Start4All: protocol for evaluating TB screening and diagnostic tests and test algorithms in the community and lower care levels in seven high-burden countries

BACKGROUND: Despite advances in TB care, ap-proximately 2.4 million people with TB remain undi-agnosed or unreported each year. A key contributor to these ‘missed millions’ is that major diagnostic gaps persist especially among underserved populations. De-veloping diagnostic algorithms that are accessible and integrated into health care systems where they are intended to be used is essential to meet WHO End TB targets. 

METHODS: Start4All a multi-country, cross-sectional diagnostic accuracy study (in Bangladesh, Brazil, Cameroon, Kenya, Malawi, Nigeria, and Viet Nam) aims to assess and model algorithms using combinations of WHO-endorsed, and experimental TB screening and diagnostic tests across the lowest levels of care and the community, compared to a sputum culture reference standard. Evaluated tools include C-reactive protein tests, computer-aided detection–interpreted chest X-rays, pooled Xpert® MTB/RIF Ultra (Xpert Ultra) testing, and a third generation lipoarabinomannan (LF-LAM) assay. 

DISCUSSION: Start4All will generate high-quality evidence to guide policy decisions on the adoption and the integration of non-sputum and laboratory independent tools to accelerate early TB detection and close the treatment gap. 

CONCLUSION: A feature of Start4All is its implementation within national TB programmes across seven high-burden countries to ensure that findings are directly translatable to policy and operational decision making. Harmonised protocols, standardised microbiological reference testing, and unified data management systems will enable cross-country comparison and strengthen the external validity of results.