A team from UCC is involved in an international effort to tackle the problem of typhoid fever, writes DICK AHLSTROM
NEW RESEARCH findings have led scientists to predict that a concerted vaccination programme might be able to wipe out the dreaded typhoid fever forever. A research team at University College Cork were key participants in the work, which delivered a great deal of new genetic information about the bacterium that causes the disease.
About 17 million cases of typhoid fever arise each year and it kills about 600,000 people annually despite the use of vaccination and also antibiotics to control it. To add to the challenge new antibiotic-resistant strains of the causative organism, Salmonella typhi, are also emerging in the Far East.
The research, published last month in the journal Nature Genetics, gives reason for hope however. It involved a number of high-profile centres including the Wellcome Trust Sanger Institute, the Institut Pasteur in Paris and the Oxford University clinical research unit in Ho Chi Minh City, Vietnam, along with UCC.
Cork's involvement was based on the expertise available from a new Science Foundation Ireland principal investigator, Prof Mark Achtman, who joined the faculty from the august Max Planck Institut in Berlin.
Achtman is an expert in the population genetics of pathogens and has major programmes running within the college's environmental research institute. These include studies of Helicobacater pylori, the bug associated with stomach ulcers; all Salmonella forms; Staphylococcus aureus which is the organism typically associated with hospital superbugs; and Yersinia pestis, which among other things causes bubonic plague.
His involvement in the study arose when a friend at the Sanger, Prof Gordon Dougan, asked him to participate in an earlier study of the genetic blueprint of the bug that causes typhoid fever, Salmonella typhi. It is a Salmonella form that has adapted to life exclusively inside of humans.
"It was a disease that only few scientists in developing countries were working on, despite its importance in the Far East and Africa," Achtman says.
That international group started studying the genomes of different strains of S typhi, but all were largely the same. "We sequenced a few genes from 26 strains and found very little genetic variation," says Achtman.
They switched tack, with postdoctoral researcher Philippe Roumagnac looking instead at "mutation diversity" between strains, their mutation-based variation. This proved much more productive and helped the team map out the genetic history of this dangerous bacterium.
That study, published in the journal Science in 2006, provided a number of things including a "beautiful phylogenetic tree", in effect a family tree of S typhi strains that showed the disease arose from a single bacterial "parent" perhaps 15,000 years ago. "Because of that we could talk about when typhoid developed and how it developed," Achtman says.
This in turn has informed the later Nature Genetics research, he adds. They used the phylogenetic tree to select strains of interest including some newly emerged strains from the Far East.
As before, they were looking for mutations or SNPs, single nucleotide polymorphisms, where a genetic variation has arisen in a strain. All the strains are superficially very similar and the team identified just 2,000 SNPs across 19 separate S typhi genomes, the sum total of the diversity between these strains.
The organism has been studied in exquisite detail and much new information has emerged that may open the way towards new treatments, the researchers believe. The points of variation may offer avenues of attack for new vaccines and new approaches that will be informed by the genetic information.
"This analysis suggests we may have found typhi's Achilles heel," suggests Dougan. "We believe that concerted vaccination programmes, combined with epidemiological studies aiming to track down and treat carriers, could be used to eradicate typhoid as a disease."
UCC played a major role in the work Achtman says, in selecting the strains, in taking out repetitive genetic sequences to deliver only data of interest and in applying an alternative method developed in Cork when scanning for SNPs.
The availability of this alternative method proved very useful in that SNPs pinpointed in Cork could be matched up with those identified at the Sanger using a different method.