Abstract
Following rapid, global clonal dominance of hypervirulent ribotypes, Clostridium difficile now constitutes the primary infectious cause of nosocomial diarrhoea. Evidence indicates at least three possible mechanisms of hypervirulence that facilitates the successful invasion of these atypical strains: 1) increased infectiousness relative to endemic strains; 2) increased symptomatic disease rate relative to endemic strains; and 3) an ability to outcompete endemic strains in the host’s gut. Stochastic simulations of an infection transmission model demonstrate clear differences between the invasion potentials of C. difficile strains utilising the alternative hypervirulence mechanisms, and provide new evidence that favours certain mechanisms (1 and 2) more than others (3). Additionally, simulations illustrate that direct competition between strains (inside the host’s gut) is not a prerequisite for the sudden switching that has been observed in prevailing ribotypes; previously dominant C. difficile strains can be excluded by hypervirulent ribotypes through indirect (exploitative) competition.
Highlights
Clostridium difficile is a globally significant enteric pathogen with rapid emergence in the Americas, Asia, Oceania and Europe[1]
These categories consist of people who are unexposed to C. difficile and who are susceptible to colonization (U); exposed to endemic strains (E) or to hypervirulent strains (Eh); colonized with endemic strains (C) or with hypervirulent strains (Ch); and suffering symptomatic disease from endemic strains (D) or hypervirulent strains (Dh)
The key mechanisms by which hypervirulent strains differ from normal endemic strains are: 1) the rate of transmission is higher for hypervirulent strains (β h > β ); 2) the proportion that experience symptomatic disease is higher for hosts infected with hypervirulent strains (ε h > ε ); and 3) individuals that are already colonized with normal endemic strains can be colonized by hypervirulent strains (α > 0)
Summary
Clostridium difficile ribotype 027 received: 10 November 2014 accepted: 03 July 2015 Published: 28 July 2015 displacement of endemic strains: an epidemiological model. We use ribotype 027 to demonstrate the invasion dynamics of hypervirulent strains because it was the causative agent of the largest recorded outbreak of C. difficile and because the considerable literature pertaining to this particular strain facilitates more accurate model parameterisation. In vitro studies conducted by Merrigan and colleagues[8] examined the accumulation of spores over the bacterial growth cycle and demonstrated that hypervirulent strains sporulated earlier and accumulated significantly more spores per total volume of culture than non-hypervirulent strains This increased rate of sporulation may explain, at least in part, the observation of unusually high relapse rates associated with hypervirulent strains (in the order of 4-fold according to Marsh et al.9) because patients are more likely to contaminate their local environment and subsequently re-infect themselves. To offer unique perspective to the critical epidemiological question of which mechanism underlies the rapid global spread (and for many regions, the subsequent clonal dominance) of ribotype 027, we analysed the simulated invasion of hypervirulent C. difficile following its introduction into a human community
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