NCT07517471

Start4All SCREEN-TB PROTOCOL

Start4All - Start Taking Action for TB Diagnosis SCREEN-TB

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 37,000 (estimated)
• Sponsor: Liverpool School of Tropical Medicine · Academic / Other
• Sex: All
• Age: 10 Years
• Healthy volunteers: Accepted

Summary

Tuberculosis (TB) remains the leading cause of death from a single infectious agent globally, with millions of people still undiagnosed or diagnosed late. Conventional case-finding strategies rely heavily on symptom screening using the WHO Four-Symptom Screen ((W4SS; comprising any one of current cough, fever, night sweats, or weight loss) and sputum testing, but these approaches miss a substantial proportion of individuals with active TB disease, particularly those who are asymptomatic or unable to produce sputum. Missed and delayed diagnoses drive ongoing transmission and undermine global TB elimination goals. Recent evidence has shown that diagnostic tools which are more accessible, even if somewhat less sensitive, can still substantially improve TB case detection by reducing diagnostic loss associated with access barriers. This suggests that near point-of-care (NPOC) tests might be highly cost-effective in many settings, because the gains from earlier diagnosis, reduced delays, and broader reach could outweigh losses from slightly lower accuracy. The purpose of this study is to evaluate new, symptom-agnostic screening and diagnostic approaches that can be implemented at lower-level health facilities in high TB-burden, low and middle-income (LMIC) countries for adults ≥15 years and 10-14 years old young adolescents

Detailed description

The study will generate evidence on the performance, cost-effectiveness, feasibility, acceptability, and scalability of symptom-agnostic algorithms initiated by of computer-aided detection chest radiography (CAD CXR-AI) and near point-of-care (NPOC) molecular assays applied to tongue and sputum swabs. These tools have the potential to identify TB earlier, including among asymptomatic individuals, and to reduce dependence on sputum-based diagnostics alone. The research questions being addressed are of direct global relevance. There is currently limited real-world evidence on: how CAD CXR-AI and NPOC tongue swab and sputum swab assays compare as initial screening tools; how they can be integrated with WHO-recommended low-complexity nucleic acid amplification tests (LC-NAATs), in efficient algorithms; and whether these approaches can be delivered effectively in primary care and outpatient settings in high TB burden LMIC. Data generated through this study will directly inform WHO guideline development and national TB programme decisions, especially concerning the detection of asymptomatic TB and the role of non-sputum samples.

Conditions

• TB - Tuberculosis

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Near point of care (NPOC) NAATs	* Near point of care instrument that can test tongue swabs and sputum swabs. * Rapid molecular detection system for detecting infectious diseases included TB, able to provide accurate test results that are comparable to top laboratory PCR tests, while it is easier to use and move around and only takes 15 to 35 minutes to conclude the result.
DIAGNOSTIC_TEST	Low-complexity nucleic acid amplification tests (LC-NAATs)	Semi-quantitative, nested real-time polymerase chain reaction (PCR) diagnostic test for the detection of Mycobacterium tuberculosis (MTB) complex DNA in unprocessed sputum samples\[18\]. It can also detect rifampicin-resistance associated mutations in MTB. Results are automatically displayed on the screen of the system in less than 80 minutes
DIAGNOSTIC_TEST	LC-NAAT using pooled testing	Pooled testing involves combining equal volumes from multiple individuals' samples and testing them together using a single test\[. Pools will be created using remaining samples from 2-4 participants who have screened positive and were able to produce a sputum, guided by CAD CXR-AI thresholds\[20\]. To the possible extend, pools will be suggested by CAD band score: CAD \<0.3 pooled together and 0.3 ≤ CAD \< 0.8 pooled together.
DIAGNOSTIC_TEST	Portable Chest X-ray Image Acquisition	Portable X-ray systems are designed to bring diagnostic imaging to environments where conventional radiography is impractical. They are lightweight, compact, and battery-powered, making them suitable for use in remote or resource-limited settings, or for reaching people with limited mobility. Depending on the model, they can produce between 100 and 400 images on a full charge, allowing extended use without access to electricity.
DIAGNOSTIC_TEST	Computer-Aided Detection (CAD) Chest X-ray (CXR-AI)	Computer-aided detection (CAD) software for chest X-rays is designed to support rapid, automated screening for tuberculosis and other thoracic abnormalities. Software for the study has not been selected yet. It will be a WHO-approved CAD software with final selection through tender processes and in compliance with national regulatory approvals. Operating on mobile or computer platforms, these tools can analyse chest X-rays in less than a minute, distinguishing normal from abnormal scans and highlighting findings in the lungs, pleura, mediastinum, bones, diaphragm, and heart. In addition to detecting disease, some systems can assist clinicians with tasks such as verifying device placement and measuring distances from anatomical landmarks.
OTHER	Screen TB&HIV sub-study diagnostic test	The SCREEN TB\&HIV substudy is implemented only in Cameroon, Nigeria and Kenya. HIV testing will therefore not be conducted in Bangladesh or Viet Nam, as HIV testing is not part of routine care pathways at the participating facilities and the study does not introduce additional HIV testing. In addition, Bangladesh and Viet Nam have substantially lower HIV prevalence, making implementation of the HIV substudy operationally unnecessary and not aligned with clinical need
OTHER	Screen TB&HIV sub-study diagnostic test	The CD4 cell count is performed in venous blood in HIV positive patients to assess progression of HIV disease, including risk for developing opportunistic infections. The normal range of CD4 count is from 500 to 1500 cells/mm3 of blood, and it progressively decreases over time in persons who are not receiving or not responding well to ART. Someone with a CD4 count below 200 is described as having advanced HIV disease.
OTHER	Screen TB&HIV sub-study diagnostic test	LAM is a glycolipid of the cell wall of Mycobacterium tuberculosis. LAM is excreted in urine, where it can be detected using rapid lateral flow tests. In inpatient settings, WHO strongly recommends using LAM to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children with signs and symptoms of TB (pulmonary and/or extrapulmonary), or with advanced HIV disease (1) or who are seriously ill (2) or else irrespective of signs and symptoms of TB and with a CD4 cell count of less than 200 cells/mm3\[23\]. In outpatient settings, WHO suggests using LF-LAM to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: with signs and symptoms of TB (pulmonary and/or extrapulmonary) or seriously ill; or else irrespective of signs and symptoms of TB and with a CD4 cell count of less than 100 cells/mm3\[23\]. LAM tests evaluated in SCREEN TB\&HIV are:

Timeline

• Start date: 2026-04-01
• Primary completion: 2027-01-01
• Completion: 2027-05-01
• First posted: 2026-04-08
• Last updated: 2026-04-08