Using Whole-Genome Sequencing to Control Hospital Infection
Using Whole-Genome Sequencing to Control Hospital Infection
More and more laboratories around the world have begun to tackle hospital outbreaks with WGS. In England, University of Birmingham microbial geneticist Nicholas Loman and his staff recently applied WGS to a Salmonella outbreak at Heartlands Hospital, ultimately tracing the source of the outbreak to a broader outbreak affecting other parts of the United Kingdom and Europe. "Ideally, we will be able to analyze the isolates in the context of everyone else's data to see what's going on at a larger scale, and we want to do it on a very rapid time scale," Loman says.
At other hospitals researchers have studied antimicrobial-resistant outbreaks of K. pneumoniae,P. aeruginosa,Vibrio cholerae, and Enterobacter cloacae. The decreasing size and expense of DNA sequencers has also enabled the use of WGS in less affluent health-care settings. Loman's graduate student Joshua Quick recently returned from Guinea, where he spearheaded a program to sequence the genomes of all Ebola virus samples isolated at local hospitals as a way of mapping virus transmission. And University of Oxford microbiologist Stephen Baker used WGS to investigate an outbreak of antimicrobial-resistant K. pneumoniae that struck the pediatric wards at a Kathmandu hospital, killing 75% of the affected children.
Sequencing of previously collected samples showed that the bacteria had been transmitted around the Nepali hospital for at least six months before hospital officials became aware of the outbreak. Baker showed that after the bacterium first arrived, various evolutionary factors led to the acquisition of more virulence genes and multidrug resistance, which is what led to such a deadly outbreak. "We would never have known that this specific Klebsiella strain was such a recurring problem without that sequencing data," Baker says.
Baker's results, which showed that the bacteria responsible for an outbreak can arrive in a hospital long before the outbreak occurs, support the idea that WGS can play an important role in routine surveillance, says University of Birmingham's Loman. "These infections don't come from nowhere," he says. "Genomic surveillance can identify potential outbreaks before hospitals are even aware of the problem."
Loman points to a recent study of his in which he sequenced P. aeruginosa isolates from environmental samples and burn patients at Queen Elizabeth Hospital Birmingham. Of the 141 isolates sequenced, Loman and his graduate student Quick identified several patients who had Pseudomonas infections genetically identical to bacteria found on water taps and showerheads. This route of transmission was known to exist, but it hadn't been documented in that hospital before.
Nearly halfway around the world, microbiologist Stephen Salipante and colleagues at the University of Washington in Seattle used a similar technique to prospectively survey all the bacteria recovered from the intensive care units of a hospital over the course of a year. Not only did Salipante's team discover infections caused by novel bacterial species, they also identified a surprising number of cryptic transmissions by asymptomatic individuals. Two-thirds of the recovered isolates were associated with clinically significant infection in patients.
However, adds Salipante, it is unclear whether transmission had occurred in the hospital or whether patients had been exposed prior to admission to bacteria that were endemic in the community. It is also unclear whether the bacteria caused the disease or were just associated with it. "We were really surprised at the intrapatient sharing of isolates, and we don't really know where these transmissions originate," he says.
Gaining Ground
More and more laboratories around the world have begun to tackle hospital outbreaks with WGS. In England, University of Birmingham microbial geneticist Nicholas Loman and his staff recently applied WGS to a Salmonella outbreak at Heartlands Hospital, ultimately tracing the source of the outbreak to a broader outbreak affecting other parts of the United Kingdom and Europe. "Ideally, we will be able to analyze the isolates in the context of everyone else's data to see what's going on at a larger scale, and we want to do it on a very rapid time scale," Loman says.
At other hospitals researchers have studied antimicrobial-resistant outbreaks of K. pneumoniae,P. aeruginosa,Vibrio cholerae, and Enterobacter cloacae. The decreasing size and expense of DNA sequencers has also enabled the use of WGS in less affluent health-care settings. Loman's graduate student Joshua Quick recently returned from Guinea, where he spearheaded a program to sequence the genomes of all Ebola virus samples isolated at local hospitals as a way of mapping virus transmission. And University of Oxford microbiologist Stephen Baker used WGS to investigate an outbreak of antimicrobial-resistant K. pneumoniae that struck the pediatric wards at a Kathmandu hospital, killing 75% of the affected children.
Sequencing of previously collected samples showed that the bacteria had been transmitted around the Nepali hospital for at least six months before hospital officials became aware of the outbreak. Baker showed that after the bacterium first arrived, various evolutionary factors led to the acquisition of more virulence genes and multidrug resistance, which is what led to such a deadly outbreak. "We would never have known that this specific Klebsiella strain was such a recurring problem without that sequencing data," Baker says.
Baker's results, which showed that the bacteria responsible for an outbreak can arrive in a hospital long before the outbreak occurs, support the idea that WGS can play an important role in routine surveillance, says University of Birmingham's Loman. "These infections don't come from nowhere," he says. "Genomic surveillance can identify potential outbreaks before hospitals are even aware of the problem."
Loman points to a recent study of his in which he sequenced P. aeruginosa isolates from environmental samples and burn patients at Queen Elizabeth Hospital Birmingham. Of the 141 isolates sequenced, Loman and his graduate student Quick identified several patients who had Pseudomonas infections genetically identical to bacteria found on water taps and showerheads. This route of transmission was known to exist, but it hadn't been documented in that hospital before.
Nearly halfway around the world, microbiologist Stephen Salipante and colleagues at the University of Washington in Seattle used a similar technique to prospectively survey all the bacteria recovered from the intensive care units of a hospital over the course of a year. Not only did Salipante's team discover infections caused by novel bacterial species, they also identified a surprising number of cryptic transmissions by asymptomatic individuals. Two-thirds of the recovered isolates were associated with clinically significant infection in patients.
However, adds Salipante, it is unclear whether transmission had occurred in the hospital or whether patients had been exposed prior to admission to bacteria that were endemic in the community. It is also unclear whether the bacteria caused the disease or were just associated with it. "We were really surprised at the intrapatient sharing of isolates, and we don't really know where these transmissions originate," he says.
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