Abstract
BackgroundThe control of Clostridium difficile infection is a major international healthcare priority, hindered by a limited understanding of transmission epidemiology for these bacteria. However, transmission studies of bacterial pathogens are rapidly being transformed by the advent of next generation sequencing.ResultsHere we sequence whole C. difficile genomes from 486 cases arising over four years in Oxfordshire. We show that we can estimate the times back to common ancestors of bacterial lineages with sufficient resolution to distinguish whether direct transmission is plausible or not. Time depths were inferred using a within-host evolutionary rate that we estimated at 1.4 mutations per genome per year based on serially isolated genomes. The subset of plausible transmissions was found to be highly associated with pairs of patients sharing time and space in hospital. Conversely, the large majority of pairs of genomes matched by conventional typing and isolated from patients within a month of each other were too distantly related to be direct transmissions.ConclusionsOur results confirm that nosocomial transmission between symptomatic C. difficile cases contributes far less to current rates of infection than has been widely assumed, which clarifies the importance of future research into other transmission routes, such as from asymptomatic carriers. With the costs of DNA sequencing rapidly falling and its use becoming more and more widespread, genomics will revolutionize our understanding of the transmission of bacterial pathogens.
Highlights
The control of Clostridium difficile infection is a major international healthcare priority, hindered by a limited understanding of transmission epidemiology for these bacteria
This proportion was much higher in ST1 (63%, 167/267), consistent with the epidemic nature of this C. difficile lineage [5,6]
We do not infer that all these pairs represent direct transmissions, because showing this would require the ability to rule in when transmission happened whereas this study focused on ruling out when it did not
Summary
The control of Clostridium difficile infection is a major international healthcare priority, hindered by a limited understanding of transmission epidemiology for these bacteria. A widely held assumption that much transmission occurs in hospitals between symptomatic patients was reinforced when enhanced infection control introduced in England in 2007 was followed by declines in the incidence of CDI [3]. In a previous study [12], we used comprehensive epidemiological information on patient admissions and ward movements within the Oxfordshire hospitals [13] to discriminate routes of nosocomial transmission between symptomatic cases sharing the same MLST type. This study found fewer cases of CDI than anticipated that could be attributed to acquisitions from other symptomatic patients sharing space and time on a hospital ward [12]. Whole genomes were sequenced to provide a genetic resolution that is directly informative about fine scale patterns of transmission
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