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Title: The 1996 central Scotland outbreak of Escheria coli 0157:H7 : investigation of clinical presentations and consequences
Author: Dundas, Stephanie
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2002
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In 1996 a large outbreak of Escherichia coli (E. coli) 0157 occurred in central Scotland. The outbreak recorded the largest number of adults with HUS and consequently the largest number of deaths, ever attributed to E. coli 0157. This unfortunate event provided opportunity to investigate severe acute disease and the chronic sequelae of infection. The retrospective studies aimed to assess host factors associated with the development of the haemolytic uraemic syndrome (HUS), to identify the earliest laboratory predictors of HUS, to develop a community monitoring protocol able to detect those with early HUS, to define the role of therapeutic plasma exchange (TPE) in the treatment of adults with HUS and to determine genetically mediated inflammatory responses associated with the severity of acute disease. The studies of chronic disease investigated renal function abnormalities in cases surviving HUS, and gastrointestinal complications and quality of life (QOL) in all cases. 512 cases were provisionally identified and 270 were confirmed by stool culture. 120 cases were admitted to hospital, 34 developed HUS and 17 died. Children and older adults were at greatest risk of HUS. However high white cell count (WCC) at presentation was as least as good a predictor of HUS as age. Acquired risk factors for HUS were low gastric acid and antibiotic therapy prior to symptom onset. 186 patients were assessed for blood group markers (ABO, Lewis and P). Blood group O and absent or weak expression of the PI erythrocyte antigen were associated with HUS. Very high levels of TNFa, implicated in the pathogenesis of HUS, were produced by leucocytes of P-negative individuals. Adults in Lanarkshire who developed HUS were treated with TPE, which is unproven and controversial in the context of E. coli 0157. The mortality associated with HUS was 45%, which compares favorably with previously reported mortality of 88%. Therefore TPE appears to be a promising treatment. Thirty per cent of children develop chronic renal disease following VTEC induced HUS but there was no information on the renal outcome of adults. In Lanarkshire 12 of 22 adults with HUS survived the acute illness. To the third anniversary chronic renal disease was demonstrated in all; one progressed to ESRD, three developed CRF and eight had clear evidence of renal insufficiency. Comparison with a control group confirmed that these changes could not simply be attributed to age. Prospective investigation determined the prevalence of irritable bowel syndrome (IBS) after E. coli 0157 infection and its impact QOL. On the second and third anniversaries of infection IBS was significantly higher in cases compared to matched controls. Almost forty per cent of cases developed new IBS within three years of infection. Cases with IBS had significantly lower SF-36 scores in all scales particularly those reflecting mental health. Therefore IBS is common after E. coli 0157 with a detrimental effect on QOL. This thesis provides new insight into the pathogenesis and clinical consequences of disease due to E. coli 0157, particularly in adults a previously undocumented group.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available