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Advanced imaging technologies can detect evidence of asymptomatic tuberculosis in the lungs years before symptoms or routine tests can.

Researchers from CIDRI Africa and ³Ô¹ÏºÚÁÏ undertook the largest study of its kind to follow individuals with a high-risk of tuberculosis (TB) with sensitive imaging over five-years.

Global estimates suggest that up to one quarter of the world’s population have been infected by the bacteria Mycobacterium tuberculosis. However, this figure is based largely on tests showing an immune response to the bacterium, not direct evidence of infection. Most people with a positive immune response never develop disease. Predicting who will progress to TB remains one of the most urgent gaps in TB prevention.

In the study researchers followed 250 HIV-negative, asymptomatic people in Khayelitsha, Cape Town, South Africa who were household contacts of drug-resistant TB cases. Each participant received an 18‑fluorodeoxyglucose PET‑CT scan as well as an AI‑read digital chest X‑ray. Participants were monitored for up to five years.

During the follow‑up period, 18 individuals were diagnosed and treated for TB. Six were identified early through enhanced screening at the start of the study, five of whom would have been missed by routine rapid molecular testing, while the remaining 12 were diagnosed with TB after a median of 3 years. Many of these participants were still asymptomatic at the time bacteria was detected in their sputum, highlighting that transmission may occur before routine systems detect disease.

PET‑CT is the most sensitive imaging tool for research use and revealed a wide spectrum of lung abnormalities. However, those whose PET‑CT scans displayed a specific set of abnormalities associated with TB disease processes at the start of the study were more than 28 times more likely to be diagnosed with TB during follow-up compared with individuals whose scans appeared normal.

Therefore while 205 of the 250 showed an immune response to the bacterium, it was the 29 with lung abnormalities on PET-CT associated with TB that were at the highest risk of TB diagnosis.

“Identifying those most likely to develop TB is crucial if we want to prevent transmission and intervene earlier,” said first author Professor Hanif Esmail, Clinical Senior Lecturer at UCL. 

“These findings position PET‑CT as a powerful research tool for understanding how TB progresses in the body. While the method is too costly and complex for large-scale public health use, its precision offers valuable insights for clinical research studies to develop improved diagnostics and therapeutics,” said co-senior author Associate Professor Anna Coussens, University of Cape Town.

More immediately impactful, however, was the performance of AI‑interpreted chest X-rays. Although less sensitive than PET‑CT, the AI readings showed good alignment with PET‑CT predictions, suggesting significant promise for mass screening.

“AI-read chest X-rays could play a vital role in strengthening TB control strategies through mass-screening efforts,” said co-senior author Professor Robert J Wilkinson, Professor in Infectious Disease, Department of Infectious Disease.

The study highlights a critical advancement: the ability to identify people likely to have TB long before symptoms appear. With earlier detection comes the possibility of timely intervention—reducing transmission, preventing lung damage, and improving global TB prevention efforts.