PATHOPHYSIOLOGY OF NEMATODE INFECTIONS P.H. HOLMES University of Glasgow Veterinary School, Bearsden Road, Glasgow, G61 (Scotland) U.K.
INTRODUCTION Gastrointestinal nematodes are a major cause of impaired productivity in ruminants throughout the world. The intensive grazing systems now used in many countries have tended to accelerate the weight of challenge and control has to be attempted using expensive methods of rotational grazing and/or the frequent use of anthelmintics. Numerous studies have demonstrated that even sub-clinical levels of infection can have considerable ecomonic effects. Furthermore, the adverse effects of gastrointestinal parasites may persist after the majority of the parasite population has been eliminated. The adverse effects on productivity are manifest in a variety of ways with changes in body weight the most common feature of infection. Reductions in liveweight gain vary with the level of infection, the species of parasite and the age, nutritional and immunological status of the host but can be considerable, e.g. up to 60% reductions in liveweight gain have been reported in sheep infected with Trichostrongylus colubriformis, Ostertagia circumcincta or Haemonchus contortus (Sykes & Coop, 1976, 1977; Abbott, Parkins & Holmes, 1986). In addition to changes in body weight, alterations in body composition also occur and are an important consideration in judging the economic impact of gastrointestinal helminths. The most commonly reported changes in parasitised ruminants are decreases in the deposition of fat, protein and skeletal calcium and phosphorus together with increased body water as a percentage of body weight, relative to pair-fed controls (vide infra). Gastrointestinal helminths also adversely affect both the quantity and quality of wool production. The inter-relationship between wool production and the weight of infection has recently been demonstrated in sheep exposed to T. colubriformis or 0. circumcincta or a concurrent infection with both parasites (Steel, Jones & Symons, 1982). The effect of gastrointestinal helminth infections on milk production by dairy cows has recently been the subject of considerable interest. Early studies indicated that anthelmintic treatment of clinically healthy dairy cows around the time of parturition caused a significant increase in milk yield (Bliss & Todd, 1976). However, later studies have, in general, failed to demonstrate any significant effect of gastrointestinal nematode infection or anthelmintic treatment on milk production of dairy cows (Michel, Richards, Altman, Mulholland, Gould & Armour, 1982; Kloosterman, Borgsteede & Eysker, 1984185). Few studies have been conducted in sheep but reduced milk production has been reported in housed ewes exposed to 0. circumcincta (Leyva, Henderson & Sykes, 1982) or H. contortus (Thomas & Ali, 1983) and more recently in sheep at pasture exposed to 0. circumcincta (Sykes & Juma, 1984). It is also likely that reproductive performance may be adversely affected by infection with gastrointestinal nematodes but detailed studies have not yet been reported. In heavy infections, mortality may arise as an important cause of economic loss, whilst moderate infection frequently causes premature culling of affected animals. The clinical signs and pathological features of these infections have been reviewed on numerous occasions in the past (e.g. Bremner, 1982; Sykes, 1983; Holmes, 1985). However, whereas the effects are well established, the precise mechanisms involved and the relative importance of different influences are still unclear. FEED INTAKE A common feature of infections with gastrointestinal nematodes is a reduction in voluntary food intake and this is widely recognised as a major factor in the pathogenesis of such infections. The degree of inappetence varies and is generally dose-related. Reductions of 20% or more in feed intake have been 443
frequently reported in lambs infected with T. cohbriformis (e.g. Sykes & Coop, 1976) or 0. circwncincta (COOP, Sykes & Angus, 1982). Recently the degree of inappetance in lambs infected with H. contort~s has been shown to vary not only with the level and duration of infection but also with the level of protein nutrition (Abbott et al., 1986). Similar reductions in feed intake have been reported in cattle following infection with T. uxei (Ross, Purcell & Todd, 1969), 0. ostertagi (Entrocasso, Parkins, Armour, Bairden & McWilliam, 1986 a), Cooperia pectinatu (Bremner, 1982), C. oncopkorcl (Armour, Bairden, Holmes, Parkins, Ploeger, Salman & McWilliam, unpublished) and Oesopkugostomum radiutum (Bremner, 1969). Despite the obvious importance of inappetance in parasitised ruminants, it remains to be determined why it occurs. A valuable review highlighting the limited state of present knowledge has recently been presented by Symons (1985). Numerous explanations have been offered but none of them is entirely satisfactory. Several authors in the past have suggested that pain may be important (Andrews, 1939; Gibson, 1955) but this is difficult to assess. It is also possible that alterations in gastrointestinal motility and digesta flow, even in the absence of diarrhoea, could be linked with changes in voluntary feed intake (Gregory, 1985). Changes in abomasal pH have been frequently reported in ruminants infected with abomasal parasites such as Ostertugia spp. (Ritchie, Anderson, Armour, Jarrett, Jennings & Urquhart, 1966) and occasionally in cases of intestinal trichostrongylosis (Barker & Titchen, 1982). Whether such changes are directly associated with reductions in appetite is not known but resultant alterations in protein digestion and the availability of amino acids for absorption could be important since the latter have been shown to stimulate appetite (Leng, 1981). Altered plasma concentrations of gastrointestinal hormones, and especially cholecystokinin (CCK), have also been implicated as a cause of inappetance in parasitised ruminants (Symons & Hennessy, 1981; Titchen, 1982). However, recent experiments using a radioimmunoassay have failed to show any increase in plasma CCK in inappetant sheep infected with trichostrongylosis and it is now uncertain whether this hormone plays a significant role in bringing about the relatively long-lasting inappetance commonly observed in parasitised ruminants (Symons, 1985). GASTROINTESTINAL
DIGESTION AND ABSORPTION
Although reduced appetite has a pronounced effect on the performance of infected ruminants, studies utilising pair feeding techniques have demonstrated that inappetance is not the only consequence of infection and such animals frequently show reduced utilisation of nutrients relative to parasite-free animals on the same feed intake. In view of their location and pathogenic effects in infected animals, it is generally assumed that gut parasites must be associated with changes in gastrointestinal function. However, so far it has been difficult to relate the two. This is partly because the number of studies has been limited and partly because it is difficult to evaluate the impact which dysfunction in one part of the tract may have on the whole animal. Nevertheless, some recent studies permit a better assessment of the effects of nematodes on gastrointestinal motility, digestion and absorption. Effects of nematode infections on motility have been investigated only in a small number of experiments. In lambs infected with T. cohbriformis it has been reported that digesta flow from the rumen was reduced but increased in the small and large intestine (Roseby, 1977). More recent studies have shown that subclinical infections of sheep with T. colubriformis alter the normal pattern of gastrointestinal motility in the absence of any diarrhoea and cause inhibition of abomasal and proximal small intestinal motility and digesta flow. However, the increased frequency of Migrating Myoelectric Complexes (MMCs) helps to maintain digesta flow through the proximal small intestine (Gregory, Wenham, Poppi, Coop, MacRae & Miller, 1985). Earlier studies on the influence of gastrointestinal nematodes on motility have generally used very heavy single infections which have resulted in diarrhoea accompanied by differing degrees of disruption of the normal pattern of gastrointestinal motility (Bueno, Dorchies & Ruckebusch, 1975; Bueno, Dakkak & Fioramonti, 1982). From the limited studies conducted on gastrointestinal motility in parasitised ruminants, it can be concluded that infections of the abomasum, small intestine and possibly the large intestine can seriously disturb the normal pattern of gastrointestinal motility and digesta flow, even in the absence of diarrhoea (reviewed by Gregory, 1985). Where studied, the rate of flow through the gut was reduced rather than increased, an effect which appears to be partly due to reduced food intake and partly to the influence of the parasites per se. With clinical infections, the onset of diarrhoea is preceded by the disruption of MMCs and severe inhibition of the reticula-rumen and abomasum, at which time there may be an increase in the bacterial populations which could contribute to the occurrence of the diarrhoea.
Pathophysiology of Nematodes
Gastrointestinal secretions have also been shown to be altered in parasitised ruminants. Infections of the abomasum with Ostertagia spp. and H. contortus are associated with elevations of abomasal pH and rises in blood pepsinogen concentrations. However, the impact of these changes on digestion are uncertain. One interesting facet related to acid secretion in the abomasum is the finding that the levels of gastrin in the blood are greatly elevated in sheep infected with 0. circumcincta (Anderson, Hansky & Titchen, 1981). Furthermore, elevations in plasma gastrin have been detected within 24 hours of direct transfer of adult Ostertagia spp. into the abomasum of previously uninfected sheep (Titchen, 1982) and calves (McKellar, Duncan, Armour & McWilliam, 1986). Such results imply that parasites or their secretions may have a direct effect on gastrin secretion or activity. In contrast, in sheep experimentally infected with intestinal nematodes (T. colubriformis) in which gastric secretion is also reduced, plasma gastrin levels are depressed (Titchen, 1982). Intestinal secretions are also affected by gastrointestinal nematodes. Reference has already been made to the possibility that CCK levels may be elevated in lambs infected with T. colubriformis (Symons & Hennessy, 1981) and this hormone is known to play an important role in the control of hepatic and pancreatic exocrine secretions. Further research is also likely to demonstrate that a number of other gastrointestinal hormones are altered in parasitised animals and these could influence both intestinal secretions and motility. Parasitic infections of the small intestine are associated with decreased activity of a variety of brush border enzymes (Jones, 1983) probably as a result of mucosal damage. In view of the structural damage and altered motility and secretions, numerous attempts have been made to determine whether impaired digestion and absorption are major causes of poor utilisation of food by parasitised ruminants. Although some studies suggest a reduction in the digestion or absorption of dietary nitrogen or other nutrients, such values are poor indicators of malabsorption. This is largely because of the significant passage of endogenous nitrogen and other materials into the gastrointestinal tract of parasitised animals (ride infra). Fewer difficulties arise with the evaluation of the results of balance studies using pair fed controls, though they still fail to permit direct assessment of digestion and absorption in different parts of the gastrointestinal tract. Ideally such studies should be conducted in animals with indwelling gastrointestinal cannulae. The results of such studies are discussed later but, in general, they indicate that impaired digestion and absorption are not important causes of the poor utilisation of nutrients by parasitised ruminants, rather, it is the increased metabolic demands on the host as a result of the parasites’ activities. These aspects are discussed in the following sections. PROTEIN METABOLISM A distinctive feature of gastrointestinal parasitism is loss of proteins into the gastrointestinal tract. The proteins represent plasma and red cells, exfoliated epithelial cells and mucus. Radioisotopic techniques have permitted measurement of blood protein losses into the tract and these techniques have been applied to a wide range of gastrointestinal nematode infections. The results have consistently shown high losses of plasma proteins in infected ruminants and in infections associated with gastrointestinal haemorrhage such as H. contortus (and Oe. radiatum), there is also a massive loss of red cells (Bremner, 1969; Holmes & Maclean, 1971; Dargie, 1975; Abbott et al., 1986). Unfortunately, methods to quantify losses of exfoliated epithelial cells and mucus are not yet available. However, there is little doubt that they are increased in parasitised ruminants. In both T. colubriformis and T. vitrinus infections of lambs, the elongated crypts contain increased mitotic figures (Coop & Angus, 1975; Coop, Angus & Sykes, 1979) and this is indicative of increased cell proliferation. Furthermore, it has been found that 3H-thymidine uptake by the abomasal mucosa is increased in sheep infected with H. contortus (Rowe, Abbott, Dargie & Holmes, 1982) which, again, is indicative of increased cell turnover. Another possible source of endogenous protein loss is an increase in mucus production as proliferation of goblet cells at the site of infection has been reported in sheep (Armour, Jarrett &Jennings, 1966) and in cattle (Murray, Jennings & Armour, 1970). Nitrogen balance studies have demonstrated that reduced nitrogen retention is a characteristic effect of helminth infections and is associated with depressed growth rates and other effects on productivity. In the majority of experiments, this has been associated with increased urinary nitrogen (N) loss (Parkins, Holmes & Bremner, 1973; Roseby, 1977; Sykes & Coop, 1976). However, nitrogen balance studies do not permit direct assessment of the levels of endogenous protein loss or the fate of the proteins within the tract. Such information can only be obtained from animals with indwelling gastrointestinal cannulae. Studies in cannulated sheep infected with 0. circumcincta or T. colubriformis indicated that nitrogen digestion and absorption was influenced by the site of infection and the level of feed intake (Steel, 1974, 1978). Later studies have tended to confirm these findings. A study by Rowe et a/. (1982) in sheep infected
with the abomasal parasite, H. contortus, and sheep “sham” parasitised by infusing similar amounts of blood (200 ml/day) into the abomasum as that lost by infected sheep, showed that the blood loss accounted for virtually all the increase in N flow into the duodenum (-6 g N/day) and this was all absorbed by the end of the ileum. In contrast, Poppi, MacRae & Corrigall (1981) and Kimambo (unpublished Ph.D. Thesis, University of Aberdeen, 1985) suggested that in lambs infected with T. colubriformis, plasma protein only accounted for about one fifth of the nitrogen lost into the small intestine, with about 3-5 g N/day extra reaching the terminal ileum. In these studies digestion and absorption of protein was estimated by the disappearance of ?S-labelled microbial protein and this was found to be unaffected by infection with T. colubriformis, i.e. a digestibility coefficient of 0.72. Measurement of the plasma protein leak usingVrCl3 indicated a loss of about 1.2 g N/day. If it can be assumed that the extra plasma protein N was digested at the same efficiency as that of microbial protein or possibly higher (Bown, Poppi & Sykes, 1984), it would have contributed about 0.35 g N/day to the N leaving the terminal ileum. The extra 2.75 to 3.0 g N/d reaching the terminal ileum not accountable in this way would appear to be derived from other sources. Since it is thought that mucus is neither digested nor absorbed in the small intestine, this may form a major source of the extra ileal nitrogen. Confirmation of this possibility depends upon the development of techniques for quantifying mucus secretion. The possibilty of increased intestinal secretions of cysteine-rich mucoproteins in parasitised sheep and the unavailability of the cysteine moiety for reabsorption by the time the digesta reaches the terminal ileum (Walker, Weeks & Armstrong, 1979) is consistent with the finding that requrements for sulphur containing amino acids are increased by about 50% in sheep infected with I’. colubriformis (Steel & Hennessy, 1975). Attempts to evaluate protein deposition and tissue metabolism in parasitised hosts have been limited. One approach has been to examine feed utilisation in infected animals. For example, in lambs chronically infected with 0. circumcinctu Sykes & Coop (1977) and Coop et al. (1982) demonstrated a significant reduction in the deposition of fat and protein in infected animals compared with pair-fed controls. More recently, carcase evaluation studies have been conducted in cattle infected with mixed trichostrongyles (Entrocasso, Parkins, Armour, Bairden & McWilliam (in press(b)) and at slaughter various parameters of protein deposition were found to be reduced in parasitised animals compared with parasite-free controls. A series of studies by Symons and his co-workers to examine tissue protein synthesis using ‘C-L-leucine and ‘C-L-tyrosine in parasitised animals is particularly relevant (reviewed by Symons, 1985). Early experiments indicated that protein synthesis was reduced in skeletal muscle of pair-fed controls as well as infected sheep (Symons &Jones, 1975). However, in later experiments with tyrosine by Jones & Symons (1982), the fractional synthetic rate (FSR) and protein synthesis/d by the semitendinosus muscle and kidney cortex were reduced in infected animals but not in pair-fed controls, although the level of inappetance was much less than in the earlier studies. The rate of protein synthesis by the liver was increased in infected animals but not in pair-fed controls. Earlier studies showed that protein synthesis by homogenates of wool follicles of sheep with trichostrongylosis was depressed by over 50% (Symons & Jones, 1975). Measurements of protein synthesis by the gastrointestinal tract have for technical reasons so far been restricted to guinea-pigs infected with T. colubriformis. In such animals the amount of protein synthesis/d was increased in both the small and large intestine (Symons &Jones, 1983). It is important that this finding is confirmed in ruminants as these sites of increased protein synthesis may be an important cause of reduced nutrient utilisation by infected sheep and cattle. As a result of such studies, Symons (1985) concluded that, due to inappetance, gastrointestinal losses of protein and increased rates of gastrointestinal tissue protein metabolism, there is a net movement of amino acid nitrogen from muscle and skin to the liver and gastrointestinal tract which decreases the availability for growth and milk and wool production. However, it is still not possible to construct accurate balance sheets of protein synthesis in parasitised ruminants nor is there any detailed information on the underlying mechanisms, including hormonal, which may be responsible for the changes in protein synthesis. ENERGY METABOLISM There is a shortage of information on energy metabolism in parasitised ruminants. Reduced feed intake is undoubtedly a major factor limiting the availability of energy for maintenance and growth. Reductions in apparent energy digestibility have been reported (Sykes & Coop, 1977; MacRae, Smith, Sharman, Corrigall & Coop, 1982; Entrocasso et al., 1986a) but these have in general been very small, even in diarrhoeic animals. Similarly, the few measurements that have been made of heat production have failed to show any significant differences between infected and control animals (Randall & Gibbs, 1982; MacRae et a/., 1982; Stevenson, Thomas & Holmes, unpublished observations). However, comparative slaughter
Pathophysiolugy of Nematodes
experiments in lambs infected with T. colubriformis (Sykes & Coop, 1976) or 0. circumcincta (Coop et al., 1982) have shown such animals to have a lower energy retention than parasite-free pair-fed controls. The reasons for this have not been accurately determined. Recent findings, for example, that lambs with subclinical haemonchosis had higher levels of methane production than controls (Stevenson, Thomas & Holmes, unpublished observations) suggest that increased methane production along with urinary urea excretion could account for part of the reduced retention of digestible energy (DE). However, the most likely cause for the reduction in the efficiency of utilisation of DE, which is supported by the findings of Jones & Symons (1982) and Symons & Jones (1983), is that there are marked increases in synthetic rates of protein in the liver and gastrointestinal tissue. It is difficult to estimate the true cost of protein synthesis but if a value of 30kJMEig protein is assumed, it has been calculated that the 50% reduction in energy retention reported by Sykes & Coop (1976) in lambs infected with T. cofubr~formi~ would be accounted for by the additional synthesis of about 30 g protein/day (Sykes, 1983). This is in reasonable agreement with the estimates of Jones & Symons (1982) for increased synthesis of 50 g protein/day of gastrointestinal tissue. At the present time such figures must remain only estimates due to the lack of appropriate techniques for compartmentalising energy costs for protein synthesis. MINERAL METABOLISM A number of workers have demonstrated that skeletal growth and mineralisation are impaired in sheep infected with T. co~ubriform~s (Reveron, Topps & Gelman, 1974; Sykes & Coop, 1976), T. l~ifrinus(Sykes, Coop & Angus, 1979) or 0. circumrincta (Sykes, Coop & Angus, 1977). For example, Sykes et al. (1977) found that lambs infected by continuous dosing with 0. circumcincta deposited bone minerals (Ca and P) at only 35% of that of non-infected pair-fed controls. In lambs infected with T. colubriformis the effect was even greater and almost complete cessation of skeletal growth and mineralisation have been reported (Sykes & Coop, 1976). There are several possible causes for impaired skeletal growth in parasitised sheep and these appear to be related to the level and site of infection. In lambs infected with the abomasal parasite 0. circumcincta the skeletal changes have been attributed to deficiencies of protein and energy induced by the parasite leading to a matrix osteoporosis (Sykes et af., 1977). The results of experiments using @Ca and “P by Wilson & Field (1983) support this view since neither phosphorus or calcium absorption were found to be affected. In sheep infected with T. colubriformis and other intestinal nematodes, reduced bone matrix synthesis due to an induced protein deficiency probably also occurs but it is exacerbated by a reduction in the apparent absorption of P (Sykes & Coop, 1976; Poppi, MacRae, Brewer, Dewey & Walker, 1985) and the true absorption of phosphorus (Wilson & Field, 1983). There are also increased losses of endogenous P and Ca as a result of intestinal parasitism but apparently not with abomasal infections (Wilson & Field, 1983). The net effect of this is to induce a P deficiency, leading to a reduced flow of salivary P and a reduction in the plasma concentration of P. The effect on Ca metabolism was found to be limited to an increase in endogenous faecal excretion. WATER AND ELECTROLYTE
Diarrhoea is commonly reported in parasitised ruminants and especially in those at pasture. In experimental infections increases in the water content of the faeces leading to frank diarrhoea have been reported in moderate to heavy infections of all the important gastrointestinal nematodes except Haemonthus spp. In abomasal infections with Ostertagiu spp. the onset of diarrhoea has been found to coincide with the maturation of larvae into young adults. This also corresponds with the time that many of the pathophysiological changes such as inappetance, plasma protein losses and negative nitrogen balance are particularly pronounced (Holmes & Maclean, 1971; Parkins et al., 1973). Associated with this stage of abomasal infection, water turnover is markedly altered (Holmes & Bremner, 1971). In calves infected with 0. ostertugi significantly greater amounts of water (about 20%) may be excreted in both urine and faeces (Parkins, Bairden & Armour, 1982). However, diarrhoea may not necessarily be accompanied by an overall increase in fluid loss. Bremner (1982) showed that, although faecal water losses in calves with heavy infections of C. pectinatu were higher than in worm-free controls, urine losses were considerably below normal so, contrary to expectation, infected calves lost less water than worm-free controls and also excreted less sodium. However, potassium losses in infected calves were more then ten times those of controls and this may be indicative of the massive sloughing of intestinal epithelial cells which is thought to occur in gastrointestinal nematode infections (vide supra). It is also of interest that, in
P. H. Holmes
calves with severe infections of C. pectin&z, plasma volumes are decreased and haemoconcentration occurs. In contrast, expansion of the plasma volume has been reported in many other nematode infections of ruminants (e.g. Holmes & Maclean, 1971; Dargie, 1975; Abbott, Parkins & Holmes, 1985b). The reasons for these differences are not clear, nor is it known why changes in plasma volume commonly occur in parasitised ruminants, although is is assumed this must reflect changes in hormone balance. Various studies have demonstrated that the water rentention of parasitised ruminants is commonly higher than in parasite-free controls (Halliday, Dalton, Anderson & Mulligan, 1965; Entrocasso et ul., 198613; Abbott et al., 1986). Such changes in water retention clearly demonstrate that tissue loss attributable to parasitic infections cannot be reliably determined from changes in body weight alone. FACTORS MODULATING HOST RESPONSES In addition to the pathogenic mechanisms associated with different species of parasite and the different levels of infection, it is now recognised that there are a number of host factors which can influence the pathophysiology of parasitic infections. These include the genetic background of the host, the plane of nutrition and immunological status. Genetic resistance to parasitic infections has been recently reviewed by Dargie (1982). Over the past 50 years there have been several studies to investigate the influence of nutritional factors on the pathogenesis of gastrointestinal nemataode infection. The early studies (Whitlock, 1949; Gibson, 1963) generally indicated that animals on improved planes of nutrition resist parasitism better than those on poorer planes. However, the mechanisms involved have rarely been elucidated. Some workers have suggested that initial establishment is not affected but the infection may be prolonged and the fecundity of the parasites enhanced by low protein diets (Bawden, 1969, while others have suggested that parasite establishment is altered by the level of protein nutrition (Preston & Allonby, 1978). Unfortunately many of the experiments conducted in the past have been unsatisfactory either because of inadequate controls or poorly formulated diets. Recent studies conducted in lambs infected with H. contortus (Abbott, Parkins & Holmes, 1985a, b, 1986) attempted to overcome some of these difficulties by using pair-fed controls and a compounded diet which only differed in protein content. In summary, the results showed that the protein content of the diet per se did not influence the establishment of single primary infections. However, lambs given a low protein diet showed more severe clinical signs such as weight loss, anaemia and inappetance despite similar levels of blood loss. These effects can also be accentuated by genetic factors since breeds particularly susceptible to haemonchosis, such as Merino and Finn Dorset, are more severely affected than relatively less susceptible breeds, such as Scottish Blackface, on low levels of protein nutrition (Abbott et al., 1985a, b). In Finn Dorset lambs subjected to continuous infections, those animals given a high protein diet developed resistance to reinfection, whilst those on a low plane of nutrition did not (Holmes, Abbott & Parkins, 1986). Such studies illustrate the importance of suboptimal nutrition in field situations where the problem may be further exacerbated by the additional metabolic demands arising from the extensive searching for food on poor quality pasture. The immunological status and age of the host may also influence the pathogenesis of nematode infections. The majority of experimental infections have been conducted in young ruminants and it is in such animals that the major effects of infection are observed. However, it is now becoming apparent that older animals at pasture which are generally judged to be relatively immune, on the basis of low parasite burdens, may suffer production losses when exposed to larval challenge (Anderson, 1973; Barger & Southcott, 1975). Later studies by Yakoob, Holmes & Armour (1983) confirmed that immune ewes challenged with a mixed trichostrongyle infection (90% 0. circumcincta) showed marked pathophysiological disturbances and particularly a doubling of plasma pepsinogen levels, albumin catabolism and losses of plasma proteins into the gastrointestinal tract and that, if larval challenge was continued, these effects could persist for several months (Stevenson, Holmes & Armour, unpublished observations). The results of studies with the intestinal nematode T. colubriformis have been inconclusive. In studies by Barger & Southcott (1975) wool growth was reduced by larval challenge of naturally immune sheep. However, studies in which lambs have been made resistant to infection by vaccination with gammairradiated larvae failed to demonstrate any effects on productivity as a result of continuous larval challenge. Nevertheless, the onset of challenge of immune sheep with T. colubriformis larvae has been shown to be associated with a transient rise in enteric losses of protein (Jones, Steel & Wagland, unpublished observations; Joint Meeting of the Australian and New Zealand Societies for Parasitology, Christchurch, Aug. 1984; Kimambo, 1985, thesis cited above). In conclusion, the results indicate that the response of immune sheep to larval challenge varies with the species of parasite and the method of immunisation. Further studies are required to elucidate the
mechanisms involved. It is also important to investigate the inter-relationships between nutrition and the development of immunological responses to gastrointestinal nematodes (Wagland, Steel, Windon & Dineen, 1984; Holmes et al., 1986). SUMMARY Gastrointestinal nematodes are a major cause of reduced productivity in ruminants. An important feature of such infections is reduced feed intake, the aetiology of which remains uncertain. Alterations in gastrointestinal motility and digesta flow may be partially responsible for the inappetance as well as being associated with the occurrence of diarrhoea. However, digestion and absorption are, in general, not significantly impaired. The other distinctive feature of gastrointestinal parasitism is loss of proteins into the gastrointestinal tract and resultant changes in host metabolism account for much of the reduced protein and energy retention by infected animals. Mineral metabolism and water and electrolyte balance are also frequently disturbed. These pathophysiolog~cal effects may be modulated by a number of factors, including the nutritional and immunological status of the host. Details of the precise mechanisms involved in these interactions and several other aspects of the pathophysiology of nematode infections still require investigation. REFERENCES PARKINS J.J. & HOLMES P.H. 1985a. Influence of dietary protein on parasite establishment and Dorset and Scottish Blackface lambs given a single moderate infection of Haemonch~s contortus. Research in Veterinary Science 38: 6-13. ABBOTT EM., PARKINS J.J. & HOLMES P.H. 1985b. Influence of dietary protein on the pathophysiology of ovine haemonchosis in Finn Dorset and Scottish Blackface lambs given a single moderate infection. Research in Veterinary Science 38: 54-60. ABBOTT E.M., PARKINS J.J. & HOLMES P.H. (1986). The effect of dietary protein on the pathogenesis of acute ovine haemonchosis. Veierinary Parasitology. In press. ANDERSON N. 1973. Trichostrongyloid infections of sheep in a winter rainfall region. II. Epizootioiogical studies in the western district of Victoria. Australian Journal of Agricultural Research 24: 599-6ll. ANDERSON N., HANSKY J. & TITCHEN D.A. 1981. Effect of Ostertagja &~rc~fmcj~lcfuinfections on plasma gastrin in sheep. Purasifofogy 82: 761-770. ANDREWS J.S. 1939. Experimental trichostrongylosis in sheep and goats. Journul of Agr~cu~utra~ Research 58: 401410. ARMOUR J., JARRETT W.F.H. & JENNZ~VFS F.W. 1966. Experimental Ostertagia circumcincta in sheep. Development and pathogenesis of a single infection. American Journal of Veterinary Research 27: 1267-1278. BARGER LA. & SOUTHCOTT W.H. 1975. Trichostrongylosis and wool growth. The wool growth response of resistant grazing sheep to larval challenge. Australian Journal of Experimental Agriculture and Animal Husbandry ABBOTT EM.,
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nematode inhabiting the small intestine. International Journal for Parasitology 12: 345-3.56. BAWDEN R.J. 1969. The establishment and survival of Oesophagostomum columbianum in male and female sheep given high and low protein diets. Australian Journal of Agricultural Research 20: 1151-l 1.59. BLISS D.H. & TODD A.C. 1976. Milk production by Vermont dairy cattle after deworming. Veterinary Medicine and Small Animal Clinician 68: 1034-1038. POPPI D.P. & SYKES A.R. 1984. The effect of a mixed nematode infection on the site of plasma protein absorption in the small intestine. Cunad~an Journal of Animal Science64 (Suppi.): 197-198. BREMNER K.C. 1969. Pathogenic factors in experimental bovine oesophagosomosis. HI. Demonstration of proteinlosing enteropathy with “0-albumin. Experimental Parasitology 24: 364-374. BREMNER K.C. 1982. The pathophysiotogy of parasitic gastroenteritis of cattle. In: Biology and Control of Endoparusites pp 277-289 (Edited by Symons. L.E.A., Donald, A. & Dineen, J.) Academic Press, Australia. BUENO L., DORCHIES P. & RU~KEBUSCH Y. 1975. Analyse Clectromyographicuq des perturbations matrices likes aux strongyloses gastro-intestinales chez les ovins. Comptes rendus des seances de la Societe’de Biologie 169: 1627-1632. BUENO L., DAKKAK A. & FIORAMONTI J. 1982. Gastro-duodenal motor and transit disturbances associated with Haemonchus contortus infection in sheep. Parasitology 84: 357-374. COOP R.L. & ANGUS K.W. 1975. The effect of continuous doses of Trichostrongylus colubriformis larvae on the intestinal mucosa of sheep and on liver Vitaman A concentration. Parasitology 70: l-9. COOP R.L., ANGUS K.W. & SYKES A.R. 1979. Chronic infection with Trichostrongylus vitrinus in sheep. Pathological changes in the small intestine. Research in Veterinary Science 26: 363-371. COOP R.L., SYKES A.R. & ANGUS K.W. 1982. The effect of three levels of intake of Ostertagia circt*mcinctalarvae on growth rate, food intake and body composition of growing lambs. Journal of Agr~cu~fura~ Science (Cambridge) 90: 247-255. BOWN M.D.,
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