Optimizing tuberculosis case finding by a step wise approach using host transcriptomics, bacterial metagenomics and sputum free sampling adopted for high endemic areas - a randomized clinical trial

In 2020, WHO estimated that among 10 million new tuberculosis (TB) cases, 3 million are undiagnosed and only 57% bacteriologically confirmed.

In a cluster-randomised trial in Ethiopia and Guinea Bissau implementing a clinical scoring tool (TBscore), we recently showed a 4-fold increasein case detection rate in Ethiopia.

Buidling on our network and clinical trial experience, we now plan to conduct a randomised trial in 2023-24 at health care facilities in Ethiopia and Guinea Bissau to evaluate an optimized diagnostic procedure (ODP) compared with standard care in an effort to enhance early case finding and treatment aiming for sustainable development in low resource settings by limiting TB associated mortality.

The ODP consists of a step wise approach by analysing (i) smear microscopy and PCR in pooled sputum and a recently developed sputum free technique using face mask sampling, (ii) a clinical follow up where computer assisted chest X-ray evaluation will be followed by (iii) a benchtop sequencing technology adopted for field use (Oxford nanopore) combining mycobacterial metagenomics and a validated host transcriptomic signature (RISK6).

The main outcomes are the the rate of patients diagnosed and treated for TB within one week compared to standard of care and the difference in diagnostic yield between face mask sampling and conventional sputum.

Optimizing early diagnosis in treatment using nove strategies are essential to reach the goal of reducing TB world-wide.