Scientists say they are close to developing a blood test that could identify millions of people who spread tuberculosis unknowingly, after discovering a group of biological markers that are found in high levels among infectious patients.
The study, led by the University of Southampton with collaboration from the University of Cape Town and Cayetano Heredia University in Lima, Peru, used a new technique that identified a set of six proteins that are highly accurate in pinpointing TB.
Lead author Dr Hannah Schiff, a respiratory expert at Southampton, said if successfully produced, a test could help identify the estimated 3m cases which were missed last year, mostly in developing countries.
“TB remains a global catastrophe because our efforts to control the spread are hindered by inadequate testing, which is slow and reliant on specialist equipment and labs. A third of people who get infected go undiagnosed and remain infectious.”
The Independent reports that for their study, the researchers combined a new measurement technique with deep mathematical analysis to identify these six new markers of TB disease.
“It could lead to a transformative alternative to diagnosing the condition – a simple test that detects proteins in the bloodstream whose levels differ between people with TB, healthy individuals and those suffering from other respiratory illnesses,” Schiff said.
For the study, published in the Journal of Clinical Investigation Insight, the team examined proteins found in the blood of people with active TB in Africa and South America.
The scientists compared the biomarkers with those found in healthy people and patients with lung infections, identifying 118 proteins that differed significantly between the groups.
They then narrowed these down to the six proteins which, they say, can be used to distinguish contagious patients with TB from people in good health or with lung conditions.
Study co-director Dr Diana Garay-Baquero, also from Southampton, said the findings were a roadmap to developing a TB test that would be as simple as the lateral flows used during the Covid-19 pandemic.
“These new markers are truly exciting but the important work now is to develop these into tests that can be used for the millions of people who transmit TB without knowing it.
“As the pandemic confirmed, we ignore highly infectious airborne diseases at our peril.”
Study details
Integrated plasma proteomics identifies tuberculosis-specific diagnostic biomarkers
Hannah Schiff, Diana Garay-Baquero, Paul Elkington et al.
Published in JCI on 21 March 2023
Abstract
Novel biomarkers to identify infectious patients transmitting Mycobacterium tuberculosis are urgently needed to control the global tuberculosis (TB) pandemic. We hypothesised that proteins released into the plasma in active pulmonary TB are clinically useful biomarkers to distinguish TB cases from healthy individuals and patients with other respiratory infections. We applied a highly sensitive non-depletion tandem mass spectrometry discovery approach to investigate plasma protein expression in pulmonary TB cases compared to healthy controls in South African and Peruvian cohorts. Bioinformatic analysis using linear modelling and network correlation analyses identified 118 differentially expressed proteins, significant through three complementary analytical pipelines. Candidate biomarkers were subsequently analysed in two validation cohorts of differing ethnicity using antibody-based proximity extension assays. TB-specific host biomarkers were confirmed. A six-protein diagnostic panel, comprising FETUB, FCGR3B, LRG1, SELL, CD14 and ADA2, differentiated patients with pulmonary TB from healthy controls and patients with other respiratory infections with high sensitivity and specificity in both cohorts. This biomarker panel exceeds the World Health Organisation Target Product Profile specificity criteria for a triage test for TB. The new biomarkers have potential for further development as near-patient TB screening assays, thereby helping to close the case-detection gap that fuels the global pandemic.
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Why SA men have much higher TB mortality risk than women
Most TB patients don’t have persistent cough – global study