Genomics may help identify pathogens during outbreaks

Metagenomics may have the potential to be used as a culture-independent approach to identify pathogens during diarrheal disease outbreaks, recent data suggest.

“During an outbreak, rapid and accurate pathogen identification and characterization is essential for the management of individual cases and of an entire outbreak,” the researchers wrote in the Journal of the American Medical Association. “Often, however, in vitro culture proves slow, difficult, or even impossible, and recognition of an outbreak strain can be difficult if it does not belong to a known variety or species for which specific laboratory tests and diagnostic criteria already exist.”

The researchers conducted a retrospective analysis that included 45 fecal samples from patients who presented with diarrhea during an outbreak of Shiga-toxigenic Escherichia coli (STEC) 0104:H4 in Germany in 2011. The researchers then performed high-throughput sequencing on the samples and then a three-phase bioinformatics analysis.

During phase one, the researchers constructed a draft genome using the data obtained from the sequencing. In phase two, the coverage of the outbreak strain genome was determined in the samples: It was recovered from 10 samples at greater than 10-fold coverage and from 26 samples at greater than onefold coverage. Lastly, in phase three, sequences from Clostridium difficile, Campylobacter jejuni, C. concisus and Salmonella enterica were recovered.

“These results illustrate the potential of metagenomics as an open-ended, culture-independent approach for the identification and characterization of bacterial pathogens during an outbreak of diarrheal disease,” the researchers wrote. “Challenges include speeding up and simplifying workflows, reducing costs and improving diagnostic sensitivity, all of which are likely to depend in turn on improvements in sequencing technologies.”

In an accompanying editorial, David A. Relman, MD, of Stanford University School of Medicine, wrote that microbial genome and community sequence data are destined to affect clinical and public health decision significantly, but there are many more questions, especially about its clinical role.

“From the perspective of an outbreak investigator, this is an important achievement,” Relman wrote. “However, from the perspective of a clinician caring for individual patients, this is only a mixed success story. Clinician-investigators know that there remain many critical, clinically relevant questions that demand more than genome sequence data, requiring biological measurements and a deeper understanding of the ecological and clinical setting.”

For more information:

Loman N. JAMA. 2013;309:1502-1510.

Relman D. JAMA. 2013;309:1531-1532.

Disclosure: The researchers report financial relationships with Gilead, Illumina, Merck Sharp & Dohme and Novartis. Relman reports financial relationships with Cepheid Corp., NanoBio Corp., Novartis Vaccines and Procter & Gamble.