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A study of what genetic factors make someone more likely to progress to active TB is one subject that soon will be tackled by the new TB Epidemiologic Studies Consortium (TBES). If researchers find genes linked to resistance or susceptibility, think how much easier a contact investigation could be, says Mary Reichler, MD, the principal investigator for the new study. "We know only one in 10 people who are latently infected goes on to develop active disease," says Reichler. "If we could devise a test for those determinants, you could theoretically pick out those people and know that they would probably be the only ones who’d need isoniazid prophylaxis."
Genes linked to susceptibility or resistance could also play a starring role in a preventive treatment, Reichler adds. "The idea is that you’d only vaccinate people who are skin-test positive and who have this certain set of genes," she explains. It’s not as far-fetched as it might sound. Previous studies have identified seven genes where a variant has been tied to susceptibility to (or protection from) disease, Reichler says. One problem is that the studies have been conducted in specific non-U.S. populations, so results may not apply to Americans.
Reichler’s work will also look at genetic propensities to becoming latently infected with TB. Again, previous studies in the field are of limited usefulness, in this instance because they’ve been conducted only in areas where TB is endemic, making it hard to know whether infections are recent or not.
In the big picture, immunologic and genetic factors play only one part in whether a person gets infected or develops TB, Reichler notes. Other factors include case infectiousness, environment, and factors related to the organism itself. "We don’t yet know how big a part host factors play," Reichler points out. Plus, among host factors, no one knows yet how big a part is played by genetic factors.
Contracts for the study have been awarded to seven sites, with an eighth site under consideration, Reichler says. Funding for the contracts is already secure.