Background

The tuberculosis disease burden is not falling fast enough to reach the first (2020) milestones of the End TB Strategy. The gap between the reported 6.4 million and the estimated 10 million active cases is due to a combination of under-reporting of detected cases and under-diagnosis. Proposed initiatives include detecting and treating 40 million people with TB from 2018–2022. Increased diagnostic research plays an important part in this initiative: there are currently no point-of-care tests for TB to be used at the basic healthcare facility, which performs 60% of TB tests, and there are no tests available for the detection of individuals most at-risk of developing the disease for targeted prevention.

Objectives

To refine the bio-signature for global use, the study will combine information from previous and current biomarker testing in African individuals with that from a concurrent evaluation of biomarkers using serum samples from Asia, Eastern Europe and South America.

To refine the POC device, we will conduct field-testing of the proposed device in a laboratory-free manner in three African sites and Vietnam. To optimise the bio-signature and refinement of the device, the design of the point-of-care multi-biomarker test (POC-MBT) will undergo field testing and evaluation in the same sites.

Other point-of-care investigations – the Cepheid 3-gene Xpert test, Quantum POC (Q-POC) and high sensitivity urinary lipoarabinomannan (LAM); as well as several central laboratory quantitative reverse transcription PCR sequences will concurrently be evaluated for diagnostic utility.

Study design

In this study, we will conduct a prospective study to recruit three parallel arms:

• Aim 1a (Triage TB): testing of new diagnostics in 300 adult and children participants aged 12-70 years with suspected active TB disease.
• Aim 1b (ChilDx): testing new diagnostics in 300 children aged three months to 12 years of age with suspected active TB disease.
• Aim 2 (Exposed) testing new diagnostics for the incident and sub-clinical TB, which are 320 adult and children close contacts of TB patients between the ages of 12 and 70.