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1.
Křížová-Forstová V Lamka J Cvilink V Hanušová V Skálová L 《Research in veterinary science》2011,91(3):333-341
Benzimidazoles are frequently and widely used veterinary anthelmintics. Unfortunately, an administration of these anthelmintics does not always result in the expected therapeutic success. Many host-related factors modify pharmacokinetic behavior and efficacy of a chosen anthelmintic. Pharmacokinetics of anthelmintics varies among animals of different species, sex and age. Also diseases, medication, feed and environmental conditions can significantly affect behavior of anthelmintics and resultant drug efficacy in animals. The presented review gathers information, gained in last 20 years, on factors which bring about the variability in performance of benzimidazole anthelmintics in food-producing animals. It is focused particularly on differences in absorption and metabolism of these anthelmintics as these stages of the pharmacokinetic process seem to be the most important for the overall anthelmintic efficacy. The consequences of abnormalities and alterations in pharmacokinetics of benzimidazole anthelmintics are summarized and discussed. 相似文献
2.
《Research in veterinary science》2012,92(3):333-341
Benzimidazoles are frequently and widely used veterinary anthelmintics. Unfortunately, an administration of these anthelmintics does not always result in the expected therapeutic success. Many host-related factors modify pharmacokinetic behavior and efficacy of a chosen anthelmintic. Pharmacokinetics of anthelmintics varies among animals of different species, sex and age. Also diseases, medication, feed and environmental conditions can significantly affect behavior of anthelmintics and resultant drug efficacy in animals. The presented review gathers information, gained in last 20 years, on factors which bring about the variability in performance of benzimidazole anthelmintics in food-producing animals. It is focused particularly on differences in absorption and metabolism of these anthelmintics as these stages of the pharmacokinetic process seem to be the most important for the overall anthelmintic efficacy. The consequences of abnormalities and alterations in pharmacokinetics of benzimidazole anthelmintics are summarized and discussed. 相似文献
3.
Reinemeyer CR 《Veterinary parasitology》2012,185(1):9-15
Since 2002, selected populations of Parascaris equorum in several countries have been reported to survive treatment with macrocyclic lactone (M/L) anthelmintics. Clinical treatment failures are characterized by negligible fecal egg count reduction, but M/L resistance has been confirmed in ascarids by controlled efficacy testing. Resistance was selected by current parasite control practices for foals, which often include exclusive and excessively frequent use of M/L dewormers, thereby minimizing refugia within the host and in the environment. Chemical control of M/L-resistant isolates can be accomplished with pyrimidine and/or benzimidazole anthelmintics, but a few M/L-resistant populations have recently exhibited resistance to pyrantel pamoate as well. Some specimens of Oxyuris equi regularly survive treatment with macrocyclic lactones, but it is uncertain whether this constitutes resistance or merely confirms the incomplete oxyuricidal efficacy of virtually all broad spectrum equine anthelmintics. Variations in other biological parameters of Oxyuris and Parascaris, specifically atypical infection of older hosts and shorter prepatent periods, have been reported anecdotally. These changes may represent genetic modifications that have evolved in parallel with resistance as a result of anthelmintic selection pressure. 相似文献
4.
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. 相似文献
5.
Coles GC 《The Veterinary record》2002,151(6):165-169
It is suggested that the major factor in avoiding the development of anthelmintic resistance is the percentage of worms that do not encounter the anthelmintics (worms in refugia). This in turn is determined by the numbers of larvae on pasture, the percentage of animals treated and whether any stages in the host can avoid the action of anthelmintic. To maintain anthelmintic efficacy the percentage of worms in refugia must be sufficiently large. In cattle, this should involve treating only first-year animals and using a different pasture each year for calves. For sheep, only animals that have to be treated should be dosed with anthelmintic and clean grazing strategies that involve the use of anthelmintics should be avoided. For horses, reliance should be placed on the removal of faeces from pasture and only treating when the animals' condition requires it. Without a change in anthelmintic use there is the likelihood of increasing numbers of cases for which no anthelmintic is effective and animal welfare may be compromised. 相似文献
6.
The effects of anthelmintic drugs on intermediary metabolism of parasites can be examined using techniques developed for the investigation of metabolic regulation. Most attention has been paid to the pathways of respiratory metabolism in parasites, since maintenance of high energy levels is essential to an organism's survival. Respiratory metabolism is thus a prime target for anthelmintic attack. Parasites differ from their hosts in a number of pathways of respiratory metabolism and they produce incompletely-oxidised organic acids as end products.A variety of anthelmintic drugs have been shown to inhibit some enzymes of these pathways, including phosphoenolpyruvate carboxykinase, malate dehydrogenase, and the fumarate reductase, ‘succinoxidase’ and succinate decarboxylase systems. Energy synthesis in mitochondria from parasites is also inhibited by many anthelmintics: this target is a particularly important one since its properties differ significantly from those of the host. This process requires considerable study and it may not necessarily be valid to equate ‘uncoupling’ in mammalian tissues with that in parasite tissues. Changes in ATP levels affect flux through the respiratory pathways; a complete assessment of effects of anthelminstics on the respiratory pathways of parasites would include measurement of the uptake and utilization of carbon sources (e.g., glucose and glycogen), of metabolic intermediates, including adenine nucleotides, and of excreted end products. Sites of change can then be identified and studied in greater detail.Comparison of the effect of mebendazole in vivo and in vitro on unrelated species, Moniezia expansa and Fasciola hepatica adults, sheds some light on the mechanism of its anthelmintic effects. This drug elicits similar changes in proportions and totals of adenine nucleotides in the two species, but it differs in the rapidly of its effect, its effect on glucose uptake and glycogen depletion, and in changes in respiratory end product. Consequently mebendazole may not act in the same way against these two species. It also affects a number of other systems in other parasites: the suggestion of a single ‘mode of action’ may be inappropriate for this compound.Respiratory metabolism is not the only system affected by anthelmintics: other parasite systems are also attacked, but the final effect of lethal anthelmintic is observed as changes in the respiratory metabolic pathways. Some anthelmintics, for example, levamisole, affect the respiratory pathway directly, but also affect other systems (the nervous system in the case of levamisole) and may be effective in vitro but not in vivo. In these cases it is necessary to distinguish between effects that may be subordinate to a primary effect, and to take host and permeability factors into account. 相似文献
7.
Bartram DJ Leathwick DM Taylor MA Geurden T Maeder SJ 《Veterinary parasitology》2012,186(3-4):151-158
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. 相似文献
8.
J. B. Matthews 《Equine Veterinary Education》2008,20(10):552-560
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. 相似文献
9.
Resistance to benzimidazole anthelmintics in small strongyles (Cyathostominae) of horses in Denmark. 总被引：2，自引：0，他引：2
H. Bjrn Chr. Sommer H. Schougrd Sv. Aa. Henriksen P. Nansen 《Acta veterinaria Scandinavica》1991,32(2):253-260
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. 相似文献
10.
Ketzis JK Vercruysse J Stromberg BE Larsen M Athanasiadou S Houdijk JG 《Veterinary parasitology》2006,139(4):321-335
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. 相似文献
11.
G C Coles 《Veterinary parasitology》1988,27(1-2):89-96
Benzimidazole- and levamisole-resistant Ostertagia circumcincta from sheep have been reported from several countries, but there are no reports of anthelmintic-resistant O. ostertagi in cattle, where resistance has been confirmed in controlled trials. The reasons for this may include (1) the biology of the worm, (2) avoidance of drug action by inhibition, (3) host metabolism of drugs, (4) less anthelmintic used in cattle than in sheep, (5) high costs of controlled trials, (6) lack of adequate in vitro tests to detect resistant worms and (7) lack of reporting of anthelmintic failures. Reduced efficacy of the anthelmintics levamisole and thiabendazole to adult O. ostertagi and of modern benzimidazoles to the inhibited L4 larvae has been reported in cattle. This latter effect might, in part, represent a stage-specific expression of resistance. Although anthelmintic resistance in O. ostertagi is not known to be a problem at present, it could potentially become a serious issue. 相似文献
12.
von Samson-Himmelstjerna G 《Veterinary parasitology》2012,185(1):2-8
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. 相似文献
13.
Sánchez Bruni SF Fusé LA Moreno L Saumell CA Alvarez LI Fiel C McKellar QA Lanusse CE 《Equine veterinary journal》2005,37(3):257-262
REASONS FOR PERFORMING THE STUDY: The study of novel pharmacological strategies to control parasitism in horses is required since many parasite species have developed resistance to anthelmintic drugs. OBJECTIVES: To evaluate the effects of piperonyl butoxide (PB) (a metabolic inhibitor) on the plasma availability and enantiomeric behaviour of oxfendazole (OFZ) given orally to horses, and to compare the clinical efficacy of OFZ given either alone or co-administered with PB in naturally parasitised horses. METHODS: Fifteen naturally parasitised crossbred male ponies were allocated into 3 groups (n = 5) and treated orally as follows: Group I (control) received distilled water as placebo; Group II was dosed with OFZ (10 mg/kg bwt); and Group III was treated with OFZ (10 mg/kg bwt) co-administered with PB (63 mg/kg bwt). Jugular blood samples were obtained over 120 h post treatment. Three weeks after treatments, all experimental horses were subjected to euthanasia. RESULTS: The observed maximum plasma concentration (Cmax) and area under the concentration vs. time curve (AUC) values for OFZ increased 3- and 5-fold, respectively, in the presence of PB. The plasma concentration profiles of fenbendazole (FBZ), a metabolite generated from OFZ, were significantly lower after the treatment with OFZ alone (AUC = 0.8 microg x h/ml) compared to those obtained after the OFZ + PB treatment (AUC = 2.7 microg x h/ml). The enhanced pharmacokinetic profiles correlated with increased anthelmintic efficacy. The combination OFZ + PB showed 100% efficacy against mature nematode parasites. The efficacy against cyathostome L3 larvae increased from 94% (Group II) to 98.7% (Group III). Consistently, the number of L4 larvae recovered from OFZ + PB treated horses (Group III) (n = 146) was significantly lower (P<0.05) than that recovered from Group II (n = 1397). CONCLUSIONS: The use of PB as a metabolic inhibitor may be useful to enhance OFZ activity against mature and migrating larvae of different parasite species in horses. POTENTIAL RELEVANCE: Metabolic inhibitors may be used to enhance the activity of benzimidazole anthelmintics and extend the effective lifespan of benzimidazole drugs in the face of increasing resistance. 相似文献
14.
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. 相似文献
15.
Voigt K Scheuerle M Hamel D Pfister K 《Tier?rztliche Praxis. Ausgabe G, Grosstiere/Nutztiere》2012,40(2):107-111
High perinatal mortality, low milk yields and occasional ewe deaths were investigated in a Dorper sheep flock in Southern Germany. Parasitic gastroenteritis due to Trichostrongylus spp. associated with severe weight loss despite regular anthelmintic treatments of the flock was identified as the underlying cause. A faecal egg count reduction (FECR) test revealed zero reduction after treatment with ivermectin or albendazole, respectively, and a FECR of 57.9% following treatment with levamisole. These results indicate a lack of, or considerably reduced efficacy of substances from all three classical groups of anthelmintics and demonstrate that triple anthelmintic resistance is also present in Germany. The introduction of resistant worm populations with imported livestock, excessive use of anthelmintic drugs and under-dosing of goats have possibly led to the problem in the flock described. Veterinary advice on anthelmintic treatments and responsible parasite control programmes are therefore crucial in small ruminant flocks. 相似文献
16.
Helminth infections are an important cause of lost productivity in livestock world-wide, often necessitating anthelmintic treatment. However, a large part of the anthelmintics are used indiscriminately because the parasite levels are too low to justify treatment or because the treatments are not correctly programmed, resulting in undertreatment or overtreatment. The objective of this paper is to discuss possible thresholds for anthelmintic treatment of some of the more important helminth infections in livestock, i.e. gastrointestinal nematodes, lungworms and liver fluke, to promote a more appropriate use of anthelmintics. When possible, a distinction is made between therapeutic thresholds, production-based thresholds and preventive thresholds. A "therapeutic threshold" is intended to identify (an) animal(s) with parasite levels that necessitate immediate treatment. The therapeutic threshold is basically the diagnosis of clinical disease, and can be determined relatively easily for the parasites discussed in this paper. A "production-based threshold" is intended to measure the effects of sub-clinical parasitism on productivity parameters, such as weight gain and milk yield, before clinical disease occurs. Finally, a "preventive threshold" is meant to predict future infection levels, to enable the application of appropriate control measures. 相似文献
17.
Swarnkar CP Sanyal PK Singh D Khan FA Bhagwan PS 《Veterinary research communications》1998,22(8):545-551
The pharmacokinetics of albendazole was studied in sheep following single oral and intraruminal administration at nematocidal dose rates. The disposition curves of its metabolites indicated increased uptake of the drug in sheep following intraruminal as compared to oral dosing (p<0.05). The increased bioavailability of benzimidazole anthelmintics given by the intraruminal route could be exploited for optimizing the use of anthelmintic for sustained parasite control in small ruminants. 相似文献
18.
A survey was undertaken to assess the prevalence of anthelmintic resistance in sheep nematode populations on 40 commercial farms distributed throughout the central tablelands of New South Wales. Representatives of the 2 major groups of broad spectrum anthelmintics with different modes of action (thiabendazole and levamisole) were used at the manufacturer's recommended dose rates. Efficacy was assessed on the basis of the reduction in faecal strongyle egg counts 7 days after treatment. An efficacy of less than 90% using both anthelmintics was obtained on 4 farms. Thiabendazole had an efficacy of less than 90% on a further 21 farms and levamisole had an efficacy of less than 90% on an additional 4 farms. There was no evidence of anthelmintic resistance on 8 farms, while the remaining 3 had insignificant parasite burdens. Based on larval cultures from faeces, Ostertagia and Trichostrongylus were the most significant species in resistant populations. Haemonchus burdens were sporadic and levels of resistance relatively low. Nematodirus burdens were widespread but no evidence of resistance was detected. 相似文献
19.
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. 相似文献
20.
This paper describes the nematode control strategy adopted by a Scottish hill sheep farmer. It provides an example of the limited use of anthelmintic drugs, targeted towards control of the periparturient rise in faecal nematode egg output in ewes and exploitation of grazing management, resulting in limited exposure of naive sheep to infective larvae on pasture. Resistance to benzimidazole, imidazothiazole and macrocyclic lactone anthelmintics, and to a combination of a macrocyclic lactone and imidazothiazole anthelmintic drugs was diagnosed. The targeted use of a persistent anthelmintic drug to control a periparturient rise in faecal nematode egg output in ewes may be unnecessary and selects strongly for resistance when the reservoir of anthelmintic-susceptible nematodes in refugia is small at the time of treatment. However, the use of a persistent anthelmintic drug in a selective proportion of ewes can be important and probably does not select strongly for resistance when the reservoir of anthelmintic-susceptible nematodes in refugia is large at the time of treatment. The former circumstances might arise on many Scottish hill sheep farms, whereas the latter may occur on upland and lowground farms, depending on previous grazing management, anthelmintic use and winter weather conditions. These factors must be taken into account when preparing sustainable health plans for nematode parasite control in individual sheep flocks. 相似文献