Researchers at the National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Center (BRC) have developed a novel approach to studying the progression of tuberculosis (TB) from infection to disease. The researchers report that the new approach can identify people at increased risk of developing the disease that current methods of testing would not.

Their study is published in The Lancet Microbe in an article titled, “PET-CT-guided characterization of progressive, preclinical tuberculosis infection and its association with low-level circulating Mycobacterium tuberculosis DNA in household contacts in Leicester, U.K.: a prospective cohort study.”

The researchers did a prospective 12-month cohort study in healthy, asymptomatic adults (aged ≥16 years) who were household contacts of patients with pulmonary tuberculosis, and who had a clinical phenotype of latent tuberculosis infection, in Leicester, U.K.

Pranabashis Haldar, PhD, clinical senior lecturer in respiratory medicine at the University of Leicester and a principal investigator at the NIHR Leicester BRC, where the research was carried out, said: “Tuberculosis rates in the U.K. and around the world are not declining despite global efforts.”

TB is a bacterial disease that causes significant lung damage and can, without treatment, be fatal. It is spread in aerosol by inhaling droplets containing the bacteria. Most people that become infected live with the infection and remain well; however in a small proportion, the infection is not controlled and can progress to cause disease.

Current tests of TB infection use either a skin test or a blood test, called an interferon gamma release assay (IGRA) to detect an immune response to the infection. However, these tests cannot distinguish between those that are at high or low risk.

In this study, researchers used PET-CT, a highly sensitive form of imaging, as a novel way of looking at how the infection progresses, and to identify people at greater risk of developing the disease.

Participants underwent chest radiography and an IGRA to screen for TB infection. The research team then used two new methods of monitoring the progression of the disease over the following year: PET-CT imaging tools and a new blood test.

Jee Whang Kim, PhD, a clinical research fellow from the University of Leicester, who conducted the study said: “In PET-CT scans, patients are given fluorodeoxyglucose (FDG), a radiotracer which is similar to naturally occurring glucose (a type of sugar) that the body uses it in a similar way. By analyzing the areas where the radiotracer is taken up, it’s possible to identify areas in the body where something might be going on.”

The researchers concluded: “Our results are exciting for two reasons. Firstly, they show that PET-CT could be an effective tool for identifying people with higher risk TB infection. This can help us to perform studies to develop new tests and evaluate new treatments, including vaccines more efficiently and at lower cost.

“Secondly, our findings suggest that TB bacteria are found in blood more often than has previously been thought and importantly, the presence of the bacteria in blood may be an indicator of uncontrolled or progressive TB infection.”

Their findings could help with global efforts to reduce the spread of the disease.

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