Anthelmintic resistance in New Zealand

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

Management of gastrointestinal nematode parasites on sheep farms in New Zealand

AIM: To report current farmer opinions and farming practices relating to control of gastrointestinal nematodes and anthelmintic resistance on sheep farms in New Zealand. METHODS: An interview-based cross-sectional study of grazing management and anthelmintic usage was conducted by veterinarians on 80 randomly selected sheep farms in New Zealand. RESULTS: Useable data were returned by 74/80 (92%) farmers who participated in the study. However, despite contacting 400 farmers the target sample size of 100 farms was not reached. The results indicated that only 31% of farms had previously tested for drench resistance, that effective quarantine-drenching of imported stock was not always carried out, and that farmers were more likely to integrate cattle than ewes into their grazing management of lambs. Furthermore, the number of drenches given to lambs had changed little in 25 years. The use of faecal egg counting by farmers has increased. CONCLUSIONS: Dependence on anthelmintics continues to be high on sheep farms in New Zealand. Whilst the number of drench treatments has changed little, there is more widespread use of persistent or long-acting treatments. Farmers need to be encouraged to monitor the resistance status of nematode populations on their farms and use this information to develop strategies aimed at maintaining susceptible alleles within the parasite populations and conserving the efficacy of existing drug families.     

Management of gastrointestinal nematode parasites on sheep farms in New Zealand

AIM: To report current farmer opinions and farming practices relating to control of gastrointestinal nematodes and anthelmintic resistance on sheep farms in New Zealand.

METHODS: An interview-based cross-sectional study of grazing management and anthelmintic useage was conducted by veterinarians on 80 randomly selected sheep farms in New Zealand.

RESULTS: Useable data were returned by 74/80 (92%) farmers who participated in the study. However, despite contacting 400 farmers the target sample size of 100 farms was not reached. The results indicated that only 31% of farms had previously tested for drench resistance, that effective quarantine-drenching of imported stock was not always carried out, and that farmers were more likely to integrate cattle than ewes into their grazing management of lambs. Furthermore, the number of drenches given to lambs had changed little in 25 years. The use of faecal egg counting by farmers has increased.

CONCLUSIONS: Dependence on anthelmintics continues to be high on sheep farms in New Zealand. Whilst the number of drench treatments has changed little, there is more widespread use of persistent or long-acting treatments. Farmers need to be encouraged to monitor the resistance status of nematode populations on their farms and use this information to develop strategies aimed at maintaining susceptible alleles within the parasite populations and conserving the efficacy of existing drug families.     

A survey of helminth control practices on sheep farms in Great Britain and Ireland

A telephone survey of 600 farmers throughout Great Britain and Ireland was conducted in order to characterise helminth control practices, and identify factors correlated with perceived anthelmintic failure. Overall, 93% of surveyed farmers routinely treated their sheep against nematodes, 67% against liver fluke and 58% against tapeworms. Anthelmintic resistance in nematodes was perceived by farmers to be present on 10% of farms. Farmers who dosed ewes at mating were more likely to have observed anthelmintic failure, than those who were aware of national guidelines on parasite control. However, objective assessment of anthelmintic efficacy had only been undertaken on 19% of farms. Ewes were treated at mating and lambing on 63% and 62% of farms, respectively. On average, lambs were treated 3.6 times annually, depending on geographical region and on dates of lambing and finishing. Although 'quarantine' treatments were widely administered to bought-in stock, these were appropriately applied in only 3% of cases. This study provides baseline data against which the impact of future anthelmintic information campaigns can be assessed; it will facilitate the development of rational, farm-level mathematical models in support of sustainable parasite control, and will aid in the design of farm management practices that prolong the effective lifespan of novel classes of anthelmintic.     

Managing anthelmintic resistance: Is it feasible in New Zealand to delay the emergence of resistance to a new anthelmintic class?

The recent registration in New Zealand of the first new class of broad-spectrum anthelmintic, for use against nematode parasites of ruminants, in nearly three decades has raised the possibility that parasite management practices could be improved to minimise the emergence of resistance to the new drug. A review of knowledge pertaining to the selection of anthelmintic resistance in nematode parasites of sheep highlights a number of management practices which could be altered to achieve this.

A number of previously common practices such as whole-flock treatment of adult ewes around lambing, and treatment of lambs as they are moved onto pastures with low parasite contamination have been clearly identified as high risk for selecting resistant parasites. Once high-risk practices have been identified steps can be taken to either eliminate their use or mitigate the associated risk. Much of the focus on the management of resistance around the world is on the retention of susceptible genotypes in refugia. While approaches to retaining unselected parasites are likely to vary around the world, empirical studies indicate that the practice is likely to be effective at slowing the development of resistance. The challenge for farmers and advisors will be to strike a balance between retaining sufficient susceptible para-sites to usefully delay the development of resistance while not unduly compromising animal performance and farm profitability. The merits of combining different classes of anthelmintic in order to slow the development of resistance remains somewhat contentious in some countries. However, the attributes of oral anthelmintics are such that they seem likely to meet most, if not all, of the criteria for combinations to be highly effective at slowing the build-up of resistance in nematode parasites.

It is evident that considerable progress has been made in understanding the factors involved in selecting anthelmintic-resistant nematodes since the last broad-spectrum anthelmintic class was released in the early 1980s. Therefore, it should be possible to manage a new class of anthelmintic in such a way as to significantly extend its effective life. The challenge is likely to be in convincing farmers of the merits of adopting such pro-active strategies.     

Frequent deworming in horses; it usually does not do any good, but it often harms

Due to excessive and inappropriate use of dewormers anthelmintic resistance has developed as a significant problem in horse parasites in the Netherlands. Since it is unlikely that new classes of anthelmintics against horse nematodes will be introduced in the near future, it is important to use the present drugs wisely. Veterinarians should advice horse owners about worm control programs with a more targeted approach. The number of anthelmintic treatments should be reduced and, through selective anthelmintic treatments, further development of anthelmintic resistance should be delayed. Preferably, horses with a low faecal egg count should not be treated at all to ascertain a reduction of the selection pressure for anthelmintic resistance. The propensity for low faecal egg counts is hereditary. This implies that mature horses with consistent low egg counts can be detected by faecal examination and that it is not necessary to repeat faecal examination each time in these animals. New horses on the farm should always be dewormed on arrival and should be introduced only after the efficacy of treatment has been determined. Anthelmintic resistance can also be introduced with the arrival of a new animal that is infected with drug-resistant parasites.     

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.     

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.     

Anthelmintic resistance and management of nematode parasites on beef cattle-rearing farms in the North Island of New Zealand

AIM: To provide information on current farmers' opinions and farming practices thought to be related to anthelmintic resistance, and to test for associations between the presence of anthelmintic resistance and management practices on beef-cattle rearing farms in the North Island of New Zealand. METHODS: A study using an interview-based questionnaire about management of internal parasites was conducted on 62 beef cattle-rearing farms in the North Island of New Zealand, using case-control analyses to test for associations between management practices and the presence or absence of resistance to ivermectin or albendazole. Resistance was inferred from faecal nematode egg count (FEC) reduction (FECR) tests (FECRTs) when there was <90% reduction in FEC 7-10 days after treatment of calves <12 months of age. RESULTS: Of the 59 farmers who completed the questionnaire, most (n=40) ranked parasites highly, and at about the same level as quality and quantity of feed, as important production-limiting factors for their enterprises. In contrast, anthelmintic resistance was not perceived to be a problem on 13 farms, and its importance was rated low on 24, moderate on 15, and high on only six farms. Despite all farms having planned parasite control programmes, there was heavy reliance on clinical signs of parasitism to determine frequency of treatments. About one in three farmers with beef breeder cows routinely treated their calves at marking, one in five treated mixed-age cows, and almost half treated rising 2-year-old cows before calving. One in four farmers used anthelmintics on calves on 8-12 occasions in their first year of life. Co-grazing with other species was rare, but follow-on grazing within 3 months after older cattle or sheep was common. On most farms, grazing cattle was restricted to part of the farm, a finding with implications for parasite control and persistence of larvae in refugia. Macrocyclic lactone (ML) anthelmintics or their combinations with other action families were currently, and for the past 5 years, used more frequently than benzimidazoles and levamisole, and benzimidazole-levamisole combinations. The prevalence of resistance to ivermectin was high (82%) and no plausible model of associations could be constructed from the data. The prevalence of resistance to albendazole was 60%, and the risk of resistance increased as the number of rising 1-year-old cattle present mid-winter increased, and decreased as the number of breeding cows >2 years old present mid-winter increased. CONCLUSION: It is clear that in practice anthelmintic resistance is a secondary consideration to obtaining productivity advantages from the use of anthelmintics in beef cattle. Farmers' opinions were divided on many issues and the overall impression was of confused and diverse thinking regarding the principles of the use of anthelmintics. The overall outlook regarding anthelmintic resistance in cattle is bleak unless the need for integrated and long-term research activities is acted upon soon.     

Prevalence of anthelmintic resistance on sheep farms in New Zealand

AIM: To establish the prevalence of anthelmintic resistance in parasitic nematodes on sheep farms in New Zealand. METHODS: A cross-sectional prevalence study was conducted, using a standardised faecal nematode egg count (FEC) reduction (FECR) test (FECRT) for ivermectin, at a full (0.2 mg/kg) and half (0.1 mg/kg) dose rate, and albendazole, levamisole and albendazole-levamisole in combination, on 60 lambs (n=10 per group) on farms selected from throughout New Zealand. Farms that conformed with selection criteria were chosen at random (n=80) or with a history of suspected resistance to macrocyclic lactone (ML) anthelmintics (n=32). Resistance to an anthelmintic was inferred when there was <95% reduction in FEC 7-10 days after treatment. Larval cultures were performed for all control groups and for treated groups for which resistance was evident. RESULTS: Of the farms randomly selected, 36% showed > or =95% FECR for all anthelmintics tested; resistance to ivermectin at 0.1 and 0.2 mg/kg liveweight was evident on 36% and 25% of these farms, respectively. Resistance to both ivermectin (0.2 mg/kg) and levamisole was evident on 8/80 (10%) farms, to ivermectin and albendazole on 10/80 (13%) farms, and to ivermectin, levamisole and albendazole on 6/80 (8%) farms. The prevalence of resistance to a half dose of ivermectin tended to be more prevalent on farms with a history of suspected ML resistance (p=0.06). Resistance to albendazole was seen across all the main parasite genera, and to levamisole in Nematodirus, Ostertagia (= Teladorsagia) and Trichostrongylus species. Resistance to ivermectin was dominated by Ostertagia spp, although Cooperia, Nematodirus and Trichostrongylus species were also implicated. CONCLUSION: Anthelmintic resistance in parasitic nematodes of sheep is common in New Zealand. Not only was resistance to albendazole and levamisole common, but resistance to the ML, ivermectin, was at a higher prevalence than expected. Sheep farmers and advisors in New Zealand need to re-evaluate the way they manage parasites, and more research is urgently needed if the steady decline in anthelmintic susceptibility is to be halted.     

Anthelmintic resistance and management of nematode parasites on beef cattle-rearing farms in the North Island of New Zealand

AIM: To provide information on current farmers’ opinions and farming practices thought to be related to anthelmintic resistance, and to test for associations between the presence of anthelmintic resistance and management practices on beef cattle- rearing farms in the North Island of New Zealand.

METHODS: A study using an interview-based questionnaire about management of internal parasites was conducted on 62 beef cattle-rearing farms in the North Island of New Zealand, using case-control analyses to test for associations between management practices and the presence or absence of resistance to ivermectin or albendazole. Resistance was inferred from faecal nematode egg count (FEC) reduction (FECR) tests (FECRTs) when there was <90% reduction in FEC 7-10 days after treatment of calves <12 months of age.

RESULTS: Of the 59 farmers who completed the questionnaire, most (n=40) ranked parasites highly, and at about the same level as quality and quantity of feed, as important production-limiting factors for their enterprises. In contrast, anthelmintic resistance was not perceived to be a problem on 13 farms, and its importance was rated low on 24, moderate on 15, and high on only six farms. Despite all farms having planned parasite control programmes, there was heavy reliance on clinical signs of parasitism to determine frequency of treatments. About one in three farmers with beef breeder cows routinely treated their calves at marking, one in five treated mixed-age cows, and almost half treated rising 2-year-old cows before calving. One in four farmers used anthelmintics on calves on 8–12 occasions in their first year of life. Co-grazing with other species was rare, but follow-on grazing within 3 months after older cattle or sheep was common. On most farms, grazing cattle was restricted to part of the farm, a finding with implications for parasite control and persistence of larvae in refugia. Macrocyclic lactone (ML) anthelmintics or their combinations with other action families were currently, and for the past 5 years, used more frequently than benzimidazoles and levamisole, and benzimidazole-levami- sole combinations. The prevalence of resistance to ivermectin was high (82%) and no plausible model of associations could be constructed from the data. The prevalence of resistance to albendazole was 60%, and the risk of resistance increased as the number of rising 1-year-old cattle present mid-winter increased, and decreased as the number of breeding cows >2 years old present mid-winter increased.

CONCLUSION: It is clear that in practice anthelmintic resistance is a secondary consideration to obtaining productivity advantages from the use of anthelmintics in beef cattle. Farmers’ opinions were divided on many issues and the overall impres- sion was of confused and diverse thinking regarding the principles of the use of anthelmintics. The overall outlook regarding anthelmintic resistance in cattle is bleak unless the need for integrated and long-term research activities is acted upon soon.     

A questionnaire study on parasite control practices on UK breeding Thoroughbred studs

Reasons for performing study: Improved education of veterinarians and equine owners/managers is essential in implementing parasite control strategies that are less reliant on chemicals. Methods: This questionnaire study, conducted on 61 UK Thoroughbred (TB) establishments during 2009 and 2010, was designed to obtain an understanding of current helminth control practices on studs. To our knowledge, this is the first occasion that statements obtained from TB studs via questionnaire have been supported by statistical analysis. Results: Despite many respondents indicating high levels of concern regarding anthelmintic resistance, 56% of these establishments that received visiting equines co‐grazed these animals with permanent stock and <74% administered anthelmintics prior to integration. In the 12 months preceding the study, most respondents administered frequent macrocyclic lactone (ML) treatments, with none appearing to leave any animals in groups untreated at each administration. Indiscriminate whole group treatments with MLs and movement of animals to ‘clean grazing’ post treatment (reported by >25% of respondents), indicates that many stud owners/managers are not aware of the strong risk factors for the development of anthelmintic resistance. Few studs had conducted faecal egg count (FEC) analysis in the past and only 22% indicated that they considered this form of analysis beneficial in determining anthelmintic choice. Conclusions and potential relevance: The challenge now is to convince stud owners/managers to deviate from their current practices to control strategies that are more likely to preserve anthelmintic efficacy. Veterinarians need to get more involved in implementing these control strategies, with better emphasis placed on the role of diagnostic tests in facilitating targeted treatments and in investigating anthelmintic sensitivity in the associated nematode populations.     

The comparative efficacy of abamectin, monepantel and an abamectin/derquantel combination against fourth-stage larvae of a macrocyclic lactone-resistant Teladorsagia spp. isolate infecting sheep

Anthelmintic resistance by gastrointestinal nematodes of sheep continues to be an issue of global interest. While the recent introduction in some countries of one or two new anthelmintic classes (amino-acetonitrile derivatives [AAD] and spiroindoles [SI]) has been welcomed, it is important that there is no relaxation in parasite control and the management of drug resistance. Monepantel (an AAD) was the first new anthelmintic to be approved for use (New Zealand, 2009) and was followed a year later in the same country by a combination of derquantel (a SI) and abamectin. The present study determined the efficacy of the new anthelmintic products and abamectin against fourth-stage larvae of macrocyclic lactone-resistant Teladorsagia spp. in lambs. Efficacies were calculated by comparing post-mortem nematode burdens of treated animals with those of untreated control sheep, and were 98.5, 86.3 and 34.0% for monepantel, abamectin/derquantel and abamectin, respectively. The nematode burdens of monepantel- and abamectin/derquantel-treated sheep were significantly lower than those sheep treated with abamectin and the untreated controls. Similarly, the burden of the monepantel group was significantly lower than that of the abamectin/derquantel group. These findings provide an opportunity to reinforce the recommendation that farmers and animal health advisors need to know the resistance status of nematode populations on subject farms to ensure effective control programs are designed and implemented. Such control programs should include an appropriate choice of anthelmintic(s), monitoring parasite burdens for correct timing of treatments, and pasture management to reduce larval challenge balanced with the maintenance of drug-susceptible populations in refugia.     

Slowing the spread of anthelmintic resistant nematodes of sheep and goats in the United Kingdom.

Anthelmintic resistant nematodes pose an increasing threat to animal welfare and lamb production on lowland sheep farms in the United Kingdom. Based on published information on anthelmintic resistance in nematodes and insecticide resistance in arthropods, seven recommendations are made for reducing the development and spread of anthelmintic resistant nematodes. The two most important are probably to prevent the introduction of resistant worms through the purchase of stock and to reduce the reliance on frequent anthelmintic treatments by using epidemiological principles of nematode control.     

RESISTANCE TO BENZIMIDAZOLE ANTHELMINTICS IN EQUINE STRONGYLES

A survey was conducted to determine whether benzimidazole resistant populations of equine strongyles are present in New South Wales and north central Victoria; what is their frequency and geographical distribution; which species are involved; and whether different methods of parasite control could be related to the occurrence and frequency of anthelmintic resistant populations. Resistant populations of strongyles were found over wide areas of New South Wales and in north central Victoria. There was no relationship between geographical location and the occurrence of benzimidazole resistance. The species involved were small strongyles of the sub-family Cyathostominae. There was a direct correlation between the occurrence of resistance (including the level at which it is present) and the frequency of use of benzimidazole anthelmintics. Examination of management practices showed that resistance is not an important problem on farms where different chemical classes of anthelminitcs were used in a slow rotation programme; combination anthelmintic therapy (for example, benzimidazole/piperazine/organophosphates) was used and anthelmintic treatment was given at intervals of not less than 16 weeks. Tentative suggestions are made for the control of small strongyles in the light of an emerging resistance problem.     

Recent developments in the management of anthelmintic resistance in small ruminants – an Australasian perspective

Abstract

There have been a number of significant advances in recent years to the theory and practice of managing anthelmintic resistance in sheep in Australasia. The general principles of resistance management are, firstly identification and mitigation of high-risk practices, secondly using effective anthelmintics, and thirdly maintaining a refuge of unselected parasites. The first of these principles has been updated recently with the findings from a series of farm-based trials in New Zealand, in which the economic benefits of both short- and long-acting anthelmintic treatments in ewes pre-lambing were found to be inconsistent and not always positive. There have also been significant changes to the second principle, particularly given the introduction of new active families onto the market. Evidence continues to favour the use of combination products to maximise efficacy and delay the onset of treatment-failure. Many farmers have readily accepted the effectiveness of maintaining a refuge of unselected parasites; the challenge for researchers and advisers is now to improve adoption of properly designed and implemented resistance management programmes. A recently completed education programme in New Zealand has demonstrated that when this is achieved, then anthelmintic resistance can be controlled, and in many cases reduced in severity.     

Resistance to moxidectin and abamectin in naturally acquired Ostertagia circumcincta infections in sheep

AIM: To investigate the occurrence of resistance to macrocyclic lactone (ML) anthelmintics by Ostertagia circumcincta in lambs on a sheep and cattle property in the North Island of New Zealand. METHODS: Thirty lambs were randomly allocated to one of five equal-sized groups, consisting of an untreated control and four treatment groups. The treatments, which were administered at the manufacturer's recommended dose rates, included oral moxidectin, oral abamectin (both at 0.2 mg/kg), an albendazole-levamisole combination, and an albendazole-levamisole-ivermectin combination. Post mortem worm counts were undertaken 7 days after treatment to determine the efficacy of each anthelmintic. RESULTS: The albendazole-levamisole and albendazole-levamisole-ivermectin combinations both reduced O. circumcincta burdens to zero whereas for moxidectin and abamectin efficacies of only 72% and 29%, respectively, were recorded. CONCLUSIONS: These results clearly demonstrated the occurrence of resistance to MLs by O. circumcincta. Although this is not the first occasion where resistance to this anthelmintic family has been detected in this parasite in sheep in New Zealand, it is the first instance that resistance to either moxidectin or abamectin has been reported.     

Modelling the benefits of a new class of anthelmintic in combination

Since 2009 two new classes of anthelmintics have been registered for use in sheep in New Zealand. This raises challenging questions about how such new actives should be used, not only to minimise the development of resistance to them, thereby ensuring their availability as effective treatments for as long as possible, but also to minimise the further development of resistance to the other anthelmintic classes. One strategy which appears to offer considerable potential for slowing the development of resistance is the use of combinations of different anthelmintic classes, although this approach remains contentious in some countries. The potential benefit of using anthelmintics in combination is particularly relevant to two recently released anthelmintic compounds because one, monepantel, is presently only available as a single active product while the other, derquantel, is only available in combination with abamectin. A simulation modelling approach was used to investigate the potential benefits of using anthelmintics in combination. The rate at which resistance develops to a new 'active' when used alone was compared to an equivalent compound used in combination with a second compound from an alternative class (in this case, abamectin), when various levels of resistance occur to the second active. In addition, the potential of a new active to reduce further development of resistance to the second compound in the combination was evaluated. Finally, the use of combinations as compared to sequential or rotational use patterns, in the presence of side resistance between two actives was investigated. The modelling simulations suggest a significant advantage to both compounds when they are used in combination, especially if both initially have high efficacy. The development of resistance to the new active was delayed, although to a lesser extent, even when the efficacy of the second active in the combination was only 50%. Under a 'low-refugia' management environment resistance to all actives developed more rapidly, and the advantage of using actives in combination was reduced. When used in conjunction with other resistance management strategies, a combination containing a new active prevented further development of resistance to the older class. Using actives in combination was superior to using them individually either sequentially or in rotation, even in the presence of side-resistance between the two anthelmintic classes.     

Will technology provide solutions for drug resistance in veterinary helminths?

Drug resistance in veterinary helminths affects a growing number of livestock producers on a global basis. The parasites infecting the major species of livestock are presently showing resistance in varying degrees to the commonly used classes of anthelmintics. The degree and extent of this problem especially with respect to multidrug resistance (MDR) in nematode populations is likely to increase. Finding solutions to the spread of resistance requires knowledge of the drugs' modes of action and mechanisms of resistance. This knowledge can then be applied to detect and monitor the state of resistance. Here we present a brief overview of resistance mechanisms and some of the technologies being used to study them. We also discuss some of the strategies for slowing the spread of resistance. The issue of reversal of drug resistance is analysed under consideration of recent progress in the field of MDR reversal in non-infectious diseases. Finally, we propose an application of currently available technologies that could assist in the detection and monitoring of anthelmintic resistance. Taking into account the significant complexity of the genetic mechanism of anthelmintic resistance in and between the various species, we suggest to undertake a co-ordinated effort to systematically identify anthelmintic-related single nucleotide polymorphisms (SNPs) in the most important helminth parasites. Monitoring the state of resistance in field populations could be achieved with a SNP-based protocol for genotyping the many genes known or suspected to contribute to the modes of action or mechanisms of resistance to the various classes of anthelmintics. If significant associations between genotypes and phenotypes exist within a species, then a single test with sufficient SNPs could potentially have universal applicability. These could then be explored for the development of new molecular diagnostic procedures. New classes of anthelmintics are needed, but until they are developed and available to the producers, technology can assist to achieve the goal of better sustainability in anthelmintic usage.     

Use of anthelmintics by New England sheep producers

Six hundred and sixty-five New England sheep producers responded to a postal survey on management practices, anthelmintic use, and the perceived failure of anthelmintics to control nematodes. Although the average farm had 34.8 lambs and 29.8 stock sheep, 59.8% and 50.3% of the total number of lambs and stock sheep were on 16.5% of the farms, which had greater than 50 lambs. About 54% of the lambs were born in January and February. Spring markets and confinement rearing were popular, as only 45.7% of the total lambs grazed summer pasture. Most producers (81.5%) treated their stock sheep (and lambs) for nematodiasis 2 to 4 times per year (mean, 3.3), generally before lambing, before pasturing, midsummer, and/or before breeding. Only 27.5% of the producers indicated distinct drenching management for grazing lambs. There was little use of preventive control, such as spring prophylaxis (0.5%) or dosing in midsummer and moving animals to safe pasture (2.9%). More than one anthelmintic class was used on 59.6% of the farms, with a mean of 1.88 anthelmintics per farm. Though 53.7% of the producers had a policy of alternating anthelmintic classes within a year, only 11.6% alternated anthelmintics annually. Levamisole and thiabendazole were the anthelmintics most frequently used by 81.8% and 61.6% of producers, respectively. However, 26.5% and 16.2% of the farms used fenbendazole and phenothiazine, respectively. The presence of gastrointestinal nematode resistance to anthelmintics was suggested, because 35.4% of the producers had discontinued using at least one anthelmintic that they considered to be ineffective. The anthelmintic that was most frequently discontinued was thiabendazole.(ABSTRACT TRUNCATED AT 250 WORDS)