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ASM Speaker Calls For Early Pathogen Sequencing As Part of Outbreak Surveillance

ATLANTA (GenomeWeb) – A clinical microbiologist has called for changes to how infectious disease clusters are spotted in hospitals. Pathogen sequencing should have a more prominent role, argued the London School of Hygiene and Tropical Medicine's Sharon Peacock.

Detecting outbreaks and preventing their further spread is critically important and only becoming more important as outbreak risks increase. Peacock, who is also affiliated with the Wellcome Trust Sanger Institute, argued in her talk during the opening session of the ASM Microbe 2018 meeting here that relying earlier on sequencing could uncover outbreaks quickly, preventing their spread. She further described how she and her colleagues have implemented such a sequencing-based surveillance approach.

"We can dramatically improve the way we detect outbreaks in hospital," she said during her talk.

Currently, Peacock said, the strategies commonly used to identify outbreaks don't differ that much from what John Snow did in 1854 London to trace a cholera outbreak to the Broad Street water pump. Both now and then, investigators rely on an approach that combines surveillance, epidemiological investigation, and then intervention.

Today, hospitals keep an eye out for certain indicator organisms and determine whether the patients harboring them overlapped in time or place, and if that indicates an outbreak, Peacock said. She also argued that some of the current surveillance approaches of examining the antibiotic resistance patterns and bacterial typing of suspected clusters of infections lack sensitivity and specificity.

Instead, she offered a redesign of the surveillance approach. It instead with routine sequencing of nosocomial pathogens, and then, using the sequencing data to gauge genetic relatedness among different samples, determines whether there's a high, possible, or low risk of an outbreak. Peacock added that her approach would also shorten the number of steps and time from detecting an outbreak and limit its spread.

In particular, she said a red flag is sent up for certain target pathogens, prompting DNA to be extracted from a colony pick and sent for library preparation and sequencing. "We want to get to the sample as soon as possible," Peacock said.

She noted that she typically has the sequencing run overnight on the Illumina MiSeq platform so there are results in the morning. On the second day, the sequencing file is uploaded into a cloud-based pipeline and the data is compared to a pathogen database. A report is then generated for the infection control team that includes an estimate of outbreak risk that's based on expected mutation rates and genetic diversity.

Peacock noted that in 2012 she and her colleagues showed that sequencing could identify an outbreak that conventional approaches missed. As they reported at the time in Lancet Infectious Diseases, the team used whole-genome sequencing to assess a potential methicillin-resistant Staphylococcus aureus (MRSA) outbreak in a special care baby unit at a hospital in Cambridge, UK.

The infection-control team identified 12 infants who had MRSA infections during a six-month period in 2011, but using conventional approaches, the team said there was not enough evidence to support the conclusion of an outbreak. However, when Peacock and her colleagues sequenced those and other MRSA samples, they found 14 of 17 infants eventually infected harbored genetically related MRSA strains. In all, they uncovered 26 infected individuals, including infants, mothers, and others in the community.

Early detection, Peacock said, could limit future transmissions and morbidity. She noted that as a result of the special care baby unit outbreak, there were 12 visits to primary care doctors, five to the emergency room, and two hospital admissions that could potentially have been avoided.

Sequencing can also rule out an outbreak, Peacock said. For example, she and her colleagues sequenced samples from a putative MRSA outbreak. The infection control team in this case, based on overlapping hospital times and similar antibiotic susceptibility profiles, concluded there was a likely outbreak. But by sequencing samples and constructing a phylogenetic tree, she and her colleagues found that the MRSA samples were not closely related.

Even though sequencing is an added cost, Peacock has calculated that it could lead to cost savings. She noted that if the current standard approach identifies a cluster after two initial cases have transmitted the pathogen to a further three, her approach could possibly identify the outbreak after the first two cases and prevent the next three infections from occurring and their associated costs.

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