ArticleThe Lancet. Global health2024
Blood RNA biomarkers for tuberculosis screening in people living with HIV before antiretroviral therapy initiation: a diagnostic accuracy study.
Article in The Lancet. Global health, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 19 citations in OpenAlex.
- Monocyte-Amplified Transcriptional Signatures of Human Diseases.bioRxiv : the preprint server for biology · 2026Article
- Sputum scarcity and associated factors in people undergoing tuberculosis testing in South Africa, Uganda, India, and the Philippines: an analysis of cross-sectional observational data.EClinicalMedicine · 2026Article
- Circulating non-canonical small non-coding RNAs as novel diagnostic biomarkers for tuberculosis.Microbiology spectrum · 2026Article
- Nasal Gene Expression in ART-Naive Adults with HIV and Pulmonary Tuberculosis in Uganda.medRxiv : the preprint server for health sciences · 2026Article
- Diagnostic value of miR-155, miR-29a and lncRNAs (NEAT1, GAS5 and COX2) in HIV, tuberculosis, and HIV/TB co-infection.Scientific reports · 2026Article
- Host-response biomarkers for precision tuberculosis: from immune transcriptomic signatures to clinical risk stratification.Frontiers in cell and developmental biology · 2026Review
- Peripheral blood cellular dynamics during the progression of human tuberculosis.Scientific reports · 2025Article
- Blood RNA biomarkers and C-reactive protein for triage of adult patients with tuberculosis lymphadenitis and pericarditis in South Africa: a single-centre, prospective, observational, diagnostic accuracy study.The Lancet. Microbe · 2025Observational
- Oral washes and tongue swabs for Xpert MTB/RIF Ultra-based tuberculosis diagnosis in people with and without the ability to make sputum.Research square · 2025Article
- Evaluation of host-immune biomarker signatures as multiplex qPCR diagnostic assays: a pilot study toward meeting WHO target product profiles for TB diagnosis in India.Frontiers in tuberculosis · 2025Article
- Resolution of tuberculosis blood RNA signatures fails to discriminate persistent sputum culture positivity after 8 weeks of anti-tuberculous treatment.The European respiratory journal · 2024Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundUndiagnosed tuberculosis remains a major threat for people living with HIV. Multiple blood transcriptomic biomarkers have shown promise for tuberculosis diagnosis. We sought to evaluate their diagnostic accuracy and clinical utility for systematic pre-antiretroviral therapy (ART) tuberculosis screening.
methodsWe enrolled consecutive adults (age ≥18 years) referred to start ART at a community health centre in Cape Town, South Africa, irrespective of symptoms. Sputa were obtained (using induction if required) for two liquid cultures. Whole-blood RNA samples underwent transcriptional profiling using a custom Nanostring gene panel. We measured the diagnostic accuracy of seven candidate RNA signatures (one single gene biomarker [BATF2] and six multigene biomarkers) for the reference standard of Mycobacterium tuberculosis culture status, using area under the receiver-operating characteristic curve (AUROC) analysis, and sensitivity and specificity at prespecified thresholds (two standard scores above the mean of healthy controls; Z2). Clinical utility was assessed by calculating net benefit in decision curve analysis. We compared performance with C-reactive protein (CRP; threshold ≥5 mg/L), WHO four-symptom screen (W4SS), and the WHO target product profile for tuberculosis triage tests.
findingsA total of 707 people living with HIV (407 [58%] female and 300 [42%] male) were included, with median CD4 count 306 cells per mm
interpretationRNA biomarkers showed better clinical utility to guide confirmatory tuberculosis testing for people living with HIV before ART initiation than symptom-based screening, but their performance did not exceed that of CRP and fell short of WHO recommended targets. Interferon-independent approaches might be required to improve accuracy of host-response biomarkers to support tuberculosis screening before ART initiation.
fundingSouth African Medical Research Council, European and Developing Countries Clinical Trials Partnership 2, National Institutes of Health National Institute of Allergy and Infectious Diseases, The Wellcome Trust, National Institute for Health and Care Research, Royal College of Physicians London.
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