feature
New York City is known for its hot, dog days of summer, when air conditioners buzz
across the city. When Kimberlee Musser, PhD, answered a call from the New York City
(NYC) Public Health Laboratory in July 2015, it turned out to be directly related to these
crucial cooling systems.
miles from the Opera House Hotel. Although there was some heterogeneity, the isolates
from the East Bronx and South Bronx were quite similar.
Musser, who oversees bacterial disease testing at the Wadsworth Center—New
York’s state PHL—had worked with the NYC laboratory just months earlier to screen
building cooling tower water for Legionella pneumophila, the causative agent for
the sometimes fatal pneumonia known as Legionnaires disease—spread through
aerosolized water. City health officials suspected a Legionnaires disease outbreak was
unfolding in the South Bronx. And they wanted to stop it.
“Then we stepped back and realized something,” said Musser. “Sometimes you have
to think about which reference genome you’re using to align your sequence data
to.” The Wadsworth scientists had been using a genome from a 1976 Legionnaire’s
disease outbreak in Philadelphia, and had been able to match 88% of the genome with
confidence. Then they switched to one of the environmental strains from the Opera
House Hotel “to understand if we were missing anything by not using the whole
genome.” (In this case, CDC did the testing using a PacBio WGS platform, which is able
to perform long reads and generate a completed, closed genome.)
Musser and her staff agreed to support the public health investigation by once again
screening cooling tower water and potable water via PCR (327 water samples in
all) and conducting WGS on clinical and environmental samples (80 samples over a
two-week period). At the same time, NYC and Wadsworth scientists performed pulsed
field gel electrophoresis on all Legionella isolates and CDC scientists performed a
second typing method, sequence-based typing, on a subset of isolates.
Results were stark: The 41 clinical isolates from the South Bronx outbreak and five
environmental isolates from the Opera House Hotel were identical. Moreover, the East
Bronx clinical and environmental isolates differed from the South Bronx isolates by just
eight base pairs—out of a 3.4 million-base-pair genome. Several historic Legionella
isolates recovered from NYC and Wadsworth archives were also one to eight base pairs
different from the South Bronx strain.
“When we looked at all of that data,” said Musser, “we could determine that there was
one hotel, the Opera House Hotel, that had several environmental isolates that matched
well to all of the epi-linked cases in the South Bronx. It looked like a solid investigation.”
Said Musser, “WGS provided extra discrimination in a situation where it was really
needed.” She said, “We think this strain has been in NYC at least since 2007 and slowly
evolving in different niches. We’re calling it a persistent endemic strain.”
Then a second, smaller Legionella outbreak was detected in the East Bronx.
Subsequent testing led authorities to a cooling tower on a college campus about seven
Needless to say, the state governor and NYC health commissioner promulgated new
regulations requiring registration, regular testing and, where necessary, disinfection of
all water cooling towers to help prevent future problems.
One of the biggest advantages of the technology, said
Robert Myers, PhD, is its “pretty exquisite discrimination”
among microbes, enabling epidemiologists to identify novel
microbes and to tightly define outbreak definitions
CDC’s AMD program currently funds about two dozen program areas.
Armstrong said those likely to experience “the earliest impact” are food safety,
TB, influenza and antimicrobial resistance.
The technology is most useful in situations where investigators need a lot
of information from one isolate, such as virulence markers, drug resistance
markers, drug resistance mechanisms (such as p