Advances in tuberculosis diagnostics and biomarkers, 2020-26: scientific evidence, recommendations, gaps, and developmental priorities.
Significant advances in TB diagnostics have been made, but key gaps remain, particularly in biomarker development for distinguishing infection from disease.
Where it sits
this study against the rest of the aod-9604 corpusSummary and findings
The paper reviews advancements in tuberculosis diagnostics and biomarkers from 2020 to 2025, focusing on WHO policy updates. It highlights the integration of digital chest radiography and molecular diagnostics like NAATs for improved TB detection and drug resistance testing. Despite progress, significant gaps in performance and implementation remain.
Abstract
Major advances in tuberculosis diagnostics and biomarker research from 2020 to 2025 have informed updated WHO policy guidance, consolidating recommendations for the detection of tuberculosis disease and drug resistance within a single framework. These recommendations align screening, diagnosis, and drug-resistance testing across populations and specimen types. Digital chest radiography, increasingly supported by computer-aided detection, is now a core WHO-recommended screening and triage tool, improving case detection and referral for confirmatory testing at scale. Decentralised molecular diagnosis has expanded through diversified deployment of WHO-recommended rapid diagnostic test classes, particularly low-complexity automated nucleic acid amplification tests (NAATs), including the Xpert MTB/RIF Ultra and Truenat platforms. These tests are complemented by low-complexity manual NAATs such as tuberculosis loop-mediated isothermal amplification and by emerging near point-of-care molecular platforms under evaluation. Latest WHO policy updates have also introduced a new class of near point-of-care NAATs designed for decentralised use, alongside novel specimen types such as tongue swabs for individuals unable to produce sputum, and programmatic innovations, including sputum pooling, to improve efficiency. Expanded use of molecular diagnostics across non-sputum specimens, including stool, gastric aspirate, and nasopharyngeal samples, together with simplified workflows, has improved bacteriological confirmation in children and other sputum-scarce populations. Rapid molecular drug-resistance testing has advanced with Xpert MTB/XDR, and targeted next-generation sequencing is now recognised as a WHO-endorsed approach for comprehensive drug-susceptibility testing at reference laboratory level. Urine lipoarabinomannan-based assays improve diagnostic yield in people with HIV, particularly those with advanced disease, although performance limitations constrain broader use. Substantial performance, implementation, and equity gaps remain. In parallel, host blood transcriptomic signatures show strong short-term prognostic and triage performance, and additional proteomic, metabolomic, cellular, imaging, and pathogen-derived biomarkers are advancing through clinical evaluation. However, no biomarker has yet met the WHO target product profile criteria for a point-of-care test that reliably distinguishes M tuberculosis infection from tuberculosis disease, including asymptomatic or minimally symptomatic tuberculosis disease, often described in the research literature as subclinical tuberculosis.
Background
Tuberculosis remains a major global health challenge, necessitating improved diagnostic and drug resistance testing methods. Recent years have seen significant technological advancements in this field, prompting updates to WHO guidelines. This paper reviews these developments, emphasizing their potential to enhance TB detection and management.
Methods
The study is a review of advancements in TB diagnostics and biomarkers from 2020 to 2025. It evaluates WHO policy updates and technological innovations, including digital radiography and molecular diagnostics. The paper discusses various diagnostic platforms and specimen types but does not report specific study designs or sample sizes.
Results
The integration of digital chest radiography and computer-aided detection has improved TB case detection and referral. Molecular diagnostics, particularly NAATs, have expanded, with new platforms facilitating decentralized testing. Despite these advancements, no biomarker has achieved the WHO target for distinguishing TB infection from disease.
Interpretation
While the advancements in TB diagnostics are promising, the lack of biomarkers meeting WHO criteria for point-of-care testing limits their clinical impact. The review highlights significant progress in technology and policy but underscores the need for further research to address existing gaps. The findings align with prior literature on the importance of molecular diagnostics but emphasize ongoing challenges in implementation and equity.
Key findings
- Digital chest radiography is now a core WHO-recommended screening tool.
- Xpert MTB/RIF Ultra and Truenat platforms are key NAATs for TB diagnosis.
- New near point-of-care NAATs have been introduced for decentralized use.
- Urine lipoarabinomannan-based assays improve diagnostic yield in HIV patients.
- No biomarker yet meets WHO criteria for distinguishing TB infection from disease.
Limitations
- No specific quantitative outcomes reported
- Focuses on policy and technology, not clinical efficacy
- No biomarker meets WHO criteria for TB infection vs disease
- Performance and equity gaps remain