Search

This review article provides an historical perspective on some of the major research advances of relevance to ruminant livestock gastrointestinal nematode control over the last 50 years. Over this period, gastrointestinal nematode control has been dominated by the use of broad-spectrum anthelmintic drugs. Whilst this has provided unprecedented levels of successful control for many years, this approach has been gradually breaking down for more than two decades and is increasingly unsustainable which is due, at least in part, to the emergence of anthelmintic drug resistance and a number of other factors discussed in this article. We first cover the remarkable success story of the discovery and development of broad-spectrum anthelmintic drugs, the changing face of anthelmintic drug discovery research and the emergence of anthelmintic resistance. This is followed by a review of some of the major advances in the increasingly important area of non-pharmaceutical gastrointestinal nematode control including immunology and vaccine development, epidemiological modelling and some of the alternative control strategies such as breeding for host resistance, refugia-based methods and biological control. The last 50 years have witnessed remarkable innovation and success in research aiming to improve ruminant livestock gastrointestinal nematode control, particularly given the relatively small size of the research community and limited funding. In spite of this, the growing global demand for livestock products, together with the need to maximise production efficiencies, reduce environmental impacts and safeguard animal welfare – as well as specific challenges such as anthelmintic drug resistance and climate change– mean that gastrointestinal nematode researchers will need to be as innovative in the next 50 years as in the last.

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.

Effects of gastrointestinal parasitism on sheep productivity are usually described using live weight change, however carcass productivity is more accurately described using dressing percentage (carcass weight as a proportion of live weight). This experiment had a 2 × 2 × 2 factorial design whereby 10-month-old Merino wethers were fed lucerne (Medicago sativa) diets (fresh lucerne or lucerne chaff) with 2 levels of carboxymethycellulose (CMC) inclusion (0% or 8% CMC) and nematode larval challenge (no larval challenge or 10,000 Teladorsagia circumcincta and 10,000 Trichostrongylus colubriformis per week). Sheep were weighed and euthanased 50 or 51 days after larval challenge and CMC supplementation commenced. Weight of the carcass (hot standard carcass weight) and gastrointestinal organs (full and empty) were recorded and expressed as a proportion of live weight. Larval challenged sheep had a worm egg count (mean ± standard error) of 173 ± 38 eggs per gram of faeces and total worm count of 30,237 ± 2013 at slaughter. Larval challenged sheep had 1.3% lower dressing percentage (p = 0.048), and 2% heavier full (p = 0.007) and 1.2% heavier empty gastrointestinal tracts (p = 0.012) compared to unchallenged sheep. There was no effect of CMC inclusion or lucerne type (fresh or chaff) on gastrointestinal tract weight or dressing percentage. Larval challenged sheep had 1.1% heavier full (p < 0.001) and 0.6% heavier empty (p < 0.001) small intestines, and 0.6% heavier full (p = 0.005) and 0.3% heavier empty (p = 0.026) large intestines compared to unchallenged sheep. Use of live weight change or other measures based on live weight (e.g. feed conversion efficiency) to assess the impact of nematode challenge in sheep may underestimate carcass productivity losses associated with larval challenge in sheep even at moderate levels of larval intake and without overt clinical signs of parasitism. Measurement of carcass weight and/or lean meat yield may better reflect the true economic effects of parasitism in sheep

Little is known of the prevalence of Cryptosporidium and Giardia parasites in sheep and the genotypes that they harbor, although potentially sheep may contribute significantly to contamination of watersheds. In the present study, conducted in Western Australia, a total of 1,647 sheep fecal samples were screened for the presence of Cryptosporidium and Giardia spp. using microscopy, and a subset ( n = 500) were screened by PCR and genotyped. Analysis revealed that although both parasites were detected in a high proportion of samples by PCR (44% and 26% for Giardia and Cryptosporidium spp., respectively), with the exception of one Cryptosporidium hominis isolate, the majority of isolates genotyped are not commonly found in humans. These results suggest that the public health risk of sheep-derived Cryptosporidium and Giardia spp. in catchment areas and effluent may be overestimated and warrant further investigation.

Haemonchus placei is an abomasal parasite of cattle, primarily in tropical and subtropical areas of the world. In Australia, this nematode can be extremely pathogenic in summer rainfall areas, particularly in the hot, sub-tropical Kimberley region, in the far north of the state of Western Australia (WA). Although cattle are occasionally transferred to southern parts of WA, it was believed that H. placei did not occur in southern regions of WA, as it is less cold-adapted than Haemonchus contortus, and the free-living stages would not develop during the cold winter and dry summer periods. Here, we show that, although H. contortus is found in cattle in the temperate southern region of WA, it appears that H. placei also occurs in southern WA. While investigating the prevalence of anthelmintic resistance in nematodes of cattle in WA, the existence of H. placei was suspected on a range of participating farms, following the morphological examination of third-stage larvae cultured from faeces, and of adult worms recovered from sheep experimentally infected with these larvae. Genomic DNAs from individual worms as well as eggs from pooled faecal samples from seven farms in southern WA were subjected to PCR-based mutation scanning and sequence analyses of the second internal transcribed spacer (ITS-2) of nuclear ribosomal DNA. The results showed that both H. contortus and H. placei were harboured by cattle. This first record of H. placei in cattle in southern WA raises questions as to the prevalence and distribution of this parasite in other temperate and cool climatic regions of Australia. Although clinical disease due to H. placei has not yet been seen in southern WA, global, climatic trends might suggest an increased importance of this parasite in the longer term.

Nine flocks of sheep with a high prevalence (>30%) of diarrhoea and severe breech faecal soiling were investigated over a three-year period to examine the causes of diarrhoea in sheep with low mean faecal worm egg counts (WEC). All nine flocks were located in the southwest of Western Australia in areas with a winter rainfall pattern (Mediterranean climate). There was no difference (p=0.304) in WEC of diarrhoeic sheep (loose faeces and severe breech faecal soiling) and "normal sheep" (pelleted faeces and mild or no breech faecal soiling). Teladorsagia (Ostertagia) circumcincta and Trichostrongylus spp. were the nematodes most commonly identified by total worm counts and differentiation of larvae recovered from faeces and pasture. Larval stages of strongyle worms accounted for the largest proportion of total worm counts in both diarrhoeic and normal sheep. Adult worm burdens were small in most sheep. Diarrhoeic sheep had higher numbers of fourth stage larvae than normal sheep (p=0.046). There was no histopathological evidence of bacterial or viral causes of diarrhoea in any of the flocks or bacteriological evidence of bacterial infections associated with diarrhoea. Two flocks had marginal selenium glutathione peroxidase (selenium) levels. One flock was diagnosed with helminthosis based on rising WEC and high total worm counts. Larval hypersensitivity diarrhoea, nutritional factors or a combination of these two factors were the most likely causes of diarrhoea in the other eight flocks based on exclusion of other known causes of diarrhoea. Treatment with moxidectin and an ivermectin controlled-release capsule did not change faecal moisture content of treated sheep compared to untreated sheep three to five weeks after treatment. The findings suggest that the immune response to strongyle larvae may explain some cases of low WEC diarrhoea observed during winter-spring in immunocompetent mature sheep grazing in Mediterranean environments.

The viability of small-ruminant enterprises is under threat in some locations because anthelmintic resistance continues to increase in prevalence and severity. Despite this, no new anthelmintic group has been developed for many years, and animal health companies seem unconvinced of the commercial justification for new compounds for the ruminant market. It is now argued, however, that market conditions are becoming favourable because of increases in multiple-drug resistance in nematodes of ruminants and other hosts and because few non-chemical options exist. A new anthelmintic is urgently needed and will find ready acceptance in an increasing market, and with better knowledge of resistance management, greater product longevity can be achieved.

Extract From the announcement of the discovery of the anthelmintic properties of a new group of compounds, the amino-acetonitrile derivatives (AAD) (Kaminsky et al. 2008a), progress towards a product available to sheep owners has been impressively rapid. An increasing cascade of publications report efficacy of the compound chosen for commercial development (Kaminsky et al. 2008b), monepantel, against a wide range of nematodes of economic significance in sheep. These demonstrate high efficacy against both mature and larval stages and strains resistant to other anthelmintics (Hosking et al. 2008, 2009; Kaminsky et al. 2009; Sager et al. 2009). Field studies in New Zealand further confirm the efficacy (Mason et al. 2009) and experimental studies in Australia substantiate its safety (Malikides et al. 2009a b) in sheep. There is no doubting the potential of monepantel, due for imminent release by Novartis New Zealand Ltd, for a major impact where anthelmintic resistance threatens worm control in sheep...