Rapid diagnosis within reach for TB ‘missed millions’ researchers find

Researchers at Liverpool School of Tropical Medicine have concluded that rapid diagnosis is within reach for the ‘missed millions’ of people living with TB.

Dr Tom Wingfield at Liverpool School of Tropical Medicine and Dr Tushar Garg, technical officer for Stop TB Partnership, conducted the largest study of pooled tuberculosis (TB) testing ever and found that examining sputum samples from several people in a single molecular test cartridge halves the number of cartridges needed to make successful diagnoses.

Their paper on the performance and costs of pooled testing for molecular detection of TB has been published in The Lancet Global Health. It demonstrates that the technique could double the speed of testing, enabling thousands more patients to be tested and diagnosed around the globe.

The study was carried out by Start4All, a four-year Unitaid-funded partnership led by LSTM, with the Stop TB Partnership and research partners in seven high TB-burden countries.

Informing WHO guidelines

The findings are so significant they directly informed World Health Organization guidelines on pooled testing issued earlier this year.

Dr Wingfield, deputy director of LSTM’s Centre for Tuberculosis Research and Principal Investigator on Start4All, said: “This is the evidence that took pooled testing from a promising idea to a WHO recommendation, and it comes from routine laboratories and clinics in the countries that need it most, not from a research setting.

“Pooling needs no new technology. It makes smarter use of the machines and cartridges laboratories already have, so that many more people can receive a rapid molecular test from the same budget.

“That is what reaching the missed millions looks like in practice.”

Large-scale study

Between November 2023 and February 2025 more than 14,000 people with symptoms of TB in Bangladesh, Brazil, Cameroon, Kenya, Malawi, Nigeria and Vietnam took part in the study, through community screening, primary health centres and district hospitals.

Each person’s sputum was tested on its own and again as part of a pool of up to four specimens on Xpert MTB/RIF Ultra, the most widely used rapid molecular TB test.

Dr Wingfield’s study is the first to measure pooled testing against culture, the reference standard for TB diagnosis, rather than only against individual molecular testing.

Pooled testing used just over 7,000 cartridges instead of the roughly 14,000 that individual testing required, a 51% reduction, cutting the cost of each test from nearly US$8 to less than US$4.

A slight drop in sensitivity (3.1% less compared to individual testing) was mostly in specimens containing a very low TB bacterial load. Among people whose individual test showed a high, medium or low load, the pooled result agreed with the individual test more than 96% of the time.

Cyrille Mbuli, from the Bamenda Center for Health Promotion and Research, the collaborating partner of Start4All in Cameroon, said: “The TB programmes have been asking a simple question: what do we give up when we pool tests, and what do we gain?

“The Start4All results confirm what our laboratories have seen: pooling lets us test almost twice as many people for the same investment.”

Deadliest single infection

Global efforts to tackle TB – the deadliest single infection which kills around 1.3 million people a year – are hampered by the large number who remain undiagnosed, untreated and unknowingly spreading TB in their homes and communities.

Chronic underinvestment has led to limited and inequitable access to WHO-recommended molecular rapid diagnostic tests, which only one-in-two people globally receive as their initial test.

This research is already having a real world impact in communities around the world through the creation of a new toolkit for healthcare professionals and a test cost calculator developed by Stop TB Partnership.

Dr Wingfield’s paper is one of a series of Start4All outputs on pooled testing:

• a multicountry qualitative study in BMJ Open, led by Dr Vibol Iem at LSTM, found that laboratory staff, programme managers and people with TB in the seven countries considered pooled sputum testing feasible and acceptable;
• a cross-sectional study in Clinical Microbiology and Infection reported the diagnostic accuracy and potential resource savings of pooled testing among adults in Vietnam.

In the next phase of Start4All, pooled testing will be combined with computer-aided chest X-ray triage and expanded to tongue swab specimens, supporting simpler and scalable approaches that can expand access to molecular TB testing.

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