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Sequencing Study Suggests Range of C. difficile Infection Sources

NEW YORK (GenomeWeb News) – Exposure to symptomatic individuals within healthcare settings may account for just a fraction of Clostridium difficile infections, according to a study from the UK appearing online last night in the New England Journal of Medicine.

A team led by investigators at the University of Oxford and Leeds General Infirmary did whole-genome sequencing on samples from more than 1,000 patients diagnosed with C. difficile infections at Oxfordshire hospital or community settings over three-and-a-half years, from the fall of 2007 and spring of 2011.

Results of the group's sequence analysis suggested nearly half of new infections turning up during that time frame involved isolates too genetically distinct to have been transmitted from other patients with symptomatic C. difficile infections. In addition, a substantial fraction of isolates sharing genetic ties to earlier infections could not be epidemiologically linked to another infected person or healthcare source.

"These data show that in the majority of cases, C. difficile infection is not transmitted from another symptomatic patient," corresponding author David Eyre, with the National Institute for Health Research Oxford Biomedical Researcher Centre, and his co-authors wrote.

Efforts to rein in new C. difficile infections have largely centered on preventing transmission by individuals showing obvious symptoms of infection, the researchers noted. But the complete suite of potential C. difficile reservoirs has not been completely characterized, suggesting infectious bugs may come from other sources as well.

"[T]here are multiple other potential sources," they wrote, "including patients with asymptomatic colonization and sources in the wider environment, such as water, farm animals or pets, and food."

To delve into the sources of infections in one community over several years, the group used Illumina instruments to take a crack at sequencing 1,250 isolates from individuals with symptomatic C. difficile infections reported in Oxfordshire between late 2007 and early 2011 — both in the community and at four local hospitals.

With data from 1,223 successfully sequenced isolates, researchers tracked down SNPs that proved useful for delineating relationships between the isolates and determining some of their transmission patterns.

For example, the team found that roughly a third of the isolates collected after the spring of 2008 shared close genetic ties with at least one of the isolates linked to an earlier case, differing at two SNPs or fewer — a level of relatedness that's believed to reflect C. difficile transmission within a few months.

With the help of epidemiological data, the team determined that around 38 percent of those cases involved direct transmission from another infected individual. Other transmission events were suspected to involve isolates picked up within hospital wards and/or from other forms of hospital contact.

Even so, more than 100 of the cases that clustered with those occurring earlier could not be traced back to contact with potential infection sources in the participating healthcare settings.

And hundreds more isolates — some 45 percent of those collected after April 2008 — differed at 10 SNPs or more from cases examined between late 2007 and early 2008, the researchers reported. That hints at still other routes of transmission, perhaps involving individuals who carry C. difficile without showing symptoms of infection by the bug.

"Some patients with genetically distinct isolates may have acquired C. difficile infection from sources outside Oxfordshire, but given the patients' median age of 78 years, it is more likely that most organisms were acquired from asymptomatic persons or some other environmental reservoir," they wrote.