The pathogenicity of Clostridium difficile

AbstractIt is now well established that the major virulence factors of C. difficile are the two toxins A and B. However, the organism possesses an array of other putative virulence factors that may be important for localisation within the colon, and in evasion of the immune system. It has been observed that certain types of C. difficile are more commonly found causing disease than others, and this seems to be independent of toxin production. Is this simply a reflection of their abundance in the hospital environment, or is it due to their virulence determinants? This review covers our current knowledge of the modes of action of toxins A and B at the cellular and molecular level. Many unanswered questions are posed that require answers before we can fully understand the pathogenic mechanisms of the organism and be in a position to manage better the spectrum of diseases it causes

Association between Key-Gaskell syndrome and infection by Clostridium botulinum type C/D

There is growing evidence that equine dysautonomia is a toxicoinfection with Clostridium botulinum type C. The possibility that feline dysautonomia has the same aetiology was investigated by attempting to detect botulinum type C neurotoxin in the food, faeces and the contents of the ileum of affected cats, and by serology. The toxin was detected directly in four of eight affected cats and after enrichment in seven of them, and in their dried food. No toxin was detected in healthy control cats or in their tinned food. Recent exposure to the organism was assessed by the detection of immunoglobulin A (IgA) in the faeces of healthy control cats and affected cats. The levels of IgA antibodies to the toxin and to surface antigens of C. botulinum type C in the faeces of the affected cats 14 weeks after the outbreak were significantly higher than in the faeces of the control cats

Spatio-temporal stochastic modelling of clostridium difficile

Clostridium difficile-associated diarrhoea (CDAD) occurs sporadically or in small discrete outbreaks. Stochastic models may help to inform hospital infection control strategies. Bayesian framework using data augmentation and Markov chain Monte Carlo methods were applied to a spatio-temporal model of CDAD. Model simulations were validated against 17 months of observed data from two 30-bedded medical wards for the elderly. Simulating the halving of transmission rates of C. difficile from other patients and the environment reduced CDAD cases by 15%. Doubling the rate at which patients become susceptible increased predicted CDAD incidence by 63%. By contrast, doubling environmental load made hardly any difference, increasing CDAD incidence by only 3%. Simulation of different interventions indicates that for the same effect size, reducing patient susceptibility to infection is more effective in reducing the number of CDAD cases than lowering transmission rates

Humoral immune response as predictor of recurrence in Clostridium difficile infection

Molecular basis of bacterial pathogenesis, virulence factors and antibiotic resistanc

Changes in anti-endotoxin-IgG antibody and endotoxaemia in three cases of gram-negative septic shock.

Circulating endotoxin levels and IgG antibodies to a range of Gram-negative bacterial lipopolysaccharides (LPS) (endotoxins) of different sizes and structures were measured daily in three cases of septic shock. There was an inverse relationship between endotoxin levels and cross-reactive antibodies to the core glycolipid (CGL) region of lipopolysaccharide. This suggests that antibody to LPS-CGL was initially consumed by a superabundance of endotoxin, and that a resurgence of intrinsic anti-LPS-CGL antibody levels may be associated with a reduction of circulating endotoxin. The implications of these findings for passive antibody therapy of septic shock are discussed