Open research questions in Tuberculosis Research and Epidemiology

What the literature leaves open

• The high cost of whole genome sequencing, - The need for a more efficient and cost-effective approach for identifying transmission clusters, - The challenge of distinguishing between recent and distant transmission events

  A rationalized molecular and genomic coupled strategy to get a snapshot of the tuberculosis transmission in Madrid · 2026 · DOI

• The study only applied to TB cases diagnosed in 2019 and 2021, - The observation period was limited to 6 months, - The study did not include a systematic population-based data

  A rationalized molecular and genomic coupled strategy to get a snapshot of the tuberculosis transmission in Madrid · 2026 · DOI

• The study did not fully elucidate the association between CD4+CD8+ double-positive T cells and TB susceptibility, - The study used a European-ancestry GWAS cohorts, - The study had a limited number of samples

  CD4+CD8+ double-positive T cells are associated with severity of tuberculosis · 2026 · DOI

• Further research is needed to understand the mechanisms underlying the progression from latent Mtb infection to active disease, - Investigation of the potential diagnostic and prognostic value of DP T cells in active TB, - Exploration of the causal relationships between immune phenotypes and TB via Mendelian randomization

  CD4+CD8+ double-positive T cells are associated with severity of tuberculosis · 2026 · DOI

• Further studies are needed to investigate the effectiveness of targeted interventions in improving MDR/RR-TB treatment outcomes in older adults, - Research should focus on identifying and addressing system-level barriers to MDR/RR-TB care, - Studies should explore the impact of demographic and clinical factors on MDR/RR-TB treatment outcomes

  Severe pre-treatment attrition in the care cascade: clinical outcomes and risk factors among older MDR/RR-TB patients in China · 2026 · DOI

• The lack of age-stratified analyses of the MDR/RR-TB care cascade. The need to quantify attrition across the care pathway for older patients. The need to identify key demographic, clinical, and system-level factors associated with disparities in treatment outcomes.

  Severe pre-treatment attrition in the care cascade: clinical outcomes and risk factors among older MDR/RR-TB patients in China · 2026 · DOI

• The study notes that underdiagnosis and underreporting remain relevant in Indonesia despite improvements in surveillance. The study identifies reverse causation or service allocation as a potential challenge in analyzing healthcare availability. The study notes that geographic differences in notification burden may partly reflect case detection capacity.

  Persistent and emerging tuberculosis notification burden across 514 districts and cities in Indonesia, 2021–2025: a nationwide spatiotemporal study for public health prioritisation · 2026 · DOI

• Notified TB counts are not equivalent to epidemiological incidence, - Underdiagnosis and underreporting remain relevant in Indonesia, - The ecological design supports population-level inference and cannot establish individual-level or causal effects, - Healthcare availability may be affected by reverse causation or service allocation

  Persistent and emerging tuberculosis notification burden across 514 districts and cities in Indonesia, 2021–2025: a nationwide spatiotemporal study for public health prioritisation · 2026 · DOI

• Further research is needed to understand the factors contributing to the high positivity rates in high-burden villages, - Studies should investigate the cost-effectiveness of IGRA testing in different burden settings, - Research should explore the use of village surveillance history and individual information to optimize testing yield

  Pre-screening village tuberculosis notification rates and the yield of interferon-gamma release assay testing in a rural health-examination campaign in Xinjiang, China · 2026 · DOI

• Less is known about how people receiving TB treatment experience the interconnected processes of internalised, family, and public/social stigma. The study aims to address this gap by exploring the stigma and stigmatization experienced by people with TB receiving treatment in two urban healthcare settings in Jakarta, Indonesia.

  TB Stigma and Stigmatization Experienced by People with Tuberculosis: A Qualitative Study in Jakarta, Indonesia · 2026 · DOI

• The study faces challenges in interpreting the findings due to the lack of a complete denominator of all presumptive TB patients in the hospital catchment area. The study faces challenges in generalizing the findings to the entire population of the Upper East Region. The study faces challenges in addressing the gaps in case detection and access to health services in the region.

  Annual trends in Mycobacterium tuberculosis detection and rifampicin resistance at a regional referral hospital in Northern Ghana, 2019–2024 · 2026 · DOI

• further studies are needed to understand the population-level TB incidence, - research on the factors associated with rifampicin resistance is necessary, - studies on the effectiveness of GeneXpert testing in different settings are required

  Annual trends in Mycobacterium tuberculosis detection and rifampicin resistance at a regional referral hospital in Northern Ghana, 2019–2024 · 2026 · DOI

• Implementation costs of mobile CXR screening interventions are variable and underreported. There is a need to evaluate the costs of implementing general-population mobile CXR screening in peri-urban Uganda.

  Resources to implement general population mobile chest x-ray screening for tuberculosis in Uganda: A trial-based costing analysis · 2026 · DOI

• Lack of systematic surveillance of M. orygis. Limited resources and funding for disease surveillance and control. Weak surveillance systems in animals and humans, particularly in developing and resource-limited countries.

  Mycobacterium orygis and its unseen impact: re-evaluating zoonotic tuberculosis in animal and human populations · 2025 · DOI

• Lack of systematic surveillance, - Limited information on the specific phenotypic and biochemical characteristics of M. orygis, - Inadequate funding leads to insufficient infrastructure and poor quality care

  Mycobacterium orygis and its unseen impact: re-evaluating zoonotic tuberculosis in animal and human populations · 2025 · DOI

• The study notes that drug-resistant TB, especially extensively drug-resistant TB, increased significantly between 1990 and 2021. The burden of TB is highest in low-SDI regions, particularly among children under 5. The study highlights the need for targeted public health interventions tailored to the unique epidemiological patterns of TB in children and adolescents.

  Global burden and trend of tuberculosis in children and adolescents (under 15 years old) from 1990 to 2021, with projections to 2040 · 2025 · DOI

• The burden of TB in children and adolescents under 15 is not well quantified. There is a lack of understanding of the trends and projections of TB in this age group. The study aims to address this gap by evaluating TB trends and projecting future trends.

  Global burden and trend of tuberculosis in children and adolescents (under 15 years old) from 1990 to 2021, with projections to 2040 · 2025 · DOI

• Further research is needed to explore the impact of the COVID-19 pandemic on DRTB epidemiology. Studies should analyze both MDRTB and EDRTB separately to better understand their trends and patterns. Research should incorporate predictive modeling using real-world surveillance data to anticipate future DRTB trends.

  Trends and forecast of drug-resistant tuberculosis: a global perspective from the GBD study 2021 · 2025 · DOI

• Previous studies have primarily examined multidrug-resistant tuberculosis and did not separately analyze extensively drug-resistant tuberculosis. There is a lack of predictive modeling using real-world surveillance data to anticipate future multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis trends. The impact of the COVID-19 pandemic on drug-resistant tuberculosis epidemiology has not been extensively explored.

  Trends and forecast of drug-resistant tuberculosis: a global perspective from the GBD study 2021 · 2025 · DOI

• heterogeneity of patient populations affected by DM-TB comorbidity, - challenges in translating biomarkers into clinical practice, - limited performance of biomarkers in certain populations such as smear-negative TB and HIV co-infected individuals

  Recent advances in biomarkers for diabetes mellitus and tuberculosis comorbidity: a comprehensive review · 2025 · DOI

• The paper identifies the need for early detection and effective management of diabetes mellitus and tuberculosis comorbidity. There is a gap in the understanding of biomarkers associated with DM-TB comorbidity, particularly in diverse populations.

  Recent advances in biomarkers for diabetes mellitus and tuberculosis comorbidity: a comprehensive review · 2025 · DOI

• Further studies are needed to establish prevention measures for the promotion of healthy lifestyles and TB management among household contacts, - Research on the effectiveness of tailored interventions in improving knowledge, attitude, and practice toward TB prevention and management is needed

  Knowledge, attitude, and practice toward tuberculosis prevention and management among household contacts in Suzhou Hospital, Jiangsu province, China · 2024 · DOI

• Yet the precise mode of action of its active form, pyrazinoic acid (POA), remains unclear.

  Pyrazinamide kills Mycobacterium tuberculosis via pH-driven weak-acid permeation and cytosolic acidification · 2026 · DOI

• While griselimycin is a promising antimycobacterial compound, its poorly understood structure-activity relationship has stalled derivatization.

  Molecular Determinants Governing the Antitubercular Activity of Griselimycin · 2026 · DOI

• However, the functional impact of most variable SSRs, particularly those within more complex repeat sequences than HT, remains unclear.

  Variation in multiple classes of simple sequence repeats can alter drug susceptibility in Mycobacterium tuberculosis · 2026 · DOI

Most-cited papers in Tuberculosis Research and Epidemiology

• Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence · Nature · 1998 · 6,528 citations
• Tuberculosis Associated with Infliximab, a Tumor Necrosis Factor α–Neutralizing Agent · New England Journal of Medicine · 2001 · 2,938 citations
• Global Burden of Tuberculosis · JAMA · 1999 · 2,064 citations
• Efficacy of BCG Vaccine in the Prevention of Tuberculosis · JAMA · 1994 · 2,059 citations
• The Growing Burden of Tuberculosis · Archives of Internal Medicine · 2003 · 1,788 citations
• Rapid Molecular Detection of Tuberculosis and Rifampin Resistance · New England Journal of Medicine · 2010 · 1,775 citations
• Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa · The Lancet · 2006 · 1,170 citations
• Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis · The Lancet · 1993 · 1,027 citations
• Drivers of tuberculosis epidemics: The role of risk factors and social determinants · Social Science & Medicine · 2009 · 814 citations
• Cigarette Smoking and Infection · Archives of Internal Medicine · 2004 · 788 citations

Most recent work

• Pulmonary Tuberculosis Detection with MiniDock MTB Using Swab Samples · New England Journal of Medicine · 2026
• Efficacy and safety of VPM1002 and Immuvac in preventing tuberculosis: phase 3 randomised clinical trial (PreVenTB trial) · BMJ · 2026
• Tuberculosis in older adults (≥ 65 years): Global trends, sex differences, and regional variations, 2000–2023 · BMC Geriatrics · 2026
• Pyrazinamide kills Mycobacterium tuberculosis via pH-driven weak-acid permeation and cytosolic acidification · bioRxiv · 2026
• Mycobacterium tuberculosis Genes Needed for Intra-alveolar Resuscitation After Airborne Transmission · bioRxiv · 2026
• Discovery and development of a new oxazolidinone with reduced toxicity for the treatment of tuberculosis · Nature Medicine · 2026
• Airway immune signatures of protection and disease progression in recent human tuberculosis household contacts · Nature Immunology · 2026
• Long-term risk of death after tuberculosis diagnosis and treatment · Nature Medicine · 2026
• High-throughput characterization of Mycobacterium tuberculosis gene function across diverse conditions · PLOS Biology · 2026
• Development of a Rapid Automated Point-of-Care Test for Mycobacterium tuberculosis Detection from Tongue Swabs and Sputum Specimens on the DASH(R) Rapid PCR System · medRxiv · 2026

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