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TropicalMed
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Tuberculosis Diagnosis: Current, Ongoing and Future Approaches
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Tuberculosis Diagnosis: Current, Ongoing and Future Approaches

A special issue of Tropical Medicine and Infectious Disease (ISSN 2414-6366). This special issue belongs to the section "Infectious Diseases".

Deadline for manuscript submissions: closed (15 June 2026) | Viewed by 9946

Editor

Dr. Philippa J. Randall

E-Mail Website
Guest Editor
1. Department of Medicine, University of Cape Town, Cape Town 7925, South Africa
2. Antrum Biotech, Old Main Building, Groote Schuur Hospital, Observatory, Cape Town 7925, South Africa
Interests: tuberculosis; diagnostics; immunology; biomarker discovery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tuberculosis (TB) remains a significant global health challenge, with millions affected annually. This Special Issue, entitled ‘Tuberculosis Diagnosis: Current, Ongoing and Future Approaches’, aims to provide a comprehensive overview of the diagnostic landscape, highlighting advancements, ongoing research, and future directions in TB diagnostics.

This Special Issue aims to focus on traditional diagnostic methods, which, despite their limitations, remain widely used in many regions. We also aim to explore the integration of molecular diagnostics, which have improved the sensitivity and specificity of TB detection.

Future directions in TB diagnostics involve the development of rapid, accurate, and cost-effective point-of-care diagnostics. This includes the exploration of novel biomarkers for non-sputum-based tests and the application of artificial intelligence in radiological imaging to enhance diagnostic accuracy. These are crucial for populations unable to produce sputum, such as children and severely ill patients.

This Special Issue also aims to focus on the challenges faced in resource-limited settings and the need for diagnostics that can address drug-resistant TB strains. The potential of multiomics approaches and the discovery of theranostic markers for personalized treatment regimens will also be explored, thereby emphasising the importance of aligning diagnostic advancements with shorter TB drug regimens and improving healthcare delivery systems to ensure the uptake of new technologies.

Contributions to this Special Issue should aim to provide a platform for discussing the current state and future prospects of TB diagnostics. By highlighting innovative approaches and addressing existing challenges, we seek to aid in the global effort to combat TB effectively. The ultimate goal is to ensure that diagnostic advancements are accessible and applicable across diverse healthcare settings, thereby improving TB management and outcomes worldwide.

Dr. Philippa J. Randall
Guest Editor

Manuscript Submission Information

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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. Tropical Medicine and Infectious Disease is an international peer-reviewed open access monthly 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 2700 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
  • diagnostics
  • drug-resistant tuberculosis
  • point-of-care
  • novel biomarkers
  • multiomics approaches

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Related Special Issue

Published Papers (6 papers)

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Research

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10 pages, 1518 KB  
Article
Implementation of Open PCR System for the Detection of TB/DR-TB and NTM in Sputum Samples from Suspected Pulmonary Tuberculosis Patients in Medan, Indonesia
by R Lia Kusumawati, Mirzan Hasibuan, Nisrina Tari, Gema Nazri Yanni, Laura Isa Ginting, Cynthia Gozali and Tryna Tania
Trop. Med. Infect. Dis. 2026, 11(6), 168; https://doi.org/10.3390/tropicalmed11060168 - 18 Jun 2026
Viewed by 797
Abstract
(1) Background: Indonesia faces the dual challenge of a high tuberculosis (TB) burden and increasing drug resistance. Conventional molecular diagnostics frequently fail to detect isoniazid resistance and nontuberculous mycobacteria (NTM). This study evaluates a domestic multiplex Open PCR system in Medan, Indonesia. (2) [...] Read more.
(1) Background: Indonesia faces the dual challenge of a high tuberculosis (TB) burden and increasing drug resistance. Conventional molecular diagnostics frequently fail to detect isoniazid resistance and nontuberculous mycobacteria (NTM). This study evaluates a domestic multiplex Open PCR system in Medan, Indonesia. (2) Methods: From July to November 2025, 1569 sputum specimens from suspected TB patients were analysed using the Indigen MTB/NTM/DR-TB Real-time PCR Kit Gen 2. (3) Results: Mycobacterial DNA was detected in 421 specimens (26.8%). Among these, 396 (94.1%) were drug-susceptible TB, while 16 (3.8%) showed resistance, predominantly INH mono-resistance (n = 14; 0.89% of total). Additionally, 9 cases (2.1%) involved NTM or TB-NTM co-infections. Tertiary hospitals showed significantly higher positivity rates (33.5%) than primary care (18.9%; p < 0.001). TB status was significantly associated with male (p = 0.0052) and older age (p = 0.006), whereas resistance profiles and NTM distribution were consistent across all demographic groups (p > 0.80). (4) Conclusions: This study describes the implementation and diagnostic yield of a domestic multiplex Open PCR system in Medan, Indonesia. By bridging diagnostic gaps across a decentralized referral network, this facilitates rapid and targeted therapy. Integrating multiplex domestic innovations into national diagnostic algorithms is essential for achieving Indonesia’s TB elimination targets. Full article
(This article belongs to the Special Issue Tuberculosis Diagnosis: Current, Ongoing and Future Approaches)
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13 pages, 282 KB  
Article
Rural Residence and One-Person Households Are Associated with Diagnostic Delay in Pulmonary Tuberculosis in a Low-Incidence European Setting
by Tatjana Munko, Vesna Vukičević Lazarević, Jelena Barišić, Marina Perković and Tanja Vignjević
Trop. Med. Infect. Dis. 2026, 11(5), 120; https://doi.org/10.3390/tropicalmed11050120 - 4 May 2026
Viewed by 562
Abstract
Objectives: Diagnostic delay in pulmonary tuberculosis remains a significant barrier to effective disease control, even in low-incidence settings. This study aimed to identify factors associated with total delay and its components among adults with pulmonary tuberculosis in such a setting. Patients and methods: [...] Read more.
Objectives: Diagnostic delay in pulmonary tuberculosis remains a significant barrier to effective disease control, even in low-incidence settings. This study aimed to identify factors associated with total delay and its components among adults with pulmonary tuberculosis in such a setting. Patients and methods: A retrospective observational study was conducted on adults with pulmonary tuberculosis treated at a tuberculosis care centre in Croatia. Total delay was defined as the interval between symptom onset and treatment initiation. Data were collected through structured patient interviews using a standardized questionnaire, medical record review, and routine tuberculosis notification forms from the national public health registry. Sociodemographic and clinical predictors were evaluated using multivariable linear and logistic regression analyses. Results: Among 116 participants, the median total delay was 85 days (interquartile range 48.5–155.3). Rural residence was the strongest independent predictor, with patients experiencing an 88% longer delay than urban residents (p = 0.006). Individuals living in one-person households had a 49% longer delay (p = 0.047). Absence of chest pain was associated with shorter delay (−38%, p = 0.032) and lower odds of extreme delay (odds ratio 0.39, p = 0.047). Retired status independently predicted prolonged health system delay (42.1 days longer) and treatment delay (3.4 days longer). Conclusion: Prolonged delay may become increasingly important in the context of population ageing and changing household structures. Targeted strategies focused on rural, retired, and people living in one-person households may improve the timeliness of tuberculosis detection in settings where declining incidence can reduce clinical suspicion. Full article
(This article belongs to the Special Issue Tuberculosis Diagnosis: Current, Ongoing and Future Approaches)
12 pages, 1194 KB  
Article
Strengthening the National Reference Laboratory in the Republic of Congo: An Investment Imperative for Tuberculosis Diagnostics
by Darrel Ornelle Elion Assiana, Franck Hardain Okemba-Okombi, Salomon Tchuandom Bonsi, Freisnel Hermeland Mouzinga, Juliet E. Bryant, Jean Akiana, Tanou Joseph Kalivogui, Alain Disu Kamalandua, Nuccia Saleri, Lionel Caruana, Hugues Traoré Asken and Dissou Affolabi
Trop. Med. Infect. Dis. 2026, 11(1), 23; https://doi.org/10.3390/tropicalmed11010023 - 13 Jan 2026
Cited by 3 | Viewed by 1493
Abstract
National Tuberculosis Reference Laboratories (NTRLs) are central to tuberculosis (TB) control programs. Between 2018 and 2024, the Republic of Congo, a country of 6 million inhabitants, achieved a transformative strengthening of its TB diagnostic system, coordinated by the NTRL. Strategic investments, supported mainly [...] Read more.
National Tuberculosis Reference Laboratories (NTRLs) are central to tuberculosis (TB) control programs. Between 2018 and 2024, the Republic of Congo, a country of 6 million inhabitants, achieved a transformative strengthening of its TB diagnostic system, coordinated by the NTRL. Strategic investments, supported mainly by international partners, enabled a substantial decentralization of services, expanding the diagnostic network from 38 to 113 diagnostic and testing centers and increasing GeneXpert sites from 3 to 31. The expansion of the diagnostic network and specimen referral system was associated with a reduced structural gap in diagnostic coverage by extending access to GeneXpert testing to a larger number of peripheral and previously underserved centers. Critically, the establishment of a BSL-3 laboratory and the deployment of advanced assays like Xpert MTB/XDR ended the reliance on overseas testing by introducing in-country capacity for multidrug-resistant and pre-extensively drug-resistant TB detection. These systemic improvements were associated with significant positive outcomes, including an annual molecular testing surging from 11,609 in 2022 to over 27,000 in 2024 and bacteriological confirmation rates rising from 34 to 73%. This comprehensive laboratory systems strengthening, which also facilitated cross-programmatic initiatives like HIV and Mpox testing integration, underscores how sustained investment in infrastructure, logistics, and quality management is fundamental to improving case detection, surveillance, and progress toward the WHO End TB Strategy milestones. Full article
(This article belongs to the Special Issue Tuberculosis Diagnosis: Current, Ongoing and Future Approaches)
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11 pages, 353 KB  
Article
Comparison of Interferon-Gamma Release Assay and Tuberculin Skin Test in Screening for Latent Tuberculous Infection Among Students from High-Burden Areas: A Prospective Head-to-Head Study in Qingdao, China
by Zhongdong Wang, Kun Zhang, Haiyan Sun, Xuekui Li, Song Song, Meng Chen, Honghong Xu, Huaqiang Zhang, Yu Pang and Xiaoqi Dai
Trop. Med. Infect. Dis. 2025, 10(11), 311; https://doi.org/10.3390/tropicalmed10110311 - 31 Oct 2025
Viewed by 1993
Abstract
Background: Identifying latent tuberculosis infection (LTBI) is critical for pediatric TB control in China, especially among students from high-burden areas. With no gold-standard test, we compared the tuberculin skin test (TST) and interferon-gamma release assay (IGRA), focusing on factors related to test discordance. [...] Read more.
Background: Identifying latent tuberculosis infection (LTBI) is critical for pediatric TB control in China, especially among students from high-burden areas. With no gold-standard test, we compared the tuberculin skin test (TST) and interferon-gamma release assay (IGRA), focusing on factors related to test discordance. Materials and Methods: TST was administered to 1047 local and 900 migrant students; all migrants also received IGRA. TST cutoffs of 5 mm and 10 mm were applied. Agreement was measured using Cohen’s Kappa, and determinants of discordance were analyzed with binary logistic regression. Results: Migrant students had higher TST positivity than locals (28.89% vs. 19.67%, p < 0.001). The agreement between IGRA and TST-12 mm (k = 0.491) was higher than that observed for TST-10 mm (k = 0.466) and TST-5 mm (k = 0.356). Subgroup analyses across sex, residence, ethnicity, BMI, TB contact, and BCG history confirmed superior consistency for TST-12 mm. Individuals without BCG vaccination were less likely to show discordance between IGRA and TST-12 mm (OR = 0.32, 95% CI: 0.10–0.81). Conclusions: Using a 12 mm cutoff improves TST accuracy for students from high-burden areas. IGRA should be preferred for individuals with BCG vaccination history. Full article
(This article belongs to the Special Issue Tuberculosis Diagnosis: Current, Ongoing and Future Approaches)
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11 pages, 1111 KB  
Article
A High Burden of Infectious Tuberculosis Cases Among Older Children and Young Adolescents of the Female Gender in Ethiopia
by Zewdu Dememew, Atakilt Deribew, Amtatachew Zegeye, Taye Janfa, Teshager Kegne, Yohannes Alemayehu, Asfawosen Gebreyohannes, Sidhartha Deka, Pedro Suarez, Daniel Datiko and Dan Schwarz
Trop. Med. Infect. Dis. 2025, 10(3), 79; https://doi.org/10.3390/tropicalmed10030079 - 17 Mar 2025
Cited by 4 | Viewed by 3291
Abstract
The study was conducted in all regions of Ethiopia, except Tigray. It describes types of Tuberculosis (TB) based on gender, age, region, HIV status, and geographic setting in Ethiopia. It is a cross-sectional study that utilized the Ministry of Health’s District Health Information [...] Read more.
The study was conducted in all regions of Ethiopia, except Tigray. It describes types of Tuberculosis (TB) based on gender, age, region, HIV status, and geographic setting in Ethiopia. It is a cross-sectional study that utilized the Ministry of Health’s District Health Information System-based reporting to analyze all types of TB from July 2022 to March 2024. In total, 290,450 TB cases were detected: 42.6% (123,871) were female, 9.4% (27,160) were children (under 15 years of age), and 14.5% (42,228) were adolescents (10–19 years of age). About 48% (20,185) of adolescent TB cases were bacteriologically confirmed, of which 47.5% were females. Compared to children <5 years, the male-to-female ratio is 26% higher among older children (5–9 years of age) (Adjusted Odds Ratio (AOR): 1.26, 95% Confidence Interval (CI): 0.51–2.01)) and 53% higher among adolescents (AOR: 1.53, 95% CI 0.87–2.18). In short, about half of TB cases are infectious among older children and young adolescents of the female gender in Ethiopia. TB among these age categories may be addressed through the integration of TB services with reproductive health services and youth-friendly and pediatric clinics. Full article
(This article belongs to the Special Issue Tuberculosis Diagnosis: Current, Ongoing and Future Approaches)
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Review

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31 pages, 2163 KB  
Review
Current and Emerging Diagnostic Approaches for Tuberculosis in People Living with HIV: Challenges and Future Perspectives
by Guillermo Eduardo Cuéllar-Nevárez, José Rafael Linares Morales, Luis Arturo Camacho Silvas, Sandra Guadalupe Chavarría Hidalgo, Guadalupe Virginia Nevárez-Moorillón and Karla Elva Loza Solano
Trop. Med. Infect. Dis. 2026, 11(8), 213; https://doi.org/10.3390/tropicalmed11080213 - 28 Jul 2026
Viewed by 478
Abstract
Tuberculosis (TB) remains a leading cause of morbidity and mortality among people living with human immunodeficiency virus (HIV), in whom immunosuppression often results in atypical clinical manifestations, paucibacillary disease, extrapulmonary involvement, and disseminated forms that complicate timely diagnosis. This narrative review summarizes current [...] Read more.
Tuberculosis (TB) remains a leading cause of morbidity and mortality among people living with human immunodeficiency virus (HIV), in whom immunosuppression often results in atypical clinical manifestations, paucibacillary disease, extrapulmonary involvement, and disseminated forms that complicate timely diagnosis. This narrative review summarizes current and emerging diagnostic approaches for TB-HIV, with emphasis on their diagnostic performance, clinical applicability, implementation challenges, and potential integration into future algorithms. Conventional methods, including sputum smear microscopy, mycobacterial culture, and chest radiography, remain relevant but have important limitations in people living with HIV (PLHIV), particularly in advanced immunosuppression. Rapid molecular tests, especially Xpert MTB/RIF and Xpert MTB/RIF Ultra, have improved early detection of Mycobacterium tuberculosis and rifampicin resistance, although diagnostic gaps persist in sputum-scarce and extrapulmonary disease. Non-sputum-based tests, particularly WHO-recommended urine LF-LAM and emerging next-generation assays such as FujiLAM II, offer important opportunities for severely ill patients and those with advanced HIV disease. Host-derived biomarkers, transcriptomic signatures, and artificial intelligence-assisted chest imaging may further strengthen screening, triage, and diagnostic prioritization. Integrated, context-adapted diagnostic algorithms combining microbiological, molecular, urinary, imaging, and host-response tools are needed to improve early TB detection and reduce mortality in resource-limited settings. Full article
(This article belongs to the Special Issue Tuberculosis Diagnosis: Current, Ongoing and Future Approaches)
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