Trichostrongylus colubriformis infection damages intestine brush board cells and could negatively impact postabsorptive parameters of Santa Ines lambs.

This study aimed to evaluate histological, digestive and postabsorptive physiological parameters in Santa Ines lambs infected with Trichostrongylus colubriformis and fed different levels of phosphorus. Therefore, eighteen Santa Ines, castrated male, six-month old, healthy lambs (initial body weight 22.4 ± 2.7 kg) were distributed in one of four treatments arranged in a 2 × 2 split-plot arrangement: Sufficient dietary P level and uninfected (SPui; n = 4), Sufficient dietary P level and infected (SPi; n = 5), Deficient dietary P level and uninfected (DPui; n = 4), Deficient dietary P level and infected (DPi; n = 5). Infected lambs received, orally, a single pulse dose of 40.000 T. colubriformis infective larval stage (L3). Animals were fed Tifton 85 hay (Cynodon ssp.; 60%), and cassava meal and maize gluten meal (40%). Measurement of nutrient apparent digestibility and nitrogen metabolism were performed in individual metabolic stalls. To achieve the trial results, it was measured methane emissions in respiratory chambers, urine purine derivatives, ruminal short-chain fatty acids (SCFA), histological cuts of duodenal mucosal tissues and passage rates fluxes, analyzed by external (Yb, Cr, and Co) and internal (iNDF) markers. Statistical procedures were performed in R studio. The fixed main effects of treatment and the interactions were tested by ANOVA, and means compared by Duncan's test at 5% significance. Apparent digestibility was not affected by treatments, however, nitrogen retained decreased (P < 0.01) and urinary nitrogen losses increased (P < 0.01) in infected animals. Small intestine digesta content, empty segment weight, and length were higher in infected animals (P < 0.05). Passage rate was not majorly affected by infection or dietary P levels. Methane emissions, SCFA concentrations, and purine derivative excretion were also not affected by treatments. Regarding the histology, the vilosity weight (P < 0.05), and crypt depth (P < 0.01) decreased in infected animals. In conclusion, T. colubriformis infection can damage intestinal mucosa and affect nitrogen metabolism, but did not affect the digesta transit, and nutrient digestibility. The P dietary levels did not promote any modification in GIT physiological parameters tested in this study.

Phosphorus kinetics in lambs experimentally infected with Trichostrongylus colubriformis with the use of 32P.

This study was conducted to evaluate the metabolism and phosphorus (P) kinetics in lambs experimentally infected with Trichostrongylus colubriformis using the isotope dilution technique and modelling. Fifteen male lambs (21.1 ±â€¯1.50 kg) of the Santa Inês hair breed of approximately six months old, distributed in the treatments infected (I, n = 8) and control (C, n = 7) were used. The infected lambs received serial infections with 5000 T. colubriformis larvae, three times per week, for 3 weeks (45 000 T. colubriformis total larvae). After 66 days of the last inoculation of infective larvae, 6.6 MBq of 32P were injected in each lamb to evaluate the P kinetics. Blood, faeces and urine samples were collected in the following seven days and the slaughter of lambs were carried out on the last day in order to collect bone and soft tissues (Liver, kidney, heart and muscle) samples. To analyse P flows, the biomathematical model with four compartments (C1 - gastrointestinal tract, C2 - plasma, C3 - bone and C4 - soft tissue) was used. Similar P intake (VI) between treatments (C and I) was verified. Lower absorption of endogenous (Vaf) and dietary P (Vaa), as well as, lower amount of endogenous P (from saliva) that reaches the gastrointestinal tract (VIT), consequently, higher excretion of dietary P (VFD) were verified in infected lambs (P < 0.1). Additionally, in infected lambs, the P bioavailability was lower compared to control lambs. With the lower absorption (VaT) of P in infected lambs, there was, consequently, lower distribution to bones and soft tissues (VeD2) and lower P deposition in the bones (VO+D). It was concluded that P metabolism of lambs infected with T. colubriformis was altered, with reduced intestinal absorption and bioavailability, increased faecal loss and reduced P flow to the bone.

Efferent intestinal lymph protein responses in nematode-resistant, -resilient and -susceptible lambs under challenge with Trichostrongylus colubriformis.

The mechanisms underlying resistance to challenge by gastrointestinal nematode parasites in sheep are complex. Using DIGE, we profiled ovine lymph proteins in lambs with host resistance (R), resilience (Ri) or susceptibility (S) to a daily trickle challenge with the nematode Trichostrongylus colubriformis. Efferent intestinal lymph was collected prior to infection (day 1) and on days 5 and 10 post-infection. Eight proteins identified by LC-MS/MS, showed differences relating to host genotype. Of these, Serpin A3-3 and Serpin A3-7 have not been reported previously in the lymph proteome. Three acute phase proteins showed significant differences relating to interactions between breeding line and parasite challenge, including complement C3ß, C3α and haptoglobin (Hp) ß. In the R lambs C3α was significantly up regulated (P<0.05) on day 10, while in the Ri lambs Hp ß was significantly down regulated (P<0.05). In the S lambs, levels of C3ß were up regulated and levels of Hp ß down regulated (both P<0.05) on day 10. Hence we demonstrate that acute phase inflammation proteins contribute to differences in the innate immune response of sheep to challenge by T. colubriformis. The findings may lead to the development of new approaches to combat nematode infestations in sheep production systems. BIOLOGICAL SIGNIFICANCE: Breeding lines of sheep with resistance (R), resilience (Ri) or susceptibility (S) to nematode infections provide an experimental model to examine the biological mechanisms underlying the ability of some sheep to expel worms and remain healthy without the use of an anthelmintic. Using proteomics we identified differences in the expression of acute phase lymph proteins in the R, Ri and S lambs. The results will assist the development of alternative control strategies to manage nematode infections in livestock.

Valine partitioning and kinetics between the gastrointestinal tract and hind limbs in lambs with an adult Trichostrongylus colubriformis burden.

Intestinal parasitic infection increases the demand for AA because of increased protein synthesis in the intestine and increased luminal losses of AA, and these increased demands may be supported by increased mobilization of AA from the skeletal muscles. Two experiments were conducted to determine the effects of parasitic infection on valine kinetics within the gastrointestinal tract and hind limbs of lambs fed fresh forages. On d 1, lambs were given 6,000 stage-3 Trichostrongylus colubriformis larvae per day for 6 d (n = 6) or kept as parasite-free controls (n = 6) and fed fresh lucerne (Medicago sativa; Exp. 1) or fresh sulla (Hedysarum coronarium; Exp. 2). On d 48, valine kinetics within the mesenteric- (MDV) and portal-drained viscera (PDV) and hind limbs were obtained by carrying out concurrent infusions of para-amminohippuric acid into the mesenteric vein and indocyanin green into the abdominal aorta (for blood flow), and [3,4-(3)H]valine into the jugular vein and [1-(13)C]valine into the abomasum for 8 h (for kinetics). During the infusions, blood was collected from the mesenteric and portal veins and from the mesenteric artery and vena cava, and plasma was harvested. After the 8-h infusion, lambs were euthanized, ileal digesta were collected, and tissues were sampled from the intestine and muscle (biceps femoris). Tissues, digesta, and plasma were analyzed for valine concentration, specific radioactivity, and isotopic enrichment. In both experiments, intestinal worm burdens on d 48 were greater in parasitized lambs (P = 0.0001 and 0.003). In Exp. 1, parasitic infection increased (P = 0.03) the total valine irreversible loss rate (ILR) in the MDV and PDV. In Exp. 2, luminal ILR of valine in the MDV was reduced (P = 0.01); however, ILR of valine in the PDV was unaffected. Despite these changes within the MDV and PDV, parasitic infection did not affect the ILR of valine within the hind limbs, and valine transport rates were largely unchanged. We suggest that the increased mobilization of AA from the hind limbs that might have occurred in the early phase of inflammation was no longer required when the parasitic infection was established. The MDV and PDV data may indicate that the non-MDV parts of the PDV play an important role in this adaptation, which warrants further study.

Nutritional sensitivity of resistance to Trichostrongylus colubriformis in lactating ewes.

It has been suggested that the periparturient breakdown of immunity to parasites has a nutritional basis. Our overall hypothesis is that it results from a prioritized scarce metabolizable protein (MP) allocation to reproductive functions (e.g. milk production) rather than to immune functions. We have earlier shown that the relationship between MP supply, milk production and resistance to the abomasal nematode Teladorsagia circumcincta provides support for this hypothesis. Because nutritional sensitivity of resistance to parasites may differ between parasite species, we used the same nutritional protocol to test the overall hypothesis with a different parasite. Thus, five levels of dietary MP, ranging from 0.60 to 1.2 times assumed requirements, were offered for 4 weeks post-parturition to twin-rearing Greyface ewes, experimentally infected with the small intestinal nematode Trichostrongylus colubriformis. We hypothesized that the initial increments of MP supply would increase milk production without affecting the degree of breakdown of immunity whilst later increments would reduce the degree of breakdown of immunity. Indeed, the data suggest that the first two increments of MP supply increased milk production, whilst final worm burdens were reduced from the second increment onwards. MP supply did not affect mucosal mast cell concentration but increased globule leukocyte concentration. These results support the overall hypothesis that scarce MP allocation is prioritized to milk production over immune functions. In addition, the contrast between effects of MP supply on resistance to T. colubriformis and to T. circumcincta supports the view that periparturient immunity to small intestinal nematodes may be less sensitive to nutrient scarcity than periparturient immunity to abomasal nematodes.

Gastrointestinal nematode challenge induces some conserved gene expression changes in the gut mucosa of genetically resistant sheep.

Sheep have a varying ability to resist infection with gastrointestinal nematodes. This ability is due in part to genetic differences that exist between individuals. In order to define these differences we have used real-time PCR to quantify gene expression responses in the gut mucosal surface of genetically resistant and susceptible sheep, following a nematode challenge. Expression profiles were determined in response to two different nematode species, Haemonchus contortus and Trichostrongylus colubriformis, and in divergent sheep originating from two different genetic backgrounds. Results show that the response generated differs between resistant and susceptible animals and is further impacted by the origin of the sheep and nematode species used for challenge. However, some conserved features of a response mounted by a resistant or a susceptible animal were identified. Genes found to be more abundantly expressed in resistant animals include markers of an early inflammatory response, several Toll-like receptors (TLR2, 4, 9) and free radical producing genes (DUOX1 and NOS2A). Conversely, genes differentiating susceptible animals indicate a prolonged response and development of a chronic inflammatory state, characterised by elevated expression of members of the NF-kappabeta signalling pathway (IKBKB and NFKBIA) together with delayed expression of regulatory markers such as IL2RA (CD25), IL10 and TGFbeta2. While multiple nematode response pathways were identified, the identification of conserved aspects of the response which associate with resistance provides evidence that alternative nematode control strategies, such as breeding for resistant animals, may be feasible.

Intestinal, hepatic, splanchnic and hindquarter amino acid and metabolite partitioning during an established Trichostrongylus colubriformis infection in the small intestine of lambs fed fresh Sulla (Hedysarum coronarium).

Increased partitioning of amino acids (AA) from skeletal muscle to the intestine and immune system during parasitic infection may be the cause of poor growth in parasitised animals. The effect of an established Trichostrongylus colubriformis infection (6000 L3 T. colubriformis larvae for 6 d (n 5) or kept as parasite-free controls (n 6)) on AA fluxes across the mesenteric-drained viscera, portal-drained viscera (PDV), liver, total splanchnic tissues (TSP) and hindquarters were determined in lambs fed fresh Sulla (Hedysarum coronarium; 800 g DM/d) 48 d post-infection. The lambs were infused with rho-aminohippuric acid (PAH; 723 mg/h) into the mesenteric vein for 8 h to measure TSP plasma flow. Concurrently, indocyanine green (ICG; 14.6 mg/h) was infused into the abdominal aorta to measure plasma flow across the hindquarters. Blood was continuously collected from the mesenteric, portal and hepatic veins, vena cava and the mesenteric artery and plasma harvested. PAH, ICG, AA, metabolite and insulin concentrations were measured. Intestinal worm burdens on day 48 post-infection were higher in the infected lambs (P 0.10). There was a 28 % reduction in the release of AA from the PDV of infected lambs (P < 0.05). The uptakes of most AA were similar in the liver; however, there was increased uptake (P < 0.10) of AA by the TSP of infected lambs. Despite this reduction in AA availability at the liver, there was no effect of parasitic infection on AA uptake across the hindquarters (P < 0.05).

Whole-body valine and cysteine kinetics and tissue fractional protein synthesis rates in lambs fed Sulla (Hedysarum coronarium) and infected or not infected with adult Trichostrongylus colubriformis.

Poor growth during parasitic infection may be due to a redistribution of amino acids away from skeletal muscle protein synthesis to the intestinal site of infection. The effect of a Trichostrongylus colubriformis infection on whole-body amino acid kinetics and tissue fractional protein synthesis rates were determined in lambs fed fresh Sulla (Hedysarum coronarium; 800 g DM/d). Lambs were dosed with 6000 L3 Trichostrongylus colubriformis larvae daily for 6 d (n 6) or kept as parasite-free controls (n 6). On day 45 post-infection, the lambs received an intravenous injection of 2H2O and infusions (8 h) of [35S]sulphate to measure the size of the whole-body water and sulphate pools, respectively. On day 48, the lambs were continuously infused for 8 h with [3,4-3H]valine into the jugular vein as well as with [1-13C]valine and [35S]cysteine into the abomasum. After the 8 h infusions, the lambs were killed and tissue samples collected from the duodenum, ileum, mesenteric lymph nodes, liver, spleen, thymus, muscle and skin. Feed intake (769 v. 689 (sd 47) g DM/d) was not affected by infection, whereas liveweight gains (50 v. -50 (sd 70) g/d) were lower and intestinal worm burdens (240 v. 18,000 (sd 7000) worms) higher in the infected lambs. Parasitic infection increased the fractional protein synthesis rates in the small intestine, mesenteric lymph nodes and liver but did not affect skin and skeletal muscle fractional protein synthesis rates during the established parasitic infection.

Influence of the route of administration on efficacy and tissue distribution of ivermectin in goat.

The tissue concentration and efficacy of ivermectin after per os and subcutaneous administration were compared in goats experimentally infected with Trichostrongylus colubriformis (ivermectin-susceptible strain, INRA). Infected goats (n = 24) were treated per os (n = 9) or subcutaneously (n = 9) with ivermectin, 0.2 mg/kg, or kept as not treated controls. The faecal egg counts and small intestine worm counts were determined. Ivermectin concentration was measured in the plasma, gastrointestinal tract, lung, skin or hair, liver and adipose tissues at 0, 2, 7 and 17 days post-treatment. The efficacy of ivermectin against T. colubriformis infection in goat was 98.7 and 99.9% for subcutaneous and oral administration, respectively. Ivermectin concentration declined with time and only residual concentration was measured at 17 days post-treatment in plasma and gastrointestinal tract. Ivermectin concentration was higher after subcutaneous compared to per os injection in most of the tissue examined. In skin, hair and subcutaneous adipose tissue ivermectin persisted at significant concentrations 17 days post-treatment for both routes of administration. In our experimental conditions, ivermectin provides similar efficacy against T. colubriformis after subcutaneous or per os administration in goat. However, the lower ivermectin levels in tissues after per os administration suggest that the lasting of efficacy may be shortened after per os compared to subcutaneous administration especially in animals with poor body condition in pasture where re-infection occurs quickly after anthelmintic treatment.

Interleukin-6 expression in gut of parasite challenged sheep.

Following challenge with Trichosirongylus colubrifonizis, increased numbers of T-cells and immunoglobulin responses are seen in the intestine of sheep immunised by repeated infection with live worms. IL-6 mRNA expression in the small intestine from T. colubriformis-immunised and naive sheep was determined by in situ hybridisation, whereas CD4(+), IgA(+), IgG(+) cells in the gut were evaluated by immunohistochemistry. There was constitutive expression of IL-6 mRNA by cells in the naive gut, and the number of these cells was increased by parasite challenge. There were corresponding increases in numbers of CD4(+) and TCR gamma/delta(+) T-cells and IgG(+) B-cells. Our data are consistent with a role for IL-6, perhaps produced by CD4(+) and/or TCR gamma/delta(+) T-cells or B-cells, in B-cell terminal differentiation. Infiltration of B-cells, particularly IgG(+) B-cells, may reflect parasite immunity in the host.

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.

Trichostrongylus colubriformis infection in rabbits: persistence of the distal adaptive response to parasitism after anthelmintic treatment.

Mucosal changes associated with anthelmintic treatment in Trichostrongylus colubriformis-infected rabbits were assessed along the entire length of the small intestine. The following groups, each of five rabbits, were compared: infected (group I); infected and treated on day 21 with fenbendazole (group IT); uninfected but given fenbendazole on day 21 (group C, controls). All animals were killed on day 28. In the proximal part of the small intestine of group I rabbits, the worms were associated with shortening of the villi and a significant depletion in alkaline phosphatase activity, which differed significantly from the findings in groups C and IT. In the same region, no difference was found between groups C and IT. In the distal small intestine, hypertrophy of villi and crypts (an adaptive response to the infection), coupled with an increase in enzymic activity, were present in both groups I and IT, in contrast to group C. These results suggest that a complete mucosal restoration occurred within 7 days of anthelmintic treatment in the parasitized part of the intestine. In contrast, the adaptive response observed beyond the main site of parasitism was not abolished by treatment. The functional significance of these findings is discussed in relation to the compensatory growth commonly observed after anthelmintic treatment in ruminants.

The influence of a heavy infection with sensitive and resistant strains of Ostertagia circumcincta and with Trichostrongylus colubriformis on the pharmacokinetics of febantel in lambs.

Plasma concentrations of febantel and its major metabolites, fenbendazole, oxfendazole and fenbendazole sulphone, were determined after oral administration of 7.5 mg/kg febantel in lambs before and 28 days after infection with 100,000 L3 larvae of a benzimidazole (BZ)-sensitive or BZ-resistant strain of Ostertagia circumcincta or with 75,000 L3 larvae of a BZ-sensitive Trichostrongylus colubriformis strain. The febantel concentrations were always low, and in only a few samples were higher than the limit of detection. A mean decrease in the area under the curve (AUC) for the three metabolites of 10.2%, 16.4% and 4.9% in lambs infected, respectively, with BZ-sensitive O. circumcincta, BZ-resistant O. circumcincta and T. colubriformis was observed. The Cmax for all the metabolites was higher in the BZ-sensitive O. circumcincta group than in the naive sheep, while the Tmax occurred earlier. The Cmax and the Tmax values for all the metabolites were lower in the BZ-resistant O. circumcincta group than in their own naive controls. In the T. colubriformis group the Cmax values of the metabolites were lower and the Tmax occurred much later.

The effect of reduced feed intake on the efficacy of oxfendazole against benzimidazole resistant Haemonchus contortus and Trichostrongylus colubriformis in sheep.

Within 12 h of reducing the daily intake of a 50:50 lucerne and wheaten hay ration from 800 to 400 g, there was an increase in digesta marker concentration indicating a reduction in the flow rate of digesta fluid and particulates through the abomasum of sheep. The efficacy of the recommended dose of oxfendazole (OFZ) was then tested against benzimidazole resistant Trichostrongylus colubriformis and Haemonchus contortus in sheep whose feed intake was halved 36 h before and after drug treatment. In animals fed the reduced ration there was a 60% reduction of T. colubriformis and 94% reduction of H. contortus compared with a 19% and 60% reduction respectively on the higher feed intake. It is therefore suggested that greater anthelmintic efficacy can be achieved in sheep by temporary feed reduction.

Influence of subclinical nematodosis on the kinetic disposition of fenbendazole in buffaloes.

The disposition kinetics of fenbendazole was studied in buffaloes subclinically infected with gastrointestinal nematodes. There was significantly reduced uptake of the drug in infected animals compared to uninfected controls. The pH of the duodenal liquor was highly alkaline compared to the acidic pH in uninfected animals. The egg count in the faeces never became zero though the numbers were reduced to a great extent compared to pre-treatment values. The influence of the host's physiology on the reduced bioavailability of fenbendazole is discussed.

Comparative kinetic disposition of oxfendazole in sheep and goats before and during infection with Haemonchus contortus and Trichostrongylus colubriformis.

The kinetic disposition of [14C]-oxfendazole (OFZ) and its metabolites, fenbendazole (FBZ) and fenbendazole sulphone (FBZ.SO2), in plasma and abomasal fluid were determined in Merino sheep and Angora goats before and during infection with Trichostrongylus colubriformis and Haemonchus contortus. The systemic availability (area under the plasma curve, AUC) of OFZ was significantly lower in goats (13.5 micrograms.h/ml) than in sheep (22.2 micrograms.h/ml) and was reduced with infection in goats (5.6 micrograms.h/ml) and sheep (15.1 micrograms.h/ml). The elimination of plasma [14C] was faster in goats than in sheep. The responses observed for [14C] were a reflection of the behaviour of OFZ. The concentration of OFZ and metabolites in abomasal fluid were similar in both species in the absence or presence of infection. However, as the mean flow rate of abomasal fluid was slower in goats (240 ml/h) than in sheep (488 ml/h), only 7% of the dose passed the pylorus in abomasal fluid of goats compared with 14% in sheep. The presence of gastrointestinal nematodes generally increased abomasal fluid flow rate but neither species nor infection had any effect on the rate or extent of [14C] excretion in urine or faeces. It is suggested that goats possess a faster hepatic metabolism than sheep resulting in more rapid elimination of OFZ.

The influence of Ostertagia circumcincta and Trichostrongylus colubriformis infections on the pharmacokinetics of febantel in lambs.

Plasma concentrations of febantel and its major metabolites fenbendazole, oxfendazole and oxfendazole sulphone were determined after oral administration of 7.5 mg/kg febantel in lambs before and 28 days after infection with 50,000 L3 larvae of Ostertagia circumcincta or Trichostrongylus colubriformis. The febantel concentrations were always very low and only in a few samples higher than the detection limit. The mean decrease in AUC for the three metabolites for the infected sheep in comparison to the parasite naïve sheep was 13.9% +/- 4.1% (mean +/- SEM) and 23.7% +/- 5.3% in the O. circumcincta infected and the T. colubriformis infected lambs respectively. This reduction was only significant for the T. colubriformis infected group. In order to determine a more complete pharmacokinetic profile, febantel was injected intravenously at a dose of 2.5 mg/kg in a further study.

Nitrogen transactions along the digestive tract of lambs concurrently infected with Trichostrongylus colubriformis and Ostertagia circumcincta.

Twelve lambs, paired on the basis of live weight, were cannulated in the abomasum, in the proximal jejunum approximately 4 m distal to the pylorus and in the terminal ileum. Six were infected with 3000 Trichostrongylus colubriformis and 3000 Ostertagia circumcincta larvae each day for 18 weeks and the remainder were pair-fed to individual infected lambs. All animals were offered ryegrass (Lolium perenne)-white clover (Trifolium repens) pasture, cut daily. Dry matter (DM) intake, live weight, faecal egg concentration, plasma pepsinogen and plasma protein concentrations were measured weekly. During weeks 7 and 17 after commencement of infection, the flow of digesta along the gastrointestinal tract was measured together with enteric plasma loss and true digestion and absorption of 125I-labelled albumin in the small intestine. DM intake was depressed by parasitism, being 1331, (SE 70), 423 (SE 32) and 529 (SE 52) g/d during weeks 3, 7 and 17 respectively. The flow of nitrogen at the proximal jejunum and in faeces was increased by parasitism during week 7 and at the abomasum and ileum during week 17. Plasma protein-N loss (g/d) into the gastrointestinal tract was 0.68 (SE 0.091) and 1.97 (SE 0.139) during week 7, and 0.85 (SE 0.158) and 1.96 (SE 0.396) during week 17, in control and infected sheep respectively. True digestion and absorption of albumin in the proximal small intestine, the site of infection, was very low (mean 0.08) and was not affected by parasitism. Between the abomasum and terminal ileum absorption of albumin was high (mean 0.87) and again was not affected by parasitism. It was calculated that of the total increase in endogenous protein passing from the ileum tract as a result of infection, plasma protein comprised only a small percentage (10-36%). The major proportion of digestion and absorption of protein occurred in the distal small intestine beyond the site of infection and was not affected by infection.