A study today by researchers in the United Kingdom illustrates how genomic surveillance can shed light on the ways a common superbug can spread, often unnoticed, through hospitals and the community.
As detailed in a paper in Science Translational Medicine, the researchers used genomic sequencing data to identify clusters of people in the east of England who were carrying or infected with methicillin-resistant Staphylococcus aureus (MRSA), and followed those patients over the course of a year. When they combined the genomic information with epidemiologic data that showed where those MRSA carriers may have come into contact with one another, the results revealed an extensive series of small outbreaks in hospital wards, doctors' offices, and households that would otherwise have gone unrecognized.
The study's lead author calls the findings a "game changer" for infection prevention and control and suggests that routine genomic surveillance can be used to detect outbreaks of MRSA and other dangerous pathogens while they're happening.
"We can use sequencing to really focus our infection control attention, and become much more targeted in our activities," Sharon Peacock, PhD, MRCP, of the Wellcome Trust Sanger Institute and the London School of Hygiene and Tropical Medicine, said in an interview.
Clusters of transmission
For the prospective study, Peacock and her colleagues started by screening all samples submitted to a diagnostics laboratory by three hospitals (which routinely screen patients for MRSA on admission) and 75 general practitioner (GP) offices in the east of England from April 2012 through April 2013.
From these samples they identified 1,465 MRSA-positive patients, most of whom were colonized with the bacterium and did not have symptoms of clinical infection, and sequenced the genomes of 2,282 isolates from the samples. Nearly three quarters of the isolates belonged to clonal complex (CC) 22, the predominant healthcare-associated MRSA lineage in the United Kingdom.
Dividing those isolates into groups containing isolates that were no more than 50 single-nucleotide-polymorphisms (SNPs) different—an indication of genetically related bacteria—led to the identification of 173 different clusters containing from 2 to 44 cases and involving 598 people. The researchers then reviewed epidemiologic data for each patient, including medical records and postal codes, to explore the possible connections between the cases in each of the clusters.
"We didn't actually assume that [MRSA] transmission was based on 50 SNPs," Peacock said. "That simply gave us an epidemiological unit that we then dove into to see whether there was any evidence for contact. It's only when we could see that somebody had been in the same place at the same time that we said that a transmission event had occurred."
What the epidemiologic data revealed were several different routes of MRSA transmission. More than half of the cases (62%) were in 118 transmission clusters linked by hospital contact. Some of the MRSA carriers in these clusters had been on the same hospital ward, while others had been in multiple wards within the same hospital. This finding wasn't necessarily a surprise, given how often MRSA outbreaks occur within hospitals.
But 12% of the cases resided in 27 clusters where community connections—a common postal code, a shared GP office or long-term care facility, and in some cases a common address—were the only link. While Peacock and her colleagues can't pinpoint specifically where the transmission may have occurred in some of these cases, they believe the genetic relatedness of the isolates combined with the community connections are strongly suggestive of community transmission.
"By including patient epidemiological information, we found that residential postcodes and GP registration information were strong epidemiological markers of MRSA transmission," they write in the study.
Twenty-eight of the clusters contained a mix of people with both hospital and community connections. In some cases patients had acquired MRSA in the community and then spread it to others in a hospital. In other cases, patients caught the pathogen in the hospital and then spread it within the community.
MRSA spread 'under the radar'
Peacock says that most of these small outbreaks weren't spotted. There are several reasons for this. One is that patients move rapidly through healthcare systems, and since hospitals don't screen patients on discharge, clinicians might be unaware that a MRSA-positive patient had been on their ward. Another is that MRSA detected in a hospital patient might have been acquired elsewhere, perhaps weeks or months earlier. Finally, hospitals tend to focus on large outbreaks that occur in a single ward.
"There's more transmission going on under the radar than above the radar," Peacock said. "It has to be quite a significant outbreak in order to become clinically apparent."
In most MRSA outbreaks in hospitals, investigation doesn't begin until several cases have been identified, and genomic sequencing is used to determine the strains that cause the outbreak and the links between patients. But if genome sequencing were to be used routinely to find clusters of genetically similar cases, Peacock argues, hospitals would be able to detect these outbreaks as they're happening and intervene quickly to stop them, since sequencing can be done in 24 hours. They could also rule out suspected outbreaks.
"If we were to sequence all the MRSA that comes through the laboratory and use that to focus infection control activities…it would be a very good use of resources and would increase our detection rate," she said.
In a study that will begin in January, Peacock and her colleagues will put this hypothesis to the test, sequencing all the MRSA isolates that come through a hospital lab each day and tracking infection control response to that genomic surveillance data.
Oct 25 Sci Transl Med study
Oct 25 Wellcome Trust Sanger Institute press release