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Title: Immune responses in dairy cattle naturally exposed to Fasciola hepatica
Author: Graham-Brown, J. J.
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2016
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Fasciola hepatica is a parasitic trematode capable of infecting a range of vertebrate species including livestock and humans. Both clinical disease (fasciolosis) and sub-clinical infections are of major economic and welfare importance in food producing animals. The life cycle of F. hepatica requires an intermediate host, which in the UK is the mud snail Galba truncatula. High levels of moisture and ambient temperatures between 10-30oC provide optimal conditions for the development of both parasite and snail. As a consequence of changing weather patterns, disease prevalence has increased in recent years, whilst an over-reliance on effective anthelmintics to control disease has resulted in the selection of drug resistance within parasite populations. Studies investigating vaccination as a potential method to control F. hepatica in cattle have identified specific components of the vaccine-induced immune response such as IgG2 antibody titre and avidity, which are associated with protection. Conversely, evidence from experimental infections indicate that F. hepatica modulates the host immune system towards a non-protective type-2 response, extending parasite survival within the host. The overall objective of this thesis was to analyse the immune response in calves and adult cattle naturally exposed to, and infected with, F. hepatica. This was achieved firstly through the validation of a herd level diagnostic test to identify infected beef and dairy herds, and secondly by evaluating the type of immune response present in infected animals. The outputs will be valuable in informing vaccine development, since the type of immune response present in naturally infected cattle, will ultimately have implications for how such vaccines are applied in the field. Chapter 3 describes the validation of a composite sample analysis for fluke egg counts. A total of 138 individual samples from 7 commercial beef herds in mid-Wales were sampled. Fluke egg counts were done on individual samples in addition to composite samples composed of ten 5g samples. These data together with individual counts from a further 22 dairy farms (638 individual samples) were fitted to negative binomial distributions at the farm level. These were stochastically re-sampled to generate a range of predicted composite counts from which confidence intervals and test sensitivity were determined. When referred back to the original counts, all composite counts were within the generated confidence intervals, with the lower confidence interval indicating a 95% test sensitivity at ≥0.4 eggs per gram of faeces compared to individual count data. With the exception of lactating dairy cattle, diagnosis of F. hepatica is limited to individual faecal and/or serum sampling. This analysis represents an important development, since a validated composite worm egg count for cattle provides a simple yet effective test for screening groups of animals for infection. In chapter 4, immune responses in naïve dairy heifers (n=42) naturally exposed to F. hepatica were evaluated. Calves on 3 commercial UK dairy farms were sampled monthly over the course of their first grazing season and analysed to determine fluke infection status and parasite specific immune responses. Where infection was present, this was associated with increases in type-2 associated responses, with increases in interleukin-4 production, interleukin-5 transcription and an eosinophilia. A reduction in the type-1 associated cytokine, interferon-γ was also observed over the course of infection. These findings suggest that a natural challenge with F. hepatica induces a non-proliferative type-2 response. This has implications for vaccine development and application, since current evidence suggests that stimulation of additional components such as IgG2 antibody and strong cell mediated responses are required for protection. Chapter 5 describes a study carried out on a commercial dairy farm, characterising the immune responses in adult dairy cattle (n=27) with chronic infections. The effect of treating infected animals with triclabendazole (12mg/kg) on the immune response was also assessed. Both parasite specific and mitogen stimulated interleukin-4 production were positively associated with F. hepatica antibody titres based on linear regression analysis, whilst no such correlation was found with interferon-γ. This suggests that modulation of the immune response towards a type-2 response is a feature in chronic infections. Additionally, increases in the regulatory cytokines Transforming Growth Factor-β and interleukin-10, associated with infection in pre and post treatment groups respectively may indicate that these cytokines play a role in parasite induced immune modulation, which has been described previously in experimentally infected cattle. Overall, these results show that cattle exposed to and infected with F. hepatica under natural grazing conditions develop a type-2 immune response. This has implications for future vaccination programmes, as the presence of immune modulation arising from natural infection suggests any vaccine induced immune response should be fully developed prior to natural exposure to ensure protection. These results also highlight the importance of the impact of fluke infections on the host’s immune system and the need to investigate and better understand the relationship between F. hepatica and other co-infecting pathogens.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available