The Happy Factor treatment threshold, used to determine Targeted Selective Treatment decisions for lambs, is transferable between farms.

Weight gain-based treatment decision-making has been shown to successfully reduce the number of anthelmintic treatments without compromising production as part of a Targeted Selective Treatment (TST)-based worm control strategy in sheep. The effects of using an efficiency threshold (Standard Threshold (ST)) developed on one farm were examined to establish whether there was a need to tailor the threshold for individual farm conditions. The Standard Threshold had been used on a number of farms, and data from these trials were used here. The ideal threshold (Estimated Treatment Threshold) for each farm was calculated using the same method as the original threshold, and the effect on the number of treatments given and subsequent productivity was estimated. Estimated treatment thresholds were calculated to be higher on all farms including the original, resulting in increased numbers of treatments due. The effect of the increased number of treatments was calculated to have no effect on productivity however, and it was concluded that the ST was sufficient, at least initially, for successful implementation of TST and that further refinement could be made using locally derived data if required.

Comparison of the timing of development of immunity in Romney lambs from resistant and resilient selection lines.

Variation in the timing of development of immunity to gastro-intestinal nematode parasites was assessed in resistant and resilient Romney selection lines exposed to mixed natural infection. From weaning, at mean 92 days-of-age, animals (n = 53) were sampled for faecal egg count (FEC) expressed as eggs per gram of faeces (epg), saliva for immunoglobulin (IgG and IgA) determination and fasted live weight (LW) every 10 days until 351 days-of-age. Overall, mean back-transformed FEC were consistently low for resistant animals (<200 epg) whereas resilient counterparts' FEC increased with time to reach a peak of 1400 epg at day 230 for females and 1800 epg for males at day 280 before declining to less than 500 epg by day 300, respectively (P < 0.001). Resistant lambs reached a threshold for Trichostrongylus colubriformis L3-specific IgG which was indicative of the presence of immunity earlier at 220.6 ± 8.8 days-of-age compared with resilient-line animals which reach this threshold 40 days later at 263.4 ± 6.9 days-of-age (P < 0.001). In addition, resistant females reached sexual maturity earlier compared with their resilient counterparts viz. 263.5 ± 3.7 c.f. 274.4 ± 3.4 days-of-age, respectively, (P = 0.048). Mean fasted live weight (LW) showed a selection line by time interaction (P < 0.001) which reflected greater LW in the early phase of the study in resilient males but increasing for all groups until day 280 before declining and being similar for all groups from day 330. In summary, differences appear to exist in the timing of immune development between these Romney lines, with resistant animals developing immunity earlier and these resistant-line animals also appear to be more physiologically mature at the same chronological age than resilient animals. These observations have implications on the timing of identification and selection of resistant animals.

Immune development and performance characteristics of Romney sheep selected for either resistance or resilience to gastrointestinal nematodes.

Immunological and performance characteristics were explored in Romney sheep from lines selected for either resistance or resilience to parasite infection. At a mean 78 days-of-age, twin lambs from a line selected for resistance (RT) and lambs from a line selected for resilience (RL) were infected with the intestinal nematode Trichostrongylus colubriformis for 100 days (I) while their twin remained as an uninfected control (C). Compared with RL, RT animals had lower levels of circulating CD4+ T-cells (P = 0.003) but a greater proportion of these were activated (CD4+CD25+) in response to infection (P = 0.007). Differences between the lines in humoral immune responses to nematode infection varied with higher levels of T. colubriformis specific immunoglobulin (Ig) E in RT-I than RL-I (P = 0.002) but similar levels of both IgG (P = 0.926) and IgA (P = 0.321) responses. Temporal differences in the immune response also existed between the lines with RT-I animals displaying an earlier peak and more rapid reduction in FEC and an earlier peak in T. colubriformis specific IgA. In addition, compared with their RT-C and RL-C counterparts, infection caused a 22% reduction in feed intake from day 56 (P = 0.001) with total feed intake reduced by 15% and 9% for RT-I and RL-I, respectively. Cumulative liveweight gain was greatest for RL animals (P = 0.026) and relative to RT-C and RL-C was reduced by 5.8 kg and 4.9 kg for RT-I and RL-I, respectively. Overall, the selection lines appear to have differences in immunological characteristics that are both dependent on, and independent of parasite infection. Further, the difference in growth in the uninfected animals coupled with the similar cost of infection suggests the lower liveweight gain of RT-I compared with RL-I may be due to inherent differences between the lines in their growth potential, rather than a greater cost of infection in animals selected for resistance.

Relative maturity and the development of immunity to gastrointestinal nematodes in sheep: an overlooked paradigm?

Sheep display considerable variation in both the timing and magnitude of development of immunity to gastrointestinal nematodes (GIN). Onset of immunity is dependent on a number of factors, including antigenic stimulus, nutrition supply, age and size of the animals, the latter of which are confounded. Here, we review the factors associated with the development of immunity to GIN in sheep, particularly in the context of the role that relative maturity may have through applying the rules of genetic size scaling based on examples from published literature. Comparing animals based on their metabolic age, rather than chronological age, may provide an explanation for the timing of immune development and may reduce the variation in immune development that frequently is observed both between and within breeds. Further, this approach may help explain the phenotypic differences in animal performance between animals of varying immunological capacity to GIN through influences on mature body weight. As such, when considering factors influencing immune development to GIN, physiological age or relative maturity may be considered an overlooked paradigm. We propose it may be worthwhile to consider metabolic age when comparing the immune competence of animals to ensure the subjects are at an analogous stage of physiological development.

Direct anthelmintic and immunostimulatory effects of oral dosing semi-purified phytohaemagglutinin lectin in sheep infected with Teladorsagia circumcincta and Trichostrongylus colubriformis.

Lectins are plant secondary compounds that can have anthelmintic properties in vitro. In particular, the phytohaemagglutinin lectin extracted from Phaseolus vulgaris has been shown to inhibit the feeding of Trichostrongylus colubriformis and Teladorsagia circumcincta L1 larvae. However, little is known about the potential anthelmintic properties of this lectin in vivo and its suitability to control gastrointestinal parasite infections in lambs. In a 2 × 2 study, lambs were either orally dosed, or not, with 2.3mg semi-purified PHA lectin per kg live weight (LW) per day, whilst concurrently infected, or not, with 1000 T. circumcincta and 1000 T. colubriformis L3 infective larvae per day for 42 days. There were no adverse clinical effects observed with this dose of PHA lectin. Although worm burdens were similar, animals dosed with PHA lectin had reduced concentration of nematode eggs in the faeces compared with their non-lectin dosed counterparts (P=0.026), suggesting that there may be a direct effect of PHA lectin on parasite fecundity. Irrespective of infection, PHA lectin had immune-stimulatory properties with increased eosinophillia in both abomasal and small intestine tissue sections taken at slaughter on day 42 (P<0.02 for both) and a tendency for decreased ability of Teladorsagia larvae to penetrate abomasal tissue explants (P=0.06). Compared with infection alone, concurrent PHA lectin dosing and infection further increased the number of eosinophils (P<0.01), PAS-positive (mucin-producing cells) (P=0.03) and tended to increase the number of T helper cells (P=0.06). No interactions were observed for cell populations in small intestine tissue sections. These results suggest PHA lectin could have two possible modes of action against T. circumcincta and T. colubriformis, a direct anthelmintic effect on nematode fecundity and an indirect effect through enhancing local immune responses in the host.

Development and field evaluation of a decision support model for anthelmintic treatments as part of a targeted selective treatment (TST) regime in lambs.

The recent focus of strategies to slow the rate of development of anthelmintic resistance in gastro-intestinal parasites has centred on the need to better manage the parasite population that is unexposed to the drug, i.e. in refugia. One strategy involves the use of targeted selective treatments (TST) where anthelmintics are only administered to those individuals that are likely to benefit from it, rather than to the whole flock. However, there are few TST indicators currently available for farmers in temperate environments. Here we describe the development and field evaluation of a performance-based decision support model to identify individual animals whose performance is suffering from nematodoses, and thus, likely to benefit from an anthelmintic treatment. One hundred and ninety two twin-suckled lambs were separated into eight groups and each grazed on a one-hectare paddock and exposed to one of four anthelmintic treatment regimes. Groups of lambs received either: a whole flock anthelmintic treatment either every four weeks (neo-suppressive treatment, NST); when clinical signs of disease were evident (metaphylactic/therapeutic treatment, MT); at pre-determined times throughout the grazing season (strategic treatment, SPT) or treatment on an individual animal basis as determined by a performance-based decision support model that relied on a calculation of the efficiency of nutrient utilization (targeted selective treatment, TST). Animal performance and parasitological data were recorded every two weeks. Mean faecal egg counts were low throughout the season for the NST group and moderate for the MT, SPT and TST groups. During the entire grazing season the NST, MT, SPT and TST animals each received on average 5.0, 2.0, 3.0 and 2.6 anthelmintic treatments, respectively. Compared to the NST animals, cumulative weight gains were 11% lower at the end of the grazing season in MT animals, whereas no reduction was observed in either the SPT or TST groups. The proposed decision support system appeared to be successful in discriminating between animals which were likely to respond favourably to anthelmintic treatment and those that were not and provided a quantitative estimate of the likely response. Furthermore, 87% of animals that had a pre-treatment efficiency of nutrient utilization value lower than the suggested threshold of the model responded positively to treatment. The potential benefits of using the decision support model as a TST indicator for managing the parasite population in refugia in temperate environments are discussed.

The role of targeted selective treatments in the development of refugia-based approaches to the control of gastrointestinal nematodes of small ruminants.

Anthelmintic resistance is recognised as a major problem affecting small ruminant production worldwide and now threatens the sustainability of many of these systems. One method that has been proposed to prolong the efficacy of our current anthelmintics is the maintenance of a parasite population in refugia (unexposed to a drug) which will maintain the genes for susceptibility within the parasite population. Management strategies that employ refugia-based methods include targeted or strategically timed whole flock treatments, targeted selective treatments (TST), whereby only a proportion of the flock is treated at any one time, and the dilution of resistant with susceptible parasites. The ability to effectively target anthelmintic use relies on the identification of those animals that will most benefit from treatment. This review explains the concept of refugia, describes the role of refugia-based approaches to the management of anthelmintic resistance and reviews the markers that have been studied as indicators for TSTs as well as the implementation of refugia-based strategies. Recent results suggest that targeting anthelmintic treatment on the basis of anaemia, milk production and liveweight gain may offer a means of reducing anthelmintic usage whilst still maintaining animal performance.

Protein supply influences the nutritional penalty associated with the development of immunity in lambs infected with Trichostrongylus colubriformis.

The influence of dietary protein supply on the nutritional penalty associated with the acquisition phase of the immune response to gastrointestinal nematodes in lambs was investigated. Groups of lambs were offered either a low-protein diet (L; 62 g metabolizable protein (MP)/kg dry matter (DM)) or high-protein diet (H; 95 g MP/kg DM) while being either infected with the equivalent of 2.000 L3 Trichostrongylus colubriformis/day (IF), similarly infected and concurrently immuno-suppressed with methylprednisolone acetate (ISIF), immuno-suppressed only (IS) or kept as uninfected controls (C). Body composition of all animals was measured on days -8 and 76 of infection using X-ray computed tomography. Temporal changes in serum phosphate and serum albumin concentrations, which provided an indicator of pathological damage, in addition to patterns of total daily nematode egg excretion and comparative worm burdens at slaughter indicated that a protective immune response was developed in H-IF, but not L-IF, H-ISIF or L-ISIF groups. Compared to their respective non-infected controls, the gross efficiency of use of metabolizable energy (ME) for net energy (NE) deposition in the carcass was reduced by 0.23 in H-IF (P < 0.05), 0.13 in H-ISIF (P > 0.05), 0.49 in L-IF (P < 0.01) and 0.23 in L-ISIF (P > 0.05). It is concluded that the reduction in ME utilization and reduced performance, which can be attributed to the immunological response, are lessened in animals offered a high-protein diet. Furthermore, evidence is presented to indicate a possible association between T. colubriformis L3 IgA antibody production and loss of performance in lambs infected with this nematode.

Effects of strategic anthelmintic treatments on the milk production of dairy sheep naturally infected by gastrointestinal strongyles.

The present paper was aimed at assessing the benefit of strategic anthelmintic treatments on milk production in four commercial dairy sheep farms in Southern Italy whose animals were naturally infected by gastrointestinal (GI) strongyles and Dicrocoelium dendriticum. The scheme was based on two treatments timed in relationship to parturition, i.e. the first with moxidectin in the periparturient period and the second with netobimin at the mid/end of lactation. On each farm, two similar groups (20 animals each) were formed, one untreated control group and one group treated according to the above-mentioned scheme. Faecal egg counts (FEC) were performed on each study animal at the start of the trial and then monthly until the end of the study; in addition, milk production was recorded for each animal fortnightly in each farm for the lactation period. The results showed a significant increase in milk yield across all four farms that ranged from 19% to 44% improvement in milk yield. The benefit in milk yield in addition to considerably reduced egg output of the treated animals provide clear evidence that the two main aims of prophylactic parasite control, i.e. to maintain or improve animal performance and to reduce pasture contamination, can be achieved using strategic anthelmintic treatments.

The effect of dietary sainfoin ( Onobrychis viciifolia) on local cellular responses to Trichostrongylus colubriformis in sheep.

The effect of sainfoin (Onobrychis viciifolia) hay consumption on the pathophysiology and local cellular responses of growing lambs during infection with Trichostrongylus colubriformis was investigated. Thirty-two lambs, 16 weeks of age, were allocated to 1 of 4 treatment groups (n=8) that were offered either grass (G) or sainfoin (S) hay while concurrently either infected (+), or not (-) with 12,000 L3 T. colubriformis larvae per week for 6 weeks. Liveweight gains were affected by diet (P=0.002) and reduced by infection (P<0.05). Faecal egg count was reduced in S+compared to G+ from days 35 to 42 (P=0.001); however, total egg output, worm burdens at day 42 and worm fecundity were similar between diets (P>0.05).Feeding sainfoin appeared to enhance immune cell development with tissue eosinophils, mast cells and pan T cells present in greater concentrations in S+ than in G+ animals. However, further studies are required to determine if the enhanced immune cell development is a consequence of a greater nutrient supply or a direct influence of sainfoin metabolites on local inflammatory responses to the gastrointestinal nematode T. colubriformis.

The effect of corticosteroid treatment on local immune responses, intake and performance in lambs infected with Teladorsagia circumcincta.

The nutritional cost of, and the sequential cellular changes associated with the developing immune response to the abomasal parasite Teladorsagia circumcincta were investigated using corticosteroid-induced immune-suppression. Six-month-old lambs with minimal nematode experience were either infected with 4000 L3 T. circumcincta per day (group IF), similarly infected and concurrently immune-suppressed with methylprednisolone acetate (group ISIF), immune-suppressed only (group IS) or remained as controls (group C). Food intake, faecal egg count (FEC) and antibody titres in plasma were recorded weekly, worm burden at necropsy on day 63 p.i. and body composition by X-ray computed tomography on days -2 and 62 p.i. Furthermore, sequential immunological changes at the site of parasite infestation in the abomasal mucosa were measured from serial biopsy tissue samples taken from additional animals that were fitted with an abomasal cannula and either infected with the same regime as IF animals above (group CnIF) or concurrently infected and immune-suppressed as above (group CnISIF). Corticosteroid treatment resulted in greater FECs (P<0.01) and worm burdens (P<0.01) in both ISIF and CnISIF compared with IF and CnIF sheep, respectively. Infection reduced feed intake by 17% between 14 and 28 days p.i. (P<0.05) and efficiency of energy utilisation by 20% (P=0.07) in IF animals but not in ISIF animals. Mast cells, globule leukocytes and IgA in tissue biopsy samples were elevated in CnIF from 42 days p.i., all of which were abrogated by corticosteroid treatment. The ability to regulate the worm population appeared to be associated with a rise in tissue IgA concentration and numbers of globule leucocytes (GL). The results support the hypothesis that a majority of the production losses that occur during infection of lambs with T. circumcincta in lambs are a consequence of the host immune response. These findings may have implications for regimes that promote the development of a strong host immune reaction to gastrointestinal parasites in lambs.

Does suckling offer protection to the lamb against Teladorsagia circumcincta infection?

This study tested the hypothesis that milk has a direct effect on the establishment of infection with Teladorsagia circumcincta, and provides information on the effects of suckling on resilience to infection in young lambs. Of 46 six-week-old twin-born lambs, one from each twin was allowed to continue suckling (S-) and its twin-weaned (W-) while both were concurrently infected with an average of either 0 (-0; n=7/group), 250 (-250; n=8/group) or 1000 (-1000; n=8/group) third stage infective larvae (L3) of T. circumcincta per day, providing six treatment groups. All groups grazed minimally contaminated pasture, and after 42 days were slaughtered for necropsy. Low pasture larval contamination was confirmed in W0 and S0 lambs by faecal egg counts (FEC) of less than 30 eggs per gram (EPG) and burdens of less than 140 worms. There was no difference in FEC between weaned and suckled lambs. Within infection regime, total worm burdens were 55-60% greater in the weaned compared with their suckled counterparts (P=0.05), and represented 27 and 17%, respectively, net establishment of larvae. The greater worm burdens of both groups of weaned animals, which compared with their suckled counterparts, and of those infected with 1000 compared with 250 larvae per day, were associated with shorter female adults that had fewer eggs in utero, perhaps indicating intra-worm population regulation, but highlighting the limitation of FEC in assessing nematode burdens of such young lambs. There was no effect of infection on live weight gain of either weaned or suckled groups and the possibility was raised that, in such young lambs, immune unresponsiveness may be responsible. The major benefit of continued milk consumption appears to lie more in providing nutrients for enhanced growth rather than in improving resilience of the lambs to infection.

Trade-offs and benefits: implications of promoting a strong immunity to gastrointestinal parasites in sheep.

The search for sustainable control regimes for gastrointestinal nematode parasites in grazing livestock has resulted in strategies that include assisting sheep to promote a strong immune response. However, the immune response imposes a substantial nutritional cost to the animal which, when nutrient supply is limited, is likely to result in the diversion of nutrients away from productive function to immunological tissues. Therefore, this review examines the potential trade-offs between immune function and productivity that may arise in young grazing sheep. It is hoped that future manipulations intended to promote a strong immunity to gastrointestinal parasites in sheep may be able to minimize these trade-offs to ensure that the productivity of the host is not compromised.

Studies using Teladorsagia circumcincta in an in vitro direct challenge method using abomasal tissue explants.

An in vitro direct challenge (IVDC) method in which abomasal tissue explants maintained at 37 degrees C in Hanks/Hepes solution (pH 7.6) in a high oxygen concentration (incubator gassed with pure oxygen and sealed prior to use) were-challenged with exsheathed third stage larvae of Teladorsagia circumcincta has been used to investigate the tissue association phase of larval establishment. Studies using naïve and recently challenged immune sheep and goat abomasal tissues have shown significant reductions (P < 0.05) in the numbers of tissue associated larvae in material from immune animals. The mechanisms that affect the tissue association process appear to be labile since more larvae were recovered from the tissue digests of previously infected sheep that had not been recently exposed to larval challenge in comparison to those that had been recently challenged (P < 0.05). The method has also been used to demonstrate the influence of protein nutrition on the establishment of larvae in abomasal tissues and region specific differences in the efficacy of exclusion mechanisms. The technique appears to have potential as a means of investigating the crucial first phase of the process of establishment.