Nearly one-third of the global population is infected with TB (latent TB infection); in India alone about 40 per cent of the population is infected with TB. People with latent TB infections have TB bacteria in their bodies but the bacteria are not active; these individuals do not have active TB disease and are not contagious. Though less than 10 per cent of people infected with TB will develop the disease as they grow old, become infected with HIV or have diabetes, there is no way of knowing in advance which infected individuals will develop TB disease. Not any more.
Now, a set of 16 genes can be used as biomarkers to tease out this information. The genes become more active in those who will develop TB disease in the next one or two years than in people who will continue to stay healthy. The results were published a few days ago in The Lancet.
Since the infected population acts as a huge reservoir and as all infected people across the world cannot be given preventive TB treatment for at least six months, picking out only those who are very likely to develop the disease and providing them preventive treatment will go a long way in reducing the TB burden in the world.
“Because people only become infectious after they have fallen ill, the research may provide a way to detect and treat TB before it can be spread from one person to another,” Helen Fletcher, Director of the TB Center at the London School of Hygiene & Tropical Medicine told the journal Science.
Daniel E. Zak, the first author from the Center for Infectious Disease Research, Seattle, U.S., and others compared the blood samples of 37 adolescents who developed TB disease and 77 adolescents who continued to stay health even at the end of two years of follow–up. Based on RNA isolated from the blood samples, the researchers were able to identify 16 genes whose expression “increased” as patients were close to developing TB disease.
The robustness of the 16 genes to act as biomarkers was validated in another set of nine adolescents who developed TB disease and 30 who remained healthy despite being infected with TB. The researchers were unaware if the samples being tested came from healthy people or those with TB disease.
The test results were revalidated in two more patient samples from South Africa and Gambia. The samples were from adults who were household contacts of those with TB disease and who either developed the disease themselves or remained healthy despite being exposed to people with TB disease.
The accuracy of the biomarkers was maximum when the diagnosis was made close to the time when people became diseased. For instance, the sensitivity was 71.2 per cent when the diagnosis was made six months prior to people developing TB disease compared with nearly 63 per cent when the diagnosis was made 6-12 months before they developed TB disease; it was about 48 per cent during 12-18 months prior to TB disease diagnosis.
According to the researchers, the TB risk signature predicted disease progression despite “marked diversity” between the different groups studied, age of the population studied (adolescents and adults), different ways in which they were infected, ethnic and genetic differences, and different TB strains seen in South Africa and Gambia.
Also, the genes were “excellent” in differentiating TB disease from latent infection and from other disease states. Its ability to diagnose TB disease was unaffected by the HIV status; it was also able to diagnose childhood TB cases when the samples were culture positive. The authors suggest that the “risk signature might represent bacterial load in the lungs”.
The ability of the blood-based signatures to predict progression to active tuberculosis disease in healthy individuals can “pave the way for the establishment of diagnostic methods that are scalable and inexpensive.” “The newly described signature holds potential for highly targeted preventive therapy, and therefore for interrupting the worldwide epidemic,” they note.