Field evaluation of a point-of-care triage test for active tuberculosis (TriageTB)
Authors: Richardson Tracy R. , Smith Bronwyn , Malherbe Stephanus T. , Shaw Jane Alexandra , Noor Firdows , MacDonald Candice , van der Spuy Gian D. , Stanley Kim , Carstens Alida , Fisher Tarryn-Lee , van Rensburg Ilana , Flinn Marika , Snyders Candice , Johnson Isaac , Fransman Bernadine , Dockrell Hazel , Thwaites Guy , Thuong Nguyen Thuy Thuong , Schacht Claudia , Mayanja-Kizza Harriet , Nsereko Mary , Tjon Kon Fat Elisa M. , Corstjens Paul L.A.M. , Geluk Annemieke , Ruhwald Morton , Penn-Nicholson Adam , Chegou Novel N. , Sutherland Jayne , Walzl Gerhard ,   TrENDx consortium, Hiemstra Andriëtte , Tonsing Susanne , Tromp Gerard , Owolabi Muyiwa , Mendy Joseph , Gindeh Awa , Barry Amadou , Mbayo Georgetta , Buech Julia , Streitz Malte , Nalukwago Sophie , Namuganga Ann Ritah , Lamunu Dorcas , Odie Michael , Pierneef Louise , van Hooij Anouk , Ruhwald Morten , Belisle John , Dobos Karen , Hatherill Mark , Scriba Thomas , Winter Jill 
Published: July 2023

Abstract
Background
To improve tuberculosis (TB) diagnosis, the World Health Organisation (WHO) has called for a non-sputum based triage test to focus TB testing on people with a high likelihood of having active pulmonary tuberculosis (TB). Various host or pathogen biomarker-based testing devices are in design stage and require validity assessment. Host biomarkers have shown promise to accurately rule out active TB, but further research is required to determine generalisability. The TriageTB diagnostic test study aims to assess the accuracy of diagnostic test candidates, as well as field-test, finalise the design and biomarker signature, and validate a point-of-care multi-biomarker test (MBT).

Methods
This observational diagnostic study will evaluate sensitivity and specificity of biomarker-based diagnostic candidates including the MBT and Xpert® TB Fingerstick cartridge compared with a gold-standard composite TB outcome classification defined by symptoms, sputum GeneXpert® Ultra, smear and culture, radiological features, response to TB therapy and presence of an alternative diagnosis. The study will be conducted in research sites in South Africa, Uganda, The Gambia and Vietnam which all have high TB prevalence. The two-phase design allows for finalisation of the MBT in Phase 1 in which candidate host proteins will be evaluated on stored serum from Asia, South Africa and South America and on fingerstick blood from 50 newly recruited participants per site. The MBT test will then be locked down and validated in Phase 2 on 250 participants per site.

Discussion
By targeting confirmatory TB testing to those with a positive triage test, 75% of negative GXPU may be avoided, thereby reducing diagnostic costs and patient losses during the care cascade. This study builds on previous biomarker research and aims to identify a point-of-care test meeting or exceeding the minimum World Health Organisation target product profile of a 90% sensitivity and 70% specificity. Streamlining TB testing by identifying individuals with a high likelihood of TB should improve TB resources use and, in so doing, improve TB care.

Trial registration
NCT04232618 (clinicaltrials.gov) Date of registration: 16 January 2020.