Defining DNA differences to track and tack...( For the first time next-generation D...)

For the first time, next-generation DNA sequencing technologies have been turned on typhoid fever - a disease that kills 600,000 people each year. The results will help to improve diagnosis, tracking of disease spread and could help to design new strategies for vaccination.

The study sets a new standard for analysing the evolution and spread of a disease-causing bacterium: it is the first study of multiple samples of any bacterial pathogen at this level of detail. It uncovers previously hidden genetic signatures of the evolution of individual lineages of Salmonella Typhi.

The team developed methods that are being used to type outbreaks, allowing researchers to identify individual organisms that are spreading in the population: using Google Earth, the outbreaks can be easily visualized. The team hope that these mapping data can be used to target vaccination campaigns more successfully with the aim of eradicating typhoid fever.

Unlike most related Salmonella species, and in contrast to many other bacteria, Typhi is found only in humans and the genomes of all isolates are superficially extremely similar, hampering attempts to track infections or to type more prevalent variants. The detail of the new study transforms the ability of researchers to tackle Typhi.

"Modern genomic methods can be used to develop answers to diseases that have plagued humans for many years," explains Professor Gordon Dougan from the Wellcome Trust Sanger Institute and senior author on the study. "Genomes are a legacy of an organism's existence, indicating the paths it has taken and the route it is on. This analysis suggests we may have found Typhi's Achilles' heel: in adapting to an exclusively human lifestyle, it has become complacent, its genome is undergoing genetic decay and it's heading up an evolutionary dead end in humans.

"We believe that concerted vaccination programmes, combined with epi
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