Outbreak Breakthrough: Using Whole-Genome Sequencing to Control Hospital Infection.

The British soldier on the trauma and burns ward at Queen Elizabeth Hospital Birmingham brought home more than his injuries when he was evacuated from Afghanistan in July 2011. Like many wounded veterans,1 he also carried an opportunistic pathogen called Acinetobacter baumannii that was resistant to numerous classes of antimicrobials. If this specific strain of bacteria spread to others in the hospital, the doctors there would have few, if any, options for treating their patients. Keeping the bacterium contained through vigorous infection control procedures seemed the only hope. The level of detail provided by whole-genome sequencing could give hospitals the tools they need to stop outbreaks before they start. After a week, another patient developed symptoms of infection with A. baumannii. Basic DNA analysis in the hospital’s clinical laboratory showed the strain had the same specific molecular pattern as the soldier’s. Soon, other patients throughout the hospital began falling ill with the same infection. Physicians considered the possibility of “cryptic transmissions,” in which a person can acquire the bacterium from a carrier who isn’t even sick. But even enhanced infection control procedures such as deep cleaning and restrictions on visitors weren’t stopping the outbreak, leading hospital officials to conclude the pathogen likely was being transmitted through the environment rather than directly from person to person. If they could identify the environmental source of the infection, they could stop the outbreak. The problem was that older DNA analysis techniques did not provide enough detail on the bacteria involved to track transmission. All that officials could say with any degree of certainty was that all the affected individuals were likely part of the same outbreak. So the hospital sought advice from microbial geneticist Mark Pallen, now at the University of Warwick, who used an approach known as whole-genome sequencing (WGS) to sequence the genomes of 114 A. baumannii samples isolated from patients. By mapping the epidemiology of the WGS data, Pallen and colleagues were able to identify the environmental sources of transmission.2 What was most striking to Pallen was that most of the patients who tested positive for A. baumannii had been treated in the hospital’s operating theaters. One theater in particular was implicated in the infections of three different patients, which was confirmed by WGS of environmental and patient isolates. The operating theater was closed for deep cleaning, and the outbreak seemed over. But after a lull of six weeks, a new case turned up, which WGS linked to the original A. baumannii. With no other infected patients in the hospital, Pallen took a closer look at potential environmental sources. The researchers eventually identified a special bed for burn patients that had been used by a previous infected patient. A second round of deep cleaning finally stopped transmission for good. Today, as the cost and time required to sequence genomes has plummeted, more hospitals and health-care agencies are turning to WGS to study disease outbreaks, and the method promises to revolutionize standard methods of infection control and contact tracing during outbreaks.3 Eventually, experts say, WGS likely will be used not only to track outbreaks of pathogens but also to catalog the microbes present in a given environment and the ways in which patients and staff move these microbes from place to place, ward to ward, and person to person. With this knowledge, hospitals may even be able to stop outbreaks before they start.