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Title: Pathogenesis of Clostridium difficile and immune response in health and disease
Author: Sánchez-Hurtado, Karla
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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Most patients colonized with C. difficile remain asymptomatic. When C. difficile-associated disease (CDAD) presents, it ranges from mild diarrhoea to severe diarrhoea that can lead to severe complications which can result in colectomy or even death. It is not clear why some patients remain asymptomatic while others present severe disease but one hypothesis is that patients who develop symptoms have lower levels of specific antibodies to C. difficile than those who remain asymptomatic after colonization with C. difficile. The levels of systemic antibodies were analysed in three groups within the elderly hospitalised population of Edinburgh: a) CDAD cases; b) asymptomatic carriers of C. difficile and c) non-colonized controls. Overall, the levels of antibodies were highest in the CDAD cases and lowest in the non-colonized controls suggesting that cases are not unable to mount an adequate response. CDAD cases were more likely to be co-infected with cytomegalovirus (CMV) than asymptomatic carriers or non-colonized controls. CMV might be an indicator of severe disease or might be contributing towards the worsening of CDAD. From the data available, the CDAD cases were more likely to have received β-lactamase inhibitors than asymptomatic carriers, and ciprofloxacin was linked to susceptibility to colonization (but not to disease). The main virulence factors of C. difficile are two exotoxins which are encoded in a region of the genome named “pathogenicity locus” (PaLoc). Real-time PCR was used to investigate if antibiotics affected the expression of the PaLoc genes. The presence of clindamycin induced an increase in the levels of mRNA of the five PaLoc genes wile amoxicillin and vancomycin might help toxin release by creating pores in the C. difficile wall.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available