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Title: The role of Clostridium botulinum in the aetiology of equine grass sickness and other dysautonomias
Author: Nunn, Francesca G.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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Equine grass sickness is a primary dysautonomy of unproven aetiology that is mainly fatal, untreatable and unpreventable. Much circumstantial evidence has been demonstrated that supports the hypothesis that the disease is caused by a toxicoinfection with Clostridium botulinum type C/D. Further evidence supporting this hypothesis and an understanding of the immune response of the horse to this organism and its toxins will facilitate vaccine research and design. Serum samples from 6-month old ponies (n = 26) were assayed for antibodies against botulinum neurotoxins type C and D (BoNT/C & D) and against surface antigens (SA). Statistically significant rises in specific lgG levels against all three antigens were shown across the sampling period, demonstrating specific antibody acquisition with age. Adult horses (n = 40) were sampled fortnightly for twelve months and assayed for specific IgG against the same antigens. In this group fluctuations in specific IgG levels were observed that corresponded with changes in management. Seven acute cases of grass sickness that went to postmortem within 36h of onset of clinical signs and four control horses that went to post-mortem had both serum and gut samples taken. Specific IgA was assayed and cases demonstrated significantly more specific IgA against BoNT/C in the jejunum, ileum and caecum (P = 0.04, 0.02 and 0.006 respectively). Against BoNT/D, cases demonstrated significantly more IgA in the pharynx, duodenum and jejunum (P = 0.01, 0.01 and 0.02 respectively) and against surface antigens cases demonstrated significantly more specific IgA in the duodenum (P = 0.01). Serum samples from these acute cases were assayed for specific IgG and IgG subclasses against the same antigens and compared to co-grazing controls. Cases demonstrated lower specific IgG against surface antigens than co-grazing controls (P = 0.06). Sera from twelve chronic cases of grass sickness were assayed for specific IgG. Six horses that were subsequently euthanased demonstrated significantly lower initial IgG levels against SA (P = 0.05) than those that survived and almost significantly lower IgG levels to BoNT/C (P = 0.06) indicating that immune status at disease onset may be important in survival/prognosis. Longitudinal analysis showed that rising or falling levels of specific IgG had no influence on disease outcome. An outbreak of feline dysautonomia was investigated by bacteriological and serological techniques. BoNT/C was detected in faeces in seven of eight affected cats after enrichment and also detected in their food. No toxin was detected in the faeces of controls. Specific IgA was also present in significantly higher amounts in cases than in controls (P = < 0.001) against BoNT/C and SA. In serological studies, associations were found between low antibody levels and disease in cats but not in dogs, which lacked an age-matched control group. EGS and dysautonomias of other species appear to be associated with toxicoinfections with C. botulinum types C and/or type D. As such, a vaccine, consisting of both surface antigen and toxin components, would play a vital role in protecting animals against this distressing disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available