DNA Sequencing Technologies Help Diagnosis of Salmonella typhi

Researchers have used next-generation DNA sequencing technologies to type Salmonella typhi (Salmonella enterica serotype Typhi, elevated to species status as S. typhi), identify the strain that causes infection, identify carriers, and direct vaccination programs more efficiently. This will help to improve diagnosis, tracking of disease spread, and possibly the design of new strategies for vaccination.

Unlike most related Salmonella species, and in contrast to many other bacteria, S. 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. There are 17 million cases of typhoid fever each year--although the World Health Organization (WHO; Geneva, Switzerland; www.who.org) cautions that this is a "very conservative” estimate. Young people are most at risk: in Indonesia, 9 out of 10 cases occur in 3 to 19-year-olds.

A team of researchers at the Wellcome Trust Sanger Institute (Cambridge, UK), University College, Cork (UCC; UK), Institut Pasteur (Paris, France), and Oxford University Clinical Research Unit (Ho Chi Minh City, Vietnam) studied 19 isolates of Typhi from 10 countries, using new sequencing methods in order to capture the rare signals of genetic variation in the genome. They produced more than 1.7 billion letters of genetic sequence and found evidence of fewer than 2000 mutation events, suggesting very little evolution since the emergence of Typhi at least 15,000 years ago.

The team developed methods that are being used to type outbreaks, allowing identification of individual organisms that are spreading in the population "A key to survival of S. typhi is its ability to lie dormant in carriers, who show no symptoms but remain able to infect others,” said Kathryn Holt, a Ph.D. student at the Wellcome Trust Sanger Institute. "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.”

The study was reported in the June 27, 2008, issue of the journal Nature Genetics.


Related Links:
Wellcome Trust Sanger Institute
University College, Cork
World Health Organization