Genome sequencing used to control hospital infection

When a disease outbreak is confirmed, it's a race against time to track the source of infection and control its spread. Technology that can sequence a bacterial genome within a few days has proved crucial after being successfully used to track an outbreak last year.

On 15 July 2011, a 43-year-old woman was discharged from the 243-bed National Institutes of Health (NIH) Clinical Center ? a research hospital in Bethesda, Maryland ? following treatment for a drug-resistant strain of Klebsiella pneumoniae. Three weeks later, despite a rigorous quarantine procedure, hospital staff discovered a second case.

But the traditional technique for genetic fingerprinting, known as pulsed-field gel electrophoresis (PFGE), was unable to distinguish between the strains in the two confirmed cases. The technique was too crude, says Tara Palmore, deputy hospital epidemiologist at the NIH Clinical Center. Even if the two strains had been acquired on different continents, PFGE would have suggested they were identical, she says.

So Julie Segre of the National Human Genome Research Institute and her colleagues, who were part of a research team at the hospital, decided to sequence the genomes of the strains. "This was some of the most interesting work I've ever done in my life," says Segre. "We were in a real crisis here, trying to figure out what was going on."

The infection spread to 17 people at the rate of about one new case per week. Six patients died directly as a result. But the sequencing data ? which showed up precise differences between instances of infection, down to single genetic letters in the bacterial genome ? allowed hospital staff to work out exactly how it was spreading.

When sequences taken from two patients were genetically similar, these patients' shared characteristics were scrutinised. Equally, if the infections of two patients were not genetically close then that avenue of investigation was not pursued.

The researchers found that the original patient had infected two people, neither of whom were the second confirmed case. "The measures taken to control patient one were not sufficient," says Segre. The finding also showed that symptoms could remain hidden. "It's changed our sense of vigilance," she says.

The work helped to identify and eradicate transmission paths ? for instance, plumbing in hospital sinks was replaced to control the rate of spread. "We used the information to change the practice of the hospital," says Segre.

"It blows pulsed-field gel electrophoresis out of the water," says Palmore. But genome sequencing won't work for all pathogens. For example, Mycobacterium tuberculosis ? the pathogen behind TB ? has a very "tight" genome, says Segre, which means small differences between generations probably wouldn't show up.

With genome sequencing equipment becoming cheaper and faster, could sequencing become part of the standard response to hospital outbreaks?

"It's great to see this study," says Sharon Peacock of the University of Cambridge, who has previously advocated the use of genome sequencing for outbreak control in hospitals. "It's going to lead to a step change," she says. But we're not there yet.

For a start, the NIH Clinical Center benefits from research funding and a close-knit team of clinicians and researchers, making it an atypical subject for a case study. "One of the barriers will be in the interpretation [of sequencing results]," she says. "You're not going to want a roomful of bioinformaticians in every hospital."

Peacock sees the need for automated interpretation tools ? such as an online encyclopaedia of sequences for many different microbial species ? where the results of analyses can be looked up and cross-referenced. "The quality of answer will only be as good as the database," she says.

Journal reference: Science Transactional Medicine, DOI: 10.1126/scitranslmed.3004129

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