The FINANCIAL -- Using whole-genome sequencing, a team led by researchers from Harvard School of Public Health and the Broad Institute has traced the path of the E. coli outbreak that sickened thousands and killed over 50 people in Germany in summer 2011 and also caused a smaller outbreak in France.

According to the Harvard University, it is one of the first uses of genome sequencing to study the dynamics of a food-borne outbreak and provides further evidence that genomic tools can be used to investigate future outbreaks and provide greater insight into the emergence and spread of infectious diseases.

The study, conducted in collaboration with groups at the Pasteur Institute in France, Assistance Publique-Hôpitaux de Paris, and Statens Serum Institut in Denmark, appears on February 6, 2012 in an advance online edition of Proceedings of the National Academy of Sciences.

The outbreak in Germany, which was caused by the strain E. coli O104:H4, led to around 4,000 cases of bloody diarrhea, 850 cases of hemolytic uremic syndrome, which can lead to kidney failure, and over 50 deaths.

The source of the outbreak was traced to sprouts from an organic farm in Germany. In France, where 15 people were sickened with bloody diarrhea that progressed to HUS in nine people, the source of the outbreak was sprouts, germinated from seeds purchased at a garden retailer, that were served at a children’s community center buffet. European investigators, using traditional epidemiological methods, traced the outbreaks to a shipment of seeds from Egypt that arrived in Germany in December 2009.

The researchers, led by Grad and senior authors Hung and William Hanage, associate professor of epidemiology at HSPH, analyzed isolates of E. coli bacteria from both the German and French outbreaks. Based on conventional molecular epidemiological analysis, the E. coli strains from the outbreaks in Germany and France appear identical.

However, by harnessing the Broad’s expertise in whole-genome sequencing and analysis, the researchers were able to determine that there were small, but measurable, differences among the isolates. They made two surprising findings: All the strains connected to the larger German outbreak were found to be nearly identical, while the strains in France showed greater diversity; and the German isolates appeared to be a subset of the diversity seen in the French isolates.

Another hypothesis offered by the researchers is that there was uneven distribution of diversity in the original shipment of contaminated seeds.

As costs for genomic sequencing decline, these tools, combined with traditional epidemiological techniques, can provide greater insight into the emergence and spread of infectious diseases and will help guide preventive public health measures in the future.

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