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Biomedical subjects

R L Coop

Publications and source records attributed to R L Coop.

At least 37 records · Page 2Linked to original sources

Temporal effects of protein nutrition on the growth and immunity of lambs infected with Trichostrongylus colubriformis.

The aim of this research was to determine whether metabolisable protein supply during the early period of infection with Trichostrongylus colubriformis influenced resilience and the later stages in the development and magnitude of host resistance in previously nematode-naïve lambs. Eighty TexelxGreyface lambs were fed pelleted feeds calculated to provide grossly different amounts of metabolisable protein. Sixty of the lambs received a trickle infection of T. colubriformis and 20 lambs were kept as uninfected controls. There were four initial groups, namely infected or uninfected and fed either a moderate or a high protein feed. After 5weeks of infection, a further four groups were established by changing the feed of half of the animals fed the moderate protein feed to the high protein feed and of half of the animals fed high protein to the moderate protein feed. Live weight gain and feed conversion ratio were greatest for lambs fed the high protein feed and were reduced by infection. Faecal egg counts, worm burdens and per capita fecundity of adult female nematodes were unaffected by changes to metabolisable protein supply. Decreasing metabolisable protein supply following 5weeks of infection reduced live weight gain without any effect on resistance to T. colubriformis. Haematological variables, indicative of improved resistance, were also largely unaffected by metabolisable protein supply. It is concluded that the requirements of immune function probably had priority over those of growth and that the metabolisable protein supply provided by the moderate protein feed was sufficient to account for the requirements for the expression of immunity. It is probable that the potential for metabolisable protein supply to enhance resistance to infection from T. colubriformis is dependent on the levels and magnitude (i.e. in relation to maintenance requirements) of metabolisable protein supply being compared and the demand of other competing physiological functions.

Animals↗

The development of anthelmintic resistance in sheep nematodes.

Anthelmintic resistance now poses problems to sheep farmers throughout the world. In some Southern hemisphere countries multiple resistance has reached levels which make sheep farming non-sustainable. Evidence from studies in the UK and Europe suggests (a) that the selection process occurs over a longer time frame than in Southern tropical/temperate regions and (b) that for some of the key ovine species little or no reversion to susceptibility may occur for many years after the withdrawal of the selecting agent. The dynamics of the selection process are influenced by a number of host, parasite, drug, management and environment-dependent factors. Recent mechanistic studies on resistance against avermectins and milbemycins (AM) suggest that there may be a number of mechanisms associated with resistance at the different target sites for these drugs. Within Europe endectocides within the AM drug group have now become the crucial element in strategies aimed at controlling important diseases such as sheep scab and nematodoses. Given that there is little likelihood of a series of novel action compounds emerging in the immediate future to replace this family the conservation of efficacy of the AM group should be accorded the highest priority for research in this area.

Animal Husbandry↗

Subclinical infection with the nematode Trichostrongylus colubriformis increases gastrointestinal tract leucine metabolism and reduces availability of leucine for other tissues.

Gastrointestinal (GI) tract leucine metabolism was measured in 6- to 9-mo-old lambs subjected to trickle infection with Trichostrongylus colubriformis larvae and in separate animals that were not infected. Animals prepared with a jejunal catheter and with indwelling catheters into the aorta and the portal- (PDV) and mesenteric- (MDV) drained viscera were infused simultaneously with [1-13C] and [5,5,5-2H3] leucine to determine GI tract sequestration of leucine from arterial and luminal amino acid pools by tracer and tracee arteriovenous concentration differences. Leucine oxidative losses and net fluxes were also determined across the GI tract. Infection had no detectable effect on whole-body leucine flux, but it increased total GI tract leucine sequestration by 24% (P<.05) and GI tract oxidative losses of leucine by 22 to 41% (P<.01). Net PDV fluxes of leucine were decreased by 20 to 32% during the infection. The infection did not alter either the proportion of precursor leucine used by GI tract metabolism that was derived from the arterial leucine pool (.84 to .88) or the proportional sequestration of digesta-derived leucine during "first pass" absorptive metabolism (.12 to .18). These findings help to elucidate the metabolic basis for the reduced growth rates and nitrogen retention observed when animals are subjected to subclinical nematode infection.

Animals↗

Nutrition-parasite interaction.

The interactions between host nutrition and parasitism in ruminants are viewed within a framework that accounts for the allocation of scarce nutrient resources, such as energy and protein, between the various competing body functions of the host. These include functions that are the direct result of parasitism. Since it is proposed that the host gives priority to the reversal of the pathophysiological consequences of parasitism over other body functions, it is to be expected that improved nutrition will always lead to improved resilience. On the other hand, it is proposed that the function of growth, pregnancy and lactation are prioritised over the expression of immunity. Thus, improved nutrition may affect the degree of expression of immunity during these phases. The framework is useful at highlighting areas of future research on host/parasite/nutrition interactions. Its suggestions can account for the observations of the periparturient relaxation of immunity in reproducing females, as well as the reduction in worm burden in small ruminants supplemented with additional protein. Although developed for gastrointestinal nematodes in ruminants, the concepts of the framework should be applicable to the interactions of nutrition in other parasitic diseases.

Animal Nutritional Physiological Phenomena↗

Persistence of immunity of Nematodirus battus infection in lambs.

Fifty-four Greyface Suffolk lambs aged 3 months were allocated to six groups of seven and one group of 12. Three groups were infected continuously with Nematodirus battus larvae (L3) over a 7-week period and three groups remained worm-free. One week after the last larval dose all six groups were treated with anthelmintic and challenged with a single dose of 30,000 N. battus L3 either 1, 6 or 12 weeks post-treatment (PT) and killed 10 days later. A seventh continuously infected and treated group (n = 12) was segregated into four sub-groups of three lambs which were used as tissue cell count controls and provided data on local cellular responses prior to challenge. Lambs in the first sub-group were killed immediately after anthelmintic treatment and those in the other sub-groups were killed on the same day that the lambs in the other main groups were challenged. Overall post-challenge worm burdens did not differ significantly between previously infected and challenge control groups although they were significantly reduced in both treatment groups by Week 12 PT. The principal manifestation of acquired immunity that was maintained throughout 12 weeks without further infection was retardation in larval development. There was also evidence of preferential rejection of male worms from immune lambs. Local mast cell, but not eosinophil, responses were significantly enhanced by previous infection and persisted up to Week 12 PT. The numbers of bone marrow eosinophils were significantly increased as a result of previous infection and this response persisted up to Week 12 PT. During primary infection anti-L4 and anti-adult worm IgG responses were significantly increased in the previously infected lambs by Day 42 post-infection. Eosinophil responses during this period did not differ between groups. The inflammatory cell responses, coupled with the parasitological observations, suggest that immunity to previous infection is maintained for up to 12 weeks PT without further antigenic stimulation. This 'immunological memory' may have waned partially after 6 weeks PT although the superimposition of age resistance may have masked the effect.

Animals↗

The pathophysiology and development of immunity during long-term subclinical infection with Trichostrongylus colubriformis of sheep receiving different nutritional treatments.

The objective of this study was to investigate the relationship between protein nutrition, the pathophysiology, and acquisition and expression of immunity in long-term subclinical intestinal parasitism in sheep. Growing sheep were either uninfected controls or parasitised for 27 weeks with a daily dose of 2500 larvae of Trichostrongylus colubriformis, whilst they were given access to: (1) a low protein food, (2) a high protein food, or (3) a choice between the two foods, where they were allowed to select their diet. Blood samples were taken weekly for determination of serum albumin, total protein, Ca, P, urea and fructosamine concentrations. At the end of the study all sheep received a single (secondary) challenge infection (30,000 T. colubriformis L3) after treatment with anthelmintic to assess their immune status. The concentrations of sheep-mast cell proteinases (SMCP) in intestinal tissue, the number of circulating eosinophils and the total worm numbers recovered from the intestinal tract were used to investigate the effects of previous nutrition on the acquisition and expression of immunity. From the biochemical variables measured over 27 weeks, only serum fructosamine was affected by the interaction between feeding treatment and parasitism: fructosamine concentrations declined only in the parasitised animals on the low protein food during Weeks 6-15 of infection. This casts doubt on the usefulness of plasma fructosamine levels as an indicator of gastrointestinal parasitism, due to its being influenced by the nutritional environment. Total protein, albumin, calcium and phosphorus concentrations in the serum were affected by parasitism, but independently of feeding treatment. During the period of secondary challenge eosinophil numbers and SMCP concentrations were higher in the parasitised animals, reflecting the animals immune responsiveness. The numbers of worms recovered from the intestine of previously parasitised sheep were low; all three indicators of the development of acquired immunity were unaffected by previous nutritional treatment of the sheep. The results do not support the view that the pathophysiology of long term subclinical intestinal parasitism and the expression of acquired immunity induced by a trickle infection could be affected by the feeding treatment of the sheep (protein nutrition).

Animal Nutritional Physiological Phenomena↗

Long-term subclinical infection with Trichostrongylus colubriformis: effects on food intake, diet selection and performance of growing lambs.

Growing lambs (mean liveweight 22.4 kg) were used to test for the effects of long-term subclinical infection with Trichostrongylus colubriformis (2500 larvae per day) on the voluntary food intake (VFI), diet selection and performance of sheep given a choice between two foods of different protein content (low versus high). Sheep were either uninfected controls or parasitised for 27 weeks (Group 27P). Additional sheep were infected for either 9 or 18 weeks (before and after the development of complete resistance to parasites, as assessed by faecal egg counts) and then treated with anthelmintic to remove the parasites (Groups 9P and 18P). Group 18P remained uninfected after anthelmintic treatment whereas Group 9P was infected again for the last 9 weeks after a 9 week worm-free period. The VFI declined or remained static from Week 5 up to Week 11/12 of continuous infection, for the 27P and 18P groups. For 9P sheep, VFI recovered within a few days after the anthelmintic administration and was unaffected during re-infection over the last 9 weeks of the experiment. Diet selection changed in such a pattern that the proportion of the high protein food (prop H) in the selected diet started to increase from Week 6 of the infection. The prop H selected remained higher over the interval 10-18 weeks of the continuous infection for 27P and 18P groups than the uninfected controls. There were no significant differences in diet selection among any of the groups beyond Week 18 of the experiment. The infection caused a growth check from Week 7 to approximately Week 12/14 of dosing; these was no evidence of compensatory growth following the development of resistance or recovery. The results are consistent with the view that sheep given a choice between two appropriate foods will modify their diet selection in order to moderate the adverse effects of subclinical nematode infection. The performance and diet selection of all sheep beyond Week 18 of infection suggest that no obvious nutritional penalties are incurred with the continuation of the infection once the animals have become resistant to parasites.

Animals↗

Dietary protein influences upon immunity to Nematodirus battus infection in lambs.

Several indices of the immune response to Nematodirus battus infection in lambs offered differing levels of dietary protein were quantified. Lambs were offered either a complete basal ruminant diet (13.2% crude protein (CP)) or the same diet supplemented with fish meal as a source of rumen bypass protein (18.3% CP). Lambs from each dietary treatment group were given either a 7-week continuous trickle infection with N. battus L3 or remained uninfected. All lambs were drenched with anthelmintic at week 8 post-infection (PI), challenged with a single dose of 30,000 N. battus L3 1 week later, and killed 9 days post-challenge (PC). Previous infection induced a significant reduction in worm burdens (p < 0.001) and enhancement of immune responses when compared to challenge controls. Among previously infected lambs, protein supplementation did not reduce worm burdens significantly, although there was a trend for fewer worms in the supplemented lambs. However, a significant increase in mucosal globule leucocyte (p < 0.05) and eosinophil (p < 0.05) numbers was evident. Supplementation (p < 0.05) and previous infection (p < 0.001) both enhanced serum anti-worm IgG titres over time. Peripheral blood eosinophil counts were not affected by supplementation but were significantly elevated over time as a result of previous infection (p < 0.001). Since there were no significant differences in worm burdens of supplemented and unsupplemented previously infected lambs, it was of interest to determine whether lambs possessed an innate ability to regulate their parasite burden. Hence they were re-grouped based on an arbitrary cut-off burden of 1000 worms. High responders (HR) had burdens below 1000 worms, while low responders (LR) had burdens above this value and challenge controls were pooled. The data were re-analyzed based on these groupings and showed significant reduction in worm burdens between all three groups (p < 0.001). Globule leucocytes were the only cell type that appeared to be significantly more abundant in the intestinal mucosa of HR (p < 0.001). Serum antibody responses (p < 0.05) and peripheral blood eosinophil counts (p < 0.01) were significantly elevated over time in accord with the degree of responsiveness. The results of this study suggest that supplementation of protein upon an adequate basal diet of lambs previously exposed to N. battus does not significantly enhance worm regulation despite significant increases in cellular and antibody responses. The immunity acquired is characterized by reduction in worm burdens, elevated anti-worm antibodies and a cellular inflammatory response. The identification of HR and LR essentially shows that when the protein supply is adequate, the predominant host effect influencing the pathogenicity of the parasites is the level of genetically determined susceptibility of the host.

Analysis of Variance↗

Effect of dietary protein on the regulation of populations of Nematodirus battus by lambs.

Two groups of seven and two groups of six lambs were offered either a complete basal ruminant diet (13.2 per cent crude protein [CP]) (groups 2 and 4) or the same diet supplemented with fish meal (18.3 per cent CP) (groups 1 and 3). Groups 1 and 2 were infected daily for seven weeks with Nematodirus battus larvae (L3) and groups 3 and 4 served as uninfected challenge controls. All the groups were treated with anthelmintic in the eighth week, challenged with a single dose of 30,000 N battus L3 one week later and killed nine days after the challenge. Although protein supplementation tended to enhance the regulation of the population of N battus in the lambs which had been infected continuously, the effect was not statistically significant. The worm burdens in both the groups of previously infected lambs were significantly reduced both in number and size (P < 0.001) and they had a lower proportion of male worms than the uninfected challenge controls. The lambs could be segregated into high or low responders on the basis of their worm burdens, and there was a significant reduction in worm burdens (P < 0.001) and size (P < 0.01) in parallel with the lambs' responsiveness. The identification of high and low responders shows that when the dietary protein supply is adequate the predominant effect of the host on the pathogenicity of its parasites is the host's genetically-determined susceptibility.

Animal Feed↗

The pharmacokinetics of albendazole metabolites following administration of albendazole, albendazole sulfoxide and netobimin to one-month- and eight-month-old sheep.

The principal metabolites detected in plasma of sheep following oral administration of albendazole (ABZ), albendazole sulfoxide (ABSO) and netobimin (NTB) each at 5.0 mg kg-1 body weight were ABSO and albendazole sulfone (ABSO2). The areas under the plasma concentration-time curve (AUC) for ABSO and ABSO2 were significantly (P < 0.05) larger following administration for ABSO than NTB in 1-month- and 8-month-old sheep. The AUC for the ABSO and ABSO2 metabolites were larger following administration of ABZ than NTB in 1-month- but not 8-month-old sheep and the AUC of the ABSO and ABSO2 metabolites were greater following ABSO than ABZ as parent compound in 8-month-old sheep only. The larger AUC values for metabolites following administration of ABSO as the parent compound were generally coincident with significantly higher maximum (Cmax) concentrations and not with persistence in the body, since mean residence times (MRT) of the metabolites were not significantly different from those determined following ABZ and NTB as parent compounds. The lower metabolite concentration following administration of NTB may have been a feature of its requirement for metabolic conversion and its larger molecular weight. Correction of AUC values for molecular weight removed any significant differences between AUC values for either metabolite in 8-month-old lambs. The corrected metabolite AUCs following NTB were, however, significantly lower than those following ABSO administration in 1-month-old lambs, suggesting that immature metabolic processes in these animals contributed to the lower relative bioavailability of NTB in this age group. Age did not affect the disposition of metabolites following ABZ or ABSO but the AUC of the ABSO metabolite following NTB was significantly (P = 0.014) lower in 1-month- than in 8-month-old sheep.

Aging↗

Effect of dietary protein supplementation on the development of immunity to Ostertagia circumcincta in growing lambs.

Thirty four-and-a-half-month-old worm-free lambs were used to determine whether the rate of development of immunity to Ostertagia circumcincta infection in growing lambs could be influenced by the addition of a by-pass protein supplement. Sixteen lambs (groups 1 and 2) were fitted with an abomasal catheter and infected daily with 2000 O circumcincta L3 for eight weeks. Group 1 lambs received 45 g of crude protein day-1 (sodium caseinate) as a continuous infusion into the abomasum from week-1 to week 8. At week 9, groups 1 and 2, together with eight naive controls (group 3), were treated with anthelmintic and challenged one week later with 50,000 O circumcincta L3 and killed after a further 10 days. An additional six worm-free lambs provided feed intake and growth rate data. All the lambs were offered a complete ruminant ration (167 g crude protein kg-1) ad libitum. The cumulative liveweight gain of both the trickle-infected groups was less than that of the controls. The mean faecal egg counts were lower in group 1 from day 39 after infection and the mean worm burdens were significantly lower than in group 2. Total Ostertagia populations did not differ significantly between group 3 and either group 1 or 2 lambs. Early L4 stages constituted a greater percentage of the total worm population in group 1 (79.5) and group 2 (48.5) than in the challenge controls (group 3) (20.4). The trickle-infected lambs also had higher concentrations of gastric mast cell protease which correlated positively with the proportion of early L4 stages and negatively with the total worm burden. The provision of by-pass protein supplement accelerated the development of immunity to O circumcincta in these lambs.

Animals↗

A comparison of the mast cell and eosinophil responses of sheep and goats to gastrointestinal nematode infections.

The mucosal mast cell and eosinophil responses of goats and sheep to a mixed gastrointestinal nematode infection were compared. Groups of eight does and nine ewes, previously maintained on pasture and treated with anthelmintic when they were housed and five worm-free lambs were challenged with 10,000 Trichostrongylus vitrinus third stage larvae (L3) and 10,000 Teladorsagia circumcincta L3. Eleven days after challenge, the ewes had significantly (P < 0.001) lower burdens of abomasal and intestinal worms than the does or naive lambs, but significantly higher (P < 0.001) tissue concentrations of mast cell proteinase. Toluidine blue-stained sections indicated a paucity of mast cells in the does compared with the ewes, whereas the immunolocalisation of sheep mast cell proteinase revealed similar numbers of stained cells in the two species. This discrepancy was due to the relatively high proportion of globule leucocytes (77 and 91 per cent in the jejunum and abomasum, respectively) in the does compared with the ewes (7 and 24 per cent in the jejunum and abomasum, respectively). No differences were detected between the numbers of circulating or tissue eosinophils in the ewes and does.

Animals↗

The effect of subclinical intestinal nematode infection on the diet selection of growing sheep.

To test the hypothesis that subclinical gastrointestinal parasitism, associated with an impairment in N digestion and metabolism and a reduction in the voluntary feed intake (VFI), could affect the diet selection of sheep given a choice between two feeds that differed in their crude protein (CP) content, twenty-four Texel x Scottish Blackface ewe lambs growing from 28 to 48 kg live weight (LWT) were given a daily dose of 2500 larvae of the intestinal nematode Trichostrongylus colubriformis; twenty-four similar lambs were used as uninfected controls. Six infected and six control lambs were given a free choice between two pelleted feeds (10.4 MJ metabolizable energy/kg), with different CP contents (90 (L) and 214 (H) g CP/kg fresh feed respectively). In addition, eighteen parasitized and eighteen control sheep were given access ad lib. to either feed L, or feed H, or their mixture M (164 g CP/kg; twelve per feed), in order to quantify the effects of the feeds when offered alone, and to test for any interactions between feed CP content and parasitism on the performance of the lambs. Intestinal parasitism reduced significantly (P < 0.001) both the rates of LWT gain (by 30%) and VFI (by 10%). The adult and developing parasitic forms took 4 weeks to establish and develop to a significant adult worm population (as judged by the faecal egg counts and blood variables) and until then there was no effect of parasitism on the performance of the lambs. The diet selection of the lambs given a choice between two feeds was similar between the two groups in the first 4 weeks of the experiment, but differed significantly (P < 0.05) in the second part of the experiment (4th week to the end). Thus, while parasitized lambs had a reduced rate of feed intake, by changing their diet selection they achieved a daily rate of CP intake similar to the control ones. However, since the parasitized lambs had a reduced rate of LWT gain, they also consumed a higher total amount of CP to reach the same LWT. It is concluded that sheep infected daily with a small number of larvae of T. colubriformis and given a choice between two feeds that differ in their protein contents are able to modify their diet selection in order to meet the increased protein requirements resulting from such an infection.

Animals↗

Prevalence of anthelmintic-resistant nematodes in fibre-producing goats in Scotland.

Six cashmere goat herds in Scotland were surveyed to assess the prevalence of anthelmintic resistance and the species of nematode involved. Resistance was determined in vivo by a faecal egg count reduction test and in vitro using an egg hatch assay and specific faecal egg identification techniques. Benzimidazole resistance was present in five of the herds, insufficient eggs were obtained from the other herd to draw firm conclusions. Teladorsagia (Ostertagia) species predominated in four of the five herds in which resistance was detected and Haemonchus contorus was the dominant species in the other.

Animals↗

Effects of dietary molybdenum on nematode and host during Trichostrongylus vitrinus infection in lambs.

The addition of molybdenum (0.05 mmol kg-1 dry matter) to the diet of lambs exposed for four weeks to a trickle (2500 third stage larvae per day) infection with Trichostrongylus vitrinus reduced the number and length of adult worms retrieved from the small intestine 11 days later: both effects were particularly marked in female worms from female lambs (P less than 0.01). Worms from lambs given molybdenum contained less proteinase enzyme activity and secreted less proteinases in culture irrespective of the sex of the host. Pathogenicity was not attenuated by molybdenum. Damage to the intestinal mucosa was severe in both dietary groups but infected females given molybdenum developed lower plasma albumin concentrations and lighter dressed carcases than those not given molybdenum. Neither the effects on the parasite nor those on the host could be attributed simply to molybdenum-induced copper depletion, using conventional measures of copper status. Molybdenum may be toxic to T vitrinus but may also facilitate or enhance the inflammatory process limiting larval establishment or increasing parasite rejection.

Administration, Oral↗

Effects of dietary molybdenum on nematode and host during Haemonchus contortus infection in lambs.

The addition of molybdenum (0.05 mmol kg-1 dry-matter) to the diet of lambs given a trickle infection of Haemonchus contortus larvae (500 third stage larvae d-1 over six weeks) reduced mean faecal egg counts (epg) from 3952 to 2312 +/- 402 by 32 days (P less than 0.02) and greatly reduced the mean number of worms recovered from the abomasum 14 days after infection ceased (907 compared with 4167: P less than 0.01). Infection reduced haemoglobin concentrations less in lambs given molybdenum although the difference was small relative to the reduction in worm burden. Lambs not given molybdenum had low intraepithelial mast cell counts in the abomasal mucosa and less abomasal hypertrophy than expected from abomasal parasitism. Molybdenum did not consistently reduce the copper status of the host or the parasite. Previous exposure to molybdenum greatly reduced protein but not proteinase activity in, or secreted by, adult worms cultured for eight hours. It is suggested that molybdenum either increased the inflammatory response which preceded worm rejection or that it indirectly enhanced that reaction by reducing the effectiveness of copper-dependent, anti-inflammatory enzymes in the gastrointestinal mucosa.

Abomasum↗