Tuberculosis (TB) is a serious bacterial disease that primarily affects the lungs and can be deadly if left untreated. It spreads through the air when people with TB expel bacteria via droplets. While many individuals who contract TB remain asymptomatic, a small percentage do not control the infection, leading to active disease. Current TB testing methods, such as skin tests or blood tests like the interferon gamma release assay (IGRA), can detect an immune response to TB but fail to differentiate between those at high or low risk of disease progression. This limitation underscores the need for improved testing methods to identify individuals at higher risk of developing TB, allowing for more focused preventative treatment. Researchers have now introduced an innovative approach to studying the progression of TB from infection to disease, identifying and treating individuals at increased risk who might be missed by existing testing methods.

Researchers at the University of Leicester (Leicester, UK) employed PET-CT, an advanced imaging technique, to study how TB infection progresses and to identify individuals at higher risk of developing the disease. This method enabled the team to evaluate a potential new blood test to identify those at higher risk without the need to recruit a large and costly cohort. The study involved 20 adults linked to households of individuals being treated for TB. These participants underwent chest radiography and IGRA screening for TB infection. The research team then utilized two novel methods to monitor disease progression over the next year: PET-CT imaging and a unique bacteriophage-based assay called Actiphage, developed by PBD Biotech (Saskatoon, Canada). Actiphage utilizes bacteriophages, viruses that specifically infect bacterial cells, to target TB bacteria. When the bacteriophage infects TB bacteria, it releases bacterial DNA, which can then be detected, even at very low levels that other clinical tools cannot identify.

All participants in the study were asymptomatic with normal chest X-rays. They first underwent a baseline PET-CT scan. If the scan showed metabolic activity indicative of TB that could be sampled, they underwent bronchoscopy and sampling. Participants without sampleable findings on the initial PET-CT, or with negative sampling results, received a follow-up PET-CT scan after three to four months. Through PET-CT, the researchers identified four individuals from whom TB bacteria were isolated either from the lung airway or from PET-positive lymph nodes. Additionally, two more participants showed progressive changes on the second PET-CT scan. All six individuals received TB treatment, and follow-up PET-CT scans three months post-treatment showed resolving or completely resolved changes, suggesting the PET-CT changes were due to active TB infection.

The Actiphage test results were also promising. The researchers observed a significant correlation between a positive baseline Actiphage test and subsequent treatment for high-risk TB infection features. Actiphage results were positive in 12 (60%) participants at baseline and in all six of the treated PET-CT-positive participants. The study's findings led the researchers to propose that blood biomarkers aimed at detecting bacterial presence could complement existing biomarkers of the host immune response, thus improving the stratification of TB risk in individuals with TB infection.

“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,” said Dr. Pranabashis Haldar, Clinical Senior Lecturer in Respiratory Medicine at the University of Leicester. “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.” 

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