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Impact of doramectin treatment at the time of feedlot entry on the productivity of yearling steers with natural nematode infections.

OBJECTIVE: To measure the reduction in fecal nematode egg counts and productivity impact of treatment of yearling steers with doramectin at entry into the feedlot, compared with control steers treated only with fenthion. ANIMALS: 6,096 crossbred yearling steers with a mean (+/- SD) body weight of 377.0 (+/- 37) kg. PROCEDURE: Steers were implanted with zeranol and alternately separated to fill each of 24 pens. Groups of steers within 12 matched pairs of pens were randomly allocated to treatment with doramectin or no treatment with doramectin for internal nematodes. Fecal samples were collected from approximately every twentieth steer from each pen at day 0 and at reimplant (approx day 60). Each steer was weighed on day 0 and at reimplant and then mean body weights of steers per pen were determined at 120 to 140 days after trial initiation. RESULTS: Treatment steers had a significantly lower fecal egg count at reimplant than control steers. Treatment steers had a significantly greater mean daily gain during the study, significantly greater feed consumption, significantly lower feed-to-gain ratio, and significantly better quality carcass grades at slaughter. CONCLUSIONS AND CLINICAL RELEVANCE: Under the conditions of our trial, there was a significant fecal egg count reduction response to doramectin treatment, which resulted in significantly improved productivity. Results of economic analysis of return on investment indicated that even with low egg counts in heavy body weight cattle, nematode egg count reduction with doramectin significantly improved returns.

Anabolic Agents↗

Prevalence of coccidia and gastrointestinal nematode infections in cross bred goats in the dry areas of Sri Lanka.

The prevalence and intensity of oocysts of coccidia, particularly Eimeria species, and eggs of gastrointestinal nematodes in kids (2-4 months), young goats (5-12 months) and adult goats (>1 year) were determined in five large herds managed extensively in five villages in the dry zone. Of the representative samples examined, oocysts were found in 88% of kids, 91% of young goats and 83% of adults. Seven species of Eimeria were identified in faecal samples by salt flotation. Eimeria ninakohlyakimovae (31%), E. alijevi (29%) and E. arloingi (21%) were the most common species in all age categories. Other species encountered were E. christenseni (7%), E. jolchijevi (6%), E. hirchi (3%) and E. aspheronica (1%). Gastrointestinal nematode eggs were found in 89% of the kids, 94% of the young goats and 84% of the adult goats. Identification of gastrointestinal nematodes revealed Haemonchus contortus (90%) followed by Oesophogostomum spp. (8.5%) and Trichostrongylus spp. (1%) in all three age categories examined. Both Eimeria and gastrointestinal nematodes were found in 77% of the kids, 86% of the young goats and 71% of adult goats. The mean oocyst counts per gram of faeces in kids, young goats and adult goats were 9728, 1946, and 2667, respectively. The oocyst counts were not different significantly between age groups (P>0.05). The mean egg counts per gram of faeces in kids, young goats and adult goats were 1217, 1641 and 1092, respectively. The egg counts in kids were significantly lower than that in young goats (P<0.05). The intensity of Eimeria and gastrointestinal nematode infections between herds were significantly different (P<0.01).

Journal Article↗

Intraepithelial NK cell-derived IL-13 induces intestinal pathology associated with nematode infection.

IL-13 is a Th2-derived cytokine associated with pathological changes in asthma and ulcerative colitis. Moreover, it plays a major role in the control of gut nematode infection and associated immunopathology. The current paradigm is that these effects are due to T cell-derived IL-13. We show in this study that an innate source of IL-13, the intraepithelial NK cell, is responsible for the disruption of intestinal tissue architecture and induction of goblet cell hyperplasia that characterizes infection with the intestinal helminth Trichinella spiralis. IL-13 or IL-4Ralpha (but not IL-4) null mice failed to induce intestinal pathology. Unexpectedly, SCID and athymic mice developed the same pathology found in immunocompetent mice following infection. Moreover, immunodeficient mice expressed IL-13 in the intestine, and abnormal mucosal pathology was reduced by in vivo administration of a soluble IL-13 antagonist. IL-13 expression was induced in non-T intraepithelial CD3- NK cells. Epithelial cells expressed the IL-13 signaling receptor, IL-13Ralpha1, and after infection, IL-4Ralpha. Furthermore, the soluble IL-13 decoy receptor IL-13Ralpha2, which regulates IL-13 responses, was also induced upon infection. These data provide the first evidence that intestinal tissue restructuring during helminth infection is an innate event dependent on IL-13 production by NK cells resident in the epithelium of the intestine.

Animals↗

Expression and functional characterization of a single chain Fv antibody directed against secretions involved in plant nematode infection process.

Expression in plants of antibodies directed against proteins essential for pathogenesis could provide an alternative approach to engineer new resistance traits into crops. Salivary secretions of the root-knot nematode Meloidogyne incognita are known to play a key role during this nematode infection process. From a hybridoma cell line producing an IgM monoclonal antibody specific to these secretions, we have constructed a synthetic gene that encodes an antigen-binding single-chain Fv protein (scFv). The scFv gene was created by polymerase chain reaction amplification of variable domain encoding regions from the IgM antibody. The cloned scFv was initially expressed in Escherichia coli as a 33-kDa protein which could be purified to near homogeneity by immobilized metal affinity chromatography. The produced scFv is fully functional since it shows the same specificity towards a crude extract of M. incognita infective larvae as the corresponding parental IgM. Transient expression assays with tobacco leaf protoplasts using different targeting signals resulted in a high intracellular accumulation of scFv, especially when fused to the tetrapeptide KDEL retention signal. Activity analysis and stability characterization of this scFv in tobacco protoplast represent the first step before plant transformation in order to test a new form of resistance to root-knot nematode in plants.

Amino Acid Sequence↗

Epidemiology of parasitic gastrointestinal nematode infections of ruminants on smallholder farms in central Kenya.

In order to establish the infection pattern with gastrointestinal nematodes in ruminants in the central Kenya highlands, a study was carried out in 58 smallholder farms. The study involved monthly faecal examinations from sheep, goats and cattle and pasture sampling from eight communal grazing areas. Each month, six Dorper worm-free tracer lambs were introduced and four locally grazed cross-bred sheep were purchased for parasite recovery. The mean faecal egg counts (FEC) for cattle were low throughout the study period, whereas those for sheep and goats showed a seasonal pattern with high levels of infection occurring during the two main rainy seasons, especially in March, April and October. There were significant differences in egg counts over time and among farms. Haemonchus contortus was the most prevalent nematode in the tracer lambs whereas the previously exposed locally grazed sheep had significantly lower numbers of H contortus but significantly higher numbers of Trichostrongylus species The highest levels of infection in the tracer lambs occurred in November 1995 and January, May and June 1996. Based on this study, it is now possible to explore the possibility of using strategic treatments for the control of parasitic gastroenteritis in this area of Kenya.

Animal Husbandry↗

Most of the response elicited against Wolbachia surface protein in filarial nematode infection is due to the infective larval stage.

Immune responses to the intracellular Wolbachia bacteria of filarial nematodes are thought to contribute to the pathologic process of filarial infection. Here, we compare antibody responses of subjects living in an area where lymphatic filariasis is endemic with antibody responses elicited in a murine model of filarial infection, to provide evidence that the infective larval stage (L3), not adult nematodes, are the primary inducer of responses against Wolbachia. In human subjects, antibody responses to Brugia malayi Wolbachia surface protein (WSP) are most often correlated with antibody responses to the L3 stage of B. malayi. Analysis of anti-WSP responses induced in mice by different stages of the rodent filariae Litomosoides sigmodontis shows that the strongest anti-WSP response is elicited by the L3 stage. Although adult filarial nematode death may play a role in the generation of an anti-WSP response, it is the L3 stage that is the major source of immunogenic material, and incoming L3 provide a continual boosting of the anti-WSP response. Significant exposure to the endosymbiotic bacteria may occur earlier in nematode infection than previously thought, and the level of exposure to infective insect bites may be a key determinant of disease progression.

Animals↗

IFN-gamma-independent effects of IL-12 during intestinal nematode infection.

Expulsion of the gastrointestinal nematode Trichinella spiralis is associated with a pronounced mastocytosis mediated by a Th2-type response involving IL-4, IL-10, and IL-13. When exogenous rIL-12 was administered to T. spiralis-infected NIH mice, this resulted in significant suppression of intestinal mast cell responses, delayed worm expulsion, increased muscle larvae burdens, and a transient, but significant decrease in early Th2 cytokine secretion. rIL-12 treatment also altered chemokine expression in the jejunal mucosa. The effects of exogenous IL-12 administration were largely independent of IFN-gamma as shown by rIL-12 treatment of IFN-gamma knockout mice. Hence, IL-12 may play a significant biological role as a direct negative regulator of intestinal Th2 responses and may act to promote the survival of intestinal parasites in vivo also in the absence of IFN-gamma.

Animals↗

Chromosomal regions controlling resistance to gastro-intestinal nematode infections in mice.

Quantitative trait loci (QTL) associated with resistance to an intestinal worm in a well-defined murine model are described. These have been identified in an F(2) population derived from resistant (SWR) and susceptible (CBA) parental mouse strains infected with the gastro-intestinal nematode parasite Heligmosomoides polygyrus. Seven QTL located on six chromosomes are described, associated with components of the complex host response and the differential regulation of parasite survival and reproduction. The combined additive effects of the five significant QTL associated with worm survival (total worm count at necropsy) account for about 60% of the difference in worm count between the parental lines. The dominance effect for these five QTL are all in the direction of resistance, supporting the heterosis for resistance established from the mean worm count for the F(2) line relative to the parental lines. It is now possible to identify the comparative chromosomal regions of these QTL in livestock and humans and to consider the possibility of future improved control strategies. These may include breeding of resistant or tolerant livestock, development of vaccines, or identification of new anthelmintic drugs.

Animals↗

Studies on nematode infections of beef cattle in New South Wales.

The occurrence and seasonal trends of nematode parasite infections in beef cattle on the Tablelands and North Coast regions of New South Wales are described, based on worm counts from 627 spring-born steers slaughtered at 2-monthly intervals from 6 to 24 months of age. The predominant parasites were Ostertagia ostertagi, Trichostrongylus axei and Cooperia spp. Large burdens of adult Ostertagia were seen in 12-month-old animals in late winter and early spring, and later in 18- to 20-month-old cattle in the following late summer and autumn. These infections often resulted in outbreaks of clinical parasitism. Massive numbers of inhibited early fourth stage larvae (EL4) also accumulated in the yearlings during their first spring, reached peaks in mid-summer and then declined. The possibility of their resumption of development to mature worms in the late summer and autumn period is discussed. Adult T. axei showed a similar seasonal trend to Ostertagia and may have increased the severity of outbreaks of clinical disease. Cooperia populations of EL4 and adult worms were highest in weaners during winter, but lower numbers thereafter indicated a strong resistance to re-infection. In addition, Haemonchus placei occurred frequently on the North Coast both as EL4 and adults in cattle of all ages up to 20 months. Of the other cattle nematodes, Oesophagostomum radiatum and Trichuris spp occurred in low numbers, mainly in weaners. Bunstomum phlebotomum and H. contortus occurred sporadically on the North Coast and Tablelands respectively. Intestinal Trichostronglyus spp, Oesophagostomum venulosum and Dictyocaulus viviparus were seen occasionally and Nematodirus spp were not seen. There was a poor relationship between worm counts and faecal egg counts. Cooperia spp dominated the egg counts, while those for other genera were generally low and did not reflect the relative abundance or seasonal changes in worm numbers.

Animals↗

Intestinal inflammation and activation of sensory nerve pathways: a functional and morphological study in the nematode infected rat.

BACKGROUND: In the rat, gastric distension elicits an intensity dependent pseudoaffective bradycardia mediated via capsaicin sensitive afferent and cholinergic efferent vagal pathways. Inflammation alters visceral perception although the mediators responsible have not been identified. In the nematode infected rat, there is a substantial increase in neuronal substance P (SP) content of the gut. AIMS: To examine the effects of inflammation on perception of a noxious visceral stimulus and on SP and neurokinin 1 (NK-1) receptor immunoreactivity (IR) in visceral afferent pathways. METHODS: Immunohistochemistry was performed on sections from the jejunum, dorsal root ganglia (DRG), and spinal cord (T1-L1) using SP and NK-1 rabbit polyclonal antibodies. In the DRG, the number of SP-IR or NK-1-IR neurones per section was visually quantified. The pseudoaffective cardiac reflex response to gastric stimulation was compared in control and Trichinella spiralis infected rats. RESULTS: Intestinal inflammation induced a rightward shift in the intensity dependent bradycardic response to gastric distension. This was associated with a marked increase in SP-IR not only in the gut wall but also in the DRG and dorsal horn of the spine. In contrast, NK-1-IR was not increased in the gut wall. Moreover, inflammation evoked a decrease in NK-1-IR in the dorsal horn. No NK-1-IR was identified in the DRG of either control or infected animals. CONCLUSIONS: Intestinal inflammation modulates the capsaicin sensitive pseudoaffective autonomic response to gastric distension, increases SP-IR in afferent pathways, and downregulates dorsal horn NK-1-IR. As the pseudoaffective response is capsaicin sensitive, the rightward shift of the response is likely the consequence of the decrease in NK-1 receptors in the sensory pathways.

Animals↗

The effect of rotational grazing for periods of one or two weeks on the build-up of lungworm and gastro-intestinal nematode infections in calves.

An experiment was carried out with three groups of grazing calves and one housed control group to study the effect of rotational grazing for periods of 1 and 2 weeks on the build up of lungworm and gastro-intestinal nematode infections respectively. The experiment demonstrated that rotational grazing for periods of 1 week on six plots prevented the build-up of heavy lungworm infections. A build up of heavier lungworm infections was observed in a group that was rotationally grazed for periods of 2 weeks on three plots and a group which remained on one plot throughout the grazing season; there was no difference between these two groups. In all three situations, there was an adequate development of immunity against D. viviparus, as measured by worm recovery after challenge infection at the end of the experiment in comparison with worm recovery of the similarly challenged control group. Neither rotational grazing scheme protected the calves against gastrointestinal helminthiasis, because tracer calves, which grazed for 4 days only in August or October, acquired infections which would have resulted in severe illness or even death if necropsy had been postponed for a week.

Animal Husbandry↗

Jejunal circular muscle motility is decreased in nematode-infected rat.

Jejunal circular muscle motility was studied in vitro in rats 8-10 days after inoculation with the inflammation-inducing nematode Nippostrongylus brasiliensis. The passive properties of the muscle, i.e., the development of passive tension and the optimal amount of stretch for active contractions, were unchanged by infection. Infection decreased the development of active resting tension, spontaneous contractions, muscle contraction to muscarinic receptor activation, and direct electrical stimulation. Relaxation to beta-adrenergic stimulation was also decreased in tissues from infected animals. Response to cholinergic stimulation, spontaneous contractions, and active resting tension were completely dependent on extracellular calcium. The dominant response to electrical stimulation of intrinsic nerves was relaxation in control tissue and contraction in tissue from infected rats. In the presence of atropine, all tissues from control rats but only 33% of the tissues from infected rats relaxed, suggesting a marked difference in functional inhibitory innervation. The inflammation may have either decreased the circular muscle responsiveness to the inhibitory transmitter or decreased the release of this transmitter. Thus, a nematode infection produces decreased responsiveness of the intestinal circular muscle to both contracting and relaxing stimuli and causes a reduction in functional inhibitory innervation in this layer. These changes suggest mechanisms for the reduction of intestinal transit observed after some nematode infections.

Animals↗

Development and sequels of intestinal inflammation in nematode-infected rats: role of mast cells and capsaicin-sensitive afferents.

OBJECTIVES: To determine whether intestinal mast cells and capsaicin-sensitive afferent nerves are involved in the development and sequels of Nippostrongylus brasiliensis-induced intestinal inflammation in rats. METHODS: Two series of experiments were performed. In the first series, six groups of 8 rats were used to study the effects of mast cell stabilization by ketotifen. In the second series, six groups of 6 rats were used to study the effects of gut extrinsic sensory neuron depletion by capsaicin. For each series, four groups of rats were infected with N. brasiliensis and two groups were not infected. RESULTS: Infection with N. brasiliensis resulted in an increase of myeloperoxidase (MPO) activity and mast cell numbers at day 12 postinfection; MPO returned to preinfection levels by day 35 while mast cell numbers remained elevated at that time. In ketotifen-treated infected rats, the increase of MPO at day 12 was less pronounced, but MPO activity remained elevated and mast cell numbers were increased at day 35. In capsaicin-treated infected rats, the MPO increase at day 12 was augmented, and MPO was still not returned to preinfection values by day 35; in contrast, the increase of mast cell numbers at days 12 and 35 was not modified by afferent nerve depletion. CONCLUSION: Mast cell stabilization decreased jejunal inflammation during the acute stage (day 12), but prolonged the inflammatory process until at least day 35 postinfection. The data also confirmed the protective role of gut extrinsic sensory neurons against intestinal inflammation in a model of nematode infection and revealed that these afferent nerves do not seem crucial for the development of nematode-induced hypermastocytosis.

Animals↗