Brown Besier

This guideline is aimed at those who are involved in the assessment of anthelmintic efficacy in ruminant livestock species (bovine, ovine and caprine). The intent is to provide a framework that can be adopted worldwide for the testing of anthelmintics in ruminants, such that studies carried out in different countries can be compared and thereby unnecessary duplication can be reduced. Recommendations are made for the selection, housing and feeding of study animals, the type of studies required, the method used to conduct those studies, the assessment of results and the standards for defining anthelmintic efficacy.

Diarrhoea is a common, widespread and frustrating reality for sheep enterprises in most sheep producing regions globally and of particular concern in Australia as the major risk factor for breech flystrike. Parasitic disease has long been recognised as an important factor in diarrhoea in sheep, particularly the gastrointestinal nematodes (Trichostrongylus and Teladorsagia species). This review focuses on the role of parasitic infections in causing diarrhoea in sheep, with emphasis on the epidemiology of diarrhoea outbreaks related to worms and opportunities to manage the risk of diarrhoea outbreaks in sheep related to parasitic infections. Parasitic nematodes damage the gastrointestinal tract via a complex relationship between direct impacts from worms, such as physical changes to the gut mucosa, and indirect effects largely associated with the host response. Diarrhoea associated with large worm burdens is most efficiently managed through integrated parasite management programs. Despite some limitations, measuring faecal worm egg counts remains a mainstay for assessing the contribution of worms to outbreaks of diarrhoea in sheep. Larval hypersensitivity scouring is emerging as a significant cause of worm-related diarrhoea in sheep without large adult worm burdens in some geographic locations. The syndrome describes a heightened inflammatory response to the ingestion of trichostrongylid infective larvae seen in the gut of sheep with diarrhoea, and is most effectively addressed through selecting sheep for low breech soiling (‘dag scores’), as worm resistant sheep may show an increased propensity for diarrhoea, even with low rates of larval challenge. Importantly, dag should be considered as a separate trait to WEC in breeding indexes. Outbreaks of diarrhoea in young sheep are often multifactorial, and co-infections with nematodes and other infectious agents associated with diarrhoea are common. This presents challenges for the field investigation of diarrhoea in grazing sheep.

This study utilised computer simulation modelling (Risk Management Model for Nematodes) to investigate the impact of different parasite refugia scenarios on the development of anthelmintic resistance and worm control effectiveness. The simulations were conducted for adult ewe flocks in a Mediterranean climatic region over a 20 year time period. Factors explored in the simulation exercise were environment (different weather conditions), drug efficacy, the percentage of the flock left untreated, the timing of anthelmintic treatments, the initial worm egg count, and the number of drenches per annum. The model was run with variable proportions of the flock untreated (0, 10, 20, 30, 40 and 50%), with ewes selected at random so that reductions in the mean worm burden or egg count were proportional to the treated section of the flock. Treatments to ewes were given either in summer (December; low refugia potential, hence highly selective) or autumn (March; less selective due to a greater refugia potential), and the use of different anthelmintics was simulated to indicate the difference between active ingredients of different efficacy. Each model scenario was run for two environments, specifically a lower rainfall area (more selective) and a higher rainfall area (less selective) within a Mediterranean climatic zone, characterised by hot, dry summers and cool, wet winters. Univariate general linear models with least square difference post-hoc tests were used to examine differences between means of factors. The results confirmed that leaving a proportion of sheep in a flock untreated was effective in delaying the development of anthelmintic resistance, with as low as 10% of a flock untreated sufficient to significantly delay resistance, although this strategy was associated with a small reduction in worm control. Administering anthelmintics in autumn rather than summer was also effective in delaying the development of anthelmintic resistance in the lower rainfall environment where all sheep were treated, although the effect of treatment timing on worm control effectiveness varied between the environments and the proportion of ewes left untreated. The use of anthelmintics with higher efficacy delayed the development of resistance, but the initial worm egg count or number of annual treatments had no effect on either the time to resistance development or worm control effectiveness. In conclusion, the modelling study suggests that leaving a small proportion of ewes untreated, or changing the time of treatment, can delay the onset of anthelmintic resistance in a highly selective environment

The investigation aimed to assess factors affecting the uptake of novel targeted selective treatment (TST) strategies by sheep farmers in Western Australia where the most common nematode species present were Teladosagia circumcincta, Trichostrongylus spp. and Nematodirus spp. ("scour worms"). The study used a questionnaire format with questions concentrated on current worm control practices and farmers' current understanding and adoption of putative TST strategies. Participants represented a range of environments (derived from four farming regions) and sheep management situations, and it is therefore likely that the results of this investigation will apply in other locations where scour worms predominate. Sixty-five percent of participants were aware of the TST concept and 25% had implemented it in some form. The awareness of the TST approach was greatest where sheep farmers were concerned about anthelmintic resistance, where tools such as worm egg counts and faecal worm egg count resistance tests were employed, and where professional advisers were consulted regarding worm control. Respondents that sought advice chiefly from rural merchandise retailers were considerably less (0.1-0.6 times) likely to be aware of these management tools or to be aware of TST approaches. The findings indicated that the adoption of TST strategies will require greater use of professional advisers for worm control advice by sheep farmers, and that advisers are conversant with TST concepts.

This study aimed to establish whether sheep flock production losses due to nematode (worm) infections are typically greater in mature sheep selected for anthelmintic treatment at random compared to sheep selected for treatment based on low (poorer) body condition score (BCS). The study also examined the proportion of sheep in flocks that could be left untreated before production losses became evident, and projected worm egg pasture contamination. Sheep were monitored at two experimental sites in Western Australia (Mediterranean climate). Sheep were stratified for BCS, liveweight and faecal worm egg count (WEC) and allocated into treatment groups (treated or untreated), with equal numbers for each. Liveweight, BCS and WEC measurements were taken on 6 occasions at Farm A and 10 occasions at Farm B. Comparisons of sheep production (liveweight and BCS change) and pasture contamination potential (WEC) were conducted by generating “virtual flocks” of varying proportions sheep untreated (10%, 20%, 30%, 40%, and 50% untreated). For the comparison of the selection mode of sheep for treatment, the untreated sheep were either selected at random, or as the highest BCS animals at the commencement of observations. Univariate general linear models with least square difference post-hoc tests were used to examine differences between flocks for liveweight, BCS and WEC, and regression analysis was used to examine relationships between BCS and WEC, and liveweight and WEC. No difference in body weights was observed between flocks with varying proportions of ewes notionally left untreated at Farm B, and until more than 30% were left untreated at Farm A. There was no difference in BCS between flocks with varying proportions of ewes left untreated at either site. At no point were there differences in cumulative liveweight change or BCS between selection methods (BCS versus random) where the same proportion of sheep in virtual flocks were left untreated, suggesting that effort committed to individual BCS assessment would be of no benefit under these circumstances except for identifying low BCS sheep at risk of falling below critical limits associated with health or welfare risks. No consistent relationship between WEC and BCS or bodyweight was observed, indicating that BCS selection would have no lesser or greater impact on worm pasture contamination compared to random selection. Summer treatments based on a random selection index (with a minimum BCS limit), with up to 30% of adult sheep untreated can be expected to delay the development of anthelmintic resistance, with minimal adverse effect on sheep health or production.

Sheep nematode control utilising refugia-based strategies have been shown to delay anthelmintic resistance, but the optimal indices to select individuals to be left untreated under extensive sheep grazing conditions are not clear. This experiment tested the hypothesis that high body condition can indicate ability of mature sheep to better cope with worms and therefore remain untreated in a targeted treatment programme. Adult Merino ewes from flocks on two private farms located in south-west Western Australia (Farm A, n = 271, and Farm B, n = 258) were measured for body condition score (BCS), body weight and worm egg counts (WEC) on four occasions between May and December (pre-lambing, lamb marking, lamb weaning and post-weaning). Half of the ewes in each flock received anthelmintic treatments to suppress WEC over the experimental period and half remained untreated (unless critical limits were reached). Response to treatment was analysed in terms of BCS change and percentage live weight change. No effect of high or low initial WEC groups was shown for BCS response, and liveweight responses were inconsistent. A relatively greater BCS response to treatment was observed in ewes in low BCS pre-lambing compared to better-conditioned ewes on one farm where nutrition was sub-optimal and worm burdens were high. Sheep in low body condition pre-lambing were more than three times more likely to fall into a critically low BCS (<2.0) if left untreated. Recommendations can be made to treat ewes in lower BCS and leave a proportion of the higher body condition sheep untreated in a targeted selective treatment programme, to provide a population of non-resistant worms to delay the development of resistance.

As it has been 30 years since a new anthelmintic class was released, it is appropriate to review management practices aimed at slowing the development of anthelmintic resistance to all drug classes. Recommendations to delay anthelmintic resistance and provide “refugia” are reviewed and a simulation model used to find optimum treatment strategies that maintain nematode control. Simulated Australian conditions indicated that a common successful low-risk treatment program was a rapid rotation between a “triple-combination” product (benzimidazole + levamisole + abamectin) and a new high-efficacy drug (monepantel). Where Haemonchus contortus was a threat, moxidectin was required at critical times because of its persistent activity against this parasite. Leaving up to 4% of adult sheep untreated provided sufficient “refugia” for non-selected worms to reduce the risk of selecting for anthelmintic resistance without compromising nematode control. For a new anthelmintic, efficacy estimated by faecal egg count reduction (FECR) is likely to be at or close to 100%, however using current methods the 95% confidence limits (CL) for 100% are incorrectly determined as 100%. The fewer eggs counted pre-treatment, the more likely an estimate of 100% will occur, particularly if the true efficacy is >90%. A novel way to determine the lower-CL (LCL) for 100% efficacy is to reframe FECR as a binomial proportion, i.e. define: n and x as the total number of eggs counted (rather than eggs per gram of faeces) for all pre-treatment and post-treatment animals, respectively; p the proportion of resistant eggs is p = x/n and percent efficacy is 100*(1-p) (assuming equal treatment group sizes and detection levels, pre- and post-treatment). The LCL is approximated from the cumulative inverse beta distribution by: 95%LCL = 100*(1-(BETAINV(0.975,x + 1,n-x + 1))). This method is simpler than the current method, independent of the number of animals tested, and demonstrates that for 100% efficacy at least 37 eggs (not eggs per gram) need to be counted pre-treatment before the LCL can exceed 90%. When nematode aggregation is high, this method can be usefully applied to efficacy estimates lower than 100%, and in this case the 95% upper-CL (UCL) can be estimated by: 95%UCL = 100*(1-(BETAINV(0.025,x + 1,n-x + 1))), with the LCL approximated as described above. A simulation study to estimate the precision and accuracy of this method found that the more conservative 99%CL was optimum; in this case 0.975 and 0.025 are replaced by 0.995 and 0.005 to estimate the LCL and UCL, respectively.

Develop a computer simulation model that uses daily meteorological data and farm management practices to predict populations of Trichostrongylus colubriformis, Haemonchus contortus and Teladorsagia (Ostertagia) circumcincta and the evolution of anthelmintic resistance within a sheep flock. Use the model to explore if increased refugia, provided by leaving some adult sheep untreated, would delay development of anthelmintic resistance without compromising nematode control. Procedures Compare model predictions with field observations from a breeding flock in Armidale, NSW. Simulate the impact of leaving 1-10% of adult sheep untreated in diverse sheep-grazing systems. Results Predicted populations of Tr. colubriformis and T. circumcincta were less than those observed in the field, attributed to nutritional stress experienced by the sheep during drought and not accounted for by the model. Observed variation in faecal egg counts explained by the model (R2) for these species was 40-50%. The H. contortus populations and R2 were both low. Leaving some sheep untreated worked best in situations where animals were already grazing or were moved onto pastures with low populations of infective larvae. In those cases, anthelmintic resistance was delayed and nematode control was maintained when 1-4% of adult stock remained untreated. Conclusions In general, the model predicted that leaving more than 4% of adults untreated did not sufficiently delay the development of anthelmintic resistance to justify the increased production risk from such a strategy. The choice of a drug rotation strategy had an equal or larger effect on nematode control, and selection for resistance, than leaving 1-10% of adults untreated.

Objective To compare the risk of different treatment scenarios on selecting for anthelmintic resistance on Australian sheep farms. Design A computer simulation model predicted populations of Trichostrongylus colubriformis, Haemonchus contortus or Teladorsagia (Ostertagia) circumcincta, and the frequency of anthelmintic resistance genes. Method Nematode populations and the progression of drug resistance for a variety of treatment options and management practices in sheep-rearing areas of Western Australia (WA), Victoria (VIC) and New South Wales (NSW) were simulated. A scoring system was devised to measure the success of each option in delaying resistance to each anthelmintic and in controlling nematode populations. Results The best option at all sites was combining the new anthelmintic (monepantel) with a triple mixture of benzimidazole, levamisole and abamectin (COM). The next best option was: in NSW, rotation at each treatment between monepantel, moxidectin and COM; in VIC, rotation at each treatment between monepantel and COM; and in WA, rotation at each treatment between monepantel (used in winter) and COM or moxidectin (used in summer-autumn). In WA, rapid selection for resistance occurred as a consequence of summer-autumn treatments; however, if a small percentage of adult stock were left untreated then this selection could be greatly reduced. Despite purposely assuming relatively high resistance to benzimidazole and levamisole, COM was still effective in controlling worms and delaying resistance. Conclusions Because of cost constraints, it may not be feasible or profitable for producers to always use the combination of all drugs. However, the second-and third-best options still considerably slowed the development of anthelmintic resistance.