RPT-Real-life 'Contagion' uses DNA to halt outbreak

August 22, 2012|Reuters

(Repeats for wider audience)

* Whole-genome sequencing reveals how infections spread

* Company sees $1 billion U.S. market

By Sharon Begley

NEW YORK, Aug 22 (Reuters) - If Hollywood needs a plot for a
medical thriller, scientists at the National Institutes of
Health have one: Doctors, using cutting-edge technology called
whole-genome sequencing, trace an outbreak of a deadly bacterial
infection, identify precisely how it's spreading - and in the
final minutes sic poison-spewing robots on the rampaging

That's essentially what scientists did when Klebsiella
pneumoniae, a n often-lethal bacterium, spread through NIH's
research hospital in Bethesda, Maryland last year, as described
in a study published on Wednesday in the journal Science
Translational Medicine.

"With whole-genome sequencing," said microbial geneticist
Julie Segre of NIH's National Human Genome Research Institute,
who led the study, "we were able to understand how the outbreak
was moving through the hospital and identify weaknesses" in
infection-control practices, finally halting the outbreak.

The unprecedented effort to use genome sequencing to save
patients from an infectious outbreak offers hope that the
technique could fight other hospital-acquired infections. These
infections kill some 99,000 people die from such infections in
the United States every year, estimates the U.S. Centers for
Disease Control and Prevention. The added health-care costs,
according to the CDC: $4.5 billion a year.

Calling it a "compelling story," virologist and microbe
hunter Ian Lipkin of Columbia University in New York City said
the NIH scientists' feat shows what ultra-fast whole-genome
sequencing can accomplish in so-called microbial forensics. In
whole-genome sequencing, machines identify the DNA units that
make up an organism's entire genome.

Researchers were able "to implicate 'Patient Zero,' track
transmission of a drug-resistant bacterium over the course of an
important outbreak and provide insights that will inform
infection control and patient care," said Lipkin, director of
the Center for Infection and Immunity at Columbia's Mailman
School of Public Health and a scientific adviser on the 2011
film "Contagion."


The outbreak at NIH's hospital began last summer. In June a
43-year-old patient with antibiotic-resistant K. pneumoniae,
which infects the urinary tract and bloodstream and can cause
sepsis, a blood infection, was transferred to its intensive-care
unit from a New York City hospital. "Patient Zero" was put in an
isolation room; staff and visitors had to wear gowns, masks and
gloves to enter.

Three weeks after she was cured and discharged in July, a
second patient was found to be infected with K. pneumoniae.
Since he had not been on the same ward at the same time as
Patient Zero, physicians believed he probably acquired it

New cases began appearing at a rate of one a week, and soon
there were 17. Eleven patients died.

DNA fingerprinting, the 30-year-old technique that
identifies a handful of genes, was too crude to reveal whether
these infections were identical to Patient Zero's. If they were,
something had gone badly wrong with the 243-bed hospital's
infection control. If they weren't, a second source had to be

"If we had a second, separate introduction, then the
isolation procedures for the first patient had worked," said
Segre. "But if we had transmission in the hospital, then they
didn't, plus our surveillance (which had not detected any K.
pneumoniae before another patient was found to be infected)
failed to detect that pneumoniae was spreading and silently
colonizing patients."

Segre and her colleagues began sequencing the genomes of
bacteria collected from patients, using technology from 454 Life
Sciences, part of Roche Holding AG (which also made a
cameo in "Contagion").

The bacterium was evolving like a nightmarish sci-fi bug,
acquiring about one new mutation a week, estimates Segre. With
$40,000 worth of whole-genome sequencing, she and her team were
able to compare each patient's bacteria to others', eventually
inferring the outbreak route.

Verdict: All 17 patients acquired their infection from
Patient Zero, either directly or indirectly.

"The genomic data is indisputable," said Segre. "There were
weaknesses in the infection-control system." The deadly microbe
had traveled from Patient Zero to the others, via hospital staff
or equipment (on which it could survive, the scientists
discovered, even after the equipment that had been thoroughly

Some possible routes of transmission were absolved: The
microbe was not spreading via wound care, so the staff did not
have to make changes there.

The hospital did make radical changes in other practices,
though. "Equipment used in the isolation ward was no longer used
elsewhere, and staff who worked there didn't work anywhere
else," said Segre.