Tests for tuberculosis infection: landscape analysis

Abstract

Only tuberculin skin tests (TST) and two interferon-γ release assays (IGRA) – QuantiFERON-TB Gold In-Tube and T-SPOT.TB – are currently endorsed by the World Health Organization as tests for tuberculosis (TB) infection. While IGRAs are more specific than TST, they require sophisticated laboratory infrastructure and are costly to perform. However, both types of tests have limited performance to predict development of active TB. Tests with improved predictive performance and operational characteristics are needed.We reviewed the current landscape of tests for TB infection identified through a web-based survey targeting diagnostic manufacturers globally.We identified 20 tests for TB infection including 15 in-vitro tests and five skin tests. Thirteen of the in-vitro tests are whole-blood IGRA and 14 uses early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10), with or without additional antigens. Ten are based on assays other than an enzyme-linked immunosorbent assay such as a fluorescent lateral flow assay, which requires less manual operation and shorter assay time and hence is more suitable for decentralisation compared to the existing IGRA.Four of the five skin tests use ESAT-6 and CFP-10 proteins while the remaining one uses a new antigen that is specific to Mycobacterium tuberculosis complex.New tests have the potential to improve accuracy, operational characteristics and end-user access to tests for TB infection. However, published data in various populations and settings are limited for most new tests. Evaluation of these new tests in a standardised design would facilitate their endorsement and programmatic scale-up.

Evaluation of a lateral-flow nanoparticle fluorescence assay for TB infection diagnosis

“…The positive predictive value of IGRAs remains low, resulting in relatively high numbers needed to treat to prevent TB. 20 , 21 The specificity of QIAreach QFT was only marginally lower than that of QFT-Plus in our study (95.6%), which suggests that the potential roll-out of the assay in decentralised settings is very unlikely to affect adversely number needed to treat. However, further evaluations that will analyse the performance of QIAreach in culture-confirmed patients and other populations in various settings, including high TB burden and low-resource environments, will be needed to identify its role and place for routine TB infection screening.…”

“… 17 , 18 To note, this novel digital lateral flow technology provides sensitivity equivalent to ELISA, as demonstrated by the 100% positivity in specimens with TB1-Nil and TB2-Nil values <1 IU/ml, which is superior to that reported for another lateral flow-based IGRA assay. 19 , 20 By leveraging this novel digital lateral flow technology, QIAreach QFT eliminates the need for more complex ELISA-based technology currently affecting roll-out of IGRA tests in many settings. 1 , 6 , 7 .The simple design using a battery-operated rechargeable eHub allows for expanded near-patient testing in high-burden, low-resource environments, as minimal laboratory skills and infrastructure are required.…”

“…This could support the expansion of IGRA testing and TB prevention as a programmatic component in higher-incidence settings thus helping to achieve the WHO End TB programme’s ambitious goals. 8 , 20 …”

Differential Diagnosis of Latent Tuberculosis Infection and Active Tuberculosis: A Key to a Successful Tuberculosis Control Strategy

“…To overcome the deficiencies of the TST, IGRAs have been developed as an alternative immunodiagnostic approach. Thus far, there are five commercialized IGRA kits, including the T-cell spot of the TB assay (T-SPOT.TB, Oxford Immunotec, Abingdon, UK), QuantiFERON-TB Gold In-Tube (QFT-GIT, Qiagen GmbH, Hilden, Germany), QuantiFERON-TB Gold-Plus (QFT-Plus, Qiagen, MD, United States), LIAISON QuantiFERON-TB Gold Plus (LIAISON QFT-Plus, DiaSorin S.p.A., Italy), and LIOFeron TB/LTBI (LIONEX GmbH, Braunschweig, Germany) (De Maertelaere et al, 2020;Della Bella et al, 2020;Altawallbeh et al, 2021;Hamada et al, 2021). In addition, there are five products in development-T-Track (R) TB (Lophius Biosciences GmbH), VIDAS TB-IGRA (bioMérieux), Access QuantiFERON-TB (Boditech Med Inc.), ichroma TM IGRATB (Boditech Med Inc.), and IP-10 IGRA elisa/lateral flow (rBioPharm) (WHO, 2020).…”

Blue Skies research is essential for ending the Tuberculosis pandemic and advancing a personalized medicine approach for holistic management of Respiratory Tract infections.

“…Important innovations such as GeneXpert and Whole genome sequencing (WGS) platforms for rapidly detecting M.tb resistance genes have rapidly progressed from being research tools to a clinical application (Walzl G et al, 2018;WHO, 2021;Hamada et al, 2021;Satta G et al, 2018;Meehan et al, 2019). Despite these encouraging developments, the required funder investments for conduct of blue skies research by local researchers in high TB endemic countries have not been forthcoming.…”