Diagnostic Accuracy of Molecular Testing on Saliva and Oral Swabs for Pulmonary TB [TBN 073]

Who

Individuals aged ≥7 years undergoing microbiologic evaluation for possible TB disease in Cali, Colombia. Of 648 enrolled participants, 596 had final culture results; 95 had culture-confirmed TB. The nested case–control analysis included 190 matched participants with paired saliva and oral swab samples.

What

The study evaluated Xpert-Ultra testing on saliva versus oral swabs for detecting pulmonary TB. Saliva had higher sensitivity than oral swabs: 90.5% vs 71.6%; absolute difference 18.9%; P < .001. Specificity was high for both: 95.8% for saliva and 98.9% for swabs, with no statistically significant difference. Saliva also showed lower Ct values, suggesting greater Mtb DNA recovery.

When

Enrollment occurred from 31 July 2023 to 30 August 2024. Molecular testing occurred a median of 119 days after sample collection.

Where

Two public primary care centers serving the Central and Western Districts of Cali, Colombia.

Why

The study addressed the need for easier, more acceptable, non-sputum-based TB diagnostic samples, especially for people who cannot produce sputum or require induction.

How

Nested case–control study within a prospectively enrolled cohort. Culture-confirmed pulmonary TB cases were matched 1:1 to culture-negative controls by collection date, site, age group, and sex. Saliva and oral swabs were tested using Xpert-Ultra, with MGIT sputum culture as the pragmatic reference standard. Limitations include reliance on a single sputum culture and delayed index testing after sample collection.

Source: Vargas DA, Fuertes-Bucheli JF, Sanchez-Hidalgo A, Palomares Velosa J, Lasso AM, Gupta AJ, Martinez-Valencia AJ, Díaz G, Luna L, Alexander N, Ferro BE. Diagnostic Accuracy of Molecular Testing on Saliva and Oral Swabs for Pulmonary Tuberculosis. Clinical Infectious Diseases. 2026 Mar 12:ciag055. https://benangmerah.net/record/92/diagnostic-accuracy-of

Time-dependent association between cancer and risk of TB [TBN 072]

Who

Adults aged 30–90 years in Taiwan, including 457,673 newly diagnosed cancer patients and 3,738,122 matched noncancer individuals. Matching was based on sex, age, payroll bracket as socioeconomic surrogate, and calendar year.

What

Cancer diagnosis was associated with higher tuberculosis risk. During follow-up, TB incidence was 358 vs 244 per 100,000 person-years in cancer vs noncancer groups, with IRR 1.47 (95% CI 1.43–1.50; P < 0.0001). TB risk peaked around cancer diagnosis, especially within 1 year before and after diagnosis. In the peridiagnostic period, cancer remained independently associated with TB: adjusted HR 2.29 (95% CI 2.22–2.35), attenuated to HR 2.20 (95% CI 2.09–2.32) after two-stage calibration for smoking and alcohol use. Highest risks were seen in younger/middle-aged cancer patients, lung cancer, mesothelioma, esophageal cancer, and hematologic malignancies.

When

Data were retrieved from January 1, 2001 to December 31, 2015. The key “peridiagnostic period” was defined as 1 year before to 1 year after cancer diagnosis.

Where

Taiwan, using nationwide population-based databases: National Health Insurance Research Database and National Health Interview Survey.

Why

The study addressed whether cancer diagnosis is associated with time-dependent TB risk, including both prediagnostic and postdiagnostic TB risk, while accounting for measured and unmeasured confounding.

How

Retrospective population-based cohort study. Incident TB was defined by ICD-9-CM TB codes plus simultaneous prescriptions of at least two anti-TB drug categories. Analyses included incidence rate ratios, Cox proportional hazards models adjusted for comorbidities, and two-stage calibration using NHIS data to adjust for unmeasured smoking and alcohol use. Main limitation: residual confounding may remain despite calibration, and claims-based definitions depend on coding accuracy.

Strength of evidence

Observational cohort evidence; large nationwide sample and time-dependent analysis strengthen inference, but causality cannot be confirmed.

Source: Shen, B. J., & Lin, H. H. (2021). Time-dependent association between cancer and risk of tuberculosis: A population-based cohort study. International Journal of Infectious Diseases, 108, 340-346. https://benangmerah.net/record/86/time-dependent-association-between

Tuberculosis in Singapore

Yoseph Leonardo Samodra

(Jan 13, 2026)

Advancing Tuberculosis Detection Beyond Symptom- and Single-Test–Based Approaches

• Demonstrated that subclinical pulmonary TB constitutes a substantial proportion of culture-confirmed cases, with many patients lacking cough yet exhibiting radiographic abnormalities and high smear positivity, indicating overlooked transmission potential.
• Provided evidence that symptom-based screening alone is insufficient, particularly in older adults and immunocompromised populations, supporting the need for imaging- and molecular-enhanced screening strategies.
• Quantified limitations of existing diagnostic prediction models (moderate AUCs), highlighting gaps in current case-finding algorithms.
• Showed that CD8⁺ T-cell responses (QFT-Plus TB2–TB1) improve sensitivity for detecting active TB and recent infection, offering incremental diagnostic value beyond standard IGRA positivity.
• Identified biological markers that can help differentiate recent infection and active disease from remote latent TB, informing risk-stratified clinical decision-making.

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Optimizing Contact Investigation, Testing Windows, and Post-Exposure Follow-Up

• Established that over one-quarter of IGRA conversions occur after 10 weeks post-exposure, demonstrating that early repeat testing risks missing clinically relevant TB infection and early disease.
• Provided population-level evidence to support extending repeat QFT testing to ≥10 weeks in national TB contact investigation programs.
• Identified a measurable burden of active TB developing among IGRA-negative contacts, indicating residual risk despite negative screening results.
• Defined high-risk subgroups among IGRA-negative contacts (older age, diabetes, renal failure, smear-positive exposure, household or congregate settings) who warrant enhanced surveillance and prolonged follow-up (up to 24 months).
• Integrated immunological, clinical, and exposure data to inform risk-adapted contact management strategies rather than uniform testing protocols.

See also: Yoseph Samodra

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Informing Population-Level and Preventive TB Control Strategies

• Demonstrated strong dose–response and synergistic effects of multiple unhealthy lifestyle factors (smoking, underweight, inactivity, alcohol use, poor diet) on active TB risk in older adults.
• Showed that individuals with multiple lifestyle risk factors had markedly elevated TB risk (up to ninefold), particularly among those with diabetes, underscoring effect modification.
• Highlighted the importance of multisectoral, lifestyle-based TB prevention strategies alongside biomedical interventions in moderate-incidence settings.
• Provided evidence to support targeted TB preventive treatment (TPT) by combining exposure history, immunological markers, comorbidities, and lifestyle risk profiles.
• Contributed to policy-relevant evidence aligned with long-term TB elimination goals, emphasizing early detection, differentiated follow-up, and upstream risk reduction.

See also: Lin TB Lab

References:

1. Chew, Y.R., Tay, J.Y., Kyaw, W.M., Chia, P.Y. and Ng, D.H.L., 2025. Subclinical disease among people with culture-confirmed pulmonary tuberculosis in Singapore-a retrospective study. International Journal of Infectious Diseases, 153, p.107768.
2. Kyaw, W.M., Tay, J.Y., Lim, L.K.Y. and Ng, D.H.L., 2025. Time interval for QuantiFERON-TB Gold Plus conversion after last exposure with tuberculosis. ERJ Open Research, 11(3).
3. Tavitian-Exley, I., Kyaw, W.M., Kang-Yang, L.L., Foo, K., Boudville, I.C., Cutter, J.L. and Ng, D.H.L., 2024. Risk factors for tuberculosis among close IGRA-negative contacts of persons with infectious tuberculosis in Singapore. International Journal of Infectious Diseases, 147, p.107166.
4. Li, H., Chee, C.B., Geng, T., Pan, A. and Koh, W.P., 2022. Joint associations of multiple lifestyle factors with risk of active tuberculosis in the population: the Singapore Chinese Health Study. Clinical Infectious Diseases, 75(2), pp.213-220.
5. Chee, C.B.E., Kyi-Win, K., Tan, S. and Wang, Y.T., 2025. QuantiFERON-TB Gold Plus CD8+ T cell responses in contacts with tuberculosis disease and recent tuberculosis infection. Microbiology Spectrum, 13(12), pp.e01353-25.

TBN 006

Key Levers for Improving TB Detection, Adherence, and Prevention

(Yoseph Samodra)

Across diverse settings, the studies consistently show that tuberculosis outcomes are shaped by an interplay of socioeconomic conditions, patient-level behaviors, and clinical characteristics. Adherence and early detection improve when education, family support, and gender-sensitive approaches are prioritized, while poverty and socially patterned risk factors remain major drivers of disease burden.

See also: Lin TB Lab Taiwan

Patient-Level Determinants of Tuberculosis Risk and Treatment Adherence

• Medication adherence to anti-tuberculosis treatment was moderate (57.1%) and positively associated with modifiable social and behavioral factors, including education level, knowledge, attitude, employment status, and family support, indicating clear leverage points for adherence-improvement interventions.
• Gender emerged as a dominant determinant of adherence, underscoring the need for gender-sensitive counseling, follow-up, and support strategies within TB programs.
• Tuberculosis risk was strongly shaped by socioeconomic disadvantage, with household poverty showing a large independent association with TB occurrence and accounting for a substantial proportion of population-level TB burden.
• Personal risk factors—such as low education, undernutrition, smoking, alcohol excess, incarceration history, and low social capital—contributed independently to TB risk and largely followed social gradients, reinforcing the importance of addressing structural and behavioral vulnerabilities alongside biomedical care.

See also: Benang Merah Research Center

Diagnostic and Clinical Insights to Improve Case Detection and Monitoring

• Lower lung field (LLF) tuberculosis represented a clinically distinct phenotype, more common among women, individuals with higher BMI, sputum smear–negative disease, and specific Mycobacterium tuberculosis lineages, highlighting limitations of conventional sputum-based diagnostics.
• Patients with LLF TB demonstrated slower early clinical improvement despite generally favorable final outcomes, suggesting a need for enhanced diagnostic vigilance and closer early treatment monitoring to reduce missed or delayed diagnoses and potential ongoing transmission.
• Systematic symptom-based screening and use of sensitive molecular diagnostics among contacts and patients improved early identification of active TB, particularly in settings where smear negativity or atypical radiographic presentations are common.

Transmission Dynamics and Programmatic Strategies for TB Control

• Household contacts of TB patients, especially children and youth, showed measurable but heterogeneous risk of infection and disease, with evidence that youths contribute less to within-household transmission than adults, implying greater transmission risk outside the home.
• Active TB prevalence among contacts was substantially higher than in the general population, and symptom presence strongly predicted disease, supporting routine, structured contact investigation as a high-yield control strategy.
• Population-level modeling suggested that reducing poverty-related disparities could prevent a large proportion of TB cases, indicating that TB control efforts are likely to be most effective when biomedical interventions are integrated with social protection, education, and risk-factor reduction programs.

References:

1. Fitri, V.K., Zaman, C., Priyanto, A.D. and Ekawati, D., 2025. Analysis Factor of Compliance With Taking Anti-Pulmonary Tuberculosis Drugs in Patients With Pulmonary Tuberculosis. Lentera Perawat, 6(1), pp.59-68.
2. Saunders, M.J., Montoya, R., Quevedo, L., Ramos, E., Datta, S. and Evans, C.A., 2025. The social determinants of tuberculosis: a case-control study characterising pathways to equitable intervention in Peru. Infectious diseases of poverty, 14(1), p.53.
3. Tan, Q., Huang, C.C., Calderon, R., Lecca, L., Mendoza, M., Rocha, G.R., Tintaya, K., Tovar, X., Feng, J.Y., Pan, S.W. and Tseng, Y.H., 2025. Microbiological aspects and clinical impact of lower lung field tuberculosis: An observational cohort study in Peru. International Journal of Infectious Diseases, 150, p.107284.
4. Brooks, M.B., Lecca, L., Becerra, M.C., Calderon, R.I., Contreras, C.C., Jimenez, J., Yataco, R.M., Zhang, Z., Murray, M.B. and Huang, C.C., 2025. The Role of Youths in Within-Household Tuberculosis Transmission: A Household Contact Cohort Study. Clinical Infectious Diseases, p.ciaf490.
5. Njelita, I.A., Nwachukwu, C.C., Eyisi, I.G., Ezenyeaku, C.A. and Okeke, H.N., 2025. Prevalence and risk factors of active tuberculosis disease in contacts of tuberculosis cases treated in a teaching hospital in southeast Nigeria: a cross-sectional study. International Journal of Healthcare Sciences, 13(1), pp.80-89.

TBN 005

Beyond Drugs and Diagnosis

(Yoseph L. Samodra)

Age Matters

Key insights

• Older adults consistently experience worse TB-related outcomes: In Uganda, age >49 years was independently associated with lower TB treatment success, despite an overall high TSR (91.9%). In China, LTBI prevalence among adults ≥65 years reached 26.8%, confirming that older populations are a major silent reservoir of TB infection.
• Children represent the opposite diagnostic challenge: In Nigeria, stool-based Xpert testing contributed up to 17% of all bacteriologically confirmed childhood TB cases, particularly benefiting children aged 0–4 years who cannot expectorate sputum. In Indonesian orphanages, 28% of children had TB infection without active disease, underscoring prolonged exposure risks rather than clinical failure.

What is interesting

• The TB continuum looks fundamentally different by age: Elderly: high LTBI burden, comorbidities, and treatment vulnerability. Children: underdiagnosis driven by sample collection barriers rather than low disease burden.
• Advanced age alone should not exclude standard TB regimens: the Japanese cohort showed pyrazinamide did not increase mortality even in patients with a mean age ~80 years.

Applicable ideas

• Design age-stratified TB strategies: Routine LTBI screening for older adults in high-burden settings. Non-sputum diagnostics (stool Xpert) as standard of care for young children.
• Update clinician guidance to discourage age-based therapeutic conservatism when evidence does not support it (e.g., PZA avoidance).

See also: Benang Merah RC

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Social, Biological, and Environmental Risk Clusters Drive TB Vulnerability

Key insights

• Male sex repeatedly emerged as a risk factor: Lower TB treatment success in Uganda. Higher LTBI odds in elderly Chinese men. Higher childhood TB referrals and diagnoses among boys in Nigeria.
• HIV infection significantly reduced TB treatment success in Uganda, even in a region with relatively low HIV prevalence.
• Built environments strongly shape TB transmission: In Bali orphanages, poor ventilation and high indoor humidity were the strongest independent predictors of TB infection.
• Lifestyle and exposure factors matter: Former smoking and even regular exercise (likely proxying social exposure) were associated with LTBI among elderly adults in China.

What is interesting

• Risk is not driven by a single factor but by clusters: Biological (age, HIV), Social (sex, institutional living), Environmental (ventilation, humidity).
• Environmental determinants can outweigh individual clinical factors, especially in congregate settings (orphanages, elderly communities).

Applicable ideas

• Integrate environmental health interventions into TB control: Ventilation standards, humidity control, and room density guidelines for institutions.
• Treat men and people living with HIV as priority groups for adherence support and closer follow-up.
• Shift TB prevention thinking beyond healthcare delivery to housing, architecture, and infection control policy.

See also: Lin TB Lab

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Decentralization and Pragmatic Innovation Improve TB Detection and Outcomes

Key insights

• Decentralized, context-appropriate diagnostics dramatically improve yield: Stool-based Xpert testing in Nigeria enabled TB diagnosis at primary health facilities, where most children present. The AIMTB rapid assay in China showed >92% agreement with QFT-Plus, with strong diagnostic accuracy (AUC 0.95), offering a lower-cost LTBI screening option.
• Health system learning and adaptation matter: Nigeria’s success relied on guideline revisions, training, webinars, and continuous awareness, not just technology.
• Strong outcomes are achievable in rural, resource-limited settings: Uganda’s Teso region exceeded national TSR targets despite historical underperformance.

What is interesting

• Diagnostic innovation works best when it is: Simpler than the gold standard, Embedded into routine workflows, and Supported by policy and training, not pilots alone.
• Programmatic data, when analyzed rigorously (e.g., modified Poisson regression, propensity matching), can generate policy-relevant evidence at scale.

Applicable ideas

• Prioritize “good-enough” diagnostics that scale, rather than perfect but inaccessible tools.
• Pair decentralization with capacity building and guideline reform, not one-off rollouts.
• Use routinely collected program data to continuously refine TB strategies, especially for high-risk subgroups.

References:

1. Ssentongo, S.M., Oryokot, B., Opito, R., Ochieng, G., Sekiranda, P., Bakashaba, B. and Mugisha, K., 2025. Treatment success and associated factors among drug-susceptible tuberculosis patients in Teso region, Uganda: a retrospective study. Therapeutic Advances in Infectious Disease, 12, pp.1-12. See also: Dynamic TB Notes
2. Jiang, X., Feng, Y., Yu, Z., Chen, B., Wang, W., Jiang, G., Hu, L., Tong, W., Chen, Q., Zhang, M. and Zhu, Y., 2025. The latent tuberculosis infection survey using two interferon γ release assay tests among the elderly in a well-confined rural county in Eastern China. BMC geriatrics, 25(1), p.1035.
3. Nwokoye, N., Odume, B., Nwadike, P., Anaedobe, I., Mangoro, Z., Umoren, M., Ogbudebe, C., Chukwuogo, O., Useni, S., Nongo, D. and Eneogu, R., 2024. Impact of the stool-based Xpert test on childhood tuberculosis diagnosis in selected states in Nigeria. Tropical Medicine and Infectious Disease, 9(5), p.100.
4. Taniguchi, J., Jo, T., Aso, S., Matsui, H., Fushimi, K. and Yasunaga, H., 2024. Safety of pyrazinamide in elderly patients with tuberculosis in Japan: A nationwide cohort study. Respirology, 29(10), pp.905-913.
5. Clearesta, K.E., Mayangsari, A.S.M., Wati, D.K., Purniti, N.P.S., Suwarba, I.G.N.M. and Artana, I.W.D., 2024. Occurence and risk factors of tuberculosis infection in orphanage children in Bali. Paediatrica Indonesiana, 64(2), pp.152-9.

TBN 004