Sheep's Nutrient Digestion and Metabolism Affected by Nematode Infections, Notas de estudo de zootecnia

Baixe Sheep's Nutrient Digestion and Metabolism Affected by Nematode Infections e outras Notas de estudo em PDF para zootecnia, somente na Docsity! 14 Interactions between Gastrointestinal Parasites and Nutrients R.L. COOP1 AND A.R. SYKES2 1Moredun Research Institute, Pentlands Science Park, Edinburgh, UK; 2Animal and Food Sciences Division, Lincoln University, Canterbury, New Zealand Introduction Grazing sheep are invariably infected with a range of nematode species, which are the most important parasites of the gastrointestinal (GI) tract (Table 14.1) and which frequently lead to significant impairment of pro- ductivity (Sykes, 1994). Control of GI nematodes in ruminants is cur- rently achieved through prophylactic or therapeutic use of anthelmintics, combined, where farm practice allows, with grazing- management strategies that are aimed at reducing contact between the host and the infective stages of the parasite on pasture. The continued use of suppressive anthelmintic strategies is unsustainable, as nematode resistance to the three main classes of broad-spectrum anthelmintics is now widespread in small ruminants throughout many areas of the world (Waller, 1997). In many parts of the southern hemisphere, anthelmintic resistance is one of the main threats to sustainable livestock production. The ability of nematodes to rapidly develop resistance to new drug fami- lies and formulations is of paramount importance, as it is unlikely that many new drugs with novel modes of action will be licensed for future veterinary use in small ruminants, due to the high cost of development for a limited market. A further issue arising from extensive use of anthelmintics is the increasing public awareness of potential drug residues in meat and milk products and also concern about the possible ecotoxicological effects of excretion of certain anthelmintics on the envi- ronment, especially beneficial microfauna. These issues have led to a drive to find alternative sustainable control strategies for helminth infec- tions, which are less reliant on chemotherapy (Waller, 1999). One approach has been to investigate the role of dietary supplementation in enhancing the resistance and resilience of livestock that are susceptible to GI parasitism. © CAB International 2002. Sheep Nutrition (eds M. Freer and H. Dove) 313 sheep nutrition Ch 14 7/17/02 4:00 PM Page 313 In this context of parasite control involving reduced anthelmintic input, greater emphasis is being placed on recognition of sources of contamination (eggs passed in faeces) and their availability to susceptible livestock. The lat- ter is the young naïve lamb, whose protection has traditionally been pro- vided by direct anthelmintic therapy. Increasingly, it is being recognized that reduction in anthelmintic usage will be more readily achieved by limi- tation of exposure rather than chemical treatment in the face of challenge. This approach recognizes increasingly that the characteristic breakdown in established immunity, characteristic of mammals in the periparturient period, could be a major source of early-season infection to the lamb. Recent work suggests a nutritional involvement in this breakdown, which may be mitigated by supplementation (Donaldson et al., 1998). In this chapter, parasite/nutrition interactions will be considered from two aspects: first, the impact of infection on the host’s metabolic processes and, secondly, the influence of the nutritional status of the host on its abil- ity to resist or tolerate a parasitic challenge. Effects of Gastrointestinal Nematodes on Host Metabolism The consequence of parasitic infection on ruminant metabolism has been the subject of several recent reviews (MacRae, 1993; Coop and Holmes, 1996; van Houtert and Sykes, 1996). Gastrointestinal nematodes impair animal productivity primarily through reductions in voluntary feed intake and/or 314 R.L. Coop and A.R. Sykes Table 14.1. Common gastrointestinal helminths of sheep. Abomasum Teladorsagia (Ostertagia) circumcinctaa Teladorsagia (Ostertagia) trifurcata Trichostrongylus axei Haemonchus contortusa Small intestine Trichostrongylus vitrinusa Trichostrongylus colubriformisa Nematodirus battusa Nematodirus filicollis Nematodirus spathiger Cooperia curticei Strongyloides papillosus Bunostomum trigonocephalum Moniezia expansa Large intestine Chabertia ovina Oesophagostomum venulosum Oesophagostomum columbianuma Trichuris ovis aFrequently associated with outbreaks of parasitic gastroenteritis. sheep nutrition Ch 14 7/17/02 4:00 PM Page 314 al., 1986; Bown et al., 1991a). Even when the majority of the endogenous protein is reabsorbed as amino acid, experiments with pair-fed animals have shown that there is poor protein deposition in the body, probably because energy is directed to protein synthesis for the preferential repair of GI tissue and to maintain homoeostasis and replacement of endogenous secretions. Recently, the increased protein turnover of the parasitized ovine GI tract has been quantified, using trans-organ catheterization and mass isotope tracer kinetics, with leucine as the marker amino acid (Yu et al., 2000). These authors showed that sequestration of amino acid by the total GI tract from arterial pools was increased by 24% and also that the GI-tract oxidative losses of leucine were increased by 22–41% in sheep infected subclinically with T. colubriformis. A reduction in the availability of absorbed amino acids for metabolism in peripheral tissues is in agreement with the observation of reduced rates of protein synthesis in wool and muscle of sheep infected with T. colubriformis (Jones and Symons, 1982) and also with recent data (Bermingham et al., 2000), which showed that experimental T. colubriformis infection reduced liveweight gain of sheep but had no effect on the whole- body irreversible loss rate of valine or cysteine, implying repartitioning of amino acid utilization between tissues. Scarce resources, such as essential amino acids, are diverted from productive processes (growth and reproduc- tive effort) into those areas which are essential to maintain homoeostasis, such as repair of the GI tract, maintenance of blood proteins and com- ponents of the immune response and mucus production (Fig. 14.1). These effects will be exacerbated in those infections where the overall nutrient availability is further limited by reductions in voluntary feed intake. Gastrointestinal Parasites and Nutrients 317 MP Muscle Skeleton Wool Milk Epithelial cell turnover for tissue repair Albumin globulins in the liver Plasma proteins to replace leakage Peripheral inflammatory response: precursor-cell expansion Local inflammatory responses: effector-cell replication, effector-cell products, mucoproteins Lumen Gut mucosa ME Increase Decrease Fig. 14.1. Effects of gastrointestinal nematode infection on protein metabolism in sheep. The net effects are that amino acids from metabolizable protein (MP) are diverted from production (skeleton, muscle, wool and milk) to maintain integrity of the GI tract and to mount an effective local immune response. There is a concomitant diversion of metabolizable energy (ME) to the maintenance of the gut. sheep nutrition Ch 14 7/17/02 4:00 PM Page 317 The overall conclusion must be that parasitism reduces the supply of metabolizable protein (MP) while increasing demand – an induced pro- tein deficiency. Energy Gastrointestinal parasitism has a major effect on the energy metabolism of the host, largely through reductions in feed intake. This is especially the case in the young naïve lamb (MacRae et al., 1982) but also in the mature ewe during lactation following the breakdown of immunity around parturition (Leyva et al., 1982), as discussed earlier. Early experi- ments that compared energy deposition in the carcass of sheep infected with Teladorsagia circumcincta or Trichostrongylus colubriformis with that in pair-fed controls, showed significant additional effects on energy metabo- lism – namely, reduced energy deposition in the body relative to gross energy intake. This could be due to either reduced digestibility of energy or reduction in efficiency of use of digested energy. The majority of experiments have shown no change or an extremely small (1 or 2 per- centage units) reduction in feed-energy digestion (Sykes and Coop, 1976, 1977), though MacRae et al. (1982) did observe a larger reduction. Precise attribution of the cause of reduced efficiency of energy use may therefore be equivocal. However, increased protein endogenous losses (see above) must lead to increased protein synthesis by GI tissue for which there is direct evidence (Jones and Symons, 1982; Yu et al., 2000). This, together with the fact that GI tissue accounts for 30–40% of energy expenditure in the uninfected animal (see Corbett and Ball, Chapter 7, this volume), must lead to the conclusion that absorbed energy is diverted to maintenance of the alimentary tract and its immune function and away from productive functions. Efficiency of use of metabolizable energy (ME) for growth or other productive functions must, by defi- nition, be reduced. The extent of such changes in energy partitioning may well vary with the site of infection. Whereas reduction in feed intake seems to be the major cause of reduced energy deposition in infections of the abomasum, reduction in efficiency of use of digested energy seems to be more important in infections of the small intestine (Sykes, 1994). This is demonstrated graphically in Fig. 14.2. The whole subject of the nu- trient requirement of the digestive tract, especially in response to pathogens, merits further investigation. Minerals For the effects of parasitism on mineral metabolism, most information is available for calcium (Ca) and P, as GI nematode infection has a marked effect on skeletal growth and mineralization of bones (Sykes et al., 1975, 1977). The effects are influenced by the location of the parasite within the GI tract and the extent of the lesions. With intestinal nematode infection (Trichostrongylus spp.), which causes extensive villous atrophy in the ante- 318 R.L. Coop and A.R. Sykes sheep nutrition Ch 14 7/17/02 4:00 PM Page 318 Gastrointestinal Parasites and Nutrients 319 E ne rg y re te nt io n MEm Metabolizable energy intake Un inf ec ted an im al A B A C Fig. 14.2. Change in efficiency of use of metabolizable energy (ME) as a result of infection with parasites. This can occur as a result of reduction of feed intake (C), reduction in efficiency of use of energy for bodyweight gain (A) or a combination of the two (B). Abomasal infections with T. circumcincta tend to be due to changes dominated by route C and those in the intestine with T. colubriformis by route A, particularly in the initial stages of infection. MEm, maintenance ME. rior small intestine (Plate 14.1), absorption and retention of P can be markedly reduced (Poppi et al., 1985; Bown et al., 1989), leading to low- ered plasma P concentrations and depressed secretion of P in the saliva (Coop and Field, 1983). There is also evidence for increased endogenous loss of Ca (Wilson and Field, 1983), but the overall effects of intestinal par- asitism on Ca absorption are less clear, as Ca homoeostasis is regulated through Ca absorption in ruminants, rather than by renal clearance as in non-ruminants. These disturbances in P metabolism and, by association, Ca can lead to severe osteomalacia and osteoporosis in parasitized sheep. Absorption of Ca and P is unaffected by nematode infections of the abomasum (Wilson and Field, 1983) and the reduced growth of the skele- ton observed in these infections is considered to result from disturbances in protein, rather than mineral, metabolism. There is little information available for interactions between GI nematode infection and other macrominerals. Bown et al. (1989) reported that absorption of magnesium was unaffected in parasitized sheep. One study has shown that the eleva- tion of abomasal pH, typical of infections in that organ, can lead to reduc- tion in the availability of copper (Cu) from therapeutic Cu oxide wire particles (Bang et al., 1990b). Otherwise, the information regarding trace- element metabolism is sparse and, in some cases, equivocal and will be con- sidered below in relation to its influence on the resistance and resilience of sheep to parasitism. sheep nutrition Ch 14 7/17/02 4:00 PM Page 319 lowered fecundity of an established parasite population. Studies using ‘trickle’ infections of Haemonchus contortus (Abbott et al., 1988) showed that faecal egg output of an established infection could be reduced by approxi- mately 30% when sheep were fed a high-protein diet (169 g CP kg−1 dry matter (DM)) in comparison with animals offered a low-protein ration (88 g CP kg−1 DM). Approximately three times as many worms were recovered at necropsy from the sheep that were offered the low-protein ration. Experimental studies with T. colubriformis infection in growing sheep have demonstrated that provision of additional protein, either as a direct infusion into the abomasum (Bown et al., 1991b; Coop et al., 1995) or fed as a dietary supplement (Kambara et al., 1993; van Houtert et al., 1995a; Datta et al., 1998), can lower the fecundity and/or increase the rate of expulsion of parasites from the host. The decrease in faecal nematode egg count or in the apparent rate of worm expulsion appears to be influenced by the level of protein supplementation offered (van Houtert et al., 1995a; Datta et al., 1998). There is evidence that these effects of supplementation on the expres- sion of resistance are greatest in the young animal, which has the greatest demand for a high protein : energy ratio (Kambara et al., 1993). Recently, it has been demonstrated that intake of digestible energy can also increase resistance of growing sheep to T. colubriformis infection (Kahn et al., 2000). The results from studies in which grazing animals have been given a protein supplement have been more variable (van Houtert et al., 1995b, 1996). Some have shown reductions in faecal nematode egg output but no effect of additional protein on worm populations at slaughter. Recently, the long-term benefits of providing short-term (9 weeks) protein supplementa- tion to sheep have been investigated (Datta et al., 1999). Following their turnout on to infected pasture, higher liveweight gain, wool production and lower worm egg counts were recorded in sheep previously supple- mented than in unsupplemented animals. These beneficial effects of short- term protein supplementation persisted for at least 16 months. It is well established that the immune status of ewes may be relaxed to varying degrees during the periparturient period. This periparturient relax- ation of immunity (PPRI) is particularly evident for abomasal nematode infections. The timing of PPRI is variable, but, in general, the immune status of the ewe is lowered from about 2–3 weeks before and up to 6–8 weeks after parturition (McAnulty et al., 2001). Outside this period the ewe is fairly refractory to GI nematode infection. The causes of PPRI are still subject to debate, but there is supporting evidence that it may have a nutritional basis. Termination in late pregnancy or removal of lambs at birth or during lacta- tion will restore the normal immune expression of the ewe to nematode infection. In addition, the relaxation of immunity is influenced by nutritional demand, being greater in ewes carrying or rearing twin lambs compared with singles. Most of the studies of this breakdown of immunity have focused on nutrition/parasite interactions involving the abomasal nematode T. (Ostertagia) circumcincta, as this is the predominant parasite contributing to PPRI in ewes in temperate areas. Recent investigations (Donaldson et al., 1998, 2001) have experimented with ewes infected concurrently with T. cir- 322 R.L. Coop and A.R. Sykes sheep nutrition Ch 14 7/17/02 4:00 PM Page 322 cumcincta and T. colubriformis. The results indicate that supplementation with protein in late pregnancy or early lactation or both can reduce the faecal nematode egg output and, in some cases, also reduce the worm populations. Similarly, in ewes bearing or rearing twins, Houdijk et al. (2000) showed that an increased intake of MP during pregnancy and lactation improved resis- tance and resilience to experimental infections with T. circumcincta. A pivotal experiment undertaken by Donaldson et al. (1998) demon- strated that protein supply appears to be more important than energy sup- ply in these host/parasite interactions in the ewe, a finding similar to that reported for young growing animals (Bown et al., 1991b). These data and those from recent experiments (Houdijk et al., 2001a, b) support the view that an increase in MP supply or a reduction in MP demand will partially ameliorate PPRI to T. circumcincta during periods when there is a scarcity of MP. Interestingly, the studies also suggest that the effect of supplementation may be more beneficial in more fecund sheep, further strengthening the argument that competitive demand for nutrients may be the cause of PPRI in ewes. It is also known that genetic selection for enhanced resistance in sheep can reduce the extent of PPRI, and the interactions between nutrition and genotype in breeding ewes merit further research (Kahn et al., 1999). Coop and Kyriazakis (1999) have developed a framework to consider this partitioning of nutrients between somatic tissue and the immune sys- tem during different phases of the growth cycle. This argues from available information in the literature that the poor growth of lambs during early infection occurs because acquisition of immunity is more important for sur- vival and would have priority over gain in body protein and hence the high susceptibility to infection. The partitioning framework suggests that responses of the immune system to protein supplementation would be small during this early acquisition phase but would be more apparent later in a parasitic infection, when the host is expressing a degree of immunity. In contrast, in the reproductive female, it appears that immunity is fore- gone in the interests of production. In the case of the latter, however, it appears that intakes of protein more than 30% greater than the con- ventional requirement may enable maintenance of immunity (Donaldson et al., 2001). There is general recognition that the milk-fed ruminant is well protected against infection, though whether this is a direct effect of the abundant protein supply or protection from the need to graze and there- fore from exposure to infective larvae has not been tested. Investigation of the mechanisms by which nutrition influences the specific immune responses has only just started. This reflects, in part, the recent recognition of the importance of nutrition, but also the rudimentary status of our understanding of the precise immune response. There is currently an accumulation of evidence to show that supplementation with rumen- undegradable protein can increase the numbers of immune-system effector cells in the intestinal mucosa (eosinophils and mucosal mast cells (MMC)) or peripheral blood (eosinophils), or both, of young lambs exposed to nematode larvae (Kambara et al., 1993; Coop et al., 1995; van Houtert et al., 1995a; Datta et al., 1998) and in ewes around parturition (Houdijk et al., 2000). Gastrointestinal Parasites and Nutrients 323 sheep nutrition Ch 14 7/17/02 4:00 PM Page 323 In some cases, these increases in cellular responses are associated with increased resistance to nematode infection. Changes in the humoral responses following protein supplementation in sheep with intestinal nematode infections are more variable (Kambara et al., 1993). It is likely that some components of the host’s immune response may have a dispro- portionate demand for specific amino acids. For example, leukotrienes, which are involved in cell-signalling, are rich in cysteine. Similarly, the increased mucus production that frequently accompanies GI parasitism will have a high requirement for proline, threonine and serine (MacRae, 1993). Interestingly, Coop et al. (1997) showed enhanced resilience to infection and increased numbers of intestinal MMC and mast-cell protease in sheep that were ‘trickle’-infected with T. colubriformis larvae and which received an additional supplementation of ‘protected’ methionine. Although the focus has centred on protein metabolism because of the large nutritional changes induced in the host, there may well be other simi- larly specific nutrient or environmental demands in the GI mucosa. The changes in resistance to larval establishment and worm fecundity shown in response to changes in dietary molybdenum (Mo) concentration in T. colubriformis-challenged sheep were closely mirrored by changes in intesti- nal antibody, granulocyte numbers in the blood and jejunal mucosa and in vitro worm-specific proliferation of lymphocytes (McClure et al., 1999). Most other studies involving mineral nutrition have not attempted to describe the underlying mechanisms causing increased resistance. It is known that intestinal parasitism can adversely affect mineral metabolism, particularly P, and there are data to indicate that resistance to intestinal Trichostrongylus vitrinus infection in sheep offered a low-P diet (1.88 g kg−1 DM) can be lower than on a comparable normal P ration (2.75g kg−1 DM) (Coop and Field, 1983). Total worm burdens were reduced by about 87% and faecal nematode egg counts lowered in sheep that were offered the higher-P ration and ‘trickle’-infected for 14 weeks. Whether this is due to P deficiency per se or a reduced intake of MP consequent on P deficiency is, as yet, uncertain. Low P intake would be compounded by the reduction in P absorption which is a consequence of intestinal parasitism (Wilson and Field, 1983). The normal recycling of P to the rumen is reduced and Coop and Field (1983) found rumen P concentrations of only 87 mg l−1, which is below the levels at which microbial protein production is impaired. There is also evidence for the influence of trace elements on resistance to nematode infection. Suttle et al. (1992) showed that the addition of Mo to the diet of sheep infected with T. vitrinus reduced the total worm burdens by 23%. There was evidence for some direct effect on the worms, in addition to indirect effects through enhancement of the immune response. As indicated above, resistance to larval establishment and MMC populations were opti- mized at a dietary Mo concentration of 6–10 mg Mo kg−1 DM. There is also evidence for reduction in faecal egg counts in lactating sheep at pasture when treated with a cobalt bullet (T.M. Gruner and A.R. Sykes, unpub- lished). Untreated sheep had elevated methylmalonic acid concentrations, indicating impairment of the propionate-to-glucose pathway, a consequence 324 R.L. Coop and A.R. Sykes sheep nutrition Ch 14 7/17/02 4:00 PM Page 324 experimentally infected with T. colubriformis larvae and offered a CT extract incorporated into the feed showed reduced worm burdens and a lower fae- cal egg count compared with sheep fed a comparable low or moderate level of protein without CT (Athanasiadou et al., 2000a; Butter et al., 2000). In addition to the indirect action of CT, there is recent evidence which indicates that they may exert direct anthelmintic effects on GI parasites (Athanasiadou et al., 2000b). Further research is required to assess the most appropriate means of incorporating tanniferous forages into grazing strategies, as many of the plants which show promise are not tolerant to high grazing pressure and some will not persist in more northern temperate climates. Forages with a low tolerance for grazing could possibly be used for short periods of graz- ing as deworming paddocks or be ensiled or conserved and fed to ewes as a supplement during the periparturient period. References Abbott, E.M., Parkins, J.J. and Holmes, P.H. (1988) Influence of dietary protein on the pathophysiology of haemonchosis in lambs given continuous infections. Research in Veterinary Science 45, 41–49. Athanasiadou, S., Kyriazakis, I., Jackson, F. and Coop, R.L. (2000a) Consequences of long-term feeding with condensed tannins on sheep parasitised with Trichostrongylus colubriformis. International Journal for Parasitology 30, 1025–1033. Athanasiadou, S., Kyriazakis, I., Jackson, F. and Coop, R.L. (2000b) Effects of short- term exposure to condensed tannins on adult Trichostrongylus colubriformis. Veterinary Record 146, 728–732. Balic, A., Bowles, V.M. and Meeusen, E.N.T. (2000) The immunobiology of gastroin- testinal nematode infections in ruminants. Advances in Parasitology 45, 181–241. Bang, K.S., Familton, A.S. and Sykes, A.R. (1990a) Effect of copper oxide wire par- ticle treatment on establishment of major gastrointestinal nematodes in lambs. Research in Veterinary Science 49, 132–137. Bang, K.S., Familton, A.S. and Sykes, A.R. (1990b) Effect of ostertagiasis on copper status in sheep: a study involving use of copper oxide wire particles. Research in Veterinary Science 49, 306–314. Bermingham, E.N., McNabb, W.C., Reynolds, G.W., Waghorn, G.C., Sutherland, I.A., Revell, D.K. and Roy, N.C. (2000) Whole-body irreversible loss rate of cys- teine and valine in sheep with or without a Trichostrongylus colubriformis infec- tion. Asian–Australasian Journal of Animal Sciences 13, 196–199. Gastrointestinal Parasites and Nutrients 327 Table 14.2. Agriculturally useful forage plants, which contain CT and have shown potential for improving resilience/resistance to GI nematode infection in sheep. Botanical name Common name Lotus uliginosus (pedunculatus) Greater bird’s-foot trefoil Lotus corniculatus Bird’s-foot trefoil Hedysarum coronarium Sulla Onobrychis viciifolia Sainfoin sheep nutrition Ch 14 7/17/02 4:00 PM Page 327 Bown, M.D., Poppi, D.P. and Sykes, A.R. (1989) The effects of a concurrent infec- tion of Trichostrongylus colubriformis and Ostertagia circumcincta on calcium, phos- phorus and magnesium transactions along the digestive tract of lambs. Journal of Comparative Pathology 101, 11–20. Bown, M.D., Poppi, D.P. and Sykes, A.R. (1991a) Nitrogen transactions along the digestive tract of lambs concurrently infected with Trichostrongylus colubriformis and Ostertagia circumcincta. British Journal of Nutrition 66, 237–249. Bown, M.D., Poppi, D.P. and Sykes, A.R. (1991b) The effect of post-ruminal infusion of protein or energy on the pathophysiology of Trichostrongylus colubriformis infection and body composition in lambs. Australian Journal of Agricultural Research 42, 253–267. Butter, N.L., Dawson, J.M., Wakelin, D. and Buttery, P.J. (2000) Effect of dietary tannin and protein concentration on nematode infection (Trichostrongylus colu- briformis) in lambs. Journal of Agricultural Science, Cambridge 134, 89–99. Coop, R.L. and Field, A.C. (1983) Effect of phosphorus intake on growth rate, food intake and quality of the skeleton of growing lambs infected with the intestinal nematode Trichostrongylus vitrinus. Research in Veterinary Science 35, 175–181. Coop, R.L. and Holmes, P.H. (1996) Nutrition and parasite interaction. International Journal for Parasitology 26, 951–962. Coop, R.L. and Kyriazakis, I. (1999) Nutrition–parasite interaction. Veterinary Parasitology 84, 187–204. Coop, R.L., Huntley, J.F. and Smith, W.D. (1995) Effect of dietary protein supple- mentation on the development of immunity to Ostertagia circumcincta in grow- ing lambs. Research in Veterinary Science 59, 24–29. Coop, R.L., Kyriazakis, I., Huntley, J.F., Jackson, E. and Jackson, F. (1997) The influence of protein and amino acid on the resilience of sheep to intestinal par- asitism. In: Proceedings 4th International Congress for Sheep Veterinarians, Armidale, Australia. University of New England, Armidale, pp. 196–198. Datta, F.U., Nolan, J.V., Rowe, J.B. and Gray, G.D. (1998) Protein supplementation improves the performance of parasitised sheep fed a straw-based diet. International Journal for Parasitology 28, 1269–1278. Datta, F.U., Nolan, J.V., Rowe, J.B., Gray, G.D. and Crook, B.J. (1999) Long-term effects of short-term provision of protein-enriched diets on resistance to nema- tode infection and liveweight gain and wool growth in sheep. International Journal for Parasitology 29, 479–488. Donaldson, J., van Houtert, M.F.J. and Sykes, A.R. (1998) The effect of nutrition on the periparturient parasite status of mature ewes. Animal Science 67, 523–533. Donaldson, J., van Houtert, M.F.J. and Sykes, A.R. (2001) The effect of dietary fish- meal supplementation on parasite burdens of periparturient sheep. Animal Science 72, 149–158. Dynes, R.A., Ankersmit, A.E.L., Poppi, D.P., Barrell, G.K. and Sykes, A.R. (1990) Studies on the physiological basis of appetite depression in nematode infection in sheep. Proceedings of the New Zealand Society of Animal Production 50, 249–253. Dynes, R.A., Poppi, D.P., Barrell, G.K. and Sykes, A.R. (1998) Elevation of feed intake in parasite-infected lambs by central administration of a cholecystokinin receptor antagonist. British Journal of Nutrition 79, 47–54. Fox, M.T. (1997) Pathophysiology of infection with gastrointestinal nematodes in domestic ruminants: recent developments. Veterinary Parasitology 72, 285–308. Gregory, P.C., Wenham, G., Poppi, D., Coop, R.L., MacRae, J.C. and Miller, S.J. (1985) The influence of a chronic subclinical infection of Trichostrongylus colubriformis on gastrointestinal motility and digesta flow in sheep. Parasitology 91, 381–396. 328 R.L. Coop and A.R. Sykes sheep nutrition Ch 14 7/17/02 4:00 PM Page 328 Horbury, S.R., Mercer, J.G. and Chappell, L.H. (1995) Anorexia induced by the parasitic nematode Nippostrongylus brasiliensis: effects on NPY and CRF gene expression in the rat hypothalamus. Journal of Neuroendocrinology 7, 867–873. Houdijk, J.G.M., Kyriazakis, I., Jackson, F., Huntley, J.F. and Coop, R.L. (2000) Can an increased intake of metabolizable protein affect the periparturient relaxation in immunity against Teladorsagia circumcincta in sheep? Veterinary Parasitology 91, 43–62. Houdijk, J.G.M., Kyriazakis, I., Coop, R.L. and Jackson, F. (2001a) The expression of immunity to Teladorsagia circumcincta in ewes and its relationship to protein nutrition depend on body protein reserves. Parasitology 122, 661–672. Houdijk, J.G.M., Kyriazakis, I., Jackson, F. and Coop, R.L. (2001b) The relationship between protein nutrition, reproductive effort and breakdown in immunity to Teladorsagia circumcincta in periparturient ewes. Animal Science 72, 595–606. Jones, W.O. and Symons, L.E.A. (1982). Protein synthesis in the whole body, liver, skeletal muscle and kidney cortex of lambs infected by the nematode Trichostrongylus colubriformis. International Journal for Parasitology 12, 295–301. Kahn, L.P., Knox, M.R. and Gray, G.D. (1999) Enhancing immunity to nematode parasites in pregnant and lactating sheep through nutrition and genetic selec- tion. In: Recent Advances in Animal Nutrition in Australia, Vol. 12. University of New England, Armidale, Australia, pp. 15–22. Kahn, L.P., Walkden-Brown, S.W. and Lea, J.M. (2000) Dietary enhancement of resistance to Trichostrongylus colubriformis in merino weaners. Asian–Australasian Journal of Animal Sciences 13, 68–71. Kambara, T., McFarlane, R.G., Abell, T.J., McAnulty, R.W. and Sykes, A.R. (1993) The effect of age and dietary protein on immunity and resistance in lambs vaccinated with Trichostrongylus colubriformis. International Journal for Parasitology 23, 471–476. Knox, M.R. and Steel, J.W. (1999) The effects of urea supplementation on produc- tion and parasitological responses of sheep infected with Haemonchus contortus and Trichostrongylus colubriformis. Veterinary Parasitology 83, 123–135. Knox, M. and Zahari, M.W. (2000) Urea–molasses blocks for parasite control. FAO Animal Production and Health Papers 141, 23–38. Kyriazakis, I., Oldham, J.D., Coop, R.L. and Jackson, F. (1994) The effect of sub- clinical intestinal nematode infection on the diet selection of growing sheep. British Journal of Nutrition 72, 665–677. Kyriazakis, I., Anderson, D.H., Oldham, J.D., Coop, R.L. and Jackson, F. (1996) Long-term subclinical infection with Trichostrongylus colubriformis: effects on food intake, diet selection and performance of growing lambs. Veterinary Parasitology 61, 297–313. Kyriazakis, I., Tolkamp, B.J. and Hutchings, M.R. (1998) Towards a functional explanation for the occurrence of anorexia during parasitic infection. Animal Behaviour 56, 265–274. Leyva, V., Henderson, A.E. and Sykes, A.R. (1982) Effect of daily infection with Ostertagia circumcincta larvae on food intake, milk production and wool growth in sheep. Journal of Agricultural Science, Cambridge 99, 249–259. MacRae, J.C. (1993) Metabolic consequences of intestinal parasitism. Proceedings of the Nutrition Society 52, 121–130. MacRae, J.C., Smith, J.S., Sharman, G.A.M., Corrigall, W. and Coop, R.L. (1982) Energy metabolism of lambs infected with Trichostrongylus colubriformis. In: Ekern, A. and Sundstol, E. (eds) Energy Metabolism of Farm Animals. European Association of Animal Production Publication No. 29, Agricultural University of Norway, Ås, Norway, pp. 112–115. Gastrointestinal Parasites and Nutrients 329 sheep nutrition Ch 14 7/17/02 4:00 PM Page 329