Multifactor Strategies for TB Prevention and Control

1. Nutritional Status and TB Risk Evidence from a large Chinese cohort shows that higher BMI is independently protective against TB, with each one-unit increase lowering incidence by nearly 8%. Overweight and obese individuals had the lowest TB risk, while underweight participants experienced the highest, though statistical significance was limited after adjustment. This protective association held across age and sex groups, reinforcing the role of nutritional status in TB susceptibility. The findings align with prior research linking malnutrition to greater TB risk and suggest that improving BMI may have contributed to China’s recent TB declines.

See also: Yoseph Samodra

Policy implications are clear: screening should target individuals with low BMI, particularly in high-burden settings. Nutritional interventions at the community level could serve as effective TB prevention strategies alongside conventional case detection and treatment programs. By integrating dietary support into TB control frameworks, public health efforts could address both malnutrition and infection risk in a single, cost-effective approach.

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2. Community-Based TB Detection and Treatment Uganda’s national TB campaigns in 2022 demonstrated the power of community-driven interventions. Within a year, coverage expanded from 76% to 100% of districts, diagnostic unit participation doubled, and reach scaled from 2.9% to 11.6% of the population. Case notification rates jumped by 24% in the first campaign and 59% in the second, aided by mobile diagnostics, preventive therapy for 23,000 high-risk contacts, and integration of leprosy screening. Strong governmental and partner support enabled rapid expansion and ensured operational sustainability.

These results highlight that community mobilization, when coupled with logistical innovations, can dramatically improve TB detection and treatment initiation. Sustaining funding, refining operational tools, and maintaining political commitment are essential to ensuring these gains translate into lasting reductions in TB burden, especially in remote and underserved areas.

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3. TB–Diabetes Interaction and Immune Dysfunction TB patients with diabetes mellitus (TB-DM) display a distinct biological profile—marked by elevated inflammatory proteins, atherogenic lipid patterns, and sustained immune activation even after two months of therapy. These abnormalities correlate with worse outcomes, including persistent sputum positivity, suggesting prolonged infection and elevated cardiovascular risk. Hyperglycemia exacerbates immune dysfunction by impairing macrophage oxidative and cytokine responses, downregulating critical receptors, and dampening pathogen clearance.

Managing TB-DM requires a tailored approach. Beyond standard TB therapy, clinicians should consider blood glucose control, anti-inflammatory agents, and lipid-lowering treatments such as statins. Biomarkers could help predict treatment response, enabling early intervention for high-risk patients. Viewing TB-DM as a distinct phenotype, rather than a coincidental comorbidity, may improve both infection control and long-term health outcomes.

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4. Environmental and Microbiome Factors in TB Control Research in high-density urban settings confirms that overcrowded housing and close contact with TB patients are significant risk factors for infection, independent of individual knowledge or demographics. Structural interventions—improving ventilation, reducing crowding, and enhancing contact tracing—are therefore essential for disrupting transmission in these environments.

The gut microbiome also plays a critical role in TB immunity, influencing T cell activity and treatment outcomes. Long-term use of anti-TB antibiotics can disrupt this microbial balance, potentially weakening host defenses and compounding risks in patients with structural lung damage from previous infections. Integrating microbiome preservation strategies, along with post-treatment lung health monitoring, could prevent reinfection, reduce opportunistic pathogens, and improve quality of life for TB survivors.

References:

1. Chen, J., Zha, S., Hou, J., Lu, K., Qiu, Y., Yang, R., Li, L., Yang, Y. and Xu, L., 2022. Dose–response relationship between body mass index and tuberculosis in China: a population-based cohort study. BMJ open, 12(3), p.e050928.
2. Turyahabwe, S., Bamuloba, M., Mugenyi, L., Amanya, G., Byaruhanga, R., Imoko, J.F., Nakawooya, M., Walusimbi, S., Nidoi, J., Burua, A. and Sekadde, M., 2024. Community tuberculosis screening, testing and care, Uganda. Bulletin of the World Health Organization, 102(6), p.400.
3. Brake, J., Ajie, M., Sumpter, N.A., Koesoemadinata, R.C., Soetedjo, N.N., Santoso, P., Alisjahbana, B., Ruslami, R., Hill, P. and van Crevel, R., 2025. Inflammation and dyslipidaemia in combined diabetes and tuberculosis; a cohort study. iScience, 28(6).
4. Sopiani, P., Maemun, S., Azijah, I., Pratiwi, T.Z. and Saputra, R., 2025. Analysis of Risk Factors for Pulmonary Tuberculosis in Cirascas District, East Jakarta, 2022. The Indonesian Journal of Infectious Diseases, 11(1), pp.42-51.
5. Chaubey, G.K., Modanwal, R., Dilawari, R., Talukdar, S., Dhiman, A., Chaudhary, S., Patidar, A., Raje, C.I. and Raje, M., 2024. Chronic hyperglycemia impairs anti-microbial function of macrophages in response to Mycobacterium tuberculosis infection. Immunologic Research, 72(4), pp.644-653.
6. Wu, Y., Wang, C. and Li, Y., 2025. Status and outlook of pulmonary tuberculosis coinfection. Journal of Research in Medical Sciences, 30(1), p.34.

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Diagnostic Advancements and Clinical Prognostic Indicators

1. Clinical Prognostic Indicators & Treatment Monitoring

• BMI recovery during M/XDR-TB treatment was a strong predictor of survival; nearly 70% of patients gained weight, and lack of weight gain (especially among underweight and normal BMI patients) was linked to a fivefold increase in mortality.
• Early weight change during treatment (3–6 months) emerged as a potential independent prognostic factor for survival.
• Highlights the importance of integrating BMI monitoring and nutritional interventions into TB programs.

See also: Hsien-Ho Lin TB Lab

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2. Diagnostic Advancements and Test Performance

• GeneXpert enabled rapid, accurate TB and rifampicin resistance detection within two hours, supporting early treatment.
• Second-generation IGRAs showed superior sensitivity (~90%) and fewer indeterminate results compared to traditional IGRAs, especially in smear-negative and extrapulmonary TB cases.
• Lower false negatives and improved performance across HIV and diabetes patients make these new IGRAs promising for routine use.

See also: Jago Beasiswa

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3. TB and Comorbidity Management (Diabetes Focus)

• Historical and current data affirm that diabetes significantly increases TB risk, especially with poor glycemic control.
• Dual burden (TB-DM) remains prevalent in high-incidence regions, necessitating integrated care approaches.
• Evidence also suggests bidirectional interaction, with TB potentially worsening glucose tolerance.

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4. Early Detection Strategies & Screening Value

• Two-way TB screening among DM patients using symptom checklists and imaging uncovered TB cases that might be missed in routine care.
• Even with a low confirmation rate, the study demonstrated operational feasibility and value of systematic screening in high-risk populations.
• Reinforces the need to combine symptoms, imaging, and sputum tests for robust case identification.

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5. Biomarker and Immunologic Insights

• A 16-gene transcriptomic signature (COR) was successfully validated for predicting TB progression in two African cohorts.
• The COR signature, regulated by type I and II interferons, suggests interferon activity as a preclinical marker for TB.
• Transition from RNA-seq to PCR-based platforms makes gene expression tools more accessible for broader screening and risk stratification.

References:

1. Chakhaia, T., Blumberg, H.M., Kempker, R.R., Luo, R., Dzidzikashvili, N., Chincharauli, M., Tukvadze, N., Avaliani, Z., Stauber, C. and Magee, M.J., 2025. Lack of weight gain and increased mortality during and after treatment among adults with drug-resistant tuberculosis: a retrospective cohort study in Georgia, 2009–2020. ERJ Open Research.
2. Hariyanto, S.W., Avidati, H., Ulfah, U., Nurlaily, A.N. and Tejaningrum, K.D., Tuberculosis Screening in Patients with Diabetes Mellitus at the Internal Medicine Clinic of UGM Academic Hospital: Descriptive Study. Academic Hospital Journal, 7(1), p.8.
3. Petruccioli, E., Scriba, T.J., Petrone, L., Hatherill, M., Cirillo, D.M., Joosten, S.A., Ottenhoff, T.H., Denkinger, C.M. and Goletti, D., 2016. Correlates of tuberculosis risk: predictive biomarkers for progression to active tuberculosis. European Respiratory Journal, 48(6), pp.1751-1763.
4. Wati, N., Mu’awanah, I.A.U. and Amalia, A.A., 2024. Pulmonary Tuberculosis Incidence Rate with Genexpert Examination Method at Mlati II Public Health Center, Sleman In 2020-2023. International Journal of Health, Economics, and Social Sciences, 6(4), pp.1124-1129.
5. Cadena, J., Rathinavelu, S., Lopez-Alvarenga, J.C. and Restrepo, B.I., 2019. The re-emerging association between tuberculosis and diabetes: lessons from past centuries. Tuberculosis, 116, pp.S89-S97.
6. Whitworth, H.S., Badhan, A., Boakye, A.A., Takwoingi, Y., Rees-Roberts, M., Partlett, C., Lambie, H., Innes, J., Cooke, G., Lipman, M. and Conlon, C., 2019. Clinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort study. The Lancet Infectious Diseases, 19(2), pp.193-202.

Yoseph Leonardo Samodra

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Interplay Between Gut Microbiota, Host Immunity, and Lung Pathology in TB Patients

Immunomodulation of the gut microbiota plays a critical role in the host anti-TB response, aiding in the prevention of TB infection, slowing latency progression, reducing disease severity, and lowering the incidence of drug resistance and coinfection. A positive correlation has been found between gut microbiota and peripheral CD4+ T cell count in TB patients. Many anti-TB regimens include broad-spectrum antibiotics like rifampicin and moxifloxacin, which are used at high intensity and for extended periods, potentially exerting selection pressure on gut flora. Anti-TB drugs have been shown to disrupt the gut microbiome and weaken host immunity to MTB. Studies in MDR-TB patients indicate that prolonged use of second-line drugs depletes intestinal flora.

Most TB patients have underlying conditions such as diabetes, chronic kidney disease, or immunosuppression. Notably, T2DM triples the risk of developing TB, and gut microbes may act as key mediators in the link between TB and T2DM. Cytokines such as IL-10, TNF‑α, IFNs I–III, TGF‑β, IL‑35, and regulatory T cells (T‑regs) all significantly influence host immune responses to MTB. Aging TB patients also exhibit reduced respiratory clearance and weakened lung immune defenses, predisposing them to respiratory infections.

Over two-thirds of TB patients experience lasting structural lung changes. Despite treatment, these changes are often irreversible. PTB patients frequently show damage to bronchial mucosa, pulmonary edema, proliferative lesions, and caseous necrosis—conditions conducive to pathogenic colonization. Lung fibrosis and cavitation, in particular, may promote active TB coinfection and further impair lung function. The rise in invasive procedures and structural lung damage has also led to increased fungal and opportunistic infections. Bronchodilation is believed to impair mucociliary clearance, contributing to pathogen retention in the bronchial tree.

Source:

1. Wu, Y., Wang, C. and Li, Y., 2025. Status and outlook of pulmonary tuberculosis coinfection. Journal of Research in Medical Sciences, 30(1), p.34.

Chronic hyperglycemia in response to Mycobacterium tuberculosis infection

An investigation explores the impact of chronic hyperglycemia on macrophage immune responses using a combination of cell culture and diabetic mouse models. The research specifically assesses how prolonged high glucose environments influence the innate defense capability of macrophages when challenged by Mycobacterium tuberculosis (Mtb) or inflammatory stimuli such as LPS.

Results reveal that although hyperglycemia alone increases baseline ROS production, it paradoxically dampens the macrophages' ability to elevate ROS levels in response to infection or inflammation. Moreover, the capacity to produce nitric oxide and other reactive nitrogen species is significantly reduced under hyperglycemic conditions. These findings suggest that chronic high glucose exposure may desensitize macrophages to vital immune triggers.

In addition to impaired oxidative responses, macrophages in a hyperglycemic state show a dysregulated cytokine profile. They produce lower levels of key pro-inflammatory cytokines like IL-1β and IL-6 and higher levels of the anti-inflammatory cytokine IL-10. This skewed cytokine response indicates a suppression of the classical inflammatory pathway, potentially facilitating immune evasion by pathogens.

Surface expression of important macrophage receptors such as TLR-4 and differentiation markers CD11b and CD11c is also significantly decreased, further limiting the immune competence of these cells. Together, these changes illustrate that chronic hyperglycemia undermines both the detection and destruction capacities of macrophages.

The study robustly concludes that sustained hyperglycemia alters the innate immune landscape by dampening macrophage responses to infection and inflammation. This may partly explain why individuals with poorly controlled diabetes are more susceptible to infections like tuberculosis.

References:

1. Chaubey, G.K., Modanwal, R., Dilawari, R., Talukdar, S., Dhiman, A., Chaudhary, S., Patidar, A., Raje, C.I. and Raje, M., 2024. Chronic hyperglycemia impairs anti-microbial function of macrophages in response to Mycobacterium tuberculosis infection. Immunologic Research, 72(4), pp.644-653.

Tuberculosis in Jakarta

A case-control study aimed to explore the role of housing conditions and interpersonal contact in the spread of pulmonary tuberculosis (TB) among adult patients at the Ciracas Primary Health Center. The researchers focused on key environmental risk factors, notably residential density and direct contact with TB patients, given their suspected influence on TB transmission in high-density urban settings.

The methodology was well-structured for the research question. By employing a case-control design, the study efficiently compared patients diagnosed with TB (cases) and those without TB (controls). The matching technique—both frequency and individual—helped control for major confounders such as age, sex, and contact history. Data collection combined clinical records and validated questionnaires to ensure both reliability and validity of findings.

Results confirmed that high housing density and previous contact with TB patients were strongly associated with TB infection. Interestingly, despite high levels of TB-related knowledge among TB patients, this did not correlate with a lower risk of infection. Similarly, sociodemographic traits, although descriptively different between groups, were not statistically associated with TB risk.

These findings underscore the importance of environmental and behavioral interventions in TB control. The fact that good knowledge alone does not prevent disease suggests that structural conditions—like crowded living spaces—play a more decisive role. When TB patients share small, poorly ventilated homes with others, the likelihood of airborne transmission rises significantly.

To reduce TB transmission, public health strategies must move beyond individual-level education and include structural reforms. These may include improving housing conditions, enhancing ventilation, and tracing and managing close contacts of TB patients more proactively. Addressing these key factors could help break the cycle of infection in high-density communities.

References:

1. Sopiani, P., Maemun, S., Azijah, I., Pratiwi, T.Z. and Saputra, R., 2025. Analysis of Risk Factors for Pulmonary Tuberculosis in Cirascas District, East Jakarta, 2022. The Indonesian Journal of Infectious Diseases, 11(1), pp.42-51.

Tuberculosis-diabetes comorbidities

A study offers crucial insight into how diabetes mellitus alters the immune and metabolic response in individuals with tuberculosis (TB). By comparing inflammatory and lipid profiles across individuals with TB, DM, and both (TB-DM), the researchers found that TB-DM presents a unique biological signature. This includes elevated inflammatory proteins not seen in TB or DM alone, and a pro-atherogenic lipid profile marked by high VLDL and ApoB.

Notably, the study demonstrates that while inflammation generally decreases after two months of TB treatment, certain inflammatory markers remain disproportionately high in TB-DM, suggesting sustained immune activation. These inflammatory profiles were also linked to worse TB outcomes, particularly continued sputum positivity, which suggests persistent infection and increased treatment failure risk.

Lipid metabolism was equally impacted. TB-DM patients exhibited lipid patterns more closely resembling diabetic individuals, but with distinct increases in risk-associated markers like ApoB. Even during treatment, lipid levels, especially LDLs and ApoB, rose more significantly in TB-DM, reinforcing cardiovascular risk concerns.

These findings underscore the need to view TB-DM as a distinct clinical phenotype, not merely a coexistence of two conditions. Therapeutic strategies may need to be adapted for this group, including consideration of statins or anti-inflammatory agents. The data also support the potential use of inflammatory and lipid biomarkers to predict treatment response and tailor interventions.

Importantly, the study provides one of the largest datasets to date in this domain, strengthening the reliability of the conclusions and providing a framework for future personalized approaches in TB-DM care.

Sources:

1. Brake, J., Ajie, M., Sumpter, N.A., Koesoemadinata, R.C., Soetedjo, N.N., Santoso, P., Alisjahbana, B., Ruslami, R., Hill, P. and van Crevel, R., 2025. Inflammation and dyslipidaemia in combined diabetes and tuberculosis; a cohort study. iScience, 28(6).

Economic Burden and Transmission Dynamics

Economic Burden and Cost-Effectiveness of TB Treatments

• The BPaL regimen for drug-resistant TB in the Philippines significantly reduces both direct and indirect patient costs compared to existing regimens.
• Economic evaluations (ACER and ICER) showed BPaL is cost-effective under GDP-based thresholds.
• BPaL also improves treatment success rates, highlighting economic and health benefits.
• Lower catastrophic health expenditures and reduced healthcare visits make BPaL advantageous for real-world implementation.
• The study recommends national TB programs transition toward routine BPaL adoption.

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Diabetes Costs and Integration with TB Care

• DM outpatient visits in the Philippines accounted for 3–13% of all visits; monthly drug costs per patient averaged USD 7.67.
• Costs varied by diagnostic test: RPG USD 1.67, FBS USD 2.99, OGTT USD 23.72.
• Staff time was the largest cost driver for non-lab services, while consumables dominated lab costs.
• The cost per DM case detected among TB patients was lowest using RPG plus FBS algorithms (USD 17.43).
• Findings highlight the need for planning integrated TB-DM services and understanding economic burdens.

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Transmission Dynamics and Risk Factors for TB

• In Lima, Peru, genomic sequencing of 2,500 TB cases identified over 1,400 direct transmission pairs.
• Higher transmission was linked to younger age, male gender, smoking, drinking, and incarceration.
• Cavitary disease and previous TB increased transmissibility.
• The study demonstrates the power of genomic tools in identifying high-risk groups for targeted interventions.
• Former prisoners and substance users should be prioritized in TB control efforts.

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Impact of Smoking Cessation on Household TB Transmission

• Recent smoking cessation among TB patients significantly reduced TB infection risk in child contacts.
• Children of recent quitters had infection rates similar to those of never-smokers.
• Risk ratios for infection were about half compared to contacts of active smokers.
• Results were consistent after adjusting for disease severity and restricting to younger children.
• The study underscores smoking cessation as an effective, rapid intervention to lower TB spread in households.

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TB and Diabetes Syndemic: Challenges and Opportunities

• Diabetes delays TB diagnosis, worsens disease severity (e.g., cavitary lesions), and increases mortality and relapse rates.
• Hyperglycemia—whether pre-existing or treatment-induced—predicts worse TB outcomes.
• M. tuberculosis infection can disrupt metabolism, contributing to insulin resistance.
• Certain diabetes medications (e.g., metformin) may improve TB immunopathology, while TB treatments can worsen glycemic control.
• Integrated care models with enhanced screening, tailored regimens, and glycemic monitoring are critical to improving outcomes in this syndemic.

See also: Lin TB Lab

References:

1. Yamanaka, T., Castro, M.C., Ferrer, J.P., Solon, J.A., Cox, S.E., Laurence, Y.V. and Vassall, A., 2024. Health system costs of providing outpatient care for diabetes in people with TB in the Philippines. IJTLD open, 1(3), pp.124-129.
2. Evans, D., Hirasen, K., Casalme, D.J., Gler, M.T., Gupta, A. and Juneja, S., 2024. Cost and cost-effectiveness of BPaL regimen used in drug-resistant TB treatment in the Philippines. IJTLD open, 1(6), pp.242-249.
3. Chu, A.L., Lecca, L.W., Calderón, R.I., Contreras, C.C., Yataco, R.M., Zhang, Z., Becerra, M.C., Murray, M.B. and Huang, C.C., 2021. Smoking cessation in tuberculosis patients and the risk of tuberculosis infection in child household contacts. Clinical Infectious Diseases, 73(8), pp.1500-1506.
4. Trevisi, L., Brooks, M.B., Becerra, M.C., Calderón, R.I., Contreras, C.C., Galea, J.T., Jimenez, J., Lecca, L., Yataco, R.M., Tovar, X. and Zhang, Z., 2024. Who transmits tuberculosis to whom: a cross-sectional analysis of a cohort study in Lima, Peru. American Journal of Respiratory and Critical Care Medicine, 210(2), pp.222-233.
5. Magodoro, I., Kotze, L., Stek, C.J., West, A., Le Roux, A., Sobratee, N., Taliep, A., Hamada, Y., Dave, J.A., Rangaka, M.X. and Parihar, S.P., 2025. Clinical, metabolic and immune interaction between tuberculosis and diabetes mellitus: implications and opportunities for therapies. Expert Opinion on Pharmacotherapy.
6. Pratiwi, R.D., Alisjahbana, B., Subronto, Y.W., Priyanta, S. and Suharna, S., 2025. Implementation of an information system for tuberculosis in healthcare facilities in Indonesia: evaluation of its effectiveness and challenges. Archives of Public Health, 83(1), pp.1-18.

Yoseph Samodra

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