New insight into the progression of tuberculosis infection

An international research team of University of Cape Town (UCT), Stellenbosch University, NIH and UK affiliated scientists have found clear evidence of a separate stage in tuberculosis (TB) infection where people have no symptoms but are more likely to go on and develop the full disease. The findings, published in Nature Medicine (see full details below), suggest that it may be possible to identify which people are most at risk of developing tuberculosis.

Professor Robert Wilkinson is Director of CIDRI based in the Institute of Infectious Disease and Molecular Medicine (IDM) at UCT, and of the Francis Crick Institute and Imperial College London in the UK. The results offer hope in controlling the spread of disease.  "People ill with TB can infect up to 10-15 other people through close contact and if we can identify people in the transition stage before they transmit to other people, that's potentially a game-changer in terms of TB eradication."

Conventionally, TB infection is classed into two stages: 'latent' and 'active'. People with latent infection test positive for an immune response to the tuberculosis bacteria, Mycobacterium tuberculosis, but do not have the symptoms of active disease. Around 10% of people with latent TB infection progress to active disease if left untreated. However, currently there is no accurate way to predict which infected individuals will develop the disease.

The researchers screened 265 HIV-positive people for TB infection in Cape Town, South Africa, where tuberculosis incidence is high. Of those who tested positive for latent TB, 35 were recruited to the study and were followed up over a period of six months. The team used a combination of medical imaging techniques to study the patients' lungs – positron emission tomography (PET) and computed tomography (CT) scans – which highlighted areas of lung abnormalities as 'hot spots'.

"We found evidence of differences in disease progression within a group of people that currently would all be diagnosed and managed as having the same latent TB infection, as none of them showed any outward symptoms of tuberculosis," Prof Wilkinson explains. "Those that had evidence of 'subclinical' disease on the PET/CT scans were at higher risk of developing the disease."

The research was supported by the Wellcome Trust, the Bill and Melinda Gates Foundation, the US National Institutes of Health, the National Research Foundation of South Africa, the Francis Crick Institute, the Medical Research Council of South Africa, and the European Union.

Original paper:

H Esmail, RP Lai, M Lesosky, KA Wilkinson, CM Graham, AK Coussens, T Oni, JM Warwick, Q Said-Hartley, CFKoegelenberg, G Walzl, JL Flynn, DB Young, CE Barry III, A O'Garra & RJ Wilkinson. Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[18F]fluoro-D-glucose positron emission and computed tomography. Nature Medicine (2016) doi:10.1038/nm.4161.