Variation of TB prevalence across diagnostic approaches and geographical areas of Indonesia (2021) N005

A study utilized data obtained from the Health Research and Development Agency of the Tuberculosis Unit, Indonesian Ministry of Health (HRDA-MoH). The dataset included diagnostic information gathered through sputum acid-fast bacilli (AFB) examination, sputum culture, sputum genetic testing, and chest X-ray assessments. 

The original dataset covered all 34 provinces of Indonesia, which were grouped into three major regions: Sumatra, Java-Bali, and other islands (primarily in the eastern part of the country with smaller populations). A stratified multi-stage cluster sampling method was applied during the primary data collection to ensure representative coverage. The inclusion criteria comprised individuals aged 15 years and older who had resided in the selected clusters for at least one month. Individuals living in institutional or temporary settings such as military barracks, dormitories, hospitals, diplomatic residences, and hotels were excluded.

In the field, all chest X-ray images collected were sent to a central reading team for evaluation by three independent radiologists who were blinded to the field screening results. The images were classified as normal, abnormal with TB or non-TB features, or other findings. TB-related abnormalities included infiltrates, nodules, consolidation, cavitary lesions, fibrosis, calcification, pleural effusion, and pleural thickening. The central readings were used to establish the case definition for TB, while field readings guided sputum sample collection. Out of 15,446 participants, 11,202 had abnormal X-ray results, and notably, 43.6% of participants with positive X-ray findings reported no symptoms such as persistent cough or hemoptysis.

Findings from the chest X-ray readings showed a TB prevalence of 725.2 per 100,000 population aged 15 years and older. The highest prevalence occurred among individuals aged 15–24 years, with 783.8 per 100,000 population. Males had a higher prevalence (200.8 per 100,000) compared to females (133.5 per 100,000). Regional analysis revealed that the “other regions” category had the highest prevalence (864 per 100,000), followed by Sumatra and Java-Bali. The rates were generally higher in rural areas. These results underscored the substantial burden of undiagnosed or asymptomatic TB cases detected through radiographic screening.

For the sputum AFB examination, TB diagnosis was determined by identifying acid-fast bacilli in unprocessed sputum samples using the Ziehl–Neelsen staining technique. The TB prevalence based on AFB results was 256.5 per 100,000 population. The rate increased with age, peaking among those aged 65 years and older (527.6 per 100,000), and was lowest among the 15–24-year age group (137.5 per 100,000). The prevalence was markedly higher in males (392.5 per 100,000) than in females (131.0 per 100,000). Urban areas and the Sumatra region showed the highest AFB-based TB prevalence, suggesting potential demographic and regional disparities in TB infection or detection.

The culture-based diagnostic results were derived from both spot and morning sputum samples using the Lowenstein–Jensen medium. Some contamination was noted, particularly in spot sputum samples. The prevalence of culture-positive TB was 545.0 per 100,000 population, while culture-negative TB prevalence reached 945.5 per 100,000. Consistent with other diagnostic results, prevalence was higher among males (607.9 per 100,000) than females (463.0 per 100,000) and higher in urban areas than rural ones. The “other islands” region showed the highest culture-positive TB rate at 2,129.8 per 100,000 population. TB prevalence increased with age, with the highest rate found among participants aged 65 years and older (678.9 per 100,000).

Sputum genetic testing was performed using the Xpert MTB/RIF assay, an automated nucleic acid amplification technique that detects Mycobacterium tuberculosis and rifampicin resistance. The analysis identified 213 MTB-positive samples, consisting of 184 rifampicin-susceptible, 19 rifampicin-resistant, and 10 indeterminate cases. The estimated TB prevalence based on this method was 894.9 per 100,000 population. Regional distribution showed the highest prevalence in the “other regions” (941.2 per 100,000), followed by Sumatra (875.0 per 100,000) and Java-Bali (838.7 per 100,000). The highest prevalence by age group was found among individuals aged 35–44 years (933.3 per 100,000). Slight differences were noted between males and females, with slightly higher rates in males and in urban populations.

Overall, this secondary data analysis concluded that the national TB prevalence among individuals aged 15 years and older was 759.1 per 100,000 population (95% CI: 589.7–960.8). TB prevalence increased steadily with age, reaching its highest level among individuals aged 65 years and older (1,581.7 per 100,000). Urban areas consistently demonstrated higher TB prevalence across all diagnostic methods compared to rural areas, and the Sumatra region recorded the highest regional rates. These findings highlight the persistent burden of tuberculosis in Indonesia and the need for comprehensive diagnostic strategies that combine clinical, radiological, and molecular methods to improve detection and control efforts nationwide.

Source: Noviyani, A., Nopsopon, T. and Pongpirul, K., 2021. Variation of tuberculosis prevalence across diagnostic approaches and geographical areas of Indonesia. PLoS One, 16(10), p.e0258809.

Diagnostic methods for tuberculosis and their applicability in Indonesia (2019) N004

Overview of Tuberculosis (TB) Diagnostic Methods

• Tuberculin Skin Test (TST):

  • The TST is a delayed-type hypersensitivity reaction used to detect TB infection.

  • Limitations: Includes cross-reactivity with other antigens, low sensitivity and specificity, and false-positive results—especially in individuals vaccinated with BCG.

  • Procedure: Involves intradermal injection of purified protein derivative (PPD).

  • Interpretation:

    • ≥5 mm induration: positive in immunocompromised patients.

    • ≥10 mm: positive in immunocompetent children and unvaccinated adults.

    • ≥15 mm: positive in vaccinated individuals.

  • Accuracy:

    • Sensitivity/Specificity:

      • Immunocompromised: 100% / 90.3%

      • Immunocompetent: 97.2% / 91.9%

      • Vaccinated: 86.1% / 94.2%

  • Cross-reactivity with BCG and environmental mycobacteria may yield up to 86.1% false positives in vaccinated persons.

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• Interferon-Gamma Release Assay (IGRA):

  • Measures the interferon-gamma (IFN-γ) response to TB-specific antigens such as ESAT-6, CFP-10, and TB7.7.

  • Uses ELISA (e.g., QuantiFERON®-TB Gold In-Tube) or ELISpot (e.g., T-SPOT®.TB™) techniques.

  • Advantages:

    • Higher specificity than TST.

    • Not affected by BCG vaccination.

    • Especially useful for diagnosing TB in immunocompromised and TB-HIV co-infected patients.

  • Clinical Utility: Preferred for screening latent TB in patients with inflammatory diseases or compromised immunity.

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• GeneXpert MTB/RIF Assay:

  • A cartridge-based nucleic acid amplification test (NAAT) using quantitative real-time PCR (qRT-PCR).

  • Detects M. tuberculosis DNA and rifampicin resistance within 2 hours.

  • Key Features:

    • Closed amplification system minimizes cross-contamination.

    • Detects mutations in the rpoB gene, responsible for ~96% of rifampicin resistance.

    • Identifies bacteria in both positive and negative smears.

    • Can process multiple specimen types (sputum, CSF, pleural fluid, etc.).

  • Limitations:

    • False positives: due to target amplification errors.

    • False negatives: due to poor sample quality, PCR inhibitors, or reagent issues.

    • Requires stable electricity, temperature below 30°C, and regular equipment calibration.

    • Uses Bacillus globigii spores as internal controls for quality assurance.

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Transmission Factors of Tuberculosis

• Infectivity and Disease Severity:

  • Determined by sputum smear results and chest X-rays.

• Contact History and Duration:

  • Prolonged and frequent exposure increases infection risk.

• Environmental Conditions:

  • Transmission is higher in enclosed, poorly ventilated spaces.

• Strain Virulence:

  • Some M. tuberculosis strains are more infectious; extrapulmonary strains tend to cause greater macrophage damage than pulmonary strains.

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Diagnostic Indicators and Methods

• Clinical and Radiological Findings:

  • Positive acid-fast bacillus (AFB) smear or abnormal chest X-ray supports TB infection.

  • Radiographic signs include hilar lymphadenopathy, consolidation, pleural effusion, miliary lesions, atelectasis, calcifications, and tuberculoma.

• Diagnostic Workflow:

  1. AFB staining (Ziehl-Neelsen, Kinyoun–Gabbet, or Auramine-Rhodamine).

     • Fast and inexpensive; sensitivity ≈70%.

     • Operator-dependent; negative results may require further culture testing.

  2. Culture method – the gold standard.

     • Specimens: sputum, urine, CSF, pleural fluid, pus, or tissue biopsy.

     • Detects smear-negative cases and allows drug susceptibility testing.

     • Solid media: Lowenstein–Jensen, Ogawa, Middlebrook 7H10/7H11.

     • Liquid media: MGIT™ 960, Bactec™ 9000MB.

     • Higher sensitivity (10–10² CFU/ml) but slow growth (up to 8 weeks).

     • Requires skilled personnel and proper biosafety infrastructure.

  3. Serological assay (TST/Mantoux) – identifies delayed-type hypersensitivity.

  4. IGRA – measures IFN-γ response to TB-specific antigens.

  5. NAAT (GeneXpert MTB/RIF) – rapid molecular detection of TB and resistance markers.

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Diagnostic Test Performance and Availability (Summary Table)

Test	Sensitivity (%)	Specificity (%)	Availability in Indonesia
NAAT-TB detection	85	97	Limited to some labs
NAAT (GeneXpert MTB/RIF)	>92	>99	Limited to tertiary hospitals
AFB microscopy	70	≥90	Widely available
Growth detection – Liquid	90	99	Referral hospitals / some labs
Growth detection – Solid	88	99	Referral hospitals / some labs
DNA probe/HPLC identification	99	100	Research labs only
First-line drug susceptibility (liquid)	≥97	≥97	Referral hospitals / some labs
Second-line drug susceptibility (liquid)	≥92	≥97	Referral hospitals / some labs
Second-line drug susceptibility (solid)	82–99	92–100	Referral hospitals / some labs

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Tuberculosis (TB) Diagnosis in Indonesia

• General Diagnostic Approach:

  • In Indonesia, TB diagnosis is established based on a combination of clinical assessment, laboratory findings, and supporting examinations.

  • The main laboratory tests include:

    • Direct microscopic examination of sputum smears for Acid-Fast Bacilli (AFB).

    • Culture tests, using either:

      • Solid media (Lowenstein–Jensen / LJ), or

      • Liquid media (Mycobacteria Growth Indicator Tube / MGIT™ system).

    • Rapid molecular tests, particularly the GeneXpert MTB/RIF assay, which detects M. tuberculosis and rifampicin resistance.

      • Note: This test is used for diagnosis, not for treatment monitoring.

  • Supporting examinations may include radiological imaging (chest X-ray) and histopathological analysis when extrapulmonary TB is suspected.

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National Diagnostic Workflow (Ministry of Health, Indonesia)

• The Indonesian Ministry of Health provides a standardized diagnostic algorithm for TB, emphasizing stepwise evaluation and case confirmation:

  • Step 1 – Clinical Evaluation:

    • Adult patients presenting with a productive cough lasting ≥2 weeks undergo a detailed clinical examination.

  • Step 2 – Sputum Microscopy:

    • Patients are instructed to submit three sputum samples for microscopic AFB examination.

    • If any one sample is positive, the diagnosis of TB is confirmed, and treatment is initiated.

  • Step 3 – Further Testing (if microscopy negative):

    • If microscopy results are negative but clinical suspicion remains high, the patient should be referred for:

      • Chest X-ray, and/or

      • Additional tests, such as a rapid molecular assay (GeneXpert MTB/RIF) or culture.

    • A suggestive chest X-ray may justify starting TB treatment even when smear results are negative.

  • Step 4 – Limited Access Situations:

    • In healthcare settings where referral or advanced diagnostics are not possible:

      • The patient may receive a trial of broad-spectrum antibiotics.

      • Re-evaluation is conducted after treatment:

        • If symptoms improve, TB is unlikely (non-TB diagnosis).

        • If symptoms persist, repeat clinical and sputum microscopic assessments are warranted.

  • Step 5 – Drug Susceptibility Testing (DST):

    • If M. tuberculosis is successfully cultured, DST should be performed to guide effective treatment and detect potential drug resistance.

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Challenges and National Response

• Despite the presence of structured diagnostic systems, many TB cases remain unreported in Indonesia.

• To address this, several strategic measures have been implemented:

  • Mandatory TB case notification for all health facilities, including public and private hospitals, to ensure comprehensive case reporting.

  • Strengthened collaboration between healthcare sectors to identify and record patients under TB treatment.

  • Integration of GeneXpert testing into the national TB prevalence survey, enhancing case detection accuracy.

    • Previously, the survey relied on:

      • Screening for cough ≥2 weeks, and

      • Diagnosis based solely on microscopy.

    • Since 2013–2014, improved methods have been adopted:

      • Screening includes both symptom assessment and X-ray findings.

      • Diagnosis incorporates smear microscopy, culture, and GeneXpert confirmation for smear-positive samples.

• As a result of active case finding and mandatory notification, TB detection rates have significantly improved nationwide since 2016.

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Source: Susilawati, T.N. and Larasati, R., 2019. A recent update of the diagnostic methods for tuberculosis and their applicability in Indonesia: a narrative review. Medical Journal of Indonesia, 28(3), pp.284-91.

Impact of the TB response in Taiwan N003

Taiwan’s demographic and public health infrastructure has been central to shaping its TB control efforts. The island has experienced rapid demographic transitions, with fertility rates dropping from 7 births per woman in 1951 to 1.09 in 2023, one of the lowest globally. By 2023, only 135,571 newborns were registered, marking the lowest in history, while 18% of the population was aged 65 years or older—a figure projected to reach 20% by 2025, classifying Taiwan as a super-aged society. Despite these demographic pressures, Taiwan has achieved substantial progress in TB control, reducing incidence from 73 per 100,000 in 2005 to 28 in 2023, with mortality dropping from 4.3 to 1.9 per 100,000 over the same period.

These achievements reflect long-standing investments and political commitment. The Taiwan CDC, established in 1999, integrated TB control under a centralized framework, with funding fully covered by the central government. The National TB Program (NTP) introduced milestone initiatives, including the “Ten-Year Halving Tuberculosis Plan” (2006–2015), followed by the “End TB by 2035 Project” (Phase I: 2016–2020; Phase II: 2021–2025), with preparations for Phase III underway. Mandatory case reporting under the Communicable Disease Control Act is strictly enforced, with penalties for physicians and institutions failing to report, while surveillance systems such as the Notifiable Infectious Disease Reporting System (NIDRS), Laboratory Automated Reporting System (LARS), and the National TB Management System ensure comprehensive monitoring and timely data integration.

Taiwan’s National Health Insurance (NHI) plays a crucial role by ensuring universal coverage for 99% of residents. Since 1997, the “No Reporting, No Reimbursement” policy has tied reimbursement of TB services to mandatory notification, incentivizing complete case reporting. Patients can access TB diagnosis and treatment through all hospitals and nearly 90% of private clinics contracted with NHI. To encourage timely diagnosis and treatment, copayments for TB and latent TB infection (LTBI) patients are fully reimbursed by Taiwan CDC, and care for uninsured individuals is also covered. This financial safety net has minimized both patient delays and health system delays in seeking TB care.

A comprehensive patient support structure strengthens these systems. Around 700 TB case managers under a Pay-for-Performance (P4P) scheme coordinate care between clinics and public health services, while 2,500 public health nurses at 374 centers provide education, monitor adherence, and conduct contact tracing. Since 2006, Taiwan has adopted a people-centered Directly Observed Therapy (DOT) program, with government-employed DOT workers assigned to each patient. This model has significantly reduced treatment interruption, loss to follow-up, and TB-specific mortality, maintaining recurrence rates below 1% since 2008. In 2015, Taiwan introduced electronic DOT (eDOT) to enhance accessibility and privacy, which gained renewed traction after the launch of eDOT 2.0 in late 2023.

Special attention has also been given to foreign-born populations, particularly migrant workers, who exceeded 700,000 in 2023 and now account for over 9% of TB cases. Health examinations are mandated shortly after arrival and at regular intervals. Previously, workers diagnosed with TB were repatriated, but regulatory changes since 2014 have allowed them to stay for treatment under DOT. Further amendments in 2015 and 2022 shifted the decision-making power to workers themselves, dramatically increasing the proportion remaining for treatment from 10.6% in 2014 to nearly 89% in 2022. These reforms have improved TB notification among foreign patients, raising timely reporting rates to over 96%.

To alleviate the economic burden of TB, Taiwan provides targeted financial support. The Taiwan Anti-Tuberculosis Association offers an annual grant of USD 31,000 to support low-income patients lacking social welfare resources. A 2018 National TB Patient Catastrophic Cost Survey revealed that 22% of non-MDR-TB and 45% of MDR-TB households experienced catastrophic costs, primarily due to income loss and non-medical expenses rather than direct medical fees. Low household income, stigma, and inpatient care were identified as key risk factors for financial hardship. Taiwan’s system of subsidies, reimbursement of copayments, and dedicated grants reflects its commitment to reducing financial barriers and ensuring equitable access to TB treatment.

Source: Chan, P.C., Chiang, C.Y., Lee, P.H., Lo, H.Y., Chu, P.W., Chen, J.J., Kato, S. and Raviglione, M.C.B., 2025. Assessing the impact of the TB response in Taiwan–the journey towards ending TB. IJTLD open, 2(5), pp.251-259.

Tuberculosis in Patients With Chronic Mental Illness N002

Patients with mental illness were found to have a significantly higher risk of developing tuberculosis (TB). To investigate this association, this study utilized the National Health Insurance Research Database (NHIRD), a nationally representative dataset in Taiwan, to assess TB incidence among patients with chronic psychiatric disorders—including schizophrenia, bipolar disorder, schizoaffective disorder, and major depressive disorder—compared to the general population. Patients diagnosed between 2002 and 2013 were identified through the Catastrophic Illness Registry, which ensures strict clinical verification and captures only severe and persistent mental illness cases. After excluding individuals with conditions such as type 1 diabetes, cirrhosis, cancer, dialysis, HIV, past TB, and amended diagnoses, a total of 162,377 subjects were included in the analysis. TB cases were defined using the Tuberculosis Database, which requires positive culture results, radiographic abnormalities, and diagnostic confirmation.

The study population consisted of 162,161 mental illness patients and 810,805 matched controls, with no significant baseline differences in sex, age, income, urbanization level, comorbidity index, or major comorbidities, confirming effective propensity score matching. Results showed consistently higher TB incidence in mental illness patients overall (87 vs. 71 per 100,000 person-years), across both sexes, and most age groups. The difference was particularly pronounced in those aged 65 years or older (278 vs. 195). TB incidence was also higher across nearly all income levels and urbanization strata, except for rural towns where rates were slightly lower in patients with mental illness. Importantly, the elevated TB incidence was observed regardless of the presence of type 2 diabetes mellitus or chronic kidney disease.

After adjusting for confounding variables, the conditional Cox proportional hazards model confirmed a 1.48-fold increased risk of TB among patients with mental illness (95% CI: 1.38–1.59). Additional risk factors included older age, which showed a steep increase in hazard ratios (HRs ranging from 1.86 for ages 20–34 to 21.82 for ≥65 relative to <20), and lower income, which was inversely associated with TB risk. Comorbidities such as type 2 diabetes (HR: 1.22) and chronic kidney disease (HR: 1.24) further heightened susceptibility. Cumulative incidence curves demonstrated a persistently higher rate of TB in the mental illness group compared with the general population, underscoring the need for targeted TB screening and preventive strategies for this vulnerable population.

Source: Hung, L.C., Kung, P.T., Tsai, T.H., Tsai, W.C. and Huang, K.H., 2025. Risk Assessment of Tuberculosis in Patients With Chronic Mental Illness and Related Factors: A Population‐Based Cohort Study in Taiwan. The Clinical Respiratory Journal, 19(6), p.e70088.