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Diagnostics
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Innovative Approaches to Tuberculosis Screening and Diagnosis
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Innovative Approaches to Tuberculosis Screening and Diagnosis

A Special Issue of Diagnostics (ISSN 2075-4418) belonging to the section "Diagnostic Microbiology and Infectious Disease".

Deadline for manuscript submissions: 31 December 2026 | Viewed by 5844

Editors

Dr. Nguyen Nhat Linh

E-Mail Website
Guest Editor
Department for HIV, Tuberculosis, Hepatitis & Sexually Transmitted Infections (HTH), World Health Organization, CH-1211 Geneva, Switzerland
Interests: tuberculosis; public health
Dr. Dennis Falzon

E-Mail Website
Guest Editor
Department for HIV, Tuberculosis, Hepatitis & Sexually Transmitted Infections (HTH), World Health Organization, CH-1211 Geneva, Switzerland
Interests: tuberculosis; informatics; surveillance; monitoring; drug-resistant TB
Dr. Alexei Korobitsyn

E-Mail Website
Guest Editor
Department for HIV, Tuberculosis, Hepatitis & Sexually Transmitted Infections (HTH), World Health Organization, CH-1211 Geneva, Switzerland
Interests: tuberculosis

Special Issue Information

Dear Colleagues,

Screening and diagnosis play a critical role in the prevention and care of tuberculosis (TB), which remains one of the major communicable diseases of global public health importance (11 million new TB patients per year) and the single leading cause of death from an infectious agent worldwide (1.5 million TB deaths annually). Each year close to three million TB patients go undiagnosed or unreported, presenting a challenge to many countries to reduce their TB burden.

After many decades of stagnation in the technologies used to screen, detect and confirm TB, the last 15 years have seen an encouraging expansion in new TB diagnostics appearing on the market. These include molecular and other rapid biomarkers that can be used on a variety of biological specimens; interferon gamma release assays for the detection of TB infection; and low-radiation ultraportable equipment, bringing chest X-ray within reach of more populations. The application of artificial intelligence to interpret chest X-ray imaging and the signatures of cough and stethoscope sounds for TB is another promising frontier that is already being operationalized and scaled up in low-resource, high-burden settings. These developments have been matched by new treatments and care for drug-susceptible and drug-resistant TB and TB preventive treatment (TPT). The World Health Organization helps countries implement diagnostics of proven accuracy, guides manufacturers to develop technologies that better address the needs of users, and helps shape the research agenda.

As Guest Editors on this Special Issue, we invite leading researchers to contribute studies on new approaches for TB screening and diagnosis. A collection of articles with a broad scope of research will allow readers to appreciate the dynamic nature of screening and diagnostics for TB. The contributions being targeted will include, amongst others, research related to molecular diagnostics, the clinical chemistry of biomarkers, immunology, imaging, analysis of chest sounds and computer-aided detection employing artificial intelligence. We also encourage reports on the implementation of innovations, such as the cost-effectiveness of different testing strategies and information systems and field studies on the feasibility, accessibility, end-user values and equity and linkage to care of innovative approaches to the screening and diagnosis of TB disease, TB infection or post-TB impairments. We look forward to hearing from you.

Dr. Nguyen Nhat Linh
Dr. Dennis Falzon
Dr. Alexei Korobitsyn
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tuberculosis
  • diagnosis
  • screening
  • genomics
  • biomarkers
  • artificial intelligence
  • linkage to care

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Published Papers (4 papers)

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Review

22 pages, 2007 KB  
Review
Differentiating Tuberculous and Pyogenic Spondylodiscitis: Part II: MRI/CT Features, Prediction Models, and the Role of PET/CT—A Narrative Review
by Oana Maria Vanta, Anamaria Marian, Manuela Lenghel, Linda Ghib, Sonia Irina Vlaicu, Larisa Rotaru, Ileana Nicoară, Simona Rednic and Cristina Pamfil
Diagnostics 2026, 16(16), 2540; https://doi.org/10.3390/diagnostics16162540 - 12 Aug 2026
Viewed by 460
Abstract
Distinguishing tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) on imaging remains clinically important because the two entities differ in antimicrobial strategy, surgical timing, and the urgency of microbiological workup, yet no single imaging sign is pathognomonic for either diagnosis. When tissue confirmation is [...] Read more.
Distinguishing tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) on imaging remains clinically important because the two entities differ in antimicrobial strategy, surgical timing, and the urgency of microbiological workup, yet no single imaging sign is pathognomonic for either diagnosis. When tissue confirmation is delayed, imaging becomes the primary tool that shifts pre-test probability and guides biopsy strategy—a role that is particularly critical in culture-negative disease, in antibiotic-exposed patients, and in settings with limited access to rapid mycobacterial diagnostics. This narrative review maps the imaging evidence most useful for routine TS-versus-PS differentiation, synthesizes recent prediction models and quantitative tools, and evaluates the adjunctive role of 18F-FDG PET/CT in biopsy-oriented decision-making. PubMed/MEDLINE was searched from inception to 31 March 2026 using pre-specified search terms across three concept blocks. This was a narrative review without formal pooling of quantitative estimates or prospective protocol registration. A secondary Scopus search identified no additional eligible records. Priority was given to comparative TS-versus-PS imaging cohorts, meta-analyses of MRI and CT features, prediction-model studies, and the recent radiomics and PET/CT literature; radiomics and deep-learning studies are appraised as a distinct evidence tier given their retrospective single-center derivation and predominantly internal-only validation. In total, 14 comparative TS-versus-PS imaging cohorts, three meta-analyses, and 14 prediction-model, quantitative-scoring, radiomics, or deep-learning studies formed the core evidence base. MRI yields the greatest differentiating information and is the recommended first-line modality. Features favoring TS include thoracic predominance, multilevel or non-contiguous involvement, relative early disc preservation, subligamentous spread, intraosseous abscesses, thin-walled paravertebral collections, and severe vertebral collapse with kyphotic deformity. Features favoring PS include lumbar predominance, early disc-endplate destruction, homogeneous inflammatory enhancement, facet-joint arthritis, and epidural phlegmon. CT adds osseous detail—including sequestra, subligamentous bone erosion, and paravertebral calcification—and remains the primary guidance modality for biopsy. Recent prediction models combining imaging and laboratory variables have shown high discriminative performance in derivation cohorts; however, most remain internally validated and locally calibrated. Pending external validation, none should be considered ready for unmodified clinical adoption, and they should therefore be used as probability modifiers rather than stand-alone diagnostic rules. 18F-FDG PET/CT is complementary rather than primary and is most useful when MRI is contraindicated or equivocal, in hardware-associated infection, and for whole-body staging in suspected disseminated tuberculosis. Non-infectious mimics and alternative infectious diagnoses should be considered when the imaging pattern is internally inconsistent or when standard cultures remain negative. Imaging findings should refine etiological probability and guide biopsy strategy, but should not replace tissue confirmation when tissue is feasible. Non-imaging evidence complementing this review is addressed in the companion manuscript, Part I. Full article
(This article belongs to the Special Issue Innovative Approaches to Tuberculosis Screening and Diagnosis)
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Figure 1

23 pages, 809 KB  
Review
Differentiating Tuberculous and Pyogenic Spondylodiscitis: Part I—Epidemiology, Clinical Features, Laboratory Markers, and Tissue-Based Diagnosis
by Anamaria Marian, Oana Maria Vanța, Valentin Danci, Larisa Rotaru, Maria-Magdalena Tămaș, Rodica Ungur, Simona Rednic and Cristina Pamfil
Diagnostics 2026, 16(14), 2243; https://doi.org/10.3390/diagnostics16142243 - 17 Jul 2026
Viewed by 1136
Abstract
Distinguishing tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) remains difficult when presentation is non-specific, blood cultures are negative, or initial biopsy is non-diagnostic. The two entities differ substantially in antimicrobial strategies, resistance testing requirements, public health interventions, and surgical thresholds, yet diagnostic delay [...] Read more.
Distinguishing tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) remains difficult when presentation is non-specific, blood cultures are negative, or initial biopsy is non-diagnostic. The two entities differ substantially in antimicrobial strategies, resistance testing requirements, public health interventions, and surgical thresholds, yet diagnostic delay is associated with neurological deficits, spinal instability, and permanent deformity. This narrative review maps the non-imaging evidence most useful for frontline differentiation between TS and PS across five domains: epidemiology and risk stratification, clinical presentation, laboratory markers, tissue acquisition and histopathology, and molecular diagnostics. PubMed/MEDLINE was searched from inception to 31 March 2026 using pre-specified Boolean search terms; a secondary Scopus search identified no additional eligible records. Following screening, approximately 90 records were included in this synthesis. Priority was given to comparative TS-versus-PS cohorts, biopsy-yield and culture-negative studies, pathology series, pediatric data, and recent molecular diagnostics literature. Epidemiological TB (tuberculosis) risk, longer symptom duration, constitutional symptoms, deformity, and a less intense acute-phase response increase the probability of TS, whereas healthcare exposure, bacteraemia, recent spinal procedures, and brisk neutrophilic inflammation favor PS. In stable patients, the highest-yield strategy is early blood cultures followed by image-guided biopsy with parallel tissue allocation for bacterial culture, mycobacterial studies, histopathology, and selected molecular assays. No single laboratory marker reliably distinguishes TS from PS without tissue confirmation. Per a 2023 systematic review and meta-analysis, image-guided percutaneous biopsy achieves microbiological confirmation in approximately one-third of cases. Histopathology demonstrating caseating granulomatous inflammation supports TS, although a substantial minority of confirmed cases lack classic features. Supported by cohort prospective data, Xpert MTB/RIF Ultra has the clearest first-line molecular role when TS is plausible and should be requested at the time of first biopsy rather than reserved for salvage testing; broader or targeted next-generation sequencing is best reserved for selected unresolved cases. Imaging differentiation is addressed in the companion manuscript, Part II. Full article
(This article belongs to the Special Issue Innovative Approaches to Tuberculosis Screening and Diagnosis)
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Figure 1

18 pages, 315 KB  
Review
Nanopore Sequencing in Mycobacterial Diagnostics: Clinical and Laboratory Roles of mNGS and tNGS
by Meng Wang
Diagnostics 2026, 16(12), 1850; https://doi.org/10.3390/diagnostics16121850 - 15 Jun 2026
Viewed by 491
Abstract
Background/Objectives: Nanopore sequencing is increasingly used in mycobacterial diagnostics, where clinical microbiologists and diagnostic laboratories must decide when broad metagenomic next-generation sequencing (mNGS) or focused targeted next-generation sequencing (tNGS) is most appropriate. This review examined reported clinical and laboratory roles of nanopore mNGS [...] Read more.
Background/Objectives: Nanopore sequencing is increasingly used in mycobacterial diagnostics, where clinical microbiologists and diagnostic laboratories must decide when broad metagenomic next-generation sequencing (mNGS) or focused targeted next-generation sequencing (tNGS) is most appropriate. This review examined reported clinical and laboratory roles of nanopore mNGS and tNGS in tuberculosis (TB) and nontuberculous mycobacterial (NTM) settings. Methods: Targeted searches of PubMed/MEDLINE, Embase, Web of Science Core Collection, and Scopus were refreshed on 4 April 2026. Thirty-five records spanning original clinical studies, evidence syntheses, and guideline-context documents were included. Results: Nanopore mNGS is most useful for broad organism detection and diagnostic rescue in unresolved pulmonary and extrapulmonary presentations, particularly when first-line testing is negative, discordant, low-yield, or when mixed infection is suspected. Nanopore tNGS appears better aligned with predefined TB confirmation and resistance-focused workflows because targeted regions allow more standardized interpretation. Agreement is strongest for rifampicin- and isoniazid-related resistance targets. In NTM settings, evidence is stronger for detection and species identification than for disease-level diagnosis. Common implementation constraints include pre-analytical variation, contamination control, host-background interference, inconsistent bioinformatics, and limited workforce capacity. Conclusions: A practical tiered approach is supported in which mNGS is positioned mainly for diagnostic rescue and discovery, whereas tNGS is considered for predefined workflows requiring standardized target interrogation and resistance-associated mutation reporting under local validation and quality systems. Full article
(This article belongs to the Special Issue Innovative Approaches to Tuberculosis Screening and Diagnosis)
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22 pages, 882 KB  
Review
Artificial Intelligence for Tuberculosis Screening and Detection: From Evidence to Policy and Implementation
by Hien Thi Thu Nguyen, Vang Le-Quy, Anh Tuan Dinh-Xuan and Linh Nhat Nguyen
Diagnostics 2026, 16(8), 1127; https://doi.org/10.3390/diagnostics16081127 - 9 Apr 2026
Cited by 2 | Viewed by 3116
Abstract
Artificial intelligence (AI) is increasingly used to support tuberculosis (TB) screening and diagnosis, particularly through computer-aided detection (CAD) applied to chest radiography (CXR). However, the programmatic value of AI depends not only on diagnostic accuracy but also on implementation context, threshold calibration, and [...] Read more.
Artificial intelligence (AI) is increasingly used to support tuberculosis (TB) screening and diagnosis, particularly through computer-aided detection (CAD) applied to chest radiography (CXR). However, the programmatic value of AI depends not only on diagnostic accuracy but also on implementation context, threshold calibration, and integration into diagnostic pathways. We conducted a narrative, state-of-the-art review of AI applications across the TB diagnosis pathway. Evidence was synthesized from World Health Organization policy documents, independent validation initiatives, and peer-reviewed studies published between 2010 and 2026, with a structured selection process aligned with PRISMA principles. CAD for CXR is the most mature AI application and is recommended by WHO for TB screening and triage among individuals aged ≥15 years in specific contexts. Across studies, CAD-CXR demonstrates sensitivity comparable to human readers, although performance varies by product, population, and imaging conditions, necessitating local threshold calibration. Evidence from implementation studies suggests improvements in screening efficiency and potential cost-effectiveness in high-burden settings. Other AI modalities, including computed tomography (CT)-based imaging analysis, point-of-care ultrasound interpretation, cough or stethoscope sound analysis, clinical risk models, and genomic resistance prediction show promising but heterogeneous results, with most requiring further independent validation and prospective evaluation. AI has the potential to strengthen TB screening and diagnostic pathways, but its impact depends on integration into health systems and evaluated using patient- and program-level outcomes rather than accuracy alone. A differentiated approach is needed, with responsible scale-up of policy-endorsed tools alongside rigorous evaluation of emerging technologies to support effective and equitable TB care. Full article
(This article belongs to the Special Issue Innovative Approaches to Tuberculosis Screening and Diagnosis)
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