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M J Stear

Publications and source records attributed to M J Stear.

At least 19 recordsLinked to original sources

The evolution and maintenance of polymorphism in the major histocompatibility complex.

Lambs with the G2 allele at the ovine major histocompatibility complex (mhc) class II locus DRB1 has previously been shown to have lower faecal nematode egg counts than lambs with the I allele at this locus. This association has been confirmed in separate cohorts from the same farm. Other alleles within the mhc have also shown associations with nematode resistance in other breeds of sheep. Therefore, variation in the mhc is responsible for part of the observed genetic variation in resistance to nematode infection. In addition to the specific effect of particular alleles, heterozygotes are also more resistant than homozygotes. This heterozygote advantage is capable of maintaining the high levels of polymorphism observed within the mhc.

Alleles↗

Variation among faecal egg counts following natural nematode infection in Scottish Blackface lambs.

Faecal egg counts were examined in 2 flocks of naturally infected Scottish Blackface sheep in southern and central Scotland. The distribution of mean counts was right skewed and similar to a gamma distribution. The counts varied with month, with mean counts rising from May to July, then falling but rising again in October, although data within each year did not always show such a clear pattern. There was no significant difference in mean egg count between the 2 farms examined. The distribution of egg count variances was also right skewed and conformed to a gamma distribution. There was a strong relationship between the mean and the variance for each population, implying that variation among populations in variances largely mirrored variation in mean egg counts. Populations with high mean egg counts and variances did not necessarily have more adult nematodes but had a greater number of adult nematodes from species other than Teladorsagia circumcincta, particularly Cooperia spp., Trichostrongylus axei and Trichostrongylus vitrinus. The contribution of different parasite species to the egg count explains the relatively poor and inconsistent fit of the negative binomial distribution to faecal egg counts in lambs.

Albendazole↗

The relationship between IgA activity against 4th-stage larvae and density-dependent effects on the number of 4th-stage larvae of Teladorsagia circumcincta in naturally infected sheep.

The number of Teladorsagia circumcincta 4th-stage larvae in naturally infected lambs from a single farm varied among lambs and among different years. Within each year the distribution of 4th-stage larvae among lambs was similar to that expected from a negative binomial distribution. The ratio of 4th-stage larvae to adult T. circumcincta was low in two years with a low mean intensity of infection but high in two years with a higher mean intensity of infection. The negative binomial distribution is defined by the mean and by k, a parameter that measures dispersion; k was low when mean infection intensity was low but higher when mean infection intensity was high. As k is an inverse index of overdispersion this indicated that the distribution of 4th-stage larvae was more overdispersed at low levels of infection. In a combined analysis, the number of adult T. circumcincta and the plasma IgA activity against 4th-stage larvae were both associated with increased numbers of 4th-stage larvae. There was a statistical interaction between the number of adults and IgA activity that moderated their combined effect.

Abomasum↗

Modeling of host genetics and resistance to infectious diseases: understanding and controlling nematode infections.

This paper considers approaches to modeling the dynamics of infectious disease and the application of such models to nematode parasite infections in ruminants. Particularly, these models are developed to account for host genetics and may be used to assess the effects of using genetics to control nematode infections. Three main issues are critically examined: the infection transmission cycle from pasture to host to pasture, the expected genetic relationships between resistance and performance, and the risks of parasite evolution in response to genetic changes in the host. To obtain answers that are realistic and of practical use, the modeling approaches require a solid grounding in biology. This biology is formalized and described using mathematical techniques, with the models parameterized using experimental or field data. Transmission dynamics have been quantified by modeling and are backed by strong experimental data. Selection for resistance will be successful in reducing egg output, pasture larval contamination and hence subsequent larval challenge. Modeling frameworks have been developed to predict genetic relationships between resistance to infectious disease and performance in general, and genetic correlations predicted for nematode resistance are close to mean published values. These predicted correlations strengthen as the larval challenge increases and the dietary (protein) adequacy decreases, however modeling challenges remain. Lastly, although convincing experimental data is not yet available, arguments based on modeling suggest that the risks of parasite evolution in response to genetic changes in the host should be less than the risks arising from other control strategies, such as anthelmintics. Thus, modeling techniques predict that selective breeding for resistance should be an effective and sustainable complementary control measure.

Animals↗

A key mechanism of pathogenesis in sheep infected with the nematode Teladorsagia circumcincta.

Infection of sheep with the abomasal nematode Teladorsagia circumcincta can cause a relative protein deficiency and reduce growth rate in growing lambs. A key event appears to be the destruction of junctions between epithelial cells. If the infection is heavy or prolonged, this leads to increased mucus production, hyperplasia, decreased acid production, gastrinemia, inappetance and pepsinogenemia. The severity of the infection depends upon the extent of concurrent infection, the nutritional status of the host and genetically controlled variation in the ability to mount protective immune responses.

Abomasum↗

The genetic control of IgA activity against Teladorsagia circumcincta and its association with parasite resistance in naturally infected sheep.

Previous studies in deliberately infected sheep have shown an association between IgA activity against 4th-stage larvae of Teladorsagia circumcincta and parasite growth, development and fecundity. The purpose of this research was to determine if these results could be confirmed in naturally infected sheep and to explore the hypothesis that plasma IgA activity could help to identify resistant lambs with shorter adult nematodes. Plasma IgA activity was skewed with most animals having relatively low levels of IgA activity. Plasma IgA activity was repeatable and highly heritable. Animals with increased IgA activity had lower egg counts and shorter adult female T. circumcincta. Therefore, under conditions of natural parasite challenge, plasma IgA activity may help to identify lambs resistant to T. circumcincta.

Animals↗

Eosinophilia as a marker of resistance to Teladorsagia circumcincta in Scottish Blackface lambs.

Faecal egg counts and peripheral blood eosinophil counts were taken from Scottish Blackface lambs following natural, predominantly Teladorsagia circumcincta infection. Peripheral eosinophil concentrations were higher in animals with lower egg counts but only in lambs that were at least 3 months of age. The reduced egg counts were due to reduced fecundity of T. circumcincta; there was no association with the number of adult T. circumcincta. Associations with the number of parasites from other species of gastrointestinal nematodes appeared to be neutral or favourable. Estimated heritabilities for eosinophil concentrations in 4- and 5-month-old lambs were 0.48 +/- 0.16 and 0.43 +/- 0.17, respectively. Therefore, under defined circumstances, eosinophil concentrations may be a useful indicator of resistance to predominantly T. circumcincta infection.

Animals↗

A microsatellite polymorphism in the gamma interferon gene is associated with resistance to gastrointestinal nematodes in a naturally-parasitized population of Soay sheep.

Free-living Soay sheep (Ovis aries) on the island of Hirta, St Kilda, Scotland, are naturally parasitized by gastrointestinal nematodes, predominantly Teladorsagia circumcincta. In this paper we show that reduced faecal egg counts (FEC) are associated with an allele at a microsatellite locus located in the first intron of the interferon gamma gene (o(IFN)-gamma) in Soay sheep lambs and yearlings, measured at approximately 4 and 16 months of age, respectively. The same allele was also associated with increased T. circumcincta-specific antibody (IgA) in lambs, but not associated significantly in yearlings. Flanking control markers failed to show a significant association with either FEC or IgA. These results suggest that a polymorphic gene conferring increased resistance to gastrointestinal nematode parasites is located at or near the interferon gamma gene, and support previous reports which have mapped a quantitative trait locus (QTL) for resistance to this region in domestic sheep. Our data are consistent with the idea that a functional polymorphism leading to reduced expression or efficacy of (IFN)-gamma could enhance the immune response to gastrointestinal nematodes by favouring the activity of the Th2 cell subset and antibody associated immune mechanisms.

Animals↗

Fructosamine concentration and resistance to natural, predominantly Teladorsagia circumcincta infection.

Fructosamine concentrations reflect protein status and because infection with Teladorsagia circumcincta can induce a relative protein deficiency, we examined the usefulness of fructosamine concentrations as markers of the intensity of infection in naturally infected lambs. Fructosamine concentration was a heritable trait and variation in fructosamine concerntrations was associated with differences in body weight, and a variety of parasitological variables; animals with increased fructosamine concentrations grew more quickly, had increased faecal egg counts in one of the three study years, had decreased pepsinogen concentrations and decreased IgA activity against 4th-stage larvae of T. circumcincta. Fructosamine concentrations were also associated with variation in the subsequent acquisition of nematodes and in the length of adult female T. circumcincta; lambs with increased fructosamine concentrations had fewer nematodes but the mean length of adult female T. circumcincta was longer. Therefore fructosamine concentrations are potentially useful indicators of the severity of nematode infection and may predict magnitude of subsequent infection.

Abomasum↗

The influence of protein supplementation on the immune response to Haemonchus contortus.

A major protective mechanism in lambs against the abomasal parasite Ostertagia (Teladorsagia) circumcincta appears to be the immunoglubulin (Ig)A-mediated suppression of worm growth and fecundity. The present study indicates that IgA may play a similar role in the control of another abomasal parasite Haemonchus contortus. Hampshire Down lambs were offered one of two diets: (i) a basal diet and (ii) a diet supplemented with additional protein. Lambs were then 'trickle' infected with H. contortus and killed 10 weeks after the start of infection. Those lambs on the supplemented diet had shorter adult worms and produced significantly more antiparasite IgA. There was a significant association between reduced female adult worm length and increased IgA against third-stage larvae. Most of the difference between the two groups in worm length could be accounted for by differences in IgA responses. Therefore, IgA may be the major mechanism controlling fecundity of H. contortus and the magnitude of the IgA response is influenced by the quality of the diet.

Animals↗

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↗

The sustainability, feasibility and desirability of breeding livestock for disease resistance.

Selective breeding for disease resistance utilises proven animal breeding methods to improve animal health, welfare and productivity. Unsurprisingly, it is receiving more and more attention from livestock breeders. However, there are a number of largely theoretical arguments that have been raised as potential problems in selection for disease resistance. These can be classified under sustainability, feasibility and desirability. This review considers each of these areas in turn. Several examples show that enhanced resistance to disease is stable under natural selection and therefore deliberate selection for disease resistance should also be stable and sustainable. The feasibility of selective breeding depends in part upon the heritability of the trait or traits used to measure disease resistance, as well as the amount of variation among animals. The heritability of traits associated with resistance to many important diseases is often high and considerable variation among animals exists. Consequently, selective breeding for enhanced disease resistance is certainly feasible. The desirability of breeding for disease resistance depends upon whether there are trade-offs with other economically important traits. By and large these remain to be defined. However, even if unfavourable associations exist, breeders can create selection indices that include traits with unfavourable associations and maximise the desired responses while attempting to minimise undesirable effects. In conclusion, so long as one or more diseases exert a significant influence on livestock production, selective breeding will be a useful tool to assist in disease control.

Animals↗

The influence of relative resistance and urea-supplementation on deliberate infection with Teladorsagia circumcincta during winter.

The consequences for lambs of infection over the winter with Teladorsagia circumcincta were quantified by deliberate, trickle infection of selected animals at 7 months of age. Infected and control uninfected animals were each allocated into four groups, relatively resistant animals on a normal diet, relatively resistant animals on an isocaloric diet supplemented with urea, and relatively susceptible animals on the same two diets. Resistance and susceptibility was assessed by faecal egg counts following natural infection during the summer preceding the deliberate infection. During the deliberate infection egg counts remained low and most parasites recovered at necropsy were inhibited larvae. Nonetheless, infection reduced weight gain, decreased albumin and fructosamine concentrations and provoked a noticeable pepsinogen and eosinophil response. As most larvae were inhibited these responses may have been largely a consequence of immuno-inflammatory responses in the host rather than the direct action of parasites themselves. Relatively resistant animals on the supplemented diet allowed fewer larvae to establish and had higher fructosamine concentrations, higher albumin concentrations and decreased pepsinogen responses. Therefore, a combination of relatively resistant sheep and nutritional supplementation appears most efficient at controlling infection.

3-Hydroxybutyric Acid↗

The influence of age on the variation among sheep in susceptibility to natural nematode infection.

A longitudinal study of faecal nematode egg counts was made in naturally infected Scottish Blackface sheep over two grazing seasons to 75 weeks of age. Although egg counts were lower in the second grazing season the variation among animals was greater. Egg counts were repeatable from 3 months of age. The repeatability of faecal egg counts within and between grazing seasons was about 0.3. Animals with lower than average egg counts in the first grazing season tended to have lower than average egg counts in the second grazing season. Therefore lambs with relatively low faecal egg counts after 3 months of age are likely to retain their advantage in the following year.

Aging↗

The use of a gamma-type function to assess the relationship between the number of adult Teladorsagia circumcincta and total egg output.

The relationship between faecal nematode egg count and the number of adult Teladorsagia circumcincta was examined in 508 naturally infected lambs at 6-7 months of age. The relationship was found to be convex and was empirically described by a gamma-type function of the form y = an(b) e(-cn), where n is the number of adult nematodes present and y is the number of nematode eggs per gramme (epg) of faeces. This equation predicted that the peak expected egg count (277 epg) would occur at a worm burden of 2,167 adult worm is consistent with the existence of severe density-dependent constraints on the fecundity of T. circumcincta.

Animals↗

Molecular markers and their use in animal breeding.

The use of DNA markers to define the genetic makeup (genotype) and predict the performance of an animal is a powerful aid to animal breeding. One strategy is known as marker-assisted selection (MAS). MAS facilitates the exploitation of existing genetic diversity in breeding populations and can be used to improve a whole range of desirable traits. DNA markers are, by definition, polymorphic, and the methods used to define DNA markers include restriction fragment length polymorphisms (RFLPs), microsatellites, and single nucleotide polymorphisms (SNPs). Linkage analysis, association analysis and analysis of gene function can be used to determine which polymorphisms are useful markers for desirable traits. Future prospects include the use of high throughput DNA microarray (DNA chip) technology which could revolutionize animal breeding in the next millennium.

Animal Husbandry↗

How lambs control infection with Ostertagia circumcincta.

Two of the most important questions for immunologists studying nematode infections are what effect does the host response have on the parasite and which components of the host response are responsible for these effects. The number of nematodes and the mean length of adult female Ostertagia circumcincta was measured in over 500 6-7 month old lambs of the Scottish Blackface breed. Quantitative genetic analyses indicated that there was substantial genetic variation among lambs in faecal egg counts and in worm length but the analyses provided no evidence for genetic variation in worm numbers. Separate analyses have shown a strong relationship between decreased worm length and decreased worm fecundity. Therefore, genetic resistance in lambs appears to be due to control of worm growth and not to control of worm numbers. The only immune response that is consistently associated with reduced worm length is the IgA response to fourth-stage larvae. The association is remarkably strong. After allowing for the influence of worm number on worm length (density-dependence) essentially all of the variation among deliberately infected lambs in worm length can be accounted for, in a statistical sense, by variation in the strength and specificity of the local IgA response. Therefore, the IgA mediated suppression of worm growth and fecundity appears to be the major mechanism of resistance to O. circumcincta in lambs.

Animals↗