TB Risk Factors & Progression Risk

· TB Diagnostic Strategies & Cost-Effectiveness

• Varies based on HIV prevalence, drug resistance, and healthcare access.
• Discrete-event simulation (DES) helps assess MDR-TB diagnostics.
• DES tool enhances decision-making in resource-limited settings.
• Incorporating disease transmission models improves predictions.

· Novel TB Vaccines & Impact

• Delay beyond 2025 could reduce effectiveness.
• Adolescent/adult-targeted vaccines may prevent 44M cases & 5M deaths by 2050.
• Accelerated rollout could prevent 65.5M cases & 7.9M deaths.
• Greatest impact in Africa, South-East Asia, and low-income nations.
• High-efficacy, long-lasting vaccines could cut TB mortality by 27%.
• Urgency for policymakers to fast-track vaccine introduction.

· TB & Air Pollution (PM2.5 Exposure)

• PM2.5 linked to higher MDR-TB infection risk and lung damage.
• Different exposure durations impact radiographic severity.
• Smoking, indoor air pollution, and biomass fuel use increase TB risk.
• Air pollution’s TB impact may be underestimated due to socioeconomic factors.

· Household & Environmental Risk Factors

• Solid fuel use contributes to TB risk but evidence remains weak.
• Fine particles, nitrogen oxides, and CO exposure linked to TB.
• Tobacco taxes could fund TB control and clean energy programs.

· Latent TB Infection (LTBI) & Progression Risk

• WHO guidelines prioritize high-risk groups for screening & treatment.
• 11 key risk populations include HIV-positive individuals, healthcare workers, and prisoners.
• Preventive treatment is crucial in the absence of an effective TB vaccine.

· TB Risk Factors by Health Condition

• Corticosteroids: Highest risk when used 30 days before TB diagnosis.
• Diabetes: TB risk 2.33x higher.
• Glomerular Diseases: TB risk 23.36x higher.
• HCV Infection: Higher risk in untreated cases (HR 2.9).
• Cancer: Children with cancer have a 16.82x higher TB risk.
• Rheumatoid Arthritis & Psoriasis: Increased risk with corticosteroid use.
• Vitamin D Deficiency: 5.68x higher risk of progressing to active TB.

See also: Lin TB Lab

Feasible TB Intervention Suggestions

1. Expand Rapid Diagnostic Tools: Increase access to cost-effective and rapid TB diagnostic methods like GeneXpert in resource-limited settings. Implement discrete-event simulation (DES) models to optimize diagnostic strategies for MDR-TB.
2. Accelerate TB Vaccine Development & Rollout: Prioritize fast-track introduction of novel TB vaccines to prevent millions of cases and deaths. Focus on high-burden regions (Africa, South-East Asia) and at-risk populations (adolescents, adults).
3. Strengthen Air Pollution Control Policies: Enforce air quality regulations to reduce PM2.5 and other TB-aggravating pollutants. Promote clean energy solutions (e.g., LPG, electricity) over biomass fuel for cooking and heating.
4. Enhance LTBI Screening & Preventive Treatment: Implement systematic LTBI screening in high-risk groups (HIV-positive individuals, healthcare workers, prisoners). Expand access to preventive therapy (e.g., isoniazid, rifapentine) to reduce progression to active TB.
5. Integrate TB Control into Non-Communicable Disease (NCD) Programs: Strengthen TB screening in diabetes, cancer, and immunosuppressed patients, given their increased TB risk. Provide corticosteroid alternatives or monitor TB risk in patients requiring immunosuppressants.
6. Tax & Regulate Tobacco to Reduce TB Risk: Increase tobacco taxes to discourage smoking, a major TB risk factor. Use tax revenue to fund TB treatment and prevention programs in low-income communities.
7. Improve TB Awareness & Health Education: Conduct public health campaigns on TB transmission, symptoms, and prevention. Educate healthcare workers on early TB detection, drug-resistant TB, and infection control practices.

References:

1. Langley, I., Doulla, B., Lin, H.H., Millington, K. and Squire, B., 2012. Modelling the impacts of new diagnostic tools for tuberculosis in developing countries to enhance policy decisions. Health care management science, 15, pp.239-253.
2. Clark, R.A., Mukandavire, C., Portnoy, A., Weerasuriya, C.K., Deol, A., Scarponi, D., Iskauskas, A., Bakker, R., Quaife, M., Malhotra, S. and Gebreselassie, N., 2023. The impact of alternative delivery strategies for novel tuberculosis vaccines in low-income and middle-income countries: a modelling study. The Lancet Global Health, 11(4), pp.e546-e555.
3. Makrufardi, F., Chuang, H.C., Suk, C.W., Lin, Y.C., Rusmawatiningtyas, D., Murni, I.K., Arguni, E., Chung, K.F. and Bai, K.J., 2024. Particulate matter deposition and its impact on tuberculosis severity: A cross-sectional study in Taipei. Science of the Total Environment, 924, p.171534.
4. Lin, H.H., Suk, C.W., Lo, H.L., Huang, R.Y., Enarson, D.A. and Chiang, C.Y., 2014. Indoor air pollution from solid fuel and tuberculosis: a systematic review and meta-analysis. The International journal of tuberculosis and lung disease, 18(5), pp.613-621.
5. Lai, T.C., Chiang, C.Y., Wu, C.F., Yang, S.L., Liu, D.P., Chan, C.C. and Lin, H.H., 2016. Ambient air pollution and risk of tuberculosis: a cohort study. Occupational and environmental medicine, 73(1), pp.56-61.
6. Lin, H.H., Murray, M., Cohen, T., Colijn, C. and Ezzati, M., 2008. Effects of smoking and solid-fuel use on COPD, lung cancer, and tuberculosis in China: a time-based, multiple risk factor, modelling study. The Lancet, 372(9648), pp.1473-1483.
7. Bigio, J., Viscardi, A., Gore, G., Matteelli, A. and Sulis, G., 2023. A scoping review on the risk of tuberculosis in specific population groups: can we expand the World Health Organization recommendations?. European Respiratory Review, 32(167).

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Paradoxical Link Between Obesity and TB

1. BMI and Drug-Resistant TB

• Underweight individuals show higher susceptibility to isoniazid (INH)-resistant TB.
• Overweight and obese patients have an increased risk of MDR-TB.
• Comorbidities like diabetes and hypertension correlate with higher drug resistance.
• Suggestion: Implement BMI-based TB screening protocols to identify at-risk individuals early.

2. Paradoxical Link Between Obesity and TB

• Obesity is directly protective against TB despite its association with diabetes.
• Higher BMI reduces TB risk even in diabetic individuals.
• Socioeconomic factors may partially explain this protective effect.
• Suggestion: Investigate mechanisms behind obesity’s protective role to refine TB prevention strategies.

3. Gaps in the TB Care Cascade

• Delays in diagnosis and treatment worsen TB outcomes.
• Country-specific factors (e.g., HIV in Kenya, MDR-TB in Moldova) influence TB burden.
• Addressing care gaps can significantly reduce TB incidence and mortality.
• Suggestion: Strengthen TB care pathways with faster diagnosis and treatment initiation.

4. Economic and Healthcare Factors in TB Control

• Higher GDP and healthcare expenditure correlate with lower TB incidence.
• Cost-effective interventions improve access to TB care.
• Financial barriers hinder TB elimination efforts in lower-income settings.
• Suggestion: Increase TB funding through sustainable health financing models.

5. Strategies for TB Elimination

• Country-specific interventions (e.g., nutrition in India, latent TB treatment in China) are essential.
• Active Case Finding (ACF) is hindered by logistical, administrative, and social barriers.
• Integrating TB screening with other health programs enhances outreach.
• Suggestion: Streamline ACF processes with digital tools and better community incentives.

References:

1. Song, W.M., Guo, J., Xu, T.T., Li, S.J., Liu, J.Y., Tao, N.N., Liu, Y., Zhang, Q.Y., Liu, S.Q., An, Q.Q. and Li, Y.F., 2021. Association between body mass index and newly diagnosed drug-resistant pulmonary tuberculosis in Shandong, China from 2004 to 2019. BMC pulmonary medicine, 21, pp.1-14.
2. Lin, H.H., Wu, C.Y., Wang, C.H., Fu, H., Lönnroth, K., Chang, Y.C. and Huang, Y.T., 2018. Association of obesity, diabetes, and risk of tuberculosis: two population-based cohorts. Clinical Infectious Diseases, 66(5), pp.699-705.
3. Vesga, J.F., Hallett, T.B., Reid, M.J., Sachdeva, K.S., Rao, R., Khaparde, S., Dave, P., Rade, K., Kamene, M., Omesa, E. and Masini, E., 2019. Assessing tuberculosis control priorities in high-burden settings: a modelling approach. The Lancet Global Health, 7(5), pp.e585-e595.
4. Menzies, N.A., Gomez, G.B., Bozzani, F., Chatterjee, S., Foster, N., Baena, I.G., Laurence, Y.V., Qiang, S., Siroka, A., Sweeney, S. and Verguet, S., 2016. Cost-effectiveness and resource implications of aggressive action on tuberculosis in China, India, and South Africa: a combined analysis of nine models. The Lancet global health, 4(11), pp.e816-e826.
5. Sorokina, M., Ukubayev, T. and Koichubekov, B., 2023. Tuberculosis incidence and its socioeconomic determinants: developing a parsimonious model. Annali di Igiene, Medicina Preventiva e di Comunita, 35(4): 468-479.
6. Houben, R.M., Menzies, N.A., Sumner, T., Huynh, G.H., Arinaminpathy, N., Goldhaber-Fiebert, J.D., Lin, H.H., Wu, C.Y., Mandal, S., Pandey, S. and Suen, S.C., 2016. Feasibility of achieving the 2025 WHO global tuberculosis targets in South Africa, China, and India: a combined analysis of 11 mathematical models. The Lancet Global Health, 4(11), pp.e806-e815.
7. Shewade, H.D., Ravichandran, P., Pradeep, S.K., Kiruthika, G., Shanmugasundaram, D., Chadwick, J., Iyer, S., Chowdhury, A., Tumu, D., Shah, A.N. and Vadera, B., 2024. Bridging the “know-do” gap to improve active case finding for tuberculosis in India: A qualitative exploration into national tuberculosis elimination program staffs’ perspectives. PloS one, 19(11), p.e0309750.

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Screening, Treatment, and Transmission Control

1. Impact of BCG Vaccination Policies on TB Epidemiology

• Stopping universal BCG vaccination does not universally increase childhood TB cases.
• Only Slovakia saw a significant rise in childhood TB rates; other countries (Norway, France, UK) remained stable or declined. See also: https://idebeasiswa.com
• Migration patterns influenced TB rates, especially in France and Norway.
• Pulmonary TB and TB lymphadenitis were the most common forms; severe TB cases stayed below 4%.
• Discontinuation could raise TB burden in high vaccine efficacy regions, but selective vaccination is a viable alternative.
• Strong surveillance and targeted vaccination strategies are necessary.

2. Challenges in Pediatric TB Diagnosis and Care

• Diagnosing pediatric TB is difficult due to sample collection challenges.
• Alternative methods (stool, nasopharyngeal aspirates) offer similar sensitivity to induced sputum.
• Many children with TB symptoms remain undiagnosed due to limited diagnostic accessibility.
• Decentralizing TB services to district hospitals (DHs) is cost-effective in high-prevalence areas.
• Extending services to primary health centers (PHCs) is less feasible due to cost and efficiency concerns.
• DHs detect more TB cases due to better diagnostic tools and referral practices.

3. Innovations in TB Diagnosis and Treatment

• A new diagnostic tool is expected to accelerate pulmonary TB burden reduction.
• Most beneficial in areas with good TB care access but limited diagnostic sensitivity.
• Less impact in reference labs with high diagnostic accuracy.
• Could improve patient trust, reduce diagnosis delays, and minimize repeated healthcare visits.

4. TB Screening, Surveillance, and Transmission Control

• Screening and treating latent and asymptomatic TB infections significantly reduce transmission rates.
• The most effective approach combines vaccination, screening, and treatment.
• Study in Eastern Cape, South Africa, identified key TB surveillance challenges: Transport issues for community health workers (CHWs). Community distrust and resource disparities between rural and urban areas. Need for tailored TB surveillance interventions.

5. TB in High-Risk Populations: Loss to Follow-Up and Occupational Risk

• Study in Kenya found a 42.4% pre-treatment loss to follow-up (PTLFU) rate in pulmonary TB patients.
• Major risk factors: limited contact details and older age (≥55 years).
• Sex, HIV status, and prior TB treatment did not significantly affect PTLFU.
• Healthcare workers (HCWs) in Taiwan have a higher TB incidence than the general population.
• HCWs have better TB outcomes due to early diagnosis, treatment, and the "healthy worker effect."

References:

1. Kobayashi, S., Yoshiyama, T., Uchimura, K., Hamaguchi, Y. and Kato, S., 2021. Epidemiology of childhood tuberculosis after ceasing universal Bacillus Calmette–Guérin vaccination. Scientific Reports, 11(1), p.15902.
2. Fu, H., Lin, H.H., Hallett, T.B. and Arinaminpathy, N., 2018. Modelling the effect of discontinuing universal Bacillus Calmette-Guérin vaccination in an intermediate tuberculosis burden setting. Vaccine, 36(39), pp.5902-5909.
3. d'Elbée, M., Harker, M., Mafirakureva, N., Nanfuka, M., Nguyet, M.H.T.N., Taguebue, J.V., Moh, R., Khosa, C., Mustapha, A., Mwanga-Amumpere, J. and Borand, L., 2024. Cost-effectiveness and budget impact of decentralising childhood tuberculosis diagnosis in six high tuberculosis incidence countries: a mathematical modelling study. EClinicalMedicine, 70, p.102528.
4. Lin, H.H., Dowdy, D., Dye, C., Murray, M. and Cohen, T., 2012. The impact of new tuberculosis diagnostics on transmission: why context matters. Bulletin of the World Health Organization, 90, pp.739-747.
5. Mulaku, M.N., Ochodo, E., Young, T. and Steingart, K.R., 2024. Pre-treatment loss to follow-up in adults with pulmonary TB in Kenya. Public Health Action, 14(1), pp.34-39.
6. Kirimi, E.M., Muthuri, G.G., Ngari, C.G. and Karanja, S., 2024. A Model for the Propagation and Control of Pulmonary Tuberculosis Disease in Kenya. Discrete Dynamics in Nature and Society, 2024(1), p.5883142.
7. Ajudua, F.I. and Mash, R.J., 2024. Implementing active surveillance for TB: A descriptive survey of healthcare workers in the Eastern Cape, South Africa. African Journal of Primary Health Care & Family Medicine, 16(1), p.4217. See also: https://tbreadingnotes.blogspot.com/2024/07/tuberculosis-in-healthcare-workers.html
8. Pan S-C, Chen Y-C, Wang J-Y, Sheng W-H, Lin H-H, Fang C-T, et al. (2015) Tuberculosis in Healthcare Workers: A Matched Cohort Study in Taiwan. PLoS ONE 10(12): e0145047.

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Social Determinants and Global TB Control

1. Air Pollution and TB Risk

• Household air pollutants (HAP), particularly PM2.5 and CO, from kerosene lighting and biomass cooking, elevate TB risk.
• PM2.5 exposure in study participants averaged 170 µg/m³, far exceeding WHO’s guideline of 25 µg/m³.
• Area PM2.5 significantly contributes to TB risk (OR 6.74), with kerosene lighting associated with increased odds (OR 3.73).
• PM exposure disrupts immune function and enhances M. tuberculosis growth, while NO2 exposure weakens host defenses.
• Reduction of air pollution is essential for TB prevention and control.

Intervention Plan: Implement a community-based program to distribute clean energy solutions (e.g., solar lighting and LPG stoves) to replace kerosene and biomass fuel. This program would also include education on proper ventilation and regular HAP monitoring to reduce PM2.5 exposure.

See also: Scholarships to Australia

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2. Nutrition and TB Dynamics

• Undernutrition is the leading risk factor for TB, impairing immunity and increasing susceptibility.
• Nutritional interventions reduce TB incidence and mortality, with a projected 23.6% reduction in TB incidence and a 35.5% decrease in mortality in high-risk populations when scaled.
• Historical case studies highlight the impact of improved nutrition on reducing TB rates during crises.
• Vitamin supplementation shows potential for TB prevention, particularly among high-risk family contacts.

Intervention Plan: Integrate nutritional support into TB care programs by providing monthly nutrient-rich food packages and micronutrient supplements to TB patients and their households. Monitor and adjust diets based on local nutritional deficiencies.

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3. Healthcare Systems and Diagnostic Gaps

• High-burden countries struggle with underinvestment, limited access to rapid molecular diagnostics, and case detection challenges.
• Only 38% of TB cases were tested using WHO-recommended diagnostics in 2021.
• Innovations like AI-assisted x-rays, oral swabs, and urine antigen tests face adoption barriers due to cost and infrastructure limitations.

Intervention Plan: Launch a mobile diagnostic initiative using AI-assisted chest x-rays and portable molecular diagnostic tools in underserved regions. Subsidize costs through public-private partnerships to improve early detection and reduce delays in TB diagnosis.

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4. Comorbidities and TB Risk

• TB-DM patients face higher metabolic disturbances, nutritional deficits, and cardiovascular risks.
• Poor glycemic control (HbA1c >10%) and vitamin D deficiency (73.68% in TB-DM group) exacerbate complications.
• Dialysis patients face elevated TB risks due to weakened immunity from oxidative stress and uremic toxins.

Intervention Plan: Develop a TB-DM management protocol that integrates glycemic control, regular vitamin D supplementation, and nutritional monitoring into existing healthcare services. Screen dialysis patients for TB risk and provide targeted prophylaxis.

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5. Social Determinants and Global TB Control

• Poverty, overcrowding, and poor living conditions are drivers of TB prevalence.
• Achieving the SDGs for TB requires sustained funding, equitable healthcare access, and addressing social determinants.
• Rapid mortality declines in some sub-Saharan African countries highlight the potential of focused interventions.

Intervention Plan: Introduce a conditional cash transfer program for TB-affected households to improve living conditions, reduce overcrowding, and provide access to healthcare. Combine this with public awareness campaigns to address stigma and encourage treatment adherence.

References:

1. Jagger, P., McCord, R., Gallerani, A., Hoffman, I., Jumbe, C., Pedit, J., Phiri, S., Krysiak, R. and Maleta, K., 2024. Household air pollution exposure and risk of tuberculosis: a case–control study of women in Lilongwe, Malawi. BMJ Public Health, 2(1).
2. Lu, J.W., Mao, J.J., Zhang, R.R., Li, C.H., Sun, Y., Xu, W.Q., Zhuang, X., Zhang, B. and Qin, G., 2023. Association between long-term exposure to ambient air pollutants and the risk of tuberculosis: A time-series study in Nantong, China. Heliyon, 9(6).
3. Reid, M., Agbassi, Y.J.P., Arinaminpathy, N., Bercasio, A., Bhargava, A., Bhargava, M., Bloom, A., Cattamanchi, A., Chaisson, R., Chin, D. and Churchyard, G., 2023. Scientific advances and the end of tuberculosis: a report from the Lancet Commission on Tuberculosis. The Lancet, 402(10411), pp.1473-1498.
4. Furin, J., Cox, H., & Pai, M. (2019). Tuberculosis. Lancet (London, England), 393(10181), 1642–1656.
5. Mandal, S., Bhatia, V., Bhargava, A., Rijal, S. and Arinaminpathy, N., 2024. The potential impact on tuberculosis of interventions to reduce undernutrition in the WHO South-East Asian Region: a modelling analysis. The Lancet Regional Health-Southeast Asia, p.100423.
6. Cegielski, J.P. and McMurray, D.N., 2004. The relationship between malnutrition and tuberculosis: evidence from studies in humans and experimental animals. The international journal of tuberculosis and lung disease, 8(3), pp.286-298.
7. Shu, C.C., Hsu, C.L., Wei, Y.F., Lee, C.Y., Liou, H.H., Wu, V.C., Yang, F.J., Lin, H.H., Wang, J.Y., Chen, J.S. and Yu, C.J., 2016. Risk of tuberculosis among patients on dialysis: the predictive value of serial interferon-gamma release assay. Medicine, 95(22), p.e3813.
8. Patel, D.G., Baral, T., Kurian, S.J., Malakapogu, P., Saravu, K. and Miraj, S.S., 2024. Nutritional status in patients with tuberculosis and diabetes mellitus: A comparative observational study. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases, 35, p.100428.

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