Advanced DNA sequencing technologies will help hone diagnosis and track how typhoid fever spreads and kills 600,000 people every year. The first-ever comprehensive study of multiple samples of any bacterial pathogen uncovers previously hidden genetic signatures of the evolution of individual lineages of Salmonella Typhi. There are an estimated 17 million cases of typhoid fever each year. Young people are most at risk: in Indonesia, nine out of ten cases occur in 3-19-year-olds. "Our new tools will assist us in tracing the source of typhoid outbreaks, potentially even to infected carriers, allowing those individuals to be treated to prevent further spread of the disease," said Kathryn Holt, a post-doctoral student at Wellcome Trust Sanger Institute and co-author of the study. The research team developed methods that are being used to type outbreaks, allowing them to identify individual organisms that are spreading among the population. Using Google Earth, the outbreaks can be easily visualised. The team hopes 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 new research 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," explained Gordon Dougan from the Wellcome Trust and the study's co-author. "Genomes are a legacy of an organism's existence, indicating the paths it has taken and the route it is on." "A key to survival of Salmonella Typhi is its ability to lie dormant in carriers, who show no symptoms but remain able to infect others," said Holt. The team studied 19 isolates of Typhi from 10 countries, using new sequencing methods that meant they could capture the rare signals of genetic variation in this stubborn genome.