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Genome Sequencing Aids Hunt for Deadly Bugs

Public-health investigators were alarmed last year when they tried to solve an outbreak of a dangerous superbug at a large Denver hospital.

Eight patients had been infected with a strain of klebsiella pneumoniae bacteria that was resistant to nearly all antibiotics. To stop it, the disease detectives needed to know where and how it was spreading. But the patients had been all over the hospital, from operating rooms to intensive care. Standard lab tests showed the cases were related to one another, but offered no clues as to how the people had been infected.

So the disease detectives turned to a technology like the one used to decode the human genome. In a laboratory at the Centers for Disease Control and Prevention in Atlanta, scientists sequenced the bacteria samples' entire DNA. They found tiny mutations that the bacteria had made as they moved from patient to patient. That helped them divide the patients into smaller clusters and pinpoint transmission to two intensive-care and two other units of the hospital. New steps were taken to prevent the spread of infections in those units.

"We were able to clarify a lot that we could not otherwise," said Erin Epson, a CDC disease detective working at the Colorado Department of Public Health and Environment and a member of the investigative team.

Used for years now in research and academia, whole-genome sequencing has become faster and cheaper, allowing it to be deployed more widely. It is a powerful new weapon that public-health scientists have begun turning to in a bid to outflank deadly microbes emerging around the world.

Public-health leaders and scientists say decoding dangerous pathogens could revolutionize the fight against outbreaks.

"We can stop outbreaks quicker and figure out ways pathogens are spreading that we don't currently know," said Thomas Frieden, the director of the CDC, which is building its capacity to sequence and analyze pathogens.

President Barack Obama's administration is seeking $40 million in fiscal 2014 for an "advanced molecular detection" initiative to expand the CDC's capacity to sequence and analyze pathogens after a panel of experts determined the agency was behind with the technology. But it isn't clear whether Congress will approve the funding for the agency, whose budget was cut by $580 million to a total of $6.29 billion this fiscal year.

Sequencing a whole genome allows scientists to identify quickly how virulent a bug is and what drugs it is resistant to. They can see how it is mutating and evolving as it jumps from one person to another, allowing them to track—and, hopefully, stop—an outbreak in real time. "The accumulations of mutations in an organism are like its history," said Duncan MacCannell, senior adviser helping lead the CDC's advanced molecular-detection work.

Federal and state officials are experimenting with whole-genome sequencing to get to the bottom of food-borne outbreaks and avoid fingering the wrong source. Using current lab methods to analyze salmonella, "it's hard to say it came from this lettuce and not that spinach," said Jill Taylor, interim director of the Wadsworth Center, New York state's public-health lab, which is working with the Food and Drug Administration to hone use of the technology. "With next-generation sequencing, you can really see the person has the same isolate [sample] as came from that lettuce. It's a much better tool to be able to say what the source was for an outbreak."

Last month, investigating an outbreak of listeria, CDC scientists compared sequenced bacteria from the suspected source, cheese, and found it to be "indistinguishable" from isolates from several suspected cases, said Peter Gerner-Smidt, branch chief of the agency's division of food-borne, waterborne and environmental diseases. They also sequenced isolates of two patients they weren't sure were part of the outbreak, he said. One was, he said.

Tuberculosis officials are working on ways to use next-generation sequencing to more rapidly identify drug-resistant forms of the disease, which are dangerous but often take weeks to confirm with current tests.

Meanwhile, scientists say the technology also helps them more deeply probe flu viruses. Life Technologies Corp., a maker of next-generation sequencing technology, set up a global influenza network earlier this year to sequence more samples once they are taken from patients, in the hope of detecting emerging strains earlier. "You're able to sample more, so you get a better idea of what is the most prevalent strain for the flu season," said a company spokesman.

Source: Wall Street Journal

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