency, to reduce further selection for resistance and to induce reversion of the resistance that has already developed.     

Prospects for Plant Anthelmintics in Tropical Veterinary Medicine

Hammond, J.A., Fielding, D. and Bishop, S.C., 1997. Prospects for plant anthelmintics in tropical veterinary medicine. Veterinary Research Communications, 21 (3), 213-228The current use of anthelmintic plants in tropical veterinary medicine is reviewed and attention is drawn to the lack of scientific evidence for the effectiveness of many now in use. The case for anthelmintic plants as a means of overcoming some of the serious limitations of manufactured anthelmintics is outlined. Reasons why anthelmintic plants are not generally used in veterinary medicine, in contrast to their greater acceptance in human medicine, are considered. Strategies for their development and use are discussed, in particular the need for in vivo trials to identify those plants which are effective and suitable for general use: attention is drawn to possible candidates, including pyrethrum and papaya latex. Those helminths of most economic importance should be targeted first. Anthelmintic plants offer a traditional alternative to manufactured anthelmintics that is both sustainable and environmentally acceptable. Such plants could have a more important role in the future control of helminth infections in the tropics.     

Managing anthelmintic resistance: Modelling strategic use of a new anthelmintic class to slow the development of resistance to existing classes

AIM: To test the hypothesis that a single strategic treatment with a new class of anthelmintic could slow the development of resistance to existing classes of anthelmintic.

METHODS: An existing model was used to simulate nematode parasite dynamics and the development of anthelmintic resistance. Variations on a five-drench preventive programme of treatments for lambs, in which either zero, the first, third or fifth treatment was substituted with a different class of drug, were compared for the time to reach treatment failure (defined as efficacy <95%). The sensitivity to variations in the death rate of adult worms, that varied from 1 to 5%, and the dominance of resistance genes were also assessed.

RESULTS: Replacing one of the five treatments with a different class of anthelmintic almost always slowed the development of resistance, and was never worse than using the same drug for all treatments. Further, there were large differences in the relative time to treatment failure depending on which treatment was substituted. Changing the first treatment always had the least benefit, whereas changing the fifth treatment always had the greatest. This pattern was independent of the daily death rate of adult worms, and was not influenced by the dominance of resistance under treatment.

CONCLUSIONS: The results indicated that strategic substitution of a single treatment with a new class of anthelmintic, at the end of a series of preventive treatments to lambs using an existing class, could slow the further development of resistance to the latter. This strategic use of a new anthelmintic class has the potential to greatly extend the life of existing anthelmintics if these are still effective.     

Anthelmintics used in treatment of parasitic infections of horses

The common anthelmintics used to treat parasitic infections of horses are described. Dosage, anthelmintic spectrum, formulation and administration, mode of action, toxicity contraindications, and resistance of parasites to anthelmintics are included.     

Climatic influences on development and survival of free-living stages of equine strongyles: implications for worm control strategies and managing anthelmintic resistance

Development of resistance to anthelmintic drugs by horse strongyles constitutes a growing threat to equine health because it is unknown when new drug classes can be expected on the market. Consequently, parasite control strategies should attempt to maintain drug efficacy for as long as possible. The proportion of a parasite population that is not exposed to anthelmintic treatment is described as being "in refugia" and although many factors affect the rate at which resistance develops, levels of refugia are considered the most important as these parasites are not selected by treatment and so provide a pool of sensitive genes in the population. Accordingly, treatment should be avoided when pasture refugia are small because such treatments will place significant selection pressure for resistance on worm populations. Given this new paradigm for parasite control, it has become important to identify seasons and circumstances wherein refugia are diminished. Free-living stages of equine strongyles are highly dependent on climatic influences, and this review summarises studies of strongyle development and survival under laboratory and field conditions in Northern (cool) temperate, Southern (warm) temperate and subtropical/tropical climates. In Northern temperate climates, refugia are smallest during the winter. In contrast, refugia are lowest during the summer in warm temperate and subtropical/tropical climates. Although adverse seasonal changes clearly have significant effects on the ability of free living stages of strongyle nematode parasites to survive and develop, available data suggest that climatic influences cannot effectively "clean" pastures from one grazing season to the next.     

Faecal worm egg count analysis for targeting anthelmintic treatment in horses: Points to consider

Equine gastrointestinal nematodes are ubiquitous; in horses that graze contaminated pasture and that are not treated appropriately, large numbers of worms can accumulate, which can lead to serious clinical disease. Nematode control has traditionally followed interval treatment regimens, which involve regular anthelmintic administration to all horses based on the strongyle egg reappearance periods of each drug, usually defined around the time of licensing. Interval treatment programmes have resulted in substantial reductions in large strongyle disease, but have made major contributions to the development of anthelmintic resistance, particularly in cyathostomins. Cyathostomin resistance to 2 of the 3 available anthelmintic classes is widespread, and resistance to both classes in single populations is not uncommon. Reduced efficacy of the most commonly used macrocyclic lactone anthelmintics, as measured by shortened egg reappearance periods after treatment, is emerging in cyathostomins. Macrocyclic lactone resistance is also now commonly reported in Parascaris equorum on stud farms. Faecal worm egg counts (FWEC) are increasingly being used as part of targeted approaches to parasite control, whereby only those horses with moderate to high FWEC within a group are treated with an anthelmintic. The objective of this approach is to reduce environmental contamination, while leaving a proportion of the worm population in some horses unexposed to selection pressure for anthelmintic resistance. This article reviews recent findings in equine parasitology research that will underpin guidelines for control, with a particular focus on how to optimise the value of FWEC methodologies and anthelmintic efficacy analyses.     

Anthelmintic resistance of nematode parasites of small ruminants in eastern Ethiopia: exploitation of refugia to restore anthelmintic efficacy

Faecal egg count reduction tests (FECRT) were conducted in May 2003 to determine the efficacy of anthelmintics used for treatment against nematode parasites in separately managed sheep and goat flocks at Alemaya University in eastern Ethiopia. These tests revealed high levels of anthelmintic resistance to albendazole, tetramisole, the combination of these two drugs, and to ivermectin in the goat flock (predominantly infected by Haemonchus contortus and Trichostrongylus spp.), whereas all drugs were highly efficacious in the sheep flock. A second FECRT confirmed these observations. Following this, a new management system was implemented on the goat flock for a period of 9 months (January-September 2004) in an attempt to restore the anthelmintic efficacy. This involved a combination of measures: eliminating the existing parasite infections in the goats, exclusion from the traditional goat pastures, and introducing communal grazing of the goats with the university sheep flock and livestock owned by neighbouring small-holder farmers. A second series of FECRTs (Tests 3 and 4) conducted 7 months after this change in management, showed high levels of efficacy to all three drugs (albendazole, tetramisole and ivermectin) in the goat flock. This is the first field study to demonstrate that anthelmintic efficacy in the control of nematode parasites of small ruminants can be restored by exploiting refugia.     

Interaction of host physiology and efficacy of antiparasitic drugs

Antiparasitic drugs must be conducted to the parasite by the host and are therefore subject to physiological and biochemical processes in the host. Usually the efficacy of an antiparasitic drug will depend on a toxic concentration being presented to the parasite for sufficient time to lead to irreversible damage. Because many drugs are, in part, absorbed and transported to the site of the parasite by the circulatory system the area under the plasma concentration curve (AUC) may reflect availability of drug to the parasite and likely efficacy. A number of host physiological factors affect the AUC. Many anthelmintics are given orally as solids. Some absorption occurs in the rumen of ruminants, but many heterocyclic compounds such as the benzimidazoles require the low pH of the abomasum or gastric stomach to render them soluble. Certain disease states, including gastrointestinal parasitism, can cause the gastric pH to rise. This may in turn reduce solubility and absorption with resultant faster rate of excretion, particularly when accompanied by diarrhoea, and a reduced AUC. Once the anthelmintic has been absorbed, after oral or systemic administration, it is usually rapidly transported to the liver. The liver and adipose tissue may store the drug, releasing it over a period to produce a sustained effect as occurs with ivermectin, or it may rapidly metabolise it. A few anthelmintics, such as febantel, probably need to be metabolised in order to become active. However, more frequently the liver is involved in oxidation or reduction, followed by conjugation with sulfate, glucuronide or glutathione to render the drug more polar, to increase its molecular weight, inactivate it and facilitate its excretion. The rate of metabolism has been found to vary considerably between species and thus different dose rates and treatment are often required to achieve adequate antiparasite activity, with species such as deer, cattle and probably goats metabolising some anthelmintics faster than sheep. Some interesting possibilities for altering the absorption and metabolism of anthelmintics by the host may allow improved efficacy and reliability of antiparasite activity without necessarily increasing the dose rate of anthelmintic.     

The reported use of drugs to prevent diseases in beef cattle in Tennessee

The National Animal Health Monitoring System (NAHMS) (Round 2) for Tennessee collected baseline data on the preventive (as opposed to therapeutic) use of drugs from 60 beef cow-calf herds selected by a random, stratified, two-stage sampling plan. Counties were selected randomly with replacement for three herd-size strata, and herds were selected within countries by an area-frame method. Data were collected during monthly interviews for 1 year (1987–1988).

Tennessee beef cattle were medicated with 31 drugs to prevent diseases. The drugs most frequently used were anthelmintics and insecticides. The diseases against which preventive drugs were most frequently used were external parasites, intestinal parasites, ‘pink eye’ (keratoconjunctivitis), anaplasmosis, and respiratory infections. Ivermectin was the most frequently used anthelmintic and the most frequently used drug. Levamisole, fenbendazole, and thiabendazole were also frequently used anthelmintics. The most frequently used insecticides were the organophosphates (including fenthion, dichlorvos, and stirofos). Antimicrobials seldom were used, suggesting that prophylactic antimicrobial use in Tennessee beef cattle may not be a major public-health concern.     

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 rapid 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.