Prevalence and treatment outcomes of LTBI among older patients with COPD in Taiwan

Who

• Population: Older adults (>60 years) with COPD diagnosed per GOLD 2023 criteria (FEV₁/FVC <70%).

• Sample: 920 eligible; 819 (89.0%) underwent LTBI screening.

  • IGRA-positive: 193 (23.6%); IGRA-indeterminate: 9 (1.1%).

  • TPT recipients: 150 IGRA-positive participants (77.7% of positives).

• Demographics: Mean age ~72 years; majority male (~85%).

• Key comorbidities: Hypertension (53.8%), hyperlipidemia (33.7%), asthma (33.1%).

• Risk behaviors: 24.3% current smokers; high cumulative smoking exposure among IGRA-positive individuals.

What

• Focus: Determining the prevalence and predictors of latent tuberculosis infection (LTBI) among older COPD patients and evaluating completion and safety of various LTBI treatment regimens.

• Main findings:

  • LTBI prevalence: 23.6% via IGRA.

  • Predictors of IGRA positivity: Greater smoking pack-years, longer COPD duration, current smoking, history of cerebrovascular accident, inhaled corticosteroid (ICS) use, and cumulative prednisolone dose >210 mg in 2 years.

  • Treatment completion: Overall TPT completion 82.0%; highest in 3HP (91.2%), lowest in 9H (50.0%).

  • Safety: Adverse drug reactions (ADRs)—especially systemic drug reactions (SDRs) and hepatotoxicity—were the leading cause of discontinuation. Ten patients experienced AECOPD during treatment; four deaths occurred (three respiratory, one cardiac and unrelated to LTBI therapy).

• Implications: Older COPD patients have substantial LTBI prevalence and multiple clinical predictors; shorter rifapentine- or rifampin-based regimens showed higher completion rates but notable SDR risk.

When

• Study period: January 2021 – February 2024.

Where

• Setting: Prospective multicenter study in Taiwan at:

  • Taichung Veterans General Hospital

  • Kaohsiung Medical University Hospital

  • National Taiwan University Hospital and affiliated centers.

Why

• Rationale: COPD patients are at high risk for reactivation TB, yet LTBI prevalence, predictors, and regimen-specific outcomes in this population are insufficiently defined. Understanding these factors is essential for optimizing LTBI strategies and supporting TB elimination efforts.

How

• Design: Prospective multicenter cohort.

• Screening: IGRA using QuantiFERON-Gold or Gold-Plus.

• Treatment: WHO-recommended LTBI regimens (1HP, 3HP, 3HR, 4R, 9H) chosen via shared decision-making and administered under directly observed preventive therapy (DOPT/eDOPT).

• Monitoring:

  • Baseline labs (CBC, liver/renal panel, hepatitis, HIV).

  • Daily or dose-based ADR monitoring; monthly or biweekly biochemical testing depending on regimen.

  • ADR causality assessed using Naranjo score; severity guided management.

• Analysis: Baseline comparisons and multivariate logistic regression to identify predictors of IGRA positivity; regimen-wise assessment of completion and ADRs.

Source: Huang, H.L., Cheng, M.H., Lee, M.R., Chien, J.Y., Lu, P.L., Sheu, C.C., Wang, J.Y., Chong, I.W., Yang, J.M. and Huang, W.C., 2025. Prevalence and treatment outcomes of latent tuberculosis infection among older patients with chronic obstructive pulmonary disease in an area with intermediate tuberculosis burden. Emerging Microbes & Infections, 14(1), p.2497302.

Recurrence of TB and associated risk factors among Non-HIV patients in Taiwan

Who

• Study population: 1,875 patients with active tuberculosis (TB) who completed anti-TB treatment at a referral medical center in Taiwan.

• Subgroups:

  • 1,514 (80.7%) with pulmonary TB.

  • 1,342 culture-confirmed pulmonary TB cases.

  • 361 (19.3%) with extrapulmonary TB.

• Demographics: Median age 67 years; 67% male; comorbidities included diabetes (21.2%), malignancy (14.4%), prior TB (11.1%); 34.3% smokers; 9% had cavitary disease; 35.5% sputum smear–positive.

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What

• Focus: Determine TB recurrence rate within 6 years after treatment and identify risk factors for recurrence; evaluate annual recurrence patterns from 2012–2019.

• Major findings:

  • Overall TB recurrence rate: 2.0% (434 per 100,000 person-years).

  • Recurrence highest in the second year post-treatment.

  • Recurrence declined in patients diagnosed after 2017.

  • Independent risk factors for recurrence:

    • BMI < 20 kg/m² (aHR ~4.4–5.0)

    • Prior TB history (aHR ~4.3–4.4)

    • 2-month sputum culture non-conversion (aHR ~3.4–4.4)

  • Recurrence risk increased with cumulative risk factors (10.8% with two; 28.6% with all three).

• Implications: Early culture conversion and nutritional status are key for risk stratification; past TB history strongly predicts recurrence; supports tailored follow-up intensity and resource allocation.

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When

• Diagnosis and inclusion period: January 1, 2012 – December 31, 2019.

• Follow-up duration: Up to 6 years post-treatment, with follow-up ending December 31, 2022.

• Median follow-up: 72 months.

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Where

• Conducted at a single referral medical center in Taiwan, a region with moderate TB burden.

• Data linked with the Taiwan CDC notification database.

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Why

• To identify clinical predictors of TB recurrence to enable risk-stratified and individualized TB management, determine who may need prolonged therapy or closer monitoring, and optimize public health resource deployment.

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How

• Study design: Single-center retrospective cohort.

• Eligibility: Bacteriologically confirmed or clinically diagnosed active TB; completed ≥6 months of guideline-based treatment; excluded those who died or were lost before treatment completion, or had HIV.

• Data collected: Demographics, comorbidities, radiologic findings, microbiology including drug resistance, treatment adherence, and sputum culture conversion at 1 and 2 months.

• Outcome definitions: TB recurrence per WHO criteria (relapse or reinfection).

• Statistical approach:

• Cox proportional hazards regression for risk factor identification.

• Kaplan–Meier survival curves.

• Death treated as a censoring event; recurrence rates expressed per person-years.

• Subgroup analyses for pulmonary and culture-confirmed pulmonary TB.

Source: Hsu, C.M., Wu, C.J., Chang, C.J., Pan, S.W., Tseng, Y.H., Huang, J.R., Su, W.J., Feng, J.Y. and Chen, Y.M., 2025. Recurrence of tuberculosis and associated risk factors among Non-HIV patients in Taiwan: A retrospective cohort study. Journal of Infection and Public Health, p.102912.

Determinants of Treatment Interruption Among Drug-Resistant Tuberculosis Patients in Medan

Who

• Participants: 104 bacteriologically confirmed DR-TB patients at H. Adam Malik General Hospital, Medan.

• Groups: 34 patients lost to follow-up and 70 who continued treatment.

• Demographics of loss-to-follow-up patients:

  • 65% aged 45–65

  • 55.9% male

  • 91.2% completed high school or equivalent

  • 58.8% employed

  • 70.6% married

What

• Study focus: Association between perceived social support and perceived quality of healthcare services with loss-to-follow-up among DR-TB patients.

• Key findings:

  • Low–moderate social support significantly predicts loss-to-follow-up (PR = 14.50; p < 0.001).

  • Patients perceiving only “adequate” healthcare provider support have nearly a six-fold higher risk of loss-to-follow-up compared with those perceiving full support (p < 0.001).

• Implications: Both social and healthcare support strongly influence treatment adherence and should be integrated into patient-centered TB management strategies in Indonesia.

When

• The study was conducted over seven months; patients included had initiated treatment between 2020 and 2024.

Where

• H. Adam Malik Hospital, Medan, Indonesia. 

Why

• To fill a gap in understanding how combined social support and healthcare service quality predict loss-to-follow-up among DR-TB patients—an area with limited evidence in Medan.

How

• Design: Observational study using purposive sampling.

• Inclusion criteria: Age ≥18 years, DR-TB default or treatment completion status, treatment initiation 2020–2024, and informed consent.

• Data collection: Medical record review plus a validated questionnaire covering demographics, treatment attitude, social support, and healthcare provider support.

• Instruments: Social support assessed using adapted versions of the MSPSS (Multidimensional Scale of Perceived Social Support) questionnaire (12 items, 3 subscales).

Source: Dalimunthe, A., Sinaga, B.Y.M., Siagian, P. and Amelia, R., 2025. Social Support and Healthcare Service Quality as Determinants of Treatment Interruption Among Drug-Resistant Tuberculosis Patients in Medan, Indonesia. Jurnal Impresi Indonesia, 4(11), pp.5176-5183.

LF-LAM TB Antigen vs Xpert MTB/RIF Diagnostic Accuracy in Underweight Suspected Pulmonary TB Patients

Who

• Participants: 52 suspected pulmonary TB patients who were HIV-negative and underweight (BMI <18.5 kg/m²).

• Demographics: 42 males and 10 females; age distribution included 1 (10–19 yrs), 20 (19–43 yrs), 17 (44–60 yrs), and 14 (>60 yrs).

• Sample selection: All were newly suspected pulmonary TB cases able to produce sputum.

• Exclusions: Patients with diabetes, hepatitis, chronic renal failure, malignancy, or HIV.

• Initial enrollment: 70 patients; 52 remained after criteria applied.

What

• Study focus: Evaluation of the LF-LAM TB-Ag urine assay versus Xpert MTB/RIF sputum assay for diagnosing pulmonary TB in underweight, HIV-negative individuals.

• Key findings:

  • LF-LAM TB-Ag sensitivity: 79.59%; specificity: 100% (using Xpert as reference).

  • Significant association between the two tests (chi-square P = 0.002).

  • LF-LAM positivity higher in severely underweight patients (80%) than mildly underweight (68.1%).

  • Xpert positivity similar across underweight categories (93.33% vs. 95.45%).

• Implication: LF-LAM TB-Ag is a potentially useful, simple screening tool for pulmonary TB in severely underweight, HIV-negative patients.

When

• Data collection period: January 2023 – June 2024.

Where

• Setting: Abdul Moeloek Hospital, Lampung Province, Indonesia.

• Location type: Inpatient wards.

Why

• Rationale: To determine whether the LF-LAM TB-Ag urine test—already known as a useful tool in severe TB or HIV-associated TB—can serve as a diagnostic alternative for pulmonary TB in non-HIV, underweight patients, a population at higher risk with limited validated screening tools.

How

• Study design: Observational diagnostic evaluation.

• Procedures:

  • LF-LAM TB-Ag test: Midstream morning urine, tested within 30–60 minutes, using the Alere Determine LAM TB-Ag kit.

  • Xpert MTB/RIF: Morning sputum mixed 2:1 with reagent, shaken 10–15 minutes, then analyzed via GeneXpert cartridge system.

• Analysis: Chi-square test comparing LF-LAM and Xpert results; subgroup analysis by severity of underweight status.

Source: Eksa, D.R., Hendarto, G.S., Sinaga, F.T., Dilangga, P., Herdato, M.J.D., Infianto, A., Ekawati, D., Gozali, A. and Ajipurnomo, A., 2025. Comparative Diagnostic Accuracy of LF-LAM TB Antigen and Xpert MTB/RIF in Pulmonary Tuberculosis among Underweight Patients. Jurnal Respirologi Indonesia, 45(4), pp.272-279.

Determinants of Tuberculosis Preventive Treatment Uptake Among Pediatric Household Contacts

Who

• Participants: 364 caregiver–child pairs who were household contacts of 114 bacteriologically confirmed pulmonary TB index cases.

• Children: Mean age 10 years 4 months (range 8 months–15 years 9 months), mostly normal or obese nutritional status.

• Caregivers: Mean age 36 years (range 16–72); 49.7% ≤35 years, 67.6% biological parents, 75% below regional minimum wage income, 61% with ≥high school education, 65.7% with good TB knowledge.

• Healthcare workers: 70 staff from 16 community health centers; all had good TPT knowledge and adequate facility/drug availability.

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What

• Study focus: Determining the rate of pediatric tuberculosis preventive therapy (TPT) administration among child household contacts in Palembang and identifying associated factors.

• Major findings:

  • Only 12 of 364 children (3.3%) received TPT.

  • Younger caregiver age (≤35 years) was significantly associated with higher likelihood of child TPT receipt (OR 11.7; aOR 12.0).

  • No significant associations were found for caregiver knowledge, education, economic status, caregiver role, or distance to health center.

  • Healthcare facility factors (knowledge, drug availability, worker profession) showed no variation and thus were not associated with TPT provision.

  • Knowledge gaps persisted: nearly half of caregivers (49.5%) answered incorrectly regarding the definition of TPT.

• Authors’ conclusion: Pediatric TPT uptake in Palembang was very low, and caregiver age was the only significant determinant of TPT administration.

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When

• Data collection: May–August 2024.

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Where

• Setting: Community health centers across Palembang, Indonesia; 16 centers involved, with highest participation from Kertapati and Sako sub-districts.

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Why

• Purpose: To determine the rate of TPT administration in children who were household contacts of pulmonary TB cases, in a context where TPT coverage was unknown and TB burden was high.

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How

• Study design: Observational study.

• Participants: Included children in household contact with bacteriologically confirmed TB cases registered for treatment; excluded children with TB/HIV, recent negative TST/IGRA, incomplete questionnaires, and parental/guardian refusal.

• Data collection: Caregiver questionnaires; healthcare worker surveys; facility assessments.

• Analysis: Bivariate and multivariate analyses of caregiver, child, household, and facility factors associated with TPT administration.

Source: Ridwan, I., Sofiah, F. and Rismarini, R., 2025. Rate of administration of tuberculosis preventive treatment to pediatric household contacts and influencing factors. Paediatrica Indonesiana, 65(5):422-430.

Respiratory isolation for tuberculosis

Tuberculosis has been recognized for thousands of years, and its story reflects the evolution of medicine itself. In the early Hippocratic corpus of the 5th–4th century BCE, chronic wasting lung diseases—likely including tuberculosis—were grouped under phthisis, meaning “to waste away.” The Hippocratic school believed the illness to be hereditary, a view shaped by its appearance among cohabitating family members. The idea of contagion surfaced in Classical Greece: Isocrates acknowledged possible transmission, while Aristotle noted that scrofulous disease in livestock could spread through “foul air.” Galen, writing in the second century BCE, leaned toward a contagious explanation and recommended treatments such as fresh air, milk, and sea voyages. Yet physicians in the Galenic tradition largely favored the miasma theory—the belief that disease arose from inhaling noxious vapors—so individuals with phthisis were not stigmatized during Greek and Roman times.

By the Middle Ages, scrofula had gained a new cultural identity. Known as the “king’s evil,” it was believed curable by the royal touch of English and French monarchs, and sufferers were sometimes treated like lepers. A shift in thinking emerged toward the end of the 18th century, when physicians encouraged patients with advanced disease to remain at home, emphasizing diet, gentle physical exercise, and fresh air rather than long, arduous journeys to coastal spas or dry climates.

The sanatorium era began in 1859, when Herman Brehmer opened the first tuberculosis sanatorium in Gobersdorf, in the Silesian Mountains. These institutions originated as therapeutic rather than public health responses. Mountain air was thought to have curative power, and Brehmer believed that TB patients had abnormally small hearts; he theorized that high-altitude air would strengthen the heart and improve health. The model spread internationally. In the United States, Edward Livingston Trudeau—himself diagnosed with tuberculosis in the early 1870s—opened the nation’s first sanatorium at Saranac Lake in 1884. The first patients were housed in the modest “Little Red” cottage, and Trudeau credited the restorative Adirondack climate with extending his life until 1915.

Even as sanatoria expanded, the scientific understanding of tuberculosis advanced dramatically. In the Islamic Golden Age, Avicenna (980–1037 CE) described phthisis as contagious and recommended isolating patients. During the Renaissance, Girolamo Fracastoro (1478–1553 CE) proposed an early germ-like theory, suggesting that diseases spread through tiny “seed-like” particles. But it was not until the 19th century that definitive evidence emerged. Inspired by Pasteur’s work, Jean Antoine Villemin demonstrated in the 1860s that tuberculosis was infectious, though he could not yet identify the organism responsible. The breakthrough came on 24 March 1882, when Robert Koch announced his discovery of the tubercle bacillus—Mycobacterium tuberculosis—and established its role through what would become known as Koch’s postulates. His work also confirmed that the disease spread directly between people via airborne droplets.

Diagnostic techniques improved quickly. Paul Ehrlich refined Koch’s staining methods, and later modifications by Ziehl and Neelsen produced the famous acid-fast stain still used in much of the world today to identify tuberculosis in sputum samples.

The mid-20th century brought the true revolution: effective antibiotic therapy. In 1941, Jörgen Lehmann, working with the Swedish firm Ferrosan, showed that para-aminosalicylate (PAS) inhibited tubercle bacteria and protected infected animals. That same year, Selman Waksman and Albert Schatz at Rutgers University isolated streptomycin from Streptomyces griseus, demonstrating its lifesaving potential in both animal models and humans. Sanatoria continued to operate into the 1960s—mainly to prevent relapse—but their importance waned rapidly with the arrival of powerful drug combinations. The discovery of isoniazid in 1952 allowed near-universal cures when given alongside streptomycin and PAS. Additional breakthroughs soon followed: rifampicin in the mid-1960s, and recognition of pyrazinamide’s sterilizing activity in the early 1970s, enabling the fully oral six-month regimen that remains the standard for treating drug-susceptible TB today.

To bridge the gap between clinical efficacy and real-world adherence, public health programs adopted directly observed therapy (DOT), in which patients take medications under supervision to ensure consistent, effective treatment. This approach, used worldwide, helps prevent relapse and reduces ongoing transmission in the community.

Source: Karakousis, P.C. and Mooney, G., 2025. Respiratory isolation for tuberculosis: a historical perspective. The Journal of Infectious Diseases, 231(1), pp.3-9.

Host Genetic Factors and Clinical Comorbidities Associated With TB Risk

Methods

• Conducted a hospital-based retrospective case–control study using data from the Taiwan Precision Medicine Initiative (TPMI) — a large-scale national genetic program led by Academia Sinica in collaboration with partner hospitals.

• Data were collected from 58,091 participants (June 2019–Dec 2021) at Taichung Veterans General Hospital (TCVGH), integrating genetic profiles with comprehensive electronic health records and medical claims.

• Genomic DNA was extracted using TIANGEN Biotech commercial kits, and DNA quality was confirmed via NanoDrop 2000 spectrophotometry.

• Genotyping performed with the Taiwan Biobank version 2 (TWBv2) Axiom Genome-Wide Array, covering ~714,000 markers enriched for clinically relevant variants (ClinVar, ACMG, GWAS Catalogue, HGMD).

• Participants:

  • TB group: 390 confirmed TB patients (after excluding non-confirmed or latent TB cases).

  • Control group: 3,909 non-TB individuals matched 1:10 by age and gender.

  • Mean age: ~70 years; 65.9% male.

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Key Findings

• Demographic & Clinical Characteristics

  • TB patients were more likely to smoke and had lower BMI than controls.

  • Common comorbidities in TB patients included COPD, bronchiectasis, diabetes, malignancy, autoimmune disease, and steroid use.

• TB Diagnosis Distribution

  • Among culture-positive cases (75.4%), 69.7% had pulmonary TB, 22.1% extra-pulmonary TB, and 8.2% had both.

• HLA Genetic Associations

  • Higher frequencies of HLA-DRB1*16:02 and HLA-DQB1*05:02 were found in TB patients.

  • HLA-DRB1*16:02 significantly associated with TB infection:

    • Adjusted OR = 1.48 (95% CI: 1.08–2.03; p = 0.014).

    • Remained an independent risk factor: OR = 1.47 (95% CI: 1.04–2.09; p = 0.030).

• Clinical Risk and Protective Factors

  • Risk factors:

    • Bronchiectasis (OR 2.76; p < 0.001)

    • Malignancy (OR 1.46; p = 0.002)

    • Diabetes (OR 1.30; p = 0.050)

    • Smoking (OR 1.42; p = 0.012)

    • Steroid use (OR 1.66; p < 0.001)

  • Protective factor:

    • Higher BMI (OR 0.87; p < 0.001)

• Gene–Environment Interaction

• Interaction analysis (adjusted for age, sex, BMI) revealed:

• No added TB risk from HLA-DRB1*16:02 among smokers.

• Significantly increased TB risk in non-smokers carrying HLA-DRB1*16:02 (OR 1.58; 95% CI: 1.02–2.46; p = 0.042).

Source: Lin, S.P., Chen, I.C., Lin, C.H., Hsiao, T.H., Liu, P.Y. and Chen, Y.M., 2025. Host Genetic Factors and Clinical Comorbidities Associated With Tuberculosis Risk. HLA, 106(3), p.e70384.